Characterization of forest litter horizons through full-wave inversion of ground-penetrating radar data

NASA Astrophysics Data System (ADS)

André, Frédéric; Jonard, Mathieu; Jonard, François; Lambot, Sébastien

2015-04-01

Decomposing litter accumulated at the soil surface in forest ecosystems play a major role in a series of ecosystem processes (soil carbon sequestration, nutrient release through decomposition, water retention, buffering of soil temperature variations, tree regeneration, population dynamics of ground vegetation and soil fauna, ...). Besides, the presence of litter is acknowledged to influence remote sensing radar data over forested areas and accurate quantification of litter radiative properties is essential for proper processing of these data. In these respects, ground-penetrating radar (GPR) presents particular interests, potentially allowing for fast and non-invasive characterization of organic layers with fine spatial and/or temporal resolutions as well as for providing detailed information on litter electrical properties which are required for modeling either active or passive microwave remote sensing data. We designed an experiment in order to analyze the backscattering from forest litter horizons and to investigate the potentialities of GPR for retrieving the physical properties of these horizons. For that purpose, we used an ultrawide band radar system connected to a transmitting and receiving horn antenna. The GPR data were processed resorting to full-wave inversion of the signal, through which antenna effects are accounted for. In a first step, GPR data were acquired over artificially reconstructed layers of three different beech litter types (i.e., (i) recently fallen litter with easily discernible plant organs (OL layer), (ii) fragmented litter in partial decomposition without entire plant organs (OF layer) and (iii) combination of OL and OF litter layers) and considering in each case a range of layer thicknesses. In a second step, so as to validate the adopted methodology in real natural conditions, GPR measurements were performed in situ along a transect crossing a wide range of litter properties in terms of thickness and composition through stands of various tree species. Results from the controlled experiment demonstrated the ability of GPR to reconstruct litter horizons, showing close correspondence between inversely estimated and measured litter layer thicknesses and providing reliable estimates of litter electromagnetic properties. This experiment also highlighted the necessity of considering scattering and dielectric losses occurring within litter for proper modeling of the GPR signal, which was accounted for through frequency dependence of an effective electrical conductivity of the litter. Similar findings emerged from the in situ experiment, though somewhat lower agreement was observed between estimated and reference layer thickness values. These results show great promise for the use of GPR for non-invasive characterization of forest litter. Index Terms: Ground-penetrating radar (GPR), forest litter, frequency dependence, scattering Reference: André F., Jonard M., Lambot S., 2015. Non-invasive forest litter characterization using full-wave inversion of microwave radar data, IEEE Transactions on Geoscience and Remote Sensing, 53(2), 828-840.

Rutgers/NJDOT Pavement Resource Program (NJDOT Statewide GPR Project Network GPR Data Collection and Analysis Update of HPMA GPR Database)

DOT National Transportation Integrated Search

2008-05-01

Center for Advanced Transportation Infrastructure (CAIT) of Rutgers University is mandated to conduct Ground Penetrating Radar (GPR) surveys to update the NJDOT's pavement management system with GPR measured pavement layer thicknesses. Based on the r...

Expression and immunoaffinity purification of recombinant soluble human GPR56 protein for the analysis of GPR56 receptor shedding by ELISA.

PubMed

Yang, Tai-Yun; Chiang, Nien-Yi; Tseng, Wen-Yi; Pan, Hsiao-Lin; Peng, Yen-Ming; Shen, Jiann-Jong; Wu, Kuo-An; Kuo, Ming-Ling; Chang, Gin-Wen; Lin, Hsi-Hsien

2015-05-01

GPR56 is a multi-functional adhesion-class G protein-coupled receptor involved in biological systems as diverse as brain development, male gonad development, myoblast fusion, hematopoietic stem cell maintenance, tumor growth and metastasis, and immune-regulation. Ectodomain shedding of human GPR56 receptor has been demonstrated previously, however the quantitative detection of GPR56 receptor shedding has not been investigated fully due to the lack of appropriate assays. Herein, an efficient system of expression and immune-affinity purification of the recombinant soluble extracellular domain of human GPR56 (sGPR56) protein from a stably transduced human melanoma cell line was established. The identity and functionality of the recombinant human sGPR56 protein were verified by Western blotting and mass spectrometry, and ligand-binding assays, respectively. Combined with the use of two recently generated anti-GPR56 monoclonal antibodies, a sensitive sandwich ELISA assay was successfully developed for the quantitative detection of human sGPR56 molecule. We found that GPR56 receptor shedding occurred constitutively and was further increased in activated human melanoma cells expressing endogenous GPR56. In conclusion, we report herein an efficient system for the production and purification of human sGPR56 protein for the establishment of a quantitative ELISA analysis of GPR56 receptor shedding. Copyright © 2014 Elsevier Inc. All rights reserved.

The Curvelet Transform in the analysis of 2-D GPR data: Signal enhancement and extraction of orientation-and-scale-dependent information

NASA Astrophysics Data System (ADS)

Tzanis, Andreas

2013-04-01

The Ground Probing Radar (GPR) has become a valuable means of exploring thin and shallow structures for geological, geotechnical, engineering, environmental, archaeological and other work. GPR images usually contain geometric (orientation/dip-dependent) information from point scatterers (e.g. diffraction hyperbolae), dipping reflectors (geological bedding, structural interfaces, cracks, fractures and joints) and other conceivable structural configurations. In geological, geotechnical and engineering applications, one of the most significant objectives is the detection of fractures, inclined interfaces and empty or filled cavities frequently associated with jointing/faulting. These types of target, especially fractures, are usually not good reflectors and are spatially localized. Their scale is therefore a factor significantly affecting their detectability. At the same time, the GPR method is notoriously susceptible to noise. Quite frequently, extraneous (natural or anthropogenic) interference and systemic noise swamp the data with unusable information that obscures, or even conceals the reflections from such targets. In many cases, the noise has definite directional characteristics (e.g. clutter). Raw GPR data require post-acquisition processing, as they usually provide only approximate target shapes and distances (depths). The purpose of this paper is to investigate the Curvelet Transform (CT) as a means of S/N enhancement and information retrieval from 2-D GPR sections (B-scans), with particular emphasis placed on the problem of recovering features associated with specific temporal or spatial scales and geometry (orientation/dip). The CT is a multiscale and multidirectional expansion that formulates a sparse representation of the input data set (Candès and Donoho, 2003a, 2003b, 2004; Candés et al., 2006). A signal representation is sparse when it describes the signal as a superposition of a small number of components. What makes the CT appropriate for processing GPR data is its capability to describe wavefronts. The roots of the CT are traced to the field of Harmonic Analysis, where curvelets were introduced as expansions for asymptotic solutions of wave equations (Smith, 1998; Candès, 1999). In consequence, curvelets can be viewed as primitive and prototype waveforms - they are local in both space and spatial frequency and correspond to a partitioning of the 2D Fourier plane by highly anisotropic elements (for the high frequencies) that obey the parabolic scaling principle, that their width is proportional to the square of their length (Smith, 1998). The GPR data essentially comprise recordings of the amplitudes of transient waves generated and recorded by source and receiver antennae, with each source/receiver pair generating a data trace that is a function of time. An ensemble of traces collected sequentially along a scan line, i.e. a GPR section or B-scan, provides a spatio-temporal sampling of the wavefield which contains different arrivals that correspond to different interactions with wave scatterers (inhomogeneities) in the subsurface. All these arrivals represent wavefronts that are relatively smooth in their longitudinal direction and oscillatory in their transverse direction. The connection between Harmonic Analysis and curvelets has resulted in important nonlinear approximations of functions with intermittent regularity (Candès and Donoho, 2004). Such functions are assumed to be piecewise smooth with singularities, i.e. regions where the derivative diverges. In the subsurface, these singularities correspond to geological inhomogeneities, at the boundaries of which waves reflect. In GPR data, these singularities correspond to wavefronts. Owing to their anisotropic shape, curvelets are well adapted to detect wavefronts at different angles and scales because aligned curvelets of a given scale, locally correlate with wavefronts of the same scale. The CT can also be viewed as a higher dimensional extension of the wavelet transform: whereas discrete wavelets are designed to provide sparse representations of functions with point singularities, curvelets are designed to provide sparse representations of functions with singularities on curves. This work investigates the utility of the CT in processing noisy GPR data from geotechnical and archaeometric surveys. The analysis has been performed with the Fast Discrete CT (FDCT - Candès et al., 2006) available from http://www.curvelet.org/ and adapted for use by the matGPR software (Tzanis, 2010). The adaptation comprises a set of driver functions that compute and display the curvelet decomposition of the input GPR section and then allow for the interactive exclusion/inclusion of data (wavefront) components at different scales and angles by cancelation/restoration of the corresponding curvelet coefficients. In this way it is possible to selectively reconstruct the data so as to abstract/retain information of given scales and orientations. It is demonstrated that the CT can be used to: (a) Enhance the S/N ratio by cancelling directional noise wavefronts of any angle of emergence, with particular reference to clutter. (b) Extract geometric information for further scrutiny, e.g. distinguish signals from small and large aperture fractures, faults, bedding etc. (c) Investigate the characteristics of signal propagation (hence material properties), albeit indirectly. This is possible because signal attenuation and temporal localization are closely associated, so that scale and spatio-temporal localization are also closely related. Thus, interfaces embedded in low attenuation domains will tend to produce sharp reflections rich in high frequencies and fine-scale localization. Conversely, interfaces in high attenuation domains will tend to produce dull reflections rich in low frequencies and broad localization. At a single scale and with respect to points (a) and (b) above, the results of the CT processor are comparable to those of the tuneable directional wavelet filtering scheme proposed by Tzanis (2013). With respect to point (c), the tuneable directional filtering appears to be more suitable in isolating and extracting information at the lower frequency - broader scale range. References Candès, E., 1999. Harmonic analysis of neural networks. Appl. Comput. Harmon. Anal., 6, 197-218. Candès, E. and Donoho, D., 2003a. Continuous curvelet transform: I. Resolution of the wavefront set. Appl. Comput. Harmon. Anal., 19, 162-197. Candès, E. and Donoho, D., 2003b. Continuous curvelet transform: II. Discretization and frames. Appl. Comput. Harmon. Anal., 19, 198-222. Candès, E. and Donoho, D., 2004. New tight frames of curvelets and optimal representations of objects with piecewise C2 singularities. Comm. Pure Appl. Math., 57, 219-266. Candès, E. J., L. Demanet, D. L. Donoho, and L. Ying, 2006. Fast discrete curvelet transforms (FDCT). Multiscale Modeling and Simulation, 5, 861-899. Smith, H. F., 1998. A Hardy space for Fourier integral operators. Journal of Geometric Analysis, 7, 629 - 653. Tzanis, A., 2010. matGPR Release 2: A freeware MATLAB® package for the analysis & interpretation of common and single offset GPR data. FastTimes, 15 (1), 17 - 43. Tzanis, A, 2013. Detection and extraction of orientation-and-scale-dependent information from two-dimensional GPR data with tuneable directional wavelet filters. Journal of Applied Geophysics, 89, 48-67. DOI: 10.1016/j.jappgeo.2012.11.007

Site-Directed Mutagenesis and Structural Studies Suggest that the Germination Protease, GPR, in Spores of Bacillus Species Is an Atypical Aspartic Acid Protease

PubMed Central

Carroll, Thomas M.; Setlow, Peter

2005-01-01

Germination protease (GPR) initiates the degradation of small, acid-soluble spore proteins (SASP) during germination of spores of Bacillus and Clostridium species. The GPR amino acid sequence is not homologous to members of the major protease families, and previous work has not identified residues involved in GPR catalysis. The current work has focused on identifying catalytically essential amino acids by mutagenesis of Bacillus megaterium gpr. A residue was selected for alteration if it (i) was conserved among spore-forming bacteria, (ii) was a potential nucleophile, and (iii) had not been ruled out as inessential for catalysis. GPR variants were overexpressed in Escherichia coli, and the active form (P41) was assayed for activity against SASP and the zymogen form (P46) was assayed for the ability to autoprocess to P41. Variants inactive against SASP and unable to autoprocess were analyzed by circular dichroism spectroscopy and multiangle laser light scattering to determine whether the variant's inactivity was due to loss of secondary or quaternary structure, respectively. Variation of D127 and D193, but no other residues, resulted in inactive P46 and P41, while variants of each form were well structured and tetrameric, suggesting that D127 and D193 are essential for activity and autoprocessing. Mapping these two aspartate residues and a highly conserved lysine onto the B. megaterium P46 crystal structure revealed a striking similarity to the catalytic residues and propeptide lysine of aspartic acid proteases. These data indicate that GPR is an atypical aspartic acid protease. PMID:16199582

Full 3D Microwave Tomography enhanced GPR surveys: a case study

NASA Astrophysics Data System (ADS)

Catapano, Ilaria; Soldovieri, Francesco; Affinito, Antonio; Hugenschmidt, Johannes

2014-05-01

Ground Penetrating Radar (GPR) systems are well assessed non-invasive diagnostic tools capable of providing high resolution images of the inner structure of the probed spatial region. Owing to this capability, GPR systems are nowadays more and more considered in the frame of civil engineering surveys since they may give information on constructive details as well as on the aging and risk factors affecting the healthiness of an infrastructure. In this frame, accurate, reliable and easily interpretable images of the probed scenarios are mandatory in order to support the management of maintenance works and assure the safety of structures. Such a requirement motivates the use of different and sophisticated data processing approaches in order to compare more than one image of the same scene, thus improving the reliability and objectiveness of the GPR survey results. Among GPR data processing procedures, Microwave Tomography approaches based on the Born approximation face the imaging as the solution of a linear inverse problem, which is solved by using the Truncated Singular Value Decomposition as a regularized inversion scheme [1]. So far, an approach exploiting a 2D scalar model of the scattering phenomenon have been adopted to process GPR data gathered along a single scan. In this case, 3D images are obtained by interpolating 2D reconstructions (this is referred commonly as pseudo 3D imaging). Such an imaging approach have provided valuable results in several real cases dealing with not only surveys for civil engineering but also archeological prospection, subservice monitoring, security surveys and so on [1-4]. These encouraging results have motivated the development of a full 3D Microwave Tomography approach capable of accounting for the vectorial nature of the wave propagation. The reconstruction capabilities of this novel approach have been assessed mainly against experimental data collected in laboratory controlled conditions. The obtained results corroborate that, the use of a full 3D scattering model allows an improved estimation of the objects shape and size with respect to pseudo 3D imaging [5]. In this communication, the performance offered by the full 3D imaging approach is investigated by using a dataset from infrastructure inspection. Since the collapse of a car park in Switzerland killing 7 firemen, "punching", where a pile remains upright but the ceiling carried by the pile falls down, is considered a serious problem The 3D tomography approach was applied to a dataset acquired in a car park in the vicinity of piles. Such datasets can be used for an assessment of the safety of such structures and can therefore be considered as relevant test cases for innovative data processing and inversion strategies. REFERENCES [1] F. Soldovieri, J. Hugenschmidt, R. Persico and G. Leone, "A linear inverse scattering algorithm for realistic GPR applications, Near Surf. Geophys., vol. 5, pp.29-42, 2007. [2] I. Catapano, L. Crocco R. Di Napoli, F. Soldovieri, A. Brancaccio, F. Pesando, A. Aiello, "Microwave tomography enhanced GPR surveys in Centaur's Domus, Regio VI of Pompeii, Italy", J. Geophys. Eng., vol.9, S92-S99, 2012. [3] I. Catapano, R. Di Napoli, F. Soldovieri, M. Bavusi, A. Loperte, J. Dumoulin, Structural monitoring via microwave tomography-enhanced GPR: the Montagnole test site, J. Geophys. Eng., vol. 9, S100-S107, 2012 [4] J. Hugenschmidt, A. Kalogeropoulos, F. Soldovieri, G. Prisco (2010) Processing Strategies for high-resolution GPR Concrete Inspections, NDT & E International, Volume 43, Issue 4: 334-342. [5] I. Catapano, A. Affinito, G. Gennarelli, F. di Maio, A. Loperte, F. Soldovieri, Full three-dimensional imaging via ground penetrating radar: assessment in controlled conditions and on field for archaeological prospecting, Appl. Phys. A: Materials Science and Processing, pp. 1-8, Article in Press

An improved interface to process GPR data by means of microwave tomography

NASA Astrophysics Data System (ADS)

Catapano, Ilaria; Affinito, Antonio; Soldovieri, Francesco

2015-04-01

Ground Penetrating Radar (GPR) systems are well assessed non-invasive diagnostic tools, which are worth being considered in civil engineering surveys since they allow to gather information on constructive materials and techniques of manmade structures as well as on the aging and risk factors affecting their healthiness. However, the practical use of GPR depends strictly on the availability of data processing tools, on one hand, capable of providing reliable and easily interpretable images of the probed scenarios and, on the other side, easy to be used by not expert users. In this frame, 2D and full 3D microwave tomographic approaches based on the Born approximation have been developed and proved to be effective in several practical conditions [1, 2]. Generally speaking, a GPR data processing chain exploiting microwave tomography is made by two main steps: the pre-processing and the data inversion. The pre-processing groups standard procedures like start time correction, muting and background removal, which are performed in time domain to remove the direct antennas coupling, to reduce noise and to improve the targets footprint. The data inversion faces the imaging as the solution of a linear inverse scattering problem in the frequency domain. Hence, a linear integral equation relating the scattered field (i.e. the data) to the unknown electric contrast function is solved by using the truncated Singular Value Decomposition (SVD) as a regularized inversion scheme. Pre-processing and the data inversion are linked by a Discrete Fourier Transform (DFT), which allows to pass from the time domain to the frequency domain. In this respect, a frequency analysis of the GPR signals (traces) is also performed to identify the actual frequency range of the data. Unfortunately, the adoption of microwave tomography is strongly subjected to the involvement of expert people capable of managing properly the processing chain. To overcome this drawback, a couple of years ago, an end-user friendly software interface was developed to make possible a simple management of 2D microwave tomographic approaches [3]. Aim of this communication, is to present a novel interface, which is a significantly improved version with respect to the previous one. In particular, the new interface allows both 2D and full 3D imaging by taking as input GPR data gathered by means of different measurement configurations, i.e. by using down looking systems, with the antenna located close to the air-medium interface or at non negligible (in terms of the probing wavelength) distance from it, as well as by means of airborne and forward looking systems. In this frame, the users can select the data format among those of the most common commercial GPR systems or process data gathered by means of GPR prototypes, provided that they are saved in ASCII format. Moreover, the users can perform all the steps, which are needed to obtain tomographic images, and select the Born approximation based approach most suitable to the adopted measurement configuration. Raw-radargrams, intermediate and final results can be displayed for users convenience. REFERENCES [1] I. Catapano, R. Di Napoli, F. Soldovieri, M. Bavusi, A. Loperte, J. Dumoulin, "Structural monitoring via microwave tomography-enhanced GPR: the Montagnole test site", J. Geophys. Eng. 9, S100-S107, 2012. [2] I. Catapano, A. Affinito, G. Gennarelli, F.di Maio, A. Loperte, F. Soldovieri, "Full three-dimensional imaging via ground penetrating radar: assessment in controlled conditions and on field for archaeological prospecting", Appl. Phys. A, 2013, DOI 10.1007/s00339-013-8053-0. [3] I. Catapano, A. Affinito, F. Soldovieri, A user friendly interface for microwave tomography enhanced GPR surveys", EGU General Assembly 2013, vol. 15.

G-protein-coupled estrogen receptor GPR30 and tamoxifen resistance in breast cancer.

PubMed

Ignatov, Atanas; Ignatov, Tanja; Weissenborn, Christine; Eggemann, Holm; Bischoff, Joachim; Semczuk, Andrzej; Roessner, Albert; Costa, Serban Dan; Kalinski, Thomas

2011-07-01

Recently, we have shown that the new G-protein-coupled estrogen receptor GPR30 plays an important role in the development of tamoxifen resistance in vitro. This study was undertaken to evaluate the correlation between GPR30 and tamoxifen resistance in breast cancer patients. GPR30 protein expression was evaluated by immunohistochemical analysis in 323 patients with primary operable breast cancer. The association between GPR30 expression and tamoxifen resistance was confirmed in a second cohort of 103 patients treated only with tamoxifen. Additionally, we evaluated GPR30 expression in 33 primary tumors and in recurrent tumors from the same patients. GPR30 expression was detected in 56.7% of the breast cancer specimens investigated and it correlated with overexpression of HER-2 (P = 0.021), EGFR (P = 0.024) and lymph node status (P = 0.047). In a first cohort, survival analysis showed that GPR30 was negatively correlated with relapse-free survival (RFS) only in patients treated with tamoxifen (tamoxifen with or without chemotherapy). GPR30 expression was associated with shorter RFS (HR = 1.768; 95% CI, 1.156-2.703; P = 0.009). In a subset of patients treated only with tamoxifen, multivariate analysis revealed that GPR30 expression is an independent unfavorable factor for RFS (HR = 4.440; 95% CI, 1.408-13.997; P = 0.011). In contrast, GPR30 tended to be a favorable factor regarding RFS in patients who did not receive tamoxifen. In 33 paired biopsies obtained before and after adjuvant therapy, GPR30 expression significantly increased only under tamoxifen treatment (P = 0.001). GPR30 expression in breast cancer independently predicts a poor RFS in patients treated with tamoxifen.

Seasonal GPR Signal Changes in Two Contrasting Soils in the Shale Hills Catchment

NASA Astrophysics Data System (ADS)

Lin, H.; Zhang, J.; Doolittle, J. A.

2011-12-01

Repeated GPR surveys in different seasons, combined with real-time soil water monitoring, provide a useful methodology to reveal subsurface hydrologic processes and their underlying mechanisms in different soils and hillslopes. This was demonstrated in the Shale Hills Critical Zone Observatory using two contrasting soils over several dry and wet seasons. Our results showed that 1) the radar reflection in the BC-C horizon interface in the deep Rushtown soil became clearer as soil became wetter, which was linked to lateral flow above this horizon interface that increased the contrast, and 2) the reflection in the soil-bedrock interface and the weathered-unweathered rock interface in the shallow Weikert soil become intermittent as soil became wetter, which was attributed to non-uniform distribution of water in bedrock fractures that created locally strong contrast, leading to point scatter of GPR reflection. This study shows the optimal time for using GPR to detect soil horizon interfaces, the value of nondestructive mapping of soil-rock moisture distribution patterns, and the possibility of identifying preferential flow pathways in the subsurface.

Revealing transient strain in geodetic data with Gaussian process regression

NASA Astrophysics Data System (ADS)

Hines, T. T.; Hetland, E. A.

2018-03-01

Transient strain derived from global navigation satellite system (GNSS) data can be used to detect and understand geophysical processes such as slow slip events and post-seismic deformation. Here we propose using Gaussian process regression (GPR) as a tool for estimating transient strain from GNSS data. GPR is a non-parametric, Bayesian method for interpolating scattered data. In our approach, we assume a stochastic prior model for transient displacements. The prior describes how much we expect transient displacements to covary spatially and temporally. A posterior estimate of transient strain is obtained by differentiating the posterior transient displacements, which are formed by conditioning the prior with the GNSS data. As a demonstration, we use GPR to detect transient strain resulting from slow slip events in the Pacific Northwest. Maximum likelihood methods are used to constrain a prior model for transient displacements in this region. The temporal covariance of our prior model is described by a compact Wendland covariance function, which significantly reduces the computational burden that can be associated with GPR. Our results reveal the spatial and temporal evolution of strain from slow slip events. We verify that the transient strain estimated with GPR is in fact geophysical signal by comparing it to the seismic tremor that is associated with Pacific Northwest slow slip events.

GPR119 agonists: a promising approach for T2DM treatment? A SWOT analysis of GPR119.

PubMed

Kang, Sang-Uk

2013-12-01

Ever since its advent as a promising therapeutic target for type 2 diabetes mellitus (T2DM), G-protein-coupled receptor 119 (GPR119) has received much interest from the pharmaceutical industry. This interest peaked in June 2010, when Sanofi-Aventis agreed to pay Metabolex (Cymabay Therapeutics) US$375 million for MBX-2982, which was a representative orally active GPR119 agonist. However, Sanofi-Aventis opted to terminate the deal in May 2011 and another leading GPR119 agonist, GSK1292263, had a loss of efficacy during its clinical trial. In this review, I discuss the pros and cons of GPR119 through a strengths, weaknesses, opportunities, and threats (SWOT) analysis and propose development strategies for the eventual success of a GPR119 agonist development program. Copyright © 2013 Elsevier Ltd. All rights reserved.

The novel estrogen receptor G-protein-coupled receptor 30 is expressed in human bone.

PubMed

Heino, Terhi J; Chagin, Andrei S; Sävendahl, Lars

2008-05-01

Estrogens have significant impact on bone mineral metabolism. Besides the classical estrogen receptors (ERalpha and ERbeta), a trans-membrane G-protein-coupled receptor (GPR30) has been demonstrated to mediate estrogenic effects. We aimed to study whether GPR30 is expressed in bone cells and if so, whether the level of expression is developmentally regulated. Metaphyseal bone biopsies were collected from the tibia in 14 boys and 6 girls, all at different stages of puberty. GPR30 protein expression was studied by immunohistochemistry in paraffin-embedded sections. GPR30-positive osteocytes and osteoblasts were quantified and linear regression analysis was applied. Cytoplasmic GPR30 expression was detected in osteoblasts, osteocytes, and osteoclasts. Osteocytes were more frequently positive for GPR30 than osteoblasts (58+/-4% vs 46+/-3% positive cells respectively, P<0.05). Detailed analysis demonstrated that GPR30 positivity declined during pubertal development in osteocytes (R=-0.56, P<0.01) but not in osteoblasts (R=-0.31, P>0.05). No sex difference was observed in the numbers of GPR30-positive osteoblasts or osteocytes. Furthermore, GPR30 expression did not correlate with chronological or bone age. In conclusion, the novel ER GPR30 is expressed in osteoblasts, osteocytes, and osteoclasts suggesting that non-genomic estrogen signaling via GPR30 may exist in bone. However, the functional role of GPR30 in bone tissue remains to be elucidated.

A Vertical Differential Configuration in GPR prospecting

NASA Astrophysics Data System (ADS)

Persico, Raffaele; Pochanin, Gennadiy; Varianytsia-Roshchupkina, Liudmyla; Catapano, Ilaria; Gennarelli, Gianluca; Soldovieri, Francesco

2015-04-01

The rejection of the direct coupling between the antennas is an issue of interest in several GPR applications, especially when it is important to distinguish the targets of interest from the clutter and the signal reflected from the air soil interface. Therefore, in this framework several hardware and software strategies have been proposed. Among the software strategies, probably the most common one is the background removal [1], whereas as an hardware strategy the differential configuration has been introduced in [2-3] and then further on studied in [4] with respect to the spatial filtering properties of the relevant mathematical operator. In particular, the studies proposed in [1] and [4] have shown that, in general, all the strategies for the rejection of the direct coupling have necessarily some drawback, essentially because it is not possible to erase all and only the undesired contributions leaving "untouched" the contributions of the targets of interest to the gathered signal. With specific regard to the differential configuration, in [2-3], the differential configuration consisted in a couple of receiving antennas symmetrically placed around the transmitting one, being the three antennas placed along the same horizontal segment. Therefore, we might define that configuration as a "horizontal differential configuration". Here, we propose a novel differential GPR configuration, where the two receiving antennas are still symmetrically located with respect to the transmitting one, but are placed piled on each other at different heights from the air-soil interface, whereas the transmitting antenna is at the medium height between the two receiving one (however, it is not at the same abscissa but at a fixed horizontal offset from the receiving antennas). Such a differential configuration has been previously presented in [5-6] and allows a good isolation between the antennas, while preserving the possibility to collect backscattered signals from both electrically small objects and interfaces. This configuration can be labeled as a vertical differential configuration. At the conference, the reconstruction capabilities of this differential GPR configuration system will be discussed by means of an analysis of the problem based on a properly designed microwave tomographic inversion approach. The proposed approach exploits the Born approximation and faces the imaging as the solution of a linear inverse scattering problem. In this way, the problem of the local minima is avoided [7] and it is possible to impose some regularization to the problem in an easy way problem [8-9]. At the conference, a theoretical analysis of the mathematical propserties of the scattering operator under the vertical differential configuration will be presented showing that, with respect to the horizontal differential configuration, the vertical one allows to reject the direct coupling between the antennas but not the coupling of the antennas occurring through the air-soil interface. On the other hand, the filtering properties of the operator at hand con be considered, let say, less severe in some cases. At the conference, both some numerical and experimental results will be shown. References [1] R. Persico, F. Soldovieri, "Effects of the background removal in linear inverse scattering", IEEE Trans. Geosci. Remote Sens, vol. 46, pp. 1104-1114, April 2008. [2] L. Gurel, U. Oguz, "Three-Dimensional FDTD modeling of a ground penetrating radar", IEEE Trans. Geosci. Remote Sens, vol. 38, pp. 1513-1521, July 2000. [3] L. Gurel, U. Oguz, "Optimization of the transmitter-receiver separation in the ground penetrating radar", IEEE Trans. Antennas and Propag., vol. 51, no 3, pp. 362-370, March 2003. [4] R. Persico, F. Soldovieri, "A microwave tomography approach for a differential configuration in GPR prospecting", IEEE Trans. Antennas and Propag., vol. 54, pp. 3541 - 3548, 2006. [5] Y.A. Kopylov, S.A. Masalov, G.P. Pochanin, "The way of isolation between transmitting and receiving modules of antenna", Patent 81652 Ukraine: IPC (2006) H01Q 9/00 H01Q 19/10 / publ. 25.01.08, Bull. N. 2 [6] G.P. Pochanin, "Some Advances in UWB GPR," in "Unexploded Ordnance Detection and Mitigation, - NATO Science for Peace and Security Series -B: Physics and Biophysics - Ed. by Jim Byrnes, Springer: Dordrecht, (The Nederland), 2009. pp.223-233. [7] R. Persico, F. Soldovieri, R. Pierri, "Convergence Properties of a Quadratic Approach to the Inverse Scattering Problem", Journal of Optical Society of America Part A, vol. 19, n. 12, pp. 2424-2428, December 2002. [8] R. Pierri, G. Leone, F. Soldovieri, R. Persico, "Electromagnetic inversion for subsurface applications under the distorted Born approximation" Nuovo Cimento, vol. 24C, N. 2, pp 245-261, March-April 2001. [9] R. Persico, Introduction to ground penetrating Radar: Inverse Scattering and data Processing, in print on Wiley and Sons, 2014, ISBN 9781118305003.

GPR30 and estrogen receptor expression: new insights into hormone dependence of inflammatory breast cancer.

PubMed

Arias-Pulido, Hugo; Royce, Melanie; Gong, Yun; Joste, Nancy; Lomo, Lesley; Lee, Sang-Joon; Chaher, Nabila; Verschraegen, Claire; Lara, Juanita; Prossnitz, Eric R; Cristofanilli, Massimo

2010-08-01

GPR30 is a novel G protein-coupled estrogen receptor (ER) associated with metastases in breast cancer (BC) and poor survival in endometrial and ovarian tumors. The association of GPR30 expression with inflammatory breast cancer (IBC), an aggressive and commonly hormone-independent form of BC, has not been studied. GPR30, ER, progesterone receptor (PR), epidermal growth factor receptor (EGFR), and HER-2 expression were assessed by immunohistochemistry (and FISH for HER-2) in 88 primary IBCs. GPR30 expression was correlated with patient overall survival (OS), disease-free survival (DFS), pathologic variables, and other biomarkers. GPR30 expression was found in 69% of IBC cases. ER, PR, HER-2, and EGFR were found in 43, 35, 39, and 34% of IBC cases, respectively. GPR30 expression correlated inversely with ER expression (P = 0.02). Co-expression of ER and GPR30 was found in 24% of IBC samples; 19% expressed only ER and 46% expressed only GPR30. Univariate analysis showed no association between GPR30 expression and OS or DFS. However, co-expression of ER and GPR30 was associated with improved OS (P < 0.03) and marginally with DFS (P < 0.06); the absence of both ER and GPR30 was associated with worse OS and DFS (P = 0.03 for both). Multivariate analysis identified ER as an independent prognostic factor of OS (P = 0.008) and DFS (P = 0.02). The majority of IBC tumors are GPR30-positive, suggesting that estrogen signaling may be active in ER-negative IBC patients. These findings suggest potential new therapeutic targets for IBC such as novel endocrine agents or direct modulation of GPR30.

Two alternatively spliced GPR39 transcripts in seabream: molecular cloning, genomic organization, and regulation of gene expression by metabolic signals.

PubMed

Zhang, Yong; Liu, Yun; Huang, Xigui; Liu, Xiaochun; Jiao, Baowei; Meng, Zining; Zhu, Pei; Li, Shuisheng; Lin, Haoran; Cheng, Christopher H K

2008-12-01

Two GPR39 transcripts, designated as sbGPR39-1a and sbGPR39-1b, were identified in black seabream (Acanthopagrus schlegeli). The deduced amino acid (aa) sequence of sbGPR39-1a contains 423 residues with seven putative transmembrane (TM) domains. On the other hand, sbGPR39-1b contains 284 aa residues with only five putative TM domains. Northern blot analysis confirmed the presence of two GPR39 transcripts in the seabream intestine, stomach, and liver. Apart from seabream, the presence of two GPR39 transcripts was also found to exist in a number of teleosts (zebrafish and pufferfish) and mammals (human and mouse). Analysis of the GPR39 gene structure in different species suggests that the two GPR39 transcripts are generated by alternative splicing. When the seabream receptors were expressed in cultured HEK293 cells, Zn(2)(+) could trigger sbGPR39-1a signaling through the serum response element pathway, but no such functionality could be detected for the sbGPR39-1b receptor. The two receptors were found to be differentially expressed in seabream tissues. sbGPR39-1a is predominantly expressed in the gastrointestinal tract. On the other hand, sbGPR39-1b is widely expressed in most central and peripheral tissues except muscle and ovary. The expression of sbGPR39-1a in the intestine and the expression of sbGPR39-1b in the hypothalamus were decreased significantly during food deprivation in seabream. On the contrary, the expression of the GH secretagogue receptors (sbGHSR-1a and sbGHSR-1b) was significantly increased in the hypothalamus of the food-deprived seabream. The reciprocal regulatory patterns of expression of these two genes suggest that both of them are involved in controlling the physiological response of the organism during starvation.

Microwave tomography for an effective imaging in GPR on UAV/airborne observational platforms

NASA Astrophysics Data System (ADS)

Soldovieri, Francesco; Catapano, Ilaria; Ludeno, Giovanni

2017-04-01

GPR was originally thought as a non-invasive diagnostics technique working in contact with the underground or structure to be investigated. On the other hand, in the recent years several challenging necessities and opportunities entail the necessity to work with antenna not in contact with the structure to be investigated. This necessity arises for example in the case of landmine detection but also for cultural heritage diagnostics. Other field of application regards the forward-looking GPR aiming at shallower hidden targets forward the platfrom (vehicle) carrying the GPR [1]. Finally, a recent application is concerned with the deployment of airborne/UAV GPR, able to ensure several advantages in terms of large scale surveys and "freedom" of logistics constraint [2]. For all the above mentioned cases, the interest is towards the development of effective data processing able to make imaging task in real time. The presentation will show different data processing strategies, based on microwave tomography [1,2], for a reliable and real time imaging in the case of GPR platforms far from the interface of the structure/underground to be investigated. [1] I. Catapano, A. Affinito, A. Del Moro,.G. Alli, and F. Soldovieri, "Forward-Looking Ground-Penetrating Radar via a Linear Inverse Scattering Approach," IEEE Transactions on Geoscience and Remote Sensing, vol. 53, pp. 5624 - 5633, Oct. 2015. [2] I. Catapano, L. Crocco, Y. Krellmann, G. Triltzsch, and F. Soldovieri, "A tomographic approach for helicopter-borne ground penetrating radar imaging," IEEE Geosci. Remote Sens. Lett., vol. 9, no. 3, pp. 378-382, May 2012.

Ground Penetrating Radar Survey at Yoros Fortesss,Istanbul

NASA Astrophysics Data System (ADS)

Kucukdemirci, M.; Yalçın, A. B.

2016-12-01

Geophysical methods are effective tool to detect the archaeological remains and materials, which were hidden under the ground. One of the most frequently used methods for archaeological prospection is Ground Penetrating Radar (GPR). This paper illustrates the small scale GPR survey to determine the buried archaeological features around the Yoros Fortress, located on shores of the Bosporus strait in Istanbul, during the archaeological excavations. The survey was carried out with a GSSI SIR 3000 system, using 400 Mhz center frequency bistatic antenna with the configuration of 16 bits dynamic range and 512 samples per scan. The data were collected along parallel profiles with an interval of 0.50 meters with zigzag profile configuration on the survey grids. The GPR data were processed by GPR-Slice V.7 (Ground Penetrating Radar Imaging Software). As a result, in the first shallow depths, some scattered anomalies were detected. These can be related to a small portion of archaeological ruins close to the surface. In the deeper levels, the geometry of the anomalies related to the possible archaeological ruins, looks clearer. Two horizontal and parallel anomalies were detected, with the direction NS in the depth of 1.45 meters, possibly related to the ancient channels.

Genetic deletion of GPR52 enhances the locomotor-stimulating effect of an adenosine A2A receptor antagonist in mice: A potential role of GPR52 in the function of striatopallidal neurons.

PubMed

Nishiyama, Keiji; Suzuki, Hirobumi; Maruyama, Minoru; Yoshihara, Tomoki; Ohta, Hiroyuki

2017-09-01

G protein-coupled receptor 52 (GPR52) is largely co-expressed with dopamine D 2 receptor (DRD2) in the striatum and nucleus accumbens, and this expression pattern is similar to that of adenosine A 2A receptor (ADORA2A). GPR52 has been proposed as a therapeutic target for positive symptoms of schizophrenia, based on observations from pharmacological and transgenic mouse studies. However, the physiological role of GPR52 in dopaminergic functions in the basal ganglia remains unclear. Here, we used GPR52 knockout (KO) mice to examine the role of GPR52 in dopamine receptor-mediated and ADORA2A-mediated locomotor activity and dopamine receptor signaling. High expression of GPR52 protein in the striatum, nucleus accumbens, and lateral globus pallidus of wild type (WT) littermates was confirmed by immunohistochemical analysis. GPR52 KO and WT mice exhibited almost identical locomotor responses to the dopamine releaser methamphetamine and the N-methyl-d-aspartate antagonist MK-801. In contrast, the locomotor response to the ADORA2A antagonist istradefylline was significantly augmented in GPR52 KO mice compared to WT mice. Gene expression analysis revealed that striatal expression of DRD2, but not of dopamine D 1 receptor and ADORA2A, was significantly decreased in GPR52 KO mice. Moreover, a significant reduction in the mRNA expression of enkephalin, a marker of the activity of striatopallidal neurons, was observed in the striatum of GPR52 KO mice, suggesting that GPR52 deletion could enhance DRD2 signaling. Taken together, these results imply the physiological relevance of GPR52 in modulating the function of striatopallidal neurons, possibly by interaction of GPR52 with ADORA2A and DRD2. Copyright © 2017 Elsevier B.V. All rights reserved.

Geophysical Investigation of Subsurface Characteristics of Icy Debris Fans with Ground Penetrating Radar in the Wrangell Mountains, Alaska

NASA Astrophysics Data System (ADS)

Smith, T. D.; Jacob, R. W.

2013-12-01

Authors Tracey Smith^1, Rob Jacob^1, Jeffrey Trop^1, Keith Williams^2 and Craig Kochel^1 Bucknell University, Geology and Environmental Geoscience Department, Lewisburg, PA UNAVCO, 6350 Nautilus Dr., Boulder, CO 80301 Icy debris fans have recently been described as deglaciation features on Earth and similar features have been observed on Mars, however, the subsurface characteristics remain unknown. We used ground penetrating radar (GPR) to non-invasively investigate the subsurface characteristics of icy debris fans near McCarthy, Alaska, USA. The three fans investigated in Alaska are the East, West, and Middle fans which are between the Nabesna ice cap and the McCarthy Glacier. Icy debris fans in general are a largely unexplored suite of paraglacial landforms and processes in alpine regions. Recent field studies focused on direct observations and depositional processes. The results showed that each fan's composition is primarily influenced by the type and frequency of mass wasting processes that supply the fan. Photographic studies show that the East fan receives far more ice and snow avalanches whereas the Middle and West fan receive fewer mass wasting events but more clastic debris is deposited on the Middle and West fan from rock falls and icy debris flows. GPR profiles and WARR surveys consisting of both, common mid-point (CMP), and common shot-point (CSP) surveys investigated the subsurface geometry of the fans and the McCarthy Glacier.All GPR surveys were collected in 2013 with 100MHz bi-static antennas. Four axial profiles and three cross-fan profiles were done on the West and Middle fans as well as the McCarthy Glacier in order to investigate the relationship between the three features. Terrestrial laser surveying of the surface and real-time kinematic GPS provided the surface elevation used to correct the GPR data for topographic changes. GPR profiles yielded reflectors that were continuous for 10+ m and hyperbolic reflections in the subsurface. The WARR surveys provided the GPR signal velocity through the subsurface material and allowed transformation of two-way traveltimes (TWTT) in GPR profiles to be converted to depth. In addition, the eight WARR surveys spaced on the fans and on the glacier provide information on variability of subsurface velocities. The profiles of the Middle and West fan have more energy returning to the surface and therefore many more reflections than profiles done on the McCarthy Glacier. Based on the WARR surveys, we interpret the lower energy return in the glacier to be caused by two reasons. 1) The increased attenuation due to wet ice versus drier ice and on the fan with GPR velocities >0.15m/ns. 2) Lack of interfaces in the glacier compared to those in the fans which are produced by the events depositing material to an ablated icy debris fan surface. The GPR profiles on the West and Middle fans show multiple point scatters at TWTT of less than 200ns. The Middle fan is distinguished from the West fan by its multiple point scatters at TWTT greater than 200ns, clearly showing the Middle fan with a greater thickness. The observations from the GPR profiles correlate with the photographic evidence for types of processes and the composition of their deposits on each fan respectively.

COST Action TU1208 - Working Group 3 - Electromagnetic modelling, inversion, imaging and data-processing techniques for Ground Penetrating Radar

NASA Astrophysics Data System (ADS)

Pajewski, Lara; Giannopoulos, Antonios; Sesnic, Silvestar; Randazzo, Andrea; Lambot, Sébastien; Benedetto, Francesco; Economou, Nikos

2017-04-01

This work aims at presenting the main results achieved by Working Group (WG) 3 "Electromagnetic methods for near-field scattering problems by buried structures; data processing techniques" of the COST (European COoperation in Science and Technology) Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar" (www.GPRadar.eu, www.cost.eu). The main objective of the Action, started in April 2013 and ending in October 2017, is to exchange and increase scientific-technical knowledge and experience of Ground Penetrating Radar (GPR) techniques in civil engineering, whilst promoting in Europe the effective use of this safe non-destructive technique. The Action involves more than 150 Institutions from 28 COST Countries, a Cooperating State, 6 Near Neighbour Countries and 6 International Partner Countries. Among the most interesting achievements of WG3, we wish to mention the following ones: (i) A new open-source version of the finite-difference time-domain simulator gprMax was developed and released. The new gprMax is written in Python and includes many advanced features such as anisotropic and dispersive-material modelling, building of realistic heterogeneous objects with rough surfaces, built-in libraries of antenna models, optimisation of parameters based on Taguchi's method - and more. (ii) A new freeware CAD was developed and released, for the construction of two-dimensional gprMax models. This tool also includes scripts easing the execution of gprMax on multi-core machines or network of computers and scripts for a basic plotting of gprMax results. (iii) A series of interesting freeware codes were developed will be released by the end of the Action, implementing differential and integral forward-scattering methods, for the solution of simple electromagnetic problems by buried objects. (iv) An open database of synthetic and experimental GPR radargrams was created, in cooperation with WG2. The idea behind this initiative is to give researchers the opportunity of testing and validating, against reliable data, their electromagnetic-modelling, inversion, imaging and processing algorithms. One of the most interesting dataset comes from the IFSTTAR Geophysical Test Site, in Nantes (France): this is an open-air laboratory including a large and deep area, filled with various materials arranged in horizontal compacted slices, separated by vertical interfaces and water-tighted in surface; several objects as pipes, polystyrene hollows, boulders and masonry are embedded in the field. Data were collected by using nine different GPR systems and at different frequencies ranging from 200 MHz to 1 GHz. Moreover, some sections of this test site were modelled by using gprMax and the commercial software CST Microwave Studio. Hence, both experimental and synthetic data are available. Further interesting datasets were collected on roads, bridges, concrete cells, columns - and more. (v) WG3 contributed to the TU1208 Education Pack, an open educational package conceived to teach GPR in University courses. (vi) WG3 was very active in offering training activities. The following courses were successfully organised: Training School (TS) "Microwave Imaging and Diagnostics" (in cooperation with the European School of Antennas; 1st edition: Madonna di Campiglio, Italy, March 2014, 2nd edition: Taormina, Italy, October 2016); TS "Numerical modelling of Ground Penetrating Radar using gprMax" (Thessaloniki, Greece, November 2015); TS "Electromagnetic Modelling Techniques for Ground Penetrating Radar" (Split, Croatia, November 2016). Moreover, WG3 organized a workshop on "Electromagnetic modelling with the Finite-Difference Time-Domain technique" (Nantes, France, February 2014) and a workshop on "Electromagnetic modelling and inversion techniques for GPR" (Davos, Switzerland, April 2016) within the 2016 European Conference on Antennas and Propagation (EuCAP). Acknowledgement: The Authors are deeply grateful to COST (European COoperation in Science and Technology, www.cost.eu), for funding and supporting the COST Action TU1208 "Civil engineering applications of Ground Penetrating Radar" (www.GPRadar.eu).

Advanced GPR imaging of sedimentary features: integrated attribute analysis applied to sand dunes

NASA Astrophysics Data System (ADS)

Zhao, Wenke; Forte, Emanuele; Fontolan, Giorgio; Pipan, Michele

2018-04-01

We evaluate the applicability and the effectiveness of integrated GPR attribute analysis to image the internal sedimentary features of the Piscinas Dunes, SW Sardinia, Italy. The main objective is to explore the limits of GPR techniques to study sediment-bodies geometry and to provide a non-invasive high-resolution characterization of the different subsurface domains of dune architecture. On such purpose, we exploit the high-quality Piscinas data-set to extract and test different attributes of the GPR trace. Composite displays of multi-attributes related to amplitude, frequency, similarity and textural features are displayed with overlays and RGB mixed models. A multi-attribute comparative analysis is used to characterize different radar facies to better understand the characteristics of internal reflection patterns. The results demonstrate that the proposed integrated GPR attribute analysis can provide enhanced information about the spatial distribution of sediment bodies, allowing an enhanced and more constrained data interpretation.

Optimizing high-resolution melting analysis for the detection of mutations of GPR30/GPER-1 in breast cancer.

PubMed

Aihara, Masamune; Yamamoto, Shigeru; Nishioka, Hiroko; Inoue, Yutaro; Hamano, Kimikazu; Oka, Masaaki; Mizukami, Yoichi

2012-06-15

G protein-coupled receptor 30/G protein estrogen receptor-1 (GPR30/GPER-1) is a novel membrane receptor for estrogen whose mRNA is expressed at high levels in estrogen-dependent cells such as breast cancer cell lines. However, mutations in GRP30 related to diseases remain unreported. To detect unknown mutations in the GPR30 open reading frame (ORF) quickly, the experimental conditions for high-resolution melting (HRM) analysis were examined for PCR primers, Taq polymerases, saturation DNA binding dyes, Mg(2+) concentration, and normalized temperatures. Nine known SNPs and 13 artificial point mutations within the GPR30 ORF, as well as single nucleotide variants in DNA extracted from subjects with breast cancers were tested under the optimal experimental conditions. The combination of Expand High Fidelity(PLUS) and SYTO9 in the presence of 2.0 mM MgCl(2) produced the best separation in melting curves of mutations in all regions of the GPR30 ORF. Under these experimental conditions, the mutations were clearly detected in both heterozygotes and homozygotes. HRM analysis of GPR30 using genomic DNA from subjects with breast cancers showed a novel single nucleotide variant, 111C>T in GPR30 and 4 known SNPs. The experimental conditions determined in this study for HRM analysis are useful for high throughput assays to detect unknown mutations within the GPR30 ORF. Copyright © 2012 Elsevier B.V. All rights reserved.

GPR Image and Signal Processing for Pavement and Road Monitoring on Android Smartphones and Tablets

NASA Astrophysics Data System (ADS)

Benedetto, Francesco; Benedetto, Andrea; Tedeschi, Antonio

2014-05-01

Ground Penetrating Radar (GPR) is a geophysical method that uses radar pulses to image the subsurface. This non-destructive method uses electromagnetic radiation and detects the reflected signals from subsurface structures. It can detect objects, changes in material, and voids and cracks. GPR has many applications in a number of fields. In the field of civil engineering one of the most advanced technologies used for road pavement monitoring is based on the deployment of advanced GPR systems. One of the most relevant causes of road pavement damage is often referable to water intrusion in structural layers. In this context, GPR has been recently proposed as a method to estimate moisture content in a porous medium without preventive calibration. Hence, the development of methods to obtain an estimate of the moisture content is a crucial research field involving economic, social and strategic aspects in road safety for a great number of public and private Agencies. In particular, a recent new approach was proposed to estimate moisture content in a porous medium basing on the theory of Rayleigh scattering, showing a shift of the frequency peak of the GPR spectrum towards lower frequencies as the moisture content increases in the soil. Addressing some of these issues, this work proposes a mobile application, for smartphones and tablets, for GPR image and signal processing. Our application has been designed for the Android mobile operating system, since it is open source and android mobile platforms are selling the most smartphones in the world (2013). The GPR map can be displayed in black/white or color and the user can zoom and navigate into the image. The map can be loaded in two different ways: from the local memory of the portable device or from a remote server. This latter possibility can be very useful for real-time and mobile monitoring of road and pavement inspection. In addition, the application allows analyzing the GPR data also in the frequency domain. It is possible to visualize the GPR spectrum, and the application returns the (abscissa of the) frequency peak of the GPR spectrum. It is also possible to visualize more GPR spectra on the same figure, in order to understand if a frequency shift (related to moisture content) has been observed. Finally, the GPR spectra can be exported as a JPEG file. This application has a strategic and innovative potentiality for all the Agencies involved in roads and highway management in order to improve the onsite efficiency and effectiveness of the works. ACKNOWLEDGMENT This work is a contribution to COST Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar."

Semblance analysis to assess GPR data from a five-year forensic study of simulated clandestine graves

NASA Astrophysics Data System (ADS)

Booth, Adam D.; Pringle, Jamie K.

2016-02-01

Ground penetrating radar (GPR) surveys have proven useful for locating clandestine graves in a number of forensic searches. There has been extensive research into the geophysical monitoring of simulated clandestine graves in different burial scenarios and ground conditions. Whilst these studies have been used to suggest optimum dominant radar frequencies, the data themselves have not been quantitatively analysed to-date. This study uses a common-offset configuration of semblance analysis, both to characterise velocity trends from GPR diffraction hyperbolae and, since the magnitude of a semblance response is proportional to signal-to-noise ratio, to quantify the strength of a forensic GPR response. 2D GPR profiles were acquired over a simulated clandestine burial, with a wrapped-pig cadaver monitored at three-month intervals between 2008 and 2013 with GPR antennas of three different centre-frequencies (110, 225 and 450 MHz). The GPR response to the cadaver was a strong diffraction hyperbola. Results show, in contrast to resistivity surveys, that semblance analysis have little sensitivity to changes attributable to decomposition, and only a subtle influence from seasonality: velocity increases (0.01-0.02 m/ns) were observed in summer, associated with a decrease (5-10%) in peak semblance magnitude, SM, and potentially in the reflectivity of the cadaver. The lowest-frequency antennas consistently gave the highest signal-to-noise ratio although the grave was nonetheless detectable by all frequencies trialled. These observations suggest that forensic GPR surveys could be undertaken with little seasonal hindrance. Whilst GPR analysis cannot currently provide a quantitative diagnostic proxy for time-since-burial, the consistency of responses suggests that graves will remain detectable beyond the five years shown here.

Civil Engineering Applications of Ground Penetrating Radar: Research Perspectives in COST Action TU1208

NASA Astrophysics Data System (ADS)

Pajewski, Lara; Benedetto, Andrea; Loizos, Andreas; Slob, Evert; Tosti, Fabio

2013-04-01

Ground Penetrating Radar (GPR) is a safe, non-destructive and non-invasive imaging technique that can be effectively used for advanced inspection of composite structures and for diagnostics affecting the whole life-cycle of civil engineering works. GPR provides high resolution images of structures and subsurface through wide-band electromagnetic waves. It can be employed for the surveying of roads, pavements, bridges, tunnels, for detecting underground cavities and voids, for utility sensing, for the inspection of buildings, reinforced concrete and pre-cast concrete structures, for geotechnical investigation, in foundation design, as well as for several other purposes. Penetration and resolution of GPR depend primarily on the transmitting frequency of the equipment, the antenna characteristics, the electrical properties of the ground or of the surveyed material, and the contrasting electrical properties of the targets with respect to the surrounding medium. Generally there is a direct relationship between the transmitter frequency and the resolution that can be obtained; conversely there is an inverse relationship between frequency and penetration depth. GPR works best in dry ground environments, but can also give good results in wet, saturated materials; it does not work well in saline conditions, in high-conductivity media and through dense clays which limit signal penetration. Different approaches can be employed in the processing of collected GPR data. Once data have been processed, they still have to be analysed. This is a challenging problem, since interpretation of GPR radargrams is typically non-intuitive and considerable expertise is needed. In the presence of a complex scenario, an accurate electromagnetic forward solver is a fundamental tool for the validation of data interpretation. It can be employed for the characterization of scenarios, as a preliminary step that precedes a survey, or to gain a posteriori a better understanding of measured data. It can be used by GPR operators to identify the signatures generated by uncommon targets or by composite structures. Repeated evaluations of the electromagnetic field scattered by known targets can be performed by a forward solver, in order to estimate - through comparison with measured data - the physics and geometry of the region investigated by the GPR. It is possible to identify three main areas, in the GPR field, that have to be addressed in order to promote the use of this technology in the civil engineering. These are: a) increase of the system sensitivity to enable the usability in a wider range of conditions; b) research novel data processing algorithms/analysis tools for the interpretation of GPR results; c) contribute to the development of new standards and guidelines and to training of end users, that will also help to increase the awareness of operators. In this framework, the COST Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar", proposed by Lara Pajewski, "Roma Tre" University, Rome, Italy, has been approved in November 2012 and is going to start in April 2013. It is a 4-years ambitious project already involving 17 European Countries (AT, BE, CH, CZ, DE, EL, ES, FI, FR, HR, IT, NL, NO, PL, PT, TR, UK), as well as Australia and U.S.A. The project will be developed within the frame of a unique approach based on the integrated contribution of University researchers, software developers, geophysics experts, Non-Destructive Testing equipment designers and producers, end users from private companies and public agencies. The main objective of the COST Action TU1208 is to exchange and increase scientific-technical knowledge and experience of GPR techniques in civil engineering, whilst promoting the effective use of this safe and non-destructive technique in the monitoring of systems. In this interdisciplinary Action, advantages and limitations of GPR will be highlighted, leading to the identification of gaps in knowledge and technology. Protocols and guidelines for European Standards will be developed, for an effective application of GPR in civil engineering. A novel GPR will be designed and realized: a multi-static system, with dedicated software and calibration procedures, able to construct real-time lane three-dimensional high resolution images of investigated areas. Advanced electromagnetic-scattering and data-processing techniques will be developed. The understanding of relationships between geophysical parameters and civil-engineering needs will be improved. Freeware software will be released, for inspection and monitoring of structures and infrastructures, buried-object localization, shape reconstruction and estimation of useful parameters. A high level training program will be organized. Mobility of early career researchers will be encouraged. The scientific work-plan of the Action is open, to ensure that experts all over the world, who did not participate in the preparation of the proposal but are interested in the project, may join the Action and participate in its activities. More information about the project can be found at http://www.cost.eu/domains_actions/tud/Actions/TU1208.

Attribute classification for generating GPR facies models

NASA Astrophysics Data System (ADS)

Tronicke, Jens; Allroggen, Niklas

2017-04-01

Ground-penetrating radar (GPR) is an established geophysical tool to explore near-surface sedimentary environments. It has been successfully used, for example, to reconstruct past depositional environments, to investigate sedimentary processes, to aid hydrogeological investigations, and to assist in hydrocarbon reservoir analog studies. Interpreting such 2D/3D GPR data, usually relies on concepts known as GPR facies analysis, in which GPR facies are defined as units composed of characteristic reflection patterns (in terms of reflection amplitude, continuity, geometry, and internal configuration). The resulting facies models are then interpreted in terms of depositional processes, sedimentary environments, litho-, and hydrofacies. Typically, such GPR facies analyses are implemented in a manual workflow being laborious and rather inefficient especially for 3D data sets. In addition, such a subjective strategy bears the potential of inconsistency because the outcome depends on the expertise and experience of the interpreter. In this presentation, we investigate the feasibility of delineating GPR facies in an objective and largely automated manner. Our proposed workflow relies on a three-step procedure. First, we calculate a variety of geometrical and physical attributes from processed 2D and 3D GPR data sets. Then, we analyze and evaluate this attribute data base (e.g., using statistical tools such as principal component analysis) to reduce its dimensionality and to avoid redundant information, respectively. Finally, we integrate the reduced data base using tools such as composite imaging, cluster analysis, and neural networks. Using field examples that have been acquired across different depositional environments, we demonstrate that the resulting 2D/3D facies models ease and improve the interpretation of GPR data. We conclude that our interpretation strategy allows to generate GPR facies models in a consistent and largely automated manner and might be helpful in variety near-surface applications.

Ground penetrating radar (GPR) analysis : Phase I.

DOT National Transportation Integrated Search

2009-11-01

"The objective of this work is to evaluate the feasibility of expanding the MDT's Ground Penetrating : Radar (GPR) program to a broader range of pavement evaluation activities. Currently, MDT uses GPR in : conjunction with its Falling Weight Deflecto...

Attenuation of inflammatory and neuropathic pain behaviors in mice through activation of free fatty acid receptor GPR40.

PubMed

Karki, Prasanna; Kurihara, Takashi; Nakamachi, Tomoya; Watanabe, Jun; Asada, Toshihide; Oyoshi, Tatsuki; Shioda, Seiji; Yoshimura, Megumu; Arita, Kazunori; Miyata, Atsuro

2015-02-12

The G-protein-coupled receptor 40 (GPR40) is suggested to function as a transmembrane receptor for medium- to long-chain free fatty acids and is implicated to play a role in free fatty acids-mediated enhancement of glucose-stimulated insulin secretion from pancreas. However, the functional role of GPR40 in nervous system including somatosensory pain signaling has not been fully examined yet. Intrathecal injection of GPR40 agonist (MEDICA16 or GW9508) dose-dependently reduced ipsilateral mechanical allodynia in CFA and SNL models and thermal hyperalgesia in carrageenan model. These anti-allodynic and anti-hyperalgesic effects were almost completely reversed by a GPR40 antagonist, GW1100. Immunohistochemical analysis revealed that GPR40 is expressed in spinal dorsal horn and dorsal root ganglion neurons, and immunoblot analysis showed that carrageenan or CFA inflammation or spinal nerve injury resulted in increased expression of GPR40 in these areas. Patch-clamp recordings from spinal cord slices exhibited that bath-application of either MEDICA16 or GW9508 significantly decreased the frequency of spontaneous excitatory postsynaptic currents in the substantia gelatinosa neurons of the three pain models. Our results indicate that GPR40 signaling pathway plays an important suppressive role in spinal nociceptive processing after inflammation or nerve injury, and that GPR40 agonists might serve as a new class of analgesics for treating inflammatory and neuropathic pain.

RNAi targeting GPR4 influences HMEC-1 gene expression by microarray analysis

PubMed Central

Ren, Juan; Zhang, Yuelang; Cai, Hui; Ma, Hongbing; Zhao, Dongli; Zhang, Xiaozhi; Li, Zongfang; Wang, Shufeng; Wang, Jiangsheng; Liu, Rui; Li, Yi; Qian, Jiansheng; Wei, Hongxia; Niu, Liying; Liu, Yan; Xiao, Lisha; Ding, Muyang; Jiang, Shiwen

2014-01-01

G-protein coupled receptor 4 (GPR4) belongs to a protein family comprised of 3 closely related G protein-coupled receptors. Recent studies have shown that GPR4 plays important roles in angiogenesis, proton sensing, and regulating tumor cells as an oncogenic gene. How GPR4 conducts its functions? Rare has been known. In order to detect the genes related to GPR4, microarray technology was employed. GPR4 is highly expressed in human vascular endothelial cell HMEC-1. Small interfering RNA against GPR4 was used to knockdown GPR4 expression in HMEC-1. Then RNA from the GPR4 knockdown cells and control cells were analyzed through genome microarray. Microarray results shown that among the whole genes and expressed sequence tags, 447 differentially expressed genes were identified, containing 318 up-regulated genes and 129 down-regulated genes. These genes whose expression dramatically changed may be involved in the GPR4 functions. These genes were related to cell apoptosis, cytoskeleton and signal transduction, cell proliferation, differentiation and cell-cycle regulation, gene transcription and translation and cell material and energy metabolism. PMID:24753754

GPR21 KO mice demonstrate no resistance to high fat diet induced obesity or improved glucose tolerance.

PubMed

Wang, Jinghong; Pan, Zheng; Baribault, Helene; Chui, Danny; Gundel, Caroline; Véniant, Murielle

2016-01-01

Gpr21 KO mice generated with Gpr21 KO ES cells obtained from Deltagen showed improved glucose tolerance and insulin sensitivity when fed a high fat diet. Further mRNA expression analysis revealed changes in Rabgap1 levels and raised the possibility that Rabgap1 gene may have been modified. To assess this hypothesis a new Gpr21 KO mouse line using TALENS technology was generated. Gpr21 gene deletion was confirmed by PCR and Gpr21 and Rabgap1 mRNA expression levels were determined by RT-PCR. The newly generated Gpr21 KO mice when fed a normal or high fat diet chow did not maintain their improved metabolic phenotype. In conclusion, Rabgap1 disturbance mRNA expression levels may have contributed to the phenotype of the originally designed Gpr21 KO mice.

The association of GPR85 with PSD-95-neuroligin complex and autism spectrum disorder: a molecular analysis.

PubMed

Fujita-Jimbo, Eriko; Tanabe, Yuko; Yu, Zhiling; Kojima, Karin; Mori, Masato; Li, Hong; Iwamoto, Sadahiko; Yamagata, Takanori; Momoi, Mariko Y; Momoi, Takashi

2015-01-01

Autism spectrum disorder (ASD) has a complex genetic etiology. Some symptoms and mutated genes, including neuroligin (NLGN), neurexin (NRXN), and SH3 and multiple ankyrin repeat domains protein (SHANK), are shared by schizophrenia and ASD. Little is known about the molecular pathogenesis of ASD. One of the possible molecular pathogenesis is an imbalance of excitatory and inhibitory receptors linked with the NLGN-PSD-95-SHANK complex via postsynaptic density protein/Drosophila disc large tumor suppressor/zonula occludens-1 protein (PDZ) binding. In the present study, we focused on GPR85 as a candidate gene for ASD because the C-terminal amino acid sequence of GPR85 [Thr-Cys-Val-Ile (YCVI)] is classified as a type II PDZ-binding motif, and GPR85 is a risk factor for schizophrenia. GPR85 is an orphan receptor that regulates neural and synaptic plasticity and modulates diverse behaviors, including learning and memory. While searching for molecules that associate with GPR85, we found that GPR85 was associated with postsynaptic density protein (PSD)-95 linked with NLGN in the brain. We examined the proteins that associate with the C-terminal sequence of GPR85 by pull-down assay and immunoblot analysis and searched for a mutation of the GPR85 gene in patients with ASD. We used immunostaining to examine the intracellular localization of mutated GPR85 and its influence on the morphology of cells and neurons. The C-terminal sequence of GPR85 interacted with PSD-95 at PDZ1, while NLGN interacted with PSD-95 at PDZ3. Two male patients with ASD from independent Japanese families possessed inherited missense mutations at conserved sites in GPR85: one had T1033C (M152T) and the other had G1239T (V221L). These mutations were located in a domain related to G protein interaction and signal transduction. In contrast to wild-type GPR85, mutated GPR85 was more preferentially accumulated, causing endoplasmic reticulum stress, and disturbed the dendrite formation of hippocampal neurons. GPR85 associated with the PSD-95 linked with NLGN, which is related to ASD. GPR85 carrying the mutations detected in ASD patients disturbed dendrite formation that could be the candidate for molecular pathogenesis of ASD through the associated NLGN-PSD-95 receptor complex.

The contribution of GPR98 and DFNB31 genes to a Spanish Usher syndrome type 2 cohort.

PubMed

García-García, Gema; Besnard, Thomas; Baux, David; Vaché, Christel; Aller, Elena; Malcolm, Sue; Claustres, Mireille; Millan, Jose M; Roux, Anne-Françoise

2013-01-01

Usher syndrome type 2 (USH2) is an autosomal recessive disease characterized by moderate to severe hearing loss and retinitis pigmentosa. To date, three disease-causing genes have been identified, USH2A, GPR98, and DFNB31, of which USH2A is clearly the major contributor. The aim of this work was to determine the contribution of GPR98 and DFNB31 genes in a Spanish cohort of USH2A negative patients using exhaustive molecular analysis, including sequencing, dosage, and splicing analysis. Linkage analysis was performed to prioritize the gene to study, followed by sequencing of exons and intron-exon boundaries of the selected gene, GPR98 (90 exons) or DFNB31 (12 exons). Functional splicing analyses and comparative genomic hybridization array to detect large rearrangements were performed when appropriate. We confirmed that mutations in GPR98 contribute a significant but minor role to Usher syndrome type 2. In a group of patients referred for molecular diagnosis, 43 had been found to be positive for USH2A mutations, the remaining 19 without USH2A alterations were screened, and seven different mutations were identified in the GPR98 gene in seven patients (five in the homozygous state), of which six were novel. All detected mutations result in a truncated protein; deleterious missense mutations were not found. No pathological mutations were identified in the DFNB31 gene. In Spain, USH2A and GPR98 are responsible for 95.8% and 5.2% of USH2 mutated cases, respectively. DFNB31 plays a minor role in the Spanish population. There was a group of patients in whom no mutation was found. These findings confirm the importance of including at least GPR98 analysis for comprehensive USH2 molecular diagnosis.

Evidence of alterations in the expression of orphan receptors GPR26 and GPR39 due to the etiology of the metabolic syndrome.

PubMed

Romero-Nava, Rodrigo; Zhou, De-Shan; García, Noemí; Ruiz-Hernández, Armando; Si, Yin-Chu; Sánchez-Muñoz, Fausto; Huang, Fengyang; Hong, Enrique; Villafaña, Santiago

2017-08-01

Metabolic syndrome (MS) is composed of several metabolic abnormalities that increase the risk of cardiovascular diseases and diabetes. Although there are treatments for the components of MS, this pathology maintains a high mortality, suggesting that there are other mechanisms in which orphan receptors such as GPR26 and GPR39 may be involved. For this reason, the aim of this work was to evaluate the expression of GPR26 and GPR39 orphan receptors in two models of MS (diet and genetics). We used male Wistar rats, which received 70% fructose in drinking water for 9 weeks, and obese Zucker rats. We measured weight, blood pressure, glucose, triglycerides, total cholesterol, HDL cholesterol, LDL cholesterol to determine the MS and the expression of the orphan receptors GPR26 and GPR39 in brain, heart, aorta, liver, and kidney by RT-PCR. The analysis of the expression of the orphan receptors GPR26 and GPR39 showed that the receptors are expressed in some tissues, but the expression of the GPR26 tends to decrease in the heart and aorta, whereas in the brain, no changes were observed, this receptor is not expressed in the liver and kidney of both strains. The expression of GPR39 isoforms depends on the tissue and MS model. We conclude that the orphan receptors GPR26, GPR39v1, and GPR39v2 are expressed in different tissues and their profile expression is dependent on the etiology of the MS.

Development of SAP-DoA techniques for GPR data processing within COST Action TU1208

NASA Astrophysics Data System (ADS)

Meschino, Simone; Pajewski, Lara; Marciniak, Marian

2016-04-01

This work focuses on the use of Sub-Array Processing (SAP) and Direction of Arrival (DoA) approaches for the processing of Ground-Penetrating Radar data, with the purpose of locating metal scatterers embedded in concrete or buried in the ground. Research activities have been carried out during two Short-Term Scientific Missions (STSMs) funded by the COST (European COoperation in Science and Technology) Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar" in May 2015 and January 2016. In applications involving smart antennas and in the presence of several transmitters operating simultaneously, it is important for a receiving array to be able to estimate the Direction of Arrival (DoA) of the incoming signals, in order to decipher how many emitters are present and predict their positions. A number of methods have been devised for DoA estimation: the MUltiple SIgnal Classification (MUSIC) and Estimation of Signal Parameters via Rotational Invariance Technique (ESPRIT) are amongst the most popular ones [1]. In the scenario considered by us, the electromagnetic sources are the currents induced on metal elements embedded in concrete or buried in the ground. GPR radargrams are processed, to estimate the DoAs of the electric field back-scattered by the sought targets. In order to work in near-field conditions, a sub-array processing (SAP) approach is adopted: the radargram is partitioned in sub-radargrams composed of few A-scans each, the dominant DoA is predicted for each sub-radargram. The estimated angles are triangulated, obtaining a set of crossings with intersections condensed around object locations. This pattern is filtered, in order to remove a noisy background of unwanted crossings, and is processed by applying the statistical procedure described in [2]. We tested our approach on synthetic GPR radargrams, obtained by using the freeware simulator gprMax implementing the Finite-Difference Time-Domain method [3]. In particular, we worked with the reference data of TU1208 Concrete Cells 1.1-1.3 [4]. Preliminary results and a description of the method have been presented in [5]. Further results have been obtained by processing radargrams obtained in the presence of modified versions of the TU1208 Concrete Cells, where we changed the positions of the reinforcing elements. As expected, we achieved better results when the distance between the scatterers was larger and their interaction weaker. By analysing in depth the results obtained for the enlarged versions of Cells 1.1-1.3, we could assess in a comprehensive way the accuracy and limits of our approach in the presence of multiple scatterers, versus their relative distance. During future STSMs, we look forward to testing our approach on experimental data. We also plan to improve the method, in order to exploit in a more advanced way the multi-frequency information enclosed in the GPR data. A final STSM will be devoted to implementing a graphical-user interface and writing a user manual, as we intend to release our codes for free public download by the end of the Action.

Exploiting spectral content for image segmentation in GPR data

NASA Astrophysics Data System (ADS)

Wang, Patrick K.; Morton, Kenneth D., Jr.; Collins, Leslie M.; Torrione, Peter A.

2011-06-01

Ground-penetrating radar (GPR) sensors provide an effective means for detecting changes in the sub-surface electrical properties of soils, such as changes indicative of landmines or other buried threats. However, most GPR-based pre-screening algorithms only localize target responses along the surface of the earth, and do not provide information regarding an object's position in depth. As a result, feature extraction algorithms are forced to process data from entire cubes of data around pre-screener alarms, which can reduce feature fidelity and hamper performance. In this work, spectral analysis is investigated as a method for locating subsurface anomalies in GPR data. In particular, a 2-D spatial/frequency decomposition is applied to pre-screener flagged GPR B-scans. Analysis of these spatial/frequency regions suggests that aspects (e.g. moments, maxima, mode) of the frequency distribution of GPR energy can be indicative of the presence of target responses. After translating a GPR image to a function of the spatial/frequency distributions at each pixel, several image segmentation approaches can be applied to perform segmentation in this new transformed feature space. To illustrate the efficacy of the approach, a performance comparison between feature processing with and without the image segmentation algorithm is provided.

GPR Technologies and Methodologies in Italy: A Review

NASA Astrophysics Data System (ADS)

Benedetto, Andrea; Frezza, Fabrizio; Manacorda, Guido; Massa, Andrea; Pajewski, Lara

2014-05-01

GPR techniques and technologies have been subject of intense research activities at the Italian level in the last 15 years because of their potential applications specifically to civil engineering. More in detail, several innovative approaches and models have been developed to inspect road pavements to measure the thickness of their layers as well as to diagnose or prevent damage. Moreover, new frontiers in bridge inspection as well as in geotechnical applications such as slides and flows have been investigated using GPR. From the methodological viewpoint, innovative techniques have been developed to solve GPR forward-scattering problems, as well to locate and classify subsurface targets in real-time and to retrieve their properties through multi-resolution strategies, and linear and non-linear methodologies. Furthermore, the application of GPR and other non-destructive testing methods in archaeological prospecting, cultural heritage diagnostics, and in the localization and detection of vital signs of trapped people has been widely investigated. More recently, new theoretical and empirical paradigms regarding water moisture evaluation in various porous media and soil characterization have been published as the results of long terms research activities. Pioneer studies are also currently under development with the scope to correlate GPR measurement with mechanical characteristics of bound and unbound construction materials. In such a framework, this abstract will be aimed at reviewing some of the most recent advances of GPR techniques and technologies within the Italian industrial and academic communities [also including their application within international projects such as FP7 ISTIMES (http://www.istimes.eu)], and at envisaging some of the most promising research trends currently under development. Acknowledgment - This work was supported by COST Action TU1208 'Civil Engineering Applications of Ground Penetrating Radar' References [1] M. Balsi, S. Esposito, F. Frezza, P. Nocito, L. Porrini, L. Pajewski, G. Schettini e C. Twizere, 'FDTD Simulation of GPR Measurements in a Laboratory Sandbox for Landmine Detection', Proc. IWAGPR 2009, Granada, Spagna, 27-29 maggio 2009, pp. 45-49. [2] M. Balsi, S. Esposito, F. Frezza, P. Nocito, P. M. Barone, S. E. Lauro, E. Mattei, E. Pettinelli, G. Schettini e C. Twizere, 'GPR Measurements and FDTD Simulations for Landmine Detection', Proc. XIII International Conference on Ground Penetrating Radar, 21-25 giugno 2010, Lecce, pp. 865-869. [3] M. Balsi, P. M. Barone, S. Esposito, F. Frezza, S. E. Lauro, P. Nocito, E. Pettinelli, G. Schettini e C. Twizere, 'FDTD Simulations and GPR Measurements for Land Mine Detection in a Controlled Environment', Atti XVIII Riunione Nazionale di Elettromagnetismo, Benevento, 6-10 settembre 2010, pp. 59-65. [4] M. Salucci, D. Sartori, N. Anselmi, A. Randazzo, G. Oliveri, and A. Massa, 'Imaging buried objects within the second-order born approximation through a multiresolution regularized Inexact-Newton method', 2013 International Symposium on Electromagnetic Theory (EMTS), (Hiroshima, Japan), May 20-24 2013. [5] L. Lizzi, F. Viani, P. Rocca, G. Oliveri, M. Benedetti and A. Massa, 'Three-dimensional real-time localization of subsurface objects - From theory to experimental validation,' 2009 IEEE International Geoscience and Remote Sensing Symposium, vol. 2, pp. II-121-II-124, 12-17 July 2009. [6] S. Meschino, L. Pajewski, M. Pastorino, A. Randazzo, and G. Schettini, 'Detection of Subsurface Metallic Utilities by Means of a SAP Technique: Comparing MUSIC- and SVM-Based Approaches', J. Appl. Geophy., vol. 97, pp. 60-68, Oct. 2013. [7] M. Pastorino, and A. Randazzo, 'Buried object detection by an Inexact-Newton applied to nonlinear inverse scattering', Int. J. of Microwave Sci. Technol., vol. 2012, Article ID 637301, 7 pages, 2012. [8] F. Soldovieri and L. Crocco, "Electromagnetic Tomography", in Subsurface Sensing, A. S. Turk, K. A. Hocaoglu, A. A. Vertiy ed., Wiley Series in Microwave and Optical Engineering (Volume 1), Sept. 2011, John Wiley & Sons, NY. [9] I. Catapano, L. Crocco, Y. Krellmann, G. Triltzsch, F. Soldovieri, "A Tomographic Approach for Helicopter-Borne Ground Penetrating Radar Imaging", IEEE Geosci. Rem. Sensing Lett., vol. 9, p. 378-382, 2012.

Gpr110 deficiency decelerates carcinogen-induced hepatocarcinogenesis via activation of the IL-6/STAT3 pathway

PubMed Central

Ma, Benting; Zhu, Junjie; Tan, Juan; Mao, Yulei; Tang, Lingyun; Shen, Chunling; Zhang, Hongxing; Kuang, Ying; Fei, Jian; Yang, Xiao; Wang, Zhugang

2017-01-01

Hepatocarcinogenesis is a complex process that includes pronounced necroinflammation, unregulated hepatocyte damage, subsequent extensive fibrosis, and carcinogenesis. GPR110 was an adhesion G protein-coupled receptor. Analysis of the expression pattern of Gpr110 in mice displayed that Gpr110 was expressed highly in liver, implicating the tissue compartments where Gpr110 could execute its functions, the role of Gpr110 in the physiological and pathological state of liver remains unclear. Based on a Gpr110 knockout mouse model, we evaluated the role of Gpr110 in hepatocarcinogenesis by using a carbon tetrachloride (CCl4)-induced liver injury and fibrosis model, as well as diethylnitrosamine (DEN) plus CCl4-induced liver cancer model. In this study, we found subdued chronic liver injury, reduced compensatory proliferation, lower liver fibrosis, but enhanced inflammation occurred in Gpr110-/- mice during CCl4 challenge. In addition, Gpr110-/- mice were resistant to liver tumorigenesis induced by DEN plus CCl4 injection. Molecular mechanisms underlying these differences correlated with augmented activation of the IL-6/STAT3 pathway, which exerted hepatoprotective effects during liver damage, fibrosis, and oncogenesis in Gpr110-/- mice. Furthermore, pharmacological inhibition of the activation of the IL-6/STAT3 pathway enhanced hepatic fibrosis and promoted DEN plus CCl4-induced carcinogenesis in Gpr110-/- mice. In summary, absence of Gpr110 decelerates liver fibrosis/cirrhosis progressing into tumorigenesis, due to strengthening activation of the IL-6/STAT3 pathway, leading to a weaker liver injury and fibrosis microenvironment. It is indicated that targeting Gpr110 and activating the IL-6/STAT3 pathway may be considered to be preventive methods for some cirrhosis transition. PMID:28401002

Effectiveness of Global Postural Re-education for Treatment of Spinal Disorders: A Meta-analysis.

PubMed

Lomas-Vega, Rafael; Garrido-Jaut, María Victoria; Rus, Alma; Del-Pino-Casado, Rafael

2017-02-01

The aim of this study was to investigate the effects of global postural re-education (GPR) on the treatment of spinal disorders by performing a systematic review and a meta-analysis. MEDLINE, Scopus, and PEDro databases were searched without language or publication date restrictions. Data on pain and function were used to evaluate the effectiveness of GPR. Randomized controlled trials and controlled clinical trials analyzing the effectiveness of GPR on spinal disorders were selected. The standardized mean difference (SMD) and the corresponding 95% confidence interval (95% CI) were calculated. The meta-analysis was performed using the Comprehensive Meta-analysis 3.3 software. Seven randomized controlled trials and 4 controlled clinical trials were included in the meta-analysis. The results showed a medium improvement on pain (SMD = -0.63; 95% CI, -0.43 to -0.83) and function (SMD = -0.48; 95% CI, -0.25 to -0.72) after GPR treatment. The positive effect, which was greater in patients with ankylosing spondylitis followed by low back pain and neck pain, was more significant during the intermediate follow-up than immediately after treatment. This meta-analysis provides reliable evidence that GPR may be an effective method for treating spinal disorders by decreasing pain and improving function.

The contribution of GPR98 and DFNB31 genes to a Spanish Usher syndrome type 2 cohort

PubMed Central

García-García, Gema; Besnard, Thomas; Baux, David; Vaché, Christel; Aller, Elena; Malcolm, Sue; Claustres, Mireille; Millan, Jose M.

2013-01-01

Background Usher syndrome type 2 (USH2) is an autosomal recessive disease characterized by moderate to severe hearing loss and retinitis pigmentosa. To date, three disease-causing genes have been identified, USH2A, GPR98, and DFNB31, of which USH2A is clearly the major contributor. The aim of this work was to determine the contribution of GPR98 and DFNB31 genes in a Spanish cohort of USH2A negative patients using exhaustive molecular analysis, including sequencing, dosage, and splicing analysis. Methods Linkage analysis was performed to prioritize the gene to study, followed by sequencing of exons and intron-exon boundaries of the selected gene, GPR98 (90 exons) or DFNB31 (12 exons). Functional splicing analyses and comparative genomic hybridization array to detect large rearrangements were performed when appropriate. Results We confirmed that mutations in GPR98 contribute a significant but minor role to Usher syndrome type 2. In a group of patients referred for molecular diagnosis, 43 had been found to be positive for USH2A mutations, the remaining 19 without USH2A alterations were screened, and seven different mutations were identified in the GPR98 gene in seven patients (five in the homozygous state), of which six were novel. All detected mutations result in a truncated protein; deleterious missense mutations were not found. No pathological mutations were identified in the DFNB31 gene. Conclusions In Spain, USH2A and GPR98 are responsible for 95.8% and 5.2% of USH2 mutated cases, respectively. DFNB31 plays a minor role in the Spanish population. There was a group of patients in whom no mutation was found. These findings confirm the importance of including at least GPR98 analysis for comprehensive USH2 molecular diagnosis. PMID:23441107

NAPL detection with ground-penetrating radar (Invited)

NASA Astrophysics Data System (ADS)

Bradford, J. H.

2013-12-01

Non-polar organic compounds are common contaminants and are collectively referred to as nonaqueous-phase liquids (NAPLs). NAPL contamination problems occur in virtually every environment on or near the earth's surface and therefore a robust suite of geophysical tools is required to accurately characterize NAPL spills and monitor their remediation. NAPLs typically have low dielectric permittivity and low electric conductivity relative to water. Thus a zone of anomalous electrical properties often occurs when NAPL displaces water in the subsurface pore space. Such electric property anomalies make it possible to detect NAPL in the subsurface using electrical or electromagnetic geophysical methods including ground-penetrating radar (GPR). The GPR signature associated with the presence of NAPL is manifest in essentially three ways. First, the decrease in dielectric permittivity results in increased EM propagation velocity. Second, the decrease in permittivity can significantly change reflectivity. Finally, electric conductivity anomalies lead to anomalous GPR signal attenuation. The conductivity anomaly may be either high or low depending on the state of NAPL degradation, but with either high or low conductivity, GPR attenuation analysis can be a useful tool for identifying contaminated-zones. Over the past 15 years I have conducted numerous modeling, laboratory, and field tests to investigate the ability to use GPR to measure NAPL induced anomalies. The emphasis of this work has been on quantitative analysis to characterize critical source zone parameters such as NAPL concentration. Often, the contaminated zones are below the conventional resolution of the GPR signal and require thin layer analysis. Through a series of field examples, I demonstrate 5 key GPR analysis tools that can help identify and quantify NAPL contaminants. These tools include 1) GPR velocity inversion from multi-fold data, 2) amplitude vs offset analysis, 3) spectral decomposition, 4) frequency dependent attenuation analysis, and 5) reflectivity inversion. Examples are taken from a variety of applications that include oil spills on the ocean, oil spills on and under sea ice, and both LNAPL and DNAPL contaminated groundwater systems. Many factors conspire to complicate field data analysis, yet careful analysis and integration of multiple techniques has proven robust. Use of these methods in practical application has been slow to take root. Nonetheless, a best practices working model integrates geophysics from the outset and mirrors the approach utilized in hydrocarbon exploration. This model ultimately minimizes site characterization and remediation costs.

Attenuation analysis of real GPR wavelets: The equivalent amplitude spectrum (EAS)

NASA Astrophysics Data System (ADS)

Economou, Nikos; Kritikakis, George

2016-03-01

Absorption of a Ground Penetrating Radar (GPR) pulse is a frequency dependent attenuation mechanism which causes a spectral shift on the dominant frequency of GPR data. Both energy variation of GPR amplitude spectrum and spectral shift were used for the estimation of Quality Factor (Q*) and subsequently the characterization of the subsurface material properties. The variation of the amplitude spectrum energy has been studied by Spectral Ratio (SR) method and the frequency shift by the estimation of the Frequency Centroid Shift (FCS) or the Frequency Peak Shift (FPS) methods. The FPS method is more automatic, less robust. This work aims to increase the robustness of the FPS method by fitting a part of the amplitude spectrum of GPR data with Ricker, Gaussian, Sigmoid-Gaussian or Ricker-Gaussian functions. These functions fit different parts of the spectrum of a GPR reference wavelet and the Equivalent Amplitude Spectrum (EAS) is selected, reproducing Q* values used in forward Q* modeling analysis. Then, only the peak frequencies and the time differences between the reference wavelet and the subsequent reflected wavelets are used to estimate Q*. As long as the EAS is estimated, it is used for Q* evaluation in all the GPR section, under the assumption that the selected reference wavelet is representative. De-phasing and constant phase shift, for obtaining symmetrical wavelets, proved useful in the sufficiency of the horizons picking. Synthetic, experimental and real GPR data were examined in order to demonstrate the effectiveness of the proposed methodology.

The orphan G protein-coupled receptor 25 (GPR25) is activated by Apelin and Apela in non-mammalian vertebrates.

PubMed

Zhang, Jiannan; Wan, Yiping; Fang, Chao; Chen, Junan; Ouyang, Wangan; Li, Juan; Wang, Yajun

2018-06-22

G protein-coupled receptor 25 (GPR25) is an orphan G protein-coupled receptor in vertebrates, that has been implicated to be associated with autoimmune diseases and regulate blood pressure in humans. However, the endogenous ligand of GPR25 remains unknown in vertebrates. Here, we reported that in non-mammalian vertebrates (zebrafish, spotted gars, and pigeons), GPR25 could be activated by Apelin and Apela peptides, which are also the two endogenous ligands of vertebrate Apelin receptor (APLNR). Using the pGL3-CRE-luciferase reporter assay and confocal microscopy, we first demonstrated that like APLNR, zebrafish GPR25 expressing in HEK293 cells could be effectively activated by zebrafish Apelin and Apela peptides, leading to the inhibition of forskolin-stimulated cAMP production and receptor internalization. Like zebrafish GPR25, pigeon and spotted gar GPR25 could also be activated by Apelin and Apela, and their activation could inhibit forskolin-induced cAMP accumulation. Interestingly, unlike zebrafish (/spotted gar/pigeon) GPR25, human GPR25 could not be activated by Apelin and Apela under the same experimental conditions. RNA-seq analysis further revealed that GPR25 is expressed in a variety of tissues, including the testes and intestine of zebrafish/spotted gars/humans, implying the potential roles of GPR25 signaling in many physiological processes in vertebrates. Taken together, our data not only provides the first proof that the orphan receptor GPR25 possesses two potential ligands 'Apelin and Apela' and its activation decreases intracellular cAMP levels in non-mammalian vertebrates, but also facilitates to unravel the physiological roles of GPR25 signaling in vertebrates. Copyright © 2018 Elsevier Inc. All rights reserved.

Measuring the electrical properties of soil using a calibrated ground-coupled GPR system

USGS Publications Warehouse

Oden, C.P.; Olhoeft, G.R.; Wright, D.L.; Powers, M.H.

2008-01-01

Traditional methods for estimating vadose zone soil properties using ground penetrating radar (GPR) include measuring travel time, fitting diffraction hyperbolae, and other methods exploiting geometry. Additional processing techniques for estimating soil properties are possible with properly calibrated GPR systems. Such calibration using ground-coupled antennas must account for the effects of the shallow soil on the antenna's response, because changing soil properties result in a changing antenna response. A prototype GPR system using ground-coupled antennas was calibrated using laboratory measurements and numerical simulations of the GPR components. Two methods for estimating subsurface properties that utilize the calibrated response were developed. First, a new nonlinear inversion algorithm to estimate shallow soil properties under ground-coupled antennas was evaluated. Tests with synthetic data showed that the inversion algorithm is well behaved across the allowed range of soil properties. A preliminary field test gave encouraging results, with estimated soil property uncertainties (????) of ??1.9 and ??4.4 mS/m for the relative dielectric permittivity and the electrical conductivity, respectively. Next, a deconvolution method for estimating the properties of subsurface reflectors with known shapes (e.g., pipes or planar interfaces) was developed. This method uses scattering matrices to account for the response of subsurface reflectors. The deconvolution method was evaluated for use with noisy data using synthetic data. Results indicate that the deconvolution method requires reflected waves with a signal/noise ratio of about 10:1 or greater. When applied to field data with a signal/noise ratio of 2:1, the method was able to estimate the reflection coefficient and relative permittivity, but the large uncertainty in this estimate precluded inversion for conductivity. ?? Soil Science Society of America.

GPR Diagnostics of columns in archaeological contexts

NASA Astrophysics Data System (ADS)

Soldovieri, Francesco; Masini, Nicola; Persico, Raffaele; Catapano, Ilaria

2017-04-01

In the last decade the use of Ground Penetrating radar (GPR) applied to cultural heritage has been strongly increasing thanks to both technological development of sensors and softwares for data processing and cultural reasons such as the increasing awareness of conservators and archaeologist of the benefits of this method in terms of reduction of costs and time and risk associated with restoration works. This made GPR a mature technique for investigating different types of works of art and building elements of historical interest, including masonry structures, frescoes, mosaics [1-3], in the context of scientific projects, decision support activities aimed at the diagnosis of decay pathologies, and educational activities. One of the most complex building elements to be investigated by GPR are the columns both for the geometry of the object and for the several expected features to be detected including fractures, dishomogeneities and metallic connection elements. The work deals with the Ground Penetrating Radar diagnostic surveys at the prestigious archaeological site of Pompei. In particular, GPR surveys were carried out in two different areas, Palestra Grande and Tempio di Giove. The first campaign was carried out also as educational activity of the "International School "GEOPHYSICS AND REMOTE SENSING FOR ARCHAEOLOGY". The School aimed at giving the opportunity to scholars, PhD students, researchers and specialists in Geophysics, Remote Sensing and Archaeology to deepen their knowledge and expertise with geophysical and remote sensing techniques for archaeology and cultural heritage documentation and management. This survey was carried on two kinds of columns, with circular and rectangular section in order to detect possible hidden defects affecting their integrity. The second survey was carried out at Tempio di Giove, on request of the Soprintendenza Pompei, in order to gain information about the presence of reinforcement structures, which may be put inside the columns during a previous work carried out about thirty years ago and whose memory documentation was lost. Both the GPR surveys were carried out by using the K2-RIS IDS system equipped with a high frequency antenna, working at the central frequency of 2GHz. Moreover, the imaging results have been obtained by processing the raw data by means of the end-user friendly software interface designed at the Institute for Electromagnetic Sensing of the Environment - National Research Council of Italy. This interface was some years ago to make possible a simple management of 2D and 3D microwave tomographic approaches based on the Born approximation [4-6].The GPR surveys have confirmed the presence of metallic elements inside few of the investigated columns. [1] Masini N., Nuzzo L., Rizzo E. 2007, GPR investigations for the study and the restoration of the Rose Window of Troia Cathedral (Southern Italy), Near Surface Geophysics, 5 (5), pp. 287-300, doi: 10.3997/1873-0604.2007010 [2] Leucci G., Masini N., Persico R., Soldovieri F. 2011. GPR and sonic tomography for structural restoration: the case of the cathedral of Tricarico, Journal of Geophysics and Engineering, 8 (3), 76-92, doi: 10.1088/1742-2132/8/3/S08 [3] Masini N., Persico R., Rizzo E., Calia A., Giannotta M.T., Quarta G., Pagliuca A. 2010, Integrated Techniques for Analysis and Monitoring of Historical Monuments: the case of S.Giovanni al Sepolcro in Brindisi (Southern Italy), Near Surface Geophysics, 8(5), 423-432, doi:10.3997/1873-0604.2010012 [4] F. Soldovieri, J. Hugenschmidt, R. Persico, G. Leone, A linear inverse scattering algorithm for realistic GPR applications. Near Surf. Geophys. 5(1), 29-42 (2007) [5] I. Catapano, A. Affinito, G. Gennarelli, F.di Maio, A. Loperte, F. Soldovieri, "Full three-dimensional imaging via ground penetrating radar: assessment in controlled conditions and on field for archaeological prospecting", Appl. Phys. A, 2013 [6] I. Catapano, A. Affinito, F. Soldovieri, A user friendly interface for microwave tomography enhanced GPR surveys", EGU General Assembly 2013, vol. 15.

Functional analysis of free fatty acid receptor GPR120 in human eosinophils: implications in metabolic homeostasis.

PubMed

Konno, Yasunori; Ueki, Shigeharu; Takeda, Masahide; Kobayashi, Yoshiki; Tamaki, Mami; Moritoki, Yuki; Oyamada, Hajime; Itoga, Masamichi; Kayaba, Hiroyuki; Omokawa, Ayumi; Hirokawa, Makoto

2015-01-01

Recent evidence has shown that eosinophils play an important role in metabolic homeostasis through Th2 cytokine production. GPR120 (FFA4) is a G protein-coupled receptor (GPCR) for long-chain fatty acids that functions as a regulator of physiological energy metabolism. In the present study, we aimed to investigate whether human eosinophils express GPR120 and, if present, whether it possesses a functional capacity on eosinophils. Eosinophils isolated from peripheral venous blood expressed GPR120 at both the mRNA and protein levels. Stimulation with a synthetic GPR120 agonist, GW9508, induced rapid down-regulation of cell surface expression of GPR120, suggesting ligand-dependent receptor internalization. Although GPR120 activation did not induce eosinophil chemotactic response and degranulation, we found that GW9508 inhibited eosinophil spontaneous apoptosis and Fas receptor expression. The anti-apoptotic effect was attenuated by phosphoinositide 3-kinase (PI3K) inhibitors and was associated with inhibition of caspase-3 activity. Eosinophil response investigated using ELISpot assay indicated that stimulation with a GPR120 agonist induced IL-4 secretion. These findings demonstrate the novel functional properties of fatty acid sensor GPR120 on human eosinophils and indicate the previously unrecognized link between nutrient metabolism and the immune system.

GPR impedance inversion for imaging and characterization of buried archaeological remains: A case study at Mudu city cite in Suzhou, China

NASA Astrophysics Data System (ADS)

Liu, Yu; Shi, Zhanjie; Wang, Bangbing; Yu, Tianxiang

2018-01-01

As a method with high resolution, GPR has been extensively used in archaeological surveys. However, conventional GPR profile can only provide limited geometry information, such as the shape or location of the interface, but can't give the distribution of physical properties which could help identify the historical remains more directly. A common way for GPR to map parameter distribution is the common-midpoint velocity analysis, but it provides limited resolution. Another research hotspot, the full-waveform inversion, is unstable and relatively dependent on the initial model. Coring method could give direct information in drilling site, while the accurate result is only limited in several boreholes. In this paper, we propose a new scheme to enhance imaging and characterization of archaeological targets by fusion of GPR and coring data. The scheme mainly involves the impedance inversion of conventional common-offset GPR data, which uses well log to compensate GPR data and finally obtains a high-resolution estimation of permittivity. The core analysis result also contributes to interpretation of the inversion result. To test this method, we did a case study at Mudu city site in Suzhou, China. The results provide clear images of the ancient city's moat and wall subsurface and improve the characterization of archaeological targets. It is shown that this method is effective and feasible for archaeological exploration.

Ferrocene tripeptide Gly-Pro-Arg conjugates: synthesis and inhibitory effects on Alzheimer's Aβ(1-42) fibrillogenesis and Aβ-induced cytotoxicity in vitro.

PubMed

Zhou, Binbin; Li, Chun-Lan; Hao, Yuan-Qiang; Johnny, Muya Chabu; Liu, You-Nian; Li, Juan

2013-01-15

Alzheimer's disease (AD) is the most common cause of dementia, and currently there is no clinical treatment to cure it or to halt its progression. Aggregation and fibril formation of β-amyloid peptides (Aβ) are central events in the pathogenesis of AD. Many efforts have been spent on the development of effective inhibitors to prevent Aβ fibrillogenesis and cause disaggregation of preformed Aβ fibrils. In this study, the conjugates of ferrocene and Gly-Pro-Arg (GPR) tripeptide, Boc-Gly-Pro-Arg(NO(2))-Fca-OMe (4, GPR-Fca) and Fc-Gly-Pro-Arg-OMe (7, Fc-GPR) (Fc: ferrocene; Fca: ferrocene amino acid) were synthesized by HOBT/HBTU protocol in solution. These ferrocene GPR conjugates were employed to inhibit Aβ(1-42) fibrillogenesis and to disaggregate preformed Aβ fibrils. The inhibitory properties of ferrocene GPR conjugates on Aβ(1-42) fibrillogenesis were evaluated by thioflavin T (ThT) fluorescence assay, and confirmed by atomic force microscopy (AFM) analysis. The interaction between the ferrocene GPR conjugates and Aβ(1-42) was monitored by electrochemical means. Our results showed that both GPR and GPR-Fca can significantly inhibit the fibril formation of Aβ(1-42), and cause disaggregation of the preformed fibrils. As expected, GPR-Fca shows stronger inhibitory effect on Aβ(1-42) fibrillogenesis than that of its parent peptide GPR. In contrast, Fc-GPR shows no inhibitory effect on fibrillogenesis of Aβ(1-42). Furthermore, GPR-Fca demonstrates significantly protection against Aβ-induced cytotoxicity and exhibits high resistance to proteolysis and good lipophilicity. Copyright © 2012 Elsevier Ltd. All rights reserved.

GPR attenuation analyses using spectral ratios of primary and multiple arrivals: examples from Welsh peat bogs

NASA Astrophysics Data System (ADS)

Booth, A.; Carless, D.; Kulessa, B.

2014-12-01

Ground penetrating radar (GPR) is widely applied to qualitative and quantitative interpretation of near-surface targets. Surface deployments of GPR most widely characterise physical properties in terms of some measure of GPR wavelet velocity. Wavelet amplitude is less-often considered, potentially due to difficulties in measuring this quantity: amplitudes are distorted by the anisotropic radiation pattern of antennas, and the ringy GPR wavelet can make successive events difficult to isolate. However, amplitude loss attributes could provide a useful means of estimating the physical properties of a target. GPR energy loss is described by the bandwidth-limited quality factor Q* which, for low-loss media, is proportional to the ratio of dielectric permittivity, ɛ, and electrical conductivity, σ. Comparing the frequency content of two arrivals yields an estimate of interval Q*, but only if they are sufficiently distinct. There may be sufficient separation between a primary reflection and its long-path multiple (i.e. a 'repeat path' of the primary reflection) therefore a dataset that is rich in multiples may be suitable for robust Q* analysis. The Q* between a primary and multiple arrival describes all frequency-dependent loss mechanisms in the interval between the free-surface and the multiple-generating horizon: assuming that all reflectivity is frequency-independent, Q* can be used to estimate ɛ and/or σ. We measure Q* according to the spectral ratio method, for synthetic and real GPR datasets. Our simulations are performed using the finite-difference algorithm GprMax, and represent our example data of GPR acquisitions over peat bogs. These data are a series of 100 MHz GPR acquisitions over sites in the Brecon Beacons National Park of South Wales. The base of the bogs (the basal peat/mineral soil contact) is often a strong multiple-generating horizon. As an example, data from Waun Ddu bog show these events lagging by ~75 ns: GPR velocity is measured here at 0.034 m/ns (relative ɛ of 77.9) and spectral ratios suggest Q* of 19.9 [-6.6 +19.4]. This Q* implies that the bulk σ of the bog is 21.7 [-10.7 +10.8] mS/m. Our measurements require in situ verification (e.g. comparison with co-located electrical resistivity profiles) but our method provides a promising addition to the suite of GPR analysis tools.

Expression and prognostic role of orphan receptor GPR110 in glioma.

PubMed

Shi, Haiping; Zhang, Shiyuan

2017-09-16

Glioma is the most common type of malignancy in the central nervous system, which has a poor prognosis due to its rapid progression and diffuse invasion. Identification of novel biomarkers for glioma would be invaluable for studying disease mechanism and improving prognosis. Orphan G protein-coupled receptor 110 (GPR110) belongs to the subfamily VI of adhesion GPCR. The knowledge of the ligand, signaling pathway or physiology function of GPR110 is poorly elucidated. The potential role of GPR110 as an oncogene in mouse has been recently reported by mutagenesis screen. However, its expression and role in human glioma hasn't been identified. Here in the current study, we initially explored the RNA and protein expression of GPR110 in patients with glioma. Statistical analysis proved that GPR110 was highly expressed in some patients, which was correlated with advanced disease stages. Furthermore, univariate and multivariate analyses revealed its role as an independent prognostic biomarker for the overall survival of glioma patients. Interestingly, cellular studies showed that overexpression or knockdown of GPR110 in U87 cells didn't affect cell proliferation and migration. However, the invasion of U87 cells was significantly enhanced by GPR110-overepxression, while inhibited by GPR110-knockdown. The detailed mechanisms remain further investigation although our results suggested the possible participation of STAT3 instead of ERK in the GPR110 signaling pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

Differential expression of G-protein-coupled estrogen receptor-30 in human myometrial and uterine leiomyoma smooth muscle.

PubMed

Tian, Ruijuan; Wang, Zengyong; Shi, Zhan; Li, Dong; Wang, Yuebing; Zhu, Yingjun; Lin, Wanjun; Gui, Yu; Zheng, Xi-Long

2013-01-01

To determine differential expression of G-protein-coupled receptor 30 (GPR30) in uterine leiomyoma and its matched myometrium. GPR30 expression examined in both tissues and cultured cells. Research laboratories. Women 35 to 50 years old with uterine leiomyomas. Hysterectomy. GPR30 expression profile. Using Western blot and real-time quantitative polymerase chain reaction analyses, we found that GPR30 was highly expressed in uterine leiomyomas compared with their matched myometrium. In only three out of nine patients examined was GPR30 protein detectable by Western blot analysis in myometrial tissues, but at statistically significantly lower levels than in their leiomyomas. Confocal microscopy revealed the nuclear localization of GPR30 in leiomyoma tissues and cultured leiomyoma smooth muscle cells (SMCs). Treatment with 0.1 μM 17β-estradiol increased mRNA expression of GPR30 in leiomyoma SMCs but decreased expression in myometrial SMCs. Treatment with G-1, a GPR30 agonist, stimulated phosphorylation of p44/42 mitogen-activated protein kinase (MAPK) in both SMC types. PD98059, the MEK inhibitor, completely inhibited G-1-induced phosphorylation of p44/42 in myometrium SMCs, but not in SMCs from leiomyoma. GPR30 is abundantly expressed in uterine leiomyomas, likely resulting from estrogen stimulation. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

A neuropeptide ligand of the G protein-coupled receptor GPR103 regulates feeding, behavioral arousal, and blood pressure in mice.

PubMed

Takayasu, Shinobu; Sakurai, Takeshi; Iwasaki, Satoshi; Teranishi, Hitoshi; Yamanaka, Akihiro; Williams, S Clay; Iguchi, Haruhisa; Kawasawa, Yuka Imamura; Ikeda, Yukio; Sakakibara, Iori; Ohno, Kousaku; Ioka, Ryoichi X; Murakami, Saori; Dohmae, Naoshi; Xie, Jian; Suda, Toshihiro; Motoike, Toshiyuki; Ohuchi, Takashi; Yanagisawa, Masashi; Sakai, Juro

2006-05-09

Here, we report the isolation and characterization of an endogenous peptide ligand of GPR103 from rat brains. The purified peptide was found to be the 43-residue RF-amide peptide QRFP. We also describe two mouse homologues of human GPR103, termed mouse GPR103A and GPR103B. QRFP binds and activates the human GPR103, as well as mouse GPR103A and GPR103B, with nanomolar affinities in transfected cells. Systematic in situ hybridization analysis in mouse brains showed that QRFP is expressed exclusively in the periventricular and lateral hypothalamus, whereas the two receptor mRNAs are distinctly localized in various brain areas without an overlap to each other. When administered centrally in mice, QRFP induced feeding behavior, accompanied by increased general locomotor activity and metabolic rate. QRFP-induced food intake was abolished by preadministration of BIBP3226, a specific antagonist for the Y1 neuropeptide Y receptor. Hypothalamic prepro-QRFP mRNA expression was up-regulated upon fasting and in genetically obese ob/ob and db/db mice. Central QRFP administration also evoked highly sustained elevation of blood pressure and heart rate. Our findings suggest that QRFP and GPR103A/B may regulate diverse neuroendocrine and behavioral functions and implicate this neuropeptide system in metabolic syndrome.

A novel loss-of-function mutation in GPR54/KISS1R leads to hypogonadotropic hypogonadism in a highly consanguineous family.

PubMed

Nimri, Revital; Lebenthal, Yael; Lazar, Liora; Chevrier, Lucie; Phillip, Moshe; Bar, Meytal; Hernandez-Mora, Eva; de Roux, Nicolas; Gat-Yablonski, Galia

2011-03-01

The G protein-coupled receptor 54 (GPR54), the kisspeptin receptor, is essential for stimulation of GnRH secretion and induction of puberty. Recently loss-of-function mutations of the GPR54 have been implicated as a cause of isolated idiopathic hypogonadotropic hypogonadism (IHH). The objective of the study was to identify the genetic cause of IHH in a consanguineous pedigree and to characterize the phenotypic features from infancy through early adulthood. In six patients with normosmic IHH belonging to two families of Israeli Muslim-Arab origin highly related to one another, DNA was analyzed for mutations in the GnRHR and GPR54 genes, with functional analysis of the mutation found. The five males underwent comprehensive endocrine evaluation and were under longitudinal follow-up; the one female presented in early adulthood. A new homozygous mutation (c.T815C) in GPR54 leading to a phenylalanine substitution by serine (p.F272S) was detected in all patients. Functional analysis showed an almost complete inhibition of kisspeptin-induced GPR54 signaling and a dramatic decrease of the mutated receptor expression at the cell surface. The males exhibited the same clinical features from infancy to adulthood, characterized by cryptorchidism, a relatively short penis, and no spontaneous pubertal development. The female patient presented at 18 yr with impuberism and primary amenorrhea. Repeated stimulation tests demonstrated complete gonadotropin deficiency throughout follow-up. A novel loss-of-function mutation (p.F272S) in the GPR54 gene is associated with familial normosmic IHH. Underdeveloped external genitalia and impuberism point to the major role of GPR54 in the activation of the gonadotropic axis from intrauterine life to adulthood.

Applications of GPR in archaeological prospecting and cultural heritage diagnostics: Research Perspectives in COST Action TU1208

NASA Astrophysics Data System (ADS)

Pajewski, Lara; Benedetto, Andrea; Schettini, Giuseppe; Soldovieri, Francesco

2013-04-01

Ground Penetrating Radar (GPR) is a safe, non-destructive and non-invasive imaging technique that can be effectively used for advanced inspection of composite structures and for diagnostics affecting the whole life-cycle of civil engineering works. GPR can also be successfully employed in archaeological prospecting and cultural heritage diagnostics. In many Countries, where the archeological patrimony is an outstanding value (as Egypt, Israel, Greece, Central and South America), GPR is usually employed both as a diagnostic tool for the preventive detection of archeological structures and as the most advanced instrument able to prospect geometry and shape of underground valuable sites. However many uncertainties persist, because of several difficulties and ambiguities due to the complexity of the image processing in heterogeneous environment. It is possible to identify three main areas, in GPR field, that have to be addressed in order to promote the use of this technology in archaeological prospecting and cultural heritage diagnostics. These are: a) increase of the system sensitivity to enable the usability in a wider range of conditions, archeological sites are often located in impervious and critical environments; b) research novel data processing algorithms/analysis tools for the interpretation of GPR results; c) contribute to the development of new standards and guidelines and to training of end users, that will also help to increase the awareness of operators. It is also important to further investigate and promote a combined use of GPR with other non-invasive advanced techniques, typically used in the archeological investigation. In this framework, the COST Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar", proposed by a research team of "Roma Tre" University, Rome, Italy, has been approved in November 2012 and is going to start in April 2013. It is a 4-years ambitious project already involving 17 European Countries (AT, BE, CH, CZ, DE, EL, ES, FI, FR, HR, IT, NL, NO, PL, PT, TR, UK), as well as Australia and U.S.A. The project will be developed within the frame of a unique approach, based on the integrated contribution of University researchers, software developers, geophysics experts, Non-Destructive Testing equipment designers and producers, end users from private companies and public agencies. The main objective of the COST Action TU1208 is to exchange and increase scientific-technical knowledge and experience of GPR techniques, whilst promoting the effective use of this safe and non-destructive technique. In this interdisciplinary Action, advantages and limitations of GPR will be highlighted, leading to the identification of gaps in knowledge and technology. Protocols and guidelines for European Standards will be developed, for an effective use of GPR in various applications. A novel GPR will be designed and realized: a multi-static system, with dedicated software and calibration procedures, able to construct real-time lane three-dimensional high resolution images of investigated areas. Advanced electromagnetic-scattering and data-processing techniques will be developed. Freeware software will be released, for inspection and monitoring of complex structures, buried-target localization, shape reconstruction and estimation of physical parameters. Particular interest will be devoted to the combined use of GPR, together with other advanced and non-invasive sensing techniques, for a multi depth, multi-resolution and multi-scale monitoring of archaeological, architectural and artistic heritage (Working Group 4). Novel procedures and techniques will be developed and tested for the study and preservation of historical buildings, bridges, monuments, sculptures, paintings, frescoes, as well as for the mapping of sites and structures present in the subsoil. During the Action lifetime, a three-years high level training program will be organized. Mobility of early career researchers will be encouraged. The scientific work-plan of the COST Action TU1208 is open, to ensure that experts all over the world, who did not participate in the preparation of the proposal but are interested in the project, may join the Action and participate in its activities. More information about the project can be found at http://www.cost.eu/domains_actions/tud/Actions/TU1208.

Small interfering RNA-mediated silencing of G-protein-coupled receptor 137 inhibits growth of osteosarcoma cells.

PubMed

Li, Hao; Fu, Xiaodong; Gao, Yingjian; Li, Xiaomiao; Shen, Yi; Wang, Weili

2018-06-01

Osteosarcoma is the most widespread primary carcinoma in bones. Osteosarcoma cells are highly metastatic and frequently develop resistance to chemotherapy making this disease harder to treat. This identifies an urgent need of novel therapeutic strategies for osteosarcoma. G-Protein-coupled receptor 137 (GPR137) is involved in several human cancers and may be a novel therapeutic target. The expression of GPR137 was assessed in one osteoblast and three human osteosarcoma cell lines via the quantitative real-time polymerase chain reaction and western blot assays. Stable GPR137 knockdown cell lines were established using an RNA interference lentivirus system. Viability, colony formation, and flow cytometry assays were performed to measure the effects of GPR137 depletion on cell growth. The underlying molecular mechanism was determined using signaling array analysis and western blot assays. GPR137 expression was higher in the three human osteosarcoma cell lines, Saos-2, U2OS, and SW1353, than in osteoblast hFOB 1.19 cells. Lentivirus-mediated small interfering RNA targeting GPR137 successfully knocked down GPR137 mRNA and protein expression in both Saos-2 and U2OS cells. In the absence of GPR137, cell viability and colony formation ability were seriously impaired. The extent of apoptosis was also increased in both cell lines. Moreover, AMP-activated protein kinase α, proline-rich AKT substrate of 40 kDa, AKT, and extracellular signal-regulated kinase phosphorylation levels were down-regulated in GPR137 knockdown cells. The results of this study highlight the crucial role of GPR137 in promoting osteosarcoma cell growth in vitro . GPR137 could serve as a potential therapeutic target against osteosarcoma.

Assessment of cell line competence for studies of pharmacological GPR30 modulation.

PubMed

Sousa, Cátia; Ribeiro, Madalena; Rufino, Ana Teresa; Leitão, Alcino Jorge; Mendes, Alexandrina Ferreira

2017-04-01

Cell lines used to study the role of the G protein-coupled receptor 30 (GPR30) or G protein-coupled estrogen receptor (GPER) as a mediator of estrogen responses have yielded conflicting results. This work identified a simple assay to predict cell line competence for pharmacological studies of GPR30. The phosphorylation or expression levels of ERK1/2, Akt, c-Fos and eNOS were evaluated to assess GPR30 activation in response to known agonists (17β-estradiol and G-1) in MCF-7 and T-47D breast cancer cell lines and in bovine aortic endothelial cells. GPR30 expression was analyzed by qRT-PCR and Western blot with two distinct antibodies directed at its carboxy and amino terminals. None of the agonists, at any of the concentrations tested, activated any of those target proteins. Additional experiments excluded the disruption of the signaling pathway, interference of phenol red in the culture medium and constitutive proteasome degradation of GPR30 as possible causes for the lack of response of the three cell lines. Analysis of receptor expression showed the absence of clearly detectable GPR30 species of 44 and 50-55 kDa previously identified in cell lines that respond to 17β-estradiol and G-1. Cells that do not express the 44 and 50-55 kDa species do not respond to GPR30 agonists. Thus, the presence or absence of these GPR30 species is a simple and rapid manner to determine whether a given cell line is suitable for pharmacological or molecular studies of GPR30 modulation.

Application of ground-penetrating radar imagery for three-dimensional visualisation of near-surface structures in ice-rich permafrost, Barrow, Alaska

USGS Publications Warehouse

Munroe, Jeffrey S.; Doolittle, James A.; Kanevskiy, Mikhail; Hinkel, Kenneth M.; Nelson, Frederick E.; Jones, Benjamin M.; Shur, Yuri; Kimble, John M.

2007-01-01

Three-dimensional ground-penetrating radar (3D GPR) was used to investigate the subsurface structure of ice-wedge polygons and other features of the frozen active layer and near-surface permafrost near Barrow, Alaska. Surveys were conducted at three sites located on landscapes of different geomorphic age. At each site, sediment cores were collected and characterised to aid interpretation of GPR data. At two sites, 3D GPR was able to delineate subsurface ice-wedge networks with high fidelity. Three-dimensional GPR data also revealed a fundamental difference in ice-wedge morphology between these two sites that is consistent with differences in landscape age. At a third site, the combination of two-dimensional and 3D GPR revealed the location of an active frost boil with ataxitic cryostructure. When supplemented by analysis of soil cores, 3D GPR offers considerable potential for imaging, interpreting and 3D mapping of near-surface soil and ice structures in permafrost environments.

Lactate produced during labor modulates uterine inflammation via GPR81 (HCA1).

PubMed

Madaan, Ankush; Nadeau-Vallée, Mathieu; Rivera, Jose Carlos; Obari, Dima; Hou, Xin; Sierra, Estefania Marin; Girard, Sylvie; Olson, David M; Chemtob, Sylvain

2017-01-01

Uterine inflammatory processes trigger prolabor pathways and orchestrate on-time labor onset. Although essential for successful labor, inflammation needs to be regulated to avoid uncontrolled amplification and resolve postpartum. During labor, myometrial smooth muscle cells generate ATP mainly via anaerobic glycolysis, resulting in accumulation of lactate. Aside from its metabolic function, lactate has been shown to activate a G protein-coupled receptor, GPR81, reported to regulate inflammation. We therefore hypothesize that lactate produced during labor may act via GPR81 in the uterus to exert in a feedback manner antiinflammatory effects, to resolve or mitigate inflammation. We sought to investigate the role of lactate produced during labor and its receptor, GPR81, in regulating inflammation in the uterus. We investigated the expression of GPR81 in the uterus and the pharmacological role of lactate acting via GPR81 during labor, using shRNA-GPR81 and GPR81 -/- mice. (1) Uterine lactate levels increased substantially from 2 to 9 mmol/L during labor. (2) Immunohistological analysis revealed expression of GPR81 in the uterus with high expression in myometrium. (3) GPR81 expression increased during gestation, and peaked near labor. (4) In primary myometrial smooth muscle cell and ex vivo uteri from wild-type mice, lactate decreased interleukin-1β-induced transcription of key proinflammatory Il1b, Il6, Ccl2, and Pghs2; suppressive effects of lactate were not observed in cells and tissues from GPR81 -/- mice. (5) Conversely, proinflammatory gene expression was augmented in the uterus at term in GPR81 -/- mice and wild-type mice treated intrauterine with lentiviral-encoded shRNA-GPR81; GPR81 silencing also induced proinflammatory gene transcription in the uterus when labor was induced by endotoxin (lipopolysaccharide). (6) Importantly, administration to pregnant mice of a metabolically stable specific GPR81 agonist, 3,5-dihydroxybenzoic acid, decreased endotoxin-induced uterine inflammation, preterm birth, and associated neonatal mortality. Collectively, our data uncover a novel link between the anaerobic glycolysis and the control of uterine inflammation wherein the high levels of lactate produced during labor act on uterine GPR81 to down-regulate key proinflammatory genes. This discovery may represent a novel feedback mechanism to regulate inflammation during labor, and conveys a potential rationale for the use of GPR81 agonists to attenuate inflammation and resulting preterm birth. Copyright © 2016 Elsevier Inc. All rights reserved.

Acidosis Activation of the Proton-Sensing GPR4 Receptor Stimulates Vascular Endothelial Cell Inflammatory Responses Revealed by Transcriptome Analysis

PubMed Central

Dong, Lixue; Li, Zhigang; Leffler, Nancy R.; Asch, Adam S.; Chi, Jen-Tsan; Yang, Li V.

2013-01-01

Acidic tissue microenvironment commonly exists in inflammatory diseases, tumors, ischemic organs, sickle cell disease, and many other pathological conditions due to hypoxia, glycolytic cell metabolism and deficient blood perfusion. However, the molecular mechanisms by which cells sense and respond to the acidic microenvironment are not well understood. GPR4 is a proton-sensing receptor expressed in endothelial cells and other cell types. The receptor is fully activated by acidic extracellular pH but exhibits lesser activity at the physiological pH 7.4 and minimal activity at more alkaline pH. To delineate the function and signaling pathways of GPR4 activation by acidosis in endothelial cells, we compared the global gene expression of the acidosis response in primary human umbilical vein endothelial cells (HUVEC) with varying level of GPR4. The results demonstrated that acidosis activation of GPR4 in HUVEC substantially increased the expression of a number of inflammatory genes such as chemokines, cytokines, adhesion molecules, NF-κB pathway genes, and prostaglandin-endoperoxidase synthase 2 (PTGS2 or COX-2) and stress response genes such as ATF3 and DDIT3 (CHOP). Similar GPR4-mediated acidosis induction of the inflammatory genes was also noted in other types of endothelial cells including human lung microvascular endothelial cells and pulmonary artery endothelial cells. Further analyses indicated that the NF-κB pathway was important for the acidosis/GPR4-induced inflammatory gene expression. Moreover, acidosis activation of GPR4 increased the adhesion of HUVEC to U937 monocytic cells under a flow condition. Importantly, treatment with a recently identified GPR4 antagonist significantly reduced the acidosis/GPR4-mediated endothelial cell inflammatory response. Taken together, these results show that activation of GPR4 by acidosis stimulates the expression of a wide range of inflammatory genes in endothelial cells. Such inflammatory response can be suppressed by GPR4 small molecule inhibitors and hold potential therapeutic value. PMID:23613998

GPR39 (zinc receptor) knockout mice exhibit depression-like behavior and CREB/BDNF down-regulation in the hippocampus.

PubMed

Młyniec, Katarzyna; Budziszewska, Bogusława; Holst, Birgitte; Ostachowicz, Beata; Nowak, Gabriel

2014-10-31

Zinc may act as a neurotransmitter in the central nervous system by activation of the GPR39 metabotropic receptors. In the present study, we investigated whether GPR39 knockout would cause depressive-like and/or anxiety-like behavior, as measured by the forced swim test, tail suspension test, and light/dark test. We also investigated whether lack of GPR39 would change levels of cAMP response element-binding protein (CREB),brain-derived neurotrophic factor (BDNF) and tropomyosin related kinase B (TrkB) protein in the hippocampus and frontal cortex of GPR39 knockout mice subjected to the forced swim test, as measured by Western-blot analysis. In this study, GPR39 knockout mice showed an increased immobility time in both the forced swim test and tail suspension test, indicating depressive-like behavior and displayed anxiety-like phenotype. GPR39 knockout mice had lower CREB and BDNF levels in the hippocampus, but not in the frontal cortex, which indicates region specificity for the impaired CREB/BDNF pathway (which is important in antidepressant response) in the absence of GPR39. There were no changes in TrkB protein in either structure. In the present study, we also investigated activity in the hypothalamus-pituitary-adrenal axis under both zinc- and GPR39-deficient conditions. Zinc-deficient mice had higher serum corticosterone levels and lower glucocorticoid receptor levels in the hippocampus and frontal cortex. There were no changes in the GPR39 knockout mice in comparison with the wild-type control mice, which does not support a role of GPR39 in hypothalamus-pituitary-adrenal axis regulation. The results of this study indicate the involvement of the GPR39 Zn(2+)-sensing receptor in the pathophysiology of depression with component of anxiety. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Constitutive Activity among Orphan Class-A G Protein Coupled Receptors.

PubMed

Martin, Adam L; Steurer, Michael A; Aronstam, Robert S

2015-01-01

The purpose of this study was to evaluate the extent of constitutive activity among orphan class-A G protein coupled receptors within the cAMP signaling pathway. Constitutive signaling was revealed by changes in gene expression under control of the cAMP response element. Gene expression was measured in Chinese hamster ovary cells transiently co-transfected with plasmids containing a luciferase reporter and orphan receptor. Criteria adopted for defining constitutive activation were: 1) 200% elevation over baseline reporter gene expression; 2) 40% inhibition of baseline expression; and 3) 40% inhibition of expression stimulated by 3 μM forskolin. Five patterns of activity were noted: 1) inhibition under both baseline and forskolin stimulated expression (GPR15, GPR17, GPR18, GPR20, GPR25, GPR27, GPR31, GPR32, GPR45, GPR57, GPR68, GPR83, GPR84, GPR132, GPR150, GPR176); 2) no effect on baseline expression, but inhibition of forskolin stimulated expression (GPR4, GPR26, GPR61, GPR62, GPR78, GPR101, GPR119); 3) elevation of baseline signaling coupled with inhibition of forskolin stimulated expression (GPR6, GPR12); 4) elevation of baseline signaling without inhibition of forskolin stimulated expression (GPR3, GPR21, GPR52, GPR65); and 5) no effect on expression (GPR1, GPR19, GPR22, GPR34, GPR35, GPR39, GPR63, GPR82, GPR85, GPR87). Constitutive activity was observed in 75% of the orphan class-A receptors examined (30 of 40). This constitutive signaling cannot be explained by simple overexpression of the receptor. Inhibition of cAMP mediated expression was far more common (65%) than stimulation of expression (15%). Orphan receptors that were closely related based on amino acid homology tended to have similar effects on gene expression. These results suggest that identification of inverse agonists may be a fruitful approach for categorizing these orphan receptors and targeting them for pharmacological intervention.

Constitutive Activity among Orphan Class-A G Protein Coupled Receptors

PubMed Central

Martin, Adam L.; Steurer, Michael A.; Aronstam, Robert S.

2015-01-01

The purpose of this study was to evaluate the extent of constitutive activity among orphan class-A G protein coupled receptors within the cAMP signaling pathway. Constitutive signaling was revealed by changes in gene expression under control of the cAMP response element. Gene expression was measured in Chinese hamster ovary cells transiently co-transfected with plasmids containing a luciferase reporter and orphan receptor. Criteria adopted for defining constitutive activation were: 1) 200% elevation over baseline reporter gene expression; 2) 40% inhibition of baseline expression; and 3) 40% inhibition of expression stimulated by 3 μM forskolin. Five patterns of activity were noted: 1) inhibition under both baseline and forskolin stimulated expression (GPR15, GPR17, GPR18, GPR20, GPR25, GPR27, GPR31, GPR32, GPR45, GPR57, GPR68, GPR83, GPR84, GPR132, GPR150, GPR176); 2) no effect on baseline expression, but inhibition of forskolin stimulated expression (GPR4, GPR26, GPR61, GPR62, GPR78, GPR101, GPR119); 3) elevation of baseline signaling coupled with inhibition of forskolin stimulated expression (GPR6, GPR12); 4) elevation of baseline signaling without inhibition of forskolin stimulated expression (GPR3, GPR21, GPR52, GPR65); and 5) no effect on expression (GPR1, GPR19, GPR22, GPR34, GPR35, GPR39, GPR63, GPR82, GPR85, GPR87). Constitutive activity was observed in 75% of the orphan class-A receptors examined (30 of 40). This constitutive signaling cannot be explained by simple overexpression of the receptor. Inhibition of cAMP mediated expression was far more common (65%) than stimulation of expression (15%). Orphan receptors that were closely related based on amino acid homology tended to have similar effects on gene expression. These results suggest that identification of inverse agonists may be a fruitful approach for categorizing these orphan receptors and targeting them for pharmacological intervention. PMID:26384023

GPR84 sustains aberrant β-catenin signaling in leukemic stem cells for maintenance of MLL leukemogenesis.

PubMed

Dietrich, Philipp A; Yang, Chen; Leung, Halina H L; Lynch, Jennifer R; Gonzales, Estrella; Liu, Bing; Haber, Michelle; Norris, Murray D; Wang, Jianlong; Wang, Jenny Yingzi

2014-11-20

β-catenin is required for establishment of leukemic stem cells (LSCs) in acute myeloid leukemia (AML). Targeted inhibition of β-catenin signaling has been hampered by the lack of pathway components amenable to pharmacologic manipulation. Here we identified a novel β-catenin regulator, GPR84, a member of the G protein-coupled receptor family that represents a highly tractable class of drug targets. High GPR84 expression levels were confirmed in human and mouse AML LSCs compared with hematopoietic stem cells (HSCs). Suppression of GPR84 significantly inhibited cell growth by inducing G1-phase cell-cycle arrest in pre-LSCs, reduced LSC frequency, and impaired reconstitution of stem cell-derived mixed-lineage leukemia (MLL) AML, which represents an aggressive and drug-resistant subtype of AML. The GPR84-deficient phenotype in established AML could be rescued by expression of constitutively active β-catenin. Furthermore, GPR84 conferred a growth advantage to Hoxa9/Meis1a-transduced stem cells. Microarray analysis demonstrated that GPR84 significantly upregulated a small set of MLL-fusion targets and β-catenin coeffectors, and downregulated a hematopoietic cell-cycle inhibitor. Altogether, our data reveal a previously unrecognized role of GPR84 in maintaining fully developed AML by sustaining aberrant β-catenin signaling in LSCs, and suggest that targeting the oncogenic GPR84/β-catenin signaling axis may represent a novel therapeutic strategy for AML. © 2014 by The American Society of Hematology.

G protein-coupled receptor 30 down-regulates cofactor expression and interferes with the transcriptional activity of glucocorticoid.

PubMed

Ylikomi, Timo; Vienonen, Annika; Ahola, Tytti M

2004-11-01

G protein-coupled receptor 30 (GPR30) has previously been described to be important in steroid-mediated growth and to inhibit cell proliferation. Here we investigated whether the effect of GPR30 on cell growth is dependent on steroid hormone receptors. We stably introduced GPR30 in immortalized normal mammary epithelial (HME) cells using retroviruses for gene delivery. GPR30 inhibited the growth and proliferation of the cells. They expressed glucocorticoid receptor, but not estrogen or progesterone receptor. GPR30 down-regulated the expression of cofactor transcription intermediary factor 2 (TIF2) analyzed using quantitative RT-PCR analysis, and also diminished the expression of TIF2 at protein level analyzed by Western blotting using nuclear extracts from mammary epithelial cells. When HME cells were transiently transfected with the glucocorticoid response element MMTV-luc reporter plasmid, stable expression of GPR30 resulted in the abolition of ligand-induced transactivation of the promoter. In COS cells, transient transfection of GPR30 with glucocorticoid receptor alpha resulted in an abrogation of the MMTV-luc and GRE-luc reporter activities induced by dexamethasone. The results suggest a novel mechanism by which membrane-initiated signaling interferes with steroid signaling.

PAVECHECK : integrating deflection and GPR for network condition surveys.

DOT National Transportation Integrated Search

2009-01-01

The PAVECHECK data integration and analysis system was developed to merge Falling Weight : Deflectometer (FWD) and Ground Penetrating Radar (GPR) data together with digital video images of : surface conditions. In this study Global Positioning System...

Hydrostratigraphic analysis of the MADE site with full-resolution GPR and direct-push hydraulic profiling

USGS Publications Warehouse

Dogan, M.; Van Dam, R. L.; Bohling, Geoffrey C.; Butler, J.J.; Hyndman, D.W.

2011-01-01

Full-resolution 3D Ground-Penetrating Radar (GPR) data were combined with high-resolution hydraulic conductivity (K) data from vertical Direct-Push (DP) profiles to characterize a portion of the highly heterogeneous MAcro Dispersion Experiment (MADE) site. This is an important first step to better understand the influence of aquifer heterogeneities on observed anomalous transport. Statistical evaluation of DP data indicates non-normal distributions that have much higher similarity within each GPR facies than between facies. The analysis of GPR and DP data provides high-resolution estimates of the 3D geometry of hydrostratigraphic zones, which can then be populated with stochastic K fields. The lack of such estimates has been a significant limitation for testing and parameterizing a range of novel transport theories at sites where the traditional advection-dispersion model has proven inadequate. ?? 2011 by the American Geophysical Union.

Stepped-frequency GPR for utility line detection using polarization-dependent scattering

NASA Astrophysics Data System (ADS)

Jensen, Ole K.; Gregersen, Ole G.

2000-04-01

A GPR for detection of buried cables and pipes is developed by Ekko Dane Production in cooperation with Aalborg University. The appearance is a 'lawn mower' model including antennas, electronics and on-line data processing. A successful result is obtained by combining dedicated hardware and signal processing. The inherent signal to clutter ratio is bad, but making measurements at many polarization angles and subsequent signal processing improves the ratio. A simple model of the polarization dependence of the scattering from the target is used. The method is improved by combining the polarization filtering with averaging over small horizontal displacements. A stepped frequency measurement system is used. The method often implies long measurement times, but this problem is overcome by development of fast RF-electronics. Standard signal processors are used for real-time data processing. Several antenna array configurations are tested and optimized for low coupling between transmitter and receiver and for a short impulse response. A large number of tests have been made for different targets, e.g. metal cables and plastic pipes filled with air or water. Tests have been made under realistic ground conditions, including sand, wet clay, pavements and grass covered soil. The results show reliable detection even when the conditions are difficult.

Sea Ice Thickness Measurement by Ground Penetrating Radar for Ground Truth of Microwave Remote Sensing Data

NASA Astrophysics Data System (ADS)

Matsumoto, M.; Yoshimura, M.; Naoki, K.; Cho, K.; Wakabayashi, H.

2018-04-01

Observation of sea ice thickness is one of key issues to understand regional effect of global warming. One of approaches to monitor sea ice in large area is microwave remote sensing data analysis. However, ground truth must be necessary to discuss the effectivity of this kind of approach. The conventional method to acquire ground truth of ice thickness is drilling ice layer and directly measuring the thickness by a ruler. However, this method is destructive, time-consuming and limited spatial resolution. Although there are several methods to acquire ice thickness in non-destructive way, ground penetrating radar (GPR) can be effective solution because it can discriminate snow-ice and ice-sea water interface. In this paper, we carried out GPR measurement in Lake Saroma for relatively large area (200 m by 300 m, approximately) aiming to obtain grand truth for remote sensing data. GPR survey was conducted at 5 locations in the area. The direct measurement was also conducted simultaneously in order to calibrate GPR data for thickness estimation and to validate the result. Although GPR Bscan image obtained from 600MHz contains the reflection which may come from a structure under snow, the origin of the reflection is not obvious. Therefore, further analysis and interpretation of the GPR image, such as numerical simulation, additional signal processing and use of 200 MHz antenna, are required to move on thickness estimation.

Role of GPR30 in estrogen-induced prostate epithelial apoptosis and benign prostatic hyperplasia.

PubMed

Yang, Deng-Liang; Xu, Jia-Wen; Zhu, Jian-Guo; Zhang, Yi-Lin; Xu, Jian-Bang; Sun, Qing; Cao, Xiao-Nian; Zuo, Wu-Lin; Xu, Ruo-Shui; Huang, Jie-Hong; Jiang, Fu-Neng; Zhuo, Yang-Jia; Xiao, Bai-Quan; Liu, Yun-Zhong; Yuan, Dong-Bo; Sun, Zhao-Lin; He, Hui-Chan; Lun, Zhao-Rong; Zhong, Wei-De; Zhou, Wen-Liang

2017-06-03

Several studies have implicated estrogen and the estrogen receptor (ER) in the pathogenesis of benign prostatic hyperplasia (BPH); however, the mechanism underlying this effect remains elusive. In the present study, we demonstrated that estrogen (17β-estradiol, or E2)-induced activation of the G protein-coupled receptor 30 (GPR30) triggered Ca 2+ release from the endoplasmic reticulum, increased the mitochondrial Ca 2+ concentration, and thus induced prostate epithelial cell (PEC) apoptosis. Both E2 and the GPR30-specific agonist G1 induced a transient intracellular Ca 2+ release in PECs via the phospholipase C (PLC)-inositol 1, 4, 5-triphosphate (IP 3 ) pathway, and this was abolished by treatment with the GPR30 antagonist G15. The release of cytochrome c and activation of caspase-3 in response to GPR30 activation were observed. Data generated from the analysis of animal models and human clinical samples indicate that treatment with the GPR30 agonist relieves testosterone propionate (TP)-induced prostatic epithelial hyperplasia, and that the abundance of GPR30 is negatively associated with prostate volume. On the basis of these results, we propose a novel regulatory mechanism whereby estrogen induces the apoptosis of PECs via GPR30 activation. Inhibition of this activation is predicted to lead to abnormal PEC accumulation, and to thereby contribute to BPH pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of antenna orientation on 3-D ground penetrating radar surveys: an archaeological perspective

NASA Astrophysics Data System (ADS)

Lualdi, Maurizio; Lombardi, Federico

2014-02-01

This paper investigates the impact that the GPR antenna orientation, or survey direction, has on migrated image resulting from 3-D georadar acquisitions carried out on heterogeneous and anisotropic subsurface. This feature is related to the directional dependency of wave propagation effects, such as dispersion, absorption, depolarization, and scattering phenomena. We provide a proof of this with two field examples, demonstrating that a 3-D survey performed along a single direction could bring weak results in terms of target detection and reconstruction. To overcome this risk, we show the improvements that the combination of GPR 3-D data acquired along different directions on the same area can obtain: an enhancement of target detection probability and the practical advantage for the end-user of looking through a single image. Further on, we develop a stacking scheme that employs a threshold associated with amplitude comparison to adaptively handle the combination of georadar data volumes.

Construction of reactive potential energy surfaces with Gaussian process regression: active data selection

NASA Astrophysics Data System (ADS)

Guan, Yafu; Yang, Shuo; Zhang, Dong H.

2018-04-01

Gaussian process regression (GPR) is an efficient non-parametric method for constructing multi-dimensional potential energy surfaces (PESs) for polyatomic molecules. Since not only the posterior mean but also the posterior variance can be easily calculated, GPR provides a well-established model for active learning, through which PESs can be constructed more efficiently and accurately. We propose a strategy of active data selection for the construction of PESs with emphasis on low energy regions. Through three-dimensional (3D) example of H3, the validity of this strategy is verified. The PESs for two prototypically reactive systems, namely, H + H2O ↔ H2 + OH reaction and H + CH4 ↔ H2 + CH3 reaction are reconstructed. Only 920 and 4000 points are assembled to reconstruct these two PESs respectively. The accuracy of the GP PESs is not only tested by energy errors but also validated by quantum scattering calculations.

GPR data processing computer software for the PC

USGS Publications Warehouse

Lucius, Jeffrey E.; Powers, Michael H.

2002-01-01

The computer software described in this report is designed for processing ground penetrating radar (GPR) data on Intel-compatible personal computers running the MS-DOS operating system or MS Windows 3.x/95/98/ME/2000. The earliest versions of these programs were written starting in 1990. At that time, commercially available GPR software did not meet the processing and display requirements of the USGS. Over the years, the programs were refined and new features and programs were added. The collection of computer programs presented here can perform all basic processing of GPR data, including velocity analysis and generation of CMP stacked sections and data volumes, as well as create publication quality data images.

Current uses of ground penetrating radar in groundwater-dependent ecosystems research.

PubMed

Paz, Catarina; Alcalá, Francisco J; Carvalho, Jorge M; Ribeiro, Luís

2017-10-01

Ground penetrating radar (GPR) is a high-resolution technique widely used in shallow groundwater prospecting. This makes GPR ideal to characterize the hydrogeological functioning of groundwater-dependent ecosystems (GDE). This paper reviews current uses of GPR in GDE research through the construction of a database comprising 91 worldwide GPR case studies selected from the literature and classified according to (1) geological environments favouring GDE; (2) hydrogeological research interests; and (3) field technical and (4) hydrogeological conditions of the survey. The database analysis showed that inland alluvial, colluvial, and glacial formations were the most widely covered geological environments. Water-table depth was the most repeated research interest. By contrast, weathered-marl and crystalline-rock environments as well as the delineation of salinity interfaces in coastal and inland areas were less studied. Despite that shallow groundwater propitiated GDE in almost all the GPR case studies compiled, only one case expressly addressed GDE research. Common ranges of prospecting depth, water-table depth, and volumetric water content deduced by GPR and other techniques were identified. Antenna frequency of 100MHz and the common offset acquisition technique predominated in the database. Most of GPR case studies were in 30-50° N temperate latitudes, mainly in Europe and North America. Eight original radargrams were selected from several GPR profiles performed in 2014 and 2015 to document database classes and identified gaps, as well as to define experimental ranges of operability in GDE environments. The results contribute to the design of proper GPR surveys in GDE research. Copyright © 2017 Elsevier B.V. All rights reserved.

Analysis of G-Protein Coupled Receptor 30 (GPR30) on Endothelial Inflammation.

PubMed

Chakrabarti, Subhadeep; Davidge, Sandra T

2016-01-01

The female sex hormone estrogen (the most common form 17-β-estradiol or E2) is known to have both anti-inflammatory and pro-inflammatory effects. Given the diversity of estrogen responses mediated through its three distinct receptors, namely, estrogen receptor α (ERα), ERβ, and the G-protein coupled receptor 30 (GPR30), it is plausible that different receptors have specific modulatory effects on inflammation in different tissues. We have shown that activation of GPR30 exerted anti-inflammatory effects as demonstrated by significant attenuation of tumor necrosis factor (TNF)-mediated upregulation of adhesion molecules in isolated human umbilical vein endothelial cells. Interestingly, estrogen alone had no such effect and blockade of classical ERs restored the anti-inflammatory effect, suggesting that this effect was dependent on GPR30 and opposed to classical ERs. These findings were further validated by the negation of anti-inflammatory GPR30 effects by classical ER agonists. This chapter focuses on multiple pharmacological options to activate GPR30 and the use of TNF activated endothelial cells as a model system for inflammatory response as assessed by adhesion molecule detection through western blotting.

Application of GPCR Structures for Modelling of Free Fatty Acid Receptors.

PubMed

Tikhonova, Irina G

2017-01-01

Five G protein-coupled receptors (GPCRs) have been identified to be activated by free fatty acids (FFA). Among them, FFA1 (GPR40) and FFA4 (GPR120) bind long-chain fatty acids, FFA2 (GPR43) and FFA3 (GPR41) bind short-chain fatty acids and GPR84 binds medium-chain fatty acids. Free fatty acid receptors have now emerged as potential targets for the treatment of diabetes, obesity and immune diseases. The recent progress in crystallography of GPCRs has now enabled the elucidation of the structure of FFA1 and provided reliable templates for homology modelling of other FFA receptors. Analysis of the crystal structure and improved homology models, along with mutagenesis data and structure activity, highlighted an unusual arginine charge-pairing interaction in FFA1-3 for receptor modulation, distinct structural features for ligand binding to FFA1 and FFA4 and an arginine of the second extracellular loop as a possible anchoring point for FFA at GPR84. Structural data will be helpful for searching novel small-molecule modulators at the FFA receptors.

Ground penetrating radar (GPR) analysis : Phase II field evaluation.

DOT National Transportation Integrated Search

2011-10-01

"The objective of this work was to evaluate the feasibility and value of expanding the MDT's Ground : Penetrating Radar (GPR) program to pavement design and rehabilitation, and to network level : evaluation. Phase I of this project concluded that in ...

Neuro-psychopharmacological perspective of Orphan receptors of Rhodopsin (class A) family of G protein-coupled receptors.

PubMed

Khan, Muhammad Zahid; He, Ling

2017-04-01

In the central nervous system (CNS), G protein-coupled receptors (GPCRs) are the most fruitful targets for neuropsychopharmacological drug development. Rhodopsin (class A) is the most studied class of GPCR and includes orphan receptors for which the endogenous ligand is not known or is unclear. Characterization of orphan GPCRs has proven to be challenging, and the production pace of GPCR-based drugs has been incredibly slow. Determination of the functions of these receptors may provide unexpected insight into physiological and neuropathological processes. Advances in various methods and techniques to investigate orphan receptors including in situ hybridization and knockdown/knockout (KD/KO) showed extensive expression of these receptors in the mammalian brain and unmasked their physiological and neuropathological roles. Due to these rapid progress and development, orphan GPCRs are rising as a new and promising class of drug targets for neurodegenerative diseases and psychiatric disorders. This review presents a neuropsychopharmacological perspective of 26 orphan receptors of rhodopsin (class A) family, namely GPR3, GPR6, GPR12, GPR17, GPR26, GPR35, GPR39, GPR48, GPR49, GPR50, GPR52, GPR55, GPR61, GPR62, GPR63, GPR68, GPR75, GPR78, GPR83, GPR84, GPR85, GPR88, GPR153, GPR162, GPR171, and TAAR6. We discussed the expression of these receptors in mammalian brain and their physiological roles. Furthermore, we have briefly highlighted their roles in neurodegenerative diseases and psychiatric disorders including Alzheimer's disease, Parkinson's disease, neuroinflammation, inflammatory pain, bipolar and schizophrenic disorders, epilepsy, anxiety, and depression.

The Proton-Sensing G-Protein Coupled Receptor GPR4 Promotes Angiogenesis in Head and Neck Cancer

PubMed Central

Chen, Xiaohong; Zhong, Qi; Huang, Junwei; Zhang, Yang; Guo, Wei; Yang, Zheng; Ding, Shuo; Chen, Ping

2016-01-01

Squamous cell carcinoma of the head and neck (SCCHN) is an aggressive disease with poor survival and is the sixth most common cancer worldwide. Gastroesophageal reflux is a common event in SCCHN patients. GPR4 is a proton-sensing G-protein coupled receptor, which can be activated by acidosis. The objective of this study was to explore the role of GPR4 in acid exposure and tumor angiogenesis in SCCHN. In this study, we confirmed that overexpressing GPR4 in SCCHN cells could increase the expression and secretion of IL6, IL8 and VEGFA at pH 5.9. This effect could be inhibited by SB203580 (a p38 inhibitor). Western blot analysis indicated that phosphorylation of p38 increased in GPR4 infected cells at pH 5.9, which could be inhibited by SB203580. In tube formation assay, HMEC-1 cells were incubated with conditioned medium (CM, pH 5.9, 6.5, 7.4) derived from control and GPR4 infected SCCHN cells. Tube length was significantly increased in HMEC-1 cells incubated with CM from GPR4 infected cells compared with control cells at pH5.9, which indicated the pro-angiogenic effect of GPR4 in acidic pH. The neutralizing antibodies of IL6, IL8 and VEGFA could inhibit tube formation of HMEC-1 cells. In vivo, the effect of GPR4 on angiogenesis was investigated with the chick chorioallantoic membrane (CAM) model. Control and GPR4 infected SCCHN cells were seeded onto the upper CAM surface (n = 5 in each group) and 5 μL DMEM/F12 (pH 5.9, 6.5, 7.4) was added to the surface of the cell every 24 h. Four days later, the upper CAM were harvested and the ratio of the vascular area to the CAM area was quantified using Image-Pro Plus 6.0 software. GPR4 infected cells could recruit more vascular than control cells at pH5.9. In conclusion, we suggested that GPR4 induces angiogenesis via GPR4-induced p38-mediated IL6, IL8 and VEGFA secretion at acidic extracellular pH in SCCHN. PMID:27078157

Exchanging knowledge and working together in COST Action TU1208: Short-Term Scientific Missions on Ground Penetrating Radar

NASA Astrophysics Data System (ADS)

Santos Assuncao, Sonia; De Smedt, Philippe; Giannakis, Iraklis; Matera, Loredana; Pinel, Nicolas; Dimitriadis, Klisthenis; Giannopoulos, Antonios; Sala, Jacopo; Lambot, Sébastien; Trinks, Immo; Marciniak, Marian; Pajewski, Lara

2015-04-01

This work aims at presenting the scientific results stemming from six Short-Term Scientific Missions (STSMs) funded by the COST (European COoperation in Science and Technology) Action TU1208 'Civil Engineering Applications of Ground Penetrating Radar' (Action Chair: Lara Pajewski, STSM Manager: Marian Marciniak). STSMs are important means to develop linkages and scientific collaborations between participating institutions involved in a COST Action. Scientists have the possibility to go to an institution abroad, in order to undertake joint research and share techniques/equipment/infrastructures that may not be available in their own institution. STSMs are particularly intended for Early Stage Researchers (ESRs), i.e., young scientists who obtained their PhD since no more than 8 years when they started to be involved in the Action. Duration of a standard STSM can be from 5 to 90 days and the research activities carried out during this short stay shall specifically contribute to the achievement of the scientific objectives of the supporting COST Action. The first STSM was carried out by Lara Pajewski, visiting Antonis Giannopoulos at The University of Edinburgh (United Kingdom). The research activities focused on the electromagnetic modelling of Ground Penetrating Radar (GPR) responses to complex targets. A set of test scenarios was defined, to be used by research groups participating to Working Group 3 of COST Action TU1208, to test and compare different electromagnetic forward- and inverse-scattering methods; these scenarios were modelled by using the well-known finite-difference time-domain simulator GprMax. New Matlab procedures for the processing and visualization of GprMax output data were developed. During the second STSM, Iraklis Giannakis visited Lara Pajewski at Roma Tre University (Italy). The study was concerned with the numerical modelling of horn antennas for GPR. An air-coupled horn antenna was implemented in GprMax and tested in a realistically modelled pavement scenario; moreover, the horn was compared with a previously-implemented ground-coupled bowtie antenna. The numerical results indicate that air-coupled antennas receive clear reflections from distinct layers within the pavement but they are incapable in the considered setting to detect cracks filled with air. On the other hand, by using ground-coupled antennas it is easier to interpret hyperbolic responses from the buried cracks. The developed modelling framework is a powerful tool in evaluating the performance of high-frequency GPR transducers in realistic situations and this approach can lead to better design of GPR antennas. The third STSM was carried out by Sonia Santos Assunçao visiting Klisthenis Dimitriadis at Geoservice (Greece). They worked at the non-destructive inspection of the Tholos Tomb of Acharnon. The unknown thickness of the Tomb walls was determined by using a GPR. Data were plotted in impressive circular radargrams. Discontinuities in the measured data were identified and associated to fissures or voids, indicating internal and superficial damages of the Tomb. A combination of GPR with electrical resistivity tomography allowed a more accurate data interpretation. Vibrations in the Tomb were quantified by using seismic measurements and endoscopy was used to confirm the thickness of the walls. During the fourth STSM, Philippe De Smedt visited Immo Trinks at the Ludwig Boltzmann Institute for Archaeological Prospection and Virtual Archaeology. The research activities regarded the reconstruction of prehistoric environments at Stonehenge, by means of multiple electromagnetic survey methods. Different datasets were processed, analysed and compared: data from a multi-receiver electromagnetic induction survey (collected by the ORBit research group from Ghent University, Belgium), and data from a 3D GPR survey (collected by the Ludwig Boltzmann Institute for Virtual Archaeology and Archaeological Prospection, Austria). The aim was that of creating a robust methodological foundation for the combined analysis of electromagnetic-induction and GPR data. The fifth STSM was carried out by Loredana Matera, who visited Jacopo Sala at 3d-radar (Norway). They tested an innovative reconfigurable stepped-frequency GPR, designed and realised in Italy. The prototype was compared with commercial equipment produced in Norway. Through laboratory experiments as well as outdoor campaigns in urban scenarios with archaeological remarks, a deeper knowledge of the Italian prototype was achieved and plans were made to improve it. Finally, Nicolas Pinel visited Sébastien Lambot at the Université catholique de Louvain (UCL); the last STSM presented in this abstract, was devoted to investigating how to model the effect of soil roughness in the inversion of ultra wide-band off-ground monostatic GPR signals. The aim of this research is the noninvasive quantification of soil properties through the use of GPR. The work focused on incorporating the improved asymptotic forward electromagnetic model developed by Pinel et al. in the multilayer Green function code developed at UCL. Acknowledgement The Authors thank COST, for funding the Action TU1208 'Civil Engineering Applications of Ground Penetrating Radar,' supporting these STSMs.

GPR101 Mutations are not a Frequent Cause of Congenital Isolated Growth Hormone Deficiency.

PubMed

Castinetti, F; Daly, A F; Stratakis, C A; Caberg, J-H; Castermans, E; Trivellin, G; Rostomyan, L; Saveanu, A; Jullien, N; Reynaud, R; Barlier, A; Bours, V; Brue, T; Beckers, A

2016-06-01

Patients with Xq26.3 microduplication present with X-linked acrogigantism (X-LAG) syndrome, an early-childhood form of gigantism due to marked growth hormone (GH) hypersecretion from mixed GH-PRL adenomas and hyperplasia. The microduplication includes GPR101, which is upregulated in patients' tumor tissue. The GPR101 gene codes for an orphan G protein coupled receptor that is normally highly expressed in the hypothalamus. Our aim was to determine whether GPR101 loss of function mutations or deletions could be involved in patients with congenital isolated GH deficiency (GHD). Taking advantage of the cohort of patients from the GENHYPOPIT network, we studied 41 patients with unexplained isolated GHD. All patients had Sanger sequencing of the GPR101 gene and array comparative genome hybridization (aCGH) to look for deletions. Functional studies (cell culture with GH secretion measurements, cAMP response) were performed. One novel GPR101 variant, c.589 G>T (p.V197L), was seen in the heterozygous state in a patient with isolated GHD. In silico analysis suggested that this variant could be deleterious. Functional studies did not show any significant difference in comparison with wild type for GH secretion and cAMP response. No truncating, frameshift, or small insertion-deletion (indel) GPR101 mutations were seen in the 41 patients. No deletion or other copy number variation at chromosome Xq26.3 was found on aCGH. We found a novel GPR101 variant of unknown significance, in a patient with isolated GH deficiency. Our study did not identify GPR101 abnormalities as a frequent cause of GH deficiency. © Georg Thieme Verlag KG Stuttgart · New York.

GPR139, an Orphan Receptor Highly Enriched in the Habenula and Septum, Is Activated by the Essential Amino Acids L-Tryptophan and L-Phenylalanine.

PubMed

Liu, Changlu; Bonaventure, Pascal; Lee, Grace; Nepomuceno, Diane; Kuei, Chester; Wu, Jiejun; Li, Qingqin; Joseph, Victory; Sutton, Steven W; Eckert, William; Yao, Xiang; Yieh, Lynn; Dvorak, Curt; Carruthers, Nicholas; Coate, Heather; Yun, Sujin; Dugovic, Christine; Harrington, Anthony; Lovenberg, Timothy W

2015-11-01

GPR139 is an orphan G-protein-coupled receptor expressed in the central nervous system. To identify its physiologic ligand, we measured GPR139 receptor activity from recombinant cells after treatment with amino acids, orphan ligands, serum, and tissue extracts. GPR139 activity was measured using guanosine 5'-O-(3-[(35)S]thio)-triphosphate binding, calcium mobilization, and extracellular signal-regulated kinases phosphorylation assays. Amino acids L-tryptophan (L-Trp) and L-phenylalanine (L-Phe) activated GPR139, with EC50 values in the 30- to 300-μM range, consistent with the physiologic concentrations of L-Trp and L-Phe in tissues. Chromatography of rat brain, rat serum, and human serum extracts revealed two peaks of GPR139 activity, which corresponded to the elution peaks of L-Trp and L-Phe. With the purpose of identifying novel tools to study GPR139 function, a high-throughput screening campaign led to the identification of a selective small-molecule agonist [JNJ-63533054, (S)-3-chloro-N-(2-oxo-2-((1-phenylethyl)amino)ethyl) benzamide]. The tritium-labeled JNJ-63533054 bound to cell membranes expressing GPR139 and could be specifically displaced by L-Trp and L-Phe. Sequence alignment revealed that GPR139 is highly conserved across species, and RNA sequencing studies of rat and human tissues indicated its exclusive expression in the brain and pituitary gland. Immunohistochemical analysis showed specific expression of the receptor in circumventricular regions of the habenula and septum in mice. Together, these findings suggest that L-Trp and L-Phe are candidate physiologic ligands for GPR139, and we hypothesize that this receptor may act as a sensor to detect dynamic changes of L-Trp and L-Phe in the brain. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Mining microarray datasets in nutrition: expression of the GPR120 (n-3 fatty acid receptor/sensor) gene is down-regulated in human adipocytes by macrophage secretions.

PubMed

Trayhurn, Paul; Denyer, Gareth

2012-01-01

Microarray datasets are a rich source of information in nutritional investigation. Targeted mining of microarray data following initial, non-biased bioinformatic analysis can provide key insight into specific genes and metabolic processes of interest. Microarrays from human adipocytes were examined to explore the effects of macrophage secretions on the expression of the G-protein-coupled receptor (GPR) genes that encode fatty acid receptors/sensors. Exposure of the adipocytes to macrophage-conditioned medium for 4 or 24 h had no effect on GPR40 and GPR43 expression, but there was a marked stimulation of GPR84 expression (receptor for medium-chain fatty acids), the mRNA level increasing 13·5-fold at 24 h relative to unconditioned medium. Importantly, expression of GPR120, which encodes an n-3 PUFA receptor/sensor, was strongly inhibited by the conditioned medium (15-fold decrease in mRNA at 24 h). Macrophage secretions have major effects on the expression of fatty acid receptor/sensor genes in human adipocytes, which may lead to an augmentation of the inflammatory response in adipose tissue in obesity.

Mining microarray datasets in nutrition: expression of the GPR120 (n-3 fatty acid receptor/sensor) gene is down-regulated in human adipocytes by macrophage secretions

PubMed Central

Trayhurn, Paul; Denyer, Gareth

2012-01-01

Microarray datasets are a rich source of information in nutritional investigation. Targeted mining of microarray data following initial, non-biased bioinformatic analysis can provide key insight into specific genes and metabolic processes of interest. Microarrays from human adipocytes were examined to explore the effects of macrophage secretions on the expression of the G-protein-coupled receptor (GPR) genes that encode fatty acid receptors/sensors. Exposure of the adipocytes to macrophage-conditioned medium for 4 or 24 h had no effect on GPR40 and GPR43 expression, but there was a marked stimulation of GPR84 expression (receptor for medium-chain fatty acids), the mRNA level increasing 13·5-fold at 24 h relative to unconditioned medium. Importantly, expression of GPR120, which encodes an n-3 PUFA receptor/sensor, was strongly inhibited by the conditioned medium (15-fold decrease in mRNA at 24 h). Macrophage secretions have major effects on the expression of fatty acid receptor/sensor genes in human adipocytes, which may lead to an augmentation of the inflammatory response in adipose tissue in obesity. PMID:25191551

Gaussian Process Regression (GPR) Representation in Predictive Model Markup Language (PMML)

PubMed Central

Lechevalier, D.; Ak, R.; Ferguson, M.; Law, K. H.; Lee, Y.-T. T.; Rachuri, S.

2017-01-01

This paper describes Gaussian process regression (GPR) models presented in predictive model markup language (PMML). PMML is an extensible-markup-language (XML) -based standard language used to represent data-mining and predictive analytic models, as well as pre- and post-processed data. The previous PMML version, PMML 4.2, did not provide capabilities for representing probabilistic (stochastic) machine-learning algorithms that are widely used for constructing predictive models taking the associated uncertainties into consideration. The newly released PMML version 4.3, which includes the GPR model, provides new features: confidence bounds and distribution for the predictive estimations. Both features are needed to establish the foundation for uncertainty quantification analysis. Among various probabilistic machine-learning algorithms, GPR has been widely used for approximating a target function because of its capability of representing complex input and output relationships without predefining a set of basis functions, and predicting a target output with uncertainty quantification. GPR is being employed to various manufacturing data-analytics applications, which necessitates representing this model in a standardized form for easy and rapid employment. In this paper, we present a GPR model and its representation in PMML. Furthermore, we demonstrate a prototype using a real data set in the manufacturing domain. PMID:29202125

Gaussian Process Regression (GPR) Representation in Predictive Model Markup Language (PMML).

PubMed

Park, J; Lechevalier, D; Ak, R; Ferguson, M; Law, K H; Lee, Y-T T; Rachuri, S

2017-01-01

This paper describes Gaussian process regression (GPR) models presented in predictive model markup language (PMML). PMML is an extensible-markup-language (XML) -based standard language used to represent data-mining and predictive analytic models, as well as pre- and post-processed data. The previous PMML version, PMML 4.2, did not provide capabilities for representing probabilistic (stochastic) machine-learning algorithms that are widely used for constructing predictive models taking the associated uncertainties into consideration. The newly released PMML version 4.3, which includes the GPR model, provides new features: confidence bounds and distribution for the predictive estimations. Both features are needed to establish the foundation for uncertainty quantification analysis. Among various probabilistic machine-learning algorithms, GPR has been widely used for approximating a target function because of its capability of representing complex input and output relationships without predefining a set of basis functions, and predicting a target output with uncertainty quantification. GPR is being employed to various manufacturing data-analytics applications, which necessitates representing this model in a standardized form for easy and rapid employment. In this paper, we present a GPR model and its representation in PMML. Furthermore, we demonstrate a prototype using a real data set in the manufacturing domain.

Examination of Single- and Multi-Channel GPR Bridge Deck Condition Assessment Methods with Comparison to Complementary NDE Results

NASA Astrophysics Data System (ADS)

Romero, Francisco A.; Manacorda, Guido; Simi, Alessandro; Gucunski, Nenad; Parvardeh, Hooman

2013-04-01

A sixteen-channel GPR system which houses both longitudinally- and transversely-polarized, 2.0 GHz antenna elements within a single housing was compared with a single-channel GPR system that was separately using both 1.5GHz and 2.6GHz antennas oriented in the transverse polarization, for the purpose of determining effectiveness of bridge deck condition assessment. The multi-channel system has obvious benefits which include closely-spaced GPR antennas (channels) that provide better lateral resolution, as well as combined data sets from co-linear antennas oriented in both the transverse and longitudinal polarizations, which has benefits for imaging within the deck's internal structure. However, the primary objective was to determine whether the multi-channel system would perform in a similar manner to proven single-channel GPR technology during an attenuation-based GPR condition assessment on an older, partially deteriorated deck in northwestern New Jersey that is annually exposed to freeze-thaw conditions as well as de-icing salts. These assessments were made by focusing on identifying the strongest reflections from the upper mat of transversely-oriented rebars within the deck and comparing reflection strength, or conversely, attenuation of the GPR signal, from each of the 'picked' GPR rebar responses. Coordinates for each of the GPR picks, along with amplitude or attenuation measurements, were gridded and contour-plotted for the purpose of identifying areas identified as either relatively deteriorated or sound. Initially, results were compared for data with no applied correction that takes into account GPR signal attenuation with increasing depth within the concrete deck. Final GPR maps were produced incorporating a depth-correction technique similar to what is described by Barnes, et. al., Romero, et. al, and Gucunski, et. al., a process which has been clearly demonstrated to better correlate GPR results with not only ground truth (cores, sounding) but also with other NDE technologies. Not only did all the single- and multi-channel system comparisons generate nearly identical deterioration maps when GPR results were compared and examined, but mapped results obtained from other NDE methods on the same deck were used to identify zones where corrosive environment (electrical resistivity - ER) elastic modulus (ultrasonic surface wave - USW), and identified delaminations (impact-echo - IE) had commonality with the GPR results. A summary of the equipment used, as well as general data collection and analysis procedures is provided for the GPR condition assessments. Brief descriptions of background and references to how the complementary NDT technologies are deployed, and how data are interpreted, are also discussed. Comparative maps for all technologies are used for illustrative purposes.

Postprandial inhibition of gastric ghrelin secretion by long-chain fatty acid through GPR120 in isolated gastric ghrelin cells and mice

PubMed Central

Lu, Xinping; Zhao, Xilin; Feng, Jianying; Liou, Alice P.; Anthony, Shari; Pechhold, Susanne; Sun, Yuxiang; Lu, Huiyan

2012-01-01

Ghrelin is a gastric peptide hormone that controls appetite and energy homeostasis. Plasma ghrelin levels rise before a meal and fall quickly thereafter. Elucidation of the regulation of ghrelin secretion has been hampered by the difficulty of directly interrogating ghrelin cells diffusely scattered within the complex gastric mucosa. Therefore, we generated transgenic mice with ghrelin cell expression of green fluorescent protein (GFP) to enable characterization of ghrelin secretion in a pure population of isolated gastric ghrelin-expressing GFP (Ghr-GFP) cells. Using quantitative RT-PCR and immunofluorescence staining, we detected a high level of expression of the long-chain fatty acid (LCFA) receptor GPR120, while the other LCFA receptor, GPR40, was undetectable. In short-term-cultured pure Ghr-GFP cells, the LCFAs docosadienoic acid, linolenic acid, and palmitoleic acid significantly suppressed ghrelin secretion. The physiological mechanism of LCFA inhibition on ghrelin secretion was studied in mice. Serum ghrelin levels were transiently suppressed after gastric gavage of LCFA-rich lipid in mice with pylorus ligation, indicating that the ghrelin cell may directly sense increased gastric LCFA derived from ingested intraluminal lipids. Meal-induced increase in gastric mucosal LCFA was assessed by measuring the transcripts of markers for tissue uptake of LCFA, lipoprotein lipase (LPL), fatty acid translocase (CD36), glycosylphosphatidylinositol-anchored HDL-binding protein 1, and nuclear fatty acid receptor peroxisome proliferator-activated receptor-γ. Quantitative RT-PCR studies indicate significantly increased mRNA levels of lipoprotein lipase, glycosylphosphatidylinositol-anchored HDL-binding protein 1, and peroxisome proliferator-activated receptor-γ in postprandial gastric mucosa. These results suggest that meal-related increases in gastric mucosal LCFA interact with GPR120 on ghrelin cells to inhibit ghrelin secretion. PMID:22678998

Three classes of ligands each bind to distinct sites on the orphan G protein-coupled receptor GPR84.

PubMed

Mahmud, Zobaer Al; Jenkins, Laura; Ulven, Trond; Labéguère, Frédéric; Gosmini, Romain; De Vos, Steve; Hudson, Brian D; Tikhonova, Irina G; Milligan, Graeme

2017-12-20

Medium chain fatty acids can activate the pro-inflammatory receptor GPR84 but so also can molecules related to 3,3'-diindolylmethane. 3,3'-Diindolylmethane and decanoic acid acted as strong positive allosteric modulators of the function of each other and analysis showed the affinity of 3,3'-diindolylmethane to be at least 100 fold higher. Methyl decanoate was not an agonist at GPR84. This implies a key role in binding for the carboxylic acid of the fatty acid. Via homology modelling we predicted and confirmed an integral role of arginine 172 , located in the 2nd extracellular loop, in the action of decanoic acid but not of 3,3'-diindolylmethane. Exemplars from a patented series of GPR84 antagonists were able to block agonist actions of both decanoic acid and 3,3'-diindolylmethane at GPR84. However, although a radiolabelled form of a related antagonist, [ 3 H]G9543, was able to bind with high affinity to GPR84, this was not competed for by increasing concentrations of either decanoic acid or 3,3'-diindolylmethane and was not affected adversely by mutation of arginine 172 . These studies identify three separable ligand binding sites within GPR84 and suggest that if medium chain fatty acids are true endogenous regulators then co-binding with a positive allosteric modulator would greatly enhance their function in physiological settings.

A large deletion in GPR98 causes type IIC Usher syndrome in male and female members of an Iranian family.

PubMed

Hilgert, N; Kahrizi, K; Dieltjens, N; Bazazzadegan, N; Najmabadi, H; Smith, R J H; Van Camp, G

2009-04-01

Usher syndrome (USH) is a clinically and genetically heterogeneous disease. The three recognised clinical phenotypes (types I, II and III; USH1, USH2 and USH3) are caused by mutations in nine different genes. USH2C is characterised by moderate to severe hearing loss, retinitis pigmentosa and normal vestibular function. One earlier report describes mutations in GPR98 (VLGR1) in four families segregating this phenotype. To detect the disease-causing mutation in an Iranian family segregating USH2C. In this family, five members had a phenotype compatible with Usher syndrome, and two others had nonsyndromic hearing loss. Mutation analysis of all 90 coding exons of GPR98. Consistent with these clinical findings, the five subjects with USH carried a haplotype linked to the USH2C locus, whereas the two subjects with nonsyndromic hearing loss did not. We identified a new mutation in GPR98 segregating with USH2C in this family. The mutation is a large deletion g.371657_507673del of exons 84 and 85, presumably leading to a frameshift. A large GPR98 deletion of 136 017 bp segregates with USH2C in an Iranian family. To our knowledge, this is only the second report of a GPR98 mutation, and the first report on male subjects with USH2C and a GPR98 mutation.

Metalloprotease cleavage of the N terminus of the orphan G protein-coupled receptor GPR37L1 reduces its constitutive activity.

PubMed

Coleman, James L J; Ngo, Tony; Schmidt, Johannes; Mrad, Nadine; Liew, Chu Kong; Jones, Nicole M; Graham, Robert M; Smith, Nicola J

2016-04-12

Little is known about the pharmacology or physiology of GPR37L1, a G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor that is abundant in the cerebellum. Mice deficient in this receptor exhibit precocious cerebellar development and hypertension. We showed that GPR37L1 coupled to the G protein Gα(s) when heterologously expressed in cultured cells in the absence of any added ligand, whereas a mutant receptor that lacked the amino terminus was inactive. Conversely, inhibition of ADAMs (a disintegrin and metalloproteases) enhanced receptor activity, indicating that the presence of the amino terminus is necessary for GPR37L1 signaling. Metalloprotease-dependent processing of GPR37L1 was evident in rodent cerebellum, where we detected predominantly the cleaved, inactive form. However, comparison of the accumulation of cAMP (adenosine 3',5'-monophosphate) in response to phosphodiesterase inhibition in cerebellar slice preparations from wild-type and GPR37L1-null mice showed that some constitutive signaling remained in the wild-type mice. In reporter assays of Gα(s) or Gα(i) signaling, the synthetic, prosaposin-derived peptide prosaptide (TX14A) did not increase GPR37L1 activity. Our data indicate that GPR37L1 may be a constitutively active receptor, or perhaps its ligand is present under the conditions that we used for analysis, and that the activity of this receptor is instead controlled by signals that regulate metalloprotease activity in the tissue. Copyright © 2016, American Association for the Advancement of Science.

An expressed sequence tag (EST) data mining strategy succeeding in the discovery of new G-protein coupled receptors.

PubMed

Wittenberger, T; Schaller, H C; Hellebrand, S

2001-03-30

We have developed a comprehensive expressed sequence tag database search method and used it for the identification of new members of the G-protein coupled receptor superfamily. Our approach proved to be especially useful for the detection of expressed sequence tag sequences that do not encode conserved parts of a protein, making it an ideal tool for the identification of members of divergent protein families or of protein parts without conserved domain structures in the expressed sequence tag database. At least 14 of the expressed sequence tags found with this strategy are promising candidates for new putative G-protein coupled receptors. Here, we describe the sequence and expression analysis of five new members of this receptor superfamily, namely GPR84, GPR86, GPR87, GPR90 and GPR91. We also studied the genomic structure and chromosomal localization of the respective genes applying in silico methods. A cluster of six closely related G-protein coupled receptors was found on the human chromosome 3q24-3q25. It consists of four orphan receptors (GPR86, GPR87, GPR91, and H963), the purinergic receptor P2Y1, and the uridine 5'-diphosphoglucose receptor KIAA0001. It seems likely that these receptors evolved from a common ancestor and therefore might have related ligands. In conclusion, we describe a data mining procedure that proved to be useful for the identification and first characterization of new genes and is well applicable for other gene families. Copyright 2001 Academic Press.

Discrimination between landmine and mine-like targets using wavelets and spectral analysis

NASA Astrophysics Data System (ADS)

Mohana, Mahmoud A.; Abbas, Abbas M.; Gomaa, Mohamed L.; Ebrahim, Shereen M.

2013-06-01

Landmine is an explosive apparatus hidden in or on the ground, which blows up when a person or vehicle passes over it. Egypt is one of the countries suffering due to the unexploded ordnance (UXO). Around 2 million UXO are present in the Egyptian soil especially at Al-Alameen province, north of the western desert. Detection of buried landmines is a problem of military and humanitarian importance. Ground penetrating radar (GPR) is a powerful and non-destructive geophysical approach with a wide range of advantages in the field of landmine inspection. In the present paper, we apply different simulation models with Vivaldi antenna and mine-like targets by using the CST Microwave studio program. The field work is carried out by using a GPR device of model SIR 2000 from GSSI (Geophysical Survey Systems Incorporation) connected to 900 MHz antenna where the targets were buried in sand soil. Depending on the fact that the receiving powers (reflected, refracted and scattered) from the different materials are different, we study the spectral power densities for the received power from the different targets. The techniques used in this study are: direct fast Fourier transform, short time Fourier transform (spectrogram), wavelets transform and denoising techniques. Our results ought to be considered as finger prints for different scanned targets during this work. So we can discriminate between landmines and mine-like targets.

Combined GPR and ERT exploratory geophysical survey of the Medieval Village of Pancorbo Castle (Burgos, Spain)

NASA Astrophysics Data System (ADS)

Fernández-Álvarez, José-Paulino; Rubio-Melendi, David; Quirós Castillo, Juan Antonio; González-Quirós, Andrés; Cimadevilla-Fuente, David

2017-09-01

Ground-penetrating Radar (GPR) and Electrical Resistivity Tomography (ERT) have been fruitfully employed for archaeological purposes. An area at the Pancorbo medieval site in Burgos (Spain) has been jointly explored by GPR and ERT in the search for the buried remains of the Pancorbo medieval village. After data collection, quality control and merging, a shallow depth of interest was identified and studied in detail. 3D resistivity simulation, considering sensible geometrical structures of the targets helped discover anomalies present in the area. On the other hand, visual GPR inspection was considerably enhanced by trace energy attribute analysis which provided a plan view of the existing anomalies. Two posterior archaeological excavations have a very good correlation between the identified anomalies and the excavated remains. The survey also provides hints for the continuation of the excavation.

GPR surveying of transport infrastructures and buildings; underground utility and void sensing - ongoing activities in Working Group 2 of COST Action TU1208

NASA Astrophysics Data System (ADS)

Pajewski, Lara; Plati, Christina; Derobert, Xavier

2015-04-01

This work aims at presenting the ongoing research activities carried out in Working Group 2 'GPR surveying of pavements, bridges, tunnels and buildings; underground utility and void sensing' of the COST (European COoperation in Science and Technology) Action TU1208 'Civil Engineering Applications of Ground Penetrating Radar' (www.GPRadar.eu). The principal goal of the COST Action TU1208 is to exchange and increase scientific-technical knowledge and experience of Ground Penetrating Radar (GPR) techniques in civil engineering, whilst simultaneously promoting throughout Europe the effective use of this safe and non-destructive technique in the monitoring of infrastructures and structures. Four Working Groups (WGs) carry out the research activities. WG1 focuses on the development of innovative GPR equipment dedicated for civil engineering applications. WG2 deals with the development of guidelines and protocols for the surveying, through the use of a GPR system, of transport infrastructure and buildings, as well as for the sensing of utilities and voids. WG3 deals with the development of electromagnetic forward and inverse scattering methods, for the characterization of GPR scenarios, as well as with data- processing algorithms for the elaboration of the data collected during GPR surveys. WG4 is concerned with the use of GPR in fields different from the civil engineering, as well as with the integration of GPR with other non-destructive testing techniques. Each WG includes several Projects. WG2 includes five Projects. Project 2.1 focuses on outlining 'Innovative inspection procedures for effective GPR surveying of critical transport infrastructures (pavements, bridges and tunnels).' Project 2.2 is concerned with the development of 'Innovative inspection procedures for effective GPR surveying of buildings.' Project 2.3 deals with identifying 'Innovative inspection procedures for effective GPR sensing and mapping of underground utilities and voids, with a focus to urban areas.' Project 2.4 focuses on the development of 'Innovative procedures for effective GPR inspection of construction materials and structures.' The WG2 also includes Project 2.5 on the 'Determination, by using GPR, of the volumetric water content in structures, sub-structures, foundations and soil,' this is a topic of great interest in civil engineering, as water infiltration is often a relevant cause of degradation of structures, such as roads of bridges, and of rebar corrosion. During the first year of the Action, information was collected and shared about state-of-the-art, ongoing studies, problems and future research needs, in the topics covered by the five above-mentioned Projects [1-3]. Based on the experience and knowledge gained from the in-depth review work carried out by WG2, several case studies were then conducted; they were presented during the Second General Meeting and the GPR 2014 conference [5, 6]. Furthermore, the extension of GPR application to railways track ballast assessment was demonstrated [7]. The WG2 identified reference test-sites, suitable to compare inspection procedures or to test GPR equipment. The IFSTTAR geophysical test site is an open-air laboratory including a large and deep area, filled with various materials arranged in horisontal compacted slices, separated by vertical interfaces and water-tighted in surface; several objects as pipes, polystyrene hollows, boulders and masonry are embedded in the field [4]. The IFSTTAR full-scale APT facility is an outdoor circular carousel dedicated to full-scale pavement experiments, consisting of a central tower and four long arms equipped with wheels, running on a circular test track [4]. Furthermore, the WG2 is building a database of available experimental results, which are at the disposal of WG3 Members to test their electromagnetic modeling/inversion/data-processing methods. Another interesting and promising WG2 initiative that has to be mentioned is the development of a Catalogue of European test sites and laboratories for the testing of GPR equipment, methodology and procedures, that is being coordinated by France and Italy. The catalogue will represent a useful tool for the GPR community and it will contribute to identifying new cooperation possibilities among research groups, to clarifying which are the missing testing facilities in the various European regions, and to addressing current or future research needs. Acknowledgement The Authors thank COST, for funding the COST Action TU1208 'Civil Engineering Applications of Ground Penetrating Radar.' References [1] Proc. First Action's General Meeting (Rome, Italy, 22-24 July 2013), 1st edition, COST Action TU1208, L. Pajewski, A. Benedetto, Eds., ISBN 978-88-548-6191-6 (Aracne, 2013). [2] Civil Engineering Applications of Ground Penetrating Radar, A. Benedetto, L. Pajewski, Eds., ISBN 978-3-319-04812-3 (Springer, 2015). [3] A. Benedetto, 'State of the Art of GPR Applications and New Trends in Transportation Infrastructures,' Future Trends in Civil Engineering, A. Ceric, S. Lakusic, Eds., ISBN 978-953-6272-65-5 (2014). [4] Proc. 2013 Working Group Progress Meeting (Nantes, France, 24-25 February 2014), COST Action TU1208, L. Pajewski, X. Derobert, Eds., ISBN 978-88-548-7223-3 (Aracne, 2014). [5] Proc. 15th International Conference on Ground Penetrating Radar - GPR2014, S. Lambot, A. Giannopoulos, L. Pajewski, F. De André, E. Slob, C. Craeye, Eds., IEEE Conf. Number 35163 (IEEE, 2014). [6] Proc. Second Action's General Meeting (Vienna, Austria, 30 April-2 May 2014), COST Action TU1208, L. Pajewski, A. Benedetto, Eds., ISBN 978-88-548-7224-0 (Aracne, 2014). [7] S. Fontul, F. De Chiara, E. Fortunato, A. Lopes, 'Evaluation of ballast condition using Ground Penetrating Radar,' The Ninth Intl. Conf. on Engineering Computational Technology (2014).

Water Leak Detection by Using Ground Penetrating Radar, Synthetic Simulation and Four-Dimensional Visualization

NASA Astrophysics Data System (ADS)

Al-Shukri, H.; Eyuboglu, S.; Mahdi, H.

2005-12-01

Many geophysical techniques have been suggested as candidates for detecting water leakage in water distribution system, including ground penetrating radar (GPR), acoustic devices, and gas sampling devices. A series of laboratory experiments were conducted to determine the validity and effectiveness of GPR in detecting water leakage in metal and plastic PVC pipes. The goal was to derive a practical and robust procedure for detecting such leakage. Initially, prototype laboratory experiments were designed to simulate leaks in both PVC and metal pipe. The experiments were very well controlled and results obtained indicate that GPR is effective in detecting subsurface water leaks. This was followed by an outdoor life size experiments. 50 feet by 30 feet by 5 feet test bed was constructed using local soil and commercial water distribution pipes. A 400 MHz antenna was used to collect three-dimensional GPR data as a function of time for a number of experiments using different type of pipes. Advanced imaging and visualization technology was used to further analyze the data. The UALR Virtual Reality Center CAVE facilities were utilized to accomplish this test. Results obtained indicate that GPR is effective in detecting subsurface water leaks in both pipes. Synthetic models of the GPR signals based on Finite Difference Time Domain Method (FDTD) were built to help select an appropriate equipment configuration (frequency band, type of antenna, and real-time imaging software) prior to data acquisition. The simulation software was used to determine the near-field radiation characteristics of the GPR antenna. Different experimental models were adapted for which observational GPR data was previously collected. Matlab regression analysis was used to generate the incident waves for each model to ensure highly accurate and controlled experiments.

Investigation of free fatty acid associated recombinant membrane receptor protein expression in HEK293 cells using Raman spectroscopy, calcium imaging, and atomic force microscopy.

PubMed

Lin, Juqiang; Xu, Han; Wu, Yangzhe; Tang, Mingjie; McEwen, Gerald D; Liu, Pin; Hansen, Dane R; Gilbertson, Timothy A; Zhou, Anhong

2013-02-05

G-protein-coupled receptor 120 (GPR120) is a previously orphaned G-protein-coupled receptor that apparently functions as a sensor for dietary fat in the gustatory and digestive systems. In this study, a cDNA sequence encoding a doxycycline (Dox)-inducible mature peptide of GPR120 was inserted into an expression vector and transfected in HEK293 cells. We measured Raman spectra of single HEK293 cells as well as GPR120-expressing HEK293-GPR120 cells at a 48 h period following the additions of Dox at several concentrations. We found that the spectral intensity of HEK293-GPR120 cells is dependent upon the dose of Dox, which correlates with the accumulation of GPR120 protein in the cells. However, the amount of the fatty acid activated changes in intracellular calcium (Ca(2+)) as measured by ratiometric calcium imaging was not correlated with Dox concentration. Principal components analysis (PCA) of Raman spectra reveals that the spectra from different treatments of HEK293-GPR120 cells form distinct, completely separated clusters with the receiver operating characteristic (ROC) area of 1, while those spectra for the HEK293 cells form small overlap clusters with the ROC area of 0.836. It was also found that expression of GPR120 altered the physiochemical and biomechanical properties of the parental cell membrane surface, which was quantitated by atomic force microscopy (AFM). These findings demonstrate that the combination of Raman spectroscopy, calcium imaging, and AFM may provide new tools in noninvasive and quantitative monitoring of membrane receptor expression induced alterations in the biophysical and signaling properties of single living cells.

Mutation analysis and molecular modeling for the investigation of ligand-binding modes of GPR84.

PubMed

Nikaido, Yoshiaki; Koyama, Yuuta; Yoshikawa, Yasushi; Furuya, Toshio; Takeda, Shigeki

2015-05-01

GPR84 is a G protein-coupled receptor for medium-chain fatty acids. Capric acid and 3,3'-diindolylmethane are specific agonists for GPR84. We built a homology model of a GPR84-capric acid complex to investigate the ligand-binding mode using the crystal structure of human active-state β2-adrenergic receptor. We performed site-directed mutagenesis to subject ligand-binding sites to our model using GPR84-Giα fusion proteins and a [(35)S]GTPγS-binding assay. We compared the activity of the wild type and mutated forms of GPR84 by [(35)S]GTPγS binding to capric acid and diindolylmethane. The mutations L100D `Ballesteros-Weinstein numbering: 3.32), F101Y (3.33) and N104Q (3.36) in the transmembrane helix III and N357D (7.39) in the transmembrane helix VII resulted in reduced capric acid activity but maintained the diindolylmethane responses. Y186F (5.46) and Y186H (5.46) mutations had no characteristic effect on capric acid but with diindolylmethane they significantly affected the G protein activation efficiency. The L100D (3.32) mutant responded to decylamine, a fatty amine, instead of a natural agonist, the fatty acid capric acid, suggesting that we have identified a mutated G protein-coupled receptor-artificial ligand pairing. Our molecular model provides an explanation for these results and interactions between GPR84 and capric acid. Further, from the results of a double stimulation assay, we concluded that diindolylmethane was a positive allosteric modulator for GPR84. © The Authors 2014. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Investigating Temporal and Spatial Variations in Near Surface Water Content using GPR

NASA Astrophysics Data System (ADS)

Hubbard, S. S.; Grote, K.; Kowalsky, M. B.; Rubin, Y.

2001-12-01

Using only conventional point or well logging measurements, it is difficult to obtain information about water content with sufficient spatial resolution and coverage to be useful for near surface applications such as for input to vadose zone predictive models or for assisting with precision crop management. Prompted by successful results of a controlled ground penetrating radar (GPR) pilot study, we are investigating the applicability of GPR methods to estimate near surface water content at a study site within the Robert Mondavi vineyards in Napa County, California. Detailed information about soil variability and water content within vineyards could assist in estimation of plantable acreage, in the design of vineyard layout and in the design of an efficient irrigation/agrochemical application procedure. Our research at the winery study site involves investigation of optimal GPR acquisition and processing techniques, modeling of GPR attributes, and inversion of the attributes for water content information over space and time. A secondary goal of our project is to compare water content information obtained from the GPR data with information available from other types of measurements that are being used to assist in precision crop management. This talk will focus on point and spatial correlation estimation of water content obtained using GPR groundwave information only, and comparison of those estimates with information obtained from analysis of soils, TDR, neutron probe and remote sensing data sets. This comparison will enable us to 1) understand the potential of GPR for providing water content information in the very shallow subsurface, and to 2) investigate the interrelationships between the different types of measurements (and associated measurement scales) that are being utilized to characterize the shallow subsurface water content over space and time.

Electromagnetic signal penetration in a planetary soil simulant: Estimated attenuation rates using GPR and TDR in volcanic deposits on Mount Etna

NASA Astrophysics Data System (ADS)

Lauro, S. E.; Mattei, E.; Cosciotti, B.; Di Paolo, F.; Arcone, S. A.; Viccaro, M.; Pettinelli, E.

2017-07-01

Ground-penetrating radar (GPR) is a well-established geophysical terrestrial exploration method and has recently become one of the most promising for planetary subsurface exploration. Several future landing vehicles like EXOMARS, 2020 NASA ROVER, and Chang'e-4, to mention a few, will host GPR. A GPR survey has been conducted on volcanic deposits on Mount Etna (Italy), considered a good analogue for Martian and Lunar volcanic terrains, to test a novel methodology for subsoil dielectric properties estimation. The stratigraphy of the volcanic deposits was investigated using 500 MHz and 1 GHz antennas in two different configurations: transverse electric and transverse magnetic. Sloping discontinuities have been used to estimate the loss tangents of the upper layer of such deposits by applying the amplitude-decay and frequency shift methods and approximating the GPR transmitted signal by Gaussian and Ricker wavelets. The loss tangent values, estimated using these two methodologies, were compared and validated with those retrieved from time domain reflectometry measurements acquired along the radar profiles. The results show that the proposed analysis, together with typical GPR methods for the estimation of the real part of permittivity, can be successfully used to characterize the electrical properties of planetary subsurface and to define some constraints on its lithology of the subsurface.

The novel cannabinoid receptor GPR55 mediates anxiolytic-like effects in the medial orbital cortex of mice with acute stress.

PubMed

Shi, Qi-Xin; Yang, Liu-Kun; Shi, Wen-Long; Wang, Lu; Zhou, Shi-Meng; Guan, Shao-Yu; Zhao, Ming-Gao; Yang, Qi

2017-08-11

The G protein-coupled receptor 55 (GPR55) is a novel cannabinoid receptor, whose exact role in anxiety remains unknown. The present study was conducted to explore the possible mechanisms by which GPR55 regulates anxiety and to evaluate the effectiveness of O-1602 in the treatment of anxiety-like symptoms. Mice were exposed to two types of acute stressors: restraint and forced swimming. Anxiety behavior was evaluated using the elevated plus maze and the open field test. We found that O-1602 alleviated anxiety-like behavior in acutely stressed mice. We used lentiviral shRNA to selective ly knockdown GPR55 in the medial orbital cortex and found that knockdown of GPR55 abolished the anxiolytic effect of O-1602. We also used Y-27632, a specific inhibitor of ROCK, and U73122, an inhibitor of PLC, and found that both inhibitors attenuated the effectiveness of O-1602. Western blot analysis revealed that O-1602 downregulated the expression of GluA1 and GluN2A in mice. Taken together, these results suggest that GPR55 plays an important role in anxiety and O-1602 may have therapeutic potential in treating anxiety-like symptoms.

Detection of Subsurface Defects in Levees in Correlation to Weather Conditions Utilizing Ground Penetrating Radar

NASA Astrophysics Data System (ADS)

Martinez, I. A.; Eisenmann, D.

2012-12-01

Ground Penetrating Radar (GPR) has been used for many years in successful subsurface detection of conductive and non-conductive objects in all types of material including different soils and concrete. Typical defect detection is based on subjective examination of processed scans using data collection and analysis software to acquire and analyze the data, often requiring a developed expertise or an awareness of how a GPR works while collecting data. Processing programs, such as GSSI's RADAN analysis software are then used to validate the collected information. Iowa State University's Center for Nondestructive Evaluation (CNDE) has built a test site, resembling a typical levee used near rivers, which contains known sub-surface targets of varying size, depth, and conductivity. Scientist at CNDE have developed software with the enhanced capabilities, to decipher a hyperbola's magnitude and amplitude for GPR signal processing. With this enhanced capability, the signal processing and defect detection capabilities for GPR have the potential to be greatly enhanced. This study will examine the effects of test parameters, antenna frequency (400MHz), data manipulation methods (which include data filters and restricting the range of depth in which the chosen antenna's signal can reach), and real-world conditions using this test site (such as varying weather conditions) , with the goal of improving GPR tests sensitivity for differing soil conditions.

A Newly Discovered Antifibrotic Pathway Regulated by Two Fatty Acid Receptors: GPR40 and GPR84.

PubMed

Gagnon, Lyne; Leduc, Martin; Thibodeau, Jean-Francois; Zhang, Ming-Zhi; Grouix, Brigitte; Sarra-Bournet, Francois; Gagnon, William; Hince, Kathy; Tremblay, Mikaël; Geerts, Lilianne; Kennedy, Christopher R J; Hébert, Richard L; Gutsol, Alex; Holterman, Chet E; Kamto, Eldjonai; Gervais, Liette; Ouboudinar, Jugurtha; Richard, Jonathan; Felton, Alexandra; Laverdure, Alexandre; Simard, Jean-Christophe; Létourneau, Sylvie; Cloutier, Marie-Pier; Leblond, Francois A; Abbott, Shaun D; Penney, Christopher; Duceppe, Jean-Simon; Zacharie, Boulos; Dupuis, Jocelyn; Calderone, Angelino; Nguyen, Quang T; Harris, Raymond C; Laurin, Pierre

2018-05-01

Numerous clinical conditions can lead to organ fibrosis and functional failure. There is a great need for therapies that could effectively target pathophysiological pathways involved in fibrosis. GPR40 and GPR84 are G protein-coupled receptors with free fatty acid ligands and are associated with metabolic and inflammatory disorders. Although GPR40 and GPR84 are involved in diverse physiological processes, no evidence has demonstrated the relevance of GPR40 and GPR84 in fibrosis pathways. Using PBI-4050 (3-pentylbenzeneacetic acid sodium salt), a synthetic analog of a medium-chain fatty acid that displays agonist and antagonist ligand affinity toward GPR40 and GPR84, respectively, we uncovered an antifibrotic pathway involving these receptors. In experiments using Gpr40- and Gpr84-knockout mice in models of kidney fibrosis (unilateral ureteral obstruction, long-term post-acute ischemic injury, and adenine-induced chronic kidney disease), we found that GPR40 is protective and GPR84 is deleterious in these diseases. Moreover, through binding to GPR40 and GPR84, PBI-4050 significantly attenuated fibrosis in many injury contexts, as evidenced by the antifibrotic activity observed in kidney, liver, heart, lung, pancreas, and skin fibrosis models. Therefore, GPR40 and GPR84 may represent promising molecular targets in fibrosis pathways. We conclude that PBI-4050 is a first-in-class compound that may be effective for managing inflammatory and fibrosis-related diseases. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

The Integration of GPR, GIS, and GPS for 3D Soil Morphologic Models

NASA Astrophysics Data System (ADS)

Tischler, M.; Collins, M. E.

2005-05-01

Ground-Penetrating Radar (GPR) has become a useful and efficient instrument for gathering information about subsurface diagnostic horizons in Florida soils. Geographic Information Systems (GIS) are a popular and valuable tool for spatial data analysis of real world features in a digital environment. Ground-Penetrating Radar can be linked to GIS by using Global Positioning Systems (GPS). By combining GPR, GPS, and GIS technologies, a more detailed geophysical survey can be completed for an area of interest by integratinghydrologic, pedologic, and geologic data. Thus, the objectives of this research were to identify subsurface soil layers using GPR and their geographic position with a highly accurate GPS; to develop a procedure to import GPR data into a popular software package, such as ArcGIS, and; to create 3D subsurface models based on the imported GPR data. The site for this study was the Plant Science Research and Education Center in Marion County, Florida. The soils are characterized by Recent-Pleistocene-age sand over the clayey, marine deposited Plio-Miocene-age Hawthorn Formation which drapes the Eocene-age Ocala Limestone. Consequently, soils in the research area vary from deep quartz sands (Typic Quartzipsamments) to shallow outcrops of the Hawthorn Formation (Arenic Hapludalfs). A GPR survey was performed on a 160 m x 320 m grid to gather data for processing. Four subsurface models estimating the depth to argillic horizon were created using a variety of specialized GPR data filters and geostatistical data analyses. The models were compared with ground-truth points that measured the depth to argillic horizon to validate each model and calculate error metrics. These models may assist research station personnel to determine best management practices (including experimental plot placement, irrigation management, fertilizer treatment, and pesticide applications). In addition, the developed methodology exploits the potential of combining GPR and GIS.

78 FR 65298 - Proposed Information Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

... the GPR, mid-year GPR and a final GPR within 90 days of grant closeout, which provide information for... to complete a GPR, which is due in October, to complete an abbreviated mid-year GPR due in April, and to complete a final GPR within 90 days of grant closeout. The GPR provides information for CNCS staff...

Broadband Ground Penetrating Radar with conformal antennas for subsurface imaging from a rover

NASA Astrophysics Data System (ADS)

Stillman, D. E.; Oden, C. P.; Grimm, R. E.; Ragusa, M.

2015-12-01

Ground-Penetrating Radar (GPR) allows subsurface imaging to provide geologic context and will be flown on the next two martian rovers (WISDOM on ExoMars and RIMFAX on Mars 2020). The motivation of our research is to minimize the engineering challenges of mounting a GPR antenna to a spacecraft, while maximizing the scientific capabilities of the GPR. The scientific capabilities increase with the bandwidth as it controls the resolution. Furthermore, ultra-wide bandwidth surveys allow certain mineralogies and rock units to be discriminated based on their frequency-dependent EM or scattering properties. We have designed and field-tested a prototype GPR that utilizes bi-static circularly polarized spiral antennas. Each antenna has a physical size of 61 x 61 x 4 cm, therefore two antennas could be mounted to the underbelly of a MSL-class rover. Spiral antennas were chosen because they have an inherent broadband response and provide a better low frequency response compared with similarly sized linearly polarized antennas. A horizontal spiral radiator emits energy both upward and downward directions. After the radiator is mounted to a metal surface (i.e. the underside of a rover), a cavity is formed that causes the upward traveling energy to reverberate and cause unwanted interference. This interference is minimized by 1) using a high metallization ratio on the spiral to reduce cavity emissions, and 2) placing absorbing material inside the cavity. The resulting antennas provide high gain (0 to 8 dBi) from 200 to 1000 MHz. The low frequency response can be improved by increasing the antenna thickness (i.e., cavity depth). In an initial field test, the antennas were combined with impulse GPR electronics that had ~140 dB of dynamic range (not including antennas) and a sand/clay interface 7 feet deep was detected. To utilize the full bandwidth the antennas, a gated Frequency Modulated Continuous Waveform system will be developed - similar to RIMFAX. The goal is to reach a total system dynamic range of 180 dB in order to provide significant penetration.

Comparison of air-coupled GPR data analysis results determined by multiple analysts

NASA Astrophysics Data System (ADS)

Martino, Nicole; Maser, Ken

2016-04-01

Current bridge deck condition assessments using ground penetrating radar (GPR) requires a trained analyst to manually interpret substructure layering information from B-scan images in order to proceed with an intended analysis (pavement thickness, concrete cover, effects of rebar corrosion, etc.) For example, a recently developed method to rapidly and accurately analyze air-coupled GPR data based on the effects of rebar corrosion, requires that a user "picks" a layer of rebar reflections in each B-scan image collected along the length of the deck. These "picks" have information like signal amplitude and two way travel time. When a deck is new, or has little rebar corrosion, the resulting layer of rebar reflections is readily evident and there is little room for subjectivity. However, when a deck is severely deteriorated, the rebar layer may be difficult to identify, and different analysts may make different interpretations of the appropriate layer to analyze. One highly corroded bridge deck, was assessed with a number of nondestructive evaluation techniques including 2GHz air-coupled GPR. Two trained analysts separately selected the rebar layer in each B-scan image, choosing as much information as possible, even in areas of significant deterioration. The post processing of the selected data points was then completed and the results from each analyst were contour plotted to observe any discrepancies. The paper describes the differences between ground coupled and air-coupled GPR systems, the data collection and analysis methods used by two different analysts for one case study, and the results of the two different analyses.

Microwave sensing of tree trunks

NASA Astrophysics Data System (ADS)

Jezova, Jana; Mertens, Laurence; Lambot, Sebastien

2015-04-01

The main subject of this research is the observation of the inner part of living tree trunks using ground-penetrating radar (GPR). Trees are everyday part of human life and therefore it is important to pay attention to the tree conditions. The most obvious consequence of the poor tree condition is dead or injury caused by falling tree. The trunk internal structure is divided into three main parts: heartwood, sapwood and bark, which make this medium highly anisotropic and heterogeneous. Furthermore, the properties of the wood are not only specie-dependent but also depend on genetic and on environmental conditions. In urban areas the main problem for the stability of the trees relies in the apparition of decays provoked by fungi, insect or birds. This results in cavities or decreasing of the support capacity of the tree. GPR has proved itself to be a very powerful electromagnetic tool for non-destructive detection of buried objects. Since the beginning of the 20th century it has been used in several different areas (archaeology, landmine detection, civil engineering, ...). GPR uses the principle of the scattering of the electromagnetic waves that are radiated from a transmitting antenna. Then the waves propagate through the medium and are reflected from the object and then they are received by a receiving antenna. The velocity of the scattered signal is determined primarily by the permittivity of the material. The optimal functionality of the GPR was investigated using the numerical simulation tool gprMax2D. This tool is based on a Finite-Difference Time-Domain (FDTD) numerical model. Subsequently, the GPR functionality was tested using the laboratory model of a decayed tree trunk. Afterwards, the results and lessons learnt in the simplified tests will be used in the processing of the real data and will help to achieve deeper understanding of them. The laboratory model of the tree trunk was made by plastic or carton pipes and filled by sand. Space inside the model was divided into three sections to separate parts with different moisture (heartwood and sapwood) or empty space (decays). For easier manipulation with the antenna we developed a special ruler for measuring the distance along the scans. Instead of the surveying wheel we read the distance with a camera, which was fixed on the antenna and focused on the ruler with a binary pattern. Hence, during whole measurement and the data processing we were able to identify an accurate position on the tree in view of the scan. Some preliminary measurements on the trees were also conducted. They were performed using a GSSI 900 MHz antenna. Several tree species (beech, horse-chestnut, birch, ...) in Louvain-la-Neuve and Brussels, Belgium, have been investigated to see the internal structure of the tree decays. The measurements were carried out mainly by circumferential measurement around the trunk and also by vertical measurement along the trunk for approximate detection of the cavity. The comparison between the numerical simulations, simplified tree trunk model and real data from trees is presented. This research is funded by the Fonds de la Recherche Scientifique (FNRS, Belgium) and benefits from networking activities carried out within the EU COST Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar".

IL-1β and TNFα inhibit GPR120 (FFAR4) and stimulate GPR84 (EX33) and GPR41 (FFAR3) fatty acid receptor expression in human adipocytes: implications for the anti-inflammatory action of n-3 fatty acids.

PubMed

Muredda, Laura; Kępczyńska, Małgorzata A; Zaibi, Mohamed S; Alomar, Suliman Y; Trayhurn, Paul

2018-05-01

Regulation of the expression of GPCR fatty acid receptor genes has been examined in human adipocytes differentiated in culture. TNFα and IL-1β induced a marked reduction in GPR120 expression, mRNA level falling 17-fold at 24 h in adipocytes incubated with TNFα. In contrast, GPR84 mRNA was dramatically increased by these cytokines (>500-fold for IL-1β at 4 h); GPR41 expression was also stimulated. Rosiglitazone did not affect GPR84 expression, but GPR120 and GPR41 expression increased. Dexamethasone, insulin, linoleic and docosahexaenoic acids (DHA), and TUG891 (GPR120 agonist) had little effect on GPR120 and GPR84 expression. TUG891 did not attenuate the pro-inflammatory actions of TNFα and IL-1β. DHA slightly countered the actions of IL-1β on CCL2, IL6 and ADIPOQ expression, though not on secretion of these adipokines. GPR120 and GP84 gene expression in human adipocytes is highly sensitive to pro-inflammatory mediators; the inflammation-induced inhibition of GPR120 expression may compromise the anti-inflammatory action of GPR120 agonists.

Forward-Looking IED Detector Ground Penetrating Radar

NASA Technical Reports Server (NTRS)

Kim, Soon Sam; Carnes, Steven R.; Ulmer, Christopher T.

2013-01-01

There have been many developments of mine or metal detectors based on ground penetrating radar techniques, usually in hand-held or rover-mounted devices. In most mine or metal detector applications, conditions are in a stationary mode and detection speed is not an important factor. A novel, forward-looking, stepped-frequency ground penetrating radar (GPR) has been developed with a capability to detect improvised explosive devices (IEDs) at vehicular speeds of 15 to 20 mph (24 to 32 km/h), 10 to 20 m ahead of the vehicle, to ensure adequate time for response. The GPR system employs two horn antennas (1.7 to 2.6 GHz, 20 dBi) as transmit and receive. The detector system features a user-friendly instantaneous display on a laptop PC and is a low-power-consumption (3 W) compact system with minimal impact on vehicle operations. In practice, the whole GPR system and a laptop PC can be powered by plugging into a cigarette lighter of a vehicle. The stepped-frequency continuous-wave (CW) radar scans frequency from 1.7 to 2.6 GHz in 1,000 steps of 0.9 MHz, with the full frequency scan in 60 ms. The GPR uses a bi-static configuration with one horn antenna used as a transmitter and the other used as a receiver so that isolation between transmitter and receiver is improved. Since the horn antennas (20 dBi) are mounted on the roof of a vehicle at a shallow inclination angle (15 to 25 with respect to horizontal), there is a first-order reduction in ground reflection so that a significant amount of the total reflected power received by the GPR comes from the scattering of RF energy off of buried objects. The stepped-frequency technique works by transmitting a tone at a particular frequency, while the received signal is mixed with the transmitted tone. As a result, the output of the mixer produces a signal that indicates the strength of the received signal and the extent to which it is in phase or out of phase with the transmitted tone. By taking measurements of the phase relationship between the transmitted and received signals over a wide frequency range, an interference pattern is produced showing all target reflections. When a Fourier transform is performed on this pattern, the result is a time-domain representation of targets. Among the advantages of this technique over impulse radar is the ability to transmit and receive much more total energy, and to use non-damped, highly focused horn antennas. The novelty of the IED detector GPR has been achieved by miniaturization of GPR electronics (single electronics board, 10x5x2 cm), low power consumption (3 W), faster signal processing capability, and minimal impact on vehicle operations.

Use of Ground Penetrating Radar to Study Gradient Media

NASA Astrophysics Data System (ADS)

Titov, A.

2016-12-01

Nowadays Ground Penetrating Radar (GPR) is often used to solve different problems of applied geophysics including the hydrological ones. This work was motivated by detection of weak reflections in the body of water observed during the surveys on the freshwater lakes using GPR. The same reflections were first analyzed by John Bradford in 2007. These reflections can arise from the thermal gradient layer or thermocline due to different dielectric permittivity of cold and warm water. We employed physical and mathematical modeling to identify the properties of such thermoclines. We have constructed a special GPR stand to study the gradient media in our laboratory. The stand consists of a water-filled plastic tank and plastic tubes, which gather the cold water under the warm water. Our stand allows for changing parameters of the gradient layer, such as limits of dielectric permittivity and the thickness of the gradient layer. GPR antenna was placed slightly under the water surface to remove the parasitic reflections. To visualize the thermal distribution, an infrared camera and thermal sensors were used. Analysis of the GPR traces after physical modeling, performed in the MATLAB environment, allows us to locate the weak reflection from the gradient layer. We observed that (i) the change of the gradient boundary values alters the amplitude of the signal, (ii) the arrival time of the impulse reflected from the gradient layer corresponds to the arrival time of the impulse reflected from the top boundary of this layer, and (iii) the shape of the signal reflected from the gradient layer coincides with the shape of the signal reflected from the non-gradient boundary between two bodies. The quantitative properties of thermocline can be determined using amplitude analysis of GPR signals. Finally, the developed methods were successfully applied to real field data.

Analyses and Measures of GPR Signal with Superimposed Noise

NASA Astrophysics Data System (ADS)

Chicarella, Simone; Ferrara, Vincenzo; D'Atanasio, Paolo; Frezza, Fabrizio; Pajewski, Lara; Pavoncello, Settimio; Prontera, Santo; Tedeschi, Nicola; Zambotti, Alessandro

2014-05-01

The influence of EM noises and environmental hard conditions on the GPR surveys has been examined analytically [1]. In the case of pulse radar GPR, many unwanted signals as stationary clutter, non-stationary clutter, random noise, and time jitter, influence the measurement signal. When GPR is motionless, stationary clutter is the most dominant signal component due to the reflections of static objects different from the investigated target, and to the direct antenna coupling. Moving objects like e.g. persons and vehicles, and the swaying of tree crown, produce non-stationary clutter. Device internal noise and narrowband jamming are e.g. two potential sources of random noises. Finally, trigger instabilities generate random jitter. In order to estimate the effective influence of these noise signal components, we organized some experimental setup of measurement. At first, we evaluated for the case of a GPR basic detection, simpler image processing of radargram. In the future, we foresee experimental measurements for detection of the Doppler frequency changes induced by movements of targets (like physiological movements of survivors under debris). We obtain image processing of radargram by using of GSSI SIR® 2000 GPR system together with the UWB UHF GPR-antenna (SUB-ECHO HBD 300, a model manufactured by Radarteam company). Our work includes both characterization of GPR signal without (or almost without) a superimposed noise, and the effect of jamming originated from the coexistence of a different radio signal. For characterizing GPR signal, we organized a measurement setup that includes the following instruments: mod. FSP 30 spectrum analyser by Rohde & Schwarz which operates in the frequency range 9 KHz - 30 GHz, mod. Sucoflex 104 cable by Huber Suhner (10 MHz - 18 GHz), and HL050 antenna by Rohde & Schwarz (bandwidth: from 850 MHz to 26.5 GHz). The next analysis of superimposed jamming will examine two different signal sources: by a cellular phone and by a transmitter operating in the Instrumental Scientific Medical (ISM) band (around 2.4 GHz). In the first case, signal of cellular phone is considered as an actual noise, and the measure should provide guidance on its electromagnetic compatibility, in the sense of operating limits of the GPR conditioning from the presence of signal transmitted by a cellular phone. Whereas, the analysis of superimposed signals in the ISM band is oriented to the implementation of a mobile GPR system that includes a transceiver, such as XBee, for transmitting results of localization (e.g. of buried people) to a remote station. This work is a contribution to COST Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar." J. Sachs, M. Helbig, R. Herrmann, M. Kmec, K. Schilling, E. Zaikov, and P. Rauschenbach, 'Trapped victim detection by pseudo-noise radar,' in Proc. ACWR '11 1st International Conference on Wireless Technologies for Humanitarian Relief, Amritapuri, Kollam, Kerala, India, 2011, pp. 265-272

International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G Protein–Coupled Receptors

PubMed Central

Aust, Gabriela; Araç, Demet; Engel, Felix B.; Formstone, Caroline; Fredriksson, Robert; Hall, Randy A.; Harty, Breanne L.; Kirchhoff, Christiane; Knapp, Barbara; Krishnan, Arunkumar; Liebscher, Ines; Lin, Hsi-Hsien; Martinelli, David C.; Monk, Kelly R.; Peeters, Miriam C.; Piao, Xianhua; Prömel, Simone; Schöneberg, Torsten; Schwartz, Thue W.; Singer, Kathleen; Stacey, Martin; Ushkaryov, Yuri A.; Vallon, Mario; Wolfrum, Uwe; Wright, Mathew W.; Xu, Lei; Langenhan, Tobias

2015-01-01

The Adhesion family forms a large branch of the pharmacologically important superfamily of G protein–coupled receptors (GPCRs). As Adhesion GPCRs increasingly receive attention from a wide spectrum of biomedical fields, the Adhesion GPCR Consortium, together with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification, proposes a unified nomenclature for Adhesion GPCRs. The new names have ADGR as common dominator followed by a letter and a number to denote each subfamily and subtype, respectively. The new names, with old and alternative names within parentheses, are: ADGRA1 (GPR123), ADGRA2 (GPR124), ADGRA3 (GPR125), ADGRB1 (BAI1), ADGRB2 (BAI2), ADGRB3 (BAI3), ADGRC1 (CELSR1), ADGRC2 (CELSR2), ADGRC3 (CELSR3), ADGRD1 (GPR133), ADGRD2 (GPR144), ADGRE1 (EMR1, F4/80), ADGRE2 (EMR2), ADGRE3 (EMR3), ADGRE4 (EMR4), ADGRE5 (CD97), ADGRF1 (GPR110), ADGRF2 (GPR111), ADGRF3 (GPR113), ADGRF4 (GPR115), ADGRF5 (GPR116, Ig-Hepta), ADGRG1 (GPR56), ADGRG2 (GPR64, HE6), ADGRG3 (GPR97), ADGRG4 (GPR112), ADGRG5 (GPR114), ADGRG6 (GPR126), ADGRG7 (GPR128), ADGRL1 (latrophilin-1, CIRL-1, CL1), ADGRL2 (latrophilin-2, CIRL-2, CL2), ADGRL3 (latrophilin-3, CIRL-3, CL3), ADGRL4 (ELTD1, ETL), and ADGRV1 (VLGR1, GPR98). This review covers all major biologic aspects of Adhesion GPCRs, including evolutionary origins, interaction partners, signaling, expression, physiologic functions, and therapeutic potential. PMID:25713288

The Wigner-Ville Transform, An Approach to Interpret GPR Data: Outlining a Rik Zone

NASA Astrophysics Data System (ADS)

Chavez, R. E.; Samano, M. A.; Camara, M. E.; Tejero, A.; Flores-Marquez, L. E.; Arango, C.; Velazco, V.

2006-12-01

In this investigation, a time-frequency analysis is performed, based in the decomposition of the GPR signal in high- and low-frequencies. This process is combined with a statistical approach to detect signal changes in time and position simultaneously. The spectral analysis is carried out through the Wigner-Ville distribution (WVD). A cross-correlation can be computed between the original signal and the time-frequency components to obtain structural anomalies in the GPR observations, and to perform a correlation with the available geology. An example of this methodology is presented, where a series of traces where analyzed from a GPR profile surveyed in an eastern area of Mexico City. This is a heavily urbanized region built on the bottom of an ancient lake. The sediments are poorly consolidated and the extraction water rate has increased the areas of subsidence. Nowadays, most of family homes and public buildings, mainly schools have started to suffer heavy damages. The geophysical study carried out in the area permitted to detect areas of high risk. The data analysis combined with previous geological studies, which included stratigraphic columns allowed to identify the geophysical characteristics of the area, which will allow to the authorities to plan the future development of the area.

Value of gamma-glutamyltranspeptidase-to-platelet ratio in diagnosis of hepatic fibrosis in patients with chronic hepatitis B

PubMed Central

Hu, Yan-Chao; Liu, Hao; Liu, Xiao-Yan; Ma, Li-Na; Guan, Yu-Hua; Luo, Xia; Ding, Xiang-Chun

2017-01-01

AIM To investigate the value of the gamma-glutamyltraspeptidase (GGT)-to-platelet (PLT) ratio (GPR) in the diagnosis of hepatic fibrosis in patients with chronic hepatitis B (CHB). METHODS We included 390 untreated CHB patients in this study. The GPR, aspartate aminotransferase (AST)-to-PLT ratio index (APRI), and fibrosis-4 (FIB-4) of all patients were analysed to determine if these parameter were correlated with age, gender, medical history, liver function [total bilirubin (TBil), alanine aminotransferase (ALT), and AST], GGT, PLT count, or hepatic fibrosis stage. The GPR, APRI, and FIB-4, as well as the combination of the GPR and APRI or the GPR and FIB-4 were assessed in different cirrhosis stages using receiver operating characteristic (ROC) curve analysis to evaluate their value in diagnosing hepatic fibrosis in CHB patients. RESULTS The GPR, APRI, and FIB-4 were not correlated with CHB patients’ age, gender, or disease duration (P > 0.05), but all of these parameters were positively correlated with serum ALT, AST, GGT, and PLT count (P < 0.01). Additionally, the GPR, APRI, and FIB-4 were positively correlated with hepatic fibrosis (P < 0.01); the areas under the ROC curve for the GPR in F1, F2, F3, and F4 stages were 0.723, 0.741, 0.826, and 0.833, respectively, which were significantly higher than the respective values for the FIB-4 and APRI (F1: 0.581, 0.612; F2: 0.706, 0.711; F3: 0.73, 0.751; and F4: 0.799, 0.778). The respective diagnostic cut-off points for each stage were 0.402, 0.448, 0.548, and 0.833, respectively. The diagnostic sensitivity and specificity were, respectively, 88.8% and 87.5% in F1, 72.7% and 89.7% in F2, 81.3% and 98.6% in F3, and 80% and 97.4% in F4 when the GPR and APRI were connected in parallel; 86.6% and 90.2%, 78.4% and 96%, 78.6% and 97.4%, and 73.2% and 97.9%, respectively, when the GPR and APRI were connected in series; 80.2% and 89%, 65% and 89%, 70.3% and 98.5%, and 78.8% and 96.8%, respectively, when the GPR and FIB-4 were connected in parallel; and 83.6% and 87.9%, 76.8% and 96.6%, 72.7% and 98%, and 74.4% and 97.7%, respectively, when the GPR and FIB-4 were connected in series. CONCLUSION The GPR, as a serum diagnostic index of liver fibrosis, is more accurate, sensitive, and easy to use than the FIB-4 and APRI, and the GPR can significantly improve the sensitivity and specificity of hepatic fibrosis diagnosis in CHB when combined with the FIB-4 or APRI. PMID:29151696

Targeted Inactivation of GPR26 Leads to Hyperphagia and Adiposity by Activating AMPK in the Hypothalamus

PubMed Central

Zhang, Weiping; Shi, Yuguang

2012-01-01

G-protein coupled receptor 26 (GPR26) is a brain-specific orphan GPCR with high expression in the brain region that controls satiety. Depletion of GPR26 has been shown to increase fat storage in C. elegans, whereas GPR26 deficiency in the hypothalamus is associated with high genetic susceptibility to the onset of obesity in mice. However, the metabolic function of GPR26 in mammals remains elusive. Herein, we investigated a role of GPR26 in regulating energy homeostasis by generating mice with targeted deletion of the GPR26 gene. We show that GPR26 deficiency causes hyperphagia and hypometabolism, leading to early onset of diet-induced obesity. Accordingly, GPR26 deficiency also caused metabolic complications commonly associated with obesity, including glucose intolerance, hyperinsulinemia, and dyslipidemia. Moreover, consistent with hyperphagia in GPR26 null mice, GPR26 deficiency significantly increased hypothalamic activity of AMPK, a key signaling event that stimulates appetite. In further support of a regulatory role of GPR26 in satiety, GPR26 knockout mice also demonstrate hypersensitivity to treatment of rimonabant, an endocannabinoid receptor-1 antagonist commonly used to treat obesity by suppressing appetite in humans. Together, these findings identified a key role of GPR26 as a central regulator of energy homeostasis though modulation of hypothalamic AMPK activation. PMID:22815809

Targeted inactivation of GPR26 leads to hyperphagia and adiposity by activating AMPK in the hypothalamus.

PubMed

Chen, Daohong; Liu, Xiaolei; Zhang, Weiping; Shi, Yuguang

2012-01-01

G-protein coupled receptor 26 (GPR26) is a brain-specific orphan GPCR with high expression in the brain region that controls satiety. Depletion of GPR26 has been shown to increase fat storage in C. elegans, whereas GPR26 deficiency in the hypothalamus is associated with high genetic susceptibility to the onset of obesity in mice. However, the metabolic function of GPR26 in mammals remains elusive. Herein, we investigated a role of GPR26 in regulating energy homeostasis by generating mice with targeted deletion of the GPR26 gene. We show that GPR26 deficiency causes hyperphagia and hypometabolism, leading to early onset of diet-induced obesity. Accordingly, GPR26 deficiency also caused metabolic complications commonly associated with obesity, including glucose intolerance, hyperinsulinemia, and dyslipidemia. Moreover, consistent with hyperphagia in GPR26 null mice, GPR26 deficiency significantly increased hypothalamic activity of AMPK, a key signaling event that stimulates appetite. In further support of a regulatory role of GPR26 in satiety, GPR26 knockout mice also demonstrate hypersensitivity to treatment of rimonabant, an endocannabinoid receptor-1 antagonist commonly used to treat obesity by suppressing appetite in humans. Together, these findings identified a key role of GPR26 as a central regulator of energy homeostasis though modulation of hypothalamic AMPK activation.

Remodeling of Sensorimotor Brain Connectivity in Gpr88-Deficient Mice.

PubMed

Arefin, Tanzil Mahmud; Mechling, Anna E; Meirsman, Aura Carole; Bienert, Thomas; Hübner, Neele Saskia; Lee, Hsu-Lei; Ben Hamida, Sami; Ehrlich, Aliza; Roquet, Dan; Hennig, Jürgen; von Elverfeldt, Dominik; Kieffer, Brigitte Lina; Harsan, Laura-Adela

2017-10-01

Recent studies have demonstrated that orchestrated gene activity and expression support synchronous activity of brain networks. However, there is a paucity of information on the consequences of single gene function on overall brain functional organization and connectivity and how this translates at the behavioral level. In this study, we combined mouse mutagenesis with functional and structural magnetic resonance imaging (MRI) to determine whether targeted inactivation of a single gene would modify whole-brain connectivity in live animals. The targeted gene encodes GPR88 (G protein-coupled receptor 88), an orphan G protein-coupled receptor enriched in the striatum and previously linked to behavioral traits relevant to neuropsychiatric disorders. Connectivity analysis of Gpr88-deficient mice revealed extensive remodeling of intracortical and cortico-subcortical networks. Most prominent modifications were observed at the level of retrosplenial cortex connectivity, central to the default mode network (DMN) whose alteration is considered a hallmark of many psychiatric conditions. Next, somatosensory and motor cortical networks were most affected. These modifications directly relate to sensorimotor gating deficiency reported in mutant animals and also likely underlie their hyperactivity phenotype. Finally, we identified alterations within hippocampal and dorsal striatum functional connectivity, most relevant to a specific learning deficit that we previously reported in Gpr88 -/- animals. In addition, amygdala connectivity with cortex and striatum was weakened, perhaps underlying the risk-taking behavior of these animals. This is the first evidence demonstrating that GPR88 activity shapes the mouse brain functional and structural connectome. The concordance between connectivity alterations and behavior deficits observed in Gpr88-deficient mice suggests a role for GPR88 in brain communication.

Free fatty acids-sensing G protein-coupled receptors in drug targeting and therapeutics.

PubMed

Yonezawa, Tomo; Kurata, Riho; Yoshida, Kaori; Murayama, Masanori A; Cui, Xiaofeng; Hasegawa, Akihiko

2013-01-01

G protein-coupled receptor (GPCR) (also known as seven-transmembrane domain receptor) superfamily represents the largest protein family in the human genome. These receptors respond to various physiological ligands such as photons, odors, pheromones, hormones, ions, and small molecules including amines, amino acids to large peptides and steroids. Thus, GPCRs are involved in many diseases and the target of around half of all conventional drugs. The physiological roles of free fatty acids (FFAs), in particular, long-chain FFAs, are important for the development of many metabolic disease including obesity, diabetes, and atherosclerosis. In the past half decade, deorphanization of several GPCRs has revealed that GPR40, GPR41, GPR43, GPR84 and GPR120 sense concentration of extracellular FFAs with various carbon chain lengths. GPR40 and GPR120 are activated by medium- and long-chain FFAs. GPR84 is activated by medium- chain, but not long-chain, FFAs. GPR41 and GPR43 are activated by short-chain FFAs. GPR40 is highly expressed in pancreatic beta cells and plays a crucial role in FFAs-induced insulin secretion. GPR120 is mainly expressed in enteroendocrine cells and plays an important role for FFAs-induced glucagon-like peptide-1. GPR43 is abundant in leukocytes and adipose tissue, whilst GPR41 is highly expressed in adipose tissue, the pancreas and leukocytes. GPR84 is expressed in leukocytes and monocyte/macrophage. This review aims to shed light on the physiological roles and development of drugs targeting these receptors.

Difficulties in Interpreting Ballast Degradation Level Estimates from Synthetic Ground-Penetrating Radar Data

NASA Astrophysics Data System (ADS)

Scanlan, K. M.; Hendry, M. T.; Martin, C. D.; Schmitt, D. R.

2016-12-01

As fine-grained particles accumulate within railway ballast, it becomes more susceptible to differential deformations, which leads to the loss of proper track alignment and an increased risk for car derailment. Methods for estimating the ballast degradation level from low-frequency (<1 GHz) ground-penetrating radar (GPR) measurements exist, but their applicability in a wide range of track foundation conditions has yet to be evaluated. This analysis, based on simulated GPR data, evaluates the sensitivity of these methods to changing ballast moisture contents, ballast thicknesses and subballast material types. The results highlight that small changes to the track foundation, indepedent of the concentration of degraded ballast, significantly alter the attenuation and reflectivity characteristics of the simualted GPR measurements. As such, ballast degraded to a certain level will manifest with different attenuation and reflectivity characteristics, limiting the ability to accurately and reliably detect these changes using GPR. Radar propagation velocities within the ballast are less influenced by changes in ballast depth and subballast material type. However, ambiguous propagation velocities are observed for certain ballast moisture contents and degradation levels; furthermore, velocities can only be calculated when the ballast thickness is known. These results suggest that while under certain circumstances, with additional information on the track foundation conditons, ballast degradation levels can be estimated from GPR data; in general, the complicated nature of GPR signals makes the quantificaion of ballast degradation levels difficult.

Advances Towards The Discovery of GPR55 Ligands.

PubMed

Morales, Paula; Jagerovic, Nadine

2016-01-01

The G-protein-coupled receptor 55 (GPR55) was identified in 1999. It was proposed as a novel member of the endocannabinoid system due to the fact that some endogenous, plant-derived and synthetic cannabinoid ligands act on GPR55. However, the complexity of the cellular downstream signaling pathways related to GPR55 activation delayed the discovery of selective GPR55 ligands. It was only a few years ago that the high throughput screening of libraries of pharmaceutical companies and governmental organizations allowed to identify selective GPR55 agonists and antagonists. Since then, several GPR55 modulator scaffolds have been reported. The relevance of GPR55 has been explored in diverse physiological and pathological processes revealing its role in inflammation, neuropathic pain, bone physiology, diabetes and cancer. Considering GPR55 as a new promising therapeutic target, there is a clear need for new selective and potent GPR55 modulators. This review will address a current structural update of GPR55 ligands.

E2GPR - Edit your geometry, Execute GprMax2D and Plot the Results!

NASA Astrophysics Data System (ADS)

Pirrone, Daniele; Pajewski, Lara

2015-04-01

In order to predict correctly the Ground Penetrating Radar (GPR) response from a particular scenario, Maxwell's equations have to be solved, subject to the physical and geometrical properties of the considered problem and to its initial conditions. Several techniques have been developed in computational electromagnetics, for the solution of Maxwell's equations. These methods can be classified into two main categories: differential and integral equation solvers, which can be implemented in the time or spectral domain. All of the different methods present compromises between computational efficiency, stability, and the ability to model complex geometries. The Finite-Difference Time-Domain (FDTD) technique has several advantages over alternative approaches: it has inherent simplicity, efficiency and conditional stability; it is suitable to treat impulsive behavior of the electromagnetic field and can provide either ultra-wideband temporal waveforms or the sinusoidal steady-state response at any frequency within the excitation spectrum; it is accurate and highly versatile; and it has become a mature and well-researched technique. Moreover, the FDTD technique is suitable to be executed on parallel-processing CPU-based computers and to exploit the modern computer visualisation capabilities. GprMax [1] is a very well-known and largely validated FDTD software tool, implemented by A. Giannopoulos and available for free public download on www.gprmax.com, together with examples and a detailled user guide. The tool includes two electromagnetic wave simulators, GprMax2D and GprMax3D, for the full-wave simulation of two-dimensional and three-dimensional GPR models. In GprMax, everything can be done with the aid of simple commands that are used to define the model parameters and results to be calculated. These commands need to be entered in a simple ASCII text file. GprMax output files can be stored in ASCII or binary format. The software is provided with MATLAB functions, which can be employed to import synthetic data created by GprMax using the binary-format option into MATLAB, in order to be processed and/or visualized. Further MATLAB procedures for the visualization of GprMax synthetic data have been developed within the COST Action TU1208 [2] and are available for free public download on www.GPRadar.eu. The current version of GprMax3D is compiled with OpenMP, supporting multi-platform shared memory multiprocessing which allows GprMax3D to take advantage of multiple cores/CPUs. GprMax2D, instead, exploits a single core when executed. E2GPR is a new software tool, available free of charge for both academic and commercial use, conceived to: 1) assist in the creation, modification and analysis of GprMax2D models, through a Computer-Aided Design (CAD) system; 2) allow parallel and/or distributed computing with GprMax2D, on a network of computers; 3) automatically plot A-scans and B-scans generated by GprMax2D. The CAD and plotter parts of the tool are implemented in Java and can run on any Java Virtual Machine (JVM) regardless of computer architecture. The part of the tool devoted to supporting parallel and/or distributed computing, instead, requires the set up of a Web-Service (on a server emulator or server); in fact, it is currently configured only for Windows Server and Internet Information Services (IIS). In this work, E2GPR is presented and examples are provided which demonstrate its use. The tool can be currently obtained by contacting the authors. It will soon be possible to download it from www.GPRadar.eu. Acknowledgement This work is a contribution to the COST Action TU1208 'Civil Engineering Applications of Ground Penetrating Radar.' The authors thank COST for funding the Action TU1208. References [1] A. Giannopoulos, 'Modelling ground penetrating radar by GprMax,' Construction and Building Materials, vol. 19, pp. 755-762, 2005. [2] L. Pajewski, A. Benedetto, X. Dérobert, A. Giannopoulos, A. Loizos, G. Manacorda, M. Marciniak, C. Plati, G. Schettini, I. Trinks, "Applications of Ground Penetrating Radar in Civil Engineering - COST Action TU1208," Proc. 7th International Workshop on Advanced Ground Penetrating Radar (IWAGPR), 2-5 July 2013, Nantes, France, pp. 1-6.

Structure Based Virtual Screening Studies to Identify Novel Potential Compounds for GPR142 and Their Relative Dynamic Analysis for Study of Type 2 Diabetes

NASA Astrophysics Data System (ADS)

Kaushik, Aman C.; Kumar, Sanjay; Wei, Dong Q.; Sahi, Shakti

2018-02-01

GPR142 (G protein receptor 142) is a novel orphan GPCR (G protein coupled receptor) belonging to ‘Class A’ of GPCR family and expressed in beta cells of pancreas. In this study, we reported the structure based virtual screening to identify the hit compounds which can be developed as leads for potential agonists. The results were validated through induced fit docking, pharmacophore modeling and system biology approaches. Since, there is no solved crystal structure of GPR142, we attempted to predict the 3D structure followed by validation and then identification of active site using threading and ab initio methods. Also, structure based virtual screening was performed against a total of 1171519 compounds from different libraries and only top 20 best hit compounds were screened and analyzed. Moreover, the biochemical pathway of GPR142 complex with screened compound2 was also designed and compared with experimental data. Interestingly, compound2 showed an increase in insulin production via Gq mediated signaling pathway suggesting the possible role of novel GPR142 agonists in therapy against type 2 diabetes.

Evaluation of clay content in soils for pavement engineering applications using GPR

NASA Astrophysics Data System (ADS)

Tosti, Fabio; Patriarca, Claudio; Benedetto, Andrea; Slob, Evert C.; Lambot, Sébastien

2013-04-01

Clay content significantly influences the mechanical behavior of soils, thereby playing an important role in many fields of applications such as civil engineering, geology and agriculture. In the area of pavement engineering, clay content in structural bearing courses of pavement frequently causes damages and defects, such as transversal and longitudinal cracks, or other faults. The main consequence is a lowering of both the road safety and operability, with the number of expected accidents increasing. In this study, ground-penetrating radar (GPR) laboratory tests were carried out to predict the clay amount in pavement structural layers under different clay and moisture conditions. GPR data processing is performed using two different methods. The first method is based on the Fresnel theory and focuses on the Rayleigh scattering of the radar waves. The approach is based on a different scattering of the various components of the frequency spectrum, mostly depending on both the soil texture and variation in soil moisture content. For the application of this method, we used a pulse radar with ground-coupled, 500 MHz centre-frequency antennas in a common offset, bistatic configuration. The transmitter and receiver were linked by optic fiber electronic modules. The second method is based on full-waveform inversion of the ultra wideband radar data. In particular, a specific radar-antenna electromagnetic model is used to filter out antenna effects and antenna-medium interactions from the raw radar data and retrieve the response of the soil only, expressed in terms of a layered medium Green's function. To estimate the medium geometrical and electrical values, an optimization inverse problem is formulated. For the application of that second method, we used a vector network analyzer (VNA) as continuous-wave stepped-frequency radar system to acquire data in the 500-3000 MHz frequency range. A doubled-ridged broadband horn antenna operating in far-field conditions was used as transmitter and receiver, and was connected to the radar using a high-quality coaxial cable. Typical road materials for subgrade and sub-base courses were used. In particular, three types of soils classified, respectively, as A1,A2,A3 by AASHTO were used and adequately compacted in electrically and hydraulically isolated boxes. A copper sheet was laid at the bottom of the experimental boxes to control the bottom boundary conditions in the electromagnetic model. Basically, two significant cases were considered for each soil type, taking into account the 0% and the 25% by weight of bentonite clay, respectively. Water was gradually added and GPR measurements were carried out for all moisture steps until the maximum saturation level was reached. Concerning the Rayleigh scattering method, analyses show a high consistency of the results with respect to our expectations. A negative correlation between the shift of the frequency spectrum peaks and the clay amount was demonstrated, by virtue of its strong hygroscopic properties. Similarly, the full-waveform inversion technique allowed to measure reliable electric parameters. Generally, different responses (e.g. electric conductivity and permittivity) of the 0% clay-member cases compared to those of the analogous clayey soil samples highlight the large potentiality of both methods for the detection of clay.

Activation of the omega-3 fatty acid receptor GPR120 mediates anti-inflammatory actions in immortalized hypothalamic neurons.

PubMed

Wellhauser, Leigh; Belsham, Denise D

2014-03-27

Overnutrition and the ensuing hypothalamic inflammation is a major perpetuating factor in the development of metabolic diseases, such as obesity and diabetes. Inflamed neurons of the CNS fail to properly regulate energy homeostasis leading to pathogenic changes in glucose handling, feeding, and body weight. Hypothalamic neurons are particularly sensitive to pro-inflammatory signals derived locally and peripherally, and it is these neurons that become inflamed first upon high fat feeding. Given the prevalence of metabolic disease, efforts are underway to identify therapeutic targets for this inflammatory state. At least in the periphery, omega-3 fatty acids and their receptor, G-protein coupled receptor 120 (GPR120), have emerged as putative targets. The role for GPR120 in the hypothalamus or CNS in general is poorly understood. Here we introduce a novel, immortalized cell model derived from the rat hypothalamus, rHypoE-7, to study GPR120 activation at the level of the individual neuron. Gene expression levels of pro-inflammatory cytokines were studied by quantitative reverse transcriptase-PCR (qRT-PCR) upon exposure to tumor necrosis factor α (TNFα) treatment in the presence or absence of the polyunsaturated omega-3 fatty acid docosahexaenoic acid (DHA). Signal transduction pathway involvement was also studied using phospho-specific antibodies to key proteins by western blot analysis. Importantly, rHypoE-7 cells exhibit a transcriptional and translational inflammatory response upon exposure to TNFα and express abundant levels of GPR120, which is functionally responsive to DHA. DHA pretreatment prevents the inflammatory state and this effect was inhibited by the reduction of endogenous GPR120 levels. GPR120 activates both AKT (protein kinase b) and ERK (extracellular signal-regulated kinase); however, the anti-inflammatory action of this omega-3 fatty acid (FA) receptor is AKT- and ERK-independent and likely involves the GPR120-transforming growth factor-β-activated kinase 1 binding protein (TAB1) interaction as identified in the periphery. Taken together, GPR120 is functionally active in the hypothalamic neuronal line, rHypoE-7, wherein it mediates the anti-inflammatory actions of DHA to reduce the inflammatory response to TNFα.

GPR30 decreases cardiac chymase/angiotensin II by inhibiting local mast cell number

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Zhuo; Department of Cardiology, Jinan Central Hospital, Affiliated with Shandong University, 105 Jiefang Road, Jinan, 250013; Wang, Hao

2015-03-27

Chronic activation of the novel estrogen receptor GPR30 by its agonist G1 mitigates the adverse effects of estrogen (E2) loss on cardiac structure and function. Using the ovariectomized (OVX) mRen2.Lewis rat, an E2-sensitive model of diastolic dysfunction, we found that E2 status is inversely correlated with local cardiac angiotensin II (Ang II) levels, likely via Ang I/chymase-mediated production. Since chymase is released from cardiac mast cells during stress (e.g., volume/pressure overload, inflammation), we hypothesized that GPR30-related cardioprotection after E2 loss might occur through its opposing actions on cardiac mast cell proliferation and chymase production. Using real-time quantitative PCR, immunohistochemistry, andmore » immunoblot analysis, we found mast cell number, chymase expression, and cardiac Ang II levels were significantly increased in the hearts of OVX-compared to ovary-intact mRen2.Lewis rats and the GPR30 agonist G1 (50 mg/kg/day, s.c.) administered for 2 weeks limited the adverse effects of estrogen loss. In vitro studies revealed that GPR30 receptors are expressed in the RBL-2H3 mast cell line and G1 inhibits serum-induced cell proliferation in a dose-dependent manner, as determined by cell counting, BrdU incorporation assay, and Ki-67 staining. Using specific antagonists to estrogen receptors, blockage of GPR30, but not ERα or ERβ, attenuated the inhibitory effects of estrogen on BrdU incorporation in RBL-2H3 cells. Further study of the mechanism underlying the effect on cell proliferation showed that G1 inhibits cyclin-dependent kinase 1 (CDK1) mRNA and protein expression in RBL-2H3 cells in a dose-dependent manner. - Highlights: • GPR30 activation limits mast cell number in hearts from OVX mRen2.Lewis rats. • GPR30 activation decreases cardiac chymase/angiotensin II after estrogen loss. • GPR30 activation inhibits RBL-2H3 mast cell proliferation and CDK1 expression.« less

The application of Ground Penetrating Radar analysis to investigate the impact and recovery of coastal dunes and the recurrence interval of overwash events

NASA Astrophysics Data System (ADS)

Switzer, A.; Gouramanis, C.; Bristow, C. S.; Jankaew, K.; Rubin, C. M.; Pham, D. T.; Ildefonso, S. R.; Lee, Y. S.

2013-12-01

The common techniques for investigating the impact, recovery and recurrence interval in coastal systems are point source augering or pitting and/or excavations. These techniques are time and cost intensive. Ground Penetrating Radar (GPR) presents a rapid, non-invasive, spatially-continuous technique for identifying subsurface stratigraphy. Although GPR facies are not diagnostic of a particular sedimentary characteristic, when combined with satellite imagery, they provide an avenue for reconstructing the impact and the post event recovery, or to help constrain the spatial extent of sandy deposits in the subsurface. Here, we present results from two GPR survey campaigns at Phra Thong Island, Thailand. The first campaign targeted the large scale recovery of the coast following the 2004 Indian ocean tsunami using 200 MHz antennae and the second campaign focused on a thin-bed approach aimed at imaging thin (<15 cm) sandy tsunami deposits and their associated structures using high-frequency 500 and 1000 MHz GPR antennae complemented by auger cores. The tsunami impact and recovery was reconciled by three 100 MHz GPR profiles and quasi-yearly satellite imagery. The GPR revealed the depth and extent of tsunami scour along with the sedimentary history of post tsunami coastal aggradation and recovery. The second GPR campaign captured several distinct palaeotsunami deposits as discreet thin sand layers preserved within a swale. The base of the swale and the contacts between the sandy and muddy layers are clearly imaged, although these reflectors are less consistent across the profile, suggesting that the contacts between thin sand and mud units can be accurately imaged provided the units are thicker than ca. 10cm. Our investigations show that GPR can be used to rapidly and non-invasively assess post event recovery and to image sandy washover events in muddy swales that are the result of tsunamis or storms.

High-Resolution Time-Lapse Monitoring of Unsaturated Flow using Automated GPR Data Collection

NASA Astrophysics Data System (ADS)

Mangel, A. R.; Moysey, S. M.; Lytle, B. A.; Bradford, J. H.

2015-12-01

High-resolution ground-penetrating radar (GPR) data provide the detailed information required to image subsurface structures. Recent advances in GPR monitoring now also make it possible to study transient hydrologic processes, but high-speed data acquisition is critical for this application. We therefore highlight the capabilities of our automated system to acquire time-lapse, high-resolution multifold GPR data during infiltration of water into soils. The system design allows for fast acquisition of constant-offset (COP) and common-midpoint profiles (CMP) to monitor unsaturated flow at multiple locations. Qualitative interpretation of the unprocessed COPs can provide substantial information regarding the hydrologic response of the system, such as the complexities of patterns associated with the wetting of the soil and geophysical evidence of non-uniform propagation of a wetting front. While we find that unprocessed images are informative, we show that the spatial variability of velocity introduced by infiltration events can complicate the images and that migration of the data is an effective tool to improve interpretability of the time-lapse images. The ability of the system to collect high density CMP data also introduces the potential for improving the velocity model along with the image via reflection tomography in the post-migrated domain. We show that for both simulated and empirical time-lapse GPR profiles we can resolve a propagating wetting front in the soil that is in good agreement with the response of in-situ soil moisture measurements. The data from these experiments illustrate the importance of high-speed, high-resolution GPR data acquisition for obtaining insight about the dynamics of hydrologic events. Continuing research is aimed at improving the quantitative analysis of surface-based GPR monitoring data for identifying preferential flow in soils.

Insights into the use of time-lapse GPR data as observations for inverse multiphase flow simulations of DNAPL migration

USGS Publications Warehouse

Johnson, R.H.; Poeter, E.P.

2007-01-01

Perchloroethylene (PCE) saturations determined from GPR surveys were used as observations for inversion of multiphase flow simulations of a PCE injection experiment (Borden 9??m cell), allowing for the estimation of optimal bulk intrinsic permeability values. The resulting fit statistics and analysis of residuals (observed minus simulated PCE saturations) were used to improve the conceptual model. These improvements included adjustment of the elevation of a permeability contrast, use of the van Genuchten versus Brooks-Corey capillary pressure-saturation curve, and a weighting scheme to account for greater measurement error with larger saturation values. A limitation in determining PCE saturations through one-dimensional GPR modeling is non-uniqueness when multiple GPR parameters are unknown (i.e., permittivity, depth, and gain function). Site knowledge, fixing the gain function, and multiphase flow simulations assisted in evaluating non-unique conceptual models of PCE saturation, where depth and layering were reinterpreted to provide alternate conceptual models. Remaining bias in the residuals is attributed to the violation of assumptions in the one-dimensional GPR interpretation (which assumes flat, infinite, horizontal layering) resulting from multidimensional influences that were not included in the conceptual model. While the limitations and errors in using GPR data as observations for inverse multiphase flow simulations are frustrating and difficult to quantify, simulation results indicate that the error and bias in the PCE saturation values are small enough to still provide reasonable optimal permeability values. The effort to improve model fit and reduce residual bias decreases simulation error even for an inversion based on biased observations and provides insight into alternate GPR data interpretations. Thus, this effort is warranted and provides information on bias in the observation data when this bias is otherwise difficult to assess. ?? 2006 Elsevier B.V. All rights reserved.

Allosteric ligands for the pharmacologically dark receptors GPR68 and GPR65

PubMed Central

Huang, Xi-Ping; Karpiak, Joel; Kroeze, Wesley K.; Zhu, Hu; Chen, Xin; Moy, Sheryl S.; Saddoris, Kara A.; Nikolova, Viktoriya; Farrell, Martilias S.; Wang, Sheng; Mangano, Thomas J.; Deshpande, Deepak A.; Jiang, Alice; Penn, Raymond B.; Jin, Jian; Koller, Beverly H.; Kenakin, Terry; Shoichet, Brian K.; Roth, Bryan L.

2016-01-01

At least 120 non-olfactory G protein-coupled receptors in the human genome are ”orphans” for which endogenous ligands are unknown, and many have no selective ligands, hindering elucidation of their biological functions and clinical relevance. Among these is GPR68, a proton receptor that lacks small molecule modulators for probing its biology. Yeast-based screens against GPR68 identified the benzodiazepine drug lorazepam as a non-selective GPR68 positive allosteric modulator. Over 3000 GPR68 homology models were refined to recognize lorazepam in a putative allosteric site. Docking 3.1 million molecules predicted new GPR68 modulators many of which were confirmed in functional assays. One potent GPR68 modulator—ogerin– suppressed recall in fear conditioning in wild-type, but not in GPR68 knockout mice. The same approach led to the discovery of allosteric agonists and negative allosteric modulators for GPR65. Combining physical and structure-based screening may be broadly useful for ligand discovery for understudied and orphan GPCRs. PMID:26550826

COST Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar": first-year activities and results

NASA Astrophysics Data System (ADS)

Pajewski, Lara; Benedetto, Andrea; Loizos, Andreas; Slob, Evert; Tosti, Fabio

2014-05-01

This work aims at presenting the first-year activities and results of COST (European COoperation in Science and Technology) Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar". This Action was launched in April 2013 and will last four years. The principal aim of COST Action TU1208 is to exchange and increase scientific-technical knowledge and experience of GPR techniques in civil engineering, whilst simultaneously promoting throughout Europe the effective use of this safe and non-destructive technique in the monitoring of infrastructures and structures. Moreover, the Action is oriented to the following specific objectives and expected deliverables: (i) coordinating European scientists to highlight problems, merits and limits of current GPR systems; (ii) developing innovative protocols and guidelines, which will be published in a handbook and constitute a basis for European standards, for an effective GPR application in civil- engineering tasks; safety, economic and financial criteria will be integrated within the protocols; (iii) integrating competences for the improvement and merging of electromagnetic scattering techniques and of data- processing techniques; this will lead to a novel freeware tool for the localization of buried objects, shape-reconstruction and estimation of geophysical parameters useful for civil engineering needs; (iv) networking for the design, realization and optimization of innovative GPR equipment; (v) comparing GPR with different NDT techniques, such as ultrasonic, radiographic, liquid-penetrant, magnetic-particle, acoustic-emission and eddy-current testing; (vi) comparing GPR technology and methodology used in civil engineering with those used in other fields; (vii) promotion of a more widespread, advanced and efficient use of GPR in civil engineering; and (viii) organization of a high-level modular training program for GPR European users. Four Working Groups (WGs) carry out the research activities. The first WG focuses on the design of innovative GPR equipment, on the building of prototypes and on the testing and optimisation of new systems. The second WG focuses on the GPR surveying of pavement, bridges, tunnels and buildings, as well as on the sensing of underground utilities and voids. The third WG deals with the development of electromagnetic forward and inverse scattering methods, for the characterization of GPR scenarios, as well as with data- processing algorithms for the elaboration of the data collected during GPR surveys. The fourth WG works on the use of GPR in fields different from the civil engineering, as well as on the integration of GPR with other non-destructive testing techniques. Each WG includes several Projects. COST Action TU1208 is active through a range of networking tools: meetings, workshops, conferences, training schools, short-term scientific missions, dissemination activities. During the first year of activities, a First General Meeting was organized in Rome, in July 2013, a second meeting took place in Nantes, in February 2014, and the Second General Meeting is being held jointly with the 2014 EGU General Assembly. A training school on "Microwave Imaging and Diagnostics: Theory, Techniques, and Applications", held in March 2014, was co-organised with the European School of Antennas. Four Short-Term Scientific Missions were funded, allowing young researchers to spend a period of time in an institution abroad, in order to carry out a research project contributing to the scientific objectives of the Action. The Action's activities were disseminated in international conferences [1]-[4], as well as in further workshops and meetings. Two volumes were published [5]-[6], and several scientific papers on peer-reviewed journals. A Springer book presenting the state of the art on civil engineering applications of Ground Penetrating Radar is being prepared and is going to be published in summer 2014. A COST Action is a wide bottom-up interdisciplinary science and technology network, open to researchers from universities, public and private research institutions, as well as to NGOs, industry and SMEs. At present, About 100 Institutions from 24 COST Member Countries (Austria, Belgium, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Italy, Latvia, Malta, Macedonia, The Netherlands, Norway, Poland, Portugal, Slovakia, Slovenia, Spain, Switzerland, Turkey, United Kingdom) have already joined the Action, together with an Institution from Armenia (Near Neighbour Country, NNC). Beyond European borders, six Institutions from U.S.A., one from Rwanda and one from Australia have joined the Action. Further applications from two NNCs (Egypt and Ukraine) and International Partner Countries (Hong Kong and Japan) are under examination. COST Action TU1208 is still open to the participation of new parties and it is possible to include, in the scientific work plan, new perspectives and activities. Scientists and scientific institutions willing to join COST Action TU1208 are encouraged to contact the Chair of the Action and to follow the procedure described at http://www.cost.eu/participate/join_action. For more information on COST Action TU1208, please visit www.GPRadar.eu. ----------------------------- Acknowledgement The Authors thanks COST for funding COST Action TU1208. References [1] L. Pajewski, A. Benedetto, A. Loizos, E. Slob, F. Tosti, "Civil Engineering Applications of Ground Penetrating Radar: Research Perspectives in COST Action TU1208," Geophysical Research Abstracts, European Geosciences Union (EGU) General Assembly 2013, 7-12 April 2013, Vienna, Austria, article ID EGU2013-13941. [2] L. Pajewski, A. Benedetto, G. Schettini, F. Soldovieri, "Applications of GPR in archaeological prospecting and cultural heritage diagnostics: Research Perspectives in COST Action TU1208," Geophysical Research Abstracts, European Geosciences Union (EGU) General Assembly 2013, 7-12 April 2013, Vienna, Austria, article ID EGU2013-14010. [3] L. Pajewski, A. Benedetto, X. Dérobert, A. Giannopoulos, A. Loizos, G. Manacorda, M. Marciniak, C. Plati, G. Schettini, I. Trinks, "Applications of Ground Penetrating Radar in Civil Engineering - COST Action TU1208," Proc. 7th International Workshop on Advanced Ground Penetrating Radar (IWAGPR), 2-5 July 2013, Nantes, France, pp. 1-6 (INVITED). ISBN 978-1-4799-0937-7, doi:10.1109/ IWAGPR.2013.6601528). [4] L. Pajewski, A. Benedetto, "Advanced Ground Penetrating Radar: open issues and new research opportunities in Europe," Proc. 10th European Radar Conference (EuRad), 2013 European Microwave Week (EuMW), 6-11 October 2013, Nuremberg, Germany, pp. 1847-1850. [5] Proceedings of the First Action's General Meeting (Editors: L. Pajewski and A. Benedetto; Publishing House: Aracne; Rome, July 2013; 194 pp.; ISBN 978-88-548-6191-6; o.o. 978-88-548-6190-9) - available as free download on www.GPRadar.eu [6] Booklet of Participants and Institutions (Editors: L. Pajewski and A. Benedetto; Publishing House: Aracne; Rome, July 2013; 127 pp.; ISBN 978-88-548-6192-3; o.o. 978-88-548-6190-9) - available as free download on www.GPRadar.eu

COST Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar:" ongoing research activities and mid-term results

NASA Astrophysics Data System (ADS)

Pajewski, Lara; Benedetto, Andrea; Loizos, Andreas; Slob, Evert; Tosti, Fabio

2015-04-01

This work aims at presenting the ongoing activities and mid-term results of the COST (European COoperation in Science and Technology) Action TU1208 'Civil Engineering Applications of Ground Penetrating Radar.' Almost three hundreds experts are participating to the Action, from 28 COST Countries (Austria, Belgium, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Ireland, Italy, Latvia, Malta, Macedonia, The Netherlands, Norway, Poland, Portugal, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey, United Kingdom), and from Albania, Armenia, Australia, Egypt, Hong Kong, Jordan, Israel, Philippines, Russia, Rwanda, Ukraine, and United States of America. In September 2014, TU1208 has been praised among the running Actions as 'COST Success Story' ('The Cities of Tomorrow: The Challenges of Horizon 2020,' September 17-19, 2014, Torino, IT - A COST strategic workshop on the development and needs of the European cities). The principal goal of the COST Action TU1208 is to exchange and increase scientific-technical knowledge and experience of GPR techniques in civil engineering, whilst simultaneously promoting throughout Europe the effective use of this safe and non-destructive technique in the monitoring of infrastructures and structures. Moreover, the Action is oriented to the following specific objectives and expected deliverables: (i) coordinating European scientists to highlight problems, merits and limits of current GPR systems; (ii) developing innovative protocols and guidelines, which will be published in a handbook and constitute a basis for European standards, for an effective GPR application in civil- engineering tasks; safety, economic and financial criteria will be integrated within the protocols; (iii) integrating competences for the improvement and merging of electromagnetic scattering techniques and of data- processing techniques; this will lead to a novel freeware tool for the localization of buried objects, shape-reconstruction and estimation of geophysical parameters useful for civil engineering needs; (iv) networking for the design, realization and optimization of innovative GPR equipment; (v) comparing GPR with different NDT techniques, such as ultrasonic, radiographic, liquid-penetrant, magnetic-particle, acoustic-emission and eddy-current testing; (vi) comparing GPR technology and methodology used in civil engineering with those used in other fields; (vii) promotion of a more widespread, advanced and efficient use of GPR in civil engineering; and (viii) organization of a high-level modular training program for GPR European users. Four Working Groups (WGs) carry out the research activities. WG 1 focuses on the design of innovative GPR equipment, on the building of prototypes and on the testing and optimisation of new systems. WG 2 focuses on the GPR surveying of pavement, bridges, tunnels and buildings, as well as on the sensing of underground utilities and voids. WG 3 deals with the development of electromagnetic forward and inverse scattering methods, for the characterization of GPR scenarios, as well as with data- processing algorithms for the elaboration of the data collected during GPR surveys. WG 4 works on the use of GPR in fields different from the civil engineering, as well as on the integration of GPR with other non-destructive testing techniques. Each WG includes several Projects. COST Action TU1208 is active through a range of networking tools: meetings, workshops, conferences, training schools, short-term scientific missions, dissemination activities. The Action is still open to the participation of new parties and it is possible to include, in the scientific work plan, new perspectives and activities. Scientists and scientific institutions willing to join are encouraged to contact the Chair of the Action and to follow the procedure described at http://www.cost.eu/participate/join_action. For more information on COST Action TU1208, please visit www.GPRadar.eu. Acknowledgement The Authors thank COST, for funding the Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar." References [1] L. Pajewski, A. Benedetto, X. Dérobert, A. Giannopoulos, A. Loizos, G. Manacorda, M. Marciniak, C. Plati, G. Schettini, I. Trinks, "Applications of Ground Penetrating Radar in Civil Engineering - COST Action TU1208," Proc. 7th International Workshop on Advanced Ground Penetrating Radar (IWAGPR), 2-5 July 2013, Nantes, France, pp. 1-6 (INVITED). ISBN 978-1-4799-0937-7, doi:10.1109/ IWAGPR.2013.6601528). [2] L. Pajewski, A. Benedetto, "Advanced Ground Penetrating Radar: open issues and new research opportunities in Europe," Proc. 10th European Radar Conference (EuRad), 2013 European Microwave Week (EuMW), 6-11 October 2013, Nuremberg, Germany, pp. 1847-1850. [3] 'Proceedings of the First Action's General Meeting - Rome, Italy, July 2013' 1st edition, COST Action TU1208, Aracne, L. Pajewski and A. Benedetto, Eds., Rome, Italy, July 2013, ISBN 978-88-548-6191-6, available online at www.GPRadar.eu. [4] 'Booklet of Participants and Institutions,' 1st edition, COST Action TU1208, Aracne, L. Pajewski and A. Benedetto, Eds., Rome, Italy, July 2013, ISBN 978-88-548-6192-3, available online at www.GPRadar.eu. [5] 'Proceedings of the 2014 Working Group Progress Meeting - Nantes, France, February 2014,' COST Action TU1208, Aracne, L. Pajewski and X. Derobert, Eds., Rome, Italy, May 2014, ISBN 978-88-548-7223-3, available online at www.GPRadar.eu. [6] 'Proceedings of the Second Action's General Meeting - Vienna, Austria, April-May 2014,' COST Action TU1208, Aracne, L. Pajewski and A. Benedetto, Eds., Rome, Italy, 2014, ISBN 978-88-548-7224-0. [7] 'Short Term Scientific Missions and Training Schools - Year 1,' COST Action TU1208, Aracne, L. Pajewski and M. Marciniak, Eds., Rome, Italy, 2014, ISBN 978-88-548-7225-7. [8] 'Civil Engineering Applications of Ground Penetrating Radar,' A. Benedetto and L. Pajewski Eds., Springer, July 2015, ISBN 978-3-319-04812-3 (in press). [9] 'Proceedings of the 15th International Conference on Ground Penetrating Radar - GPR2014, June 30 - July 4, 2014, Bruxelles, Belgium,' S. Lambot, A. Giannopoulos, L. Pajewski, F. De André, E. Slob, and C. Craeye, Eds., IEEE Conference Record Number: 35163, ISBN: 978-1-4799-6789-6, IEEE Part Number: CFP14538-ART, October 2014. [10] 'Near Surface Geophysics' Special Issue on 'Civil and Environmental Engineering Applications of Ground Penetrating Radar,' A. Benedetto, A. Loizos, L. Pajewski, and F. Tosti, Guest Eds., publication planned for Spring 2015. [11] IEEE Journal of Selected Topics in Applied Earth Observations and Remote Sensing (JSTARS) Special Issue on 'Ground Penetrating Radar', S. Lambot, A. Giannopoulos, L. Pajewski, E. Slob, Guest Eds., publication planned for December 2015.

Cloning and characterization of the rat free fatty acid receptor GPR120: in vivo effect of the natural ligand on GLP-1 secretion and proliferation of pancreatic beta cells.

PubMed

Tanaka, Toshiki; Yano, Takeaki; Adachi, Tetsuya; Koshimizu, Taka-aki; Hirasawa, Akira; Tsujimoto, Gozoh

2008-06-01

We have recently found that GPR120, which is abundantly expressed in intestine, functions as a receptor for unsaturated long-chain free fatty acids (FFAs) and that GPR120 stimulation promotes the secretion of glucagons-like peptide-1 (GLP-1) in the mouse (Hirasawa et al., Nat Med 11:90-94, 2005). In this study, we cloned and characterized rat GPR120 (rGPR120), and then we examined the in vivo effects of acute and long-term administration of the natural ligand alpha-linolenic acid (alpha-LA). The cloned rat GPR120 complimentary DNA had a seven transmembrane structure, and a homology comparison of human, mouse, and rat GPR120 revealed that the rat GPR120 (rGPR120) shares 85 and 98% sequence identity with the human and mouse GPR120 proteins, respectively. The tissue distribution and ligand properties of rGPR120 were similar to those of mouse GPR120. In addition, alpha-LA provoked a transient increase in [Ca2+]i levels in HEK293 cells expressing rGPR120. Furthermore, administration of alpha-LA to the rat increased plasma GLP-1 levels, and long-term administration of alpha-LA led to proliferation of pancreatic beta cells, probably because of the enhanced GLP-1 secretion. These results show that rat GPR120 is a G-protein-coupled receptor whose ligand is a free fatty acid, and it may play an important role in the FFA-associated physiological responses.

Cell adhesion controlled by adhesion G protein-coupled receptor GPR124/ADGRA2 is mediated by a protein complex comprising intersectins and Elmo-Dock.

PubMed

Hernández-Vásquez, Magda Nohemí; Adame-García, Sendi Rafael; Hamoud, Noumeira; Chidiac, Rony; Reyes-Cruz, Guadalupe; Gratton, Jean Philippe; Côté, Jean-François; Vázquez-Prado, José

2017-07-21

Developmental angiogenesis and the maintenance of the blood-brain barrier involve endothelial cell adhesion, which is linked to cytoskeletal dynamics. GPR124 (also known as TEM5/ADGRA2) is an adhesion G protein-coupled receptor family member that plays a pivotal role in brain angiogenesis and in ensuring a tight blood-brain barrier. However, the signaling properties of GPR124 remain poorly defined. Here, we show that ectopic expression of GPR124 promotes cell adhesion, additive to extracellular matrix-dependent effect, coupled with filopodia and lamellipodia formation and an enrichment of a pool of the G protein-coupled receptor at actin-rich cellular protrusions containing VASP, a filopodial marker. Accordingly, GPR124-expressing cells also displayed increased activation of both Rac and Cdc42 GTPases. Mechanistically, we uncover novel direct interactions between endogenous GPR124 and the Rho guanine nucleotide exchange factors Elmo/Dock and intersectin (ITSN). Small fragments of either Elmo or ITSN1 that bind GPR124 blocked GPR124-induced cell adhesion. In addition, Gβγ interacts with the C-terminal tail of GPR124 and promotes the formation of a GPR124-Elmo complex. Furthermore, GPR124 also promotes the activation of the Elmo-Dock complex, as measured by Elmo phosphorylation on a conserved C-terminal tyrosine residue. Interestingly, Elmo and ITSN1 also interact with each other independently of their GPR124-recognition regions. Moreover, endogenous phospho-Elmo and ITSN1 co-localize with GPR124 at lamellipodia of adhering endothelial cells, where GPR124 expression contributes to polarity acquisition during wound healing. Collectively, our results indicate that GPR124 promotes cell adhesion via Elmo-Dock and ITSN. This constitutes a previously unrecognized complex formed of atypical and conventional Rho guanine nucleotide exchange factors for Rac and Cdc42 that is putatively involved in GPR124-dependent angiogenic responses. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Several Classical Mouse Inbred Strains, Including DBA/2, NOD/Lt, FVB/N, and SJL/J, Carry a Putative Loss-of-Function Allele of Gpr84

PubMed Central

2013-01-01

G protein–coupled receptor 84 (GPR84) is a 7-transmembrane protein expressed on myeloid cells that can bind to medium-chain free fatty acids in vitro. Here, we report the discovery of a 2-bp frameshift deletion in the second exon of the Gpr84 gene in several classical mouse inbred strains. This deletion generates a premature stop codon predicted to result in a truncated protein lacking the transmembrane domains 4-7. We sequenced Gpr84 exon 2 from 58 strains representing different groups in the mouse family tree and found that 14 strains are homozygous for the deletion. Some of these strains are DBA/1J, DBA/2J, FVB/NJ, LG/J, MRL/MpJ, NOD/LtJ, and SJL/J. However, the deletion was not found in any of the wild-derived inbred strains analyzed. Haplotype analysis suggested that the deletion originates from a unique mutation event that occurred more than 100 years ago, preceding the development of the first inbred strain (DBA), from a Mus musculus domesticus source. As GPR84 ostensibly plays a role in the biology of myeloid cells, it could be relevant 1) to consider the existence of this Gpr84 nonsense mutation in several mouse strains when choosing a mouse model to study immune processes and 2) to consider reevaluating data obtained using such strains. PMID:23616478

Several classical mouse inbred strains, including DBA/2, NOD/Lt, FVB/N, and SJL/J, carry a putative loss-of-function allele of Gpr84.

PubMed

Perez, Carlos J; Dumas, Aline; Vallières, Luc; Guénet, Jean-Louis; Benavides, Fernando

2013-01-01

G protein-coupled receptor 84 (GPR84) is a 7-transmembrane protein expressed on myeloid cells that can bind to medium-chain free fatty acids in vitro. Here, we report the discovery of a 2-bp frameshift deletion in the second exon of the Gpr84 gene in several classical mouse inbred strains. This deletion generates a premature stop codon predicted to result in a truncated protein lacking the transmembrane domains 4-7. We sequenced Gpr84 exon 2 from 58 strains representing different groups in the mouse family tree and found that 14 strains are homozygous for the deletion. Some of these strains are DBA/1J, DBA/2J, FVB/NJ, LG/J, MRL/MpJ, NOD/LtJ, and SJL/J. However, the deletion was not found in any of the wild-derived inbred strains analyzed. Haplotype analysis suggested that the deletion originates from a unique mutation event that occurred more than 100 years ago, preceding the development of the first inbred strain (DBA), from a Mus musculus domesticus source. As GPR84 ostensibly plays a role in the biology of myeloid cells, it could be relevant 1) to consider the existence of this Gpr84 nonsense mutation in several mouse strains when choosing a mouse model to study immune processes and 2) to consider reevaluating data obtained using such strains.

The role of parkinson's disease-associated receptor GPR37 in the hippocampus: functional interplay with the adenosinergic system.

PubMed

Lopes, João P; Morató, Xavier; Souza, Carolina; Pinhal, Cindy; Machado, Nuno J; Canas, Paula M; Silva, Henrique B; Stagljar, Igor; Gandía, Jorge; Fernández-Dueñas, Víctor; Luján, Rafael; Cunha, Rodrigo A; Ciruela, Francisco

2015-07-01

GPR37 is an orphan G protein-coupled receptor mostly enriched in brain areas such as the cerebellum, striatum, and hippocampus. Identified as a substrate of parkin, GPR37 has been suggested to play a role in Parkinson's disease. Distributed throughout the brain, the function of GPR37, however, remains unknown. We now provide the first mapping of GPR37 within the hippocampus, where GPR37 is widely expressed and localized at the level of the extrasynaptic plasma membrane of dendritic spines, dendritic shafts, and axon terminals. GPR37 per se does not appear to play a role in learning and memory, since knocking out GPR37 (GPR37-KO) did not alter the performance in different hippocampal-related memory tasks. This is in agreement with slice electrophysiology experiments showing no differences both in short-term plasticity paired-pulse facilitation and long-term potentiation between WT and GPR37-KO mice. However, we report a potential functional interaction between GPR37 and adenosine A2A receptors (A2 A R) in the hippocampus, with A2 A R modulating the GPR37-associated phenotype. Thus, the absence of GPR37 appeared to sensitize mice to hippocampal A2 A R-mediated signaling, as observed by the effect of the A2 A R antagonist SCH58261 increasing synaptic depotentiation, reducing novel object recognition memory and reverting the anxiolytic effect of GPR37 deletion. Collectively, these findings afford insight into the localization and role of the orphan GPR37 within the hippocampus with potential involvement in A2 A R function (i.e., A2 A R sensitization). GPR37 is an orphan G protein-coupled receptor widely expressed in the hippocampus and localized at the level of the extrasynaptic plasma membrane of dendritic spines, dendritic shafts and axon terminals. This orphan receptor per se does not appear to directly control the learning and memory processes; however knocking-out GPR37 triggers anxiolytic-like effects and sensitizes mice to hippocampal A2A R-mediated signalling. © 2015 International Society for Neurochemistry.

Analysis of thin fractures with GPR: from theory to practice

NASA Astrophysics Data System (ADS)

Arosio, Diego; Zanzi, Luigi; Longoni, Laura; Papini, Monica

2017-04-01

Whenever we perform a GPR survey to investigate a rocky medium, being the ultimate purpose of the survey either to study the stability of a rock slope or to determine the soundness of a quarried rock block, we would like mainly to detect any fracture within the investigated medium and, possibly, to estimate the parameters of the fractures, namely thickness and filling material. In most of the practical cases, rock fracture thicknesses are very small when compared to the wavelength of the electromagnetic radiation generated by the GPR systems. In such cases, fractures are to be considered as thin beds, i.e. two interfaces whose distance is smaller than GPR resolving capability, and the reflected signal is the sum of the electromagnetic reverberation within the bed. According to this, fracture parameters are encoded in the thin bed complex response and in this work we propose a methodology based on deterministic deconvolution to process amplitude and phase information in the frequency domain to estimate fracture parameters. We first present some theoretical aspects related to thin bed response and a sensitivity analysis concerning fracture thickness and filling. Secondly, we deal with GPR datasets collected both during laboratory experiments and in the facilities of quarrying activities. In the lab tests fractures were simulated by placing materials with known electromagnetic parameters and controlled thickness in between two small marble blocks, whereas field GPR surveys were performed on bigger quarried ornamental stone blocks before they were submitted to the cutting process. We show that, with basic pre-processing and the choice of a proper deconvolving signal, results are encouraging although an ambiguity between thickness and filling estimates exists when no a-priori information is available. Results can be improved by performing CMP radar surveys that are able to provide additional information (i.e., variation of thin bed response versus offset) at the expense of acquisition effort and of more complex and tricky pre-processing sequences.

Genome-wide association analysis in primary sclerosing cholangitis and ulcerative colitis identifies risk loci at GPR35 and TCF4.

PubMed

Ellinghaus, David; Folseraas, Trine; Holm, Kristian; Ellinghaus, Eva; Melum, Espen; Balschun, Tobias; Laerdahl, Jon K; Shiryaev, Alexey; Gotthardt, Daniel N; Weismüller, Tobias J; Schramm, Christoph; Wittig, Michael; Bergquist, Annika; Björnsson, Einar; Marschall, Hanns-Ulrich; Vatn, Morten; Teufel, Andreas; Rust, Christian; Gieger, Christian; Wichmann, H-Erich; Runz, Heiko; Sterneck, Martina; Rupp, Christian; Braun, Felix; Weersma, Rinse K; Wijmenga, Cisca; Ponsioen, Cyriel Y; Mathew, Christopher G; Rutgeerts, Paul; Vermeire, Séverine; Schrumpf, Erik; Hov, Johannes R; Manns, Michael P; Boberg, Kirsten M; Schreiber, Stefan; Franke, Andre; Karlsen, Tom H

2013-09-01

Approximately 60%-80% of patients with primary sclerosing cholangitis (PSC) have concurrent ulcerative colitis (UC). Previous genome-wide association studies (GWAS) in PSC have detected a number of susceptibility loci that also show associations in UC and other immune-mediated diseases. We aimed to systematically compare genetic associations in PSC with genotype data in UC patients with the aim of detecting new susceptibility loci for PSC. We performed combined analyses of GWAS for PSC and UC comprising 392 PSC cases, 987 UC cases, and 2,977 controls and followed up top association signals in an additional 1,012 PSC cases, 4,444 UC cases, and 11,659 controls. We discovered novel genome-wide significant associations with PSC at 2q37 [rs3749171 at G-protein-coupled receptor 35 (GPR35); P = 3.0 × 10(-9) in the overall study population, combined odds ratio [OR] and 95% confidence interval [CI] of 1.39 (1.24-1.55)] and at 18q21 [rs1452787 at transcription factor 4 (TCF4); P = 2.61 × 10(-8) , OR (95% CI) = 0.75 (0.68-0.83)]. In addition, several suggestive PSC associations were detected. The GPR35 rs3749171 is a missense single nucleotide polymorphism resulting in a shift from threonine to methionine. Structural modeling showed that rs3749171 is located in the third transmembrane helix of GPR35 and could possibly alter efficiency of signaling through the GPR35 receptor. By refining the analysis of a PSC GWAS by parallel assessments in a UC GWAS, we were able to detect two novel risk loci at genome-wide significance levels. GPR35 shows associations in both UC and PSC, whereas TCF4 represents a PSC risk locus not associated with UC. Both loci may represent previously unexplored aspects of PSC pathogenesis. Copyright © 2012 American Association for the Study of Liver Diseases.

Unmanned Ground Vehicle for Autonomous Non-Destructive Testing of FRP Bridge Decks

NASA Astrophysics Data System (ADS)

Klinkhachorn, P.; Mercer, A. Scott; Halabe, Udaya B.; GangaRao, Hota V. S.

2007-03-01

Current non-destructive techniques for defect analysis of FRP bridge decks have a narrow scope. These techniques are very good at detecting certain types of defects but are not robust enough to detect all defects by themselves. For example, infrared thermography (IRT) can detect air filled defects and Ground Penetrating Radar (GPR) is good at detecting water filled ones. These technologies can be combined to create a more robust defect detection scheme. To accomplish this, an Unmanned Ground Vehicle (UGV) has been designed that incorporates both IR and GPR analysis to create a comprehensive defect map of a bridge deck. The UGV autonomously surveys the deck surface and acquires data. The UGV has two 1.5 GHz ground coupled GPR antennas that are mounted on the front of the UGV to collect GPR data. It also incorporates an active heating source and a radiometric IR camera to capture IR images of the deck, even in less than ideal weather scenarios such as cold cloudy days. The UGV is designed so that it can collect data in an assembly line fashion. It moves in 1 foot increments. When moving, it collects GPR data from the two antennas. When it stops it heats a section of the deck. The next time it stops to heat a section, the IR camera is analyzing the preheated deck section while preparing for the next section. Because the data is being continually collected using this method, the UGV can survey the entire deck in an efficient and timely manner.

Characterization of Imidazopyridine Compounds as Negative Allosteric Modulators of Proton-Sensing GPR4 in Extracellular Acidification-Induced Responses

PubMed Central

Tobo, Ayaka; Tobo, Masayuki; Nakakura, Takashi; Ebara, Masashi; Tomura, Hideaki; Mogi, Chihiro; Im, Dong-Soon; Murata, Naoya; Kuwabara, Atsushi; Ito, Saki; Fukuda, Hayato; Arisawa, Mitsuhiro; Shuto, Satoshi; Nakaya, Michio; Kurose, Hitoshi; Sato, Koichi; Okajima, Fumikazu

2015-01-01

G protein-coupled receptor 4 (GPR4), previously proposed as the receptor for sphingosylphosphorylcholine, has recently been identified as the proton-sensing G protein-coupled receptor (GPCR) coupling to multiple intracellular signaling pathways, including the Gs protein/cAMP and G13 protein/Rho. In the present study, we characterized some imidazopyridine compounds as GPR4 modulators that modify GPR4 receptor function. In the cells that express proton-sensing GPCRs, including GPR4, OGR1, TDAG8, and G2A, extracellular acidification stimulates serum responsive element (SRE)-driven transcriptional activity, which has been shown to reflect Rho activity, with different proton sensitivities. Imidazopyridine compounds inhibited the moderately acidic pH-induced SRE activity only in GPR4-expressing cells. Acidic pH-stimulated cAMP accumulation, mRNA expression of inflammatory genes, and GPR4 internalization within GPR4-expressing cells were all inhibited by the GPR4 modulator. We further compared the inhibition property of the imidazopyridine compound with psychosine, which has been shown to selectively inhibit actions induced by proton-sensing GPCRs, including GPR4. In the GPR4 mutant, in which certain histidine residues were mutated to phenylalanine, proton sensitivity was significantly shifted to the right, and psychosine failed to further inhibit acidic pH-induced SRE activation. On the other hand, the imidazopyridine compound almost completely inhibited acidic pH-induced action in mutant GPR4. We conclude that some imidazopyridine compounds show specificity to GPR4 as negative allosteric modulators with a different action mode from psychosine, an antagonist susceptible to histidine residues, and are useful for characterizing GPR4-mediated acidic pH-induced biological actions. PMID:26070068

Characterization of Imidazopyridine Compounds as Negative Allosteric Modulators of Proton-Sensing GPR4 in Extracellular Acidification-Induced Responses.

PubMed

Tobo, Ayaka; Tobo, Masayuki; Nakakura, Takashi; Ebara, Masashi; Tomura, Hideaki; Mogi, Chihiro; Im, Dong-Soon; Murata, Naoya; Kuwabara, Atsushi; Ito, Saki; Fukuda, Hayato; Arisawa, Mitsuhiro; Shuto, Satoshi; Nakaya, Michio; Kurose, Hitoshi; Sato, Koichi; Okajima, Fumikazu

2015-01-01

G protein-coupled receptor 4 (GPR4), previously proposed as the receptor for sphingosylphosphorylcholine, has recently been identified as the proton-sensing G protein-coupled receptor (GPCR) coupling to multiple intracellular signaling pathways, including the Gs protein/cAMP and G13 protein/Rho. In the present study, we characterized some imidazopyridine compounds as GPR4 modulators that modify GPR4 receptor function. In the cells that express proton-sensing GPCRs, including GPR4, OGR1, TDAG8, and G2A, extracellular acidification stimulates serum responsive element (SRE)-driven transcriptional activity, which has been shown to reflect Rho activity, with different proton sensitivities. Imidazopyridine compounds inhibited the moderately acidic pH-induced SRE activity only in GPR4-expressing cells. Acidic pH-stimulated cAMP accumulation, mRNA expression of inflammatory genes, and GPR4 internalization within GPR4-expressing cells were all inhibited by the GPR4 modulator. We further compared the inhibition property of the imidazopyridine compound with psychosine, which has been shown to selectively inhibit actions induced by proton-sensing GPCRs, including GPR4. In the GPR4 mutant, in which certain histidine residues were mutated to phenylalanine, proton sensitivity was significantly shifted to the right, and psychosine failed to further inhibit acidic pH-induced SRE activation. On the other hand, the imidazopyridine compound almost completely inhibited acidic pH-induced action in mutant GPR4. We conclude that some imidazopyridine compounds show specificity to GPR4 as negative allosteric modulators with a different action mode from psychosine, an antagonist susceptible to histidine residues, and are useful for characterizing GPR4-mediated acidic pH-induced biological actions.

Targeting of the Orphan Receptor GPR35 by Pamoic Acid: A Potent Activator of Extracellular Signal-Regulated Kinase and β-Arrestin2 with Antinociceptive ActivityS⃞

PubMed Central

Zhao, Pingwei; Sharir, Haleli; Kapur, Ankur; Cowan, Alan; Geller, Ellen B.; Adler, Martin W.; Seltzman, Herbert H.; Reggio, Patricia H.; Heynen-Genel, Susanne; Sauer, Michelle; Chung, Thomas D.Y.; Bai, Yushi; Chen, Wei; Caron, Marc G.; Barak, Larry S.

2010-01-01

Known agonists of the orphan receptor GPR35 are kynurenic acid, zaprinast, 5-nitro-2-(3-phenylproplyamino) benzoic acid, and lysophosphatidic acids. Their relatively low affinities for GPR35 and prominent off-target effects at other pathways, however, diminish their utility for understanding GPR35 signaling and for identifying potential therapeutic uses of GPR35. In a screen of the Prestwick Library of drugs and drug-like compounds, we have found that pamoic acid is a potent GPR35 agonist. Pamoic acid is considered by the Food and Drug Administration as an inactive compound that enables long-acting formulations of numerous drugs, such as the antihelminthics oxantel pamoate and pyrantel pamoate; the psychoactive compounds hydroxyzine pamoate (Vistaril) and imipramine pamoate (Tofranil-PM); and the peptide hormones triptorelin pamoate (Trelstar) and octreotide pamoate (OncoLar). We have found that pamoic acid induces a Gi/o-linked, GPR35-mediated increase in the phosphorylation of extracellular signal-regulated kinase 1/2, recruitment of β-arrestin2 to GPR35, and internalization of GPR35. In mice, it attenuates visceral pain perception, indicating an antinociceptive effect, possibly through GPR35 receptors. We have also identified in collaboration with the Sanford-Burnham Institute Molecular Libraries Probe Production Center new classes of GPR35 antagonist compounds, including the nanomolar potency antagonist methyl-5-[(tert-butylcarbamothioylhydrazinylidene)methyl]-1-(2,4-difluorophenyl)pyrazole-4-carboxylate (CID2745687). Pamoic acid and potent antagonists such as CID2745687 present novel opportunities for expanding the chemical space of GPR35, elucidating GPR35 pharmacology, and stimulating GPR35-associated drug development. Our results indicate that the unexpected biological functions of pamoic acid may yield potential new uses for a common drug constituent. PMID:20826425

Buried nonmetallic object detection using bistatic ground penetrating radar with variable antenna elevation angle and height

NASA Astrophysics Data System (ADS)

Zhang, Yu; Orfeo, Dan; Burns, Dylan; Miller, Jonathan; Huston, Dryver; Xia, Tian

2017-04-01

Ground penetrating radar (GPR) has been shown to be an effective device for detecting buried objects that have little or no metal content, such as plastic, ceramic, and concrete pipes. In this paper, buried non-metallic object detection is evaluated for different antenna elevation angles and heights using a bistatic air-launched GPR. Due to the large standoff distance between antennas and the ground surface, the air-launched GPR has larger spreading loss than the hand-held GPR and vehicle-mounted GPR. Moreover, nonmetallic objects may have similar dielectric property to the buried medium, which results in further difficulty for accurate detection using air-launched GPR. To study such effects, both GPR simulations and GPR laboratory experiments are performed with various setups where antennas are placed at different heights and angles. In the experiments, the test surface areas are configured with and without rocks in order to examine surface clutter effect. The experimental results evaluate the feasibility and effectiveness of bistatic air-launched GPR for detecting buried nonmetallic objects, which provide valuable insights for subsurface scanning with unmanned aerial vehicle (UAV) mounted GPR.

A medium-chain fatty acid receptor Gpr84 in zebrafish: expression pattern and roles in immune regulation.

PubMed

Huang, Qiaoyan; Feng, Dong; Liu, Kai; Wang, Peng; Xiao, Hongyan; Wang, Ying; Zhang, Shicui; Liu, Zhenhui

2014-08-01

Gpr84 was recently identified as a receptor for medium-chain fatty acids, but its functions remain to be clarified. We reported the identification of a zebrafish Gpr84 homologue (zGpr84), which has a higher gene expression in the tissues of intestine, heart and liver. During embryogenesis, zGpr84 is maternally expressed and a significant increase is observed at segmentation period, and it is mainly restricted to the head region, pectoral fins, branchial arches, intestine and lateral line neuromast. Fasting or treatment with lipopolysaccharide (LPS) can induce significant up-regulation of zGpr84. We further demonstrated that zGpr84 is involved in the accumulation of lipid droplets in cells. Moreover, undecanoic acid (UA) can amplify LPS induced production of the proinflammatory cytokine IL-12 p40 through zGpr84, supporting the proposal that Gpr84 may play a role in directly linking fatty acid metabolism to immunological regulation. The resulting data in fish lay a foundation for a comprehensive exploration of the functions and evolution of Gpr84. Copyright © 2014 Elsevier Ltd. All rights reserved.

GPR measurements and estimation for road subgrade damage caused by neighboring train vibration load

NASA Astrophysics Data System (ADS)

Zhao, Yonghui; Lu, Gang; Ge, Shuangcheng

2015-04-01

Generally, road can be simplified as a three-layer structure, including subgrade, subbase and pavement. Subgrade is the native material underneath a constructed road. It is commonly compacted before the road construction, and sometimes stabilized by the addition of asphalt, lime or other modifiers. As the mainly supporting structure, subgrade damage would lead in pavement settlement, displacement and crack. Assessment and monitoring of the subgrade condition currently involves trial pitting and subgrade sampling. However there is a practical limit on spatial density at which trail pits and cores can be taken. Ground penetrating radar (GPR) has been widely used to characterize highway pavement profiling, concrete structure inspection and railroad track ballast estimation. GPR can improve the economics of road maintenance. Long-term train vibration load might seriously influence the stability of the subgrade of neighboring road. Pavement settlement and obvious cracks have been found at a municipal road cross-under a railway with culvert box method. GPR test was conducted to estimate the subgrade and soil within 2.0 m depth for the further road maintenance. Two survey lines were designed in each lane, and total 12 GPR sections have been implemented. Considering both the penetrating range and the resolution, a antenna with a 500 MHz central frequency was chosen for on-site GPR data collection. For data acquisition, we used the default operating environment and scanning parameters for the RAMAC system: 60kHz transmission rate, 50 ns time window, 1024 samples per scan and 0.1 m step-size. Continuous operation was used; the antenna was placed on the road surface and slowly moved along the road. The strong surrounding disturbance related to railroad and attachments, might decrease the reliability of interpretation results. Some routine process methods (including the background removing, filtering) have been applied to suppress the background noise. Additionally, attribute analysis is an important tool that focused on the multi-properties of the signal. Here, cross-correlation attribute analysis has been applied for GPR profile interpretation. It compares one trace with surrounding traces to determine degrees of similar, and improves the difference between the reflected wave from detection target and its surrounding mediums, which makes it easy to detect the anomaly that couldn't be found in original GPR time profile. It's possible to identify sections of subgrade in good or worse condition, which may require specific maintenance or trail pitting investigation.

GPR image analysis to locate water leaks from buried pipes by applying variance filters

NASA Astrophysics Data System (ADS)

Ocaña-Levario, Silvia J.; Carreño-Alvarado, Elizabeth P.; Ayala-Cabrera, David; Izquierdo, Joaquín

2018-05-01

Nowadays, there is growing interest in controlling and reducing the amount of water lost through leakage in water supply systems (WSSs). Leakage is, in fact, one of the biggest problems faced by the managers of these utilities. This work addresses the problem of leakage in WSSs by using GPR (Ground Penetrating Radar) as a non-destructive method. The main objective is to identify and extract features from GPR images such as leaks and components in a controlled laboratory condition by a methodology based on second order statistical parameters and, using the obtained features, to create 3D models that allows quick visualization of components and leaks in WSSs from GPR image analysis and subsequent interpretation. This methodology has been used before in other fields and provided promising results. The results obtained with the proposed methodology are presented, analyzed, interpreted and compared with the results obtained by using a well-established multi-agent based methodology. These results show that the variance filter is capable of highlighting the characteristics of components and anomalies, in an intuitive manner, which can be identified by non-highly qualified personnel, using the 3D models we develop. This research intends to pave the way towards future intelligent detection systems that enable the automatic detection of leaks in WSSs.

A comparison of robust principal component analysis techniques for buried object detection in downward looking GPR sensor data

NASA Astrophysics Data System (ADS)

Pinar, Anthony; Havens, Timothy C.; Rice, Joseph; Masarik, Matthew; Burns, Joseph; Thelen, Brian

2016-05-01

Explosive hazards are a deadly threat in modern conflicts; hence, detecting them before they cause injury or death is of paramount importance. One method of buried explosive hazard discovery relies on data collected from ground penetrating radar (GPR) sensors. Threat detection with downward looking GPR is challenging due to large returns from non-target objects and clutter. This leads to a large number of false alarms (FAs), and since the responses of clutter and targets can form very similar signatures, classifier design is not trivial. One approach to combat these issues uses robust principal component analysis (RPCA) to enhance target signatures while suppressing clutter and background responses, though there are many versions of RPCA. This work applies some of these RPCA techniques to GPR sensor data and evaluates their merit using the peak signal-to-clutter ratio (SCR) of the RPCA-processed B-scans. Experimental results on government furnished data show that while some of the RPCA methods yield similar results, there are indeed some methods that outperform others. Furthermore, we show that the computation time required by the different RPCA methods varies widely, and the selection of tuning parameters in the RPCA algorithms has a major effect on the peak SCR.

Activation of the novel estrogen receptor G protein-coupled receptor 30 (GPR30) at the plasma membrane.

PubMed

Filardo, E; Quinn, J; Pang, Y; Graeber, C; Shaw, S; Dong, J; Thomas, P

2007-07-01

G protein-coupled receptor 30 (GPR30), a seven-transmembrane receptor (7TMR), is associated with rapid estrogen-dependent, G protein signaling and specific estrogen binding. At present, the subcellular site of GPR30 action is unclear. Previous studies using antibodies and fluorochrome-labeled estradiol (E2) have failed to detect GPR30 on the cell surface, suggesting that GPR30 may function uniquely among 7TMRs as an intracellular receptor. Here, we show that detectable expression of GPR30 on the surface of transfected HEK-293 cells can be selected by fluorescence-activated cell sorting. Expression of GPR30 on the cell surface was confirmed by confocal microscopy using the lectin concanavalin A as a plasma membrane marker. Stimulation of GPR30-expressing HEK-293 cells with 17beta-E2 caused sequestration of GPR30 from the cell surface and resulted in its codistribution with clathrin and mobilization of intracellular calcium stores. Evidence that GPR30 signals from the cell surface was obtained from experiments demonstrating that the cell-impermeable E2-protein conjugates E2-BSA and E2-horseradish peroxidase promote GPR30-dependent elevation of intracellular cAMP concentrations. Subcellular fractionation studies further support the plasma membrane as a site of GPR30 action with specific [3H]17beta-E2 binding and G protein activation associated with plasma membrane but not microsomal, or other fractions, prepared from HEK-293 or SKBR3 breast cancer cells. These results suggest that GPR30, like other 7TMRs, functions as a plasma membrane receptor.

COST Action TU1208 - Working Group 1 - Design and realisation of Ground Penetrating Radar equipment for civil engineering applications

NASA Astrophysics Data System (ADS)

Pajewski, Lara; Benedetto, Andrea; D'Amico, Sebastiano; Ferrara, Vincenzo; Frezza, Fabrizio; Persico, Raffaele; Tosti, Fabio

2017-04-01

This work aims at presenting the main results achieved by Working Group (WG) 1 "Novel Ground Penetrating Radar instrumentation" of the COST (European COoperation in Science and Technology) Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar" (www.cost.eu, www.GPRadar.eu). The principal goal of the Action, which started in April 2013 and is ending in October 2017, is to exchange and increase scientific-technical knowledge and experience of Ground Penetrating Radar techniques in civil engineering, whilst promoting throughout Europe the effective use of this safe non-destructive technique. The Action involves more than 300 Members from 28 COST Countries, a Cooperating State, 6 Near Neighbour Countries and 6 International Partner Countries. The most interesting achievements of WG1 include: 1. The state of the art on GPR systems and antennas was composed; merits and limits of current GPR systems in civil engineering applications were highlighted and open issues were identified. 2. The Action investigated the new challenge of inferring mechanical (strength and deformation) properties of flexible pavement from electromagnetic data. A semi-empirical method was developed by an Italian research team and tested over an Italian test site: a good agreement was found between the values measured by using a light falling weight deflectometer (LFWD) and the values estimated by using the proposed semi-empirical method, thereby showing great promises for large-scale mechanical inspections of pavements using GPR. Subsequently, the method was tested on a real scale, on an Italian road in the countryside: again, a good agreement between LFWD and GPR data was achieved. As a third step, the method was tested at larger scale, over three different road sections within the districts of Madrid and Guadalajara, in Spain: GPR surveys were carried out at the speed of traffic for a total of 39 kilometers, approximately; results were collected by using different GPR antennas provided by the Italian company IDS Ingegneria dei Sistemi; in cooperation with the Spanish company Euroconsult, an instrumented lorry equipped with a curviameter was used in the same road sections. Curviameter and GPR results were compared, with very good agreement. 3. A reconfigurable stepped-frequency GPR prototype was improved and widely tested. The original version of this prototype was designed and realised in Italy, in 2008. In June 2014, with the support of the Action TU1208 (and in particular by exploiting the Short Term Scientific Mission (STSM) networking tool), this prototype was brought to Norway: tests were carried out in laboratory, on roads and archaelogical sites; results were compared with those obtained by using a commercial system manufactured by the Norwegian manufacturer 3d-radar. As a result of this work, it was possible to understand how to improve the Italian prototype. Changes to the hardware were implemented in cooperation with the company Florence Engineering. In the improved version of the prototype, a more advanced technique is used for the reconfiguration of the integration times. In July 2015, by exploiting again the STSM tool, the prototype was brought to Malta: tests were carried out in buildings, churches, archaeological and geological sites; results were compared with those obtained by using a commercial pulsed system manufactured by IDS Ingegneria dei Sistemi. It is worth pointing out that this was the first time GPR measurements were carried out in Malta, where no GPR systems are available. Finally, in January 2016 the improved prototype was again brought to Malta in order to be used during the experimental sessions of a TU1208 Training School. This is an excellent example of a successful scientific activity where STSM and TS COST networking tools were effectively exploited, the cooperation with industry was of central importance, and a less research-intensive Country was deliberately chosen, to test the improved system. 4. A cheap frequency-modulated continuous-wave GPR prototype was designed and realized by an Italian research team; detailled instructions, describing how to build this radar step-by-step, will be available by the end of the Action. The idea behind this initiative is to support and encourage institutes in less research-intensive Countries, who cannot afford a commercial system, to build their own prototype for training purposes and to start familiarizing with the GPR technique. 5. A new stepped-frequency ground-coupled multi-antenna GPR system for road and bridge inspection was developed by 3d-radar (manufacturer based in Norway) and presented during the GPR 2014 conference as a contribution to COST Action TU1208. The starting point was an analogous commercial system, with air-coupled antennas. For road inspection, air-coupled antennas offer practical advantages over ground-coupled antennas (mainly, the possibility to carry out measurements at higher speeds); moreover, they allow enhanced detection of shallow layers inside the road structure. On the other hand, data from ground-coupled array contain much more details from individual scatterers, making them more suitable to image the granularity of the road base materials and for bridge deck inspection, where reinforcement rebar has to be imaged. Ground-coupled GPR systems also provide higher penetrating depth due to a stronger coupling of energy into the ground. The novel stepped-frequency ground-coupled GPR exploits an array of boomerang-shaped monopole elements. 6. Recommendations for the safety of people and equipment during GPR prospecting were produced. Despite the increasing demand of GPR surveys all over the world, safety matters are rarely considered. The Action put efforts into debating them, with scientists and professionals performing GPR surveys. As an outcome of this activity, a book was published where a series of recommendations are provided. These include general hints, recommendations for surveys carried out in challenging environmental situations, description of risks associated to specific applications, instructions for first medical aid, information about GPR electromagnetic emissions and associated risks, and finally suggestions for a safe use of the equipment and for a respectful interaction with the environment. 7. WG1 contributed to the TU1208 Education Pack, an open-access educational package conceived to teach GPR in University courses. 8. Three Training Schools were organised on radar systems and antennas, in cooperation with the European School of Antennas (ESoA): two editions of the Training School "Future Radar Systems: Radar2020" and a Training School on "UWB Antennas, Technologies and Applications". These courses were held in the Karlsruhe Institute of Technology, in Karlsruhe, Germany. Acknowledgement: The Authors are deeply grateful to COST (European Cooperation in Science and Technology, www.cost.eu), for funding and supporting the COST Action TU1208 "Civil engineering applications of Ground Penetrating Radar" (www.GPRadar.eu).

Measuring snow water equivalent from common-offset GPR records through migration velocity analysis

NASA Astrophysics Data System (ADS)

St. Clair, James; Holbrook, W. Steven

2017-12-01

Many mountainous regions depend on seasonal snowfall for their water resources. Current methods of predicting the availability of water resources rely on long-term relationships between stream discharge and snowpack monitoring at isolated locations, which are less reliable during abnormal snow years. Ground-penetrating radar (GPR) has been shown to be an effective tool for measuring snow water equivalent (SWE) because of the close relationship between snow density and radar velocity. However, the standard methods of measuring radar velocity can be time-consuming. Here we apply a migration focusing method originally developed for extracting velocity information from diffracted energy observed in zero-offset seismic sections to the problem of estimating radar velocities in seasonal snow from common-offset GPR data. Diffractions are isolated by plane-wave-destruction (PWD) filtering and the optimal migration velocity is chosen based on the varimax norm of the migrated image. We then use the radar velocity to estimate snow density, depth, and SWE. The GPR-derived SWE estimates are within 6 % of manual SWE measurements when the GPR antenna is coupled to the snow surface and 3-21 % of the manual measurements when the antenna is mounted on the front of a snowmobile ˜ 0.5 m above the snow surface.

Analysis of ground penetrating radar data from the tunnel beneath the Temple of the Feathered Serpent in Teotihuacan, Mexico, using new multi-cross algorithms

NASA Astrophysics Data System (ADS)

López-Rodríguez, Flor; Velasco-Herrera, Víctor M.; Álvarez-Béjar, Román; Gómez-Chávez, Sergio; Gazzola, Julie

2016-11-01

The ground penetrating radar (GPR) -a non-invasive method based on the emission of electromagnetic waves and the reception of their reflections at the dielectric constant and electrical conductivity discontinuities of the materials surveyed- may be applied instead of the destructive and invasive methods used to find water in celestial bodies. As multichannel equipment is increasingly used, we developed two algorithms for multivariable wavelet analysis of GPR signals -multi-cross wavelet (MCW) and Fourier multi-cross function (FMC)- and applied them to analyze raw GPR traces of archeological subsurface strata. The traces were from the tunnel located beneath the Temple of the Feathered Serpent (The Citadel, Teotihuacan, Mexico), believed to represent the underworld, an outstanding region of the Mesoamerican mythology, home of telluric forces emanating from deities, where life was constantly created and recreated. GPR profiles obtained with 100 MHz antennas suggested the tunnel is 12-14 m deep and 100-120 m long with three chambers at its end, interpretations that were confirmed by excavations in 2014. Archeologists believe that due to the tunnel's sacredness and importance, one of the chambers may be the tomb of a ruler of the ancient city. The MCW and FMC algorithms determined the periods of subsurface strata of the tunnel. GPR traces inside-and-outside the tunnel/chamber, outside the tunnel/chamber and inside the tunnel/chamber analyzed with the MCW and filtered FMC algorithms determined the periods of the tunnel and chamber fillings, clay and matrix (limestone-clay compound). The tunnel filling period obtained by MCW analysis (14.37 ns) reflects the mixed limestone-clay compound of this stratum since its value is close to that of the period of the matrix (15.22 ns); periods of the chamber filling (11.40 ± 0.40 ns) and the matrix (11.40 ± 1.00 ns) were almost identical. FMC analysis of the tunnel obtained a period (5.08 ± 1.08 ns) close to that of the chamber (4.27 ± 0.82 ns), suggesting the tunnel and chamber are filled with similar materials. The use of both algorithms allows a deeper analysis since the similarities of the tunnel and chamber filling periods could not have been determined with the MCW algorithm alone. The successful application of the new multi-cross algorithms to archeological GPR data suggests they may also be used to search water and other resources in celestial bodies.

Inhibition of GPR137 suppresses proliferation of medulloblastoma cells in vitro.

PubMed

Wang, Chengfeng; Liang, Qinchuan; Chen, Guangming; Jing, Junjie; Wang, Shousen

2015-01-01

Medulloblastoma is the most common malignant pediatric brain tumor in children. GPR137 is a ubiquitously expressed gene in the central nervous system. It has been reported that GPR137 modulates malignant proliferation of glioma cells. However, the relationship between GPR137 and medulloblastoma is still unknown. In this study, we knocked down GPR137 in the medulloblastoma cell line Daoy via a lentivirus-based RNA interference system to explore its role in medulloblastoma. Functional analyses showed that cell proliferation and colony formation were obviously restrained in Daoy cells after GPR137 knockdown. Furthermore, knockdown of GPR137 in Daoy cells led to a significant increase in cell percentage in the G0/G1 phase but a decrease in the S phase. Additionally, the cell population in the sub-G1 phase, which represents apoptotic cells, was remarkably increased in GPR137 knockdown cells. GPR137 inhibition induced a strong proapoptotic effect in Daoy cells, as confirmed by annexin V-APC/7-AAD double staining. In conclusion, GPR137 knockdown inhibited growth of Daoy medulloblastoma cells via disturbing cell cycle progression and inducing apoptosis. Our investigation suggested that GPR137 could be a potential oncogene in medulloblastoma cells and might serve as a target for the treatment of medulloblastoma. © 2014 International Union of Biochemistry and Molecular Biology, Inc.

Sex- and age-dependent effects of Gpr30 genetic deletion on the metabolic and cardiovascular profiles of diet-induced obese mice.

PubMed

Meoli, Luca; Isensee, Jörg; Zazzu, Valeria; Nabzdyk, Christoph S; Soewarto, Dian; Witt, Henning; Foryst-Ludwig, Anna; Kintscher, Ulrich; Noppinger, Patricia Ruiz

2014-05-01

The G protein-coupled receptor 30 (GPR30) has been claimed as an estrogen receptor. However, the literature reports controversial findings and the physiological function of GPR30 is not fully understood yet. Consistent with studies assigning a role of GPR30 in the cardiovascular and metabolic systems, GPR30 expression has been reported in small arterial vessels, pancreas and chief gastric cells of the stomach. Therefore, we hypothesized a role of GPR30 in the onset and progression of cardiovascular and metabolic diseases. In order to test our hypothesis, we investigated the effects of a high-fat diet on the metabolic and cardiovascular profiles of Gpr30-deficient mice (GPR30-lacZ mice). We found that GPR30-lacZ female, rather than male, mice had significant lower levels of HDL along with an increase in fat liver accumulation as compared to control mice. However, two indicators of cardiac performance assessed by echocardiography, ejection fraction and fractional shortening were both decreased in an age-dependent manner only in Gpr30-lacZ male mice. Collectively our results point to a potential role of Gpr30 in preserving lipid metabolism and cardiac function in a sex- and age-dependent fashion. Copyright © 2014 Elsevier B.V. All rights reserved.

Differential expression of GPR15 on T cells during ulcerative colitis

PubMed Central

Adamczyk, Alexandra; Gageik, Daniel; Frede, Annika; Pastille, Eva; Hansen, Wiebke; Rueffer, Andreas; Buer, Jan; Büning, Jürgen; Langhorst, Jost

2017-01-01

G protein–coupled receptor 15 (GPR15) was recently highlighted as a colon-homing receptor for murine and human CD4+ T cells. The aim of this study was to explore the functional phenotype of human GPR15+CD4+ T cells, focusing on Tregs and effector T cells (Teffs), and to determine whether GPR15 is the driver for the migration of T cells to the colon during ulcerative colitis (UC). In the peripheral blood, GPR15 was expressed on Tregs and Teffs; both GPR15+ T cell subsets produced less IFN-γ and IL-4 but more IL-17 after stimulation and showed a higher migration activity compared with GPR15–CD4+ T cells. In UC patients, GPR15 expression was increased on Tregs in the peripheral blood but not on Teffs. Interestingly, the expression of GPR15 was significantly enhanced on colonic T cells of UC patients in noninflamed biopsies but not in inflamed biopsies. The differential expression of GPR15 in UC patients was accompanied by a significant reduction of bacterial immunoregulatory metabolites in the feces. In conclusion, GPR15 expression on CD4+ T cells is altered in UC patients, which may have implications for the development of therapeutic approaches to target T cell trafficking to the colon. PMID:28422750

GPR Use and Activities in Denmark

NASA Astrophysics Data System (ADS)

Ringgaard, Jørgen; Wisén, Roger

2014-05-01

Academic work on GPR in Denmark is performed both by the Technical University of Denmark (DTU) and the University of Copenhagen (KU). The work at DTU includes development of antennas and systems, e.g. an airborne ice-sounder GPR system (POLARIS) that today is in frequent use for monitoring of ice thickness in Greenland. DTU often collaborates with ESA (European Space Agency) regarding electromagnetic development projects. At KU there is an ongoing work with GPR applied to water resources. The main objective is to study flux of water and matter across different hydrological domains. There are several recent publications from KU describing research for data analysis and modelling as well as hydro geophysical applications. Also the Geological Survey of Denmark and Greenland (GEUS) performs frequent geological mapping with GPR. There have been mainly two actors on the Danish commercial market for several years: FalkGeo and Ramboll. Falkgeo has been active for many years acquiring data for several different applications such as archeology, utilities and roads. Their equipment pool comprises both a multichannel Terravision system form GSSI and a 2D system from Mala Geoscience with a comprehensive range of antennas. Ramboll has performed GPR surveys for two decades mainly with 2D systems from GSSI. In recent years Ramboll has also obtained a system with RTA antennas from Mala Geoscience and a multichannel system from 3D-Radar. These systems have opened markets both for deeper geological mapping and for shallow mapping. The geological mapping with the Mala system has often been combined with resistivity imaging (CVES) and refraction seismic. The 3D system has been applied in airports and on road for mapping of layer thicknesses, delamination and for control of asphalt works. Other areas comprise bridge deck evaluation and utility mapping. Ramboll also acts as client advisor for BaneDanmark, a state owned company who operates and develops the Danish state railway network. For this Ramboll has written a guideline for application of GPR on BaneDanmark railways. There are no national guidelines or test sites in Denmark. The use of GPR on roads is very limited in Denmark compared to our neighboring countries. This is possibly due to conservatism in the industry and due to the fact that Denmark decided not to participate in a collaboration between some of our neighboring countries about preparation of guidelines for application of GPR on roads, the Mara Nord Project. An improvement in accuracy and more automatized routines for mapping of delamination and stripping would also widen the market for application of GPR in airports and on roads. International guidelines for application of GPR in several fields would also help to make authorities recognize it as a valid complement and alternative to other established methods. This abstract is a contribution to COST Action TU1208.

Global Research Patterns on Ground Penetrating Radar (GPR)

NASA Astrophysics Data System (ADS)

Gizzi, Fabrizio Terenzio; Leucci, Giovanni

2018-05-01

The article deals with the analysis of worldwide research patterns concerning ground penetrating radar (GPR) during 1995-2014. To do this, the Thomson Reuters' Science Citation Index Expanded (SCI-EXPANDED) and the Social Sciences Citation Index accessed via the Web of Science Core Collection were the two bibliographic databases taken as a reference. We pay attention to the document typology and language, the publication trend and citations, the subject categories and journals, the collaborations between authors, the productivity of the authors, the most cited articles, the countries and the institutions involved, and other hot issues. Concerning the main research subfields involving GPR use, there were five, physical-mathematical, sedimentological-stratigraphical, civil engineering/engineering geology/cultural heritage, hydrological (HD), and glaciological (GL), subfields.

In vivo effects of a GPR30 antagonist.

PubMed

Dennis, Megan K; Burai, Ritwik; Ramesh, Chinnasamy; Petrie, Whitney K; Alcon, Sara N; Nayak, Tapan K; Bologa, Cristian G; Leitao, Andrei; Brailoiu, Eugen; Deliu, Elena; Dun, Nae J; Sklar, Larry A; Hathaway, Helen J; Arterburn, Jeffrey B; Oprea, Tudor I; Prossnitz, Eric R

2009-06-01

Estrogen is central to many physiological processes throughout the human body. We have previously shown that the G protein-coupled receptor GPR30 (also known as GPER), in addition to classical nuclear estrogen receptors (ER and ER), activates cellular signaling pathways in response to estrogen. In order to distinguish between the actions of classical estrogen receptors and GPR30, we have previously characterized G-1 (1), a selective agonist of GPR30. To complement the pharmacological properties of G-1, we sought to identify an antagonist of GPR30 that displays similar selectivity against the classical estrogen receptors. Here we describe the identification and characterization of G15 (2), a G-1 analog that binds to GPR30 with high affinity and acts as an antagonist of estrogen signaling through GPR30. In vivo administration of G15 revealed that GPR30 contributes to both uterine and neurological responses initiated by estrogen. The identification of this antagonist will accelerate the evaluation of the roles of GPR30 in human physiology.

GPR142 Controls Tryptophan-Induced Insulin and Incretin Hormone Secretion to Improve Glucose Metabolism

PubMed Central

Efanov, Alexander M.; Fang, Xiankang; Beavers, Lisa S.; Wang, Xuesong; Wang, Jingru; Gonzalez Valcarcel, Isabel C.; Ma, Tianwei

2016-01-01

GPR142, a putative amino acid receptor, is expressed in pancreatic islets and the gastrointestinal tract, but the ligand affinity and physiological role of this receptor remain obscure. In this study, we show that in addition to L-Tryptophan, GPR142 signaling is also activated by L-Phenylalanine but not by other naturally occurring amino acids. Furthermore, we show that Tryptophan and a synthetic GPR142 agonist increase insulin and incretin hormones and improve glucose disposal in mice in a GPR142-dependent manner. In contrast, Phenylalanine improves in vivo glucose disposal independently of GPR142. Noteworthy, refeeding-induced elevations in insulin and glucose-dependent insulinotropic polypeptide are blunted in Gpr142 null mice. In conclusion, these findings demonstrate GPR142 is a Tryptophan receptor critically required for insulin and incretin hormone regulation and suggest GPR142 agonists may be effective therapies that leverage amino acid sensing pathways for the treatment of type 2 diabetes. PMID:27322810

Targeting GPR120 and other fatty acid sensing GPCRs ameliorates insulin resistance and inflammatory diseases

PubMed Central

Talukdar, Saswata; Olefsky, Jerrold M; Osborn, Olivia

2011-01-01

The last decade has seen great progress in the understanding of the molecular pharmacology, physiological function and therapeutic potential of the G protein-coupled receptors. Free Fatty acids (FFAs) have been demonstrated to act as ligands of several GPCRs including GPR40, GPR43, GPR84, GPR119 and GPR120. We have recently shown that GPR120 acts as a physiological receptor of ω3 fatty acids in macrophages and adipocytes, which mediate potent anti-inflammatory and insulin sensitizing effects. The important role GPR120 plays in the control of inflammation raises the possibility that targeting this receptor could have therapeutic potential in many inflammatory diseases including obesity and type 2 diabetes. In this review, we discuss lipid-sensing GPCRs and highlight potential outcomes of targeting such receptors in ameliorating disease. PMID:21663979

Analysis of the Emitted Wavelet of High-Resolution Bowtie GPR Antennas

PubMed Central

Rial, Fernando I.; Lorenzo, Henrique; Pereira, Manuel; Armesto, Julia

2009-01-01

Most Ground Penetrating Radars (GPR) cover a wide frequency range by emitting very short time wavelets. In this work, we study in detail the wavelet emitted by two bowtie GPR antennas with nominal frequencies of 800 MHz and 1 GHz. Knowledge of this emitted wavelet allows us to extract as much information as possible from recorded signals, using advanced processing techniques and computer simulations. Following previously published methodology used by Rial et al. [1], which ensures system stability and reliability in data acquisition, a thorough analysis of the wavelet in both time and frequency domain is performed. Most of tests were carried out with air as propagation medium, allowing a proper analysis of the geometrical attenuation factor. Furthermore, we attempt to determine, for each antenna, a time zero in the records to allow us to correctly assign a position to the reflectors detected by the radar. Obtained results indicate that the time zero is not a constant value for the evaluated antennas, but instead depends on the characteristics of the material in contact with the antenna. PMID:22408523

GPR54 and KiSS-1: role in the regulation of puberty and reproduction.

PubMed

Kuohung, Wendy; Kaiser, Ursula B

2006-12-01

The finding of inactivating mutations in GPR54 in IHH patients and the lack of reproductive maturation of the GPR54 null mouse have uncovered a previously unrecognized role for GPR54 and KiSS-1 in the physiologic regulation of puberty and reproduction. This newly identified function for GPR54 and its cognate ligand, kisspeptin, has led to additional studies that have localized GPR54 and KiSS-1 mRNA in the hypothalamus, colocalized GPR54 in GnRH neurons, demonstrated GnRH-dependent activation of LH and FSH release by kisspeptin, and shown increased hypothalamic KiSS-1 and GPR54 mRNA levels at the time of puberty. Taken together, these findings establish the role of the kisspeptin-GPR54 system in the stimulation of GnRH neurons during puberty. The mechanisms by which kisspeptin activates GnRH release, as well as the trigger for this pathway at the onset of puberty, are yet to be elucidated. In the future, modulators of GPR54 activity, including kisspeptin, may prove valuable in clinical applications in the fields of both cancer therapy and reproductive medicine.

Metabolite-Sensing G Protein-Coupled Receptors-Facilitators of Diet-Related Immune Regulation.

PubMed

Tan, Jian K; McKenzie, Craig; Mariño, Eliana; Macia, Laurence; Mackay, Charles R

2017-04-26

Nutrition and the gut microbiome regulate many systems, including the immune, metabolic, and nervous systems. We propose that the host responds to deficiency (or sufficiency) of dietary and bacterial metabolites in a dynamic way, to optimize responses and survival. A family of G protein-coupled receptors (GPCRs) termed the metabolite-sensing GPCRs bind to various metabolites and transmit signals that are important for proper immune and metabolic functions. Members of this family include GPR43, GPR41, GPR109A, GPR120, GPR40, GPR84, GPR35, and GPR91. In addition, bile acid receptors such as GPR131 (TGR5) and proton-sensing receptors such as GPR65 show similar features. A consistent feature of this family of GPCRs is that they provide anti-inflammatory signals; many also regulate metabolism and gut homeostasis. These receptors represent one of the main mechanisms whereby the gut microbiome affects vertebrate physiology, and they also provide a link between the immune and metabolic systems. Insufficient signaling through one or more of these metabolite-sensing GPCRs likely contributes to human diseases such as asthma, food allergies, type 1 and type 2 diabetes, hepatic steatosis, cardiovascular disease, and inflammatory bowel diseases.

Characterization of GPR101 transcript structure and expression patterns

PubMed Central

Trivellin, Giampaolo; Bjelobaba, Ivana; Daly, Adrian F.; Larco, Darwin O.; Palmeira, Leonor; Faucz, Fabio R.; Thiry, Albert; Leal, Letícia F.; Rostomyan, Liliya; Quezado, Martha; Schernthaner-Reiter, Marie Helene; Janjic, Marija M.; Villa, Chiara; Wu, T. John; Stojilkovic, Stanko S.; Beckers, Albert; Feldman, Benjamin; Stratakis, Constantine A.

2016-01-01

We recently showed that Xq26.3 microduplications cause X-linked acrogigantism (X-LAG). X-LAG patients mainly present with growth hormone and prolactin-secreting adenomas and share a minimal duplicated region containing at least four genes. GPR101 was the only gene highly expressed in their pituitary lesions, but little is known about its expression patterns. GPR101 transcripts were characterized in human tissues by 5’-RACE and RNAseq, while the putative promoter was bioinformatically predicted. We investigated GPR101 mRNA and protein expression by RT-qPCR, whole-mount in situ hybridization, and immunostaining, in human, rhesus monkey, rat, and zebrafish. We identified four GPR101 isoforms characterized by different 5’ untranslated regions (UTRs) and a common 6.1 kb-long 3’UTR. GPR101 expression was very low or absent in almost all adult human tissues examined, except for specific brain regions. Strong GPR101 staining was observed in human fetal pituitary and during adolescence, whereas very weak/absent expression was detected during childhood and adult life. In contrast to humans, adult pituitaries of monkey and rat expressed GPR101, but in different cell types. Gpr101 is expressed in the brain and pituitary during rat and zebrafish development; in rat pituitary Gpr101 is expressed only after birth and showed sexual dimorphism. This study shows that different GPR101 transcripts exist and that the brain is the major site of GPR101 expression across different species, although divergent species- and temporal-specific expression patterns are evident. These findings suggest an important role for GPR101 in brain and pituitary development and likely reflect the very different growth, development and maturation patterns among species. PMID:27282544

GPR55 promotes migration and adhesion of colon cancer cells indicating a role in metastasis

PubMed Central

Andersen, L; Hasenöhrl, C; Feuersinger, D; Stančić, A; Fauland, A; Magnes, C; El‐Heliebi, A; Lax, S; Uranitsch, S; Haybaeck, J; Heinemann, A

2015-01-01

Background and Purpose Tumour cell migration and adhesion constitute essential features of metastasis. G‐protein coupled receptor 55 (GPR55), a lysophospholipid receptor, has been shown to play an important role in carcinogenesis. Here, we investigated the involvement of GPR55 in migration and metastasis of colon cancer cells. Experimental Approach Adhesion and migration assays using the highly metastatic colon cancer cell line HCT116 and an in vivo assay of liver metastasis were performed. The GPR55 antagonist CID16020046, cannabidiol, a putative GPR55 antagonist and GPR55 siRNA were used to block GPR55 activity in HCT116 colon cancer cells. Key Results HCT116 cells showed a significant decrease in adhesion to endothelial cells and in migration after blockade with CID16020046 or cannabidiol. The inhibitory effects of CID16020046 or cannabidiol were averted by GPR55 siRNA knock down in cancer cells. The integrity of endothelial cell monolayers was increased after pretreatment of HCT116 cells with the antagonists or after GPR55 siRNA knockdown while pretreatment with lysophosphatidylinositol (LPI), the endogenous ligand of GPR55, decreased integrity of the monolayers. LPI also induced migration in GPR55 overexpressing HCT116 cells that was blocked by GPR55 antagonists. In a mouse model of metastasis, the arrest of HCT116 cancer cells in the liver was reduced after treatment with CID16020046 or cannabidiol. Increased levels of LPI (18:0) were found in colon cancer patients when compared with healthy individuals. Conclusions and Implications GPR55 is involved in the migratory behaviour of colon carcinoma cells and may serve as a pharmacological target for the prevention of metastasis. © 2015 The British Pharmacological Society PMID:26436760

LH-21 and abnormal cannabidiol improve β-cell function in isolated human and mouse islets through GPR55-dependent and -independent signalling.

PubMed

Ruz-Maldonado, Inmaculada; Pingitore, Attilio; Liu, Bo; Atanes, Patricio; Huang, Guo Cai; Baker, David; Alonso, Francisco José; Bermúdez-Silva, Francisco Javier; Persaud, Shanta J

2018-04-01

To examine the effects of Abn-CBD (GPR55 agonist) and LH-21 (CB1 antagonist) on human and mouse islet function, and to determine signalling via GPR55 using islets from GPR55 -/- mice. Islets isolated from human organ donors and mice were incubated in the absence or presence of Abn-CBD or LH-21, and insulin secretion, [Ca 2+ ] i, cAMP , apoptosis, β-cell proliferation and CREB and AKT phosphorylation were examined using standard techniques. Abn-CBD potentiated glucose-stimulated insulin secretion and elevated [Ca 2+ ] i in human islets and islets from both GPR55 +/+ and GPR55 -/- mice. LH-21 also increased insulin secretion and [Ca 2+ ] i in human islets and GPR55 +/+ mouse islets, but concentrations of LH-21 up to 0.1 μM were ineffective in islets from GPR55 -/- mice. Neither ligand affected basal insulin secretion or islet cAMP levels. Abn-CBD and LH-21 reduced cytokine-induced apoptosis in human islets and GPR55 +/+ mouse islets, and these effects were suppressed after GPR55 deletion. They also increased β-cell proliferation: the effects of Abn-CBD were preserved in islets from GPR55 -/- mice, while those of LH-21 were abolished. Abn-CBD and LH-21 increased AKT phosphorylation in mouse and human islets. This study showed that Abn-CBD and LH-21 improve human and mouse islet β-cell function and viability. Use of islets from GPR55 -/- mice suggests that designation of Abn-CBD and LH-21 as a GPR55 agonist and a CB1 antagonist, should be revised. © 2017 John Wiley & Sons Ltd.

Effect of GPR84 deletion on obesity and diabetes development in mice fed long chain or medium chain fatty acid rich diets.

PubMed

Du Toit, Eugene; Browne, Liam; Irving-Rodgers, Helen; Massa, Helen M; Fozzard, Nicolette; Jennings, Michael P; Peak, Ian R

2017-04-20

Although there is good evidence showing that diets rich in medium chain fatty acids (MCFAs) have less marked obesogenic and diabetogenic effects than diets rich in long chain fatty acids (LCFAs), the role of the pro-inflammatory, medium chain fatty acid receptor (GPR84) in the aetiology of obesity and glucose intolerance is not well characterised. We set out to determine whether GPR84 expression influences obesity and glucose intolerance susceptibility in MCFA and LCFA rich diet fed mice. Wild type (WT) and GPR84 knockout (KO) mice were fed a control, MCFA or LCFA diet, and body mass, heart, liver and epididymal fat mass was assessed, as well as glucose tolerance and adipocyte size. LCFA diets increased body mass and decreased glucose tolerance in both WT and GPR84 KO animals while MCFA diets had no effect on these parameters. There were no differences in body weight when comparing WT and GPR84 KO mice on the respective diets. Glucose tolerance was also similar in WT and GPR84 KO mice irrespective of diet. Liver mass was increased following LCFA feeding in WT but not GPR84 KO mice. Hepatic triglyceride content was increased in GPR84 KO animals fed MCFA, and myocardial triglyceride content was increased in GPR84 KO animals fed LCFA. GPR84 deletion had no effects on body weight or glucose tolerance in mice fed either a high MCFA or LCFA diet. GPR84 may influence lipid metabolism, as GPR84 KO mice had smaller livers and increased myocardial triglyceride accumulation when fed LCFA diets, and increased liver triglyceride accumulation in responses to increased dietary MCFAs.

N-Arachidonyl Glycine Does Not Activate G Protein–Coupled Receptor 18 Signaling via Canonical Pathways

PubMed Central

Lu, Van B.; Puhl, Henry L.

2013-01-01

Recent studies propose that N-arachidonyl glycine (NAGly), a carboxylic analogue of anandamide, is an endogenous ligand of the Gαi/o protein–coupled receptor 18 (GPR18). However, a high-throughput β-arrestin–based screen failed to detect activation of GPR18 by NAGly (Yin et al., 2009; JBC, 18:12328). To address this inconsistency, this study investigated GPR18 coupling in a native neuronal system with endogenous signaling pathways and effectors. GPR18 was heterologously expressed in rat sympathetic neurons, and the modulation of N-type (Cav2.2) calcium channels was examined. Proper expression and trafficking of receptor were confirmed by the “rim-like” fluorescence of fluorescently tagged receptor and the positive staining of external hemagglutinin-tagged GPR18-expressing cells. Application of NAGly on GPR18-expressing neurons did not inhibit calcium currents but instead potentiated currents in a voltage-dependent manner, similar to what has previously been reported (Guo et al., 2008; J Neurophysiol, 100:1147). Other proposed agonists of GPR18, including anandamide and abnormal cannabidiol, also failed to induce inhibition of calcium currents. Mutants of GPR18, designed to constitutively activate receptors, did not tonically inhibit calcium currents, indicating a lack of GPR18 activation or coupling to endogenous G proteins. Other downstream effectors of Gαi/o-coupled receptors, G protein–coupled inwardly rectifying potassium channels and adenylate cyclase, were not modulated by GPR18 signaling. Furthermore, GPR18 did not couple to other G proteins tested: Gαs, Gαz, and Gα15. These results suggest NAGly is not an agonist for GPR18 or that GPR18 signaling involves noncanonical pathways not examined in these studies. PMID:23104136

Numerical Modelling of Ground Penetrating Radar Antennas

NASA Astrophysics Data System (ADS)

Giannakis, Iraklis; Giannopoulos, Antonios; Pajewski, Lara

2014-05-01

Numerical methods are needed in order to solve Maxwell's equations in complicated and realistic problems. Over the years a number of numerical methods have been developed to do so. Amongst them the most popular are the finite element, finite difference implicit techniques, frequency domain solution of Helmontz equation, the method of moments, transmission line matrix method. However, the finite-difference time-domain method (FDTD) is considered to be one of the most attractive choice basically because of its simplicity, speed and accuracy. FDTD first introduced in 1966 by Kane Yee. Since then, FDTD has been established and developed to be a very rigorous and well defined numerical method for solving Maxwell's equations. The order characteristics, accuracy and limitations are rigorously and mathematically defined. This makes FDTD reliable and easy to use. Numerical modelling of Ground Penetrating Radar (GPR) is a very useful tool which can be used in order to give us insight into the scattering mechanisms and can also be used as an alternative approach to aid data interpretation. Numerical modelling has been used in a wide range of GPR applications including archeology, geophysics, forensic, landmine detection etc. In engineering, some applications of numerical modelling include the estimation of the effectiveness of GPR to detect voids in bridges, to detect metal bars in concrete, to estimate shielding effectiveness etc. The main challenges in numerical modelling of GPR for engineering applications are A) the implementation of the dielectric properties of the media (soils, concrete etc.) in a realistic way, B) the implementation of the geometry of the media (soils inhomogeneities, rough surface, vegetation, concrete features like fractures and rock fragments etc.) and C) the detailed modelling of the antenna units. The main focus of this work (which is part of the COST Action TU1208) is the accurate and realistic implementation of GPR antenna units into the FDTD model. Accurate models based on general characteristics of the commercial antennas GSSI 1.5 GHz and MALA 1.2 GHz have been already incorporated in GprMax, a free software which solves Maxwell's equation using a second order in space and time FDTD algorithm. This work presents the implementation of horn antennas with different parameters as well as ridged horn antennas into this FDTD model and their effectiveness is tested in realistic modelled situations. Accurate models of soils and concrete are used to test and compare different antenna units. Stochastic methods are used in order to realistically simulate the geometrical characteristics of the medium. Regarding the dielectric properties, Debye approximations are incorporated in order to simulate realistically the dielectric properties of the medium on the frequency range of interest.

The role of G-protein receptor 84 in experimental neuropathic pain.

PubMed

Nicol, Louise S C; Dawes, John M; La Russa, Federica; Didangelos, Athanasios; Clark, Anna K; Gentry, Clive; Grist, John; Davies, John B; Malcangio, Marzia; McMahon, Stephen B

2015-06-10

G-protein receptor 84 (GPR84) is an orphan receptor that is induced markedly in monocytes/macrophages and microglia during inflammation, but its pathophysiological function is unknown. Here, we investigate the role of GPR84 in a murine model of traumatic nerve injury. Naive GPR84 knock-out (KO) mice exhibited normal behavioral responses to acute noxious stimuli, but subsequent to partial sciatic nerve ligation (PNL), KOs did not develop mechanical or thermal hypersensitivity, in contrast to wild-type (WT) littermates. Nerve injury increased ionized calcium binding adapter molecule 1 (Iba1) and phosphorylated p38 MAPK immunoreactivity in the dorsal horn and Iba1 and cluster of differentiation 45 expression in the sciatic nerve, with no difference between genotypes. PCR array analysis revealed that Gpr84 expression was upregulated in the spinal cord and sciatic nerve of WT mice. In addition, the expression of arginase-1, a marker for anti-inflammatory macrophages, was upregulated in KO sciatic nerve. Based on this evidence, we investigated whether peripheral macrophages behave differently in the absence of GPR84. We found that lipopolysaccharide-stimulated KO macrophages exhibited attenuated expression of several proinflammatory mediators, including IL-1β, IL-6, and TNF-α. Forskolin-stimulated KO macrophages also showed greater cAMP induction, a second messenger associated with immunosuppression. In summary, our results demonstrate that GPR84 is a proinflammatory receptor that contributes to nociceptive signaling via the modulation of macrophages, whereas in its absence the response of these cells to an inflammatory insult is impaired. Copyright © 2015 Nicol et al.

The Role of G-Protein Receptor 84 in Experimental Neuropathic Pain

PubMed Central

Nicol, Louise S.C.; Dawes, John M.; La Russa, Federica; Didangelos, Athanasios; Clark, Anna K.; Gentry, Clive; Grist, John; Davies, John B.; Malcangio, Marzia

2015-01-01

G-protein receptor 84 (GPR84) is an orphan receptor that is induced markedly in monocytes/macrophages and microglia during inflammation, but its pathophysiological function is unknown. Here, we investigate the role of GPR84 in a murine model of traumatic nerve injury. Naive GPR84 knock-out (KO) mice exhibited normal behavioral responses to acute noxious stimuli, but subsequent to partial sciatic nerve ligation (PNL), KOs did not develop mechanical or thermal hypersensitivity, in contrast to wild-type (WT) littermates. Nerve injury increased ionized calcium binding adapter molecule 1 (Iba1) and phosphorylated p38 MAPK immunoreactivity in the dorsal horn and Iba1 and cluster of differentiation 45 expression in the sciatic nerve, with no difference between genotypes. PCR array analysis revealed that Gpr84 expression was upregulated in the spinal cord and sciatic nerve of WT mice. In addition, the expression of arginase-1, a marker for anti-inflammatory macrophages, was upregulated in KO sciatic nerve. Based on this evidence, we investigated whether peripheral macrophages behave differently in the absence of GPR84. We found that lipopolysaccharide-stimulated KO macrophages exhibited attenuated expression of several proinflammatory mediators, including IL-1β, IL-6, and TNF-α. Forskolin-stimulated KO macrophages also showed greater cAMP induction, a second messenger associated with immunosuppression. In summary, our results demonstrate that GPR84 is a proinflammatory receptor that contributes to nociceptive signaling via the modulation of macrophages, whereas in its absence the response of these cells to an inflammatory insult is impaired. PMID:26063927

Fatty acid 16:4(n-3) stimulates a GPR120-induced signaling cascade in splenic macrophages to promote chemotherapy resistance

PubMed Central

Houthuijzen, Julia M.; Oosterom, Ilse; Hudson, Brian D.; Hirasawa, Akira; Daenen, Laura G. M.; McLean, Chelsea M.; Hansen, Steffen V. F.; van Jaarsveld, Marijn T. M.; Peeper, Daniel S.; Jafari Sadatmand, Sahar; Roodhart, Jeanine M. L.; van de Lest, Chris H. A.; Ulven, Trond; Ishihara, Kenji; Milligan, Graeme; Voest, Emile E.

2017-01-01

Although chemotherapy is designed to eradicate tumor cells, it also has significant effects on normal tissues. The platinum-induced fatty acid 16:4(n-3) (hexadeca-4,7,10,13-tetraenoic acid) induces systemic resistance to a broad range of DNA-damaging chemotherapeutics. We show that 16:4(n-3) exerts its effect by activating splenic F4/80+/CD11blow macrophages, which results in production of chemoprotective lysophosphatidylcholines (LPCs). Pharmacologic studies, together with analysis of expression patterns, identified GPR120 on F4/80+/CD11blow macrophages as the relevant receptor for 16:4(n-3). Studies that used splenocytes from GPR120-deficient mice have confirmed this conclusion. Activation of the 16:4(n-3)-GPR120 axis led to enhanced cPLA2 activity in these splenic macrophages and secretion of the resistance-inducing lipid mediator, lysophosphatidylcholine(24:1). These studies identify a novel and unexpected function for GPR120 and suggest that antagonists of this receptor might be effective agents to limit development of chemotherapy resistance.—Houthuijzen, J. M., Oosterom, I., Hudson, B. D., Hirasawa, A., Daenen, L. G. M., McLean, C. M., Hansen, S. V. F., van Jaarsveld, M. T. M., Peeper, D. S., Jafari Sadatmand, S., Roodhart, J. M. L., van de Lest, C. H. A., Ulven, T., Ishihara, K., Milligan, G., Voest, E. E. Fatty acid 16:4(n-3) stimulates a GPR120-induced signaling cascade in splenic macrophages to promote chemotherapy resistance. PMID:28183801

Very slow growth of Escherichia coli.

PubMed Central

Chesbro, W; Evans, T; Eifert, R

1979-01-01

A recycling fermentor (a chemostat with 100% biomass feedback) was used to study glucose-limited behavior of Escherichia coli B. The expectation from mass transfer analysis that growth would asymptotically approach a limit mass determined by the glucose provision rate (GPR) and the culture's maintenance requirement was not met. Instead, growth proceeded at progressively lower rates through three distinct phases. After the fermentor was seeded, but before glucose became limiting, growth followed the usual, exponential path (phase 1). About 12 h postseeding, residual glucose in the fermentor fell below 1 microgram . ml-1 and the growth rate (dx/dt) became constant and a linear function of GPR (phase 2). The specific growth rate, mu, therefore fell continuously throughout the phase. Biomass yield and glucose assimilation (13%) were near the level for exponential growth, however, and independent of GPR over a broad range. At a critical specific growth rate (0.04 h-1 for this strain), phase 2 ended abruptly and phase 3 commenced. In phase 3, the growth rate was again constant, although lower than in phase 2, so that mu continued to fall, but growth rates and yields were praboloid functions of GPR. They were never zero, however, at any positive value of GPR. By inference, the fraction of metabolic energy used for maintenance functions is constant for a given GPR, although different for phases 2 and 3, and independent of biomass. In both phases 2 and 3, orcinol, diphenylamine, and Lowry reactive materials were secreted at near-constant rates such that over 50% as much biosynthetic mass was secreted as was retained by the cells. Images PMID:378981

The G protein-coupled receptor GPR30 inhibits proliferation of estrogen receptor-positive breast cancer cells.

PubMed

Ariazi, Eric A; Brailoiu, Eugen; Yerrum, Smitha; Shupp, Heather A; Slifker, Michael J; Cunliffe, Heather E; Black, Michael A; Donato, Anne L; Arterburn, Jeffrey B; Oprea, Tudor I; Prossnitz, Eric R; Dun, Nae J; Jordan, V Craig

2010-02-01

The G protein-coupled receptor GPR30 binds 17beta-estradiol (E(2)) yet differs from classic estrogen receptors (ERalpha and ERbeta). GPR30 can mediate E(2)-induced nongenomic signaling, but its role in ERalpha-positive breast cancer remains unclear. Gene expression microarray data from five cohorts comprising 1,250 breast carcinomas showed an association between increased GPR30 expression and ERalpha-positive status. We therefore examined GPR30 in estrogenic activities in ER-positive MCF-7 breast cancer cells using G-1 and diethylstilbestrol (DES), ligands that selectively activate GPR30 and ER, respectively, and small interfering RNAs. In expression studies, E(2) and DES, but not G-1, transiently downregulated both ER and GPR30, indicating that this was ER mediated. In Ca(2+) mobilization studies, GPR30, but not ERalpha, mediated E(2)-induced Ca(2+) responses because E(2), 4-hydroxytamoxifen (activates GPR30), and G-1, but not DES, elicited cytosolic Ca(2+) increases not only in MCF-7 cells but also in ER-negative SKBr3 cells. Additionally, in MCF-7 cells, GPR30 depletion blocked E(2)-induced and G-1-induced Ca(2+) mobilization, but ERalpha depletion did not. Interestingly, GPR30-coupled Ca(2+) responses were sustained and inositol triphosphate receptor mediated in ER-positive MCF-7 cells but transitory and ryanodine receptor mediated in ER-negative SKBr3 cells. Proliferation studies involving GPR30 depletion indicated that the role of GPR30 was to promote SKBr3 cell growth but reduce MCF-7 cell growth. Supporting this, G-1 profoundly inhibited MCF-7 cell growth, potentially via p53 and p21 induction. Further, flow cytometry showed that G-1 blocked MCF-7 cell cycle progression at the G(1) phase. Thus, GPR30 antagonizes growth of ERalpha-positive breast cancer and may represent a new target to combat this disease.

Hetero-oligomeric Complex between the G Protein-coupled Estrogen Receptor 1 and the Plasma Membrane Ca2+-ATPase 4b*

PubMed Central

Tran, Quang-Kim; VerMeer, Mark; Burgard, Michelle A.; Hassan, Ali B.; Giles, Jennifer

2015-01-01

The new G protein-coupled estrogen receptor 1 (GPER/GPR30) plays important roles in many organ systems. The plasma membrane Ca2+-ATPase (PMCA) is essential for removal of cytoplasmic Ca2+ and for shaping the time courses of Ca2+-dependent activities. Here, we show that PMCA and GPER/GPR30 physically interact and functionally influence each other. In primary endothelial cells, GPER/GPR30 agonist G-1 decreases PMCA-mediated Ca2+ extrusion by promoting PMCA tyrosine phosphorylation. GPER/GPR30 overexpression decreases PMCA activity, and G-1 further potentiates this effect. GPER/GPR30 knockdown increases PMCA activity, whereas PMCA knockdown substantially reduces GPER/GPR30-mediated phosphorylation of the extracellular signal-related kinase (ERK1/2). GPER/GPR30 co-immunoprecipitates with PMCA with or without treatment with 17β-estradiol, thapsigargin, or G-1. Heterologously expressed GPER/GPR30 in HEK 293 cells co-localizes with PMCA4b, the main endothelial PMCA isoform. Endothelial cells robustly express the PDZ post-synaptic density protein (PSD)-95, whose knockdown reduces the association between GPER/GPR30 and PMCA. Additionally, the association between PMCA4b and GPER/GPR30 is substantially reduced by truncation of either or both of their C-terminal PDZ-binding motifs. Functionally, inhibition of PMCA activity is significantly reduced by truncation of GPER/GPR30's C-terminal PDZ-binding motif. These data strongly indicate that GPER/GPR30 and PMCA4b form a hetero-oligomeric complex in part via the anchoring action of PSD-95, in which they constitutively affect each other's function. Activation of GPER/GPR30 further inhibits PMCA activity through tyrosine phosphorylation of the pump. These interactions represent cross-talk between Ca2+ signaling and GPER/GPR30-mediated activities. PMID:25847233

Similarities and differences between the responses induced in human phagocytes through activation of the medium chain fatty acid receptor GPR84 and the short chain fatty acid receptor FFA2R.

PubMed

Sundqvist, Martina; Christenson, Karin; Holdfeldt, André; Gabl, Michael; Mårtensson, Jonas; Björkman, Lena; Dieckmann, Regis; Dahlgren, Claes; Forsman, Huamei

2018-05-01

GPR84 is a recently de-orphanized member of the G-protein coupled receptor (GPCR) family recognizing medium chain fatty acids, and has been suggested to play important roles in inflammation. Due to the lack of potent and selective GPR84 ligands, the basic knowledge related to GPR84 functions is very limited. In this study, we have characterized the GPR84 activation profile and regulation mechanism in human phagocytes, using two recently developed small molecules that specifically target GPR84 agonistically (ZQ16) and antagonistically (GLPG1205), respectively. Compared to our earlier characterization of the short chain fatty acid receptor FFA2R which is functionally expressed in neutrophils but not in monocytes, GPR84 is expressed in both cell types and in monocyte-derived macrophages. In neutrophils, the GPR84 agonist had an activation profile very similar to that of FFA2R. The GPR84-mediated superoxide release was low in naïve cells, but the response could be significantly primed by TNFα and by the actin cytoskeleton disrupting agent Latrunculin A. Similar to that of FFA2R, a desensitization mechanism bypassing the actin cytoskeleton was utilized by GPR84. All ZQ16-mediated cellular responses were sensitive to GLPG1205, confirming the GPR84-dependency. Finally, our data of in vivo transmigrated tissue neutrophils indicate that both GPR84 and FFA2R are involved in neutrophil recruitment processes in vivo. In summary, we show functional similarities but also some important differences between GPR84 and FFA2R in human phagocytes, thus providing some mechanistic insights into GPR84 regulation in blood neutrophils and cells recruited to an aseptic inflammatory site in vivo. Copyright © 2018 Elsevier B.V. All rights reserved.

Hetero-oligomeric Complex between the G Protein-coupled Estrogen Receptor 1 and the Plasma Membrane Ca2+-ATPase 4b.

PubMed

Tran, Quang-Kim; VerMeer, Mark; Burgard, Michelle A; Hassan, Ali B; Giles, Jennifer

2015-05-22

The new G protein-coupled estrogen receptor 1 (GPER/GPR30) plays important roles in many organ systems. The plasma membrane Ca(2+)-ATPase (PMCA) is essential for removal of cytoplasmic Ca(2+) and for shaping the time courses of Ca(2+)-dependent activities. Here, we show that PMCA and GPER/GPR30 physically interact and functionally influence each other. In primary endothelial cells, GPER/GPR30 agonist G-1 decreases PMCA-mediated Ca(2+) extrusion by promoting PMCA tyrosine phosphorylation. GPER/GPR30 overexpression decreases PMCA activity, and G-1 further potentiates this effect. GPER/GPR30 knockdown increases PMCA activity, whereas PMCA knockdown substantially reduces GPER/GPR30-mediated phosphorylation of the extracellular signal-related kinase (ERK1/2). GPER/GPR30 co-immunoprecipitates with PMCA with or without treatment with 17β-estradiol, thapsigargin, or G-1. Heterologously expressed GPER/GPR30 in HEK 293 cells co-localizes with PMCA4b, the main endothelial PMCA isoform. Endothelial cells robustly express the PDZ post-synaptic density protein (PSD)-95, whose knockdown reduces the association between GPER/GPR30 and PMCA. Additionally, the association between PMCA4b and GPER/GPR30 is substantially reduced by truncation of either or both of their C-terminal PDZ-binding motifs. Functionally, inhibition of PMCA activity is significantly reduced by truncation of GPER/GPR30's C-terminal PDZ-binding motif. These data strongly indicate that GPER/GPR30 and PMCA4b form a hetero-oligomeric complex in part via the anchoring action of PSD-95, in which they constitutively affect each other's function. Activation of GPER/GPR30 further inhibits PMCA activity through tyrosine phosphorylation of the pump. These interactions represent cross-talk between Ca(2+) signaling and GPER/GPR30-mediated activities. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Deletion of Gpr55 Results in Subtle Effects on Energy Metabolism, Motor Activity and Thermal Pain Sensation.

PubMed

Bjursell, Mikael; Ryberg, Erik; Wu, Tingting; Greasley, Peter J; Bohlooly-Y, Mohammad; Hjorth, Stephan

2016-01-01

The G-protein coupled receptor 55 (GPR55) is activated by cannabinoids and non-cannabinoid molecules and has been speculated to play a modulatory role in a large variety of physiological and pathological processes, including in metabolically perturbed states. We therefore generated male mice deficient in the gene coding for the cannabinoid/lysophosphatidylinositol (LPI) receptor Gpr55 and characterized them under normal dietary conditions as well as during high energy dense diet feeding followed by challenge with the CB1 receptor antagonist/GPR55 agonist rimonabant. Gpr55 deficient male mice (Gpr55 KO) were phenotypically indistinguishable from their wild type (WT) siblings for the most part. However, Gpr55 KO animals displayed an intriguing nocturnal pattern of motor activity and energy expenditure (EE). During the initial 6 hours of the night, motor activity was significantly elevated without any significant effect observed in EE. Interestingly, during the last 6 hours of the night motor activity was similar but EE was significantly decreased in the Gpr55 KO mice. No significant difference in motor activity was detected during daytime, but EE was lower in the Gpr55 KO compared to WT mice. The aforementioned patterns were not associated with alterations in energy intake, daytime core body temperature, body weight (BW) or composition, although a non-significant tendency to increased adiposity was seen in Gpr55 KO compared to WT mice. Detailed analyses of daytime activity in the Open Field paradigm unveiled lower horizontal activity and rearing time for the Gpr55 KO mice. Moreover, the Gpr55 KO mice displayed significantly faster reaction time in the tail flick test, indicative of thermal hyperalgesia. The BW-decreasing effect of rimonabant in mice on long-term cafeteria diet did not differ between Gpr55 KO and WT mice. In conclusion, Gpr55 deficiency is associated with subtle effects on diurnal/nocturnal EE and motor activity behaviours but does not appear per se critically required for overall metabolism or behaviours.

Void detection beneath reinforced concrete sections: The practical application of ground-penetrating radar and ultrasonic techniques

NASA Astrophysics Data System (ADS)

Cassidy, Nigel J.; Eddies, Rod; Dods, Sam

2011-08-01

Ground-penetrating radar (GPR) and ultrasonic 'pulse echo' techniques are well-established methods for the imaging, investigation and analysis of steel reinforced concrete structures and are important civil engineering survey tools. GPR is, arguably, the more widely-used technique as it is suitable for a greater range of problem scenarios (i.e., from rebar mapping to moisture content determination). Ultrasonic techniques are traditionally associated with the engineering-based, non-destructive testing of concrete structures and their integrity analyses (e.g., flaw detection, shear/longitudinal velocity determination, etc). However, when used in an appropriate manner, both techniques can be considered complementary and provide a unique way of imaging the sub-surface that is suited to a range of geotechnical problems. In this paper, we present a comparative study between mid-to-high frequency GPR (450 MHz and 900 MHz) and array-based, shear wave, pulse-echo ultrasonic surveys using proprietary instruments and conventional GPR data processing and visualisation techniques. Our focus is the practical detection of sub-metre scale voids located under steel reinforced concrete sections in realistic survey conditions (e.g., a capped, relict mine shaft or vent). Representative two-dimensional (2D) sections are presented for both methods illustrating the similarities/differences in signal response and the temporal-spatial target resolutions achieved with each technique. The use of three-dimensional data volumes and time slices (or 'C-scans') for advanced interpretation is also demonstrated, which although common in GPR applications is under-utilised as a technique in general ultrasonic surveys. The results show that ultrasonic methods can perform as well as GPR for this specific investigation scenario and that they have the potential of overcoming some of the inherent limitations of GPR investigations (i.e., the need for careful antenna frequency selection and survey design in order to image through the rebar meshes). More importantly, we show that standard GPR data collection, processing and visualisation techniques can be used with both types of data without users needing to change existing operational protocols or survey criteria.

Targeting GPR120 and other fatty acid-sensing GPCRs ameliorates insulin resistance and inflammatory diseases.

PubMed

Talukdar, Saswata; Olefsky, Jerrold M; Osborn, Olivia

2011-09-01

The past decade has seen great progress in the understanding of the molecular pharmacology, physiological function and therapeutic potential of G-protein-coupled receptors (GPCRs). Free fatty acids (FFAs) have been demonstrated to act as ligands of several GPCRs including GPR40, GPR43, GPR84, GPR119 and GPR120. We have recently shown that GPR120 acts as a physiological receptor of ω3 fatty acids in macrophages and adipocytes, which mediate potent anti-inflammatory and insulin sensitizing effects. The important role GPR120 plays in the control of inflammation raises the possibility that targeting this receptor could have therapeutic potential in many inflammatory diseases including obesity and type 2 diabetes. In this review paper, we discuss lipid-sensing GPCRs and highlight potential outcomes of targeting such receptors in ameliorating disease. Copyright © 2011 Elsevier Ltd. All rights reserved.

Identification of Buried Objects in GPR Using Amplitude Modulated Signals Extracted from Multiresolution Monogenic Signal Analysis

PubMed Central

Qiao, Lihong; Qin, Yao; Ren, Xiaozhen; Wang, Qifu

2015-01-01

It is necessary to detect the target reflections in ground penetrating radar (GPR) images, so that surface metal targets can be identified successfully. In order to accurately locate buried metal objects, a novel method called the Multiresolution Monogenic Signal Analysis (MMSA) system is applied in ground penetrating radar (GPR) images. This process includes four steps. First the image is decomposed by the MMSA to extract the amplitude component of the B-scan image. The amplitude component enhances the target reflection and suppresses the direct wave and reflective wave to a large extent. Then we use the region of interest extraction method to locate the genuine target reflections from spurious reflections by calculating the normalized variance of the amplitude component. To find the apexes of the targets, a Hough transform is used in the restricted area. Finally, we estimate the horizontal and vertical position of the target. In terms of buried object detection, the proposed system exhibits promising performance, as shown in the experimental results. PMID:26690146

Rapid Detection Methods for Asphalt Pavement Thicknesses and Defects by a Vehicle-Mounted Ground Penetrating Radar (GPR) System

PubMed Central

Dong, Zehua; Ye, Shengbo; Gao, Yunze; Fang, Guangyou; Zhang, Xiaojuan; Xue, Zhongjun; Zhang, Tao

2016-01-01

The thickness estimation of the top surface layer and surface layer, as well as the detection of road defects, are of great importance to the quality conditions of asphalt pavement. Although ground penetrating radar (GPR) methods have been widely used in non-destructive detection of pavements, the thickness estimation of the thin top surface layer is still a difficult problem due to the limitations of GPR resolution and the similar permittivity of asphalt sub-layers. Besides, the detection of some road defects, including inadequate compaction and delamination at interfaces, require further practical study. In this paper, a newly-developed vehicle-mounted GPR detection system is introduced. We used a horizontal high-pass filter and a modified layer localization method to extract the underground layers. Besides, according to lab experiments and simulation analysis, we proposed theoretical methods for detecting the degree of compaction and delamination at the interface, respectively. Moreover, a field test was carried out and the estimated results showed a satisfactory accuracy of the system and methods. PMID:27929409

Rapid Detection Methods for Asphalt Pavement Thicknesses and Defects by a Vehicle-Mounted Ground Penetrating Radar (GPR) System.

PubMed

Dong, Zehua; Ye, Shengbo; Gao, Yunze; Fang, Guangyou; Zhang, Xiaojuan; Xue, Zhongjun; Zhang, Tao

2016-12-06

The thickness estimation of the top surface layer and surface layer, as well as the detection of road defects, are of great importance to the quality conditions of asphalt pavement. Although ground penetrating radar (GPR) methods have been widely used in non-destructive detection of pavements, the thickness estimation of the thin top surface layer is still a difficult problem due to the limitations of GPR resolution and the similar permittivity of asphalt sub-layers. Besides, the detection of some road defects, including inadequate compaction and delamination at interfaces, require further practical study. In this paper, a newly-developed vehicle-mounted GPR detection system is introduced. We used a horizontal high-pass filter and a modified layer localization method to extract the underground layers. Besides, according to lab experiments and simulation analysis, we proposed theoretical methods for detecting the degree of compaction and delamination at the interface, respectively. Moreover, a field test was carried out and the estimated results showed a satisfactory accuracy of the system and methods.

The role of the obestatin/GPR39 system in human gastric adenocarcinomas.

PubMed

Alén, Begoña O; Leal-López, Saúl; Alén, María Otero; Viaño, Patricia; García-Castro, Victoria; Mosteiro, Carlos S; Beiras, Andrés; Casanueva, Felipe F; Gallego, Rosalía; García-Caballero, Tomás; Camiña, Jesús P; Pazos, Yolanda

2016-02-02

Obestatin, a 23-amino acid peptide encoded by the ghrelin gene, and the GPR39 receptor were reported to be involved in the control of mitogenesis of gastric cancer cell lines; however, the relationship between the obestatin/GPR39 system and gastric cancer progression remains unknown. In the present study, we determined the expression levels of the obestatin/GPR39 system in human gastric adenocarcinomas and explored their potential functional roles. Twenty-eight patients with gastric adenocarcinomas were retrospectively studied, and clinical data were obtained. The role of obestatin/GPR39 in gastric cancer progression was studied in vitro using the human gastric adenocarcinoma AGS cell line. Obestatin exogenous administration in these GPR39-bearing cells deregulated the expression of several hallmarks of the epithelial-mesenchymal transition (EMT) and angiogenesis. Moreover, obestatin signaling promoted phenotypic changes via GPR39, increasingly impacting on the cell morphology, proliferation, migration and invasion of these cells. In healthy human stomachs, obestatin expression was observed in the neuroendocrine cells and GPR39 expression was localized mainly in the chief cells of the oxyntic glands. In human gastric adenocarcinomas, no obestatin expression was found; however, an aberrant pattern of GPR39 expression was discovered, correlating to the dedifferentiation of the tumor. Altogether, our data strongly suggest the involvement of the obestatin/GPR39 system in the pathogenesis and/or clinical outcome of human gastric adenocarcinomas and highlight the potential usefulness of GPR39 as a prognostic marker in gastric cancer.

The role of the obestatin/GPR39 system in human gastric adenocarcinomas

PubMed Central

Alén, Begoña O.; Leal-López, Saúl; Alén, María Otero; Viaño, Patricia; García-Castro, Victoria; Mosteiro, Carlos S.; Beiras, Andrés; Casanueva, Felipe F.; Gallego, Rosalía; García-Caballero, Tomás; Camiña, Jesús P.; Pazos, Yolanda

2016-01-01

Obestatin, a 23-amino acid peptide encoded by the ghrelin gene, and the GPR39 receptor were reported to be involved in the control of mitogenesis of gastric cancer cell lines; however, the relationship between the obestatin/GPR39 system and gastric cancer progression remains unknown. In the present study, we determined the expression levels of the obestatin/GPR39 system in human gastric adenocarcinomas and explored their potential functional roles. Twenty-eight patients with gastric adenocarcinomas were retrospectively studied, and clinical data were obtained. The role of obestatin/GPR39 in gastric cancer progression was studied in vitro using the human gastric adenocarcinoma AGS cell line. Obestatin exogenous administration in these GPR39-bearing cells deregulated the expression of several hallmarks of the epithelial-mesenchymal transition (EMT) and angiogenesis. Moreover, obestatin signaling promoted phenotypic changes via GPR39, increasingly impacting on the cell morphology, proliferation, migration and invasion of these cells. In healthy human stomachs, obestatin expression was observed in the neuroendocrine cells and GPR39 expression was localized mainly in the chief cells of the oxyntic glands. In human gastric adenocarcinomas, no obestatin expression was found; however, an aberrant pattern of GPR39 expression was discovered, correlating to the dedifferentiation of the tumor. Altogether, our data strongly suggest the involvement of the obestatin/GPR39 system in the pathogenesis and/or clinical outcome of human gastric adenocarcinomas and highlight the potential usefulness of GPR39 as a prognostic marker in gastric cancer. PMID:26716511

Identification of G-protein-coupled receptor 120 as a tumor-promoting receptor that induces angiogenesis and migration in human colorectal carcinoma.

PubMed

Wu, Q; Wang, H; Zhao, X; Shi, Y; Jin, M; Wan, B; Xu, H; Cheng, Y; Ge, H; Zhang, Y

2013-12-05

G-protein-coupled receptor 120 (GPR120) functions as a receptor for unsaturated long-chain free fatty acids and has an important role in regulating lipid and glucose metabolism. However, a role for GPR120 in the development of tumors has not yet been clarified. Here, we show that GPR120 signaling promotes angiogenic switching and motility of human colorectal carcinoma (CRC) cells. We show that the expression of GPR120 is significantly induced in CRC tissues and cell lines, which is associated with tumor progression. Activation of GPR120 signaling in human CRC promotes angiogenesis in vitro and in vivo, largely by inducing the expression and secretion of proangiogenic mediators such as vascular endothelial growth factor (VEGF), interleukin-8 and cyclooxygenase-2-derived prostaglandin E2. The PI3K/Akt-NF-κB pathway is activated by GPR120 signaling and is required for GPR120 signaling-induced angiogenic switching in CRC cells. And, GPR120 activation enhances the motility of CRC cells and induces epithelial-mesenchymal transition. Furthermore, in vivo study shows that activation of GPR120 promotes angiogenesis and tumor growth. Finally, we find that GPR120 expression is positively correlated with VEGF expression and inversely correlated with the epithelial marker E-cadherin in CRC tissues. Collectively, our results demonstrate that GPR120 functions as a tumor-promoting receptor in CRC and, therefore, shows promise as a new potential target for cancer therapeutics.

Electromagnetic simulators for Ground Penetrating Radar applications developed in COST Action TU1208

NASA Astrophysics Data System (ADS)

Pajewski, Lara; Giannopoulos, Antonios; Warren, Craig; Antonijevic, Sinisa; Doric, Vicko; Poljak, Dragan

2017-04-01

Founded in 1971, COST (European COoperation in Science and Technology) is the first and widest European framework for the transnational coordination of research activities. It operates through Actions, science and technology networks with a duration of four years. The main objective of the COST Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar" (4 April 2013 - 3 October 2017) is to exchange and increase knowledge and experience on Ground-Penetrating Radar (GPR) techniques in civil engineering, whilst promoting in Europe a wider use of this technique. Research activities carried out in TU1208 include all aspects of the GPR technology and methodology: design, realization and testing of radar systems and antennas; development and testing of surveying procedures for the monitoring and inspection of structures; integration of GPR with other non-destructive testing approaches; advancement of electromagnetic-modelling, inversion and data-processing techniques for radargram analysis and interpretation. GPR radargrams often have no resemblance to the subsurface or structures over which the profiles were recorded. Various factors, including the innate design of the survey equipment and the complexity of electromagnetic propagation in composite scenarios, can disguise complex structures recorded on reflection profiles. Electromagnetic simulators can help to understand how target structures get translated into radargrams. They can show the limitations of GPR technique, highlight its capabilities, and support the user in understanding where and in what environment GPR can be effectively used. Furthermore, electromagnetic modelling can aid the choice of the most proper GPR equipment for a survey, facilitate the interpretation of complex datasets and be used for the design of new antennas. Electromagnetic simulators can be employed to produce synthetic radargrams with the purposes of testing new data-processing, imaging and inversion algorithms, or assess the effectiveness of existing ones. A fast and accurate forward solver can also be used as part of an inverse solver. This contribution aims at presenting two electromagnetic simulators based on the Finite-Difference Time Domain (FDTD) technique and Boundary Element Method (BEM), for Ground Penetrating Radar applications. These tools have been developed by Members of the COST Action TU1208. The first simulator is the new open-source version of the software gprMax (www.GPRadar.eu), which employs Yee's algorithm to solve Maxwell's equations by using the FDTD method and includes advanced features allowing the accurate analysis of realistic scenarios. For example, a library of antennas is available and these can be directly included in the models. Moreover, it is possible to build heterogeneous media using fractals, as well as objects with rough surfaces. Anisotropic media can be defined and this allows materials such as wood and fibre-reinforced concrete to be accurately modelled. Media with arbitrary frequency-dispersive properties can be also defined and this paves the way to the use of gprMax in new areas, such as the modelling of human tissues. Optimisation of parameters based on Taguchi's method can be performed: this feature can be useful to optimise material properties based on experimental data, or to design new antennas. Additionally, a freeware and very useful CAD package was developed, conceived to ease the use of gprMax: such tool assists in the creation, modification and analysis of two-dimensional gprMax models and can also be used to plot results. The second simulator is TWiNS-II: this is free software for the analysis of multiple thin wires in the presence of two media, implementing the Galerkin-Bubnov Indirect BEM; calculations can be undertaken in the frequency or time domain. The time-domain code is focused on the assessment of current distributions along thin wire structures. The configuration that can be analyzed is a set of parallel thin wires placed in free space above a perfect ground, or above a dielectric lossless half-space. The wire array resides in a plane parallel to the interface. Within this basic geometry, the user is allowed to arbitrarily change the number, size and position of wires, their excitation characteristics and the dielectric constant of the half-space. The frequency-domain code can be used for the frequency analysis of the same wire configuration as in the time domain counterpart. In addition, the effects of losses in the ground can be taken into account. Acknowledgement: The Authors are deeply grateful to COST (European Cooperation in Science and Technology, www.cost.eu), for funding and supporting the COST Action TU1208 "Civil engineering applications of Ground Penetrating Radar" (www.GPRadar.eu).

Differential free fatty acid receptor-1 (FFAR1/GPR40) signalling is associated with gene expression or gelatinase granule release in bovine neutrophils.

PubMed

Mena, Sandra J; Manosalva, Carolina; Carretta, Maria D; Teuber, Stefanie; Olmo, Iván; Burgos, Rafael A; Hidalgo, Maria A

2016-08-01

Fatty acids have been recognized as regulators of immune function in addition to their known metabolic role. Long-chain fatty acids bind free fatty acid receptor (FFAR)-1/GPR40, which is expressed on bovine neutrophils, and increase responses such as granule release and gene expression. In this study, we investigated the molecular mechanisms governing the up-regulation of cyclooxygenase-2 (COX-2) and IL-8, as well as matrix metalloproteinase (MMP)-9 granule release in FFAR1/GPR40 agonist-stimulated neutrophils. Our results showed that natural (oleic and linoleic acid) and synthetic (GW9508) FFAR1/GPR40 agonists increased ERK1/2, p38 MAPK and Akt phosphorylation, and that the FFAR1/GPR40 antagonist GW1100 reduced these responses. We evaluated the levels of IκBα, a component of the classical activation pathway of the transcription factor NF-κB, and we observed IκBα reduction after stimulation with FFAR1/GPR40 agonists, an effect that was inhibited by GW1100 or the inhibitors UO126, SB203580 or LY294002. FFAR1/GPR40 agonists increased COX-2 and IL-8 expression, which was inhibited by GW1100 and an NF-κB inhibitor. Finally, the FFAR1/GPR40 agonist-induced MMP-9 granule release was reduced by GW1100 and UO126. In conclusion, FFAR1/GPR40 agonists differentially stimulate neutrophil functions; COX-2 and IL-8 are expressed after FFAR1/GPR40 activation via NF-κB, IκBα reduction is FFAR1/GPR40- and PI3K/MAPK-dependent, and MMP-9 granule release is FFAR1/GPR40- and ERK1/2-dependent. © The Author(s) 2016.

Targeting of free fatty acid receptor 1 in EOC: A novel strategy to restrict the adipocyte-EOC dependence.

PubMed

Munkarah, Adnan; Mert, Ismail; Chhina, Jasdeep; Hamid, Suhail; Poisson, Laila; Hensley-Alford, Sharon; Giri, Shailendra; Rattan, Ramandeep

2016-04-01

Adipocyte derived free fatty acids (FFA) promote epithelial ovarian cancer (EOC) by acting as a fuel source to support the energy requirement of the cancer cells. FFA may also exert biological effects through signaling pathways. Recently, a family of FFA activated G-protein coupled receptors (FFAR/GPCRs) was identified. Our objective was to investigate the role of FFAR/GPCRs in EOC and assess their potential as therapeutic targets. The mRNA (RT-PCR) expression of FFAR/GPCR family members (FFAR1/GPR40; FFAR2/GPR43, FFAR3/GPR41, FFAR4/GPR120 and GPR84) was examined in: (1) a syngeneic mouse model of EOC fed high energy diet (60% fat) or regular diet (30% fat), (2) EOC cell lines exposed to free fatty acids and (3) specimens from 13 histologically normal ovaries and 28 high grade ovarian serous carcinomas. The GPR 40 antagonist, GW1100, was used to inhibit FFAR1/GPR40 and cell survival was assayed by MTT in various cell lines. High Grade Serous carcinoma specimens expressed significantly increased GPR40 compared to normal ovaries (p=0.0020). Higher expression was noted in advanced stage disease. ID8 ovarian tumors from mice fed with high fat diet also showed higher GPR40 expression. Exposing EOC cells to FFAs, increased GPR40 expression. Treatment of EOC cell lines with GW100 resulted in growth inhibition and was associated with an alteration in their energy metabolism. FFA-induced cancer cell growth may be partly mediated through FFAR1/GPR40. Targeting of FFAR1/GPR40 may be an attractive treatment strategy in EOC, and possibly offers a targeted treatment for a subset of EOC patients. Copyright © 2016 Elsevier Inc. All rights reserved.

GPR-4 Is a Predicted G-Protein-Coupled Receptor Required for Carbon Source-Dependent Asexual Growth and Development in Neurospora crassa

PubMed Central

Li, Liande; Borkovich, Katherine A.

2006-01-01

The filamentous fungus Neurospora crassa is able to utilize a wide variety of carbon sources. Here, we examine the involvement of a predicted G-protein-coupled receptor (GPCR), GPR-4, during growth and development in the presence of different carbon sources in N. crassa. Δgpr-4 mutants have reduced mass accumulation compared to the wild type when cultured on high levels of glycerol, mannitol, or arabinose. The defect is most severe on glycerol and is cell density dependent. The genetic and physical relationship between GPR-4 and the three N. crassa Gα subunits (GNA-1, GNA-2, and GNA-3) was explored. All three Gα mutants are defective in mass accumulation when cultured on glycerol. However, the phenotypes of Δgna-1 and Δgpr-4 Δgna-1 mutants are identical, introduction of a constitutively activated gna-1 allele suppresses the defects of the Δgpr-4 mutation, and the carboxy terminus of GPR-4 interacts most strongly with GNA-1 in the yeast two-hybrid assay. Although steady-state cyclic AMP (cAMP) levels are normal in Δgpr-4 strains, exogenous cAMP partially remediates the dry mass defects of Δgpr-4 mutants on glycerol medium and Δgpr-4 strains lack the transient increase in cAMP levels observed in the wild type after addition of glucose to glycerol-grown liquid cultures. Our results support the hypothesis that GPR-4 is coupled to GNA-1 in a cAMP signaling pathway that regulates the response to carbon source in N. crassa. GPR-4-related GPCRs are present in the genomes of several filamentous ascomycete fungal pathogens, raising the possibility that a similar pathway regulates carbon sensing in these organisms. PMID:16896213

Aromatic D-amino acids act as chemoattractant factors for human leukocytes through a G protein-coupled receptor, GPR109B.

PubMed

Irukayama-Tomobe, Yoko; Tanaka, Hirokazu; Yokomizo, Takehiko; Hashidate-Yoshida, Tomomi; Yanagisawa, Masashi; Sakurai, Takeshi

2009-03-10

GPR109B (HM74) is a putative G protein-coupled receptor (GPCR) whose cognate ligands have yet to be characterized. GPR109B shows a high degree of sequence similarity to GPR109A, another GPCR that was identified as a high-affinity nicotinic acid (niacin) receptor. However, the affinity of nicotinic acid to GPR109B is very low. In this study, we found that certain aromatic D-amino acids, including D-phenylalanine, D-tryptophan, and the metabolite of the latter, D-kynurenine, decreased the activity of adenylate cyclase in cells transfected with GPR109B cDNA through activation of pertussis toxin (PTX)-sensitive G proteins. These D-amino acids also elicited a transient rise of intracellular Ca(2+) level in cells expressing GPR109B in a PTX-sensitive manner. In contrast, these D-amino acids did not show any effects on cells expressing GPR109A. We found that the GPR109B mRNA is abundantly expressed in human neutrophils. D-phenylalanine and D-tryptophan induced a transient increase of intracellular Ca(2+) level and a reduction of cAMP levels in human neutrophils. Furthermore, knockdown of GPR109B by RNA interference inhibited the D-amino acids-induced decrease of cellular cAMP levels in human neutrophils. These D-amino acids induced chemotactic activity of freshly prepared human neutrophils. We also found that D-phenylalanine and D-tryptophan induced chemotactic responses in Jurkat cells transfected with the GPR109B cDNA but not in mock-transfected Jurkat cells. These results suggest that these aromatic D-amino acids elicit a chemotactic response in human neutrophils via activation of GPR109B.

Activation of GPR4 by Acidosis Increases Endothelial Cell Adhesion through the cAMP/Epac Pathway

PubMed Central

Leffler, Nancy R.; Asch, Adam S.; Witte, Owen N.; Yang, Li V.

2011-01-01

Endothelium-leukocyte interaction is critical for inflammatory responses. Whereas the tissue microenvironments are often acidic at inflammatory sites, the mechanisms by which cells respond to acidosis are not well understood. Using molecular, cellular and biochemical approaches, we demonstrate that activation of GPR4, a proton-sensing G protein-coupled receptor, by isocapnic acidosis increases the adhesiveness of human umbilical vein endothelial cells (HUVECs) that express GPR4 endogenously. Acidosis in combination with GPR4 overexpression further augments HUVEC adhesion with U937 monocytes. In contrast, overexpression of a G protein signaling-defective DRY motif mutant (R115A) of GPR4 does not elicit any increase of HUVEC adhesion, indicating the requirement of G protein signaling. Downregulation of GPR4 expression by RNA interference reduces the acidosis-induced HUVEC adhesion. To delineate downstream pathways, we show that inhibition of adenylate cyclase by inhibitors, 2′,5′-dideoxyadenosine (DDA) or SQ 22536, attenuates acidosis/GPR4-induced HUVEC adhesion. Consistently, treatment with a cAMP analog or a Gi signaling inhibitor increases HUVEC adhesiveness, suggesting a role of the Gs/cAMP signaling in this process. We further show that the cAMP downstream effector Epac is important for acidosis/GPR4-induced cell adhesion. Moreover, activation of GPR4 by acidosis increases the expression of vascular adhesion molecules E-selectin, VCAM-1 and ICAM-1, which are functionally involved in acidosis/GPR4-mediated HUVEC adhesion. Similarly, hypercapnic acidosis can also activate GPR4 to stimulate HUVEC adhesion molecule expression and adhesiveness. These results suggest that acidosis/GPR4 signaling regulates endothelial cell adhesion mainly through the Gs/cAMP/Epac pathway and may play a role in the inflammatory response of vascular endothelial cells. PMID:22110680

Expression of orphan G-protein coupled receptor GPR174 in CHO cells induced morphological changes and proliferation delay via increasing intracellular cAMP

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sugita, Kazuya; Yamamura, Chiaki; Tabata, Ken-ichi

2013-01-04

Highlights: Black-Right-Pointing-Pointer Expression of GPR174 in CHO cells induces morphological changes and proliferation delay. Black-Right-Pointing-Pointer These are due to increase in intracellular cAMP concentration. Black-Right-Pointing-Pointer Lysophosphatidylserine was identified to stimulate GPR174 leading to activate ACase. Black-Right-Pointing-Pointer The potencies of fatty acid moiety on LysoPS were oleoyl Greater-Than-Or-Slanted-Equal-To stearoyl > palmitoyl. Black-Right-Pointing-Pointer We propose that GPR174 is a lysophosphatidylserine receptor. -- Abstract: We established cell lines that stably express orphan GPCR GPR174 using CHO cells, and studied physiological and pharmacological features of the receptor. GPR174-expressing cells showed cell-cell adhesion with localization of actin filaments to cell membrane, and revealed significant delaymore » of cell proliferation. Since the morphological changes of GPR174-cells were very similar to mock CHO cells treated with cholera toxin, we measured the concentration of intracellular cAMP. The results showed the concentration was significantly elevated in GPR174-cells. By measuring intracellular cAMP concentration in GPR174-cells, we screened lipids and nucleotides to identify ligands for GPR174. We found that lysophosphatidylserine (LysoPS) stimulated increase in intracellular cAMP in a dose-dependent manner. Moreover, phosphorylation of Erk was elevated by LysoPS in GPR174 cells. These LysoPS responses were inhibited by NF449, an inhibitor of G{alpha}{sub s} protein. These results suggested that GPR174 was a putative LysoPS receptor conjugating with G{alpha}{sub s}, and its expression induced morphological changes in CHO cells by constitutively activating adenylyl cycles accompanied with cell conjunctions and delay of proliferation.« less

a Webgis to Support Gpr 3d Data Acquisition: a First Step for the Integration of Underground Utility Networks in 3d City Models

NASA Astrophysics Data System (ADS)

Tabarro, P. G.; Pouliot, J.; Fortier, R.; Losier, L.-M.

2017-10-01

For the planning and sustainable development of large cities, it is critical to accurately locate and map, in 3D, existing underground utility networks (UUN) such as pipelines, cables, ducts, and channels. An emerging non-invasive instrument for collecting underground data such as UUN is the ground-penetrating radar (GPR). Although its capabilities, handling GPR and extracting relevant information from its data are not trivial tasks. For instance, both GPR and its complimentary software stack provide very few capabilities to co-visualize GPR collected data and other sources of spatial data such as orthophotography, DEM or road maps. Furthermore, the GPR interface lacks functionalities for adding annotation, editing geometric objects or querying attributes. A new approach to support GPR survey is proposed in this paper. This approach is based on the integration of multiple sources of geospatial datasets and the use of a Web-GIS system and relevant functionalities adapted to interoperable GPR data acquisition. The Web-GIS is developed as an improved module in an existing platform called GVX. The GVX-GPR module provides an interactive visualization of multiple layers of structured spatial data, including GPR profiles. This module offers new features when compared to traditional GPR surveys such as geo-annotated points of interest for identifying spatial clues in the GPR profiles, integration of city contextual data, high definition drone and satellite pictures, as-built, and more. The paper explains the engineering approach used to design and develop the Web GIS and tests for this survey approach, mapping and recording UUN as part of 3D city model.

IFNγ Induces DNA Methylation-Silenced GPR109A Expression via pSTAT1/p300 and H3K18 Acetylation in Colon Cancer.

PubMed

Bardhan, Kankana; Paschall, Amy V; Yang, Dafeng; Chen, May R; Simon, Priscilla S; Bhutia, Yangzom D; Martin, Pamela M; Thangaraju, Muthusamy; Browning, Darren D; Ganapathy, Vadivel; Heaton, Christopher M; Gu, Keni; Lee, Jeffrey R; Liu, Kebin

2015-07-01

Short-chain fatty acids, metabolites produced by colonic microbiota from fermentation of dietary fiber, act as anti-inflammatory agents in the intestinal tract to suppress proinflammatory diseases. GPR109A is the receptor for short-chain fatty acids. The functions of GPR109A have been the subject of extensive studies; however, the molecular mechanisms underlying GPR109A expression is largely unknown. We show that GPR109A is highly expressed in normal human colon tissues, but is silenced in human colon carcinoma cells. The GPR109A promoter DNA is methylated in human colon carcinoma. Strikingly, we observed that IFNγ, a cytokine secreted by activated T cells, activates GPR109A transcription without altering its promoter DNA methylation. Colon carcinoma grows significantly faster in IFNγ-deficient mice than in wild-type mice in an orthotopic colon cancer mouse model. A positive correlation was observed between GPR109A protein level and tumor-infiltrating T cells in human colon carcinoma specimens, and IFNγ expression level is higher in human colon carcinoma tissues than in normal colon tissues. We further demonstrated that IFNγ rapidly activates pSTAT1 that binds to the promoter of p300 to activate its transcription. p300 then binds to the GPR109A promoter to induce H3K18 hyperacetylation, resulting in chromatin remodeling in the methylated GPR109A promoter. The IFNγ-activated pSTAT1 then directly binds to the methylated but hyperacetylated GPR109 promoter to activate its transcription. Overall, our data indicate that GPR109A acts as a tumor suppressor in colon cancer, and the host immune system might use IFNγ to counteract DNA methylation-mediated GPR109A silencing as a mechanism to suppress tumor development. ©2015 American Association for Cancer Research.

Combined application of GPR and ERT for the assessment of a wall structure at the Heptapyrgion fortress (Thessaloniki, Greece)

NASA Astrophysics Data System (ADS)

Angelis, Dimitrios; Tsourlos, Panagiotis; Tsokas, Gregory; Vargemezis, George; Zacharopoulou, Georgia; Power, Christopher

2018-05-01

Non-destructive investigation of monuments can be an extremely valuable tool to evaluate potential structural defects and assist in developing any restoration plans. In this work, both Ground Penetrating Radar (GPR) and Electrical Resistivity Tomography (ERT) techniques were applied to a tower wall of the Heptapyrgion fortress located in Thessaloniki, Greece, which was facing significant moisture problems. GPR cross sections, mainly obtained with a 500 MHz centre frequency antenna, and ERT profiles were collected along the same survey grid on the tower wall. The gprMax numerical solver was used for the GPR forward modelling. In addition, an auxiliary program was used to design and import into gprMax complicated structures and this allowed to simulate more realistically the wall defects and moisture. The GPR simulator was used to assess and optimize the field data acquisition and processing parameters, and to assist in interpreting the GPR cross sections. The ERT sections were inverted as individual 2D lines and also, as a full 3D dataset. The final GPR and ERT data were jointly interpreted in view of the studied problem as results of both methods are highly correlated. A high moisture content area at the eastern part of the wall was identified in both GPR and ERT data, along with the interface between different phases of construction. Through the GPR data we were also able to delineate possible structural defects (cracks, small voids) which was not possible with just using the ERT data. Furthermore, a very good matching was evident between the simulated GPR modelling results incorporating field-interpreted features, and the actual field GPR results, thereby validating the proposed data interpretation. The overall survey and modelling approach produces results that are in a very good agreement between them and proved very useful in accessing the wall structure.

Post-synaptic Density-95 (PSD-95) Binding Capacity of G-protein-coupled Receptor 30 (GPR30), an Estrogen Receptor That Can Be Identified in Hippocampal Dendritic Spines*

PubMed Central

Akama, Keith T.; Thompson, Louisa I.; Milner, Teresa A.; McEwen, Bruce S.

2013-01-01

The estrogen 17β-estradiol (E2) modulates dendritic spine plasticity in the cornu ammonis 1 (CA1) region of the hippocampus, and GPR30 (G-protein coupled estrogen receptor 1 (GPER1)) is an estrogen-sensitive G-protein-coupled receptor (GPCR) that is expressed in the mammalian brain and in specific subregions that are responsive to E2, including the hippocampus. The subcellular localization of hippocampal GPR30, however, remains unclear. Here, we demonstrate that GPR30 immunoreactivity is detected in dendritic spines of rat CA1 hippocampal neurons in vivo and that GPR30 protein can be found in rat brain synaptosomes. GPR30 immunoreactivity is identified at the post-synaptic density (PSD) and in the adjacent peri-synaptic zone, and GPR30 can associate with the spine scaffolding protein PSD-95 both in vitro and in vivo. This PSD-95 binding capacity of GPR30 is specific and determined by the receptor C-terminal tail that is both necessary and sufficient for PSD-95 interaction. The interaction with PSD-95 functions to increase GPR30 protein levels residing at the plasma membrane surface. GPR30 associates with the N-terminal tandem pair of PDZ domains in PSD-95, suggesting that PSD-95 may be involved in clustering GPR30 with other receptors in the hippocampus. We demonstrate that GPR30 has the potential to associate with additional post-synaptic GPCRs, including the membrane progestin receptor, the corticotropin releasing hormone receptor, and the 5HT1a serotonin receptor. These data demonstrate that GPR30 is well positioned in the dendritic spine compartment to integrate E2 sensitivity directly onto multiple inputs on synaptic activity and might begin to provide a molecular explanation as to how E2 modulates dendritic spine plasticity. PMID:23300088

Post-synaptic density-95 (PSD-95) binding capacity of G-protein-coupled receptor 30 (GPR30), an estrogen receptor that can be identified in hippocampal dendritic spines.

PubMed

Akama, Keith T; Thompson, Louisa I; Milner, Teresa A; McEwen, Bruce S

2013-03-01

The estrogen 17β-estradiol (E2) modulates dendritic spine plasticity in the cornu ammonis 1 (CA1) region of the hippocampus, and GPR30 (G-protein coupled estrogen receptor 1 (GPER1)) is an estrogen-sensitive G-protein-coupled receptor (GPCR) that is expressed in the mammalian brain and in specific subregions that are responsive to E2, including the hippocampus. The subcellular localization of hippocampal GPR30, however, remains unclear. Here, we demonstrate that GPR30 immunoreactivity is detected in dendritic spines of rat CA1 hippocampal neurons in vivo and that GPR30 protein can be found in rat brain synaptosomes. GPR30 immunoreactivity is identified at the post-synaptic density (PSD) and in the adjacent peri-synaptic zone, and GPR30 can associate with the spine scaffolding protein PSD-95 both in vitro and in vivo. This PSD-95 binding capacity of GPR30 is specific and determined by the receptor C-terminal tail that is both necessary and sufficient for PSD-95 interaction. The interaction with PSD-95 functions to increase GPR30 protein levels residing at the plasma membrane surface. GPR30 associates with the N-terminal tandem pair of PDZ domains in PSD-95, suggesting that PSD-95 may be involved in clustering GPR30 with other receptors in the hippocampus. We demonstrate that GPR30 has the potential to associate with additional post-synaptic GPCRs, including the membrane progestin receptor, the corticotropin releasing hormone receptor, and the 5HT1a serotonin receptor. These data demonstrate that GPR30 is well positioned in the dendritic spine compartment to integrate E2 sensitivity directly onto multiple inputs on synaptic activity and might begin to provide a molecular explanation as to how E2 modulates dendritic spine plasticity.

IFNγ induces DNA methylation-silenced GPR109A expression via pSTAT1/p300 and H3K18 acetylation in colon cancer

PubMed Central

Bardhan, Kankana; Paschall, Amy V.; Yang, Dafeng; Chen, May R.; Simon, Priscilla S.; Bhutia, Yangzom; Martin, Pamela M.; Thangaraju, Muthusamy; Browning, Darren D.; Ganapathy, Vadivel; Heaton, Christopher M.; Gu, Keni; Lee, Jeffrey R.; Liu, Kebin

2015-01-01

Short-chain fatty acids, metabolites produced by colonic microbiota from fermentation of dietary fiber, act as anti-inflammatory agents in the intestinal tract to suppress proinflammatory diseases. GPR109A is the receptor for short-chain fatty acids. The functions of GPR109A has been the subject of extensive studies, however, the molecular mechanisms underlying GPR109A expression is largely unknown. We show that GPR109A is highly expressed in normal human colon tissues, but is silenced in human colon carcinoma cells. The GPR109A promoter DNA is methylated in human colon carcinoma. Strikingly, we observed that IFNγ, a cytokine secreted by activated T cells, activates GPR109A transcription without altering its promoter DNA methylation. Colon carcinoma grows significantly faster in IFNγ-deficient mice than in wildtype mice in an orthotopic colon cancer mouse model. A positive correlation was observed between GPR109A protein level and tumor-infiltrating T cells in human colon carcinoma specimens, and IFNγ expression level is higher in human colon carcinoma tissues than in normal colon tissues. We further demonstrated that IFNγ rapidly activates pSTAT1 that binds to the promoter of p300 to activate its transcription. p300 then binds to the GPR109A promoters to induce H3K18 hyperacetylation, resulting in chromatin remodeling in the methylated GPR109A promoter. The IFNγ-activated pSTAT1 then directly binds to the methylated but hyperacetylated GPR109 promoters to activate its transcription. Overall, our data indicate that GPR109A acts as a tumor suppressor in colon cancer and the host immune system might use IFNγ to counteract DNA methylation-mediated GPR109A silencing as a mechanism to suppress tumor development. PMID:25735954

Expression of the Fatty Acid Receptors GPR84 and GPR120 and Cytodifferentiation of Epithelial Cells in the Gastric Mucosa of Mouse Pups in the Course of Dietary Transition.

PubMed

Widmayer, Patricia; Kusumakshi, Soumya; Hägele, Franziska A; Boehm, Ulrich; Breer, Heinz

2017-01-01

During weaning, the ingested food of mouse pups changes from exclusively milk to solid food. In contrast to the protein- and carbohydrate-rich solid food, high fat milk is characterized primarily by fatty acids of medium chain length particularly important for the suckling pups. Therefore, it seems conceivable that the stomach mucosa may be specialized for detecting these important nutrients during the suckling phase. Here, we analyzed the expression of the G protein coupled receptors GPR84 and GPR120 (FFAR4), which are considered to be receptors for medium and long chain fatty acids (LCFAs), respectively. We found that the mRNA levels for GPR84 and GPR120 were high during the suckling period and progressively decreased in the course of weaning. Visualization of the receptor-expressing cells in 2-week-old mice revealed a high number of labeled cells, which reside in the apical as well as in the basal region of the gastric glands. At the base of the gastric glands, all GPR84-immunoreactive cells and some of the GPR120-positive cells also expressed chromogranin A (CgA), suggesting that they are enteroendocrine cells. We demonstrate that the majority of the CgA/GPR84 cells are X/A-like ghrelin cells. The high degree of overlap between ghrelin and GPR84 decreased post-weaning, whereas the overlap between ghrelin and GPR120 increased. At the apical region of the glands the fatty acid receptors were mainly expressed in unique cell types. These contain lipid-filled vacuole- and vesicle-like structures and may have absorptive functions. We detected decreased immunoreactivity for GPR84 and no lipid droplets in surface cells post-weaning. In conclusion, expression of GPR84 in ghrelin cells as well as in surface cells suggests an important role of medium chain fatty acids (MCFAs) in the developing gastric mucosa of suckling mice.

Expression of the Fatty Acid Receptors GPR84 and GPR120 and Cytodifferentiation of Epithelial Cells in the Gastric Mucosa of Mouse Pups in the Course of Dietary Transition

PubMed Central

Widmayer, Patricia; Kusumakshi, Soumya; Hägele, Franziska A.; Boehm, Ulrich; Breer, Heinz

2017-01-01

During weaning, the ingested food of mouse pups changes from exclusively milk to solid food. In contrast to the protein- and carbohydrate-rich solid food, high fat milk is characterized primarily by fatty acids of medium chain length particularly important for the suckling pups. Therefore, it seems conceivable that the stomach mucosa may be specialized for detecting these important nutrients during the suckling phase. Here, we analyzed the expression of the G protein coupled receptors GPR84 and GPR120 (FFAR4), which are considered to be receptors for medium and long chain fatty acids (LCFAs), respectively. We found that the mRNA levels for GPR84 and GPR120 were high during the suckling period and progressively decreased in the course of weaning. Visualization of the receptor-expressing cells in 2-week-old mice revealed a high number of labeled cells, which reside in the apical as well as in the basal region of the gastric glands. At the base of the gastric glands, all GPR84-immunoreactive cells and some of the GPR120-positive cells also expressed chromogranin A (CgA), suggesting that they are enteroendocrine cells. We demonstrate that the majority of the CgA/GPR84 cells are X/A-like ghrelin cells. The high degree of overlap between ghrelin and GPR84 decreased post-weaning, whereas the overlap between ghrelin and GPR120 increased. At the apical region of the glands the fatty acid receptors were mainly expressed in unique cell types. These contain lipid-filled vacuole- and vesicle-like structures and may have absorptive functions. We detected decreased immunoreactivity for GPR84 and no lipid droplets in surface cells post-weaning. In conclusion, expression of GPR84 in ghrelin cells as well as in surface cells suggests an important role of medium chain fatty acids (MCFAs) in the developing gastric mucosa of suckling mice. PMID:28871231

Deletion of Gpr55 Results in Subtle Effects on Energy Metabolism, Motor Activity and Thermal Pain Sensation

PubMed Central

Ryberg, Erik; Wu, Tingting; Greasley, Peter J.; Bohlooly-Y, Mohammad; Hjorth, Stephan

2016-01-01

The G-protein coupled receptor 55 (GPR55) is activated by cannabinoids and non-cannabinoid molecules and has been speculated to play a modulatory role in a large variety of physiological and pathological processes, including in metabolically perturbed states. We therefore generated male mice deficient in the gene coding for the cannabinoid/lysophosphatidylinositol (LPI) receptor Gpr55 and characterized them under normal dietary conditions as well as during high energy dense diet feeding followed by challenge with the CB1 receptor antagonist/GPR55 agonist rimonabant. Gpr55 deficient male mice (Gpr55 KO) were phenotypically indistinguishable from their wild type (WT) siblings for the most part. However, Gpr55 KO animals displayed an intriguing nocturnal pattern of motor activity and energy expenditure (EE). During the initial 6 hours of the night, motor activity was significantly elevated without any significant effect observed in EE. Interestingly, during the last 6 hours of the night motor activity was similar but EE was significantly decreased in the Gpr55 KO mice. No significant difference in motor activity was detected during daytime, but EE was lower in the Gpr55 KO compared to WT mice. The aforementioned patterns were not associated with alterations in energy intake, daytime core body temperature, body weight (BW) or composition, although a non-significant tendency to increased adiposity was seen in Gpr55 KO compared to WT mice. Detailed analyses of daytime activity in the Open Field paradigm unveiled lower horizontal activity and rearing time for the Gpr55 KO mice. Moreover, the Gpr55 KO mice displayed significantly faster reaction time in the tail flick test, indicative of thermal hyperalgesia. The BW-decreasing effect of rimonabant in mice on long-term cafeteria diet did not differ between Gpr55 KO and WT mice. In conclusion, Gpr55 deficiency is associated with subtle effects on diurnal/nocturnal EE and motor activity behaviours but does not appear per se critically required for overall metabolism or behaviours. PMID:27941994

Comparing ground-penetrating radar (GPR) techniques in 18th-century yard spaces

NASA Astrophysics Data System (ADS)

Carducci, Christiane M.

Yards surrounding historical homesteads are the liminal space between private houses and public space, and contain artifactural and structural remains that help us understand how the residents interfaced with the world. Comparing different yards means collecting reliable evidence, and what is missing is just as important as what is found. Excavations can rely on randomly placed 50-cm shovel test pits to locate features, but this can miss important features. Shallow geophysics, in particular ground-penetrating radar (GPR), can be used to identify features and reliably and efficiently collect evidence. GPR is becoming more integrated into archaeological investigations due to the potential to quickly and nondestructively identify archaeological features and to recent advancements in processing software that make these methods more user-friendly. The most efficacious GPR surveys must take into consideration what is expected to be below the surface, what features look like in GPR outputs, the best methods for detecting features, and the limitations of GPR surveys. Man-made landscape features are expected to have existed within yard spaces, and the alteration of these features shows how the domestic economy of the residence changed through time. This study creates an inventory of these features. By producing a standardized sampling method for GPR in yard spaces, archaeologists can quickly map subsurface features and carry out broad comparisons between yards. To determine the most effective sampling method, several GPR surveys were conducted at the 18th-century Durant-Kenrick House in Newton, Massachusetts, using varied line spacing, line direction, and bin size. Examples of the GPR signatures of features, obtained using GPR-Slice software, from the Durant-Kenrick House and similar sites were analyzed. The efficacy of each method was determined based on the number of features distinguished, clarity of the results, and the time involved. The survey at Newton showed that ground surface conditions are extremely important when using GPR. Furthermore, GPR and archaeological excavations together provide the most complete interpretation because GPR has the ability to detect large-scale features that might be missed with test units, while excavation provides more detailed information, finds small-scale objects, and can be used to test false negatives seen in GPR surveys.

Deletion of the pH sensor GPR4 decreases renal acid excretion.

PubMed

Sun, Xuming; Yang, Li V; Tiegs, Brian C; Arend, Lois J; McGraw, Dennis W; Penn, Raymond B; Petrovic, Snezana

2010-10-01

Proton receptors are G protein-coupled receptors that accept protons as ligands and function as pH sensors. One of the proton receptors, GPR4, is relatively abundant in the kidney, but its potential role in acid-base homeostasis is unknown. In this study, we examined the distribution of GPR4 in the kidney, its function in kidney epithelial cells, and the effects of its deletion on acid-base homeostasis. We observed GPR4 expression in the kidney cortex, in the outer and inner medulla, in isolated kidney collecting ducts, and in cultured outer and inner medullary collecting duct cells (mOMCD1 and mIMCD3). Cultured mOMCD1 cells exhibited pH-dependent accumulation of intracellular cAMP, characteristic of GPR4 activation; GPR4 knockdown attenuated this accumulation. In vivo, deletion of GPR4 decreased net acid secretion by the kidney and resulted in a nongap metabolic acidosis, indicating that GPR4 is required to maintain acid-base homeostasis. Collectively, these findings suggest that GPR4 is a pH sensor with an important role in regulating acid secretion in the kidney collecting duct.

Imbalance between proliferation and apoptosis-related impaired GPR30 expression is involved in preeclampsia.

PubMed

Li, Jianxin; Chen, Zhu; Zhou, Xiaobo; Shi, Shuming; Qi, Hongbo; Baker, Philip N; Zhang, Hua

2016-11-01

The proliferation and apoptosis of cells in the placenta play a critical role in preeclampsia (PE) in which estrogen has been implicated via estrogen receptors (ERs). A novel ER, G-protein-coupled receptor 30 (GPR30), has recently been shown to be involved in PE. We investigated the basic levels of proliferation and apoptosis in normal placentae and placentae with PE and compared GPR30 expression levels between the two groups. We demonstrated that low GPR30 expression levels, more apoptosis, and less proliferation were associated with PE. Moreover, our in vitro study showed that both the selective GPR30 agonist G1 and the general ER agonist 17-β-estradiol were able to protect the placenta from hypoxia-reoxygenation injuries, resulting in decreased apoptosis and increased proliferation. Furthermore, this protective effect was abolished by the addition of the selective GPR30 inhibitor G15. These results provide evidence that (1) GPR30 is involved in regulating cell proliferation and apoptosis; (2) pharmacologic upregulation of GPR30 is beneficial for PE management; (3) GPR30 may therefore be an interventional target for pregnancies complicated by PE.

GPR30 Activation Contributes to the Puerarin-Mediated Neuroprotection in MPP+-Induced SH-SY5Y Cell Death.

PubMed

Cheng, Yue-Fa; Zhu, Guoqi; Wu, Qing-Wen; Xie, Yue-Sheng; Jiang, Yan; Guo, Lan; Guan, Ya-Li; Liu, Ying-Shuo; Zhang, Jun

2017-02-01

The neuroprotective action of puerarin in Parkinson's disease (PD) models has been well investigated. However, the mechanisms involved in protection have not been completely understood. G protein-coupled receptor 30 (GPR30) is a G protein-coupled estrogen receptor and considered a potential target in the neuroprotection against PD. In this study, we investigated whether puerarin prevented against 1-methyl-4-phenylpyridinium (MPP + )-induced cell death via GPR30. Our results showed that the GPR30 agonist, G1, exhibited puerarin-mediated neuroprotection against MPP + -induced cell death of SH-SY5Y cells. This protective action was reversed by the GPR30 antagonist. Moreover, a time- and concentration-dependent effect of puerarin on GPR30 expression was verified at the protein level but not at the mRNA level. Further, we showed that an mTor-dependent new GPR30 synthesis contributed to the protection conferred by puerarin. Finally, glial cell line-derived neurotrophic factor (GDNF) levels were enhanced by puerarin and G1 in both control and MPP + -lesioned cells via GPR30. Taken together, our data strongly suggest that puerarin prevents MPP + -induced cell death via facilitating GPR30 expression and GDNF release.

Recent accumulation rates of an Alpine glacier derived from repeated airborne GPR and firn cores

NASA Astrophysics Data System (ADS)

Sold, Leo; Huss, Matthias; Eichler, Anja; Schwikowski, Margit; Hoelzle, Martin

2014-05-01

The topmost areas of glaciers contain a valuable record of their past accumulation rates. The water equivalent of annual firn layers can be used to initiate or extend existing time series of local mass balance and, ultimately, to consolidate the knowledge on the response of glaciers to changing climatic conditions. Measurements of the thickness and density of firn layers typically involve drilling in remote areas and core analysis and are thus expensive in terms of time and effort. Here, we discuss measurements from 2012 on Findelengletscher, Switzerland, a large Alpine valley glacier, using two in-situ firn cores and airborne Ground-Penetrating Radar (GPR). The firn cores were analysed regarding their density, major ions and deuterium concentration. The ammonium (NH4+) concentration is known to show seasonality due to a higher source activity and pronounced vertical transportation in the atmosphere in summer. The deuterium concentration serves as a proxy for air temperature during precipitation formation. Together, they provide depth and dating of annual summer surfaces. GPR has previously been used for a non-destructive assessment of internal layers in snow, firn and ice. Signal reflections indicate changes in the dielectric properties of the material, e.g. density changes at former summer surfaces. Airborne surveys allow measurements to be taken in remote and inaccessible areas. However, to transfer information from the GPR pulse travel time to the depth domain, the dielectric permittivity of the material is required, that changes with density of the firn. We observed a good agreement of the GPR signal with pronounced changes in the density profile, ice layers and peak contents of major ions. This underlines the high potential of GPR for detecting firn layers. However, not all peak-densities and thick ice layers represent a former glacier summer surface but can also be due to melting and refreezing during winter. We show that up to four years of annual accumulation on Findelengletscher can be reconstructed from repeated GPR measurements alone. A simple transient spatial model for firn compaction is calibrated based on a comparison with GPR data of 2013 at positions were profiles intersect. Density and water equivalent of firn layers can then be extracted along the measured GPR profiles. However, if no in-situ information from firn cores is available, the dating of reflectors as former annual summer surfaces must be verified by external information such as modelled mass balance to avoid misinterpretations. We show that helicopter-borne GPR is an effective method to derive several years of past accumulation rates of mountain glaciers. It benefits but does not depend exclusively on the time-matched availability of firn cores when overlapping profiles are mapped in subsequent years.

Developing ground penetrating radar (GPR) for enhanced root and soil organic carbon imaging: Optimizing bioenergy crop adaptation and agro-ecosystem services

NASA Astrophysics Data System (ADS)

Hays, D. B.; Delgado, A.; Bruton, R.; Dobreva, I. D.; Teare, B.; Jessup, R.; Rajan, N.; Bishop, M. P.; Lacey, R.; Neely, H.; Hons, F.; Novo, A.

2016-12-01

Selection of the ideal high biomass energy feedstock and crop cultivars for our national energy and production needs should consider not only the value of the harvested above ground feedstock, but also the local and global environmental services it provides in terms of terrestrial carbon (C) phyto-sequestration and improved soil organic matter enrichment. Selection of ideal crops cultivars is mature, while biofuel feedstock is well under way. What is lacking, however, is high throughput phenotyping (HTP) and integrated real-time data analysis technologies for selecting ideal genotypes within these crops that also confer recalcitrant high biomass or perennial root systems not only for C phyto-sequestration, but also for adaptation to conservation agro-ecosystems, increasing soil organic matter and soil water holding capacity. In no-till systems, significant studies have shown that increasing soil organic carbon is derived primarily from root and not above ground biomass. As such, efforts to increase plant soil phyto-sequestration will require a focus on developing optimal root systems within cultivated crops. We propose to achieve a significant advancement in the use of ground penetrating radar (GPR) as one approach to phenotype root biomass and 3D architecture, and to quantify soil carbon sequestration. In this context, GPR can be used for genotypic selection in breeding nurseries and unadapted germplasm with favorable root architectures, and for assessing management and nutrient practices that promote root growth. GPR has been used for over a decade to successfully map coarse woody roots. Only few have evaluated its efficacy for imaging finer fibrous roots found in grasses, or tap root species. The objectives of this project is to: i) Empirically define the optimal ground penetrating radar (GPR)-antenna array for 3D root and soil organic carbon imaging and quantification in high biomass grass systems; and ii) Develop novel 3- and 4-dimensional data analysis methodologies for using GPR for non-invasive crop root and soil C phyto-sequestration 3-D imaging and quantification within a spatially variable soil matrix. Current results and future directions will be presented and discussed.

G protein-coupled receptor 84 controls osteoclastogenesis through inhibition of NF-κB and MAPK signaling pathways.

PubMed

Park, Ji-Wan; Yoon, Hye-Jin; Kang, Woo Youl; Cho, Seungil; Seong, Sook Jin; Lee, Hae Won; Yoon, Young-Ran; Kim, Hyun-Ju

2018-02-01

GPR84, a member of the G protein-coupled receptor family, is found predominantly in immune cells, such as macrophages, and functions as a pivotal modulator of inflammatory responses. In this study, we investigated the role of GPR84 in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. Our microarray data showed that GPR84 was significantly downregulated in osteoclasts compared to in their precursors, macrophages. The overexpression of GPR84 in bone marrow-derived macrophages suppressed the formation of multinucleated osteoclasts without affecting precursor proliferation. In addition, GPR84 overexpression attenuated the induction of c-Fos and nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), which are transcription factors that are critical for osteoclastogenesis. Furthermore, knockdown of GPR84 using a small hairpin RNA promoted RANKL-mediated osteoclast differentiation and gene expression of osteoclastogenic markers. Mechanistically, GPR84 overexpression blocked RANKL-stimulated phosphorylation of IκBα and three MAPKs, JNK, ERK, and p38. GPR84 also suppressed NF-κB transcriptional activity mediated by RANKL. Conversely, GPR84 knockdown enhanced RANKL-induced activation of IκBα and the three MAPKs. Collectively, our results revealed that GPR84 functions as a negative regulator of osteoclastogenesis, suggesting that it may be a potential therapeutic target for osteoclast-mediated bone-destructive diseases. © 2017 Wiley Periodicals, Inc.

G protein-coupled receptor 30 is critical for a progestin-induced growth inhibition in MCF-7 breast cancer cells.

PubMed

Ahola, Tytti M; Manninen, Tommi; Alkio, Niina; Ylikomi, Timo

2002-09-01

The issue of how progesterone affects mammary gland growth is controversial, and the mechanism governing the effects of the hormone remains mostly unknown. We have previously shown that G protein-coupled receptor 30 (GPR30) is a progestin target gene whose expression correlates with progestin-induced growth inhibition in breast cancer cells. In this study, we investigate the role of GPR30 in regulating cell proliferation and mediating progestin-induced growth inhibition. When progestin failed to inhibit the growth of MCF-7 cells and instead stimulated growth, GPR30 was down-regulated. In this way, the inhibitory or stimulatory affects that progestin has on proliferation correlated with the level of expression of GPR30. Transient expression of GPR30 resulted in a marked inhibition of cell proliferation independent of estrogen treatment. GPR30 antisense was used to evaluate the role of GPR30 expression in progestin-induced growth inhibition. A diminished GPR30 mRNA expression by the antisense stimulated growth. Interestingly, GPR30 antisense abrogated the growth inhibitory effect of progestin and progesterone. Indeed, progestin induced 1) a reduction in cell proliferation, 2) G1-phase arrest, and 3) down-regulation of cyclin D1 was diminished. These data suggest that the orphan receptor, GPR30, is important for the inhibitory effect of progestin on growth.

Estradiol and tamoxifen induce cell migration through GPR30 and activation of focal adhesion kinase (FAK) in endometrial cancers with low or without nuclear estrogen receptor α (ERα).

PubMed

Tsai, Chia-Lung; Wu, Hsien-Ming; Lin, Chiao-Yun; Lin, Yi-Jun; Chao, Angel; Wang, Tzu-Hao; Hsueh, Swei; Lai, Chyong-Huey; Wang, Hsin-Shih

2013-01-01

Estrogens and tamoxifen (an antiestrogen) exert their actions by activation of estrogen receptor (ER) through genomic and non-genomic mechanisms and are implicated in the development of endometrial cancer. Previous reports have demonstrated that estradiol and tamoxifen induce proliferation of human endometrial cancer cells through GPR30 (non-genomic ER) signaling pathway. Herein, we demonstrate that phosphorylation of focal adhesion kinase (FAK) is involved in cell migration induced by estradiol, tamoxifen and G1 (a GPR30 agonist) through the transmembrane ER (GPR30) in endometrial cancer cell lines with or without ERα (Ishikawa and RL95-2). Additionally, the GPR30-mediated cell migration was further abolished by administration of either specific RNA interference targeting GPR30 or an FAK inhibitor. Moreover, we have validated that the signaling between GPR30 and phosphorylated FAK is indeed mediated by the EGFR/PI3K/ERK pathway. Clinically, a significant correlation between levels of GPR30 and phophorylated FAK (pFAK) observed in human endometrial cancer tissues with low or without ERα further suggested that estrogen-induced phosphorylation of FAK and cell migration were most likely triggered by GPR30 activation. These results provided new insights for understanding the pathophysiological functions of GPR30 in human endometrial cancers.

A FDTD solution of scattering of laser beam with orbital angular momentum by dielectric particles: Far-field characteristics

NASA Astrophysics Data System (ADS)

Sun, Wenbo; Hu, Yongxiang; Weimer, Carl; Ayers, Kirk; Baize, Rosemary R.; Lee, Tsengdar

2017-02-01

Electromagnetic (EM) beams with orbital angular momentum (OAM) may have great potential applications in communication technology and in remote sensing of the Earth-atmosphere system and outer planets. Study of their interaction with optical lenses and dielectric or metallic objects, or scattering of them by particles in the Earth-atmosphere system, is a necessary step to explore the advantage of the OAM EM beams. In this study, the 3-dimensional (3D) scattered-field (SF) finite-difference time domain (FDTD) technique with the convolutional perfectly matched layer (CPML) absorbing boundary conditions (ABC) is applied to calculate the scattering of the purely azimuthal (the radial mode number is assumed to be zero) Laguerre-Gaussian (LG) beams with the OAM by dielectric particles. We found that for OAM beam's interaction with dielectric particles, the forward-scattering peak in the conventional phase function (P11) disappears, and light scattering peak occurs at a scattering angle of 15° to 45°. The disappearance of forward-scattering peak means that, in laser communications most of the particle-scattered noise cannot enter the receiver, thus the received light is optimally the original OAM-encoded signal. This feature of the OAM beam also implies that in lidar remote sensing of the atmospheric particulates, most of the multiple-scattering energy will be off lidar sensors, and this may result in an accurate profiling of particle layers in the atmosphere or in the oceans by lidar, or even in the ground when a ground penetration radar (GPR) with the OAM is applied. This far-field characteristics of the scattered OAM light also imply that the optical theorem, which is derived from plane-parallel wave scattering case and relates the forward scattering amplitude to the total cross section of the scatterer, is invalid for the scattering of OAM beams by dielectric particles.

Expression of the long-chain fatty acid receptor GPR120 in the gonadotropes of the mouse anterior pituitary gland.

PubMed

Moriyama, Ryutaro; Deura, Chikaya; Imoto, Shingo; Nose, Kazuhiro; Fukushima, Nobuyuki

2015-01-01

G-protein-coupled receptor 120 (GPR120) has been known to be a receptor of long-chain fatty acids. Here, we investigated GPR120 expression in the mouse pituitary gland via real-time PCR, in situ hybridization, and immunohistochemistry. GPR120 mRNA was abundantly expressed in the pituitary gland of ad-lib fed animals. In situ hybridization and immunohistochemistry revealed GPR120 expression in the gonadotropes of the anterior pituitary gland, but not in thyrotropes, somatotropes, lactotropes, corticotropes, melanotropes, and the posterior pituitary gland. Furthermore, 24 h of fasting induced an increase in GPR120 mRNA expression in the pituitary gland. These results demonstrate that GPR120 in mouse pituitary gonadotropes is upregulated by fasting and that it may play a role in controlling gonadotropin secretion.

Inflammatory changes in adipose tissue enhance expression of GPR84, a medium-chain fatty acid receptor: TNFα enhances GPR84 expression in adipocytes.

PubMed

Nagasaki, Hiroshi; Kondo, Takaaki; Fuchigami, Masahiro; Hashimoto, Hiroyuki; Sugimura, Yoshihisa; Ozaki, Nobuaki; Arima, Hiroshi; Ota, Akira; Oiso, Yutaka; Hamada, Yoji

2012-02-17

In this study we aimed to identify the physiological roles of G protein-coupled receptor 84 (GPR84) in adipose tissue, together with medium-chain fatty acids (MCFAs), the specific ligands for GPR84. In mice, high-fat diet up-regulated GPR84 expression in fat pads. In 3T3-L1 adipocytes, co-culture with a macrophage cell line, RAW264, or TNFα remarkably enhanced GPR84 expression. In the presence of TNFα, MCFAs down-regulated adiponectin mRNA expression in 3T3-L1 adipocytes. Taken together, our results suggest that GPR84 emerges in adipocytes in response to TNFα from infiltrating macrophages and exacerbates the vicious cycle between adiposity and diabesity. Copyright © 2012 Federation of European Biochemical Societies. All rights reserved.

Fatty acid receptor GPR120: a novel marker for human melanoma.

PubMed

Kleemann, Johannes; Hrgovic, Igor; Ter-Nedden, Jan; Kleimann, Pia; Steinhorst, Katja; Härle, Katja; Müller, Jutta; Kaufmann, Roland; Meissner, Markus; Kippenberger, Stefan

2018-03-21

The correlation between ultraviolet radiation of the skin and melanoma incidence in humans is well established. Interestingly, epidemiologic data suggest also a correlation to an increased BMI pointing to metabolic trigger factors in melanoma pathogenesis. To substantiate this connection, we studied the expression of G-protein-coupled receptor 120 (GPR120), a receptor sensitive to unsaturated long-chain free fatty acids in melanoma tissues. One-hundred fourteen tissue sections histologically confirmed as nevi (n=32), primary melanoma (n=39), and melanoma metastasis (n=43) were immunohistochemically stained against GPR120. The staining was evaluated by three trained dermatopathologists and independently scored. Compared with nevi, primary melanoma and melanoma metastasis showed significantly higher levels of GPR120 staining. Only three out of 32 nevi showed strong GPR120 expression [median immunoreactivity-scoring system (IRS) score: 1, range: 0-10], whereas in primary melanomas 14 out of 39 were highly GPR120-positive (median IRS score: 7, range: 0-12) and in melanoma metastasis 27 out of 43 were highly GPR120-positive (median IRS score: 9, range: 0-12). GPR120 expression and tumor thickness (mm) show a statistically significant correlation in primary melanoma (P=0.011). Moreover, GPR120-positive staining was found throughout the epidermis and in sebaceous and sweat glands, which is yet not described. This study identified GPR120 as a novel marker for melanoma, indicating that melanoma cells are sensitive to free fatty acids. It is tempting to speculate that pharmacologically interfering with GPR120 signaling might improve melanoma therapy.

Quantifying reinforced concrete bridge deck deterioration using ground penetrating radar

NASA Astrophysics Data System (ADS)

Martino, Nicole Marie

Bridge decks are deteriorating at an alarming rate due to corrosion of the reinforcing steel, requiring billions of dollars to repair and replace them. Furthermore, the techniques used to assess the decks don't provide enough quantitative information. In recent years, ground penetrating radar (GPR) has been used to quantify deterioration by comparing the rebar reflection amplitudes to technologies serving as ground truth, because there is not an available amplitude threshold to distinguish healthy from corroded areas using only GPR. The goal of this research is to understand the relationship between GPR and deck deterioration, and develop a model to determine deterioration quantities with GPR alone. The beginning of this research determines that not only is the relationship between GPR and rebar corrosion stronger than the relationship between GPR and delaminations, but that the two are exceptionally correlated (90.2% and 86.6%). Next, multiple bridge decks were assessed with GPR and half-cell potential (HCP). Statistical parameters like the mean and skewness were computed for the GPR amplitudes of each deck, and coupled with actual corrosion quantities based on the HCP measurements to form a future bridge deck model that can be used to assess any deck with GPR alone. Finally, in order to understand exactly which component of rebar corrosion (rust, cracking or chloride) attenuates the GPR data, computational modeling was carried out to isolate each variable. The results indicate that chloride is the major contributor to the rebar reflection attenuation, and that computational modeling can be used to accurately simulate GPR attenuation due to chloride.

G Protein-Coupled Receptor 30 (GPR30) Expression Pattern in Inflammatory Bowel Disease Patients Suggests its Key Role in the Inflammatory Process. A Preliminary Study.

PubMed

Włodarczyk, Marcin; Sobolewska-Włodarczyk, Aleksandra; Cygankiewicz, Adam I; Jacenik, Damian; Piechota-Polańczyk, Aleksandra; Stec-Michalska, Krystyna; Krajewska, Wanda M; Fichna, Jakub; Wiśniewska-Jarosińska, Maria

2017-03-01

G protein-coupled receptor 30 (GPR30) is a recently de-orphanized estrogen receptor that mediates the effects of estrogens on different cells. It has been postulated that in inflammatory bowel diseases (IBD) activation of GPR30 blocks the pathways dependent on pro-inflammatory cytokines. The aim of our study was to investigate GPR30 expression in patients with IBD and its potential implication in future therapies. Fifty-seven patients were enrolled in our study: 20 subjects with Crohn's disease (CD), 22 with ulcerative colitis (UC) and 15 controls. In each subject, biopsies were taken from various left-colonic locations. Gene and protein expression of GPR30 was quantified using real time RT-PCR or Western blot. GPR30 mRNA and protein expression were detected in all tested colonic tissues. No significant differences in GPR30 gene expression were observed. In non-inflamed areas, GPR30 protein was strongly increased in CD patients, but moderately in UC patients (p= 0.014 and p=0.143, respectively, vs. controls). In CD patients, a significantly lower GPR30 protein content in inflamed than in non-inflamed tissue was observed (p=0.039). The change was independent of patient gender. Our observations indicate that GPR30 may play a role in the development and progression of inflammatory lesions in IBD, thus affecting disease severity, and consequently IBD treatment. Therefore, GPR30 may become an attractive target for novel anti-IBD drugs, particularly in CD.

Geophysical Surveys for Locating Buried Utilities, Lake Pontchartrain Levees, New Orleans

DTIC Science & Technology

2014-06-01

4 Figure 3. GPR concepts...this study. Electromagnetic (EM) induction, magnetic, and ground penetrating radar ( GPR ) geophysical methods were evaluated to determine which...surveys GPR is a ground-based geophysical instrument that transmits high- frequency EM pulses into the subsurface. The GPR system consists of a

GPR98 mutations cause Usher syndrome type 2 in males.

PubMed

Ebermann, I; Wiesen, M H J; Zrenner, E; Lopez, I; Pigeon, R; Kohl, S; Löwenheim, H; Koenekoop, R K; Bolz, H J

2009-04-01

Mutations in the large GPR98 gene underlie Usher syndrome type 2C (USH2C), and all patients described to date have been female. It was speculated that GPR98 mutations cause a more severe, and eventually lethal, phenotype in males. We describe for the first time two male patients with USH2 with novel GPR98 mutations. Clinical characterization of a male patient and his affected sister revealed a typical USH2 phenotype in both. GPR98 may have been excluded from systematic investigation in previous studies, and the proportion of patients with USH2C probably underestimated. GPR98 should be considered in patients with USH2 of both sexes.

In vivo functions of GPR30/GPER-1, a membrane receptor for estrogen: from discovery to functions in vivo.

PubMed

Mizukami, Yoichi

2010-01-01

G protein-coupled receptor 30/G protein-coupled estrogen receptor-1 (GPR30/GPER-1) was reported as a novel membrane receptor for estrogen in 2005. However, the research on GPR30 has produced conflicting reports with regard to its intracellular localization, the tissue distribution of its expression, and some its functions. Recently, in addition to the finding of G-1, a GPR30 agonist, GPR30 KO mice have been produced in laboratories, and this has significantly increased the confidence in the data. In this review, the intrinsic appearance of GPR30 is approached based mainly on data obtained in vivo.

Estimating active layer thickness and volumetric water content from ground penetrating radar measurements in Barrow, Alaska

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jafarov, E. E.; Parsekian, A. D.; Schaefer, K.

Ground penetrating radar (GPR) has emerged as an effective tool for estimating active layer thickness (ALT) and volumetric water content (VWC) within the active layer. In August 2013, we conducted a series of GPR and probing surveys using a 500 MHz antenna and metallic probe around Barrow, Alaska. Here, we collected about 15 km of GPR data and 1.5 km of probing data. We describe the GPR data processing workflow from raw GPR data to the estimated ALT and VWC. We then include the corresponding uncertainties for each measured and estimated parameter. The estimated average GPR-derived ALT was 41 cm,more » with a standard deviation of 9 cm. The average probed ALT was 40 cm, with a standard deviation of 12 cm. The average GPR-derived VWC was 0.65, with a standard deviation of 0.14.« less

GPR40 agonists for the treatment of type 2 diabetes: life after 'TAKing' a hit.

PubMed

Mancini, A D; Poitout, V

2015-07-01

The free fatty acid receptor GPR40 has been proposed as a potential target for type 2 diabetes (T2D) pharmacotherapy. This idea has been validated in both preclinical and clinical studies, in which activation of GPR40 was shown to improve glycaemic control by stimulating glucose-dependent insulin secretion; however, the recent termination of phase III clinical trials using the GPR40 agonist TAK-875 (fasiglifam) has raised important questions regarding the long-term safety and viability of targeting GPR40 and, more specifically, about our understanding of this receptor's basic biology. In the present review, we provide a summary of established and novel concepts related to GPR40's pharmacobiology and discuss the current status and future outlook for GPR40-based drug development for the treatment of T2D. © 2015 John Wiley & Sons Ltd.

Estimating active layer thickness and volumetric water content from ground penetrating radar measurements in Barrow, Alaska

DOE PAGES

Jafarov, E. E.; Parsekian, A. D.; Schaefer, K.; ...

2018-01-09

Ground penetrating radar (GPR) has emerged as an effective tool for estimating active layer thickness (ALT) and volumetric water content (VWC) within the active layer. In August 2013, we conducted a series of GPR and probing surveys using a 500 MHz antenna and metallic probe around Barrow, Alaska. Here, we collected about 15 km of GPR data and 1.5 km of probing data. We describe the GPR data processing workflow from raw GPR data to the estimated ALT and VWC. We then include the corresponding uncertainties for each measured and estimated parameter. The estimated average GPR-derived ALT was 41 cm,more » with a standard deviation of 9 cm. The average probed ALT was 40 cm, with a standard deviation of 12 cm. The average GPR-derived VWC was 0.65, with a standard deviation of 0.14.« less

Development of novel ligands for peptide GPCRs.

PubMed

Moran, Brian M; McKillop, Aine M; O'Harte, Finbarr Pm

2016-12-01

Incretin based glucagon-like peptide-1 receptor (GLP-1R) agonists which target a G-protein coupled receptor (GPCR) are currently used in the treatment of type 2 diabetes. This review focuses on GPCRs from pancreatic β-cells, including GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucagon, somatostatin, pancreatic polypeptide (PP), cholecystokinin (CCK), peptide YY (PYY), oxyntomodulin (OXM) and ghrelin receptors. In addition, fatty acids GPCRs are thought to have an increasing role in regulating peptide secretions namely short fatty acids GPCR (GPR41, GPR43), medium chain fatty acid GPCR (GPR84), long chain fatty acid GPCR (GPR40, GPR120) and cannabinoid-like GPCR (GPR55, GPR119). Several pre-clinical and clinical trials are currently ongoing in peptide GPCR based therapies, including dual and triple agonist peptides which activate two or more GPCRs simultaneously. Copyright © 2016 Elsevier Ltd. All rights reserved.

Protection of Primary Dopaminergic Midbrain Neurons by GPR139 Agonists Supports Different Mechanisms of MPP+ and Rotenone Toxicity

PubMed Central

Bayer Andersen, Kirsten; Leander Johansen, Jens; Hentzer, Morten; Smith, Garrick Paul; Dietz, Gunnar P. H.

2016-01-01

The G-protein coupled receptor 139 (GPR139) is expressed specifically in the brain in areas of relevance for motor control. GPR139 function and signal transduction pathways are elusive, and results in the literature are even contradictory. Here, we examined the potential neuroprotective effect of GPR139 agonism in primary culture models of dopaminergic (DA) neuronal degeneration. We find that in vitro GPR139 agonists protected primary mesencephalic DA neurons against 1-methyl-4-phenylpyridinium (MPP+)-mediated degeneration. Protection was concentration-dependent and could be blocked by a GPR139 antagonist. However, the protection of DA neurons was not found against rotenone or 6-hydroxydopamine (6-OHDA) mediated degeneration. Our results support differential mechanisms of toxicity for those substances commonly used in Parkinson’s disease (PD) models and potential for GPR139 agonists in neuroprotection. PMID:27445691

GPR56/ADGRG1 regulates development and maintenance of peripheral myelin.

PubMed

Ackerman, Sarah D; Luo, Rong; Poitelon, Yannick; Mogha, Amit; Harty, Breanne L; D'Rozario, Mitchell; Sanchez, Nicholas E; Lakkaraju, Asvin K K; Gamble, Paul; Li, Jun; Qu, Jun; MacEwan, Matthew R; Ray, Wilson Zachary; Aguzzi, Adriano; Feltri, M Laura; Piao, Xianhua; Monk, Kelly R

2018-03-05

Myelin is a multilamellar sheath generated by specialized glia called Schwann cells (SCs) in the peripheral nervous system (PNS), which serves to protect and insulate axons for rapid neuronal signaling. In zebrafish and rodent models, we identify GPR56/ADGRG1 as a conserved regulator of PNS development and health. We demonstrate that, during SC development, GPR56-dependent RhoA signaling promotes timely radial sorting of axons. In the mature PNS, GPR56 is localized to distinct SC cytoplasmic domains, is required to establish proper myelin thickness, and facilitates organization of the myelin sheath. Furthermore, we define plectin-a scaffolding protein previously linked to SC domain organization, myelin maintenance, and a series of disorders termed "plectinopathies"-as a novel interacting partner of GPR56. Finally, we show that Gpr56 mutants develop progressive neuropathy-like symptoms, suggesting an underlying mechanism for peripheral defects in some human patients with GPR56 mutations. In sum, we define Gpr56 as a new regulator in the development and maintenance of peripheral myelin. © 2018 Ackerman et al.

Genetic Coding Variant in GPR65 Alters Lysosomal pH and Links Lysosomal Dysfunction with Colitis Risk.

PubMed

Lassen, Kara G; McKenzie, Craig I; Mari, Muriel; Murano, Tatsuro; Begun, Jakob; Baxt, Leigh A; Goel, Gautam; Villablanca, Eduardo J; Kuo, Szu-Yu; Huang, Hailiang; Macia, Laurence; Bhan, Atul K; Batten, Marcel; Daly, Mark J; Reggiori, Fulvio; Mackay, Charles R; Xavier, Ramnik J

2016-06-21

Although numerous polymorphisms have been associated with inflammatory bowel disease (IBD), identifying the function of these genetic factors has proved challenging. Here we identified a role for nine genes in IBD susceptibility loci in antibacterial autophagy and characterized a role for one of these genes, GPR65, in maintaining lysosome function. Mice lacking Gpr65, a proton-sensing G protein-coupled receptor, showed increased susceptibly to bacteria-induced colitis. Epithelial cells and macrophages lacking GPR65 exhibited impaired clearance of intracellular bacteria and accumulation of aberrant lysosomes. Similarly, IBD patient cells and epithelial cells expressing an IBD-associated missense variant, GPR65 I231L, displayed aberrant lysosomal pH resulting in lysosomal dysfunction, impaired bacterial restriction, and altered lipid droplet formation. The GPR65 I231L polymorphism was sufficient to confer decreased GPR65 signaling. Collectively, these data establish a role for GPR65 in IBD susceptibility and identify lysosomal dysfunction as a potentially causative element in IBD pathogenesis with effects on cellular homeostasis and defense. Copyright © 2016 Elsevier Inc. All rights reserved.

Orphan Gpr182 suppresses ERK-mediated intestinal proliferation during regeneration and adenoma formation

PubMed Central

Kechele, Daniel O.; Blue, R. Eric; Zwarycz, Bailey; Espenschied, Scott T.; Mah, Amanda T.; Siegel, Marni B.; Perou, Charles M.; Ding, Shengli; Magness, Scott T.; Lund, P. Kay

2017-01-01

Orphan GPCRs provide an opportunity to identify potential pharmacological targets, yet their expression patterns and physiological functions remain challenging to elucidate. Here, we have used a genetically engineered knockin reporter mouse to map the expression pattern of the Gpr182 during development and adulthood. We observed that Gpr182 is expressed at the crypt base throughout the small intestine, where it is enriched in crypt base columnar stem cells, one of the most active stem cell populations in the body. Gpr182 knockdown had no effect on homeostatic intestinal proliferation in vivo, but led to marked increases in proliferation during intestinal regeneration following irradiation-induced injury. In the ApcMin mouse model, which forms spontaneous intestinal adenomas, reductions in Gpr182 led to more adenomas and decreased survival. Loss of Gpr182 enhanced organoid growth efficiency ex vivo in an EGF-dependent manner. Gpr182 reduction led to increased activation of ERK1/2 in basal and challenge models, demonstrating a potential role for this orphan GPCR in regulating the proliferative capacity of the intestine. Importantly, GPR182 expression was profoundly reduced in numerous human carcinomas, including colon adenocarcinoma. Together, these results implicate Gpr182 as a negative regulator of intestinal MAPK signaling–induced proliferation, particularly during regeneration and adenoma formation. PMID:28094771

The l-α-Lysophosphatidylinositol/GPR55 System and Its Potential Role in Human Obesity

PubMed Central

Moreno-Navarrete, José María; Catalán, Victoria; Whyte, Lauren; Díaz-Arteaga, Adenis; Vázquez-Martínez, Rafael; Rotellar, Fernando; Guzmán, Rocío; Gómez-Ambrosi, Javier; Pulido, Marina R.; Russell, Wendy R.; Imbernón, Mónica; Ross, Ruth A.; Malagón, María M.; Dieguez, Carlos; Fernández-Real, José Manuel; Frühbeck, Gema; Nogueiras, Ruben

2012-01-01

GPR55 is a putative cannabinoid receptor, and l-α-lysophosphatidylinositol (LPI) is its only known endogenous ligand. We investigated 1) whether GPR55 is expressed in fat and liver; 2) the correlation of both GPR55 and LPI with several metabolic parameters; and 3) the actions of LPI on human adipocytes. We analyzed CB1, CB2, and GPR55 gene expression and circulating LPI levels in two independent cohorts of obese and lean subjects, with both normal or impaired glucose tolerance and type 2 diabetes. Ex vivo experiments were used to measure intracellular calcium and lipid accumulation. GPR55 levels were augmented in the adipose tissue of obese subjects and further so in obese patients with type 2 diabetes when compared with nonobese subjects. Visceral adipose tissue GPR55 correlated positively with weight, BMI, and percent fat mass, particularly in women. Hepatic GPR55 gene expression was similar in obese and type 2 diabetic subjects. Circulating LPI levels were increased in obese patients and correlated with fat percentage and BMI in women. LPI increased the expression of lipogenic genes in visceral adipose tissue explants and intracellular calcium in differentiated visceral adipocytes. These findings indicate that the LPI/GPR55 system is positively associated with obesity in humans. PMID:22179809

G protein‐coupled receptor 37‐like 1 modulates astrocyte glutamate transporters and neuronal NMDA receptors and is neuroprotective in ischemia

PubMed Central

Jolly, Sarah; Bazargani, Narges; Quiroga, Alejandra C.; Pringle, Nigel P.

2017-01-01

Abstract We show that the G protein‐coupled receptor GPR37‐like 1 (GPR37L1) is expressed in most astrocytes and some oligodendrocyte precursors in the mouse central nervous system. This contrasts with GPR37, which is mainly in mature oligodendrocytes. Comparison of wild type and Gpr37l1–/– mice showed that loss of GPR37L1 did not affect the input resistance or resting potential of astrocytes or neurons in the hippocampus. However, GPR37L1‐mediated signalling inhibited astrocyte glutamate transporters and – surprisingly, given its lack of expression in neurons – reduced neuronal NMDA receptor (NMDAR) activity during prolonged activation of the receptors as occurs in ischemia. This effect on NMDAR signalling was not mediated by a change in the release of D‐serine or TNF‐α, two astrocyte‐derived agents known to modulate NMDAR function. After middle cerebral artery occlusion, Gpr37l1 expression was increased around the lesion. Neuronal death was increased by ∼40% in Gpr37l1–/– brain compared to wild type in an in vitro model of ischemia. Thus, GPR37L1 protects neurons during ischemia, presumably by modulating extracellular glutamate concentration and NMDAR activation. PMID:28795439

The oral lipid sensor GPR120 is not indispensable for the orosensory detection of dietary lipids in mice

PubMed Central

Ancel, Déborah; Bernard, Arnaud; Subramaniam, Selvakumar; Hirasawa, Akira; Tsujimoto, Gozoh; Hashimoto, Toshihiro; Passilly-Degrace, Patricia; Khan, Naim-Akhtar; Besnard, Philippe

2015-01-01

Implication of the long-chain fatty acid (LCFA) receptor GPR120, also termed free fatty acid receptor 4, in the taste-guided preference for lipids is a matter of debate. To further unravel the role of GPR120 in the “taste of fat”, the present study was conducted on GPR120-null mice and their wild-type littermates. Using a combination of morphological [i.e., immunohistochemical staining of circumvallate papillae (CVP)], behavioral (i.e., two-bottle preference tests, licking tests and conditioned taste aversion) and functional studies [i.e., calcium imaging in freshly isolated taste bud cells (TBCs)], we show that absence of GPR120 in the oral cavity was not associated with changes in i) gross anatomy of CVP, ii) LCFA-mediated increases in intracellular calcium levels ([Ca2+]i), iii) preference for oily and LCFA solutions and iv) conditioned avoidance of LCFA solutions. In contrast, the rise in [Ca2+]i triggered by grifolic acid, a specific GPR120 agonist, was dramatically curtailed when the GPR120 gene was lacking. Taken together, these data demonstrate that activation of lingual GPR120 and preference for fat are not connected, suggesting that GPR120 expressed in TBCs is not absolutely required for oral fat detection in mice PMID:25489006

GPR3 Stimulates Aβ Production via Interactions with APP and β-Arrestin2

PubMed Central

Nelson, Christopher D.; Sheng, Morgan

2013-01-01

The orphan G protein-coupled receptor (GPCR) GPR3 enhances the processing of Amyloid Precursor Protein (APP) to the neurotoxic beta-amyloid (Aβ) peptide via incompletely understood mechanisms. Through overexpression and shRNA knockdown experiments in HEK293 cells, we show that β-arrestin2 (βarr2), a GPCR-interacting scaffold protein reported to bind γ-secretase, is an essential factor for GPR3-stimulated Aβ production. For a panel of GPR3 receptor mutants, the degree of stimulation of Aβ production correlates with receptor-β-arrestin binding and receptor trafficking to endocytic vesicles. However, GPR3’s recruitment of βarr2 cannot be the sole explanation, because interaction with βarr2 is common to most GPCRs, whereas GPR3 is relatively unique among GPCRs in enhancing Aβ production. In addition to β-arrestin, APP is present in a complex with GPR3 and stimulation of Aβ production by GPR3 mutants correlates with their level of APP binding. Importantly, among a broader selection of GPCRs, only GPR3 and prostaglandin E receptor 2 subtype EP2 (PTGER2; another GPCR that increases Aβ production) interact with APP, and PTGER2 does so in an agonist-stimulated manner. These data indicate that a subset of GPCRs, including GPR3 and PTGER2, can associate with APP when internalized via βarr2, and thereby promote the cleavage of APP to generate Aβ. PMID:24069330

GPR3 Receptor, a Novel Actor in the Emotional-Like Responses

PubMed Central

Valverde, Olga; Célérier, Evelyne; Baranyi, Mária; Vanderhaeghen, Pierre; Maldonado, Rafael; Sperlagh, Beata; Vassart, Gilbert; Ledent, Catherine

2009-01-01

GPR3 is an orphan G protein-coupled receptor endowed with constitutive Gs signaling activity, which is expressed broadly in the central nervous system, with maximal expression in the habenula. We investigated the consequences of its genetic deletion in several behavioral paradigms and on neurotransmission. Compared to wild-type, hippocampal neurons from Gpr3−/− mice displayed lower basal intracellular cAMP levels, consistent with the strong constitutive activity of GPR3 in transiently transfected cells. Behavioral analyses revealed that Gpr3−/− mice exhibited a high level of avoidance of novel and unfamiliar environment, associated with increased stress reactivity in behavioral despair paradigms and aggressive behavior in the resident-intruder test. On the contrary, no deficit was found in the learning ability to avoid an aversive event in active avoidance task. The reduced ability of Gpr3 −/− mice to cope with stress was unrelated to dysfunction of the hypothalamic-pituitary-adrenal axis, with Gpr3−/− mice showing normal corticosterone production under basal or stressful conditions. In contrast, dramatic alterations of monoamine contents were found in hippocampus, hypothalamus and frontal cortex of Gpr3−/− mice. Our results establish a link between tonic stimulation of the cAMP signaling pathway by GPR3 and control of neurotransmission by monoamines throughout the forebrain. GPR3 qualifies as a new player in the modulation of behavioral responses to stress and constitutes a novel promising pharmacological target for treatment of emotional disorders. PMID:19259266

Pharmacology of GPR55 in yeast and identification of GSK494581A as a mixed-activity glycine transporter subtype 1 inhibitor and GPR55 agonist.

PubMed

Brown, Andrew J; Daniels, Dion A; Kassim, Mumta; Brown, Sue; Haslam, Carl P; Terrell, Victoria R; Brown, Jason; Nichols, Paula L; Staton, Penny C; Wise, Alan; Dowell, Simon J

2011-04-01

GPR55 is a G protein-coupled receptor activated by L-α-lysophosphatidylinositol and suggested to have roles in pain signaling, bone morphogenesis, and possibly in vascular endothelial cells. It has affinity for certain cannabinoids (molecules that interact with the cannabinoid CB(1) and CB(2) receptors), but investigation of its functional role in cell-based systems and in tissue has been limited by a lack of selective pharmacological tools. Here, we present our characterization of GPR55 in the yeast Saccharomyces cerevisiae and in human embryonic kidney (HEK293) cells. We describe GSK494581A (1-{2-fluoro-4-[1-(methyloxy)ethyl]phenyl}-4-{[4'-fluoro-4-(methylsulfonyl)-2-biphenylyl]carbonyl}piperazine), a selective small-molecule ligand of GPR55 identified through diversity screening. GSK494581A is one of a series of benzoylpiperazines originally identified and patented as inhibitors of the glycine transporter subtype 1 (GlyT1). The structure-activity relationship between GPR55 and GlyT1 is divergent across this series. The most GPR55-selective example is GSK575594A (3-fluoro-4-(4-{[4'-fluoro-4-(methylsulfonyl)-2-biphenylyl]carbonyl}-1-piperazinyl)aniline), which is approximately 60-fold selective for GPR55 (pEC(50) = 6.8) over GlyT1 (pIC(50) = 5.0). Several exemplars with activity at GPR55 and GlyT1 have been profiled at a broad range of other molecular targets and are inactive at cannabinoid receptors and all other targets tested. The benzoylpiperazine agonists activate human GPR55 but not rodent GPR55, suggesting that the relatively low level of sequence identity between these orthologs (75%) translates to important functional differences in the ligand-binding site.

Extracellular acidification activates ovarian cancer G-protein-coupled receptor 1 and GPR4 homologs of zebra fish

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mochimaru, Yuta; Azuma, Morio; Oshima, Natsuki

2015-02-20

Mammalian ovarian G-protein-coupled receptor 1 (OGR1) and GPR4 are identified as a proton-sensing G-protein-coupled receptor coupling to multiple intracellular signaling pathways. In the present study, we examined whether zebra fish OGR1 and GPR4 homologs (zOGR1 and zGPR4) could sense protons and activate the multiple intracellular signaling pathways and, if so, whether the similar positions of histidine residue, which is critical for sensing protons in mammalian OGR and GPR4, also play a role to sense protons and activate the multiple signaling pathways in the zebra fish receptors. We found that extracellular acidic pH stimulated CRE-, SRE-, and NFAT-promoter activities in zOGR1more » overexpressed cells and stimulated CRE- and SRE- but not NFAT-promoter activities in zGPR4 overexpressed cells. The substitution of histidine residues at the 12th, 15th, 162th, and 264th positions from the N-terminal of zOGR1 with phenylalanine attenuated the proton-induced SRE-promoter activities. The mutation of the histidine residue at the 78th but not the 84th position from the N-terminal of zGPR4 to phenylalanine attenuated the proton-induced SRE-promoter activities. These results suggest that zOGR1 and zGPR4 are also proton-sensing G-protein-coupled receptors, and the receptor activation mechanisms may be similar to those of the mammalian receptors. - Highlights: • Zebra fish OGR1 and GPR4 homologs (zOGR1, zGPR4) are proton-sensing receptors. • The signaling pathways activated by zOGR1 and zGPR4 are different. • Histidine residues critical for sensing protons are conserved.« less

The cannabinoid receptor CB1 modulates the signaling properties of the lysophosphatidylinositol receptor GPR55.

PubMed

Kargl, Julia; Balenga, Nariman; Parzmair, Gerald P; Brown, Andrew J; Heinemann, Akos; Waldhoer, Maria

2012-12-28

The G protein-coupled receptor (GPCR) 55 (GPR55) and the cannabinoid receptor 1 (CB1R) are co-expressed in many tissues, predominantly in the central nervous system. Seven transmembrane spanning (7TM) receptors/GPCRs can form homo- and heteromers and initiate distinct signaling pathways. Recently, several synthetic CB1 receptor inverse agonists/antagonists, such as SR141716A, AM251, and AM281, were reported to activate GPR55. Of these, SR141716A was marketed as a promising anti-obesity drug, but was withdrawn from the market because of severe side effects. Here, we tested whether GPR55 and CB1 receptors are capable of (i) forming heteromers and (ii) whether such heteromers could exhibit novel signaling patterns. We show that GPR55 and CB1 receptors alter each others signaling properties in human embryonic kidney (HEK293) cells. We demonstrate that the co-expression of FLAG-CB1 receptors in cells stably expressing HA-GPR55 specifically inhibits GPR55-mediated transcription factor activation, such as nuclear factor of activated T-cells and serum response element, as well as extracellular signal-regulated kinases (ERK1/2) activation. GPR55 and CB1 receptors can form heteromers, but the internalization of both receptors is not affected. In addition, we observe that the presence of GPR55 enhances CB1R-mediated ERK1/2 and nuclear factor of activated T-cell activation. Our data provide the first evidence that GPR55 can form heteromers with another 7TM/GPCR and that this interaction with the CB1 receptor has functional consequences in vitro. The GPR55-CB1R heteromer may play an important physiological and/or pathophysiological role in tissues endogenously co-expressing both receptors.

Comparing the GPR responses of real experiment and simulation of cavity

NASA Astrophysics Data System (ADS)

Yu, H.; Nam, M. J.; Kim, C.; Lee, D. K.

2017-12-01

Seoul, capital city of South Korea, has been suffering from ground subsidence mainly caused by cavities beneath the road. Urban subsidence usually brings serious social problems such as damages of human life, properties and so on. To prevent ground subsidence, Korea government embark much money in developing techniques to detect cavities in advance. Ground penetrating radar (GPR) is known as the most effective method among geophysical surveys in exploring underground cavitied but shallow ones only. For the study of GPR responses for underground cavities, real scale physical models have been made and GPR surveys are conducted. In simulating cavities with various sizes at various depths, spheres of polystyrene have been used since the electric permittivity of polystyrene has a similar value to that of the air. However, the real scale experiments only used simple shapes of cavities due to its expensive construction cost and further changing in shapes of cavities is limited once they are built. For not only comparison between field responses for the physical model and numerical responses but also for analyzing GPR responses for more various cavity shapes in numerous environments, we conducted numerical simulation of GPR responses using three-dimensional (3D) finite difference time domain (FDTD) GPR modeling algorithm employing staggered grid. We first construct numerical modeling for models similar to the physical models to confirm considering radiation pattern in numerical modeling of GPR responses which is critical to generate similar responses to field GPR data. Further, GPR responses computed for various shapes of cavities in several different environments determine not only additional construction of the physical cavities but also analyze the characteristics of GPR responses.

Microbial short chain fatty acid metabolites lower blood pressure via endothelial G protein-coupled receptor 41.

PubMed

Natarajan, Niranjana; Hori, Daijiro; Flavahan, Sheila; Steppan, Jochen; Flavahan, Nicholas A; Berkowitz, Dan E; Pluznick, Jennifer L

2016-11-01

Short chain fatty acid (SCFA) metabolites are byproducts of gut microbial metabolism that are known to affect host physiology via host G protein-coupled receptor (GPCRs). We previously showed that an acute SCFA bolus decreases blood pressure (BP) in anesthetized mice, an effect mediated primarily via Gpr41. In this study, our aims were to identify the cellular localization of Gpr41 and to determine its role in BP regulation. We localized Gpr41 to the vascular endothelium using RT-PCR: Gpr41 is detected in intact vessels (with endothelium) but is absent from denuded vessels (without endothelium). Furthermore, using pressure myography we confirmed that SCFAs dilate resistance vessels in an endothelium-dependent manner. Since we previously found that Gpr41 mediates a hypotensive response to acute SCFA administration, we hypothesized that Gpr41 knockout (KO) mice would be hypertensive. Here, we report that Gpr41 KO mice have isolated systolic hypertension compared with wild-type (WT) mice; diastolic BP was not different between WT and KO. Older Gpr41 KO mice also exhibited elevated pulse wave velocity, consistent with a phenotype of systolic hypertension; however, there was no increase in ex vivo aorta stiffness (measured by mechanical tensile testing). Plasma renin concentrations were also similar in KO and WT mice. The systolic hypertension in Gpr41 KO is not salt sensitive, as it is not significantly altered on either a high- or low-salt diet. In sum, these studies suggest that endothelial Gpr41 lowers baseline BP, likely by decreasing active vascular tone without altering passive characteristics of the blood vessels, and that Gpr41 KO mice have hypertension of a vascular origin. Copyright © 2016 the American Physiological Society.

The Cannabinoid Receptor CB1 Modulates the Signaling Properties of the Lysophosphatidylinositol Receptor GPR55*

PubMed Central

Kargl, Julia; Balenga, Nariman; Parzmair, Gerald P.; Brown, Andrew J.; Heinemann, Akos; Waldhoer, Maria

2012-01-01

The G protein-coupled receptor (GPCR) 55 (GPR55) and the cannabinoid receptor 1 (CB1R) are co-expressed in many tissues, predominantly in the central nervous system. Seven transmembrane spanning (7TM) receptors/GPCRs can form homo- and heteromers and initiate distinct signaling pathways. Recently, several synthetic CB1 receptor inverse agonists/antagonists, such as SR141716A, AM251, and AM281, were reported to activate GPR55. Of these, SR141716A was marketed as a promising anti-obesity drug, but was withdrawn from the market because of severe side effects. Here, we tested whether GPR55 and CB1 receptors are capable of (i) forming heteromers and (ii) whether such heteromers could exhibit novel signaling patterns. We show that GPR55 and CB1 receptors alter each others signaling properties in human embryonic kidney (HEK293) cells. We demonstrate that the co-expression of FLAG-CB1 receptors in cells stably expressing HA-GPR55 specifically inhibits GPR55-mediated transcription factor activation, such as nuclear factor of activated T-cells and serum response element, as well as extracellular signal-regulated kinases (ERK1/2) activation. GPR55 and CB1 receptors can form heteromers, but the internalization of both receptors is not affected. In addition, we observe that the presence of GPR55 enhances CB1R-mediated ERK1/2 and nuclear factor of activated T-cell activation. Our data provide the first evidence that GPR55 can form heteromers with another 7TM/GPCR and that this interaction with the CB1 receptor has functional consequences in vitro. The GPR55-CB1R heteromer may play an important physiological and/or pathophysiological role in tissues endogenously co-expressing both receptors. PMID:23161546

Atypical Responsiveness of the Orphan Receptor GPR55 to Cannabinoid Ligands*

PubMed Central

Kapur, Ankur; Zhao, Pingwei; Sharir, Haleli; Bai, Yushi; Caron, Marc G.; Barak, Larry S.; Abood, Mary E.

2009-01-01

The cannabinoid receptor 1 (CB1) and CB2 cannabinoid receptors, associated with drugs of abuse, may provide a means to treat pain, mood, and addiction disorders affecting widespread segments of society. Whether the orphan G-protein coupled receptor GPR55 is also a cannabinoid receptor remains unclear as a result of conflicting pharmacological studies. GPR55 has been reported to be activated by exogenous and endogenous cannabinoid compounds but surprisingly also by the endogenous non-cannabinoid mediator lysophosphatidylinositol (LPI). We examined the effects of a representative panel of cannabinoid ligands and LPI on GPR55 using a β-arrestin-green fluorescent protein biosensor as a direct readout of agonist-mediated receptor activation. Our data demonstrate that AM251 and SR141716A (rimonabant), which are cannabinoid antagonists, and the lipid LPI, which is not a cannabinoid receptor ligand, are GPR55 agonists. They possess comparable efficacy in inducing β-arrestin trafficking and, moreover, activate the G-protein-dependent signaling of protein kinase CβII. Conversely, the potent synthetic cannabinoid agonist CP55,940 acts as a GPR55 antagonist/partial agonist. CP55,940 blocks GPR55 internalization, the formation of β-arrestin GPR55 complexes, and the phosphorylation of ERK1/2; CP55,940 produces only a slight amount of protein kinase CβII membrane recruitment but does not stimulate membrane remodeling like LPI, AM251, or rimonabant. Our studies provide a paradigm for measuring the responsiveness of GPR55 to a variety of ligand scaffolds comprising cannabinoid and novel compounds and suggest that at best GPR55 is an atypical cannabinoid responder. The activation of GPR55 by rimonabant may be responsible for some of the off-target effects that led to its removal as a potential obesity therapy. PMID:19723626

Involvement of estrogen receptor variant ER-alpha36, not GPR30, in nongenomic estrogen signaling.

PubMed

Kang, Lianguo; Zhang, Xintian; Xie, Yan; Tu, Yaping; Wang, Dong; Liu, Zhenming; Wang, Zhao-Yi

2010-04-01

Accumulating evidence suggested that an orphan G protein-coupled receptor (GPR)30, mediates nongenomic responses to estrogen. The present study was performed to investigate the molecular mechanisms underlying GPR30 function. We found that knockdown of GPR30 expression in breast cancer SK-BR-3 cells down-regulated the expression levels of estrogen receptor (ER)-alpha36, a variant of ER-alpha. Introduction of a GPR30 expression vector into GPR30 nonexpressing cells induced endogenous ER-alpha36 expression, and cotransfection assay demonstrated that GPR30 activated the promoter activity of ER-alpha36 via an activator protein 1 binding site. Both 17beta-estradiol (E2) and G1, a compound reported to be a selective GPR30 agonist, increased the phosphorylation levels of the MAPK/ERK1/2 in SK-BR-3 cells, which could be blocked by an anti-ER-alpha36-specific antibody against its ligand-binding domain. G1 induced activities mediated by ER-alpha36, such as transcription activation activity of a VP16-ER-alpha36 fusion protein and activation of the MAPK/ERK1/2 in ER-alpha36-expressing cells. ER-alpha36-expressing cells, but not the nonexpressing cells, displayed high-affinity, specific E2 and G1 binding, and E2- and G1-induced intracellular Ca(2+) mobilization only in ER-alpha36 expressing cells. Taken together, our results demonstrated that previously reported activities of GPR30 in response to estrogen were through its ability to induce ER-alpha36 expression. The selective G protein-coupled receptor (GPR)30 agonist G1 actually interacts with ER-alpha36. Thus, the ER-alpha variant ER-alpha36, not GPR30, is involved in nongenomic estrogen signaling.

Downregulation of GPR83 in the hypothalamic preoptic area reduces core body temperature and elevates circulating levels of adiponectin.

PubMed

Dubins, Jeffrey S; Sanchez-Alavez, Manuel; Zhukov, Victor; Sanchez-Gonzalez, Alejandro; Moroncini, Gianluca; Carvajal-Gonzalez, Santos; Hadcock, John R; Bartfai, Tamas; Conti, Bruno

2012-10-01

The G protein-coupled receptor 83 (GPR83) was recently demonstrated in warm sensitive neurons (WSN) of the hypothalamic preoptic area (POA) that participate in temperature homeostasis. Thus, we investigated whether GPR83 may have a role in regulating core body temperature (CBT) by reducing its expression in the POA. Dissipation of energy in the form of heat is the primary mode of energy expenditure in mammals and can ultimately affect energy homeostasis. Thus, we also measured the level of important regulators of metabolism. Downregulation of GPR83 was obtained by lentiviral short-hairpin RNAs (shGPR83) vectors designed and selected for their ability to reduce GPR83 levels in vitro. Mice received POA injection of shGPR83 or non-silencing vectors and were monitored for CBT, motor activity, food intake body weight and circulating levels of IGF-1, insulin, leptin and adiponectin. Down-regulation of GPR83 in the POA resulted in a small (0.15°C) but significant reduction of CBT during the dark/active cycle of the day. Temperature reduction was followed by increased body weight gain independent of caloric intake. shGPR83 mice also had increased level of circulating adiponectin (31916±952 pg/mL vs. 23474±1507 pg/mL, P<.01) while no change was observed for insulin, IGF-1 or leptin. GPR83 may participate in central thermoregulation and the central control of circulating adiponectin. Further work is required to determine how GPR83 can affect POA WSN and what are the long term metabolic consequences of its down-regulation. Copyright © 2012 Elsevier Inc. All rights reserved.

Differential requirements of arrestin-3 and clathrin for ligand-dependent and -independent internalization of human G protein-coupled receptor 40.

PubMed

Qian, Jing; Wu, Chun; Chen, Xiaopan; Li, Xiangmei; Ying, Guoyuan; Jin, Lili; Ma, Qiang; Li, Guo; Shi, Ying; Zhang, Guozheng; Zhou, Naiming

2014-11-01

G protein-coupled receptor 40 (GPR40) is believed to be an attractive target to enhance insulin secretion in patients with type 2 diabetes. GPR40 has been found to couple to Gq protein, leading to the activation of phospholipase C and subsequent increases in the intracellular Ca(2+) level. However, the underlying mechanisms that regulate the internalization and desensitization of GPR40 remain to be elucidated. In the present study, a construct of GPR40 fused with enhanced green fluorescent protein (EGFP) at its C-terminus was constructed for direct imaging of the localization and internalization of GPR40 by confocal microscopy. In stably transfected HEK-293 cells, GPR40 receptors underwent rapid agonist-induced internalization and constitutive ligand-independent internalization. Our data demonstrated that the agonist-mediated internalization of GPR40 was significantly blocked by hypertonic sucrose treatment and by siRNA mediated depletion of the heavy chain of clathrin. In contrast, constitutive GPR40 internalization was not affected by hypertonic sucrose or by knock-down of clathrin expression, but it was affected by treatment with methyl-β-cyclodextrin (MβCD) and nystatin. Furthermore, our results using an arrestin-3-EGFP redistribution assay and siRNA-mediated knock-down of arrestin-3 and GRK2 expression revealed that arrestin-3 and GRK2 play an essential role in the regulation of agonist-mediated GPR40 internalization, but are not involved in the regulation of constitutive GPR40 internalization. Additionally, our observation showed that upon activation by agonist, the internalized GPR40 receptors were rapidly recycled back to the plasma membrane via Rab4/Rab5 positive endosomes, whereas the constitutively internalized GPR40 receptors were recycled back to the cell surface through Rab5 positive endosomes. Because FFA receptors exhibit a high level of homology, our observations could be applicable to other members of this family. Copyright © 2014 Elsevier Inc. All rights reserved.

Obstructive sleep apnea and obesity are associated with reduced GPR 120 plasma levels in children.

PubMed

Gozal, David; Kheirandish-Gozal, Leila; Carreras, Alba; Khalyfa, Abdelnaby; Peris, Eduard

2014-05-01

Obstructive sleep apnea (OSA) is a common health problem, particularly in obese children, in whom a vicious cycle of obesity and OSA interdependencies promotes increased food intake. G protein-coupled receptor 120 (GPR 120) is a long-chain free fatty acid (FFA) receptor that plays an important role in energy homeostasis, and protects against insulin resistance and systemic inflammation. We hypothesized that GPR 120 levels would be reduced in children with OSA, particularly among obese children. Cross-sectional prospectively recruited cohort. Academic pediatric sleep program. Two hundred twenty-six children (mean age: 7.0 ± 2.1 y) underwent overnight polysomnographic evaluation and a fasting blood draw the morning after the sleep study. In addition to lipid profile, homeostasis model assessment of insulin resistance (HOMA-IR) and high-sensitivity C-reactive protein (hsCRP) assays, monocyte GPR 120 expression, and plasma GPR 120 levels were assessed using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay kits. Obese children and those with OSA had significantly lower GPR 120 monocyte expression and plasma GPR 120 levels. Furthermore, when both obesity and OSA were present, GPR 120 levels were lowest. Linear associations emerged between GPR 120 plasma levels and body mass index (BMI) z score, as well as with apnea-hypopnea index (AHI), saturation of peripheral oxygen (SpO2) nadir, and respiratory arousal index (RAI), with RAI remaining statistically significant when controlling for age, ethnicity, sex, and BMI z score (P < 0.001). Similarly, HOMA-IR was significantly associated with GPR 120 levels, but neither low density lipoprotein nor high density lipoprotein cholesterol or hsCRP levels exhibited significant correlations. G protein-coupled receptor 120 (GPR 120) levels are reduced in pediatric OSA and obesity (particularly when both are present) and may play a role in modulating the degree of insulin resistance. The short- and long-term significance of reduced GPR 120 relative to food intake and glycemic deregulation remains undefined.

Hypothalamic GPR40 signaling activated by free long chain fatty acids suppresses CFA-induced inflammatory chronic pain.

PubMed

Nakamoto, Kazuo; Nishinaka, Takashi; Sato, Naoya; Mankura, Mitsumasa; Koyama, Yutaka; Kasuya, Fumiyo; Tokuyama, Shogo

2013-01-01

GPR40 has been reported to be activated by long-chain fatty acids, such as docosahexaenoic acid (DHA). However, reports studying functional role of GPR40 in the brain are lacking. The present study focused on the relationship between pain regulation and GPR40, investigating the functional roles of hypothalamic GPR40 during chronic pain caused using a complete Freund's adjuvant (CFA)-induced inflammatory chronic pain mouse model. GPR40 protein expression in the hypothalamus was transiently increased at day 7, but not at days 1, 3 and 14, after CFA injection. GPR40 was co-localized with NeuN, a neuron marker, but not with glial fibrillary acidic protein (GFAP), an astrocyte marker. At day 1 after CFA injection, GFAP protein expression was markedly increased in the hypothalamus. These increases were significantly inhibited by the intracerebroventricular injection of flavopiridol (15 nmol), a cyclin-dependent kinase inhibitor, depending on the decreases in both the increment of GPR40 protein expression and the induction of mechanical allodynia and thermal hyperalgesia at day 7 after CFA injection. Furthermore, the level of DHA in the hypothalamus tissue was significantly increased in a flavopiridol reversible manner at day 1, but not at day 7, after CFA injection. The intracerebroventricular injection of DHA (50 µg) and GW9508 (1.0 µg), a GPR40-selective agonist, significantly reduced mechanical allodynia and thermal hyperalgesia at day 7, but not at day 1, after CFA injection. These effects were inhibited by intracerebroventricular pretreatment with GW1100 (10 µg), a GPR40 antagonist. The protein expression of GPR40 was colocalized with that of β-endorphin and proopiomelanocortin, and a single intracerebroventricular injection of GW9508 (1.0 µg) significantly increased the number of neurons double-stained for c-Fos and proopiomelanocortin in the arcuate nucleus of the hypothalamus. Our findings suggest that hypothalamic GPR40 activated by free long chain fatty acids might have an important role in this pain control system.

G-Protein-Coupled Receptor Gpr17 Expression in Two Multiple Sclerosis Remyelination Models.

PubMed

Nyamoya, Stella; Leopold, Patrizia; Becker, Birte; Beyer, Cordian; Hustadt, Fabian; Schmitz, Christoph; Michel, Anne; Kipp, Markus

2018-06-05

In multiple sclerosis patients, demyelination is prominent in both the white and gray matter. Chronic clinical deficits are known to result from acute or chronic injury to the myelin sheath and inadequate remyelination. The underlying molecular mechanisms of remyelination and its failure remain currently unclear. Recent studies have recognized G protein-coupled receptor 17 (GPR17) as an important regulator of oligodendrocyte development and remyelination. So far, the relevance of GPR17 for myelin repair was mainly tested in remyelinating white matter lesions. The relevance of GPR17 for gray matter remyelination as well as remyelination of chronic white matter lesions was not addressed so far. Here, we provide a detailed characterization of GPR17 expression during experimental de- and remyelination. Experimental lesions with robust and limited endogenous remyelination capacity were established by either acute or chronic cuprizone-induced demyelination. Furthermore, remyelinating lesions were induced by the focal injection of lysophosphatidylcholine (LPC) into the corpus callosum. GPR17 expression was analyzed by complementary techniques including immunohistochemistry, in situ hybridization, and real-time PCR. In control animals, GPR17 + cells were evenly distributed in the corpus callosum and cortex and displayed a highly ramified morphology. Virtually all GPR17 + cells also expressed the oligodendrocyte-specific transcription factor OLIG2. After acute cuprizone-induced demyelination, robust endogenous remyelination was evident in the white matter corpus callosum but not in the gray matter cortex. Endogenous callosal remyelination was paralleled by a robust induction of GPR17 expression which was absent in the gray matter cortex. Higher numbers of GPR17 + cells were as well observed after LPC-induced focal white matter demyelination. In contrast, densities of GPR17 + cells were comparable to control animals after chronic cuprizone-induced demyelination indicating quiescence of this cell population. Our findings demonstrate that GPR17 expression induction correlates with acute demyelination and sufficient endogenous remyelination. This strengthens the view that manipulation of this receptor might be a therapeutic opportunity to support endogenous remyelination.

Increased Retinal Expression of the Pro-Angiogenic Receptor GPR91 via BMP6 in a Mouse Model of Juvenile Hemochromatosis

PubMed Central

Arjunan, Pachiappan; Gnanaprakasam, Jaya P.; Ananth, Sudha; Romej, Michelle A.; Rajalakshmi, Veeranan-Karmegam; Prasad, Puttur D.; Martin, Pamela M.; Gurusamy, Mariappan; Thangaraju, Muthusamy; Bhutia, Yangzom D.; Ganapathy, Vadivel

2016-01-01

Purpose Hemochromatosis, an iron-overload disease, occurs as adult and juvenile types. Mutations in hemojuvelin (HJV), an iron-regulatory protein and a bone morphogenetic protein (BMP) coreceptor, underlie most of the juvenile type. Hjv−/− mice accumulate excess iron in retina and exhibit aberrant vascularization and angiomas. A succinate receptor, GPR91, is pro-angiogenic in retina. We hypothesized that Hjv−/− retinas have increased BMP signaling and increased GPR91 expression as the basis of angiomas. Methods Expression of GPR91 was examined by qPCR, immunofluorescence, and Western blot in wild-type and Hjv−/− mouse retinas and pRPE cells. Influence of excess iron and BMP6 on GPR91 expression was investigated in ARPE-19 cells, and wild-type and Hjv−/− pRPE cells. Succinate was used to activate GPR91 and determine the effects of GPR91 signaling on VEGF expression. Signaling of BMP6 was studied by the expression of Smad1/5/8 and pSmad4, and the BMP-target gene Id1. The interaction of pSmad4 with GPR91 promoter was studied by ChIP. Results Expression of GPR91 was higher in Hjv−/− retinas and RPE than in wild-type counterparts. Unexpectedly, BMP signaling was increased, not decreased, in Hjv−/− retinas and RPE. Bone morphogenetic protein 6 induced GPR91 in RPE, suggesting that increased BMP signaling in Hjv−/− retinas was likely responsible for GPR91 upregulation. Exposure of RPE to excess iron and succinate as well as BMP6 and succinate increased VEGF expression. Bone morphogenetic protein 6 promoted the interaction of pSmad4 with GPR91 promoter in RPE. Conclusions G-protein-coupled receptor 91 is a BMP6 target and Hjv deletion enhances BMP signaling in retina, thus underscoring a role for excess iron and hemochromatosis in abnormal retinal vascularization. PMID:27046124

Increased Retinal Expression of the Pro-Angiogenic Receptor GPR91 via BMP6 in a Mouse Model of Juvenile Hemochromatosis.

PubMed

Arjunan, Pachiappan; Gnanaprakasam, Jaya P; Ananth, Sudha; Romej, Michelle A; Rajalakshmi, Veeranan-Karmegam; Prasad, Puttur D; Martin, Pamela M; Gurusamy, Mariappan; Thangaraju, Muthusamy; Bhutia, Yangzom D; Ganapathy, Vadivel

2016-04-01

Hemochromatosis, an iron-overload disease, occurs as adult and juvenile types. Mutations in hemojuvelin (HJV), an iron-regulatory protein and a bone morphogenetic protein (BMP) coreceptor, underlie most of the juvenile type. Hjv(-/-) mice accumulate excess iron in retina and exhibit aberrant vascularization and angiomas. A succinate receptor, GPR91, is pro-angiogenic in retina. We hypothesized that Hjv(-/-) retinas have increased BMP signaling and increased GPR91 expression as the basis of angiomas. Expression of GPR91 was examined by qPCR, immunofluorescence, and Western blot in wild-type and Hjv(-/-) mouse retinas and pRPE cells. Influence of excess iron and BMP6 on GPR91 expression was investigated in ARPE-19 cells, and wild-type and Hjv(-/-) pRPE cells. Succinate was used to activate GPR91 and determine the effects of GPR91 signaling on VEGF expression. Signaling of BMP6 was studied by the expression of Smad1/5/8 and pSmad4, and the BMP-target gene Id1. The interaction of pSmad4 with GPR91 promoter was studied by ChIP. Expression of GPR91 was higher in Hjv(-/-) retinas and RPE than in wild-type counterparts. Unexpectedly, BMP signaling was increased, not decreased, in Hjv(-/-) retinas and RPE. Bone morphogenetic protein 6 induced GPR91 in RPE, suggesting that increased BMP signaling in Hjv(-/-) retinas was likely responsible for GPR91 upregulation. Exposure of RPE to excess iron and succinate as well as BMP6 and succinate increased VEGF expression. Bone morphogenetic protein 6 promoted the interaction of pSmad4 with GPR91 promoter in RPE. G-protein-coupled receptor 91 is a BMP6 target and Hjv deletion enhances BMP signaling in retina, thus underscoring a role for excess iron and hemochromatosis in abnormal retinal vascularization.

GPR30 as an initiator of tamoxifen resistance in hormone-dependent breast cancer.

PubMed

Mo, Zhiqiang; Liu, Manran; Yang, Fangfang; Luo, Haojun; Li, Zhenhua; Tu, Gang; Yang, Guanglun

2013-11-29

Tamoxifen is widely used to treat hormone-dependent breast cancer, but its therapeutic benefit is limited by the development of drug resistance. Here, we investigated the role of estrogen G-protein coupled receptor 30 (GPR30) on Tamoxifen resistance in breast cancer. Primary tumors (PTs) of breast cancer and corresponding metastases (MTs) were used to evaluate the expression of GPR30 and epidermal growth factor receptor (EGFR) immunohistochemically. Tamoxifen-resistant (TAM-R) subclones derived from parent MCF-7 cells were used to investigate the role of GPR30 in the development of tamoxifen resistance, using MTT assay, western blot, RT-PCR, immunofluorescence, ELISA and flow cytometry. TAM-R xenografts were established to assess anti-tumor effects of combination therapy with GPR30 antagonist G15 plus 4-hydroxytamoxifen (Tam), using tumor volume measurement and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). In 53 human breast cancer specimens, GPR30 expression in MTs increased compared to matched PTs; in MTs, the expression patterns of GPR30 and EGFR were closely related. Compared to parent MCF-7 cells, TAM-R cells had greater growth responses to 17β-estradiol (E2), GPR30 agonist G1 and Tam, and significantly higher activation of Mitogen-activated protein (MAP) kinases; but this increased activity was abolished by G15 or AG1478. In TAM-R cells, GPR30 cell-surface translocation facilitated crosstalk with EGFR, and reduced cAMP generation, attenuating inhibition of EGFR signaling. Combination therapy both promoted apoptosis in TAM-R cells and decreased drug-resistant tumor progression. Long-term endocrine treatment facilitates the translocation of GPR30 to cell surfaces, which interferes with the EGFR signaling pathway; GPR30 also attenuates the inhibition of MAP kinases. These factors contribute to tamoxifen resistance development in breast cancer. Combination therapy with GPR30 inhibitors and tamoxifen may provide a new therapeutic option for drug-resistant breast cancer.

Embelin and its derivatives unravel the signaling, proinflammatory and antiatherogenic properties of GPR84 receptor.

PubMed

Gaidarov, Ibragim; Anthony, Todd; Gatlin, Joel; Chen, Xiaohua; Mills, David; Solomon, Michelle; Han, Sangdon; Semple, Graeme; Unett, David J

2018-05-01

GPR84 is an orphan G-protein coupled receptor, expressed on monocytes, macrophages and neutrophils and is significantly upregulated by inflammatory stimuli. The physiological role of GPR84 remains largely unknown. Medium chain fatty acids (MCFA) activate the receptor and have been proposed to be its endogenous ligands, although the high concentrations of MCFAs required for receptor activation generally exceed normal physiological levels. We identified the natural product embelin as a highly potent and selective surrogate GPR84 agonist (originally disclosed in patent application WO2007027661A2, 2007) and synthesized close structural analogs with widely varying receptor activities. These tools were used to perform a comprehensive study of GPR84 signaling and function in recombinant cells and in primary human macrophages and neutrophils. Activation of recombinant GPR84 by embelin in HEK293 cells results in G i/o as well as G12/13-Rho signaling. In human macrophages, GPR84 initiates PTX sensitive Erk1/2 and Akt phosphorylation, PI-3 kinase activation, calcium flux, and release of prostaglandin E2. In addition, GPR84 signaling in macrophages elicits G i Gβγ-mediated augmentation of intracellular cAMP, rather than the decrease expected from G iα engagement. GPR84 activation drives human neutrophil chemotaxis and primes them for amplification of oxidative burst induced by FMLP and C5A. Loss of GPR84 is associated with attenuated LPS-induced release of proinflammatory mediators IL-6, KC-GROα, VEGF, MIP-2 and NGAL from peritoneal exudates. While initiating numerous proinflammatory activities in macrophages and neutrophils, GPR84 also possesses GPR109A-like antiatherosclerotic properties in macrophages. Macrophage receptor activation leads to upregulation of cholesterol transporters ABCA1 and ABCG1 and stimulates reverse cholesterol transport. These data suggest that GPR84 may be a target of therapeutic value and that distinct modes of receptor modulation (inhibition vs. stimulation) may be required for inflammatory and atherosclerotic indications. Copyright © 2018 Elsevier Ltd. All rights reserved.

A Comprehensive Analysis of Swiss Alpine Glaciers Using Helicopter-Borne Ground-Penetrating-Radar

NASA Astrophysics Data System (ADS)

Rabenstein, L.; Maurer, H.; Bauder, A.; Langhammer, L.; Lucas, C.; Rutishauser, A.; Lathion, P.

2014-12-01

Detailed information exists on the surface area of glaciers in Switzerland and long-term mass balance observations are available but because glacial thickness remains elusive and so only a rough estimate of the present ice volume is available. After the successful recording of approximately 1000 km of helicopter ground penetrating radar (GPR) profiles on Swiss glaciers during the last three years, the Swiss Competence Center for Energy Research (SCCER) and the Swiss Geophysical Commission (SGPK) began an initiative to obtain for the first time an accurate estimate of the total ice volume located in the Swiss Alps. Steps towards this goal include the delineation of 3D bedrock topography beneath glacerized regions. The final ice volume estimation will comprise an ice flux computation model constrained by a dense network of helicopter-borne GPR profiles. Different systems that have been recently tested for acquiring helicopter GPR data in the Swiss Alps include towed systems (the HERA-G+ and the BGR-P30) and rigidly mounted systems of standard commercial GPR ground units (the GSSI and PulsEkko), all operating in the frequency range of 30 to 70 Mhz. Some measurements were ground-truthed using the same GPR antenna systems. Analyses of these data sets revealed a wealth of useful information on the glacier bed topography and some internal structures. For instance, at depths between 30 and 60 m, we often observe zones of low backscattering followed by a more reflective zone. In the glacial accumulation areas these features are interpreted as firn layers, in which the water percolates down to its base. The same test flights also provided useful technical information on the radar installation. For towed systems it is difficult to maintain a constant orientation of the antennas during the flight. In contrast, the rigidly mounted systems do not suffer from the orientation problem, but ringing effects are pronounced. We applied an SVD-based (singular value decomposition) multi-channel filter, which enabled this "system ringing" to be removed. Mostly, ground GPR surveys on coincident lines produce better quality GPR images of the glacier bed. However, it turned out that the orientation of the antennas relative to the glacier may be more important to retrieve good quality GPR data, than the surveying mode (airborne or ground).

Resolution of lava tubes with ground penetrating radar: preliminary results from the TubeX project

NASA Astrophysics Data System (ADS)

Esmaeili, S.; Kruse, S.; Garry, W. B.; Whelley, P.; Young, K.; Jazayeri, S.; Bell, E.; Paylor, R.

2017-12-01

As early as the mid 1970's it was postulated that planetary tubes or caves on other planetary bodies (i.e., the Moon or Mars) could provide safe havens for human crews, protect life and shield equipment from harmful radiation, rapidly fluctuating surface temperatures, and even meteorite impacts. What is not clear, however, are the exploration methods necessary to evaluate a potential tube-rich environment to locate suitable tubes suitable for human habitation. We seek to address this knowledge gap using a suite of instruments to detect and document tubes in a terrestrial analog study at Lava Beds National Monument, California, USA. Here we describe the results of ground penetrating radar (GPR) profiles and light detection and ranging (LiDAR) scans. Surveys were conducted from the surface and within four lava tubes (Hercules Leg, Skull, Valentine and, Indian Well Caves) with varying flow composition, shape, and complexity. Results are shown across segments of these tubes where the tubes are <1 m to ranging > 10 m in height and the ceilings are 1 - 10 m below the surface. The GPR profiles over the tubes are, as expected, complex, due to scattering from fractures in roof material and three-dimensional heterogeneities. Point clouds derived from the LiDAR scans of both the interior and exterior of the lava tubes provide precise positioning of the tube geometry and depth of the ceiling and floor with respect to the surface topography. GPR profiles over LiDAR-mapped tube cross-sections are presented and compared against synthetic models of radar response to the measured geometry. This comparison will help to better understand the origins of characteristic features in the radar profiles. We seek to identify the optimal data processing and migration approaches to aid lava tube exploration of planetary surfaces.

Road analysis: a tool for cost-effective rehabilitation measures for Finnish roads

NASA Astrophysics Data System (ADS)

Roimela, Petri; Salmenkaita, Seppo; Maijala, Pekka; Saarenketo, Timo

2000-04-01

Public funding for road network maintenance has decreased 30% during the last few years in Finland. Reduced resources, together with the current rehabilitation strategies, will in the long term result in increasing deterioration of the Finnish road network. For this reason road rehabilitation funding should be focused more specifically on those roads and road sections requiring measures and these measures should be optimized to ensure that only the specific problem structure will be repaired. Roadscanners Oy, in cooperation with the Finnish National Road Administration (Finnra), has developed a new and effective Road Analysis technique to survey the condition of roads and road networks. Road Analysis is based on the integrated analysis of the measured data collected from the road under survey. The basic survey methods used in Road Analysis include Ground Penetrating Data (GPR), falling weight deflectometer (FWD), roughness and rutting measurements, pavement distress mapping and GPS-positioning, as well as reference drilling based on preliminary GPR data analysis. The collected road survey data is processed, interpreted, analyzed and classified using Road Doctor software, specifically developed for this purpose. GPR measurements in road analysis are carried out using a 400 MHz ground-coupled antenna and a 1.0 GHz horn antenna. Horn antenna data is used to measure the thickness of the pavement and base course layers, as well as to evaluate their quality based on their dielectric properties. The 400 MHz ground-coupled data is used to estimate the thickness of the pavement structure and embankment. Ground-coupled antenna data is used for subgrade quality estimations and in evaluating the causes of subgrade- related frost defects. GPR data also provides important location information about special structures, such as steel reinforcements, cables and pipelines. Road Analysis includes a classification of the critical elements affecting the lifetime of the road: (1) overall pavement condition, (2) condition assessment of the unbound pavement structure, (3) road fatigue related to subgrade frost-action, (4) drainage condition and (5) local damages, such as settlements of the surveyed road. The results of Road Analysis provide a better understanding of the causes of defects occurring on the road and allow more precise rehabilitation measures for problem layers.

Resolving carbonate platform geometries on the Island of Bonaire, Caribbean Netherlands through semi-automatic GPR facies classification

NASA Astrophysics Data System (ADS)

Bowling, R. D.; Laya, J. C.; Everett, M. E.

2018-07-01

The study of exposed carbonate platforms provides observational constraints on regional tectonics and sea-level history. In this work Miocene-aged carbonate platform units of the Seroe Domi Formation are investigated on the island of Bonaire, located in the Southern Caribbean. Ground penetrating radar (GPR) was used to probe near-surface structural geometries associated with these lithologies. The single cross-island transect described herein allowed for continuous mapping of geologic structures on kilometre length scales. Numerical analysis was applied to the data in the form of k-means clustering of structure-parallel vectors derived from image structure tensors. This methodology enables radar facies along the survey transect to be semi-automatically mapped. The results provide subsurface evidence to support previous surficial and outcrop observations, and reveal complex stratigraphy within the platform. From the GPR data analysis, progradational clinoform geometries were observed on the northeast side of the island which support the tectonics and depositional trends of the region. Furthermore, several leeward-side radar facies are identified which correlate to environments of deposition conducive to dolomitization via reflux mechanisms.

A subagging regression method for estimating the qualitative and quantitative state of groundwater

NASA Astrophysics Data System (ADS)

Jeong, Jina; Park, Eungyu; Han, Weon Shik; Kim, Kue-Young

2017-08-01

A subsample aggregating (subagging) regression (SBR) method for the analysis of groundwater data pertaining to trend-estimation-associated uncertainty is proposed. The SBR method is validated against synthetic data competitively with other conventional robust and non-robust methods. From the results, it is verified that the estimation accuracies of the SBR method are consistent and superior to those of other methods, and the uncertainties are reasonably estimated; the others have no uncertainty analysis option. To validate further, actual groundwater data are employed and analyzed comparatively with Gaussian process regression (GPR). For all cases, the trend and the associated uncertainties are reasonably estimated by both SBR and GPR regardless of Gaussian or non-Gaussian skewed data. However, it is expected that GPR has a limitation in applications to severely corrupted data by outliers owing to its non-robustness. From the implementations, it is determined that the SBR method has the potential to be further developed as an effective tool of anomaly detection or outlier identification in groundwater state data such as the groundwater level and contaminant concentration.

Resolving Carbonate Platform Geometries on the Island of Bonaire, Caribbean Netherlands through Semi-Automatic GPR Facies Classification

NASA Astrophysics Data System (ADS)

Bowling, R. D.; Laya, J. C.; Everett, M. E.

2018-05-01

The study of exposed carbonate platforms provides observational constraints on regional tectonics and sea-level history. In this work Miocene-aged carbonate platform units of the Seroe Domi Formation are investigated, on the island of Bonaire, located in the Southern Caribbean. Ground penetrating radar (GPR) was used to probe near-surface structural geometries associated with these lithologies. The single cross-island transect described herein allowed for continuous mapping of geologic structures on kilometer length scales. Numerical analysis was applied to the data in the form of k-means clustering of structure-parallel vectors derived from image structure tensors. This methodology enables radar facies along the survey transect to be semi-automatically mapped. The results provide subsurface evidence to support previous surficial and outcrop observations, and reveal complex stratigraphy within the platform. From the GPR data analysis, progradational clinoform geometries were observed on the northeast side of the island which supports the tectonics and depositional trends of the region. Furthermore, several leeward-side radar facies are identified which correlate to environments of deposition conducive to dolomitization via reflux mechanisms.

Ground Penetrating Radar For Estimating Root Biomass Through Empirical Analysis

NASA Astrophysics Data System (ADS)

Wolfe, M.; Dobreva, I. D.; Delgado, A.; Hays, D. B.; Bishop, M. P.; Huo, D.; Wang, X.; Teare, B. L.; Burris, S.

2017-12-01

Variability in soil carbon storage due to agricultural practices is an important component of the carbon cycle. Enhancing soil organic content is a means for restoring degraded soils and for improving soil quality, but also for carbon sequestration. In particular, accurate estimates of soil organic content are essential for quantifying carbon sequestration capabilities of agricultural systems. This project aims to advance the technological and analytical capabilities of Ground Penetrating Radar (GPR) for diagnoses of the soil carbon storage occurring due to the perennial grasses which are often utilized as biofuels. A new GPR processing workflow applied via a prototype software was tested on simulated GPR data of roots with different densities and depths to determine the sensitivity and capability of this technology to quantify these parameters. Field experiments were also conducted in long-term trials of different genotypes of perennial grasses over field sites in Texas to determine the application in authentic environments. GPR scans and soil samples were collected, and root dry biomass was obtained. Evaluation of pre-processing techniques was conducted to provide optimal resolution for assessment. The novel backscatter spatial structure workflow was implemented, and empirical relationships between root biomass and GPR derived observations were developed. Preliminary results suggest that the backscatter spatial structure changes in the presence of high density root biomass conditions, and these variations are indicative of root zone depth and density. Our results illustrate promising applications in root detection, and therefore, the soil organic content accumulation that is pertinent to a healthy soil system.

Investigating the Capabilities of Ground Penetrating Radar for Imaging Shallow Experimental Fractures

NASA Astrophysics Data System (ADS)

Dogan, M.; Moysey, S. M.; Murdoch, L. C.; Denison, J. L. S.; Ahmadian, M.

2017-12-01

We have used ground penetrating radar (GPR) to image fractures formed in shallow sediments as a result of high-pressure injection. Understanding fracture formation and behavior is important for a variety of reasons, ranging from validating fracture formation theories to characterizing fracture networks induced for enhancing recovery schemes in low permeability rocks. GPR is a high resolution geophysical method that is sensitive to electromagnetic property changes in the subsurface. The resolution of GPR is, however, typically on the order of ¼ of the wavelength, which for the 900MHz GPR data is on the order of 2-5cm. Thus it was not clear prior to the experiment whether it would be possible for GPR to image the fractures formed during the injection. We found that the GPR was indeed able to image the fractures very well as they evolved through time. Over the course of the experiment, we were able to collect pseudo-3D data that allowed us to monitor the growth of the fracture over time. The experiment was also repeated for different injection materials to examine how the fill in the fractures impacts the GPR signal. From the GPR data we are able to reconstruct the approximate three-dimensional shape of the facture over time. At the end of the experiment, the experimental cells were trenched so that the actual fracture distribution could be mapped. Overall, the GPR interpretation showed reasonable agreement with what we could observed in the trenches. The experimental results suggest that GPR characterization of fractures is feasible.

G-protein coupled receptor 30 (GPR30): a novel regulator of endothelial inflammation.

PubMed

Chakrabarti, Subhadeep; Davidge, Sandra T

2012-01-01

Estrogen, the female sex hormone, is known to exert anti-inflammatory and anti-atherogenic effects. Traditionally, estrogen effects were believed to be largely mediated through the classical estrogen receptors (ERs). However, there is increasing evidence that G-protein coupled receptor 30 (GPR30), a novel estrogen receptor, can mediate many estrogenic effects on the vasculature. Despite this, the localization and functional significance of GPR30 in the human vascular endothelium remains poorly understood. Given this background, we examined the subcellular location and potential anti-inflammatory roles of GPR30 using human umbilical vein endothelial cells as a model system. Inflammatory changes were induced by treatment with tumor necrosis factor (TNF), a pro-inflammatory cytokine involved in atherogenesis and many other inflammatory conditions. We found that GPR30 was located predominantly in the endothelial cell nuclei. Treatment with the selective GPR30 agonist G-1 partially attenuated the TNF induced upregulation of pro-inflammatory proteins such as intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). This effect was completely abolished by the selective GPR30 antagonist G-15, suggesting that it was indeed mediated in a GPR30 dependent manner. Interestingly, estrogen alone had no effects on TNF-treated endothelium. Concomitant activation of the classical ERs blocked the anti-inflammatory effects of G-1, indicating opposing effects of GPR30 and the classical ERs. Our findings demonstrate that endothelial GPR30 is a novel regulator of the inflammatory response which could be a potential therapeutic target against atherosclerosis and other inflammatory diseases.

Interpreting DNAPL saturations in a laboratory-scale injection using one- and two-dimensional modeling of GPR Data

USGS Publications Warehouse

Johnson, R.H.; Poeter, E.P.

2005-01-01

Ground-penetrating radar (GPR) is used to track a dense non-aqueous phase liquid (DNAPL) injection in a laboratory sand tank. Before modeling, the GPR data provide a qualitative image of DNAPL saturation and movement. One-dimensional (1D) GPR modeling provides a quantitative interpretation of DNAPL volume within a given thickness during and after the injection. DNAPL saturation in sublayers of a specified thickness could not be quantified because calibration of the 1D GPR model is nonunique when both permittivity and depth of multiple layers are unknown. One-dimensional GPR modeling of the sand tank indicates geometric interferences in a small portion of the tank. These influences are removed from the interpretation using an alternate matching target. Two-dimensional (2D) GPR modeling provides a qualitative interpretation of the DNAPL distribution through pattern matching and tests for possible 2D influences that are not accounted for in the 1D GPR modeling. Accurate quantitative interpretation of DNAPL volumes using GPR modeling requires (1) identification of a suitable target that produces a strong reflection and is not subject to any geometric interference; (2) knowledge of the exact depth of that target; and (3) use of two-way radar-wave travel times through the medium to the target to determine the permittivity of the intervening material, which eliminates reliance on signal amplitude. With geologic conditions that are suitable for GPR surveys (i.e., shallow depths, low electrical conductivities, and a known reflective target), the procedures in this laboratory study can be adapted to a field site to delineate shallow DNAPL source zones.

9- and 13-HODE regulate fatty acid binding protein-4 in human macrophages, but does not involve HODE/GPR132 axis in PPAR-γ regulation of FABP4

PubMed Central

Shashidhar, Venkatesh; Collier, Fiona; Hodge, Jason; Rush, Catherine; Malabu, Usman; Baune, Bernhard; Kennedy, Richard Lee

2018-01-01

Background: Both activation of monocytes and increased serum fatty acid binding protein-4 (FABP4) occur in diabetes and are associated with increased atherosclerosis. The oxidized lipid, 9-hydroxyoctadecadienoic acid (9-HODE) increases FABP4 in macrophages, and is a ligand for G protein-coupled receptor 132 (GPR132). We investigated the involvement of GPR132 in mediating the 9-, 13-HODE stimulation of FABP4 secretion, and whether GPR132 expression is increased in monocytes from patients with type 2 diabetes. Methods: The effects of siRNA silencing of GPR132 gene and of the PPAR-γ antagonist T0070907 were studied in THP-1 cells. Serum levels of FABP4 and other adipokines were measured in patients with diabetes, and monocyte subpopulations were analyzed using flow cytometry. GPR132 mRNA was quantified in isolated CD14+ cells. Results: 9-HODE and 13-HODE increased FABP4 expression in THP-1 monocytes and macrophages, and also increased GPR132 expression. Silencing of GPR132 did not influence the increase in FABP4 with 9-HODE, 13-HODE, or rosiglitazone (ROSI). By contrast, T0070907 inhibited the effect of all three ligands on FABP4 expression. Diabetic subjects had increased serum FABP4, and activated monocytes. They also expressed higher levels of GPR132 mRNA in CD14+ cells. Conclusions: We conclude that GPR132 is an independent monocyte activation marker in diabetes, but does not contribute to PPAR-γ-mediated induction of FABP4 by HODEs.

HOMEOSTATIC REGULATION OF KCC2 ACTIVITY BY THE ZINC RECEPTOR mZnR/GPR39 DURING SEIZURES

PubMed Central

Gilad, David; Shorer, Sharon; Ketzef, Maya; Friedman, Alon; Sekler, Israel; Aizenman, Elias; Hershfinkel, Michal

2015-01-01

The aim of this study was to investigate the role of the synaptic metabotropic zinc receptor mZnR/GPR39 in physiological adaptation to epileptic seizures. We previously demonstrated that synaptic activation of mZnR/GPR39 enhances inhibitory drive in the hippocampus by upregulating neuronal K+/Cl− co-transporter 2 (KCC2) activity. Here, we first show that mZnR/GPR39 knockout (KO) adult mice have dramatically enhanced susceptibility to seizures triggered by a single intraperitoneal injection of kainic acid, when compared to wild type (WT) littermates. Kainate also substantially enhances seizure-associated gamma oscillatory activity in juvenile mZnR/GPR39 KO hippocampal slices, a phenomenon that can be reproduced in WT tissue by extracellular Zn2+ chelation. Importantly, kainate-induced synaptic Zn2+ release enhances surface expression and transport activity of KCC2 in WT, but not mZnR/GPR39 KO hippocampal neurons. Kainate-dependent upregulation of KCC2 requires mZnR/GPR39 activation of the Gαq/phospholipase C/extracellular regulated kinase (ERK1/2) signaling cascade. We suggest that mZnR/GPR39-dependent upregulation of KCC2 activity provides homeostatic adaptation to an excitotoxic stimulus by increasing inhibition. As such, mZnR/GPR39 may provide a novel pharmacological target for dampening epileptic seizure activity. PMID:25562657

The oral lipid sensor GPR120 is not indispensable for the orosensory detection of dietary lipids in mice.

PubMed

Ancel, Déborah; Bernard, Arnaud; Subramaniam, Selvakumar; Hirasawa, Akira; Tsujimoto, Gozoh; Hashimoto, Toshihiro; Passilly-Degrace, Patricia; Khan, Naim-Akhtar; Besnard, Philippe

2015-02-01

Implication of the long-chain fatty acid (LCFA) receptor GPR120, also termed free fatty acid receptor 4, in the taste-guided preference for lipids is a matter of debate. To further unravel the role of GPR120 in the "taste of fat", the present study was conducted on GPR120-null mice and their wild-type littermates. Using a combination of morphological [i.e., immunohistochemical staining of circumvallate papillae (CVP)], behavioral (i.e., two-bottle preference tests, licking tests and conditioned taste aversion) and functional studies [i.e., calcium imaging in freshly isolated taste bud cells (TBCs)], we show that absence of GPR120 in the oral cavity was not associated with changes in i) gross anatomy of CVP, ii) LCFA-mediated increases in intracellular calcium levels ([Ca(2+)]i), iii) preference for oily and LCFA solutions and iv) conditioned avoidance of LCFA solutions. In contrast, the rise in [Ca(2+)]i triggered by grifolic acid, a specific GPR120 agonist, was dramatically curtailed when the GPR120 gene was lacking. Taken together, these data demonstrate that activation of lingual GPR120 and preference for fat are not connected, suggesting that GPR120 expressed in TBCs is not absolutely required for oral fat detection in mice. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

Long non-coding RNA GPR65-1 is up-regulated in gastric cancer and promotes tumor growth through the PTEN-AKT-slug signaling pathway.

PubMed

Li, Yansen; Shen, Zhanlong; Wang, Bo; Ye, Chunxiang; Lai, Zhiyong; Jiang, Hongpeng; Wang, Zhu; Jiang, Kewei; Ye, Yingjiang; Wang, Shan

2018-04-02

Increasing evidence has shown that abnormal expression of lncRNAs is involved in various biological behaviors and major cellular pathways of human cancers. However, the role of lncRNAs in the progression of gastric cancer has not been adequately investigated. Therefore, in this study, we investigated the expression levels of linc-GPR65-1 using Quantitative real-time PCR (qRT-PCR) and found that linc-GPR65-1 was significantly up-regulated in 50 gastric cancer tissues compared to the corresponding normal tissues. In addition, increased linc-GPR65-1 expression was associated with TNM stage (P = 0.037), tumor size (P = 0.024), distal metastasis (P = 0.023), and poor prognosis of gastric cancer patients. Moreover, functional assays indicated that decreased linc-GPR65-1 expression inhibited the aggressive phenotypes of gastric cancer cells, and enhanced linc-GPR65-1 expression resulted in the opposite phenomenon. Then, a cancer signaling phosphoantibody microarray was conducted to explore the potential mechanisms of linc-GPR65-1 in regulating gastric cancer progression and observed that linc-GPR65-1 could regulate the PTEN-AKT-slug signaling pathway. These data showed that linc-GPR65-1, regulating the PTEN-AKT-slug signaling pathway, might act as a tumor promoter and serve as a novel target for gastric cancer prevention and therapy.

Insights into unbound-bound states of GPR142 receptor in a membrane-aqueous system using molecular dynamics simulations.

PubMed

Kaushik, Aman Chandra; Sahi, Shakti

2018-05-01

G protein coupled receptors (GPCRs) are source machinery in signal transduction pathways and being one of the major therapeutic targets play a significant in drug discovery. GPR142, an orphan GPCR, has been implicated in the regulation of insulin, thereby having a crucial role in Type II diabetes management. Deciphering of the structures of orphan, GPCRs (O-GPCRs) offer better prospects for advancements in research in ion translocation and transduction of extracellular signals. As the crystallographic structure of GPR142 is not available in PDB, therefore, threading and ab initio-based approaches were used for 3D modeling of GPR142. Molecular dynamic simulations (900 ns) were performed on the 3D model of GPR142 and complexes of GPR142 with top five hits, obtained through virtual screening, embedded in lipid bilayer with aqueous system using OPLS force field. Compound 1, 3, and 4 may act as scaffolds for designing potential lead agonists for GPR142. The finding of GPR142 MD simulation study provides more comprehensive representation of the functional properties. The concern for Type II diabetes is increasing worldwide and successful treatment of this disease demands novel drugs with better efficacy.

Regulation of GPR119 receptor activity with endocannabinoid-like lipids.

PubMed

Syed, Samreen K; Bui, Hai Hoang; Beavers, Lisa S; Farb, Thomas B; Ficorilli, James; Chesterfield, Amy K; Kuo, Ming-Shang; Bokvist, Krister; Barrett, David G; Efanov, Alexander M

2012-12-15

The GPR119 receptor plays an important role in the secretion of incretin hormones in response to nutrient consumption. We have studied the ability of an array of naturally occurring endocannabinoid-like lipids to activate GPR119 and have identified several lipid receptor agonists. The most potent receptor agonists identified were three N-acylethanolamines: oleoylethanolamine (OEA), palmitoleoylethanolamine, and linoleylethanolamine (LEA), all of which displayed similar potency in activating GPR119. Another lipid, 2-oleoylglycerol (2-OG), also activated GPR119 receptor but with significantly lower potency. Endogenous levels of endocannabinoid-like lipids were measured in intestine in fasted and refed mice. Of the lipid GPR119 agonists studied, the intestinal levels of only OEA, LEA, and 2-OG increased significantly upon refeeding. Intestinal levels of OEA and LEA in the fasted mice were low. In the fed state, OEA levels only moderately increased, whereas LEA levels rose drastically. 2-OG was the most abundant of the three GPR119 agonists in intestine, and its levels were radically elevated in fed mice. Our data suggest that, in lean mice, 2-OG and LEA may serve as physiologically relevant endogenous GPR119 agonists that mediate receptor activation upon nutrient uptake.

Stimulation of GPR30 increases release of EMMPRIN-containing microvesicles in human uterine epithelial cells.

PubMed

Burnett, Lindsey A; Light, Mallory M; Mehrotra, Pavni; Nowak, Romana A

2012-12-01

Uterine remodeling is highly dependent on the glycosylated transmembrane protein extracellular matrix metalloproteinase (MMP) inducer (EMMPRIN). Previous studies indicate estradiol can increase EMMPRIN expression in uterine cells and promote subsequent induction of MMP production. The aim of this study was to investigate the role of G protein-coupled receptor 30 (GPR30) stimulation on EMMPRIN microvesicle release in the human uterine epithelial cell line hTERT-EEC (EECs). We examined EMMPRIN release by human EECs in response to GPR30 stimulation by microvesicle isolation, Western blot, and immunocytochemistry. We employed a pharmacological approach using the GPR30-selective agonist G1 and the antagonist G15 to determine the receptor specificity of this response. We demonstrated GPR30 expression in EECs and release of EMMPRIN in microvesicles in response to stimulation of GPR30. G1, estradiol, and cholera toxin stimulated EMMPRIN release in microvesicles as detected by Western blot and immunocytochemistry, indicating that stimulation of GPR30 can induce EMMPRIN microvesicle release. These data indicate that EMMPRIN release in microvesicles can be mediated by stimulation of GPR30 in human EECs, suggesting that inappropriate stimulation or expression of this receptor may be significant in uterine pathology.

The gamma-glutamyl transpeptidase to platelet ratio (GPR) predicts significant liver fibrosis and cirrhosis in patients with chronic HBV infection in West Africa.

PubMed

Lemoine, Maud; Shimakawa, Yusuke; Nayagam, Shevanthi; Khalil, Mustapha; Suso, Penda; Lloyd, Jo; Goldin, Robert; Njai, Harr-Freeya; Ndow, Gibril; Taal, Makie; Cooke, Graham; D'Alessandro, Umberto; Vray, Muriel; Mbaye, Papa Saliou; Njie, Ramou; Mallet, Vincent; Thursz, Mark

2016-08-01

Simple and inexpensive non-invasive fibrosis tests are highly needed but have been poorly studied in sub-Saharan Africa. Using liver histology as a gold standard, we developed a novel index using routine laboratory tests to predict significant fibrosis in patients with chronic HBV infection in The Gambia, West Africa. We prospectively assessed the diagnostic accuracy of the novel index, Fibroscan, aspartate transaminase-to-platelet ratio index (APRI), and Fib-4 in Gambian patients with CHB (training set) and also in French and Senegalese CHB cohorts (validation sets). Of 135 consecutive treatment-naïve patients with CHB who had liver biopsy, 39% had significant fibrosis (Metavir fibrosis stage ≥F2) and 15% had cirrhosis (F4). In multivariable analysis, gamma-glutamyl transpeptidase (GGT) and platelet count were independent predictors of significant fibrosis. Consequently, GGT-to-platelet ratio (GPR) was developed. In The Gambia, the area under the receiver operating characteristic curve (AUROC) of the GPR was significantly higher than that of APRI and Fib-4 to predict ≥F2, ≥F3 and F4. In Senegal, the AUROC of GPR was significantly better than Fib-4 and APRI for ≥F2 (0.73, 95% CI 0.59 to 0.86) and better than Fib-4 and Fibroscan for ≥F3 (0.93, 0.87 to 0.99). In France, the AUROC of GPR to diagnose ≥F2 (0.72, 95% CI 0.59 to 0.85) and F4 (0.87, 0.76 to 0.98) was equivalent to that of APRI and Fib-4. The GPR is a more accurate routine laboratory marker than APRI and Fib-4 to stage liver fibrosis in patients with CHB in West Africa. The GPR represents a simple and inexpensive alternative to liver biopsy and Fibroscan in sub-Saharan Africa. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Downregulation of leptin receptor and kisspeptin/GPR54 in the murine hypothalamus contributes to male hypogonadism caused by high-fat diet-induced obesity.

PubMed

Zhai, Lingling; Zhao, Jian; Zhu, Yiming; Liu, Qiannan; Niu, Wenhua; Liu, Chengyin; Wang, Yi

2018-06-13

Obesity may lead to male hypogonadism, the underlying mechanism of which remains unclear. In the present study, we established a murine model of male hypogonadism caused by high-fat diet-induced obesity to verify the following hypotheses: 1) an increased leptin level may be related to decreased secretion of GnRH in obese males, and 2) repression of kisspeptin/GPR54 in the hypothalamus, which is associated with increased leptin levels, may account for the decreased secretion of GnRH and be involved in secondary hypogonadism (SH) in obese males. Male mice were fed high-fat diet for 19 weeks and divided by body weight gain into diet-induced obesity (DIO) and diet-induced obesity resistant (DIO-R) group. The effect of obesity on the reproductive organs in male mice was observed by measuring sperm count and spermatozoid motility, relative to testis and epididymis weight, testosterone levels, and pathologic changes. Leptin, testosterone, estrogen, and LH in serum were detected by ELISA method. Leptin receptor (Ob-R), Kiss1, GPR54, and GnRH mRNA were measured by real-time PCR in the hypothalamus. Expression of kisspeptin and Ob-R protein was determined by Western blotting. Expression of GnRH and GPR54 protein was determined by immunohistochemical analysis. We found that diet-induced obesity decreased spermatozoid motility, testis and epididymis relative coefficients, and plasma testosterone and luteinizing hormone levels. An increased number and volume of lipid droplets in Leydig cells were observed in the DIO group compared to the control group. Significantly, higher serum leptin levels were found in the DIO and DIO-R groups. The DIO and DIO-R groups showed significant downregulation of the GnRH, Kiss1, GPR54, and Ob-R genes. We also found decreased levels of GnRH, kisspeptin, GPR54, and Ob-R protein in the DIO and DIO-R groups. These lines of evidence suggest that downregulation of Ob-R and kisspeptin/GPR54 in the murine hypothalamus may contribute to male hypogonadism caused by high-fat diet-induced obesity.

Evaluation of 3D Ground Penetrating Radar Efficiency for Abandoned Tailings Pond Internal Structure Analysis and Risk Assessment

NASA Astrophysics Data System (ADS)

Cortada, Unai; Martínez, Julián; Hidalgo, Mª Carmen; Rey, Javier

2017-04-01

Evaluation of 3D Ground Penetrating Radar Efficiency for Abandoned Tailings Pond Internal Structure Analysis and Risk Assessment Abandoned tailings ponds constitute a severe environmental problem in old Pb mining districts due to their high contents in metallic and semi-metallic elements. In most of the cases, there is a lack of information about the construction procedures and the previous environmental situation, which hinders the environmental risk evaluation. In these cases, Ground Penetrating Radar (GPR) could be an interesting technique to analyze the internal structure of the tailings ponds and detect vulnerable zones for leaching processes. Consequently, the GPR could help in the abandoned tailings ponds environmental risk assessment. In this study, a GPR 3D campaign was carried out with a 250 MHz frequency antenna in order to evaluate the efficiency of this technique in both the analysis of internal structures and the environmental risk assessment. Subsequently, 2D and 3D models were undertaken to represent graphically the obtained results. The studied tailings pond is located in the Guadiel river bank, a water course draining the mining district of Linares, Spain. The dam is 150 m length and 80 m width. The GPR 3D was done in a selected area near the central part of the pond. The analyzed grid was 25x50 m and the spacing of the slides was 1 m. The study revealed that the contact between the tailings and the substratum is located at 2.5 m. No intermediate layer was found, which means that the tailings pond was heightened on the fluvial terrace without any insulation system. Inside the first meter of the pond, a cross stratification was identified. The orientation of those laminations changed with the depth, which means that the stockpiling was performed from the different sides of the tailings pond. Furthermore, the direction of these stratifications is slightly concentric to the middle of the dam which could be associated with a central drainage system. Therefore, the internal zone of the tailings pond appears to be the most vulnerable for leaching processes that could contaminate the groundwater. Thus, this technique gave detailed information of the internal structure at the first meters despite the rapid attenuation of the GPR signal. In consequence, the GPR 3D with 250 MHz antenna appears to be effective for the detection of the tailings ponds cross stratification and the tailings-soil contact in dams with less than 5 meters of thickness.

G-protein-coupled receptor 81 promotes a malignant phenotype in breast cancer through angiogenic factor secretion.

PubMed

Lee, Yu Jin; Shin, Kyeong Jin; Park, Soo-Ah; Park, Kyeong Su; Park, Seorim; Heo, Kyun; Seo, Young-Kyo; Noh, Dong-Young; Ryu, Sung Ho; Suh, Pann-Ghill

2016-10-25

G-protein-coupled receptor 81 (GPR81) functions as a receptor for lactate and plays an important role in the regulation of anti-lipolytic effects in adipocytes. However, to data, a role for GPR81 in the tumor microenvironment has not been clearly defined. Here, GPR81 expression in breast cancer patients and several breast cancer cell lines was significantly increased compared with normal mammary tissues and cells. GPR81 knockdown resulted in impaired breast cancer growth and led to apoptosis both in vitro and in vivo. Furthermore, the inhibition of GPR81 signaling suppressed angiogenesis through a phosphoinositide 3-OH kinase (PI3K)/Akt-cAMP response element binding protein (CREB) pathway, which led to decreased production of the pro-angiogenic mediator amphiregulin (AREG). Overall, these findings identify GPR81 as a tumor-promoting receptor in breast cancer progression and suggest a novel mechanism that regulates GPR81-dependent activation of the PI3K/Akt signaling axis in tumor microenvironment.

Progress in quantitative GPR development at CNDE

NASA Astrophysics Data System (ADS)

Eisenmann, David; Margetan, F. J.; Chiou, C.-P.; Roberts, Ron; Wendt, Scott

2014-02-01

Ground penetrating radar (GPR) uses electromagnetic (EM) radiation pulses to locate and map embedded objects. Commercial GPR instruments are generally geared toward producing images showing the location and extent of buried objects, and often do not make full use of available absolute amplitude information. At the Center for Nondestructive Evaluation (CNDE) at Iowa State University efforts are underway to develop a more quantitative approach to GPR inspections in which absolute amplitudes and spectra of measured signals play a key role. Guided by analogous work in ultrasonic inspection, there are three main thrusts to the effort. These focus, respectively, on the development of tools for: (1) analyzing raw GPR data; (2) measuring the EM properties of soils and other embedding media; and (3) simulating GPR inspections. This paper reviews progress in each category. The ultimate goal of the work is to develop model-based simulation tools that can be used assess the usefulness of GPR for a given inspection scenario, to optimize inspection choices, and to determine inspection reliability.

Characterisation and optimisation of Ground Penetrating Radar antennas

NASA Astrophysics Data System (ADS)

Warren, Craig; Giannopoulos, Antonios

2014-05-01

Research on the characterisation and optimisation of Ground Penetrating Radar (GPR) antennas will be presented as part of COST Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar". This work falls within the remit of Working Group 1 - "Novel GPR instrumentation" which focuses on the design of innovative GPR equipment for Civil Engineering (CE) applications, on the building of prototypes and on the testing and optimisation of new systems. The diversity of applications of GPR has meant there are a number of different GPR antenna designs available to the end-user as well as those being used in the research community. The type and size of a GPR antenna is usually dependent on the application, e.g. low frequency antennas, which are physically larger, are used where significant depth of penetration is important, whereas high frequency antennas, which are physically smaller, are used where less penetration and better resolution are required. Understanding how energy is transmitted and received by a particular GPR antenna has many benefits: it could lead to more informed usage of the antenna in GPR surveys; improvements in antenna design; and better interpretation of GPR signal returns from the ground/structure. The radiation characteristics of a particular antenna are usually investigated by studying the radiation patterns and directivity. For GPR antennas it is also important to study these characteristics when the antenna is in different environments that would typically be encountered in GPR surveys. In this work Finite-Difference Time-Domain (FDTD) numerical models of GPR antennas have been developed. These antenna models replicate all the detailed geometry and main components of the real antennas. The models are representative of typical high-frequency, high-resolution GPR antennas primarily used in CE for the evaluation of structural features in concrete: the location of rebar, conduits, and post-tensioned cables, as well as the estimation of material thickness on bridge decks and pavements. Radiation patterns obtained using the antenna models as well as physical measurements have been used to investigate the radiation characteristics of high-frequency GPR antennas. Studies were conducted with homogeneous materials of different dielectric constants (Er=3, 10, 30, & 72) and at a range of observation distances. The first objective was to compare, using the FDTD antenna model, 'traditional' transmitted field patterns with field patterns obtained using responses from a target spaced at regular intervals around the circumference of a circle, i.e. received energy. Our initial results show, for the same dielectric and observation distance, E- and H-field patterns obtained using the received energy approach have a significantly narrower main lobe than the traditional transmitted patterns. This raises the question of which approach is more beneficial for the characterisation of GPR antennas, and hence better interpretation of GPR responses. The second objective was to compare modelled field patterns with measured patterns obtained from a commercial high-frequency GPR antenna using the received energy approach. The measurements were made in different oil-in-water emulsions which were used to simulate materials with different permittivities and conductivities. Initial comparisons of the measured and modelled data show a very good correlation, which validates use of the antenna model for further studies.

Electromagnetic modelling of Ground Penetrating Radar responses to complex targets

NASA Astrophysics Data System (ADS)

Pajewski, Lara; Giannopoulos, Antonis

2014-05-01

This work deals with the electromagnetic modelling of composite structures for Ground Penetrating Radar (GPR) applications. It was developed within the Short-Term Scientific Mission ECOST-STSM-TU1208-211013-035660, funded by COST Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar". The Authors define a set of test concrete structures, hereinafter called cells. The size of each cell is 60 x 100 x 18 cm and the content varies with growing complexity, from a simple cell with few rebars of different diameters embedded in concrete at increasing depths, to a final cell with a quite complicated pattern, including a layer of tendons between two overlying meshes of rebars. Other cells, of intermediate complexity, contain pvc ducts (air filled or hosting rebars), steel objects commonly used in civil engineering (as a pipe, an angle bar, a box section and an u-channel), as well as void and honeycombing defects. One of the cells has a steel mesh embedded in it, overlying two rebars placed diagonally across the comers of the structure. Two cells include a couple of rebars bent into a right angle and placed on top of each other, with a square/round circle lying at the base of the concrete slab. Inspiration for some of these cells is taken from the very interesting experimental work presented in Ref. [1]. For each cell, a subset of models with growing complexity is defined, starting from a simple representation of the cell and ending with a more realistic one. In particular, the model's complexity increases from the geometrical point of view, as well as in terms of how the constitutive parameters of involved media and GPR antennas are described. Some cells can be simulated in both two and three dimensions; the concrete slab can be approximated as a finite-thickness layer having infinite extension on the transverse plane, thus neglecting how edges affect radargrams, or else its finite size can be fully taken into account. The permittivity of concrete can be defined through a constant real value, or else its frequency-dispersion properties can be taken into account by incorporating into the model Debye approximations. The electromagnetic source can be represented as a simple line of current (in the case of two-dimensional models), a Hertzian dipole, a bow tie antenna, or else, the realistic description of a commercial antenna can be included in the model [2]. Preliminary results for some of the proposed cells are presented, obtained by using GprMax [3], a freeware tool which solves Maxwell's equations by using a second order in space and time Finite-Difference Time-Domain algorithm. B-Scans and A-Scans are calculated at 1.5 GHz, for the total electric field and for the field back-scattered by targets embedded in the cells. A detailed description of the structures, together with the relevant numerical results obtained to date, are available for the scientific community on the website of COST Action TU1208, www.GPRadar.eu. Research groups working on the development of electromagnetic forward- and inverse-scattering techniques, as well as on imaging methods, might test and compare the accuracy and applicability of their approaches on the proposed set of scenarios. The aim of this initiative is not that of identifying the best methods, but more properly to indicate the range of reliability of each approach, highlighting its advantages and drawbacks. In the future, the realisation of the proposed concrete cells and the acquisition of GPR experimental data would allow a very effective benchmark for forward and inverse scattering methods. References [1] R. Yelf, A. Ward, "Nine steps to concrete wisdom." Proc. 13th International Conference on Ground Penetrating Radar, Lecce, Italy, 21-25 June 2010, pp. 1-8. [2] C. Warren, A. Giannopoulos, "Creating FDTD models of commercial GPR antennas using Taguchi's optimisation method." Geophysics (2011), 76, article ID G37. [3] A. Giannopoulos, "Modelling ground penetrating radar by GPRMAX." Construction and Building Materials (2005), 19, pp. 755-762.

Bisphenol A at a low concentration boosts mouse spermatogonial cell proliferation by inducing the G protein-coupled receptor 30 expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheng, Zhi-Guo; Huang, Wei; Liu, Yu-Xiang

Bisphenol A (BPA) is one of the most prevalent chemicals in daily-use materials, therefore, human exposure to BPA is ubiquitous. We found that low concentrations of BPA stimulate the spermatogonial GC-1 cells proliferation by G protein-coupled receptor 30 (GPR30)-mediated epidermal growth factor receptor (EGFR)-extracellular regulated kinase (ERK)-c-Fos pathway. However, through the same pathway GPR30 expression has been shown to be induced by EGF, an EGFR ligand. Thus, we want to know if low concentrations of BPA are able to induce the GPR30 expression and the possible mechanism(s) in GC-1 cells. By transient transfection with expression plasmids, 10{sup −9} M BPAmore » significantly transactivates the Gpr30-5′-flanking region through activating the GPR30, cGMP-dependent protein kinase (PKG), estrogen receptor-α (ER-α), and EFGR-ERK pathways. Furthermore, an activator protein-1 (AP-1) site located within this region is found to be responsible for the transactivation of BPA. Expectedly, through the same pathways, BPA significantly induces the gene and protein expression of GPR30. c-Fos is further observed to be strongly recruited to the AP-1 site in a chromatin immunoprecipitation assay and its dysfunction on the AP-1 site markedly suppresses the expression of GPR30, p-ERK1/2, p-Ser118-ER-α and cell proliferation by BPA. Our results demonstrate that a low-concentration BPA induces GPR30 expression through the GPR30-EFGR-ERK-c-Fos, ER-α, and PKG pathways, presumably boosting the cells proliferation via a regulatory loop. The present study provides a novel insight into the potential role of GPR30 in the initiation and progression of male germ cell cancer induced by environmentally relevant BPA. - Highlights: ► Low concentrations of BPA activate the PKG and GPR30-EFGR-ERK-ER-α pathways. ► Low concentrations of BPA activate the AP-1 site of Gpr30-5′-flanking region. ► Low concentrations of BPA induce the expression of GPR30 gene and protein. ► Low concentrations of BPA boost GC-1 cells proliferation via a regulatory loop.« less

Effect of Cold Temperature on the Dielectric Constant of Soil

DTIC Science & Technology

2012-04-01

explosive device (IED) threats is ground-penetrating radar ( GPR ). Proper development of GPR technology for this application requires a unique...success or failure of GPR as a detection technique. One soil property of interest to radar engineers is the dielectric constant. Previous...results to temperatures, moisture levels, and frequencies relevant to GPR systems. 2. Dielectric Constant and the Ring-resonator Concept The two

The zinc sensing receptor, ZnR/GPR39, controls proliferation and differentiation of colonocytes and thereby tight junction formation in the colon

PubMed Central

Cohen, L; Sekler, I; Hershfinkel, M

2014-01-01

The intestinal epithelium is a renewable tissue that requires precise balance between proliferation and differentiation, an essential process for the formation of a tightly sealed barrier. Zinc deficiency impairs the integrity of the intestinal epithelial barrier and is associated with ulcerative and diarrheal pathologies, but the mechanisms underlying the role of Zn2+ are not well understood. Here, we determined a role of the colonocytic Zn2+ sensing receptor, ZnR/GPR39, in mediating Zn2+-dependent signaling and regulating the proliferation and differentiation of colonocytes. Silencing of ZnR/GPR39 expression attenuated Zn2+-dependent activation of ERK1/2 and AKT as well as downstream activation of mTOR/p70S6K, pathways that are linked with proliferation. Consistently, ZnR/GPR39 silencing inhibited HT29 and Caco-2 colonocyte proliferation, while not inducing caspase-3 cleavage. Remarkably, in differentiating HT29 colonocytes, silencing of ZnR/GPR39 expression inhibited alkaline phosphatase activity, a marker of differentiation. Furthermore, Caco-2 colonocytes showed elevated expression of ZnR/GPR39 during differentiation, whereas silencing of ZnR/GPR39 decreased monolayer transepithelial electrical resistance, suggesting compromised barrier formation. Indeed, silencing of ZnR/GPR39 or chelation of Zn2+ by the cell impermeable chelator CaEDTA was followed by impaired expression of the junctional proteins, that is, occludin, zonula-1 (ZO-1) and E-cadherin. Importantly, colon tissues of GPR39 knockout mice also showed a decrease in expression levels of ZO-1 and occludin compared with wildtype mice. Altogether, our results indicate that ZnR/GPR39 has a dual role in promoting proliferation of colonocytes and in controlling their differentiation. The latter is followed by ZnR/GPR39-dependent expression of tight junctional proteins, thereby leading to formation of a sealed intestinal epithelial barrier. Thus, ZnR/GPR39 may be a therapeutic target for promoting epithelial function and tight junction barrier integrity during ulcerative colon diseases. PMID:24967969

The zinc sensing receptor, ZnR/GPR39, controls proliferation and differentiation of colonocytes and thereby tight junction formation in the colon.

PubMed

Cohen, L; Sekler, I; Hershfinkel, M

2014-06-26

The intestinal epithelium is a renewable tissue that requires precise balance between proliferation and differentiation, an essential process for the formation of a tightly sealed barrier. Zinc deficiency impairs the integrity of the intestinal epithelial barrier and is associated with ulcerative and diarrheal pathologies, but the mechanisms underlying the role of Zn(2+) are not well understood. Here, we determined a role of the colonocytic Zn(2+) sensing receptor, ZnR/GPR39, in mediating Zn(2+)-dependent signaling and regulating the proliferation and differentiation of colonocytes. Silencing of ZnR/GPR39 expression attenuated Zn(2+)-dependent activation of ERK1/2 and AKT as well as downstream activation of mTOR/p70S6K, pathways that are linked with proliferation. Consistently, ZnR/GPR39 silencing inhibited HT29 and Caco-2 colonocyte proliferation, while not inducing caspase-3 cleavage. Remarkably, in differentiating HT29 colonocytes, silencing of ZnR/GPR39 expression inhibited alkaline phosphatase activity, a marker of differentiation. Furthermore, Caco-2 colonocytes showed elevated expression of ZnR/GPR39 during differentiation, whereas silencing of ZnR/GPR39 decreased monolayer transepithelial electrical resistance, suggesting compromised barrier formation. Indeed, silencing of ZnR/GPR39 or chelation of Zn(2+) by the cell impermeable chelator CaEDTA was followed by impaired expression of the junctional proteins, that is, occludin, zonula-1 (ZO-1) and E-cadherin. Importantly, colon tissues of GPR39 knockout mice also showed a decrease in expression levels of ZO-1 and occludin compared with wildtype mice. Altogether, our results indicate that ZnR/GPR39 has a dual role in promoting proliferation of colonocytes and in controlling their differentiation. The latter is followed by ZnR/GPR39-dependent expression of tight junctional proteins, thereby leading to formation of a sealed intestinal epithelial barrier. Thus, ZnR/GPR39 may be a therapeutic target for promoting epithelial function and tight junction barrier integrity during ulcerative colon diseases.

Civil Engineering Applications of Ground Penetrating Radar in Finland

NASA Astrophysics Data System (ADS)

Pellinen, Terhi; Huuskonen-Snicker, Eeva; Olkkonen, Martta-Kaisa; Eskelinen, Pekka

2014-05-01

Ground penetrating radar (GPR) has been used in Finland since 1980's for civil engineering applications. First applications in this field were road surveys and dam inspections. Common GPR applications in road surveys include the thickness evaluation of the pavement, subgrade soil evaluation and evaluation of the soil moisture and frost susceptibility. Since the 1990's, GPR has been used in combination with other non-destructive testing (NDT) methods in road surveys. Recently, more GPR applications have been adopted, such as evaluating bridges, tunnels, railways and concrete elements. Nowadays, compared with other countries GPR is relatively widely used in Finland for road surveys. Quite many companies, universities and research centers in Finland have their own GPR equipment and are involved in the teaching and research of the GPR method. However, further research and promotion of the GPR techniques are still needed since GPR could be used more routinely. GPR has been used to evaluate the air void content of asphalt pavements for years. Air void content is an important quality measure of pavement condition for both the new and old asphalt pavements. The first Finnish guideline was released in 1999 for the method. Air void content is obtained from the GPR data by measuring the dielectric value as continuous record. To obtain air void content data, few pavement cores must be taken for calibration. Accuracy of the method is however questioned because there are other factors that affect the dielectric value of the asphalt layer, in addition to the air void content. Therefore, a research project is currently carried out at Aalto University in Finland. The overall objective is to investigate if the existing GPR technique used in Finland is accurate enough to be used as QC/QA tool in assessing the compaction of asphalt pavements. The project is funded by the Finnish Transport Agency. Further research interests at Aalto University include developing new microwave asphalt radar for the thickness evaluation of thin asphalt layers. This work benefited from networking activities carried out within the EU funded COST Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar".

Estimating water content in an active landfill with the aid of GPR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yochim, April, E-mail: ayochim@regionofwaterloo.ca; Zytner, Richard G., E-mail: rzytner@uoguelph.ca; McBean, Edward A., E-mail: emcbean@uoguelph.ca

Highlights: • Limited information in the literature on the use of GPR to measure in situ water content in a landfill. • Developed GPR method allows measurement of in situ water content in a landfill. • Developed GPR method is appealing to waste management professionals operating landfills. - Abstract: Landfill gas (LFG) receives a great deal of attention due to both negative and positive environmental impacts, global warming and a green energy source, respectively. However, predicting the quantity of LFG generated at a given landfill, whether active or closed is difficult due to the heterogeneities present in waste, and themore » lack of accurate in situ waste parameters like water content. Accordingly, ground penetrating radar (GPR) was evaluated as a tool for estimating in situ water content. Due to the large degree of subsurface heterogeneity and the electrically conductive clay cap covering landfills, both of which affect the transmission of the electromagnetic pulses, there is much scepticism concerning the use of GPR to quantify in situ water content within a municipal landfill. Two landfills were studied. The first landfill was used to develop the measurement protocols, while the second landfill provided a means of confirming these protocols. GPR measurements were initially completed using the surface GPR approach, but the lack of success led to the use of borehole (BH) GPR. Both zero offset profiling (ZOP) and multiple offset gathers (MOG) modes were tried, with the results indicating that BH GPR using the ZOP mode is the most simple and efficient method to measure in situ water content. The best results were obtained at a separation distance of 2 m, where higher the water content, smaller the effective separation distance. However, an increase in water content did appear to increase the accuracy of the GPR measurements. For the effective separation distance of 2 m at both landfills, the difference between GPR and lab measured water contents were reasonable at 33.9% for the drier landfill and 18.1% for the wetter landfill. Infiltration experiments also showed the potential to measure small increases in water content.« less

Hypothalamic GPR40 Signaling Activated by Free Long Chain Fatty Acids Suppresses CFA-Induced Inflammatory Chronic Pain

PubMed Central

Nakamoto, Kazuo; Nishinaka, Takashi; Sato, Naoya; Mankura, Mitsumasa; Koyama, Yutaka; Kasuya, Fumiyo; Tokuyama, Shogo

2013-01-01

GPR40 has been reported to be activated by long-chain fatty acids, such as docosahexaenoic acid (DHA). However, reports studying functional role of GPR40 in the brain are lacking. The present study focused on the relationship between pain regulation and GPR40, investigating the functional roles of hypothalamic GPR40 during chronic pain caused using a complete Freund's adjuvant (CFA)-induced inflammatory chronic pain mouse model. GPR40 protein expression in the hypothalamus was transiently increased at day 7, but not at days 1, 3 and 14, after CFA injection. GPR40 was co-localized with NeuN, a neuron marker, but not with glial fibrillary acidic protein (GFAP), an astrocyte marker. At day 1 after CFA injection, GFAP protein expression was markedly increased in the hypothalamus. These increases were significantly inhibited by the intracerebroventricular injection of flavopiridol (15 nmol), a cyclin-dependent kinase inhibitor, depending on the decreases in both the increment of GPR40 protein expression and the induction of mechanical allodynia and thermal hyperalgesia at day 7 after CFA injection. Furthermore, the level of DHA in the hypothalamus tissue was significantly increased in a flavopiridol reversible manner at day 1, but not at day 7, after CFA injection. The intracerebroventricular injection of DHA (50 µg) and GW9508 (1.0 µg), a GPR40-selective agonist, significantly reduced mechanical allodynia and thermal hyperalgesia at day 7, but not at day 1, after CFA injection. These effects were inhibited by intracerebroventricular pretreatment with GW1100 (10 µg), a GPR40 antagonist. The protein expression of GPR40 was colocalized with that of β-endorphin and proopiomelanocortin, and a single intracerebroventricular injection of GW9508 (1.0 µg) significantly increased the number of neurons double-stained for c-Fos and proopiomelanocortin in the arcuate nucleus of the hypothalamus. Our findings suggest that hypothalamic GPR40 activated by free long chain fatty acids might have an important role in this pain control system. PMID:24349089

Real-time prediction and gating of respiratory motion using an extended Kalman filter and Gaussian process regression

NASA Astrophysics Data System (ADS)

Bukhari, W.; Hong, S.-M.

2015-01-01

Motion-adaptive radiotherapy aims to deliver a conformal dose to the target tumour with minimal normal tissue exposure by compensating for tumour motion in real time. The prediction as well as the gating of respiratory motion have received much attention over the last two decades for reducing the targeting error of the treatment beam due to respiratory motion. In this article, we present a real-time algorithm for predicting and gating respiratory motion that utilizes a model-based and a model-free Bayesian framework by combining them in a cascade structure. The algorithm, named EKF-GPR+, implements a gating function without pre-specifying a particular region of the patient’s breathing cycle. The algorithm first employs an extended Kalman filter (LCM-EKF) to predict the respiratory motion and then uses a model-free Gaussian process regression (GPR) to correct the error of the LCM-EKF prediction. The GPR is a non-parametric Bayesian algorithm that yields predictive variance under Gaussian assumptions. The EKF-GPR+ algorithm utilizes the predictive variance from the GPR component to capture the uncertainty in the LCM-EKF prediction error and systematically identify breathing points with a higher probability of large prediction error in advance. This identification allows us to pause the treatment beam over such instances. EKF-GPR+ implements the gating function by using simple calculations based on the predictive variance with no additional detection mechanism. A sparse approximation of the GPR algorithm is employed to realize EKF-GPR+ in real time. Extensive numerical experiments are performed based on a large database of 304 respiratory motion traces to evaluate EKF-GPR+. The experimental results show that the EKF-GPR+ algorithm effectively reduces the prediction error in a root-mean-square (RMS) sense by employing the gating function, albeit at the cost of a reduced duty cycle. As an example, EKF-GPR+ reduces the patient-wise RMS error to 37%, 39% and 42% in percent ratios relative to no prediction for a duty cycle of 80% at lookahead lengths of 192 ms, 384 ms and 576 ms, respectively. The experiments also confirm that EKF-GPR+ controls the duty cycle with reasonable accuracy.

Estrogenic G protein-coupled receptor 30 signaling is involved in regulation of endometrial carcinoma by promoting proliferation, invasion potential, and interleukin-6 secretion via the MEK/ERK mitogen-activated protein kinase pathway.

PubMed

He, Yin-Yan; Cai, Bin; Yang, Yi-Xia; Liu, Xue-Lian; Wan, Xiao-Ping

2009-06-01

The regulatory mechanism of endometrial carcinoma and the signal transduction pathways involved in hormone action are poorly defined. It has become apparent that the G protein-coupled receptor (GPR) 30 mediates the non-genomic signaling of 17beta-estradiol (E2). Here we show that GPR30 is highly expressed in endometrial cancer tissues and cancer cell lines and positively regulates cell proliferation and invasion. GPR30 expression was detected in 50 human endometrial carcinomas. The transcription level of GPR30 was significantly higher in the tissue of endometrial carcinoma than in normal endometrium (P < 0.05). Immunohistochemical assays revealed that the positive expression rate of GPR30 protein in endometrial carcinoma tissue (35/50, 70%) was statistically higher than in normal endometrium tissue (8/30, 26.67%) (chi2 = 14.16, P = 0.0002). GPR30 overexpression was correlated with high-grade endometrial carcinoma. GPR30 expression was also found in two human endometrial cancer cell lines: RL95-2 (estrogen receptor positive) and KLE (estrogen receptor negative). The roles of GPR30 in proliferative and invasive responses to E2 and G1, a non-steroidal GPR30-specific agonist, in RL95-2 and KLE cell lines were then explored. We showed that E2 and G1 could initiate the MAPK/ERK mitogen-activated protein kinase pathway in both cell lines. What's more, E2 and G1 promoted KLE and RL95-2 proliferation and stimulated matrix metalloproteinase production and activity via the GPR30-mediated MEK/ERK mitogen-activated protein kinase pathway, as well as increased interleukin-6 secretion. These findings suggest that GPR30-mediated non-genomic signaling could play an important role in endometrial cancer.

Expression and functional roles of estrogen receptor GPR30 in human intervertebral disc.

PubMed

Wei, Aiqun; Shen, Bojiang; Williams, Lisa A; Bhargav, Divya; Yan, Feng; Chong, Beng H; Diwan, Ashish D

2016-04-01

Estrogen withdrawal, a characteristic of female aging, is associated with age-related intervertebral disc (IVD) degeneration. The function of estrogen is mediated by two classic nuclear receptors, estrogen receptor (ER)-α and -β, and a membrane bound G-protein-coupled receptor 30 (GPR30). To date, the expression and function of GPR30 in human spine is poorly understood. This study aimed to evaluate GPR30 expression in IVD, and its role in estrogen-related regulation of proliferation and apoptosis of disc nucleus pulposus (NP) cells. GPR30 expression was examined in 30 human adult NP and 9 fetal IVD. Results showed that GPR30 was expressed in NP cells at both mRNA and protein levels. In human fetal IVD, GPR30 protein was expressed in the NP at 12-14 weeks gestation, but was undetectable at 8-11 weeks. The effect of 17β-estradiol (E2) on GPR30-mediated proliferation and interleukin-1β (IL-1β)-induced apoptosis of NP cells was investigated. Cultured NP cells were treated with or without E2, GPR30 antagonist G36, and ER antagonist ICI 182,780. NP cell viability was tested by MTS assay. Apoptosis was determined by flow cytometry using fluorescence labeled annexin-V, TUNEL assay and immumnocytochemical staining of activated caspase-3. E2 enhanced cell proliferation and prevented IL-1β-induced cell death, but the effect was partially blocked by G36 and completely abrogated by a combination of ICI 182,780 and G36. This study demonstrates that GPR30 is expressed in human IVD to transmit signals triggering E2-induced NP cell proliferation and protecting against IL-1β-induced apoptosis. The effects of E2 on NP cells require both GPR30 and classic estrogen receptors. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

G protein-coupled receptor 30 (GPR30) mediates gene expression changes and growth response to 17beta-estradiol and selective GPR30 ligand G-1 in ovarian cancer cells.

PubMed

Albanito, Lidia; Madeo, Antonio; Lappano, Rosamaria; Vivacqua, Adele; Rago, Vittoria; Carpino, Amalia; Oprea, Tudor I; Prossnitz, Eric R; Musti, Anna Maria; Andò, Sebastiano; Maggiolini, Marcello

2007-02-15

Estrogens play a crucial role in the development of ovarian tumors; however, the signal transduction pathways involved in hormone action are still poorly defined. The orphan G protein-coupled receptor 30 (GPR30) mediates the nongenomic signaling of 17beta-estradiol (E2) in a variety of estrogen-sensitive cancer cells through activation of the epidermal growth factor receptor (EGFR) pathway. Whether estrogen receptor alpha (ERalpha) also contributes to GPR30/EGFR signaling is less understood. Here, we show that, in ERalpha-positive BG-1 ovarian cancer cells, both E2 and the GPR30-selective ligand G-1 induced c-fos expression and estrogen-responsive element (ERE)-independent activity of a c-fos reporter gene, whereas only E2 stimulated an ERE-responsive reporter gene, indicating that GPR30 signaling does not activate ERalpha-mediated transcription. Similarly, both ligands up-regulated cyclin D1, cyclin E, and cyclin A, whereas only E2 enhanced progesterone receptor expression. Moreover, both GPR30 and ERalpha expression are required for c-fos stimulation and extracellular signal-regulated kinase (ERK) activation in response to either E2 or G-1. Inhibition of the EGFR transduction pathway inhibited c-fos stimulation and ERK activation by either ligand, suggesting that in ovarian cancer cells GPR30/EGFR signaling relays on ERalpha expression. Interestingly, we show that both GPR30 and ERalpha expression along with active EGFR signaling are required for E2-stimulated and G-1-stimulated proliferation of ovarian cancer cells. Because G-1 was able to induce both c-fos expression and proliferation in the ERalpha-negative/GPR30-positive SKBR3 breast cancer cells, the requirement for ERalpha expression in GPR30/EGFR signaling may depend on the specific cellular context of different tumor types.

Central Agonism of GPR120 Acutely Inhibits Food Intake and Food Reward and Chronically Suppresses Anxiety-Like Behavior in Mice

PubMed Central

Fisette, Alexandre; Fernandes, Maria F.; Hryhorczuk, Cécile; Poitout, Vincent; Alquier, Thierry; Fulton, Stephanie

2016-01-01

Background: GPR120 (FFAR4) is a G-protein coupled receptor implicated in the development of obesity and the antiinflammatory and insulin-sensitizing effects of omega-3 (ω-3) polyunsaturated fatty acids. Increasing central ω-3 polyunsaturated fatty acid levels has been shown to have both anorectic and anxiolytic actions. Despite the strong clinical interest in GPR120, its role in the brain is largely unknown, and thus we sought to determine the impact of central GPR120 pharmacological activation on energy balance, food reward, and anxiety-like behavior. Methods: Male C57Bl/6 mice with intracerebroventricular cannulae received a single injection (0.1 or 1 µM) or continuous 2-week infusion (1 µM/d; mini-pump) of a GPR120 agonist or vehicle. Free-feeding intake, operant lever-pressing for palatable food, energy expenditure (indirect calorimetry), and body weight were measured. GPR120 mRNA expression was measured in pertinent brain areas. Anxiety-like behavior was assessed in the elevated-plus maze and open field test. Results: GPR120 agonist injections substantially reduced chow intake during 4 hours postinjection, suppressed the rewarding effects of high-fat/-sugar food, and blunted approach-avoidance behavior in the open field. Conversely, prolonged central GPR120 agonist infusions reduced anxiety-like behavior in the elevated-plus maze and open field, yet failed to affect free-feeding intake, energy expenditure, and body weight on a high-fat diet. Conclusion: Acute reductions in food intake and food reward suggest that GPR120 could mediate the effects of central ω-3 polyunsaturated fatty acids to inhibit appetite. The anxiolytic effect elicited by GPR120 agonist infusions favors the testing of compounds that can enter the brain to activate GPR120 for the mitigation of anxiety. PMID:26888796

The novel endocannabinoid receptor GPR55 is activated by atypical cannabinoids but does not mediate their vasodilator effects

PubMed Central

Johns, D G; Behm, D J; Walker, D J; Ao, Z; Shapland, E M; Daniels, D A; Riddick, M; Dowell, S; Staton, P C; Green, P; Shabon, U; Bao, W; Aiyar, N; Yue, T-L; Brown, A J; Morrison, A D; Douglas, S A

2007-01-01

Background and purpose: Atypical cannabinoids are thought to cause vasodilatation through an as-yet unidentified ‘CBx' receptor. Recent reports suggest GPR55 is an atypical cannabinoid receptor, making it a candidate for the vasodilator ‘CBx' receptor. The purpose of the present study was to test the hypothesis that human recombinant GPR55 is activated by atypical cannabinoids and mediates vasodilator responses to these agents. Experimental approach: Human recombinant GPR55 was expressed in HEK293T cells and specific GTPγS activity was monitored as an index of receptor activation. In GPR55-deficient and wild-type littermate control mice, in vivo blood pressure measurement and isolated resistance artery myography were used to determine GPR55 dependence of atypical cannabinoid-induced haemodynamic and vasodilator responses. Key results: Atypical cannabinoids O-1602 and abnormal cannabidiol both stimulated GPR55-dependent GTPγS activity (EC50 approximately 2 nM), whereas the CB1 and CB2-selective agonist WIN 55,212-2 showed no effect in GPR55-expressing HEK293T cell membranes. Baseline mean arterial pressure and heart rate were not different between WT and GPR55 KO mice. The blood pressure-lowering response to abnormal cannabidiol was not different between WT and KO mice (WT 20±2%, KO 26±5% change from baseline), nor was the vasodilator response to abnormal cannabidiol in isolated mesenteric arteries (IC50 approximately 3 μ M for WT and KO). The abnormal cannabidiol vasodilator response was antagonized equivalently by O-1918 in both strains. Conclusions: These results demonstrate that while GPR55 is activated by atypical cannabinoids, it does not appear to mediate the vasodilator effects of these agents. PMID:17704827

Epidermal growth factor induces G protein-coupled receptor 30 expression in estrogen receptor-negative breast cancer cells.

PubMed

Albanito, Lidia; Sisci, Diego; Aquila, Saveria; Brunelli, Elvira; Vivacqua, Adele; Madeo, Antonio; Lappano, Rosamaria; Pandey, Deo Prakash; Picard, Didier; Mauro, Loredana; Andò, Sebastiano; Maggiolini, Marcello

2008-08-01

Different cellular receptors mediate the biological effects induced by estrogens. In addition to the classical nuclear estrogen receptors (ERs)-alpha and -beta, estrogen also signals through the seven-transmembrane G-protein-coupled receptor (GPR)-30. Using as a model system SkBr3 and BT20 breast cancer cells lacking the classical ER, the regulation of GPR30 expression by 17beta-estradiol, the selective GPR30 ligand G-1, IGF-I, and epidermal growth factor (EGF) was evaluated. Transient transfections with an expression plasmid encoding a short 5'-flanking sequence of the GPR30 gene revealed that an activator protein-1 site located within this region is required for the activating potential exhibited only by EGF. Accordingly, EGF up-regulated GPR30 protein levels, which accumulated predominantly in the intracellular compartment. The stimulatory role elicited by EGF on GPR30 expression was triggered through rapid ERK phosphorylation and c-fos induction, which was strongly recruited to the activator protein-1 site found in the short 5'-flanking sequence of the GPR30 gene. Of note, EGF activating the EGF receptor-MAPK transduction pathway stimulated a regulatory loop that subsequently engaged estrogen through GPR30 to boost the proliferation of SkBr3 and BT20 breast tumor cells. The up-regulation of GPR30 by ligand-activated EGF receptor-MAPK signaling provides new insight into the well-known estrogen and EGF cross talk, which, as largely reported, contributes to breast cancer progression. On the basis of our results, the action of EGF may include the up-regulation of GPR30 in facilitating a stimulatory role of estrogen, even in ER-negative breast tumor cells.

Activation of GPR55 increases neural stem cell proliferation and promotes early adult hippocampal neurogenesis.

PubMed

Hill, Jeremy D; Zuluaga-Ramirez, Viviana; Gajghate, Sachin; Winfield, Malika; Persidsky, Yuri

2018-06-11

The cannabinoid system exerts functional regulation of neural stem cell (NSC) proliferation and adult neurogenesis, yet not all effects of cannabinoid-like compounds seen can be attributed to the cannabinoid 1 receptor (CB 1 R) or cannabinoid 2 receptor (CB 2 R). The recently de-orphaned GPR55 has been shown to be activated by numerous cannabinoid ligands suggesting that GPR55 is a third cannabinoid receptor. Here we examined the role of GPR55 activation in NSC proliferation and early adult neurogenesis. The effects of GPR55 agonists (LPI, O-1602, ML184) on human NSC proliferation in vitro were assessed by flow cytometry. hNSC differentiation was determined by flow cytometry, qPCR, and immunohistochemistry. Immature neuron formation in the hippocampus of C57BL/6 and GPR55 -/- mice was evaluated by immunohistochemistry. Activation of GPR55 significantly increased proliferation rates of hNSCs in vitro. These effects were attenuated by ML193, a selective GPR55 antagonist. ML184 significantly promoted neuronal differentiation in vitro while ML193 reduced differentiation rates as compared to vehicle treatment. Continuous administration into the hippocampus of O-1602 via cannula connected to osmotic pump resulted in increased Ki67+ cells within the dentate gyrus. O-1602 increased immature neuron generation as assessed by DCX+ and BrdU+ cells as compared to vehicle treated animals. GPR55 -/- animals displayed reduced rates of proliferation and neurogenesis within the hippocampus while O-1602 had no effect as compared to vehicle controls. Together, these findings suggest GPR55 activation as a novel target and strategy to regulate NSC proliferation and adult neurogenesis. This article is protected by copyright. All rights reserved.

Design of a low cost miniaturized SFCW GPR with initial results

NASA Astrophysics Data System (ADS)

Duggal, Swati; Sinha, Piyush; Gupta, Manish; Patel, Anand; Vedam, V. V.; Mevada, Pratik; Chavda, Rajesh; Shah, Amita; Putrevu, Deepak

2016-05-01

This paper discusses about the design &developmental of Ground Penetrating Radar (GPR), various scientific and commercial applications of GPR along with the testing and results of GPR at Antarctica for Ice thickness measurement. GPR instruments are categorised as per their frequency of operation, which is inversely proportional to the depth of penetration. GPRs are also categorized as per method of operation which is time-domain or frequency-domain. Indian market is presently procuring GPRs from only foreign suppliers. Space Applications Centre (SAC) had taken up GPR as R&D Technological development with a view to benchmark the technology which may be transferred to local industry for mass production of instrument at a relatively cheaper cost (~20 times cheaper). Hence, this instrument presents a viable indigenous alternative. Also, the design and configuration was targeted for terrestrial as well as future interplanetary (Lander/Rover) missions of ISRO to map subsurface features. The developed GPR has a very large bandwidth (100%, i.e. bandwidth of 500MHz with centre-frequency of 500MHz) and high dynamic range along with the advantage of being highly portable (<10kg). The system was configured as a Stepped-Frequency-Continuous-Wave (SFCW) GPR which is a frequency domain GPR with the aim to increase the detection capabilities with respect to current systems. In order to achieve this goal, innovative electronic equipment have been designed and developed. Three prototypes were developed and two of them have been delivered for Indian Scientific Expedition to Antarctica (ISEA) in 2013 and 2014-15, respectively and promising results have been obtained. The results from the same closely compare with that from commercial GPR too.

Gpr109a Limits Microbiota-Induced IL-23 Production To Constrain ILC3-Mediated Colonic Inflammation.

PubMed

Bhatt, Brinda; Zeng, Peng; Zhu, Huabin; Sivaprakasam, Sathish; Li, Siyi; Xiao, Haiyan; Dong, Lixin; Shiao, Pamela; Kolhe, Ravindra; Patel, Nikhil; Li, Honglin; Levy-Bercowski, Daniel; Ganapathy, Vadivel; Singh, Nagendra

2018-04-15

A set of coordinated interactions between gut microbiota and the immune cells surveilling the intestine play a key role in shaping local immune responses and intestinal health. Gpr109a is a G protein-coupled receptor expressed at a very high level on innate immune cells and previously shown to play a key role in the induction of colonic regulatory T cells. In this study, we show that Gpr109a -/- Rag1 -/- mice exhibit spontaneous rectal prolapse and colonic inflammation, characterized by the presence of an elevated number of IL-17-producing Rorγt + innate lymphoid cells (ILCs; ILC3). Genetic deletion of Rorγt alleviated the spontaneous colonic inflammation in Gpr109a -/- Rag1 -/- mice. Gpr109a-deficient colonic dendritic cells produce higher amounts of IL-23 and thereby promote ILC3. Moreover, the depletion of gut microbiota by antibiotics treatment decreased IL-23 production, ILC3, and colonic inflammation in Gpr109a -/- Rag1 -/- mice. The ceca of Gpr109a -/- Rag1 -/- mice showed significantly increased colonization by members of Bacteroidaceae , Porphyromonadaceae , Prevotellaceae, Streptococcaceae , Christensenellaceae , and Mogibacteriaceae , as well as IBD-associated microbiota such as Enterobacteriaceae and Mycoplasmataceae , compared with Rag1 -/- mice, housed in a facility positive for Helicobacter and murine norovirus. Niacin, a Gpr109a agonist, suppressed both IL-23 production by colonic DCs and ILC3 number in a Gpr109a-dependent manner. Collectively, our data present a model suggesting that targeting Gpr109a will be potentially beneficial in the suppression of IL-23-mediated immunopathologies. Copyright © 2018 by The American Association of Immunologists, Inc.

Ground penetrating radar evaluation and implementation.

DOT National Transportation Integrated Search

2014-07-01

Six commercial ground penetrating radar (GPR) : systems were evaluated to determine the state-of-the-art of GPR technologies for railroad track : substructure inspection. : Phase 1 evaluated GPR ballast inspection : techniques by performing testing a...

A selective antagonist reveals a potential role of G protein-coupled receptor 55 in platelet and endothelial cell function.

PubMed

Kargl, Julia; Brown, Andrew J; Andersen, Liisa; Dorn, Georg; Schicho, Rudolf; Waldhoer, Maria; Heinemann, Akos

2013-07-01

The G protein-coupled receptor 55 (GPR55) is a lysophosphatidylinositol (LPI) receptor that is also responsive to certain cannabinoids. Although GPR55 has been implicated in several (patho)physiologic functions, its role remains enigmatic owing mainly to the lack of selective GPR55 antagonists. Here we show that the compound CID16020046 ((4-[4-(3-hydroxyphenyl)-3-(4-methylphenyl)-6-oxo-1H,4H,5H,6H-pyrrolo[3,4-c]pyrazol-5-yl] benzoic acid) is a selective GPR55 antagonist. In yeast cells expressing human GPR55, CID16020046 antagonized agonist-induced receptor activation. In human embryonic kidney (HEK293) cells stably expressing human GPR55, the compound behaved as an antagonist on LPI-mediated Ca²⁺ release and extracellular signal-regulated kinases activation, but not in HEK293 cells expressing cannabinoid receptor 1 or 2 (CB₁ or CB₂). CID16020046 concentration dependently inhibited LPI-induced activation of nuclear factor of activated T-cells (NFAT), nuclear factor κ of activated B cells (NF-κB) and serum response element, translocation of NFAT and NF-κB, and GPR55 internalization. It reduced LPI-induced wound healing in primary human lung microvascular endothelial cells and reversed LPI-inhibited platelet aggregation, suggesting a novel role for GPR55 in platelet and endothelial cell function. CID16020046 is therefore a valuable tool to study GPR55-mediated mechanisms in primary cells and tissues.

G protein-coupled receptor 30 localizes to the endoplasmic reticulum and is not activated by estradiol.

PubMed

Otto, Christiane; Rohde-Schulz, Beate; Schwarz, Gilda; Fuchs, Iris; Klewer, Mario; Brittain, Dominic; Langer, Gernot; Bader, Benjamin; Prelle, Katja; Nubbemeyer, Reinhard; Fritzemeier, Karl-Heinrich

2008-10-01

The classical estrogen receptor (ER) mediates genomic as well as rapid nongenomic estradiol responses. In case of genomic responses, the ER acts as a ligand-dependent transcription factor that regulates gene expression in estrogen target tissues. In contrast, nongenomic effects are initiated at the plasma membrane and lead to rapid activation of cytoplasmic signal transduction pathways. Recently, an orphan G protein-coupled receptor, GPR30, has been claimed to bind to and to signal in response to estradiol. GPR30 therefore might mediate some of the nongenomic estradiol effects. The present study was performed to clarify the controversy about the subcellular localization of GPR30 and to gain insight into the in vivo function of this receptor. In transiently transfected cells as well as cells endogenously expressing GPR30, we confirmed that the receptor localized to the endoplasmic reticulum. However, using radioactive estradiol, we observed only saturable, specific binding to the classical ER but not to GPR30. Estradiol stimulation of cells expressing GPR30 had no impact on intracellular cAMP or calcium levels. To elucidate the physiological role of GPR30, we performed in vivo experiments with estradiol and G1, a compound that has been claimed to act as selective GPR30 agonist. In two classical estrogen target organs, the uterus and the mammary gland, G1 did not show any estrogenic effect. Taken together, we draw the conclusion that GPR30 is still an orphan receptor.

The G-protein coupled receptor, GPR84 regulates IL-4 production by T lymphocytes in response to CD3 crosslinking.

PubMed

Venkataraman, Chandrasekar; Kuo, Frederick

2005-11-15

The orphan G-protein coupled receptor, GPR84 is highly expressed in the bone marrow, and in splenic T cells and B cells. In this study, GPR84-deficient mice were generated to understand the biological function of this orphan receptor. The proliferation of T and B cells in response to various mitogens was normal in GPR84-deficient mice. Interestingly, primary stimulation of T cells with anti-CD3 resulted in increased IL-4 but not IL-2 or IFN-gamma production in GPR84(-/-) mice compared to wild-type mice. Augmented IL-4 production in GPR84-deficient T cells was not related to increased frequency of IL-4-secreting cells in response to anti-CD3 stimulation. In fact, stimulation with anti-CD3 and anti-CD28 resulted in increased levels of IL-4 but not IFN-gamma steady-state mRNA in GPR84(-/-) T cells. In addition, Th2 effector cells generated in vitro from GPR84(-/-) mice produced higher levels of IL-4, IL-5 and IL-13 compared to wild-type mice. However, there was no detectable difference in the extent of IL-4 and IL-5 production between the two groups of mice in response to antigen stimulation of spleen cells, isolated from mice previously immunized with OVA in alum. These studies reveal a novel role for GPR84 in regulating early IL-4 gene expression in activated T cells.

Differential phosphorylation signals control endocytosis of GPR15

PubMed Central

Okamoto, Yukari; Shikano, Sojin

2017-01-01

GPR15 is an orphan G protein–coupled receptor (GPCR) that serves for an HIV coreceptor and was also recently found as a novel homing receptor for T-cells implicated in colitis. We show that GPR15 undergoes a constitutive endocytosis in the absence of ligand. The endocytosis was clathrin dependent and partially dependent on β-arrestin in HEK293 cells, and nearly half of the internalized GPR15 receptors were recycled to the plasma membrane. An Ala mutation of the distal C-terminal Arg-354 or Ser-357, which forms a consensus phosphorylation site for basophilic kinases, markedly reduced the endocytosis, whereas phosphomimetic mutation of Ser-357 to Asp did not. Ser-357 was phosphorylated in vitro by multiple kinases, including PKA and PKC, and pharmacological activation of these kinases enhanced both phosphorylation of Ser-357 and endocytosis of GPR15. These results suggested that Ser-357 phosphorylation critically controls the ligand-independent endocytosis of GPR15. The functional role of Ser-357 in endocytosis was distinct from that of a conserved Ser/Thr cluster in the more proximal C-terminus, which was responsible for the β-arrestin– and GPCR kinase–dependent endocytosis of GPR15. Thus phosphorylation signals may differentially control cell surface density of GPR15 through endocytosis. PMID:28615320

Modulation of l-α-Lysophosphatidylinositol/GPR55 Mitogen-activated Protein Kinase (MAPK) Signaling by Cannabinoids*

PubMed Central

Anavi-Goffer, Sharon; Baillie, Gemma; Irving, Andrew J.; Gertsch, Jürg; Greig, Iain R.; Pertwee, Roger G.; Ross, Ruth A.

2012-01-01

GPR55 is activated by l-α-lysophosphatidylinositol (LPI) but also by certain cannabinoids. In this study, we investigated the GPR55 pharmacology of various cannabinoids, including analogues of the CB1 receptor antagonist Rimonabant®, CB2 receptor agonists, and Cannabis sativa constituents. To test ERK1/2 phosphorylation, a primary downstream signaling pathway that conveys LPI-induced activation of GPR55, a high throughput system, was established using the AlphaScreen® SureFire® assay. Here, we show that CB1 receptor antagonists can act both as agonists alone and as inhibitors of LPI signaling under the same assay conditions. This study clarifies the controversy surrounding the GPR55-mediated actions of SR141716A; some reports indicate the compound to be an agonist and some report antagonism. In contrast, we report that the CB2 ligand GW405833 behaves as a partial agonist of GPR55 alone and enhances LPI signaling. GPR55 has been implicated in pain transmission, and thus our results suggest that this receptor may be responsible for some of the antinociceptive actions of certain CB2 receptor ligands. The phytocannabinoids Δ9-tetrahydrocannabivarin, cannabidivarin, and cannabigerovarin are also potent inhibitors of LPI. These Cannabis sativa constituents may represent novel therapeutics targeting GPR55. PMID:22027819

Stimulation of GPR30 Increases Release of EMMPRIN-Containing Microvesicles in Human Uterine Epithelial Cells

PubMed Central

Light, Mallory M.; Mehrotra, Pavni; Nowak, Romana A.

2012-01-01

Context: Uterine remodeling is highly dependent on the glycosylated transmembrane protein extracellular matrix metalloproteinase (MMP) inducer (EMMPRIN). Previous studies indicate estradiol can increase EMMPRIN expression in uterine cells and promote subsequent induction of MMP production. Objective: The aim of this study was to investigate the role of G protein-coupled receptor 30 (GPR30) stimulation on EMMPRIN microvesicle release in the human uterine epithelial cell line hTERT-EEC (EECs). Design: We examined EMMPRIN release by human EECs in response to GPR30 stimulation by microvesicle isolation, Western blot, and immunocytochemistry. We employed a pharmacological approach using the GPR30-selective agonist G1 and the antagonist G15 to determine the receptor specificity of this response. Results: We demonstrated GPR30 expression in EECs and release of EMMPRIN in microvesicles in response to stimulation of GPR30. G1, estradiol, and cholera toxin stimulated EMMPRIN release in microvesicles as detected by Western blot and immunocytochemistry, indicating that stimulation of GPR30 can induce EMMPRIN microvesicle release. Conclusions: These data indicate that EMMPRIN release in microvesicles can be mediated by stimulation of GPR30 in human EECs, suggesting that inappropriate stimulation or expression of this receptor may be significant in uterine pathology. PMID:23012390

Ground Penetrating Radar Imaging of Ancient Clastic Deposits: A Tool for Three-Dimensional Outcrop Studies

NASA Astrophysics Data System (ADS)

Akinpelu, Oluwatosin Caleb

The growing need for better definition of flow units and depositional heterogeneities in petroleum reservoirs and aquifers has stimulated a renewed interest in outcrop studies as reservoir analogues in the last two decades. Despite this surge in interest, outcrop studies remain largely two-dimensional; a major limitation to direct application of outcrop knowledge to the three dimensional heterogeneous world of subsurface reservoirs. Behind-outcrop Ground Penetrating Radar (GPR) imaging provides high-resolution geophysical data, which when combined with two dimensional architectural outcrop observation, becomes a powerful interpretation tool. Due to the high resolution, non-destructive and non-invasive nature of the GPR signal, as well as its reflection-amplitude sensitivity to shaly lithologies, three-dimensional outcrop studies combining two dimensional architectural element data and behind-outcrop GPR imaging hold significant promise with the potential to revolutionize outcrop studies the way seismic imaging changed basin analysis. Earlier attempts at GPR imaging on ancient clastic deposits were fraught with difficulties resulting from inappropriate field techniques and subsequent poorly-informed data processing steps. This project documents advances in GPR field methodology, recommends appropriate data collection and processing procedures and validates the value of integrating outcrop-based architectural-element mapping with GPR imaging to obtain three dimensional architectural data from outcrops. Case studies from a variety of clastic deposits: Whirlpool Formation (Niagara Escarpment), Navajo Sandstone (Moab, Utah), Dunvegan Formation (Pink Mountain, British Columbia), Chinle Formation (Southern Utah) and St. Mary River Formation (Alberta) demonstrate the usefulness of this approach for better interpretation of outcrop scale ancient depositional processes and ultimately as a tool for refining existing facies models, as well as a predictive tool for subsurface reservoir modelling. While this approach is quite promising for detailed three-dimensional outcrop studies, it is not an all-purpose panacea; thick overburden, poor antenna-ground coupling in rough terrains typical of outcrops, low penetration and rapid signal attenuation in mudstone and diagenetic clay- rich deposits often limit the prospects of this novel technique.

Gaussian Process Regression for Predictive But Interpretable Machine Learning Models: An Example of Predicting Mental Workload across Tasks

PubMed Central

Caywood, Matthew S.; Roberts, Daniel M.; Colombe, Jeffrey B.; Greenwald, Hal S.; Weiland, Monica Z.

2017-01-01

There is increasing interest in real-time brain-computer interfaces (BCIs) for the passive monitoring of human cognitive state, including cognitive workload. Too often, however, effective BCIs based on machine learning techniques may function as “black boxes” that are difficult to analyze or interpret. In an effort toward more interpretable BCIs, we studied a family of N-back working memory tasks using a machine learning model, Gaussian Process Regression (GPR), which was both powerful and amenable to analysis. Participants performed the N-back task with three stimulus variants, auditory-verbal, visual-spatial, and visual-numeric, each at three working memory loads. GPR models were trained and tested on EEG data from all three task variants combined, in an effort to identify a model that could be predictive of mental workload demand regardless of stimulus modality. To provide a comparison for GPR performance, a model was additionally trained using multiple linear regression (MLR). The GPR model was effective when trained on individual participant EEG data, resulting in an average standardized mean squared error (sMSE) between true and predicted N-back levels of 0.44. In comparison, the MLR model using the same data resulted in an average sMSE of 0.55. We additionally demonstrate how GPR can be used to identify which EEG features are relevant for prediction of cognitive workload in an individual participant. A fraction of EEG features accounted for the majority of the model’s predictive power; using only the top 25% of features performed nearly as well as using 100% of features. Subsets of features identified by linear models (ANOVA) were not as efficient as subsets identified by GPR. This raises the possibility of BCIs that require fewer model features while capturing all of the information needed to achieve high predictive accuracy. PMID:28123359

GPR monitoring of rock mass stability in selected post-mining region in Poland

NASA Astrophysics Data System (ADS)

Golebiowski, T.

2012-04-01

Mining activity conducted over a period of many years may cause significant changes in the geological medium and in effect leads to strong degradation of the surface in mining and post-mining regions. One of the most dangerous effects of mining activity is appearance of sinkholes on the ground surface. These phenomena are related to the changes of initial stress-strain state of the rock mass as a result of mining works and the creation of fractures which migrate from excavations to the ground surface. The paper presents the results of selected GPR surveys carried out in the area of the coal mine "Siersza" in two sites, i.e. in the town of Siersza and in the village of Mloszowa (Upper Silesia, South Poland). The aim of the GPR research was 3D visualisation of fractured zones distribution generated by the mining activity and an attempt to make prediction where sinkholes would appear. In order to realize this aim the measurements were conducted in 4D mode (i.e. time-space analysis), which allowed to observe the fractured zones migration towards the ground surface. In order to obtain 4D information (x-y-z-t) GPR surveys were conducted for several years, along the same parallel profiles, separated by a constant distance equals 2.5m. The terrain measurements were carried out with RAMAC and PROEX GPR systems using 250, 200, 100 and 50 MHz antennae. Because of the limited length of this paper, only selected results from the 200-250 MHz antennae are presented. The results were presented in the form of the distribution of GPR signals energies calculated from Hilbert transform, applying the technique of energy inversion. In the site of Siersza, on the basis of 4D GPR visualisation, regions threatened with the formation of sinkholes were distinguished. A few years after the research, 2 cavities appeared in this site which proved that the interpretation was correct. Another fractured zone in this site was confirmed by a borehole. In the site of Mloszowa the GPR measurements were carried out in the region of already existing sinkhole (with the diameter of about 15m and the depth of about 10m) in order to detect the distribution of dangerous fractures around this sinkhole. As the results of GPR research has shown, fractured zones in this site developed quickly as a result of superimposition of fractures induced by mining activity and the processes of suffusion and congelifraction. GPR monitoring of the rock mass stability in mining and post-mining areas is very important because sinkholes threaten the live of people and stability of structures and installations. As it was shown in the paper, the GPR method gives very good results for the prediction of sinkholes creation if it is applied in 4D mode. A limitation of this method is the depth penetration, i.e. a dozen or so meters with resolution which allows to detect fractures and strong attenuation of electromagnetic waves in the clay formations. The research was financed from the funds of National Science Center, on the basis of agreement no. UMO-2011/01/B/ST7/06178 and decision no. DEC-2011/01/B/ST7/06178.

GPR 120: The Potential Target for Obesity Treatment.

PubMed

Tanagho, Peter A; Shohdy, Kyrillus S

2016-01-01

G protein coupled receptor 120 (GPR120) is a class of receptors in the gastrointestinal tract (GIT) that is implicated in nutrient sensing and body weight regulation. Functions of GPR120 are thought to be mediated by the release of a group of hormones known as incretins, such as glucagon like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP). We have searched PubMed with the keywords "GPR120","GLP-1" and "obesity". Relevant studies were retrieved and included in the review. Recently, many exogenous compounds have been investigated in their role in the release of GLP-1 and in causing weight loss in obese rats. However, some results question the putative role of GPR120 in metabolic homeostasis. Herein, we evaluate the potential use of GPR120 as a target receptor in obesity and found it to be ubiquitous throughout the GIT, with various functions in each site. In order to find the optimal drug, the role of GPR120 in each site needs to be defined and selectivity of the potential drug needs to be studied to ensure the success of this growing line of obesity management.

GPR84 deficiency reduces microgliosis, but accelerates dendritic degeneration and cognitive decline in a mouse model of Alzheimer's disease.

PubMed

Audoy-Rémus, Julie; Bozoyan, Lusine; Dumas, Aline; Filali, Mohammed; Lecours, Cynthia; Lacroix, Steve; Rivest, Serge; Tremblay, Marie-Eve; Vallières, Luc

2015-05-01

Microglia surrounds the amyloid plaques that form in the brains of patients with Alzheimer's disease (AD), but their role is controversial. Under inflammatory conditions, these cells can express GPR84, an orphan receptor whose pathophysiological role is unknown. Here, we report that GPR84 is upregulated in microglia of APP/PS1 transgenic mice, a model of AD. Without GPR84, these mice display both accelerated cognitive decline and a reduced number of microglia, especially in areas surrounding plaques. The lack of GPR84 affects neither plaque formation nor hippocampal neurogenesis, but promotes dendritic degeneration. Furthermore, GPR84 does not influence the clinical progression of other diseases in which its expression has been reported, i.e., experimental autoimmune encephalomyelitis (EAE) and endotoxic shock. We conclude that GPR84 plays a beneficial role in amyloid pathology by acting as a sensor for a yet unknown ligand that promotes microglia recruitment, a response affecting dendritic degeneration and required to prevent further cognitive decline. Copyright © 2015 Elsevier Inc. All rights reserved.

Medium-chain fatty acids as ligands for orphan G protein-coupled receptor GPR84.

PubMed

Wang, Jinghong; Wu, Xiaosu; Simonavicius, Nicole; Tian, Hui; Ling, Lei

2006-11-10

Free fatty acids (FFAs) play important physiological roles in many tissues as an energy source and as signaling molecules in various cellular processes. Elevated levels of circulating FFAs are associated with obesity, dyslipidemia, and diabetes. Here we show that GPR84, a previously orphan G protein-coupled receptor, functions as a receptor for medium-chain FFAs with carbon chain lengths of 9-14. Medium-chain FFAs elicit calcium mobilization, inhibit 3',5'-cyclic AMP production, and stimulate [35S]guanosine 5'-O-(3-thiotriphosphate) binding in a GPR84-dependent manner. The activation of GPR84 by medium-chain FFAs couples primarily to a pertussis toxin-sensitive G(i/o) pathway. In addition, we show that GPR84 is selectively expressed in leukocytes and markedly induced in monocytes/macrophages upon activation by lipopolysaccharide. Furthermore, we demonstrate that medium-chain FFAs amplify lipopolysaccharide-stimulated production of the proinflammatory cytokine interleukin-12 p40 through GPR84. Our results indicate a role for GPR84 in directly linking fatty acid metabolism to immunological regulation.

G protein-coupled receptor 56 regulates mechanical overload-induced muscle hypertrophy.

PubMed

White, James P; Wrann, Christiane D; Rao, Rajesh R; Nair, Sreekumaran K; Jedrychowski, Mark P; You, Jae-Sung; Martínez-Redondo, Vicente; Gygi, Steven P; Ruas, Jorge L; Hornberger, Troy A; Wu, Zhidan; Glass, David J; Piao, Xianhua; Spiegelman, Bruce M

2014-11-04

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha 4 (PGC-1α4) is a protein isoform derived by alternative splicing of the PGC1α mRNA and has been shown to promote muscle hypertrophy. We show here that G protein-coupled receptor 56 (GPR56) is a transcriptional target of PGC-1α4 and is induced in humans by resistance exercise. Furthermore, the anabolic effects of PGC-1α4 in cultured murine muscle cells are dependent on GPR56 signaling, because knockdown of GPR56 attenuates PGC-1α4-induced muscle hypertrophy in vitro. Forced expression of GPR56 results in myotube hypertrophy through the expression of insulin-like growth factor 1, which is dependent on Gα12/13 signaling. A murine model of overload-induced muscle hypertrophy is associated with increased expression of both GPR56 and its ligand collagen type III, whereas genetic ablation of GPR56 expression attenuates overload-induced muscle hypertrophy and associated anabolic signaling. These data illustrate a signaling pathway through GPR56 which regulates muscle hypertrophy associated with resistance/loading-type exercise.

GPR40 partial agonists and AgoPAMs: Differentiating effects on glucose and hormonal secretions in the rodent

PubMed Central

Pachanski, Michele J.; Kirkland, Melissa E.; Kosinski, Daniel T.; Mane, Joel; Cheewatrakoolpong, Boonlert; Xue, Jiyan; Szeto, Daphne; Forrest, Gail; Miller, Corin; Bunzel, Michelle; Plummer, Christopher W.; Chobanian, Harry R.; Miller, Michael W.; Souza, Sarah; Thomas-Fowlkes, Brande S.; Ogawa, Aimie M.; Weinglass, Adam B.; Di Salvo, Jerry; Li, Xiaoyan; Feng, Yue; Tatosian, Daniel A.; Howard, Andrew D.; Colletti, Steven L.

2017-01-01

GPR40 agonists are effective antidiabetic agents believed to lower glucose through direct effects on the beta cell to increase glucose stimulated insulin secretion. However, not all GPR40 agonists are the same. Partial agonists lower glucose through direct effects on the pancreas, whereas GPR40 AgoPAMs may incorporate additional therapeutic effects through increases in insulinotrophic incretins secreted by the gut. Here we describe how GPR40 AgoPAMs stimulate both insulin and incretin secretion in vivo over time in diabetic GK rats. We also describe effects of AgoPAMs in vivo to lower glucose and body weight beyond what is seen with partial GPR40 agonists in both the acute and chronic setting. Further comparisons of the glucose lowering profile of AgoPAMs suggest these compounds may possess greater glucose control even in the presence of elevated glucagon secretion, an unexpected feature observed with both acute and chronic treatment with AgoPAMs. Together these studies highlight the complexity of GPR40 pharmacology and the potential additional benefits AgoPAMs may possess above partial agonists for the diabetic patient. PMID:29053717

An interpretation model of GPR point data in tunnel geological prediction

NASA Astrophysics Data System (ADS)

He, Yu-yao; Li, Bao-qi; Guo, Yuan-shu; Wang, Teng-na; Zhu, Ya

2017-02-01

GPR (Ground Penetrating Radar) point data plays an absolutely necessary role in the tunnel geological prediction. However, the research work on the GPR point data is very little and the results does not meet the actual requirements of the project. In this paper, a GPR point data interpretation model which is based on WD (Wigner distribution) and deep CNN (convolutional neural network) is proposed. Firstly, the GPR point data is transformed by WD to get the map of time-frequency joint distribution; Secondly, the joint distribution maps are classified by deep CNN. The approximate location of geological target is determined by observing the time frequency map in parallel; Finally, the GPR point data is interpreted according to the classification results and position information from the map. The simulation results show that classification accuracy of the test dataset (include 1200 GPR point data) is 91.83% at the 200 iteration. Our model has the advantages of high accuracy and fast training speed, and can provide a scientific basis for the development of tunnel construction and excavation plan.

G protein-coupled receptor 56 regulates mechanical overload-induced muscle hypertrophy

PubMed Central

White, James P.; Wrann, Christiane D.; Rao, Rajesh R.; Nair, Sreekumaran K.; Jedrychowski, Mark P.; You, Jae-Sung; Martínez-Redondo, Vicente; Gygi, Steven P.; Ruas, Jorge L.; Hornberger, Troy A.; Wu, Zhidan; Glass, David J.; Piao, Xianhua; Spiegelman, Bruce M.

2014-01-01

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha 4 (PGC-1α4) is a protein isoform derived by alternative splicing of the PGC1α mRNA and has been shown to promote muscle hypertrophy. We show here that G protein-coupled receptor 56 (GPR56) is a transcriptional target of PGC-1α4 and is induced in humans by resistance exercise. Furthermore, the anabolic effects of PGC-1α4 in cultured murine muscle cells are dependent on GPR56 signaling, because knockdown of GPR56 attenuates PGC-1α4–induced muscle hypertrophy in vitro. Forced expression of GPR56 results in myotube hypertrophy through the expression of insulin-like growth factor 1, which is dependent on Gα12/13 signaling. A murine model of overload-induced muscle hypertrophy is associated with increased expression of both GPR56 and its ligand collagen type III, whereas genetic ablation of GPR56 expression attenuates overload-induced muscle hypertrophy and associated anabolic signaling. These data illustrate a signaling pathway through GPR56 which regulates muscle hypertrophy associated with resistance/loading-type exercise. PMID:25336758

Magnetic and GPR surveys of a former munitions foundry site at the Denver Federal Center

USGS Publications Warehouse

Campbell, David L.; Beanland, Shay; Lucius, Jeffrey E.; Powers, Michael H.

2000-01-01

We made magnetometer and ground penetrating radar (GPR) surveys over part of the foundation of a World War II-era foundry located on the Denver Federal Center. The site contains a number of highly magnetic source bodies, concrete foundation walls, and underground openings, buried under a clay cap. The cap is several feet thick and has a conductivity of about 35 mS/m, making the features underneath it a poor target for conventional GPR. Indeed, the raw data look unlike typical GPR data, but rather show reverberation (?) bands under sidewalks and other shallow buried sources. Using a newly-written computer package, we made plan maps of the GPR response at different time slices. The sliced GPR data did not outline buried foundry foundations, as we had hoped it might. The resulting plan maps of the sliced data show sidewalks and other blobby features, some of which correspond to magnetometer highs.

G protein-coupled receptor 30 in tumor development.

PubMed

Wang, Dengfeng; Hu, Lina; Zhang, Guonan; Zhang, Lin; Chen, Chen

2010-08-01

Estrogen plays several important physiological and pathological functions in not only reproductive system but many other systems as well. Its transcriptional activation has been traditionally described as being mediated by classic nuclear estrogen receptors (ERs). It is however established recently that a novel functional estrogen transmembrane receptor, G protein-coupled receptor 30 (GPR30), modulates both rapid non-genomic events and genomic transcriptional events of estrogen. It has been demonstrated that GPR30 promotes the progress of estrogen-related tumors through mitogen-activated protein kinase (MAPK) signaling pathways. Effects mediated by GPR30 are maintained when classic ERs are absent or blocked. In addition, GPR30 is involved in drug resistance, which is often occurring during cancer treatments. All these new findings strongly imply that GPR30 may be an important therapeutic target for estrogen-related tumors. Simultaneously blocking both GPR30 and classic ERs may be a better strategy for the treatment of estrogen-related tumors.

Use of GPR Surveys in Historical Archaeology Studies at Gainesville Mississippi

NASA Technical Reports Server (NTRS)

Goodwin, Ben; Giardino, Marco; Spruce, Joe

2002-01-01

Ground Penetrating Radar (GPR) was used in recent surveys to acquire subsurface geophysical data for historic sites at Gainesville, Mississippi, a town abandoned in 1962 with the building of the John C. Stennis Space Center. Prior to GPR data collection, a 20- by 20-meter grid was established using UTM map projection and GPS for locating cell corners. Lines of GPR data were then collected every 25 centimeters. The images were then processed, and coregistered to georeferenced aerial and satellite imagery. This procedure is enabling analysts to assess the GPR imagery more effectively in a geospatial context. Field validation of anomalies created by known subsurface features from both recent and historic sources is allowing soil attributes, such as variations in Relative Dielectric Permittivity, to be tested more accurately. Additional work is assessing how GPR data can be effectively combined with other forms of remote sensing to direct archaeological surveys and excavations.

Geophysical detection of on-site wastewater plumes in the North Carolina Coastal Plain, USA

NASA Astrophysics Data System (ADS)

Smith, Matthew

Nonpoint source pollution (NPS) continues to be the leading cause of water quality degradation in the United States. On-site wastewater systems (OWS) contribute to NPS; however, due to the range of system designs and complexity of the subsurface, OWS contributions to groundwater pollution are not well understood. As the population of coastal North Carolina continues to increase, better methods to locate and characterize wastewater impacted groundwater are needed. Previous studies have demonstrated the ability of non-intrusive geophysical methods to provide high resolution information on various contaminants in different geologic settings. The goals of this study were to evaluate the utility of ground penetrating radar (GPR) and capacitively coupled resistivity (CCR) for detecting OWS components, delineating associated wastewater plumes, and monitoring temporal variations in groundwater quality. Cross-sectional and three dimensional (3D) geophysical surveys were conducted periodically over a one year period (February 2011--January 2012) at two schools utilizing OWS in the lower Neuse River Basin (NRB) in the North Carolina Coastal Plain (NCCP). Cores were collected at both study sites; as well as monthly groundwater depth, temperature, and specific conductivity measurements to better constrain the geophysical interpretations. Additionally, dissolved inorganic nitrogen (DIN) and Cl concentrations were monitored bi-monthly to assess nutrient transport at the sites. The 3D GPR surveys effectively located the wastewater drainage trenches at both sites, in close agreement with locations described in as-built OWS blueprints. Regression analysis of resistivity versus groundwater specific conductivity revealed an inverse relationship, suggesting resistivity ≤ 250 ohm.m was indicative of wastewater impacted groundwater at both sites. The 3D resistivity models identified regions of low resistivity beneath the drainfields relative to background values. Regression analysis of GPR signal absolute peak amplitude (APA) versus groundwater specific conductivity revealed a decrease in APA indicative of radar signal attenuation at locations where groundwater specific conductivity was elevated. The 3D GPR models identified regions of attenuated radar signal beneath the drainfields relative to background locations. Comparisons of groundwater specific conductivity, GPR, and CCR lateral wastewater plume estimates indicated similar dimensions at both sites. The sensitivity of resistivity measurements tended to decline with increased water-table depth; although, differences in resistivity associated with seasonal water-table depth changes were noticeable. Overall, results of this study suggest that GPR and CCR surveys combined with sediment, hydrologic, and water quality data may provide reliable information on the location of OWS components and extent of associated wastewater plumes. The GPR surveys successfully located the wastewater drainage trenches and helped image the uppermost surface of the wastewater plumes. The CCR surveys delineated the lateral wastewater plume dimensions and revealed temporal changes in groundwater quality associated with differences in groundwater recharge.

Quantitative analysis of ground penetrating radar data in the Mu Us Sandland

NASA Astrophysics Data System (ADS)

Fu, Tianyang; Tan, Lihua; Wu, Yongqiu; Wen, Yanglei; Li, Dawei; Duan, Jinlong

2018-06-01

Ground penetrating radar (GPR), which can reveal the sedimentary structure and development process of dunes, is widely used to evaluate aeolian landforms. The interpretations for GPR profiles are mostly based on qualitative descriptions of geometric features of the radar reflections. This research quantitatively analyzed the waveform parameter characteristics of different radar units by extracting the amplitude and time interval parameters of GPR data in the Mu Us Sandland in China, and then identified and interpreted different sedimentary structures. The results showed that different types of radar units had specific waveform parameter characteristics. The main waveform parameter characteristics of sand dune radar facies and sandstone radar facies included low amplitudes and wide ranges of time intervals, ranging from 0 to 0.25 and 4 to 33 ns respectively, and the mean amplitudes changed gradually with time intervals. The amplitude distribution curves of various sand dune radar facies were similar as unimodal distributions. The radar surfaces showed high amplitudes with time intervals concentrated in high-value areas, ranging from 0.08 to 0.61 and 9 to 34 ns respectively, and the mean amplitudes changed drastically with time intervals. The amplitude and time interval values of lacustrine radar facies were between that of sand dune radar facies and radar surfaces, ranging from 0.08 to 0.29 and 11 to 30 ns respectively, and the mean amplitude and time interval curve was approximately trapezoidal. The quantitative extraction and analysis of GPR reflections could help distinguish various radar units and provide evidence for identifying sedimentary structure in aeolian landforms.

Analyses of GPR signals for characterization of ground conditions in urban areas

NASA Astrophysics Data System (ADS)

Hong, Won-Taek; Kang, Seonghun; Lee, Sung Jin; Lee, Jong-Sub

2018-05-01

Ground penetrating radar (GPR) is applied for the characterization of the ground conditions in urban areas. In addition, time domain reflectometry (TDR) and dynamic cone penetrometer (DCP) tests are conducted for the accurate analyses of the GPR images. The GPR images are acquired near a ground excavation site, where a ground subsidence occurred and was repaired. Moreover, the relative permittivity and dynamic cone penetration index (DCPI) are profiled through the TDR and DCP tests, respectively. As the ground in the urban area is kept under a low-moisture condition, the relative permittivity, which is inversely related to the electromagnetic impedance, is mainly affected by the dry density and is inversely proportional to the DCPI value. Because the first strong signal in the GPR image is shifted 180° from the emitted signal, the polarity of the electromagnetic wave reflected at the dense layer, where the reflection coefficient is negative, is identical to that of the first strong signal. The temporal-scaled GPR images can be accurately converted into the spatial-scaled GPR images using the relative permittivity determined by the TDR test. The distribution of the loose layer can be accurately estimated by using the spatial-scaled GPR images and reflection characteristics of the electromagnetic wave. Note that the loose layer distribution estimated in this study matches well with the DCPI profile and is visually verified from the endoscopic images. This study demonstrates that the GPR survey complemented by the TDR and DCP tests, may be an effective method for the characterization of ground conditions in an urban area.

GPR43 activation enhances psoriasis-like inflammation through epidermal upregulation of IL-6 and dual oxidase 2 signaling in a murine model.

PubMed

Nadeem, Ahmed; Ahmad, Sheikh F; Al-Harbi, Naif O; El-Sherbeeny, Ahmed M; Al-Harbi, Mohammed M; Almukhlafi, Talal S

2017-05-01

The gut is densely inhabited by commensal bacteria, which metabolize dietary fibers/undigested carbohydrates and produce short-chain fatty acids such as acetate. GPR43 is one of the receptors to sense short-chain fatty acids, and expressed in various immune and non-immune cells. Acetate/GPR43 signaling has been shown to affect various inflammatory diseases through Th17 responses and NADPH oxidase (NOX)-derived reactive oxygen species (ROS) generation. However, no study has previously explored the effects of GPR43 activation during psoriasis-like inflammation. Therefore, this study investigated the effect of acetate/phenylacetamide (GPR43 agonists) on imiquimod induced skin inflammation in mice. Mice were administered phenylacetamide/acetate followed by assessment of skin inflammation, NOXs (NOX-2, NOX-4, dual oxidases), and Th17 related signaling. Our study showed induction of epidermal GPR43 after imiquimod treatment, i.e. psoriasis-like inflammation. Acetate administration in psoriatic mice led to further increase in skin inflammation (ear thickness/myeloperoxidase activity) with concurrent increase in Th17 immune responses and epidermal dual oxidase-2 signaling. Further, topical application of GPR43 agonist, phenylacetamide led to enhanced ear thickness with concomitant epidermal IL-6 signaling as well as dual oxidase-2 upregulation which may be responsible for increased psoriasis-like inflammation. Taken together, dual oxidase-2 and IL-6 play important roles in GPR43-mediated skin inflammation. The current study suggests that GPR43 activation in psoriatic patients may lead to aggravation of psoriatic inflammation. Copyright © 2017 Elsevier Inc. All rights reserved.

GPR120 in adipocytes has differential roles in the production of pro-inflammatory adipocytokines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hasan, Arif Ul, E-mail: ahasan@med.kagawa-u.ac.jp; Department of Pharmacology, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793; Ohmori, Koji

How nutritional excess leads to inflammatory responses in metabolic syndrome is not well characterized. Here, we evaluated the effects of ω-3 polyunsaturated fatty acid specific G-protein coupled receptor 120 (GPR120) activation on inflammatory pathways in adipocytes, and the influence of this process on macrophage migration. Using 3T3-L1 adipocytes, we found that agonizing GPR120 using its synthetic ligand, GSK137647, attenuated both basal and lipopolysaccharide-induced production of interleukin-6 (IL-6) and C-C motif chemokine ligand 2 (CCL2). Moreover, the intervention reduced the phosphorylation of nuclear factor kappa B inhibitor alpha (IκBα) and nuclear translocation of nuclear factor kappa-B p65 subunit (p65). Furthermore, themore » silencing of GPR120 itself reduced IL-6 and CCL2 mRNA expression. Inhibition of protein kinase C (PKC) augmented the down-regulatory effect of GSK137647 on IL-6 and CCL2 mRNA. Using a luciferase assay to measure promoter activity of the IL-6 gene in mouse embryonic fibroblasts, we demonstrated that exogenous transfection of GPR120 alone reduced the promoter activity, which was augmented by GSK137647. Inhibition of PKC further reduced the promoter activity. Nevertheless, RAW 264.7 macrophages grown in conditioned medium collected from GSK137647-treated adipocytes attenuated the expressions of matrix metalloproteinases-9 and -3, and tissue inhibitor of metalloproteinase-1. Conditioned medium also inhibited the lipopolysaccharide-induced migration of these macrophages. Taken together, these findings provide critical evidence that although GPR120 is associated with a PKC-mediated pro-inflammatory pathway, the direct inhibitory effects of GPR120 on the nuclear factor kappa B pathway are anti-inflammatory. Moreover, GPR120 activity can attenuate the adipocyte-mediated enhanced production of extracellular matrix-modulating factors in macrophages and can reduce their migration by a paracrine mechanism. - Highlights: • Agonizing GPR120 differentially regulates the pro-inflammatory adipocytokines. • Agonizing GPR120 in adipocytes attenuates NF-κB mediated IL-6 and CCL2 production. • Agonizing GPR120 concomitantly triggers a PKC mediated pro-inflammatory pathway. • However, the resulted effect in adipocytes remains anti-inflammatory. • Agonizing GPR120 in adipocytes reduces macrophage migration in a paracrine manner.« less

Effect of medium electrophysical parameters and their temperature dependences on wideband electromagnetic pulse propagation

NASA Astrophysics Data System (ADS)

Volkomirskaya, L. B.; Gulevich, O. A.; Reznikov, A. E.

2017-03-01

The dielectric permittivity of fiery spoil tips (Shakhty town, Rostov Region) is studied with the use of a GROT 12E remote-controlled ground-penetrating radar (GPR). An anomalous zone in a combustion source is shown to be clearly pronounced in GPR data due to the temperature dependence of the dielectric permittivity of these spoil tips. To substantiate this statement, the GPR data are compared with direct measurements of soil temperatures at depths from 1.5 to 2.5 m. The experimental results are compared with the variable spectral range of a GPR sounding pulse. GPR is shown to be a promising tool for the mapping of temperature-contrast underground objects.

G protein-coupled receptor 30 regulates trophoblast invasion and its deficiency is associated with preeclampsia.

PubMed

Tong, Chao; Feng, Xiang; Chen, Jun; Qi, Xingchen; Zhou, Liyuan; Shi, Shuming; Kc, Kamana; Stanley, Joanna L; Baker, Philip N; Zhang, Hua

2016-04-01

Preeclampsia is known to be associated with reduced circulating levels of estrogen. The effects of estrogen in preeclampsia are normally mediated by the classical estrogen receptors. Intriguingly, a novel estrogen receptor, G protein-coupled receptor 30 (GPR30), has been recently found to play an important role in several estrogenic effects. However, the mechanisms by which GPR30 may mediate the development of preeclampsia remain unknown. We observed that the expression of GPR30 in placental trophoblast cells is lower in preeclamptic placentas compared with normotensive controls. We then investigated the role of GPR30 in trophoblast cell invasion by utilizing placental explants and the immortalized human trophoblast cell line (HTR8/SVneo). The selective GPR30 agonist G1 and a general estrogen receptors agonist 17-β-estradiol (E2) both improved trophoblast cells invasion by upregulating MMP9 expression and the PI3K-Akt signaling pathway. This effect was abolished by a selective GPR30 inhibitor G15, implying that GPR30 may be involved in regulating trophoblast invasion, and that down-regulation of this receptor may result in the development of preeclampsia. The present study suggests that GPR30 is a critical regulator of trophoblast cell invasion, and as such may be a potential therapeutic interventional target for preeclampsia and other pregnancy complications resulting from impaired trophoblast invasion.

Soluble Fibre Meal Challenge Reduces Airway Inflammation and Expression of GPR43 and GPR41 in Asthma.

PubMed

Halnes, Isabel; Baines, Katherine J; Berthon, Bronwyn S; MacDonald-Wicks, Lesley K; Gibson, Peter G; Wood, Lisa G

2017-01-10

Short chain fatty acids (SCFAs) are produced following the fermentation of soluble fibre by gut bacteria. In animal models, both dietary fibre and SCFAs have demonstrated anti-inflammatory effects via the activation of free fatty acid receptors, such as G protein-coupled receptor 41 and 43 (GPR41 and GPR43). This pilot study examined the acute effect of a single dose of soluble fibre on airway inflammation-including changes in gene expression of free fatty acid receptors-in asthma. Adults with stable asthma consumed a soluble fibre meal ( n = 17) containing 3.5 g inulin and probiotics, or a control meal ( n = 12) of simple carbohydrates. Exhaled nitric oxide (eNO) was measured and induced sputum was collected at 0 and 4 h for differential cell counts, measurement of interleukin-8 (IL-8) protein concentration, and GPR41 and GPR43 gene expression. At 4 h after meal consumption, airway inflammation biomarkers, including sputum total cell count, neutrophils, macrophages, lymphocytes, sputum IL-8, and eNO significantly decreased compared to baseline in the soluble fibre group only. This corresponded with upregulated GPR41 and GPR43 sputum gene expression and improved lung function in the soluble fibre group alone. Soluble fibre has acute anti-inflammatory effects in asthmatic airways. Long-term effects of soluble fibre as an anti-inflammatory therapy in asthma warrants further investigation.

Association of a reduction of G-protein coupled receptor 30 expression and the pathogenesis of preeclampsia

PubMed Central

Feng, Xiang; Zhou, Liyuan; Mao, Xun; Tong, Chao; Chen, Xuyang; Zhao, Diqi; Baker, Philip N.; Xia, Yinyin; Zhang, Hua

2017-01-01

Preeclampsia is a pregnancy-specific disorder, which is a leading cause of maternal and perinatal mortality and morbidity. A lower increase of estrogen, compared with the increase in progesterone, is associated with pathogenesis of the disease during pregnancy. G-protein-coupled receptor 30 (GPR30) mediates the action of estrogen, however remains to be investigated in preeclampsia. The levels of GPR30 were measured in placentae from uncomplicated pregnancies and pregnancies complicated by preeclampsia using immunohistochemistry and western blotting. GPR30 expression was additionally measured in placental HTR8/SVneo cells following 17β-estrogen (E2) treatment in normal or hypoxia-reoxygenation conditions by western blotting. In addition, the outgrowth of HTR8/SVneo cells following E2 treatment in hypoxia-reoxygenation conditions was measured. Levels of GPR30 were significantly reduced in placentae from women with preeclampsia as compared with uncomplicated pregnancies. Treatment with E2 significantly increased the expression of GPR30 in HTR8/SVneo cells, in normal and hypoxia-reoxygenation conditions. Furthermore, treatment with E2 increased the outgrowth of HTR8/SVneo cells in hypoxia-reoxygenation conditions. The present study demonstrated lowered placental expression of GPR30 in preeclampsia. Estrogen treatment increases GPR30 expression in extravillous trophoblast and GPR30 may be involved in extravillous trophoblast invasion. PMID:28849224

Application of ground-penetrating radar methods in determining hydrogeologic conditions in a karst area, west-central Florida

USGS Publications Warehouse

Barr, G.L.

1993-01-01

Ground-penetrating radar (GPR) is useful as a surface geophysical method for exploring geology and subsurface features in karst settings. Interpretation of GPR data was used to infer lithology and hydrogeologic conditions in west-central Florida. This study demonstrates how GPR methods can be used to investigate the hydrogeology of an area. GPR transmits radio- frequency electromagnetic waves into the ground and receives reflected energy waves from subsurface interfaces. Subsurface profiles showing sediment thickness, depth to water table and clay beds, karst development, buried objects, and lake-bottom structure were produced from GPR traverses obtained during December 1987 and March 1990 in Pinellas, Hillsborough, and Hardee Counties in west-central Florida. Performance of the GPR method is site specific, and data collected are principally affected by the sediment and pore fluids, conductances and dielectric constants. Effective exploration depths of the GPR surveys through predominately unsaturated and saturated sand and clay sediments at five study sites ranged from a few feet to greater than 50 feet below land surface. Exploration depths were limited when high conductivity clay was encountered, whereas greater exploration depths were possible in material composed of sand. Application of GPR is useful in profiling subsurface conditions, but proper interpretation depends upon the user's knowledge of the equipment and the local hydrogeological setting, as well as the ability to interpret the graphic profile.

Characterization for capillary barriers effects in a sand box test using time-lapsed GPR measurements

NASA Astrophysics Data System (ADS)

Kuroda, S.; Ishii, N.; Morii, T.

2017-12-01

Capillary barriers have been known as the method to protect subsurface regions against infiltration from soil surface. It is caused by essentially heterogeneous structure in permeability or soil physical property and produce non-uniform infiltration process then, in order to estimate the actual situation of the capillary barrier effect, the site-characterization with imaging technique like geophysical prospecting is effective. In this study, we examine the applicability of GPR to characterization for capillary barriers. We built a sand box with 90x340x90cm in which a thin high-permeable gravel layer was embedded as a capillary barrier. We conducted an infiltration test in the sand box using porous tube array for irrigation. It is expected to lead to non-uniform flow of soil water induced by capillary barrier effects. We monitored this process by various types of GPR measurements, including time-lapsed common offset profiling (COP) with multi- frequency antenna and transmission measurements like cross-borehole radar. At first, we conducted GPR common-offset survey. It could show the depth of capillary barrier in sand box. After that we conducted the infiltration test and GPR monitoring for infiltration process. GPR profiles can detect the wetting front and estimate water content change in the soil layer above the capillary barrier. From spatial change in these results we can estimate the effect of capillary barrier and the zone where the break through occur or not. Based on these results, we will discuss the applicability of GPR for monitoring the phenomena around the capillary barrier of soil. At first, we conducted GPR common-offset survey. It could show the depth of capillary barrier in sand box. After that we conducted the infiltration test and GPR monitoring for infiltration process. GPR profiles can detect the wetting front and estimate water content change in the soil layer above the capillary barrier. From spatial change in these results we can estimate the effect of capillary barrier and the zone where the break through occur. Based on these results, we will discuss the applicability of GPR for monitoring the phenomena around the capillary barrier of soil.

A Ground Penetrating Radar (GPR) Survey of KIilbourne Hole, Southern New Mexico: Implication for Paleohydrology and Near Surface Geophysical Exploration of Mars and the Moon

NASA Astrophysics Data System (ADS)

Rhodes, N.; Hurtado, J. M.

2013-05-01

Features such as the Home Plate plateau on Mars, a suspected remnant of a phreatomagmatic eruption, can reveal important information about paleohydrologic conditions. The types and sizes of pyroclastic rocks produced by a phreatomagmatic eruption are indicative of the behavior of the explosion and the characteristics of the groundwater reservoir. Analysis of the pyroclast size distribution can be used to determine magma volatile content. We conduct an analysis of pyroclast size distribution using Ground Penetrating Radar (GPR) to make a quantitative estimate of the presence of past groundwater at Kilbourne Hole, a well-known phreatomagmatic crater located in southern Dona Ana County, New Mexico. As basaltic magma intruded the groundwater reservoir in the mid-Pleistocene, the water vaporized and caused a phreatomagmatic explosion that excavated the 2-km wide and 200-m deep depression. The pyroclastic units produced during a phreatomagmatic explosion are proportional to the size and the duration of the explosion and the size of the groundwater reservoir such that the wetter the eruption, the stronger the explosion. In a violent volcanic eruption, magma changes from a liquid into solid fragments and the explosion releases kinetic energy (Ek) by ejecting liquid water, vapor water (with mass Mw) and solid fragments (with mass Mf) at an ejection velocity (Ve). In order to determine Mw, we must know Ve. The relationship between Ve and the distance from center of the eruption (R) is such that Ve exponentially decreases with time (t) and R. A numerical model relating pyroclast size and Ve for material ejected in Hawaiian and Plinian eruptions shows that clast size also exponentially decreases with decreasing Ve. Based on these relationships, we use GPR to map the ejected clast size distribution as a function of distance from the edge of Kilbourne Hole in an effort to determine Ve and Mw. GPR surveys were performed in January 2012 and January 2013 using a Noggins 250 MHz radar system. We designed the surveys to detect volcanic bombs in the shallow subsurface and to map radial variations in their sizes. Six GPR lines were extended radially in each cardinal direction from the rim of Kilbourne Hole, and, as a control, fifteen short GPR lines were performed along an accessible cliff where visible volcanic bombs and blocks are exposed. We are able to visualize 58 bombs and blocks along one of the six GPR lines within the maximum penetration depth of 2.4-3.2 m. From the resulting GPR profiles, we measured the width and the length of the bombs. The largest dimension of each bomb was plotted against distance from crater rim, and the obtained exponential relationship between bomb size and distance will be applied to a numerical model of ejecta dispersal from transient volcanic explosions to solve for Ve and Mw. This case study at Kilbourne Hole serves as a planetary analog for similar surveys that could be done on Mars and on the Moon.

Evaluation of ground-penetrating radar to detect free-phase hydrocarbons in fractured rocks - Results of numerical modeling and physical experiments

USGS Publications Warehouse

Lane, J.W.; Buursink, M.L.; Haeni, F.P.; Versteeg, R.J.

2000-01-01

The suitability of common-offset ground-penetrating radar (GPR) to detect free-phase hydrocarbons in bedrock fractures was evaluated using numerical modeling and physical experiments. The results of one- and two-dimensional numerical modeling at 100 megahertz indicate that GPR reflection amplitudes are relatively insensitive to fracture apertures ranging from 1 to 4 mm. The numerical modeling and physical experiments indicate that differences in the fluids that fill fractures significantly affect the amplitude and the polarity of electromagnetic waves reflected by subhorizontal fractures. Air-filled and hydrocarbon-filled fractures generate low-amplitude reflections that are in-phase with the transmitted pulse. Water-filled fractures create reflections with greater amplitude and opposite polarity than those reflections created by air-filled or hydrocarbon-filled fractures. The results from the numerical modeling and physical experiments demonstrate it is possible to distinguish water-filled fracture reflections from air- or hydrocarbon-filled fracture reflections, nevertheless subsurface heterogeneity, antenna coupling changes, and other sources of noise will likely make it difficult to observe these changes in GPR field data. This indicates that the routine application of common-offset GPR reflection methods for detection of hydrocarbon-filled fractures will be problematic. Ideal cases will require appropriately processed, high-quality GPR data, ground-truth information, and detailed knowledge of subsurface physical properties. Conversely, the sensitivity of GPR methods to changes in subsurface physical properties as demonstrated by the numerical and experimental results suggests the potential of using GPR methods as a monitoring tool. GPR methods may be suited for monitoring pumping and tracer tests, changes in site hydrologic conditions, and remediation activities.The suitability of common-offset ground-penetrating radar (GPR) to detect free-phase hydrocarbons in bedrock fractures was evaluated using numerical modeling and physical experiments. The results of one- and two-dimensional numerical modeling at 100 megahertz indicate that GPR reflection amplitudes are relatively insensitive to fracture apertures ranging from 1 to 4 mm. The numerical modeling and physical experiments indicate that differences in the fluids that fill fractures significantly affect the amplitude and the polarity of electromagnetic waves reflected by subhorizontal fractures. Air-filled and hydrocarbon-filled fractures generate low-amplitude reflections that are in-phase with the transmitted pulse. Water-filled fractures create reflections with greater amplitude and opposite polarity than those reflections created by air-filled or hydrocarbon-filled fractures. The results from the numerical modeling and physical experiments demonstrate it is possible to distinguish water-filled fracture reflections from air- or hydrocarbon-filled fracture reflections, nevertheless subsurface heterogeneity, antenna coupling changes, and other sources of noise will likely make it difficult to observe these changes in GPR field data. This indicates that the routine application of common-offset GPR reflection methods for detection of hydrocarbon-filled fractures will be problematic. Ideal cases will require appropriately processed, high-quality GPR data, ground-truth information, and detailed knowledge of subsurface physical properties. Conversely, the sensitivity of GPR methods to changes in subsurface physical properties as demonstrated by the numerical and experimental results suggests the potential of using GPR methods as a monitoring tool. GPR methods may be suited for monitoring pumping and tracer tests, changes in site hydrologic conditions, and remediation activities.

Investigating the nature of the GPR antenna orientation effect on temperate glaciers

NASA Astrophysics Data System (ADS)

Langhammer, Lisbeth; Rabenstein, Lasse; Bauder, Andreas; Lathion, Patrick; Maurer, Hansruedi

2015-04-01

In the recent years the bedrock topography of the Swiss Alpine Glaciers has been mapped by ground-based and helicopter-borne GPR (Ground Penetrating Radar) as part of an ongoing comprehensive inventory initiated by the ETH Zürich, the Swiss Competence Center for Energy Research (SCCER) and the Swiss Geophysical Commission (SGPK). Our recorded GPR data of glacier bedrock topography highlights the need of a better understanding of the interaction between GPR systems and the glacierized subsurface in high mountain terrain. The Otemma glacier in the Pennine Alps, Valais, has been subject to repeated profiling with commercial GPR ground units (pulseEKKO and GSSI) operating at frequencies ranging from 15-67 MHz deployed at the surface and mounted on a helicopter. Our data shows significant quality differences between similar GPR profiles, which could not be explained by system failure or technical discrepancies. To investigate the issue, we conducted antenna rotation experiments at several locations on the glacier surface. The results indicate a strong relationship between the orientation of the bistatic antennas and the flow direction of the glacier. Possible explanation for our observations range from anisotropy effects in glacier ice, the influence of directional characteristics of the GPR antennas or distinctive features of the bedrock topography. To explain our results, we perform 3D GPR modeling of the glacier body with the FDTD electromagnetic simulator gprMax. A basic homogenous three-dimensional model of the glacier will be replaced by varying bedrock topography along a transect. Internal structures such as water layers and inclusion will be imbedded in the simulations. Currently ground based GPR surveys produce higher quality data with respect to the visibility of glacier bed reflections. We intent to enhance our operating system and antenna installation on the helicopter based on the results of the simulations to achieve similar quality standards. The objective is to successfully map the bedrock topography of the Swiss glaciers in the next three years.

Palmitoylethanolamide Modulates GPR55 Receptor Signaling in the Ventral Hippocampus to Regulate Mesolimbic Dopamine Activity, Social Interaction, and Memory Processing.

PubMed

Kramar, Cecilia; Loureiro, Michael; Renard, Justine; Laviolette, Steven R

2017-01-01

Introduction: The GPR55 receptor has been identified as an atypical cannabinoid receptor and is implicated in various physiological processes. However, its functional role in the central nervous system is not currently understood. The presence of GPR55 receptor in neural regions such as the ventral hippocampus (vHipp), which is critical for cognition, recognition memory, and affective processing, led us to hypothesize that intra-vHipp GPR55 transmission may modulate mesolimbic activity states and related behavioral phenomena. The vHipp is involved in contextual memory and affective regulation through functional interactions with the mesolimbic dopamine system. Materials and Methods: Using a combination of in vivo electrophysiology and behavioral pharmacological assays in rats, we tested whether intra-vHipp activation of GPR55 receptor transmission with the fatty acid amide, palmitoylethanolamide (PEA), a lipid neuromodulator with agonist actions at the GPR55 receptor, may modulate mesolimbic dopaminergic activity states. We further examined the potential effects of intra-vHipp PEA in affective, cognitive and contextual memory tasks. Discussion: We report that intra-vHipp PEA produces a hyper-dopaminergic state in the mesolimbic system characterized by increased firing and bursting activity of ventral tegmental area dopaminergic neuron populations. Furthermore, while PEA-induced activation of GPR55 transmission had no effects on opiate-related reward-related memory formation, we observed strong disruptions in social interaction and recognition memory, spatial location memory, and context-independent associative fear memory formation. Finally, the effects of intra-vHipp PEA were blocked by a selective GPR55 receptor antagonist, CID160 and were dependent upon NMDA receptor transmission, directly in the vHipp. Conclusions: The present results add to a growing body of evidence demonstrating important functional roles for GPR55 signaling in cannabinoid-related neuronal and behavioral phenomena and underscore the potential for GPR55 signaling in the mediation of cannabinoid-related effects independently of the CB1/CB2 receptor systems.

Evidence for the putative cannabinoid receptor, GPR55, mediated inhibitory effects on intestinal contractility in mice

PubMed Central

Ross, Gracious R; Lichtman, Aron; Dewey, William L; Akbarali, Hamid I

2012-01-01

Background Cannabinoids inhibit intestinal motility via presynaptic cannabinoid receptor type I(CB1) in enteric neurons while cannabinoid receptor type II (CB2) receptors are located mainly in immune cells. The recently deorphanized G-protein-coupled receptor, GPR55, has been proposed to be the “third” cannabinoid receptor. Although gene expression of GPR55 is evident in the gut, functional evidence for GPR55 in the gut is unknown. In this study, we tested the hypothesis that GPR55 activation inhibits neurogenic contractions in the gut. Methods We assessed the inhibitory effect of the atypical cannabinoid O-1602, a GPR55 agonist, in mouse colon. Isometric tension recordings in colonic tissue strips were used from either wild type, GPR55−/− or CB1−/−/CB2−/−knock-out mice. Results O-1602 inhibited the electrical field-induced contractions in the colon strips from wild type and CB1−/−/CB2−/− in a concentration–dependent manner, suggesting a non-CB1/CB2-receptor mediated prejunctional effect. The concentration–dependent response of O-1602 was significantly inhibited in GPR55−/− mice. O-1602 did not relax colonic strips pre-contracted with high K+ (80 mmol/l), indicating no involvement of Ca2+ channel blockade in O-1602–induced relaxation. However, 10 μmol/l O-1602 partially inhibited the exogenous acetylcholine (10 μmol/l) –induced contractions. Moreover, we also assessed the inhibitory effects of JWH 015, a CB2/GPR55 agonist on neurogenic contractions of mouse ileum. Surprisingly, the effects of JWH015 were independent of the known cannabinoid receptors. Conclusion These findings taken together suggest that activation of GPR55 leads to inhibition of neurogenic contractions in the gut, and are predominantly prejunctional. PMID:22759743

G protein-coupled receptor 91 signaling in diabetic retinopathy and hypoxic retinal diseases.

PubMed

Hu, Jianyan; Li, Tingting; Du, Xinhua; Wu, Qiang; Le, Yun-Zheng

2017-10-01

G protein-coupled receptor 91 (GPR91) is a succinate-specific receptor and activation of GPR91 could initiate a complex signal transduction cascade and upregulate inflammatory and pro-angiogenic cytokines. In the retina, GPR91 is predominately expressed in ganglion cells, a major cellular entity involved in the pathogenesis of diabetic retinopathy (DR) and other hypoxic retinal diseases. During the development of DR and retinopathy of prematurity (ROP), chronic hypoxia causes an increase in the levels of local succinate. Succinate-mediated GPR91 activation upregulates vascular endothelial growth factor (VEGF) through ERK1/2-C/EBP β (c-Fos) and/or ERK1/2-COX-2/PGE2 signaling pathways, which in turn, leads to the breakdown of blood-retina barriers in these disorders. In this review, we will have a brief introduction of GPR91 and its biological functions and a more detailed discussion about the role and mechanisms of GPR91 in DR and ROP. A better understanding of GPR91 regulation may be of great significance in identifying new biomarkers and drug targets for the prediction and treatment of DR, ROP, and hypoxic retinal diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Perception of speaker size and sex of vowel sounds

NASA Astrophysics Data System (ADS)

Smith, David R. R.; Patterson, Roy D.

2005-04-01

Glottal-pulse rate (GPR) and vocal-tract length (VTL) are both related to speaker size and sex-however, it is unclear how they interact to determine our perception of speaker size and sex. Experiments were designed to measure the relative contribution of GPR and VTL to judgements of speaker size and sex. Vowels were scaled to represent people with different GPRs and VTLs, including many well beyond the normal population values. In a single interval, two response rating paradigm, listeners judged the size (using a 7-point scale) and sex/age of the speaker (man, woman, boy, or girl) of these scaled vowels. Results from the size-rating experiments show that VTL has a much greater influence upon judgements of speaker size than GPR. Results from the sex-categorization experiments show that judgements of speaker sex are influenced about equally by GPR and VTL for vowels with normal GPR and VTL values. For abnormal combinations of GPR and VTL, where low GPRs are combined with short VTLs, VTL has more influence than GPR in sex judgements. [Work supported by the UK MRC (G9901257) and the German Volkswagen Foundation (VWF 1/79 783).

Oxysterol Sensing through the Receptor GPR183 Promotes the Lymphoid-Tissue-Inducing Function of Innate Lymphoid Cells and Colonic Inflammation.

PubMed

Emgård, Johanna; Kammoun, Hana; García-Cassani, Bethania; Chesné, Julie; Parigi, Sara M; Jacob, Jean-Marie; Cheng, Hung-Wei; Evren, Elza; Das, Srustidhar; Czarnewski, Paulo; Sleiers, Natalie; Melo-Gonzalez, Felipe; Kvedaraite, Egle; Svensson, Mattias; Scandella, Elke; Hepworth, Matthew R; Huber, Samuel; Ludewig, Burkhard; Peduto, Lucie; Villablanca, Eduardo J; Veiga-Fernandes, Henrique; Pereira, João P; Flavell, Richard A; Willinger, Tim

2018-01-16

Group 3 innate lymphoid cells (ILC3s) sense environmental signals and are critical for tissue integrity in the intestine. Yet, which signals are sensed and what receptors control ILC3 function remain poorly understood. Here, we show that ILC3s with a lymphoid-tissue-inducer (LTi) phenotype expressed G-protein-coupled receptor 183 (GPR183) and migrated to its oxysterol ligand 7α,25-hydroxycholesterol (7α,25-OHC). In mice lacking Gpr183 or 7α,25-OHC, ILC3s failed to localize to cryptopatches (CPs) and isolated lymphoid follicles (ILFs). Gpr183 deficiency in ILC3s caused a defect in CP and ILF formation in the colon, but not in the small intestine. Localized oxysterol production by fibroblastic stromal cells provided an essential signal for colonic lymphoid tissue development, and inflammation-induced increased oxysterol production caused colitis through GPR183-mediated cell recruitment. Our findings show that GPR183 promotes lymphoid organ development and indicate that oxysterol-GPR183-dependent positioning within tissues controls ILC3 activity and intestinal homeostasis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Medium-chain fatty acid-sensing receptor, GPR84, is a proinflammatory receptor.

PubMed

Suzuki, Masakatsu; Takaishi, Sachiko; Nagasaki, Miyuki; Onozawa, Yoshiko; Iino, Ikue; Maeda, Hiroaki; Komai, Tomoaki; Oda, Tomiichiro

2013-04-12

G protein-coupled receptor 84 (GPR84) is a putative receptor for medium-chain fatty acids (MCFAs), whose pathophysiological roles have not yet been clarified. Here, we show that GPR84 was activated by MCFAs with the hydroxyl group at the 2- or 3-position more effectively than nonhydroxylated MCFAs. We also identified a surrogate agonist, 6-n-octylaminouracil (6-OAU), for GPR84. These potential ligands and the surrogate agonist, 6-OAU, stimulated [(35)S]GTP binding and accumulated phosphoinositides in a GPR84-dependent manner. The surrogate agonist, 6-OAU, internalized GPR84-EGFP from the cell surface. Both the potential ligands and 6-OAU elicited chemotaxis of human polymorphonuclear leukocytes (PMNs) and macrophages and amplified LPS-stimulated production of the proinflammatory cytokine IL-8 from PMNs and TNFα from macrophages. Furthermore, the intravenous injection of 6-OAU raised the blood CXCL1 level in rats, and the inoculation of 6-OAU into the rat air pouch accumulated PMNs and macrophages in the site. Our results indicate a proinflammatory role of GPR84, suggesting that the receptor may be a novel target to treat chronic low grade inflammation associated-disease.

Medium-chain Fatty Acid-sensing Receptor, GPR84, Is a Proinflammatory Receptor

PubMed Central

Suzuki, Masakatsu; Takaishi, Sachiko; Nagasaki, Miyuki; Onozawa, Yoshiko; Iino, Ikue; Maeda, Hiroaki; Komai, Tomoaki; Oda, Tomiichiro

2013-01-01

G protein-coupled receptor 84 (GPR84) is a putative receptor for medium-chain fatty acids (MCFAs), whose pathophysiological roles have not yet been clarified. Here, we show that GPR84 was activated by MCFAs with the hydroxyl group at the 2- or 3-position more effectively than nonhydroxylated MCFAs. We also identified a surrogate agonist, 6-n-octylaminouracil (6-OAU), for GPR84. These potential ligands and the surrogate agonist, 6-OAU, stimulated [35S]GTP binding and accumulated phosphoinositides in a GPR84-dependent manner. The surrogate agonist, 6-OAU, internalized GPR84-EGFP from the cell surface. Both the potential ligands and 6-OAU elicited chemotaxis of human polymorphonuclear leukocytes (PMNs) and macrophages and amplified LPS-stimulated production of the proinflammatory cytokine IL-8 from PMNs and TNFα from macrophages. Furthermore, the intravenous injection of 6-OAU raised the blood CXCL1 level in rats, and the inoculation of 6-OAU into the rat air pouch accumulated PMNs and macrophages in the site. Our results indicate a proinflammatory role of GPR84, suggesting that the receptor may be a novel target to treat chronic low grade inflammation associated-disease. PMID:23449982

Regulating the effects of GPR21, a novel target for type 2 diabetes

NASA Astrophysics Data System (ADS)

Leonard, Siobhán; Kinsella, Gemma K.; Benetti, Elisa; Findlay, John B. C.

2016-05-01

Type 2 diabetes is a chronic metabolic disorder primarily caused by insulin resistance to which obesity is a major contributor. Expression levels of an orphan G protein-coupled receptor (GPCR), GPR21, demonstrated a trend towards a significant increase in the epididymal fat pads of wild type high fat high sugar (HFHS)-fed mice. To gain further insight into the potential role this novel target may play in the development of obesity-associated type 2 diabetes, the signalling capabilities of the receptor were investigated. Overexpression studies in HEK293T cells revealed GPR21 to be a constitutively active receptor, which couples to Gαq type G proteins leading to the activation of mitogen activated protein kinases (MAPKs). Overexpression of GPR21 in vitro also markedly attenuated insulin signalling. Interestingly, the effect of GPR21 on the MAPKs and insulin signalling was reduced in the presence of serum, inferring the possibility of a native inhibitory ligand. Homology modelling and ligand docking studies led to the identification of a novel compound that inhibited GPR21 activity. Its effects offer potential as an anti-diabetic pharmacological strategy as it was found to counteract the influence of GPR21 on the insulin signalling pathway.

Mice lacking GPR3 receptors display late-onset obese phenotype due to impaired thermogenic function in brown adipose tissue

PubMed Central

Godlewski, Grzegorz; Jourdan, Tony; Szanda, Gergő; Tam, Joseph; Resat Cinar; Harvey-White, Judith; Liu, Jie; Mukhopadhyay, Bani; Pacher, Pál; Ming Mo, Fong; Osei-Hyiaman, Douglas; George Kunos

2015-01-01

We report an unexpected link between aging, thermogenesis and weight gain via the orphan G protein-coupled receptor GPR3. Mice lacking GPR3 and maintained on normal chow had similar body weights during their first 5 months of life, but gained considerably more weight thereafter and displayed reduced total energy expenditure and lower core body temperature. By the age of 5 months GPR3 KO mice already had lower thermogenic gene expression and uncoupling protein 1 protein level and showed impaired glucose uptake into interscapular brown adipose tissue (iBAT) relative to WT littermates. These molecular deviations in iBAT of GPR3 KO mice preceded measurable differences in body weight and core body temperature at ambient conditions, but were coupled to a failure to maintain thermal homeostasis during acute cold challenge. At the same time, the same cold challenge caused a 17-fold increase in Gpr3 expression in iBAT of WT mice. Thus, GPR3 appears to have a key role in the thermogenic response of iBAT and may represent a new therapeutic target in age-related obesity. PMID:26455425

Domain analyses of Usher syndrome causing Clarin-1 and GPR98 protein models.

PubMed

Khan, Sehrish Haider; Javed, Muhammad Rizwan; Qasim, Muhammad; Shahzadi, Samar; Jalil, Asma; Rehman, Shahid Ur

2014-01-01

Usher syndrome is an autosomal recessive disorder that causes hearing loss, Retinitis Pigmentosa (RP) and vestibular dysfunction. It is clinically and genetically heterogeneous disorder which is clinically divided into three types i.e. type I, type II and type III. To date, there are about twelve loci and ten identified genes which are associated with Usher syndrome. A mutation in any of these genes e.g. CDH23, CLRN1, GPR98, MYO7A, PCDH15, USH1C, USH1G, USH2A and DFNB31 can result in Usher syndrome or non-syndromic deafness. These genes provide instructions for making proteins that play important roles in normal hearing, balance and vision. Studies have shown that protein structures of only seven genes have been determined experimentally and there are still three genes whose structures are unavailable. These genes are Clarin-1, GPR98 and Usherin. In the absence of an experimentally determined structure, homology modeling and threading often provide a useful 3D model of a protein. Therefore in the current study Clarin-1 and GPR98 proteins have been analyzed for signal peptide, domains and motifs. Clarin-1 protein was found to be without any signal peptide and consists of prokar lipoprotein domain. Clarin-1 is classified within claudin 2 super family and consists of twelve motifs. Whereas, GPR98 has a 29 amino acids long signal peptide and classified within GPCR family 2 having Concanavalin A-like lectin/glucanase superfamily. It was found to be consists of GPS and G protein receptor F2 domains and twenty nine motifs. Their 3D structures have been predicted using I-TASSER server. The model of Clarin-1 showed only α-helix but no beta sheets while model of GPR98 showed both α-helix and β sheets. The predicted structures were then evaluated and validated by MolProbity and Ramachandran plot. The evaluation of the predicted structures showed 78.9% residues of Clarin-1 and 78.9% residues of GPR98 within favored regions. The findings of present study has resulted in the three dimensional structure prediction and conserved domain analysis which will be quite beneficial in better understanding of molecular components, protein-protein interaction, clinical heterogeneity and pathophysiology of Usher syndrome.

Domain analyses of Usher syndrome causing Clarin-1 and GPR98 protein models

PubMed Central

Khan, Sehrish Haider; Javed, Muhammad Rizwan; Qasim, Muhammad; Shahzadi, Samar; Jalil, Asma; Rehman, Shahid ur

2014-01-01

Usher syndrome is an autosomal recessive disorder that causes hearing loss, Retinitis Pigmentosa (RP) and vestibular dysfunction. It is clinically and genetically heterogeneous disorder which is clinically divided into three types i.e. type I, type II and type III. To date, there are about twelve loci and ten identified genes which are associated with Usher syndrome. A mutation in any of these genes e.g. CDH23, CLRN1, GPR98, MYO7A, PCDH15, USH1C, USH1G, USH2A and DFNB31 can result in Usher syndrome or non-syndromic deafness. These genes provide instructions for making proteins that play important roles in normal hearing, balance and vision. Studies have shown that protein structures of only seven genes have been determined experimentally and there are still three genes whose structures are unavailable. These genes are Clarin-1, GPR98 and Usherin. In the absence of an experimentally determined structure, homology modeling and threading often provide a useful 3D model of a protein. Therefore in the current study Clarin-1 and GPR98 proteins have been analyzed for signal peptide, domains and motifs. Clarin-1 protein was found to be without any signal peptide and consists of prokar lipoprotein domain. Clarin-1 is classified within claudin 2 super family and consists of twelve motifs. Whereas, GPR98 has a 29 amino acids long signal peptide and classified within GPCR family 2 having Concanavalin A-like lectin/glucanase superfamily. It was found to be consists of GPS and G protein receptor F2 domains and twenty nine motifs. Their 3D structures have been predicted using I-TASSER server. The model of Clarin-1 showed only α-helix but no beta sheets while model of GPR98 showed both α-helix and β sheets. The predicted structures were then evaluated and validated by MolProbity and Ramachandran plot. The evaluation of the predicted structures showed 78.9% residues of Clarin-1 and 78.9% residues of GPR98 within favored regions. The findings of present study has resulted in the three dimensional structure prediction and conserved domain analysis which will be quite beneficial in better understanding of molecular components, protein-protein interaction, clinical heterogeneity and pathophysiology of Usher syndrome. PMID:25258483

Gaussian Process Regression Model in Spatial Logistic Regression

NASA Astrophysics Data System (ADS)

Sofro, A.; Oktaviarina, A.

2018-01-01

Spatial analysis has developed very quickly in the last decade. One of the favorite approaches is based on the neighbourhood of the region. Unfortunately, there are some limitations such as difficulty in prediction. Therefore, we offer Gaussian process regression (GPR) to accommodate the issue. In this paper, we will focus on spatial modeling with GPR for binomial data with logit link function. The performance of the model will be investigated. We will discuss the inference of how to estimate the parameters and hyper-parameters and to predict as well. Furthermore, simulation studies will be explained in the last section.

Synthesis and Agonistic Activity at the GPR35 of 5,6-Dihydroxyindole-2-carboxylic Acid Analogues

PubMed Central

2012-01-01

5,6-Dihydroxyindole-2-carboxylic acid (DHICA), an intermediate of melanin synthesis and an eumelanin building block, was recently discovered to be a GPR35 agonist with moderate potency. Here, we report the synthesis and pharmacological characterization of a series of DHICA analogues against GPR35 using both label-free dynamic mass redistribution and Tango β-arrestin translocation assays. This led to identification of novel GPR35 agonists with improved potency and/or having biased agonism. PMID:24900508

Extracting and identifying concrete structural defects in GPR images

NASA Astrophysics Data System (ADS)

Ye, Qiling; Jiao, Liangbao; Liu, Chuanxin; Cao, Xuehong; Huston, Dryver; Xia, Tian

2018-03-01

Traditionally most GPR data interpretations are performed manually. With the advancement of computing technologies, how to automate GPR data interpretation to achieve high efficiency and accuracy has become an active research subject. In this paper, analytical characterizations of major defects in concrete structures, including delamination, air void and moisture in GPR images, are performed. In the study, the image features of different defects are compared. Algorithms are developed for defect feature extraction and identification. For validations, both simulation results and field test data are utilized.

Design and Synthesis of 2-Alkylpyrimidine-4,6-diol and 6-Alkylpyridine-2,4-diol as Potent GPR84 Agonists.

PubMed

Liu, Yang; Zhang, Qing; Chen, Lin-Hai; Yang, Hui; Lu, Wei; Xie, Xin; Nan, Fa-Jun

2016-06-09

A series of alkylpyrimidine-4,6-diol derivatives were designed and synthesized as novel GRP84 agonists based on a high-throughput screening (HTS) hit 1. 6-Nonylpyridine-2,4-diol was identified as the most potent agonist of GPR84 reported so far, with an EC50 of 0.189 nM. These novel GPR84 agonists will provide valuable tools for the study of the physiological functions of GPR84.

Design and Synthesis of 2-Alkylpyrimidine-4,6-diol and 6-Alkylpyridine-2,4-diol as Potent GPR84 Agonists

PubMed Central

2016-01-01

A series of alkylpyrimidine-4,6-diol derivatives were designed and synthesized as novel GRP84 agonists based on a high-throughput screening (HTS) hit 1. 6-Nonylpyridine-2,4-diol was identified as the most potent agonist of GPR84 reported so far, with an EC50 of 0.189 nM. These novel GPR84 agonists will provide valuable tools for the study of the physiological functions of GPR84. PMID:27326330

Neural network based inspection of voids and karst conduits in hydro-electric power station tunnels using GPR

NASA Astrophysics Data System (ADS)

Kilic, Gokhan; Eren, Levent

2018-04-01

This paper reports on the fundamental role played by Ground Penetrating Radar (GPR), alongside advanced processing and presentation methods, during the tunnel boring project at a Dam and Hydro-Electric Power Station. It identifies from collected GPR data such issues as incomplete grouting and the presence of karst conduits and voids and provides full details of the procedures adopted. In particular, the application of collected GPR data to the Neural Network (NN) method is discussed.

Improving GPR Surveys Productivity by Array Technology and Fully Automated Processing

NASA Astrophysics Data System (ADS)

Morello, Marco; Ercoli, Emanuele; Mazzucchelli, Paolo; Cottino, Edoardo

2016-04-01

The realization of network infrastructures with lower environmental impact and the tendency to use digging technologies less invasive in terms of time and space of road occupation and restoration play a key-role in the development of communication networks. However, pre-existing buried utilities must be detected and located in the subsurface, to exploit the high productivity of modern digging apparatus. According to SUE quality level B+ both position and depth of subsurface utilities must be accurately estimated, demanding for 3D GPR surveys. In fact, the advantages of 3D GPR acquisitions (obtained either by multiple 2D recordings or by an antenna array) versus 2D acquisitions are well-known. Nonetheless, the amount of acquired data for such 3D acquisitions does not usually allow to complete processing and interpretation directly in field and in real-time, thus limiting the overall efficiency of the GPR acquisition. As an example, the "low impact mini-trench "technique (addressed in ITU - International Telecommunication Union - L.83 recommendation) requires that non-destructive mapping of buried services enhances its productivity to match the improvements of new digging equipment. Nowadays multi-antenna and multi-pass GPR acquisitions demand for new processing techniques that can obtain high quality subsurface images, taking full advantage of 3D data: the development of a fully automated and real-time 3D GPR processing system plays a key-role in overall optical network deployment profitability. Furthermore, currently available computing power suggests the feasibility of processing schemes that incorporate better focusing algorithms. A novel processing scheme, whose goal is the automated processing and detection of buried targets that can be applied in real-time to 3D GPR array systems, has been developed and fruitfully tested with two different GPR arrays (16 antennas, 900 MHz central frequency, and 34 antennas, 600 MHz central frequency). The proposed processing scheme take advantage of 3D data multiplicity by continuous real time data focusing. Pre-stack reflection angle gathers G(x, θ; v) are computed at nv different velocities (by the mean of Kirchhoff depth-migration kernels, that can naturally cope with any acquisition pattern and handle irregular sampling issues). It must be noted that the analysis of pre-stack reflection angle gathers plays a key-role in automated detection: targets are identified and the best local propagation velocities are recovered through a correlation estimate computed for all the nv reflection angle gathers. Indeed, the data redundancy of 3D GPR acquisitions highly improves the proposed automatic detection reliability. The goal of real-time automated processing has been pursued without the need of specific high performance processing hardware (a simple laptop is required). Moreover, the automatization of the entire surveying process allows to obtain high quality and repeatable results without the need of skilled interpreters. The proposed acquisition procedure has been extensively tested: more than 100 Km of acquired data prove the feasibility of the proposed approach.

The role of GPR1 signaling in mice corpus luteum

PubMed Central

Yang, Ya-Li; Ren, Li-Rong; Sun, Li-Feng; Huang, Chen; Xiao, Tian-Xia; Wang, Bao-Bei; Chen, Jie; Zabel, Brian A

2016-01-01

Chemerin, a chemokine, plays important roles in immune responses, inflammation, adipogenesis, and carbohydrate metabolism. Our recent research has shown that chemerin has an inhibitory effect on hormone secretion from the testis and ovary. However, whether G protein-coupled receptor 1 (GPR1), the active receptor for chemerin, regulates steroidogenesis and luteolysis in the corpus luteum is still unknown. In this study, we established a pregnant mare serum gonadotropin-human chorionic gonadotropin (PMSG-hCG) superovulation model, a prostaglandin F2α (PGF2α) luteolysis model, and follicle and corpus luteum culture models to analyze the role of chemerin signaling through GPR1 in the synthesis and secretion of gonadal hormones during follicular/luteal development and luteolysis. Our results, for the first time, show that chemerin and GPR1 are both differentially expressed in the ovary over the course of the estrous cycle, with highest levels in estrus and metestrus. GPR1 has been localized to granulosa cells, cumulus cells, and the corpus luteum by immunohistochemistry (IHC). In vitro, we found that chemerin suppresses hCG-induced progesterone production in cultured follicle and corpus luteum and that this effect is attenuated significantly by anti-GPR1 MAB treatment. Furthermore, when the phosphoinositide 3-kinase (PI3K) pathway was blocked, the attenuating effect of GPR1 MAB was abrogated. Interestingly, PGF2α induces luteolysis through activation of caspase-3, leading to a reduction in progesterone secretion. Treatment with GPR1 MAB blocked the PGF2α effect on caspase-3 expression and progesterone secretion. This study indicates that chemerin/GPR1 signaling directly or indirectly regulates progesterone synthesis and secretion during the processes of follicular development, corpus luteum formation, and PGF2α-induced luteolysis. PMID:27149986

Differential eosinophil and mast cell regulation: Mast cell viability and accumulation in inflammatory tissue are independent of proton-sensing receptor GPR65

PubMed Central

Zhu, Xiang; Mose, Eucabeth; Hogan, Simon P.

2014-01-01

Extracellular acidification has been observed in allergic inflammatory diseases. Recently, we demonstrated that the proton-sensing receptor G protein-coupled receptor 65 (GPR65) regulates eosinophil survival in an acidic environment in vitro and eosinophil accumulation in an allergic lung inflammation model. For mast cells, another inflammatory cell type critical for allergic responses, it remains unknown whether GPR65 is expressed and/or regulates mast cell viability. Thus, in the present study, we employed in vitro experiments and an intestinal anaphylaxis model in which both mastocytosis and eosinophilia can be observed, particularly in the gastrointestinal tract, to enable us to directly compare the effect of GPR65 expression on these two cell types. We identified GPR65 expression on mast cells; however, unlike eosinophil viability, mast cell viability in vitro is not affected by acidification or GPR65 expression. Mechanistically, we determined that mast cells do not respond to extracellular acidification with increased cAMP levels. Furthermore, in the intestinal anaphylaxis model, we observed a significant reduction of eosinophils (59.1 ± 9.2% decrease) in the jejunum of allergen-challenged GPR65-deficient mice compared with allergen-challenged wild-type mice, despite the degree of antigen sensitization and the expression levels of Th2 cytokines (Il4, Il13) and eosinophil chemokines (Ccl11, Ccl24) in the jejunum being comparable. In contrast, the accumulation of mast cells in allergen-challenged mice was not affected by GPR65 deficiency. In conclusion, our study demonstrates differential regulation of eosinophils and mast cells in inflammatory tissue, with mast cell viability and accumulation being independent of GPR65. PMID:24742990

GPR68, a proton-sensing GPCR, mediates interaction of cancer-associated fibroblasts and cancer cells.

PubMed

Wiley, Shu Z; Sriram, Krishna; Liang, Wenjing; Chang, Sarah E; French, Randall; McCann, Thalia; Sicklick, Jason; Nishihara, Hiroshi; Lowy, Andrew M; Insel, Paul A

2018-03-01

The microenvironment of pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense fibrotic stroma (desmoplasia) generated by pancreatic cancer-associated fibroblasts (CAFs) derived from pancreatic stellate cells (PSCs) and pancreatic fibroblasts (PFs). Using an unbiased GPCRomic array approach, we identified 82 G-protein-coupled receptors (GPCRs) commonly expressed by CAFs derived from 5 primary PDAC tumors. Compared with PSCs and PFs, CAFs have increased expression of GPR68 (a proton-sensing GPCR), with the results confirmed by immunoblotting, The Cancer Genome Atlas data, and immunohistochemistry of PDAC tumors. Co-culture of PSCs with PDAC cells, or incubation with TNF-α, induced GPR68 expression. GPR68 activation (by decreasing the extracellular pH) enhanced IL-6 expression via a cAMP/PKA/cAMP response element binding protein signaling pathway. Knockdown of GPR68 by short interfering RNA diminished low pH-induced production of IL-6 and enhancement of PDAC cell proliferation by CAF conditioned media. CAFs from other gastrointestinal cancers also express GPR68. PDAC cells thus induce expression by CAFs of GPR68, which senses the acidic microenvironment, thereby increasing production of fibrotic markers and IL-6 and promoting PDAC cell proliferation. CAF-expressed GPR68 is a mediator of low-pH-promoted regulation of the tumor microenvironments, in particular to PDAC cell-CAF interaction and may be a novel therapeutic target for pancreatic and perhaps other types of cancers.-Wiley, S. Z., Sriram, K., Liang, W., Chang, S. E., French, R., McCann, T., Sicklick, J., Nishihara, H., Lowy, A. M., Insel, P. A. GPR68, a proton-sensing GPCR, mediates interaction of cancer-associated fibroblasts and cancer cells.

Dietary Fiber Intake is Associated with Increased Colonic Mucosal GPR43+ Polymorphonuclear Infiltration in Active Crohn’s Disease

PubMed Central

Zhao, Mingli; Zhu, Weiming; Gong, Jianfeng; Zuo, Lugen; Zhao, Jie; Sun, Jing; Li, Ning; Li, Jieshou

2015-01-01

G protein-coupled receptor 43/free fatty acid receptor 2 (GPR43/FFAR2) is essential for polymorphonuclear (PMN) recruitment. We investigated the expression of GPR43/FFAR2 in the colon from Crohn’s disease patients and whether dietary fiber in enteral nutrition increases GPR43+ polymorphonuclear infiltration in mucosa. Segments of ascending colon and white blood cells from peripheral blood were obtained from 46 Crohn’s disease patients and 10 colon cancer patients. The Crohn’s disease patients were grouped by the activity of disease (active or remission) and enteral nutrition with or without dietary fiber. Histological feature, expression and location of GPR43/FFAR2 and level of tumor necrosis factor-α (TNF-α), interleukine-6 (IL-6) and myeloperoxidase were assessed. The results of hematoxylin-eosin and immunohistochemistry staining revealed that the infiltration of immune cells, including GPR43+ PMN, was more severe in active Crohn’s disease patients who consumed normal food or enteral nutrition with dietary fiber than in remission patients and colon cancer patients. This finding was supported by the results of GPR43 and myeloperoxidase expression. Active Crohn’s disease (CD) patients who consumed enteral nutrition without dietary fiber exhibited severe immune cell infiltration similar to the other active CD patients, but GPR43+ PMNs were rarely observed. The level of TNF-α mRNA in active Crohn’s disease patients was higher than those of the other patients. In conclusion, the use of dietary fiber in enteral nutrition by active Crohn’s disease patients might increase GPR43+ PMNs infiltration in colon mucosa. This effect was not observed in Crohn’s disease patients in remission. PMID:26140540

Dietary Fiber Intake is Associated with Increased Colonic Mucosal GPR43+ Polymorphonuclear Infiltration in Active Crohn's Disease.

PubMed

Zhao, Mingli; Zhu, Weiming; Gong, Jianfeng; Zuo, Lugen; Zhao, Jie; Sun, Jing; Li, Ning; Li, Jieshou

2015-07-01

G protein-coupled receptor 43/free fatty acid receptor 2 (GPR43/FFAR2) is essential for polymorphonuclear (PMN) recruitment. We investigated the expression of GPR43/FFAR2 in the colon from Crohn's disease patients and whether dietary fiber in enteral nutrition increases GPR43+ polymorphonuclear infiltration in mucosa. Segments of ascending colon and white blood cells from peripheral blood were obtained from 46 Crohn's disease patients and 10 colon cancer patients. The Crohn's disease patients were grouped by the activity of disease (active or remission) and enteral nutrition with or without dietary fiber. Histological feature, expression and location of GPR43/FFAR2 and level of tumor necrosis factor-α (TNF-α), interleukine-6 (IL-6) and myeloperoxidase were assessed. The results of hematoxylin-eosin and immunohistochemistry staining revealed that the infiltration of immune cells, including GPR43+ PMN, was more severe in active Crohn's disease patients who consumed normal food or enteral nutrition with dietary fiber than in remission patients and colon cancer patients. This finding was supported by the results of GPR43 and myeloperoxidase expression. Active Crohn's disease (CD) patients who consumed enteral nutrition without dietary fiber exhibited severe immune cell infiltration similar to the other active CD patients, but GPR43+ PMNs were rarely observed. The level of TNF-α mRNA in active Crohn's disease patients was higher than those of the other patients. In conclusion, the use of dietary fiber in enteral nutrition by active Crohn's disease patients might increase GPR43+ PMNs infiltration in colon mucosa. This effect was not observed in Crohn's disease patients in remission.

CD36- and GPR120-mediated Ca²⁺ signaling in human taste bud cells mediates differential responses to fatty acids and is altered in obese mice.

PubMed

Ozdener, Mehmet Hakan; Subramaniam, Selvakumar; Sundaresan, Sinju; Sery, Omar; Hashimoto, Toshihiro; Asakawa, Yoshinori; Besnard, Philippe; Abumrad, Nada A; Khan, Naim Akhtar

2014-04-01

It is important to increase our understanding of gustatory detection of dietary fat and its contribution to fat preference. We studied the roles of the fat taste receptors CD36 and GPR120 and their interactions via Ca(2+) signaling in fungiform taste bud cells (TBC). We measured Ca(2+) signaling in human TBC, transfected with small interfering RNAs against messenger RNAs encoding CD36 and GPR120 (or control small interfering RNAs). We also studied Ca(2+) signaling in TBC from CD36(-/-) mice and from wild-type lean and obese mice. Additional studies were conducted with mouse enteroendocrine cell line STC-1 that express GPR120 and stably transfected with human CD36. We measured release of serotonin and glucagon-like peptide-1 from human and mice TBC in response to CD36 and GPR120 activation. High concentrations of linoleic acid induced Ca(2+) signaling via CD36 and GPR120 in human and mice TBC, as well as in STC-1 cells, and low concentrations induced Ca(2+) signaling via only CD36. Incubation of human and mice fungiform TBC with lineoleic acid down-regulated CD36 and up-regulated GPR120 in membrane lipid rafts. Obese mice had decreased spontaneous preference for fat. Fungiform TBC from obese mice had reduced Ca(2+) and serotonin responses, but increased release of glucagon-like peptide-1, along with reduced levels of CD36 and increased levels of GPR120 in lipid rafts. CD36 and GPR120 have nonoverlapping roles in TBC signaling during orogustatory perception of dietary lipids; these are differentially regulated by obesity. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Agonists for G-protein-coupled receptor 84 (GPR84) alter cellular morphology and motility but do not induce pro-inflammatory responses in microglia.

PubMed

Wei, Li; Tokizane, Kyohei; Konishi, Hiroyuki; Yu, Hua-Rong; Kiyama, Hiroshi

2017-10-03

Several G-protein-coupled receptors (GPCRs) have been shown to be important signaling mediators between neurons and glia. In our previous screening for identification of nerve injury-associated GPCRs, G-protein-coupled receptor 84 (GPR84) mRNA showed the highest up-regulation by microglia after nerve injury. GPR84 is a pro-inflammatory receptor of macrophages in a neuropathic pain mouse model, yet its function in resident microglia in the central nervous system is poorly understood. We used endogenous, natural, and surrogate agonists for GPR84 (capric acid, embelin, and 6-OAU, respectively) and examined their effect on mouse primary cultured microglia in vitro. 6-n-Octylaminouracil (6-OAU), embelin, and capric acid rapidly induced membrane ruffling and motility in cultured microglia obtained from C57BL/6 mice, although these agonists failed to promote microglial pro-inflammatory cytokine expression. Concomitantly, 6-OAU suppressed forskolin-induced increase of cAMP in cultured microglia. Pertussis toxin, an inhibitor of Gi-coupled signaling, completely suppressed 6-OAU-induced microglial membrane ruffling and motility. In contrast, no 6-OAU-induced microglial membrane ruffling and motility was observed in microglia from DBA/2 mice, a mouse strain that does not express functional GPR84 protein due to endogenous nonsense mutation of the GPR84 gene. GPR84 mediated signaling causes microglial motility and membrane ruffling but does not promote pro-inflammatory responses. As GPR84 is a known receptor for medium-chain fatty acids, those released from damaged brain cells may be involved in the enhancement of microglial motility through GPR84 after neuronal injury.

β-Arrestin Recruitment and Biased Agonism at Free Fatty Acid Receptor 1*

PubMed Central

Mancini, Arturo D.; Bertrand, Gyslaine; Vivot, Kevin; Carpentier, Éric; Tremblay, Caroline; Ghislain, Julien; Bouvier, Michel; Poitout, Vincent

2015-01-01

FFAR1/GPR40 is a seven-transmembrane domain receptor (7TMR) expressed in pancreatic β cells and activated by FFAs. Pharmacological activation of GPR40 is a strategy under consideration to increase insulin secretion in type 2 diabetes. GPR40 is known to signal predominantly via the heterotrimeric G proteins Gq/11. However, 7TMRs can also activate functionally distinct G protein-independent signaling via β-arrestins. Further, G protein- and β-arrestin-based signaling can be differentially modulated by different ligands, thus eliciting ligand-specific responses (“biased agonism”). Whether GPR40 engages β-arrestin-dependent mechanisms and is subject to biased agonism is unknown. Using bioluminescence resonance energy transfer-based biosensors for real-time monitoring of cell signaling in living cells, we detected a ligand-induced GPR40-β-arrestin interaction, with the synthetic GPR40 agonist TAK-875 being more effective than palmitate or oleate in recruiting β-arrestins 1 and 2. Conversely, TAK-875 acted as a partial agonist of Gq/11-dependent GPR40 signaling relative to both FFAs. Pharmacological blockade of Gq activity decreased FFA-induced insulin secretion. In contrast, knockdown or genetic ablation of β-arrestin 2 in an insulin-secreting cell line and mouse pancreatic islets, respectively, uniquely attenuated the insulinotropic activity of TAK-875, thus providing functional validation of the biosensor data. Collectively, these data reveal that in addition to coupling to Gq/11, GPR40 is functionally linked to a β-arrestin 2-mediated insulinotropic signaling axis. These observations expose previously unrecognized complexity for GPR40 signal transduction and may guide the development of biased agonists showing improved clinical profile in type 2 diabetes. PMID:26157145

GPR120: Mechanism of action, role and potential for medical applications.

PubMed

Karakuła-Juchnowicz, Hanna; Róg, Joanna; Juchnowicz, Dariusz; Morylowska-Topolska, Justyna

2017-11-19

G protein-coupled receptors (GPCRs) constitute a family of transmembrane proteins that mediate many cellular processes. GPR120/FFAR4, a receptor from this family that is activated by fatty acids, has received considerable attention recently. This paper presents a literature review concerning the role of GPR120 and its mechanism of action in animal and human studies as well as the potential use of GPR120 for the treatment of chronic diseases. Two electronic databases - Medline and Google Scholar - were searched for available studies addressing the review topic that were written in English and published from 2000 to June 2017. The following key terms were used in the search: GPR120, FFA4, GPR120 agonist, PUFAs, EPA, DHA, adipocyte, obesity, hyperlipidemia, inflammation, cancer, diabetes, insulin resistance, taste, atherogenesis, hepatis, central nervous system. In humans, GPR120 expression is expressed in macrophages, eosinophils, and adipose tissue, in cells of the tongue, liver, lungs, small and large intestine, gastric mucosa, and pancreas, in the central nervous system and placental microvilli. Medium- and long-chain fatty acids act as ligands for the receptor. Through the internalization of beta-arrestin-2 complex and the inhibition of NF-κB, GPR120 mediates the activation of the cell's anti-inflammatory mechanisms. The receptor is also involved in the maturation of adipocytes, the modulation of insulin signalling pathways, the regulation of glucose metabolism, and the secretion of intestinal hormones. GPR120 is a promising target for the treatment of numerous diseases, whose pathophysiology is associated with low-grade inflammation. As a result of intensive searches, a likely group of synthetic agonists of the receptor was determined with potential therapeutic applications in conditions such as obesity, impaired carbohydrate metabolism, inflammatory bowel diseases, cancer, mental disorders.

β-Arrestin Recruitment and Biased Agonism at Free Fatty Acid Receptor 1.

PubMed

Mancini, Arturo D; Bertrand, Gyslaine; Vivot, Kevin; Carpentier, Éric; Tremblay, Caroline; Ghislain, Julien; Bouvier, Michel; Poitout, Vincent

2015-08-21

FFAR1/GPR40 is a seven-transmembrane domain receptor (7TMR) expressed in pancreatic β cells and activated by FFAs. Pharmacological activation of GPR40 is a strategy under consideration to increase insulin secretion in type 2 diabetes. GPR40 is known to signal predominantly via the heterotrimeric G proteins Gq/11. However, 7TMRs can also activate functionally distinct G protein-independent signaling via β-arrestins. Further, G protein- and β-arrestin-based signaling can be differentially modulated by different ligands, thus eliciting ligand-specific responses ("biased agonism"). Whether GPR40 engages β-arrestin-dependent mechanisms and is subject to biased agonism is unknown. Using bioluminescence resonance energy transfer-based biosensors for real-time monitoring of cell signaling in living cells, we detected a ligand-induced GPR40-β-arrestin interaction, with the synthetic GPR40 agonist TAK-875 being more effective than palmitate or oleate in recruiting β-arrestins 1 and 2. Conversely, TAK-875 acted as a partial agonist of Gq/11-dependent GPR40 signaling relative to both FFAs. Pharmacological blockade of Gq activity decreased FFA-induced insulin secretion. In contrast, knockdown or genetic ablation of β-arrestin 2 in an insulin-secreting cell line and mouse pancreatic islets, respectively, uniquely attenuated the insulinotropic activity of TAK-875, thus providing functional validation of the biosensor data. Collectively, these data reveal that in addition to coupling to Gq/11, GPR40 is functionally linked to a β-arrestin 2-mediated insulinotropic signaling axis. These observations expose previously unrecognized complexity for GPR40 signal transduction and may guide the development of biased agonists showing improved clinical profile in type 2 diabetes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

GPR30 Regulates Glutamate Transporter GLT-1 Expression in Rat Primary Astrocytes*

PubMed Central

Lee, Eunsook; Sidoryk-Wêgrzynowicz, Marta; Wang, Ning; Webb, Anton; Son, Deok-Soo; Lee, Kyuwon; Aschner, Michael

2012-01-01

The G protein-coupled estrogen receptor GPR30 contributes to the neuroprotective effects of 17β-estradiol (E2); however, the mechanisms associated with this protection have yet to be elucidated. Given that E2 increases astrocytic expression of glutamate transporter-1 (GLT-1), which would prevent excitotoxic-induced neuronal death, we proposed that GPR30 mediates E2 action on GLT-1 expression. To investigate this hypothesis, we examined the effects of G1, a selective agonist of GPR30, and GPR30 siRNA on astrocytic GLT-1 expression, as well as glutamate uptake in rat primary astrocytes, and explored potential signaling pathways linking GPR30 to GLT-1. G1 increased GLT-1 protein and mRNA levels, subject to regulation by both MAPK and PI3K signaling. Inhibition of TGF-α receptor suppressed the G1-induced increase in GLT-1 expression. Silencing GPR30 reduced the expression of both GLT-1 and TGF-α and abrogated the G1-induced increase in GLT-1 expression. Moreover, the G1-induced increase in GLT-1 protein expression was abolished by a protein kinase A inhibitor and an NF-κB inhibitor. G1 also enhanced cAMP response element-binding protein (CREB), as well as both NF-κB p50 and NF-κB p65 binding to the GLT-1 promoter. Finally, to model dysfunction of glutamate transporters, manganese was used, and G1 was found to attenuate manganese-induced impairment in GLT-1 protein expression and glutamate uptake. Taken together, the present data demonstrate that activation of GPR30 increases GLT-1 expression via multiple pathways, suggesting that GPR30 is worthwhile as a potential target to be explored for developing therapeutics of excitotoxic neuronal injury. PMID:22645130

Identification of Novel G Protein–Coupled Receptor 143 Ligands as Pharmacologic Tools for Investigating X-Linked Ocular Albinism

PubMed Central

De Filippo, Elisabetta; Manga, Prashiela; Schiedel, Anke C.

2017-01-01

Purpose GPR143 regulates melanosome biogenesis and organelle size in pigment cells. The mechanisms underlying receptor function remain unclear. G protein–coupled receptors (GPCRs) are excellent pharmacologic targets; thus, we developed and applied a screening approach to identify potential GPR143 ligands and chemical modulators. Methods GPR143 interacts with β-arrestin; we therefore established a β-arrestin recruitment assay to screen for compounds that modulate activity. Because GPR143 is localized intracellularly, screening with the wild-type receptor would be restricted to agents absorbed by the cell. For the screen we used a mutant receptor, which shows similar basal activity as the wild type but traffics to the plasma membrane. We tested two compound libraries and investigated validated hits for their effects on melanocyte pigmentation. Results GPR143, which showed high constitutive activity in the β-arrestin assay, was inhibited by several compounds. The three validated inhibitors (pimozide, niclosamide, and ethacridine lactate) were assessed for impact on melanocytes. Pigmentation and expression of tyrosinase, a key melanogenic enzyme, were reduced by all compounds. Because GPR143 appears to be constitutively active, these compounds may turn off its activity. Conclusions X-linked ocular albinism type I, characterized by developmental eye defects, results from GPR143 mutations. Identifying pharmacologic agents that modulate GPR143 activity will contribute significantly to our understanding of its function and provide novel tools with which to study GPCRs in melanocytes and retinal pigment epithelium. Pimozide, one of three GPR143 inhibitors identified in this study, maybe be a good lead structure for development of more potent compounds and provide a platform for design of novel therapeutic agents. PMID:28632878

Acquisition, Processing, and Analysis of Continuous Multi-Offset GPR Data for Problems in Hydrogeophysics: Is it Worth the Cost? (Invited)

NASA Astrophysics Data System (ADS)

Bradford, J. H.

2009-12-01

Commercial development of multi-channel ground-penetrating radar (GPR) systems has made acquisition of continuous multi-offset (CMO) data more cost effective than ever. However, additional operator training, equipment costs, field and analysis time, and computation requirements necessarily remain substantially higher than conventional fixed offset GPR surveys. The choice to conduct a CMO survey is a target driven optimization problem where in many cases the added value outweighs the additional cost. Drawing examples from surface water, groundwater, snow, and glacier hydrology, I demonstrate a range of information that can be derived from CMO data with particular emphasis on estimating material properties of relevance to hydrological problems. Careful data acquisition is key to accurate property measurements. CMO geometries can be constructed with a single-channel system although with a significant loss of time and personnel efficiency relative to modern multi-channel systems. Using procedures such as common-midpoint stacking and pre-stack velocity filtering, it is possible to substantially improve the signal-to-noise ratio in GPR reflection images. However, the primary advantage of CMO data is dense sampling of a wide aperture of travelpaths through the subsurface. These data provide the basis for applying tomographic imaging techniques. Reflection velocity tomography in the pre-stack migration domain provides a robust approach to constructing accurate and detailed electromagnetic velocity models. These models in turn are used in conjunction with petrophysical models to estimate hydrologic properties such as porosity. Additionally, we can utilize the velocity models in conjunction with analysis of the frequency dependent attenuation to evaluate real and complex dielectric permittivity. The real and complex components of dielectric permittivity may have differing sensitivity to different components of the hydrologic system. Understanding this behavior may lead to improved understanding of relevant lithologic properties such as bulk clay content or fluid chemical composition during biodegradation of hydrocarbon contaminants. In addition to velocity tomography, CMO data enable reflection attenuation difference tomography. While time-lapse attenuation difference tomography using crosswell GPR transmission data is a well established technique for imaging conductive tracers in groundwater systems, it is not common for reflection data. Numerical examples based on a realistic aquifer model show that surface data can provide resolution of conductive tracer zones that is comparable to cross well data, thereby minimizing the need for invasive and expensive boreholes.

Performance of hybrid and single-frequency impulse GPR antennas on USGA sporting greens

USDA-ARS?s Scientific Manuscript database

The utility of employing ground-penetrating radar (GPR) technologies for environmental surveys can vary, depending upon the physical properties of the site. Environmental conditions can fluctuate, altering soil properties. Operator proficiency and survey methodology will also influence GPR findings....

Virtual and biomolecular screening converge on a selective agonist for GPR30.

PubMed

Bologa, Cristian G; Revankar, Chetana M; Young, Susan M; Edwards, Bruce S; Arterburn, Jeffrey B; Kiselyov, Alexander S; Parker, Matthew A; Tkachenko, Sergey E; Savchuck, Nikolay P; Sklar, Larry A; Oprea, Tudor I; Prossnitz, Eric R

2006-04-01

Estrogen is a hormone critical in the development, normal physiology and pathophysiology of numerous human tissues. The effects of estrogen have traditionally been solely ascribed to estrogen receptor alpha (ERalpha) and more recently ERbeta, members of the soluble, nuclear ligand-activated family of transcription factors. We have recently shown that the seven-transmembrane G protein-coupled receptor GPR30 binds estrogen with high affinity and resides in the endoplasmic reticulum, where it activates multiple intracellular signaling pathways. To differentiate between the functions of ERalpha or ERbeta and GPR30, we used a combination of virtual and biomolecular screening to isolate compounds that selectively bind to GPR30. Here we describe the identification of the first GPR30-specific agonist, G-1 (1), capable of activating GPR30 in a complex environment of classical and new estrogen receptors. The development of compounds specific to estrogen receptor family members provides the opportunity to increase our understanding of these receptors and their contribution to estrogen biology.

The G-protein-coupled receptor, GPR84, is important for eye development in Xenopus laevis.

PubMed

Perry, Kimberly J; Johnson, Verity R; Malloch, Erica L; Fukui, Lisa; Wever, Jason; Thomas, Alvin G; Hamilton, Paul W; Henry, Jonathan J

2010-11-01

G-protein-coupled receptors (GPCRs) represent diverse, multifamily groups of cell signaling receptors involved in many cellular processes. We identified Xenopus laevis GPR84 as a member of the A18 subfamily of GPCRs. During development, GPR84 is detected in the embryonic lens placode, differentiating lens fiber cells, retina, and cornea. Anti-sense morpholino oligonucleotide-mediated knockdown and RNA rescue experiments demonstrate GPR84's importance in lens, cornea, and retinal development. Examination of cell proliferation using an antibody against histone H3 S10P reveals significant increases in the lens and retina following GPR84 knockdown. Additionally, there was also an increase in apoptosis in the retina and lens, as revealed by TUNEL assay. Reciprocal transplantation of the presumptive lens ectoderm between uninjected controls and morpholino-injected embryos demonstrates that GPR84 is necessary in the retina for proper development of the retina, as well as other eye tissues including the lens and cornea. © 2010 Wiley-Liss, Inc.

The G-protein-coupled receptor, GPR84, is important for eye development in Xenopus laevis

PubMed Central

Perry, Kimberly J.; Johnson, Verity R.; Malloch, Erica L.; Fukui, Lisa; Wever, Jason; Thomas, Alvin G.; Hamilton, Paul W.; Henry, Jonathan J.

2010-01-01

G-protein-coupled receptors (GPCRs) represent diverse, multifamily groups of cell signaling receptors involved in many cellular processes. We identified Xenopus laevis GPR84 as a member of the A18 subfamily of GPCRs. During development, GPR84 is detected in the embryonic lens placode, differentiating lens fiber cells, retina and cornea. Anti-sense morpholino oligonucleotide-mediated knockdown and RNA rescue experiments demonstrate GPR84’s importance in lens, cornea and retinal development. Examination of cell proliferation using an antibody against histone H3 S10P reveals significant increases in the lens and retina following GPR84 knockdown. Additionally, there was also an increase in apoptosis in the retina and lens, as revealed by TUNEL assay. Reciprocal transplantation of the presumptive lens ectoderm between uninjected controls and morpholino injected embryos demonstrates that GPR84 is necessary in the retina for proper development of the retina, as well as other eye tissues including the lens and cornea. PMID:20925114

Gpr132 sensing of lactate mediates tumor–macrophage interplay to promote breast cancer metastasis

PubMed Central

Chen, Peiwen; Zuo, Hao; Xiong, Hu; Kolar, Matthew J.; Chu, Qian; Saghatelian, Alan; Siegwart, Daniel J.; Wan, Yihong

2017-01-01

Macrophages are prominent immune cells in the tumor microenvironment that exert potent effects on cancer metastasis. However, the signals and receivers for the tumor–macrophage communication remain enigmatic. Here, we show that G protein-coupled receptor 132 (Gpr132) functions as a key macrophage sensor of the rising lactate in the acidic tumor milieu to mediate the reciprocal interaction between cancer cells and macrophages during breast cancer metastasis. Lactate activates macrophage Gpr132 to promote the alternatively activated macrophage (M2)-like phenotype, which, in turn, facilitates cancer cell adhesion, migration, and invasion. Consequently, Gpr132 deletion reduces M2 macrophages and impedes breast cancer lung metastasis in mice. Clinically, Gpr132 expression positively correlates with M2 macrophages, metastasis, and poor prognosis in patients with breast cancer. These findings uncover the lactate-Gpr132 axis as a driver of breast cancer metastasis by stimulating tumor–macrophage interplay, and reveal potential new therapeutic targets for breast cancer treatment. PMID:28049847

2-D and 3-D Difraction Stake Migration Method Using GPR: A Case Study in Canakkale (Turkey)

NASA Astrophysics Data System (ADS)

Çaǧlar Yalçiner, Cahit

In this study, ground-penetrating radar (GPR) method was applied for Clandestine cemetery detection in Ηanakkale (Dardanelles), west Turkey. Investigated area was a historical area which was used as tent hospitals during the World War I. The study area was also used to bury soldiers who died during the treatment process in tent hospitals. Because of agricultural activity grave stones were used by local people, thus, most of the graves were lost in the field. 45 GPR profiles were applied with a GPR system (RAMAC) equipped with 250 MHz central frequency shielded antenna. After main processing steps on raw data, migration was applied to improve section resolution and develop the realism of the subsurface images. Although the GPR in results before migration the anomalous zones are visible, after migration the results became much more visible both in the profiles and 3D illustrations, thus, migrated GPR data were preferred to locate the buried martyrdoms.

Novel Therapeutic GPCRs for Psychiatric Disorders

PubMed Central

Komatsu, Hidetoshi

2015-01-01

G protein-coupled receptors (GPCRs) are the most common targets of the neuropharmacological drugs in the central nervous system (CNS). GPCRs are activated by manifold neurotransmitters, and their activation in turn evokes slow synaptic transmission. They are deeply involved in multiple neurological and psychiatric disorders such as Parkinson’s disease and schizophrenia. In the brain, the striatum is strongly innervated by the ventral tegmental area (VTA) and plays a central role in manifestation of psychiatric disorders. Recently, anatomical and comprehensive transcriptome analysis of the non-odorant GPCR superfamily revealed that the orphan GPCRs GPR88, GPR6, and GPR52, as well as dopamine D1 and D2 receptors and the adenosine A2a receptor, are the most highly enriched in the rodent striatum. Genetically engineered animal models and molecular biological studies have suggested that these striatally enriched GPCRs have a potential to be therapeutic psychiatric receptors. This review summarizes the current understanding of the therapeutic GPCR candidates for psychiatric disorders. PMID:26101869

Novel Therapeutic GPCRs for Psychiatric Disorders.

PubMed

Komatsu, Hidetoshi

2015-06-19

G protein-coupled receptors (GPCRs) are the most common targets of the neuropharmacological drugs in the central nervous system (CNS). GPCRs are activated by manifold neurotransmitters, and their activation in turn evokes slow synaptic transmission. They are deeply involved in multiple neurological and psychiatric disorders such as Parkinson's disease and schizophrenia. In the brain, the striatum is strongly innervated by the ventral tegmental area (VTA) and plays a central role in manifestation of psychiatric disorders. Recently, anatomical and comprehensive transcriptome analysis of the non-odorant GPCR superfamily revealed that the orphan GPCRs GPR88, GPR6, and GPR52, as well as dopamine D1 and D2 receptors and the adenosine A2a receptor, are the most highly enriched in the rodent striatum. Genetically engineered animal models and molecular biological studies have suggested that these striatally enriched GPCRs have a potential to be therapeutic psychiatric receptors. This review summarizes the current understanding of the therapeutic GPCR candidates for psychiatric disorders.

GPR applications in Civil Engineering in Spain - state-of-the-art

NASA Astrophysics Data System (ADS)

Pérez Gracia, Vega; Solla, Mercedes; Santos-Assunçao, Sonia; Lorenzo, Henrique

2014-05-01

GPR was introduced in Spain in 1990, and the first significant work was the PhD thesis of H. Lorenzo in 1994. Due to its versatile applicability, the employ has been increased and actually, GPR is extensively used in detection of pipes, wiring and urban services mainly. During the last years, this method was also widely utilized in the detection of graves from the civil war and in forensic studies, with irregular results. It was also commonly applied in archaeology. Actually exists more than 20 private companies offering geotechnical services by means of GPR. Also, several public institutions as Universities and Research Institutes base part of their research in GPR or in GPR applications. Notwithstanding, no training courses of specific formation on GPR is offered, but in several doctorate programs it is possible to work with GPR. Also, in many schools, GPR is part of the geophysical formation of graduate students. However, no national guidelines and rules exist, and each company defines the investigation protocols. Nevertheless, one of the aims of the Comisión Española de Geodesia y Geofísica (Spanish Committee for Geodesy and Geophysics) is to define guidelines for the GPR studies. Probably, the existence of national guidelines or perhaps European guidelines could be the most effective way to promote the responsible use of GPR in different domains. On the other hand, perhaps recommendations on the use of combined methodologies could be a practical way to persuade in the application of geophysical non-destructive technologies. The CEDEX, Centro de Estudios y Experimentación de Obras Públicas (Center for Studies and Experimentation in Civil Engineering), which is a civil engineering research agency in Spain, offers different test sites to calibrate and evaluate the method. It is an autonomous organization, organically ascribed at present to the Ministry of Fomento, and functionally ascribed to the Ministries of Fomento and Medioambiente of Spain, giving assistance to various administrations, public institutions and private companies. What is more, some of the existing private companies have also minor test sites to analyze the behavior of the signal and its propagation depending on the type of asphalt concrete. GPR is used mainly in detection of pipes and urban services and various private companies are specialized in these tasks. Another widespread application is archaeological survey; one private company is also specialized in archaeology evaluations, using GPR combined with magnetometer. Forensic examinations are also common applications in Spain. Other less common applications are: regular inspection of roads, bridges and tunnels, cultural heritage buildings assessment, shallow geology studies and quality control in civil engineering. Acknowledgment The study is a contribution to the EU funded COST Action TU1208, "Civil Engineering Applications of Ground Penetrating Radar".

GPR studies over the tsunami affected Karaikal beach, Tamil Nadu, south India

NASA Astrophysics Data System (ADS)

Loveson, V. J.; Gujar, A. R.; Barnwal, R.; Khare, Richa; Rajamanickam, G. V.

2014-08-01

In this study, results of GPR profiling related to mapping of subsurface sedimentary layers at tsunami affected Karaikal beach are presented . A 400 MHz antenna was used for profiling along 262 m stretch of transect from beach to backshore areas with penetration of about 2.0 m depth (50 ns two-way travel time). The velocity analysis was carried out to estimate the depth information along the GPR profile. Based on the significant changes in the reflection amplitude, three different zones are marked and the upper zone is noticed with less moisture compared to other two (saturated) zones. The water table is noticed to vary from 0.5 to 0.75 m depth (12-15 ns) as moving away from the coastline. Buried erosional surface is observed at 1.5 m depth (40-42 ns), which represents the limit up to which the extreme event acted upon. In other words, it is the depth to which the tsunami sediments have been piled up to about 1.5 m thickness. Three field test pits were made along the transect and sedimentary sequences were recorded. The sand layers, especially, heavy mineral layers, recorded in the test pits indicate a positive correlation with the amplitude and velocity changes in the GPR profile. Such interpretation seems to be difficult in the middle zone due to its water saturation condition. But it is fairly clear in the lower zone located just below the erosional surface where the strata is comparatively more compact. The inferences from the GPR profile thus provide a lucid insight to the subsurface sediment sequences of the tsunami sediments in the Karaikal beach.

Analysis of GPR101 and AIP genes mutations in acromegaly: a multicentric study.

PubMed

Ferraù, Francesco; Romeo, P D; Puglisi, S; Ragonese, M; Torre, M L; Scaroni, C; Occhi, G; De Menis, E; Arnaldi, G; Trimarchi, F; Cannavò, S

2016-12-01

This multicentric study aimed to investigate the prevalence of the G protein-coupled receptor 101 (GPR101) p.E308D variant and aryl hydrocarbon receptor interacting protein (AIP) gene mutations in a representative cohort of Italian patients with acromegaly. 215 patients with GH-secreting pituitary adenomas, referred to 4 Italian referral centres for pituitary diseases, have been included. Three cases of gigantism were present. Five cases were classified as FIPA. All the patients have been screened for germline AIP gene mutations and GPR101 gene p.E308D variant. Heterozygous AIP gene variants have been found in 7 patients (3.2 %). Five patients carried an AIP mutation (2.3 %; 4 females): 3 patients harboured the p.R3O4Q mutation, one had the p.R304* mutation and the last one the IVS3+1G>A mutation. The prevalence of AIP mutations was 3.3 % and 2.8 % when considering only the patients diagnosed when they were <30 or <40-year old, respectively. Furthermore, 2.0 % of the patients with a pituitary macroadenoma and 4.2 % of patients resistant to somatostatin analogues treatment were found to harbour an AIP gene mutation. None of the patients was found to carry the GPR101 p.E308D variant. The prevalence of AIP gene mutations among our sporadic and familial acromegaly cases was similar to that one reported in previous studies, but lower when considering only the cases diagnosed before 40 years of age. The GPR101 p.E308D change is unlikely to have a role in somatotroph adenomas tumorigenesis, since none of our sporadic or familial patients tested positive for this variant.

A case study to detect the leakage of underground pressureless cement sewage water pipe using GPR, electrical, and chemical data.

PubMed

Liu, Guanqun; Jia, Yonggang; Liu, Hongjun; Qiu, Hanxue; Qiu, Dongling; Shan, Hongxian

2002-03-01

The exploration and determination of leakage of underground pressureless nonmetallic pipes is difficult to deal with. A comprehensive method combining Ground Penetrating Rader (GPR), electric potential survey and geochemical survey is introduced in the leakage detection of an underground pressureless nonmetallic sewage pipe in this paper. Theoretically, in the influencing scope of a leakage spot, the obvious changes of the electromagnetic properties and the physical-chemical properties of the underground media will be reflected as anomalies in GPR and electrical survey plots. The advantages of GPR and electrical survey are fast and accurate in detection of anomaly scope. In-situ analysis of the geophysical surveys can guide the geochemical survey. Then water and soil sampling and analyzing can be the evidence for judging the anomaly is caused by pipe leakage or not. On the basis of previous tests and practical surveys, the GPR waveforms, electric potential curves, contour maps, and chemical survey results are all classified into three types according to the extent or indexes of anomalies in orderto find out the leakage spots. When three survey methods all show their anomalies as type I in an anomalous spot, this spot is suspected as the most possible leakage location. Otherwise, it will be down grade suspected point. The suspect leakage spots should be confirmed by referring the site conditions because some anomalies are caused other factors. The excavation afterward proved that the method for determining the suspected location by anomaly type is effective and economic. Comprehensive method of GRP, electric potential survey, and geochemical survey is one of the effective methods in the leakage detection of underground nonmetallic pressureless pipe with its advantages of being fast and accurate.

Identification of Karstic Features in Lateritic Soil by an Integrated Geophysical Approach

NASA Astrophysics Data System (ADS)

Anbazhagan, P.; Rohit, Divyesh; Prabhakaran, Athul; Vidyaranya, B.

2018-06-01

Lateritic soils are widely spread across the southern and central parts of India. Lateritic formations usually have soft sediments, entrapped between hard to medium soft lateritic rock, which are leached due to the ingress of water during rainy seasons creating hollow sections or cavities which span over large lengths. Laterites are highly heterogeneous and prone to cavitation due to its weathering process; a sound knowledge of the subsurface condition is required before starting any construction. This study presents the application of integrated geophysical investigation for the identification of cavities at a mega construction site in Kerala State, India. Geophysical survey methods, namely ground penetrating radar (GPR) and multichannel analysis of surface waves (MASWs) techniques, are used to identify the heterogeneities in lateritic soils and localized cavities. The survey areas identified are critical sections of a mega construction project subjected to heavy dynamic and static loads. The preliminary GPR survey is carried out across the study areas at specific interval spacing to identify probable heterogeneities. Confirmative survey or detailed GPR and MASW surveys are carried out at the locations identified in the preliminary survey at close intervals to confirm the presence of an anomaly and identify its location. The anomalies in the GPR radargram are identified by visual inspection and trace amplitude approach. Using MASW survey, a 2D shear wave velocity profile is generated to identify low shear wave velocity zones which confirm the presence of an anomaly. On comparing the data from both GPR and MASW survey techniques, the underground cavities were successfully identified at multiple locations with further crosschecking with borings. The study further provided details on subsurface lithology at survey locations.

Differential effects of α4β7 and GPR15 on homing of effector and regulatory T cells from patients with UC to the inflamed gut in vivo

PubMed Central

Fischer, Anika; Zundler, Sebastian; Atreya, Raja; Rath, Timo; Voskens, Caroline; Hirschmann, Simon; López-Posadas, Rocío; Watson, Alastair; Becker, Christoph; Schuler, Gerold; Neufert, Clemens; Atreya, Imke; Neurath, Markus F

2016-01-01

Objective Gut homing of lymphocytes via adhesion molecules has recently emerged as new target for therapy in IBDs. We aimed to analyse the in vivo homing of effector (Teff) and regulatory (Treg) T cells to the inflamed gut via α4β7 and G protein receptor GPR15. Design We assessed the expression of homing receptors on T cells in peripheral blood and inflamed mucosa. We studied the migration pattern and homing of Teff and Treg cells to the inflamed gut using intravital confocal microscopy and FACS in a humanised mouse model in dextran sodium sulfate-treated NSG (NOD.Cg-Prkdcscid-Il2rgtm1Wjl/SzJ) mice. Results Expression of GPR15 and α4β7 was significantly increased on Treg rather than Teff cells in peripheral blood of patients with UC as compared with Crohn’s disease and controls. In vivo analysis in a humanised mouse model showed augmented gut homing of UC Treg cells as compared with controls. Moreover, suppression of UC (but not control) Teff and Treg cell homing was noted upon treatment with the α4β7 antibody vedolizumab. In contrast, siRNA blockade of GPR15 had only effects on homing of Teff cells but did not affect Treg homing in UC. Clinical vedolizumab treatment was associated with marked expansion of UC Treg cells in peripheral blood. Conclusions α4β7 rather than GPR15 is crucial for increased colonic homing of UC Treg cells in vivo, while both receptors control UC Teff cell homing. Vedolizumab treatment impairs homing of UC Treg cells leading to their accumulation in peripheral blood with subsequent suppression of systemic Teff cell expansion. PMID:26209553

Synthetic estrogen derivatives demonstrate the functionality of intracellular GPR30.

PubMed

Revankar, Chetana M; Mitchell, Hugh D; Field, Angela S; Burai, Ritwik; Corona, Cesear; Ramesh, Chinnasamy; Sklar, Larry A; Arterburn, Jeffrey B; Prossnitz, Eric R

2007-08-17

Estrogen mediates its effects through multiple cellular receptors. In addition to the classical nuclear estrogen receptors (ERalpha and ERbeta), estrogen also signals through the seven-transmembrane G-protein-coupled receptor (GPCR) GPR30. Although estrogen is a cell-permeable ligand, it is often assumed that all GPCRs function solely as cell surface receptors. Our previous results showed that GPR30 appeared to be expressed predominantly in the endoplasmic reticulum. A critical question that arises is whether this localization represents the site of functional receptor. To address this question, we synthesized a collection of cell-permeable and cell-impermeable estrogen derivatives. We hypothesized that if functional GPR30 were expressed at the cell surface, both permeable and impermeable derivatives would show activity. However, if functional GPR30 were predominantly intracellular, like ERalpha, only the permeable ligands should show activity. Cell permeability was assessed using cells expressing ERalpha as a model intracellular estrogen-binding receptor. Our results reveal that despite exhibiting similar binding affinities for GPR30, only the cell-permeable ligands are capable of stimulating rapid calcium mobilization and phosphoinositide 3-kinase (PI3K) activation. We conclude that GPR30 expressed intracellularly is capable of initiating cellular signaling and that there is insufficient GPR30 expressed on the cell surface to initiate signaling in response to impermeable ligands in the cell lines examined. To our knowledge, this is the first definitive demonstration of a functional intracellular transmembrane estrogen receptor.

Detecting buried explosive hazards with handheld GPR and deep learning

NASA Astrophysics Data System (ADS)

Besaw, Lance E.

2016-05-01

Buried explosive hazards (BEHs), including traditional landmines and homemade improvised explosives, have proven difficult to detect and defeat during and after conflicts around the world. Despite their various sizes, shapes and construction material, ground penetrating radar (GPR) is an excellent phenomenology for detecting BEHs due to its ability to sense localized differences in electromagnetic properties. Handheld GPR detectors are common equipment for detecting BEHs because of their flexibility (in part due to the human operator) and effectiveness in cluttered environments. With modern digital electronics and positioning systems, handheld GPR sensors can sense and map variation in electromagnetic properties while searching for BEHs. Additionally, large-scale computers have demonstrated an insatiable appetite for ingesting massive datasets and extracting meaningful relationships. This is no more evident than the maturation of deep learning artificial neural networks (ANNs) for image and speech recognition now commonplace in industry and academia. This confluence of sensing, computing and pattern recognition technologies offers great potential to develop automatic target recognition techniques to assist GPR operators searching for BEHs. In this work deep learning ANNs are used to detect BEHs and discriminate them from harmless clutter. We apply these techniques to a multi-antennae, handheld GPR with centimeter-accurate positioning system that was used to collect data over prepared lanes containing a wide range of BEHs. This work demonstrates that deep learning ANNs can automatically extract meaningful information from complex GPR signatures, complementing existing GPR anomaly detection and classification techniques.

Interaction between G Protein-Coupled Receptor 143 and Tyrosinase: Implications for Understanding Ocular Albinism Type 1.

PubMed

De Filippo, Elisabetta; Schiedel, Anke C; Manga, Prashiela

2017-02-01

Developmental eye defects in X-linked ocular albinism type 1 are caused by G-protein coupled receptor 143 (GPR143) mutations. Mutations result in dysfunctional melanosome biogenesis and macromelanosome formation in pigment cells, including melanocytes and retinal pigment epithelium. GPR143, primarily expressed in pigment cells, localizes exclusively to endolysosomal and melanosomal membranes unlike most G protein-coupled receptors, which localize to the plasma membrane. There is some debate regarding GPR143 function and elucidating the role of this receptor may be instrumental for understanding neurogenesis during eye development and for devising therapies for ocular albinism type I. Many G protein-coupled receptors require association with other proteins to function. These G protein-coupled receptor-interacting proteins also facilitate fine-tuning of receptor activity and tissue specificity. We therefore investigated potential GPR143 interaction partners, with a focus on the melanogenic enzyme tyrosinase. GPR143 coimmunoprecipitated with tyrosinase, while confocal microscopy demonstrated colocalization of the proteins. Furthermore, tyrosinase localized to the plasma membrane when coexpressed with a GPR143 trafficking mutant. The physical interaction between the proteins was confirmed using fluorescence resonance energy transfer. This interaction may be required in order for GPR143 to function as a monitor of melanosome maturation. Identifying tyrosinase as a potential GPR143 binding protein opens new avenues for investigating the mechanisms that regulate pigmentation and neurogenesis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

High resolution aquifer characterization using crosshole GPR full-waveform tomography

NASA Astrophysics Data System (ADS)

Gueting, N.; Vienken, T.; Klotzsche, A.; Van Der Kruk, J.; Vanderborght, J.; Caers, J.; Vereecken, H.; Englert, A.

2016-12-01

Limited knowledge about the spatial distribution of aquifer properties typically constrains our ability to predict subsurface flow and transport. Here, we investigate the value of using high resolution full-waveform inversion of cross-borehole ground penetrating radar (GPR) data for aquifer characterization. By stitching together GPR tomograms from multiple adjacent crosshole planes, we are able to image, with a decimeter scale resolution, the dielectric permittivity and electrical conductivity of an alluvial aquifer along cross-sections of 50 m length and 10 m depth. A logistic regression model is employed to predict the spatial distribution of lithological facies on the basis of the GPR results. Vertical profiles of porosity and hydraulic conductivity from direct-push, flowmeter and grain size data suggest that the GPR predicted facies classification is meaningful with regard to porosity and hydraulic conductivity, even though the distributions of individual facies show some overlap and the absolute hydraulic conductivities from the different methods (direct-push, flowmeter, grain size) differ up to approximately one order of magnitude. Comparison of the GPR predicted facies architecture with tracer test data suggests that the plume splitting observed in a tracer experiment was caused by a hydraulically low-conductive sand layer with a thickness of only a few decimeters. Because this sand layer is identified by GPR full-waveform inversion but not by conventional GPR ray-based inversion we conclude that the improvement in spatial resolution due to full-waveform inversion is crucial to detect small-scale aquifer structures that are highly relevant for solute transport.

Role of GPR30 in the mechanisms of tamoxifen resistance in breast cancer MCF-7 cells.

PubMed

Ignatov, Atanas; Ignatov, Tanja; Roessner, Albert; Costa, Serban Dan; Kalinski, Thomas

2010-08-01

Tamoxifen is the most frequently used anti-hormonal drug for treatment of women with hormone-dependent breast cancer. The aim of this study is to investigate the mechanism of tamoxifen resistance and the impact of the new estrogen G-protein coupled receptor (GPR30). MCF-7 cells were continuously exposed to tamoxifen for 6 months to induce resistance to the inhibitory effect of tamoxifen. These tamoxifen-resistant cells (TAM-R) exhibited enhanced sensitivity to 17-ss-estradiol and GPR30 agonist, G1, when compared to the parental cells. In TAM-R cells, tamoxifen was able to stimulate the cell growth and MAPK phosphorylation. These effects were abolished by EGFR inhibitor AG1478, GPR30 anti-sense oligonucleotide, and the selective c-Src inhibitor PP2. Only EGFR basal expression was slightly elevated in the TAM-R cells, whereas GPR30 expression and the basal phosphorylation of Akt and MAPK remained unchanged when compared to the parental cells. Interestingly, estrogen treatment significantly increased GPR30 translocation to the cell surface, which was stronger in TAM-R cells. Continuous treatment of MCF-7 cells with GPR30 agonist G1 mimics the long-term treatment with tamoxifen and increases drastically its agonistic activity. This data suggests the important role of GPR30/EGFR receptor signaling in the development of tamoxifen resistance. The inhibition of this pathway is a valid option to improve anti-hormone response in breast cancer.

COST Action TU1208 - Working Group 2 - GPR surveying of pavements, bridges, tunnels and buildings; underground utility and void sensing

NASA Astrophysics Data System (ADS)

Pajewski, Lara; Benedetto, Andrea; Derobert, Xavier; Fontul, Simona; Govedarica, Miro; Gregoire, Colette; Loizos, Andreas; Perez-Gracia, Vega; Plati, Christina; Ristic, Aleksandar; Tosti, Fabio; Van Geem, Carl

2017-04-01

This work aims at presenting the main results achieved by Working Group (WG) 2 "GPR surveying of pavements, bridges, tunnels and buildings; underground utility and void sensing" of the COST (European COoperation in Science and Technology) Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar" (www.GPRadar.eu, www.cost.eu). The principal goal of the Action, started in April 2013 and ending in October 2017, is to exchange and increase scientific-technical knowledge and experience of Ground Penetrating Radar (GPR) techniques in civil engineering, whilst promoting throughout Europe the effective use of this safe non-destructive technique. The Action involves more than 300 Members from 28 COST Countries, a Cooperating State, 6 Near Neighbour Countries and 6 International Partner Countries. The most interesting achievements of WG2 include: 1. The state of the art on the use of GPR in civil engineering was composed and open issues were identified. The few existing international/national guidelines/protocols for GPR inspection in civil engineering were reviewed and discussed. Academic end-users, private companies and stakeholders presented their point of view and needs. 2. Guidelines for investigating flexible pavement by using GPR were prepared, with particular regard to layer-thickness assessment, moisture-content sensing, pavement-damage detection and classification, and other main GPR-based investigations in pavement engineering. 3. Guidelines for GPR sensing and mapping of underground utilities and voids were prepared, with a main focus on urban areas. 4. Guidelines for GPR assessment of concrete structures, with particular regard to inspections in bridges and tunnels, were prepared. 5. A report was composed, including a series of practical suggestions and very useful information to guide GPR users during building inspection. 6. WG2 Members carried out a plethora of case studies where GPR was used to survey roads, highways, airport runways, car parkings, road tunnels, underground concrete tunnels, bridges, railways, buildings. GPR was also employed to detect cables and pipes, as well as to inspect road construction materials, joints, concrete and wood. A selection of the most interesting results will be presented during the 2017 EGU GA. 7. WG2 contributed to the TU1208 Education Pack, an open-access educational package conceived to teach GPR in University courses. 8. In cooperation with the other Working Groups, WG2 organized Tutorials on Ground Penetrating Radar (Brussels, Belgium, July 2014, and London, United Kingdom, March 2015), as well as Training Schools on "Civil engineering applications of Ground Penetrating Radar" (Pisa, Italy, September 2014), "Applications of Ground Penetrating Radar in urban areas: the sensitive case of historical cities" (Cracow, Poland, May 2015), "Ground Penetrating Radar for road pavement assessment and detection of buried utilities" (London, United Kingdom, October 2015), "Applications of GPR to civil engineering and archaeology" (Valletta, Malta, January 2016), "Non-destructive testing techniques for civil engineering" (Barcelona, Spain, March 2016), and finally "Ground Penetrating Radar for the assessment of transport infrastructure" (Osijek, Croatia, March 2017). 9. In cooperation with the other Working Groups, WG2 organized a series of national events devoted to fostering the interaction with stakeholders, new potential GPR end-users, and interested citizens. During such events, participants could discover what is GPR and how this technique can be effectively used in civil engineering works as well as in different fields ("TU1208 GPR Road Show"). Acknowledgement: The Authors are deeply grateful to COST (European Cooperation in Science and Technology, www.cost.eu), for funding and supporting the COST Action TU1208 "Civil engineering applications of Ground Penetrating Radar" (www.GPRadar.eu).

Identification, localisation and functional implication of 26RFa orthologue peptide in the brain of zebra finch (Taeniopygia guttata).

PubMed

Tobari, Y; Iijima, N; Tsunekawa, K; Osugi, T; Haraguchi, S; Ubuka, T; Ukena, K; Okanoya, K; Tsutsui, K; Ozawa, H

2011-09-01

Several neuropeptides with the C-terminal Arg-Phe-NH(2) (RFa) sequence have been identified in the hypothalamus of a variety of vertebrates. The present study was conducted to isolate novel RFa peptides from the zebra finch brain. Peptides were isolated by immunoaffinity purification using an antibody that recognises avian RFa peptides. The isolated peptide consisted of 25 amino acids with RFa at its C-terminus. The sequence was SGTLGNLAEEINGYNRRKGGFTFRFa. Alignment of the peptide with vertebrate 26RFa has revealed that the identified peptide is the zebra finch 26RFa. We also cloned the precursor cDNA encoding this peptide. Synteny analysis of the gene showed a high conservation of this gene among vertebrates. In addition, we cloned the cDNA encoding a putative 26RFa receptor, G protein-coupled receptor 103 (GPR103) in the zebra finch brain. GPR103 cDNA encoded a 432 amino acid protein that has seven transmembrane domains. In situ hybridisation analysis in the brain showed that the expression of 26RFa mRNA is confined to the anterior-medial hypothalamic area, ventromedial nucleus of the hypothalamus and the lateral hypothalamic area, the brain regions that are involved in the regulation of feeding behaviour, whereas GPR103 mRNA is distributed throughout the brain in addition to the hypothalamic nuclei. When administered centrally in free-feeding male zebra finches, 26RFa increased food intake 24 h after injection without body mass change. Diencephalic GPR103 mRNA expression was up-regulated by fasting for 10 h. Our data suggest that the hypothalamic 26RFa-its receptor system plays an important role in the central control of food intake and energy homeostasis in the zebra finch. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

Air-launched GPR evaluation for rapid assessment of MoDOT bridge decks.

DOT National Transportation Integrated Search

2015-03-01

This study demonstrated the utility of the air-launched ground penetrating radar (GPR) tool in terms of : evaluating the condition of MoDOT bridge decks. The objective was to confirm that the air-launched GPR : tool can be implemented as a part of a ...

GPR-Based Water Leak Models in Water Distribution Systems

PubMed Central

Ayala-Cabrera, David; Herrera, Manuel; Izquierdo, Joaquín; Ocaña-Levario, Silvia J.; Pérez-García, Rafael

2013-01-01

This paper addresses the problem of leakage in water distribution systems through the use of ground penetrating radar (GPR) as a nondestructive method. Laboratory tests are performed to extract features of water leakage from the obtained GPR images. Moreover, a test in a real-world urban system under real conditions is performed. Feature extraction is performed by interpreting GPR images with the support of a pre-processing methodology based on an appropriate combination of statistical methods and multi-agent systems. The results of these tests are presented, interpreted, analyzed and discussed in this paper.

Expression of Estrogen Receptors Alpha (ER-α), Beta (ER-β), and G Protein-Coupled Receptor 30 (GPR30) in Testicular Tissue of Men with Klinefelter Syndrome.

PubMed

Bernardino, R L; Alves, M G; Silva, J; Barros, A; Ferraz, L; Sousa, M; Sá, R; Oliveira, P F

2016-06-01

Men with Klinefelter syndrome (KS) present severe hormonal dysregulation, particularly elevated serum estradiol concentration. Estrogens act through specific receptors and regulate testes development and spermatogenesis. Herein, we evaluated GPR30, ERα, and ERβ mRNA expression in testis of KS men and men with 46XY karyotype by reverse transcriptase and quantitative PCR. ERβ transcripts are the most abundant in testicular tissue of 46XY men. Notably, testicular GPR30 transcription in KS men was approximately 12 times higher. Since GPR30 is essential to mediate estrogen effects over steroidogenesis, our data illustrate that GPR30 may underpin the testicular alterations observed in KS men. © Georg Thieme Verlag KG Stuttgart · New York.

The research on the buried public monumental complexes of Lupiae (Lecce) by geophysical prospecting

NASA Astrophysics Data System (ADS)

Leucci, Giovanni; De Giorgi, Lara; Di Giacomo, Giacomo; Ditaranto, Imma; Miccoli, Ilaria; Scardozzi, Giuseppe

2017-10-01

Ongoing and extensive urbanisation may threaten important archaeological structures that are still buried in urban areas. The ground penetrating radar (GPR) method is the most promising alternative for resolving buried archaeological structures in urban territories. This paper presents a case study that involves a geophysical survey employing the surface three-dimensional (3D) GPR techniques, in order to archaeologically characterise the investigated areas. The site is located in the south-western sector of the historical centre of Lecce (Apulia, Italy), where the modern city overlaps the main public monuments of the Roman municipium of Lupiae, only partially preserved or excavated: the amphitheatre, the theatre, the baths and maybe also the Forum. GPR measurements, integrated with the results of archaeological excavations and the topographical surveys of the preserved remains, were carried out in several areas regarding sectors of the ancient roman city. The GPR data were collected along a dense network of parallel profiles. The GPR sections were processed applying specific filters to the data in order to enhance their information content. The GPR images significantly contributed in reconstructing the complex subsurface properties in these modern urban areas. Strong GPR reflections features were correlated with possible ancient structures and they were integrated in the digital archaeological map of the city.

Synthesis and characterization of iodinated tetrahydroquinolines targeting the G protein-coupled estrogen receptor GPR30.

PubMed

Ramesh, Chinnasamy; Nayak, Tapan K; Burai, Ritwik; Dennis, Megan K; Hathaway, Helen J; Sklar, Larry A; Prossnitz, Eric R; Arterburn, Jeffrey B

2010-02-11

A series of iodo-substituted tetrahydro-3H-cyclopenta[c]quinolines was synthesized as potential targeted imaging agents for the G protein-coupled estrogen receptor GPR30. The affinity and specificity of binding to GPR30 versus the classical estrogen receptors ER alpha/beta and functional responses associated with ligand-binding were determined. Selected iodo-substituted tetrahydro-3H-cyclopenta[c]quinolines exhibited IC(50) values lower than 20 nM in competitive binding studies with GPR30-expressing human endometrial cancer cells. These compounds functioned as antagonists of GPR30 and blocked estrogen-induced PI3K activation and calcium mobilization. The tributylstannyl precursors of selected compounds were radiolabeled with (125)I using the iodogen method. In vivo biodistribution studies in female ovariectomized athymic (NCr) nu/nu mice bearing GPR30-expressing human endometrial tumors revealed GPR30-mediated uptake of the radiotracer ligands in tumor, adrenal, and reproductive organs. Biodistribution and quantitative SPECT/CT studies revealed structurally related differences in the pharmacokinetic profiles, target tissue uptake, and metabolism of the radiolabeled compounds as well as differences in susceptibility to deiodination. The high lipophilicity of the compounds adversely affects the in vivo biodistribution and clearance of these radioligands and suggests that further optimization of this parameter may lead to improved targeting characteristics.

If training data appears to be mislabeled, should we relabel it? Improving supervised learning algorithms for threat detection in ground penetrating radar data

NASA Astrophysics Data System (ADS)

Reichman, Daniël.; Collins, Leslie M.; Malof, Jordan M.

2018-04-01

This work focuses on the development of automatic buried threat detection (BTD) algorithms using ground penetrating radar (GPR) data. Buried threats tend to exhibit unique characteristics in GPR imagery, such as high energy hyperbolic shapes, which can be leveraged for detection. Many recent BTD algorithms are supervised, and therefore they require training with exemplars of GPR data collected over non-threat locations and threat locations, respectively. Frequently, data from non-threat GPR examples will exhibit high energy hyperbolic patterns, similar to those observed from a buried threat. Is it still useful therefore, to include such examples during algorithm training, and encourage an algorithm to label such data as a non-threat? Similarly, some true buried threat examples exhibit very little distinctive threat-like patterns. We investigate whether it is beneficial to treat such GPR data examples as mislabeled, and either (i) relabel them, or (ii) remove them from training. We study this problem using two algorithms to automatically identify mislabeled examples, if they are present, and examine the impact of removing or relabeling them for training. We conduct these experiments on a large collection of GPR data with several state-of-the-art GPR-based BTD algorithms.

Antagonists for the orphan G-protein-coupled receptor GPR55 based on a coumarin scaffold.

PubMed

Rempel, Viktor; Volz, Nicole; Gläser, Franziska; Nieger, Martin; Bräse, Stefan; Müller, Christa E

2013-06-13

The orphan G-protein-coupled receptor GPR55, which is activated by 1-lysophosphatidylinositol and interacts with cannabinoid (CB) receptor ligands, has been proposed as a new potential drug target for the treatment of diabetes, Parkinson's disease, neuropathic pain, and cancer. We applied β-arrestin assays to identify 3-substituted coumarins as a novel class of antagonists and performed an extensive structure-activity relationship study for GPR55. Selectivity versus the related receptors CB1, CB2, and GPR18 was assessed. Among the 7-unsubstituted coumarins selective, competitive GPR55 antagonists were identified, such as 3-(2-hydroxybenzyl)-5-isopropyl-8-methyl-2H-chromen-2-one (12, PSB-SB-489, IC50 = 1.77 μM, pA2 = 0.547 μM). Derivatives with long alkyl chains in position 7 were potent, possibly allosteric GPR55 antagonists which showed ancillary CB receptor affinity. 7-(1,1-Dimethyloctyl)-5-hydroxy-3-(2-hydroxybenzyl)-2H-chromen-2-one (69, PSB-SB-487, IC50 = 0.113 μM, KB = 0.561 μM) and 7-(1,1-dimethylheptyl)-5-hydroxy-3-(2-hydroxybenzyl)-2H-chromen-2-one (67, PSB-SB-1203, IC50 = 0.261 μM) were the most potent GPR55 antagonists of the present series.

Reck and Gpr124 Are Essential Receptor Cofactors for Wnt7a/Wnt7b-Specific Signaling in Mammalian CNS Angiogenesis and Blood-Brain Barrier Regulation.

PubMed

Cho, Chris; Smallwood, Philip M; Nathans, Jeremy

2017-08-30

Reck, a GPI-anchored membrane protein, and Gpr124, an orphan GPCR, have been implicated in Wnt7a/Wnt7b signaling in the CNS vasculature. We show here that vascular endothelial cell (EC)-specific reduction in Reck impairs CNS angiogenesis and that EC-specific postnatal loss of Reck, combined with loss of Norrin, impairs blood-brain barrier (BBB) maintenance. The most N-terminal domain of Reck binds to the leucine-rich repeat (LRR) and immunoglobulin (Ig) domains of Gpr124, and weakening this interaction by targeted mutagenesis reduces Reck/Gpr124 stimulation of Wnt7a signaling in cell culture and impairs CNS angiogenesis. Finally, a soluble Gpr124(LRR-Ig) probe binds to cells expressing Frizzled, Wnt7a or Wnt7b, and Reck, and a soluble Reck(CC1-5) probe binds to cells expressing Frizzled, Wnt7a or Wnt7b, and Gpr124. These experiments indicate that Reck and Gpr124 are part of the cell surface protein complex that transduces Wnt7a- and Wnt7b-specific signals in mammalian CNS ECs to promote angiogenesis and regulate the BBB. Copyright © 2017 Elsevier Inc. All rights reserved.

GPR81, a Cell-Surface Receptor for Lactate, Regulates Intestinal Homeostasis and Protects Mice from Experimental Colitis.

PubMed

Ranganathan, Punithavathi; Shanmugam, Arulkumaran; Swafford, Daniel; Suryawanshi, Amol; Bhattacharjee, Pushpak; Hussein, Mohamed S; Koni, Pandelakis A; Prasad, Puttur D; Kurago, Zoya B; Thangaraju, Muthusamy; Ganapathy, Vadivel; Manicassamy, Santhakumar

2018-03-01

At mucosal sites such as the intestine, the immune system launches robust immunity against invading pathogens while maintaining a state of tolerance to commensal flora and ingested food Ags. The molecular mechanisms underlying this phenomenon remain poorly understood. In this study, we report that signaling by GPR81, a receptor for lactate, in colonic dendritic cells and macrophages plays an important role in suppressing colonic inflammation and restoring colonic homeostasis. Genetic deletion of GPR81 in mice led to increased Th1/Th17 cell differentiation and reduced regulatory T cell differentiation, resulting in enhanced susceptibility to colonic inflammation. This was due to increased production of proinflammatory cytokines (IL-6, IL-1β, and TNF-α) and decreased expression of immune regulatory factors (IL-10, retinoic acid, and IDO) by intestinal APCs lacking GPR81. Consistent with these findings, pharmacological activation of GPR81 decreased inflammatory cytokine expression and ameliorated colonic inflammation. Taken together, these findings identify a new and important role for the GPR81 signaling pathway in regulating immune tolerance and colonic inflammation. Thus, manipulation of the GPR81 pathway could provide novel opportunities for enhancing regulatory responses and treating colonic inflammation. Copyright © 2018 by The American Association of Immunologists, Inc.

The Use of Ground Penetrating Radar and Electrical Resistivity Imaging for the Characterisation of Slope Movements in Expansive Marls

NASA Astrophysics Data System (ADS)

Rey, Isabel; Martínez, Julián; Cortada, Unai; Hildago, Mª Carmen

2017-04-01

Slope movements are one of the natural hazards that most affect linear projects, becoming an important waste of money and time for building companies. Thus, studies to identify the processes that provoke these movements, as well as to characterise the landslides are necessary. For this purpose, geophysical prospecting techniques as Ground Penetrating Radar (GPR) and Electrical Resistivity Imaging (ERI) could become useful. However, the effectiveness of these techniques in slope movement characterisation is affected by many factors, like soil humidity, grain size or failure plane depth. Therefore, studies that determine the usefulness of these techniques in different kind of soils and slope movements are required. In this study, GPR and ERI techniques efficiency for the analysis of slope movements in Upper Miocene expansive marls was evaluated. In particular, two landslides in an old regional road in the province of Jaen (Spain) were studied. A total of 53 GPR profiles were made, 31 with a 250 MHz frequency antenna and 22 with an 800 MHz frequency antenna. Marl facies rapidly attenuated the signal of the electromagnetic waves, which means that this technique only provided information of the first two meters of the subsoil. In spite of this low depth of penetration, it is necessary to point out the precision and detail undertaken. Thus, both GPR antennas gave information of the thicknesses and quality-continuity of the different soil layers. In addition, several restoration phases of the linear work were detected. Therefore, this technique was useful to detect the current state and history of the structure, even though it could not detect the shear surface of the slope movement. On the other hand, two profiles of electrical tomography were made, one in each studied sector. The profiles were configured with a total length of 189 m, with 64 electrodes and a spacing of 3 m. This allowed investigating up to 35 m depth. This penetration capability enabled to detect the depth of the shear surfaces and therefore the minimum depth at which the possible piles should be placed in the design of the restoration structures. Thus, this method was more effective than the GPR for the detection of slope surfaces in uniform expansive marls. Nevertheless, the GPR was efficient for the analysis of the previous restoration phases, which was helpful to determine any relation between them and the causes that provoked the slope movements.

Extracellular pH Regulates Zinc Signaling via an Asp Residue of the Zinc-sensing Receptor (ZnR/GPR39)*

PubMed Central

Cohen, Limor; Asraf, Hila; Sekler, Israel; Hershfinkel, Michal

2012-01-01

Zinc activates a specific Zn2+-sensing receptor, ZnR/GPR39, and thereby triggers cellular signaling leading to epithelial cell proliferation and survival. Epithelial cells that express ZnR, particularly colonocytes, face frequent changes in extracellular pH that are of physiological and pathological implication. Here we show that the ZnR/GPR39-dependent Ca2+ responses in HT29 colonocytes were maximal at pH 7.4 but were reduced by about 50% at pH 7.7 and by about 62% at pH 7.1 and were completely abolished at pH 6.5. Intracellular acidification did not attenuate ZnR/GPR39 activity, indicating that the pH sensor of this protein is located on an extracellular domain. ZnR/GPR39-dependent activation of extracellular-regulated kinase (ERK)1/2 or AKT pathways was abolished at acidic extracellular pH of 6.5. A similar inhibitory effect was monitored for the ZnR/GPR39-dependent up-regulation of Na+/H+ exchange activity at pH 6.5. Focusing on residues putatively facing the extracellular domain, we sought to identify the pH sensor of ZnR/GPR39. Replacing the histidine residues forming the Zn2+ binding site, His17 or His19, or other extracellular-facing histidines to alanine residues did not abolish the pH dependence of ZnR/GPR39. In contrast, replacing Asp313 with alanine resulted in similar Ca2+ responses triggered by ZnR/GPR39 at pH 7.4 or 6.5. This mutant also showed similar activation of ERK1/2 and AKT pathways, and ZnR-dependent up-regulation of Na+/H+ exchange at pH 7.4 and pH 6.5. Substitution of Asp313 to His or Glu residues restored pH sensitivity of the receptor. This indicates that Asp313, which was shown to modulate Zn2+ binding, is an essential residue of the pH sensor of GPR39. In conclusion, ZnR/GPR39 is tuned to sense physiologically relevant changes in extracellular pH that thus regulate ZnR-dependent signaling and ion transport activity. PMID:22879599

Extracellular pH regulates zinc signaling via an Asp residue of the zinc-sensing receptor (ZnR/GPR39).

PubMed

Cohen, Limor; Asraf, Hila; Sekler, Israel; Hershfinkel, Michal

2012-09-28

Zinc activates a specific Zn(2+)-sensing receptor, ZnR/GPR39, and thereby triggers cellular signaling leading to epithelial cell proliferation and survival. Epithelial cells that express ZnR, particularly colonocytes, face frequent changes in extracellular pH that are of physiological and pathological implication. Here we show that the ZnR/GPR39-dependent Ca(2+) responses in HT29 colonocytes were maximal at pH 7.4 but were reduced by about 50% at pH 7.7 and by about 62% at pH 7.1 and were completely abolished at pH 6.5. Intracellular acidification did not attenuate ZnR/GPR39 activity, indicating that the pH sensor of this protein is located on an extracellular domain. ZnR/GPR39-dependent activation of extracellular-regulated kinase (ERK)1/2 or AKT pathways was abolished at acidic extracellular pH of 6.5. A similar inhibitory effect was monitored for the ZnR/GPR39-dependent up-regulation of Na(+)/H(+) exchange activity at pH 6.5. Focusing on residues putatively facing the extracellular domain, we sought to identify the pH sensor of ZnR/GPR39. Replacing the histidine residues forming the Zn(2+) binding site, His(17) or His(19), or other extracellular-facing histidines to alanine residues did not abolish the pH dependence of ZnR/GPR39. In contrast, replacing Asp(313) with alanine resulted in similar Ca(2+) responses triggered by ZnR/GPR39 at pH 7.4 or 6.5. This mutant also showed similar activation of ERK1/2 and AKT pathways, and ZnR-dependent up-regulation of Na(+)/H(+) exchange at pH 7.4 and pH 6.5. Substitution of Asp(313) to His or Glu residues restored pH sensitivity of the receptor. This indicates that Asp(313), which was shown to modulate Zn(2+) binding, is an essential residue of the pH sensor of GPR39. In conclusion, ZnR/GPR39 is tuned to sense physiologically relevant changes in extracellular pH that thus regulate ZnR-dependent signaling and ion transport activity.

Full-waveform inversion of GPR data for civil engineering applications

NASA Astrophysics Data System (ADS)

van der Kruk, Jan; Kalogeropoulos, Alexis; Hugenschmidt, Johannes; Klotzsche, Anja; Busch, Sebastian; Vereecken, Harry

2014-05-01

Conventional GPR ray-based techniques are often limited in their capability to image complex structures due to the pertaining approximations. Due to the increased computational power, it is becoming more easy to use modeling and inversion tools that explicitly take into account the detailed electromagnetic wave propagation characteristics. In this way, new civil engineering application avenues are opening up that enable an improved high resolution imaging of quantitative medium properties. In this contribution, we show recent developments that enable the full-waveform inversion of off-ground, on-ground and crosshole GPR data. For a successful inversion, a proper start model must be used that generates synthetic data that overlaps the measured data with at least half a wavelength. In addition, the GPR system must be calibrated such that an effective wavelet is obtained that encompasses the complexity of the GPR source and receiver antennas. Simple geometries such as horizontal layers can be described with a limited number of model parameters, which enable the use of a combined global and local search using the Simplex search algorithm. This approach has been implemented for the full-waveform inversion of off-ground and on-ground GPR data measured over horizontally layered media. In this way, an accurate 3D frequency domain forward model of Maxwell's equation can be used where the integral representation of the electric field is numerically evaluated. The full-waveform inversion (FWI) for a large number of unknowns uses gradient-based optimization methods where a 3D to 2D conversion is used to apply this method to experimental data. Off-ground GPR data, measured over homogeneous concrete specimens, were inverted using the full-waveform inversion. In contrast to traditional ray-based techniques we were able to obtain quantitative values for the permittivity and conductivity and in this way distinguish between moisture and chloride effects. For increasing chloride content increasing frequency-dependent conductivity values were obtained. The off-ground full-waveform inversion was extended to invert for positive and negative gradients in conductivity and the conductivity gradient direction could be correctly identified. Experimental specimen containing gradients were generated by exposing a concrete slab to controlled wetting-drying cycles using a saline solution. Full-waveform inversion of the measured data correctly identified the conductivity gradient direction which was confirmed by destructive analysis. On-ground CMP GPR data measured over a concrete layer overlying a metal plate show interfering multiple reflections, which indicates that the structure acts as a waveguide. Calculation of the phase-velocity spectrum shows the presence of several higher order modes. Whereas the dispersion inversion returns the thickness and layer height, the full-waveform inversion was also able to estimate quantitative conductivity values. This abstract is a contribution to COST Action TU1208

Geological disaster survey based on Curvelet transform with borehole Ground Penetrating Radar in Tonglushan old mine site.

PubMed

Tang, Xinjian; Sun, Tao; Tang, Zhijie; Zhou, Zenghui; Wei, Baoming

2011-06-01

Tonglushan old mine site located in Huangshi City, China, is very famous in the world. However, some of the ruins had suffered from geological disasters such as local deformation, surface cracking, in recent years. Structural abnormalities of rock-mass in deep underground were surveyed with borehole ground penetrating radar (GPR) to find out whether there were any mined galleries or mined-out areas below the ruins. With both the multiresolution analysis and sub-band directional of Curvelet transform, the feature information of targets' GPR signals were studied on Curvelet transform domain. Heterogeneity of geotechnical media and clutter jamming of complicated background of GPR signals could be conquered well, and the singularity characteristic information of typical rock mass signals could be extracted. Random noise had be removed by thresholding combined with Curvelet and the statistical characteristics of wanted signals and the noise, then direct wave suppression and the spatial distribution feature extraction could obtain a better result by making use of Curvelet transform directional. GprMax numerical modeling and analyzing of the sample data have verified the feasibility and effectiveness of our method. It is important and applicable for the analyzing of the geological structure and the disaster development about the Tonglushan old mine site. Copyright © 2011 The Research Centre for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Changes in obestatin gene and GPR39 receptor expression in peripheral tissues of rat models of obesity, type 1 and type 2 diabetes.

PubMed

Kolodziejski, Pawel Antoni; Pruszynska-Oszmalek, Ewa; Sassek, Maciej; Kaczmarek, Przemyslaw; Szczepankiewicz, Dawid; Billert, Maria; Mackowiak, Paweł; Strowski, Mathias Z; Nowak, Krzysztof W

2017-04-01

Obestatin has a role in regulating food intake and energy expenditure, but the roles of obestatin and the GPR39 receptor in obesity and type 1 and type 2 diabetes mellitus (T1DM and T2DM, respectively) are not well understood. The aim of the present study was to investigate changes in obestatin and GPR39 in pathophysiological conditions like obesity, T1DM, and T2DM. Using rat models of diet-induced obesity (DIO), T1DM and T2DM (n = 14 per group), obestatin, its precursor protein preproghrelin, and GPR39 expression was investigated in tissues involved in glucose and lipid homeostasis regulation. Furthermore, serum obestatin and ghrelin concentrations were determined. Serum obestatin concentrations were positively correlated with glucagon (r = 0.6456; P < 0.001) and visfatin (r = 0.5560; P < 0.001), and negatively correlated with insulin (r = -0.4362; P < 0.05), adiponectin (r = -0.3998; P < 0.05), and leptin (r = -0.4180; P < 0.05). There were differences in GPR39 and preproghrelin expression in the three animal models. Hepatic GPR39 and preproghrelin mRNA expression was greater in T1DM, T2DM, and obese rats than in lean controls, whereas pancreatic GPR39 mRNA and protein and preproghrelin mRNA expression was decreased in T1DM, T2DM, and DIO rats. Higher GPR39 and preproghrelin protein and mRNA levels were found in adipose tissues of T1DM compared with control. In adipose tissues of T2DM and DIO rats, GPR39 protein levels were lower than in lean or T1DM rats. Preproghrelin mRNA was higher in adipose tissues of T1DM, T2DM, and DIO than lean rats. We hypothesize that changes in obestatin, GPR39, and ghrelin may contribute to metabolic abnormalities in T1DM, T2DM, and obesity. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

A guidelines handbook for GPR surveys in tunnels: a COST Action TU1208 contribution

NASA Astrophysics Data System (ADS)

Bianchini Ciampoli, Luca; Alani, Amir M.; Pajewski, Lara; Benedetto, Andrea; Loizos, Andreas; Tosti, Fabio

2016-04-01

A significant open issue concerning the reliability of geophysical methods and in particular of ground penetrating radar (GPR), both in research and professional context, is a general lack of international standards. This is a major problem to be faced, in order to gain scientific strictness for the GPR practices, and to easily extend to the international community the results achieved within the area of single virtuous countries. Producing international guidelines can represent an important step forward, in this sense. In the memorandum of understanding of the COST Action TU1208 is clearly stated that one of the main purposes of the Action is the "development of innovative protocols and guidelines which will be published in a handbook and constitute a basis for European Standards, for an effective GPR application in CE tasks; safety, economic and financial criteria will be integrated within the protocols". Of course this is not a simple task to be accomplished. Firstly, survey procedures are highly dependent on the objective of the survey itself. On the basis of the objective of each geophysical test, the GPR system, the antenna configuration, and even the processing procedures may change. Besides, these procedures are also influenced by the environmental conditions in which the tests are performed. This affects several aspects spanning from hardware to software, but including, for instance, also safety issues. Due to these reasons, one of the main goal of the COST Action TU1208 is the development of several guidelines related to the main applications of GPR in the field of civil engineering. In this work, the structure of a guidelines handbook for GPR activities in tunnels is outlined. In the first sections, the principal references in the field are provided, and the most common GPR equipment and complementary technologies are described. Subsequently, the survey methodologies are explained. Particular attention is paid to the preliminary activities to be carried out prior to the GPR surveys, which can cover an important role in such a complex environment. Lastly, the main applications of GPR technology in tunnels are discussed. Acknowledgement The Authors thank COST, for funding the Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar."

Sirtuin 3 (SIRT3) Regulates α-Smooth Muscle Actin (α-SMA) Production through the Succinate Dehydrogenase-G Protein-coupled Receptor 91 (GPR91) Pathway in Hepatic Stellate Cells*

PubMed Central

Li, Ying Hui; Choi, Dae Hee; Lee, Eun Hye; Seo, Su Ryeon; Lee, Seungkoo

2016-01-01

Sirtuin 3 (SIRT3) is an NAD+-dependent protein deacetylase. Recent studies have shown that SIRT3 expression is decreased in nonalcoholic fatty liver disease (NAFLD). Moreover, SIRT3 is a key regulator of succinate dehydrogenase (SDH), which catalyzes the oxidation of succinate to fumarate. Increased succinate concentrations and the specific G protein-coupled receptor 91 (GPR91) are involved in the activation of hepatic stellate cells (HSCs). In this study, we aimed to establish whether SIRT3 regulated the SDH activity, succinate, and GPR91 expression in HSCs and an animal model of NAFLD. Our goal was also to determine whether succinate released from hepatocytes regulated HSC activation. Inhibiting SIRT3 using SIRT3 siRNA exacerbated HSC activation via the SDH-succinate-GPR91 pathway, and SIRT3 overexpression or honokiol treatment attenuated HSC activation in vitro. In isolated liver and HSCs from methionine- and choline-deficient (MCD) diet-induced NAFLD, the expression of SIRT3 and SDH activity was decreased, and the succinate concentrations and GPR91 expression were increased. Moreover, we found that GPR91 knockdown or resveratrol treatment improved the steatosis in MCD diet-fed mice. This investigation revealed a novel mechanism of the SIRT3-SDH-GPR91 cascade in MCD diet-induced HSC activation in NAFLD. These findings highlight the biological significance of novel strategies aimed at targeting SIRT3 and GPR91 in HSCs with the goal of improving NAFLD treatment. PMID:26912655

GPR30 Activation Opposes Estrogen-Dependent Uterine Growth via Inhibition of Stromal ERK1/2 and Estrogen Receptor Alpha (ERα) Phosphorylation Signals

PubMed Central

Gao, Fei; Ma, Xinghong; Ostmann, Alicia B.

2011-01-01

Although estradiol-17β (E2)-regulated early and late phase uterine responses have been well defined, the molecular mechanisms linking the phases remain poorly understood. We have previously shown that E2-regulated early signals mediate cross talk with estrogen receptor (ER)-α to elicit uterine late growth responses. G protein-coupled receptor (GPR30) has been implicated in early nongenomic signaling mediated by E2, although its role in E2-dependent uterine biology is unclear. Using selective activation of GPR30 by G-1, we show here a new function of GPR30 in regulating early signaling events, including the inhibition of ERK1/2 and ERα (Ser118) phosphorylation signals and perturbation of growth regulation under the direction of E2 in the mouse uterus. We observed that GPR30 primarily localizes in the uterine epithelial cells, and its activation alters gene expression and mediates inhibition of ERK1/2 and ERα (Ser118) phosphorylation signals in the stromal compartment, suggesting a paracrine signaling is involved. Importantly, viral-driven manipulation of GPR30 or pharmacological inhibition of ERK1/2 activation effectively alters E2-dependent uterine growth responses. Overall, GPR30 is a negative regulator of ERα-dependent uterine growth in response to E2. Our work has uncovered a novel GPR30-regulated inhibitory event, which may be physiologically relevant in both normal and pathological situations to negatively balance ERα-dependent uterine growth regulatory functions induced by E2. PMID:21303939

The seven-transmembrane receptor Gpr1 governs processes relevant for the antagonistic interaction of Trichoderma atroviride with its host.

PubMed

Omann, Markus R; Lehner, Sylvia; Escobar Rodríguez, Carolina; Brunner, Kurt; Zeilinger, Susanne

2012-01-01

Mycoparasitic Trichoderma species are applied as biocontrol agents in agriculture to guard plants against fungal diseases. During mycoparasitism, Trichoderma directly interacts with phytopathogenic fungi, preceded by a specific recognition of the host and resulting in its disarming and killing. In various fungal pathogens, including mycoparasites, signalling via heterotrimeric G proteins plays a major role in regulating pathogenicity-related functions. However, the corresponding receptors involved in the recognition of host-derived signals are largely unknown. Functional characterization of Trichoderma atroviride Gpr1 revealed a prominent role of this seven-transmembrane protein of the cAMP-receptor-like family of fungal G-protein-coupled receptors in the antagonistic interaction with the host fungus and governing of mycoparasitism-related processes. Silencing of gpr1 led to an avirulent phenotype accompanied by an inability to attach to host hyphae. Furthermore, gpr1-silenced transformants were unable to respond to the presence of living host fungi with the expression of chitinase- and protease-encoding genes. Addition of exogenous cAMP was able to restore host attachment in gpr1-silenced transformants but could not restore mycoparasitic overgrowth. A search for downstream targets of the signalling pathway(s) involving Gpr1 resulted in the isolation of genes encoding e.g. a member of the cyclin-like superfamily and a small secreted cysteine-rich protein. Although silencing of gpr1 caused defects similar to those of mutants lacking the Tga3 Gα protein, no direct interaction between Gpr1 and Tga3 was observed in a split-ubiquitin two-hybrid assay.

Differential phosphorylation signals control endocytosis of GPR15.

PubMed

Okamoto, Yukari; Shikano, Sojin

2017-08-15

GPR15 is an orphan G protein-coupled receptor (GPCR) that serves for an HIV coreceptor and was also recently found as a novel homing receptor for T-cells implicated in colitis. We show that GPR15 undergoes a constitutive endocytosis in the absence of ligand. The endocytosis was clathrin dependent and partially dependent on β-arrestin in HEK293 cells, and nearly half of the internalized GPR15 receptors were recycled to the plasma membrane. An Ala mutation of the distal C-terminal Arg-354 or Ser-357, which forms a consensus phosphorylation site for basophilic kinases, markedly reduced the endocytosis, whereas phosphomimetic mutation of Ser-357 to Asp did not. Ser-357 was phosphorylated in vitro by multiple kinases, including PKA and PKC, and pharmacological activation of these kinases enhanced both phosphorylation of Ser-357 and endocytosis of GPR15. These results suggested that Ser-357 phosphorylation critically controls the ligand-independent endocytosis of GPR15. The functional role of Ser-357 in endocytosis was distinct from that of a conserved Ser/Thr cluster in the more proximal C-terminus, which was responsible for the β-arrestin- and GPCR kinase-dependent endocytosis of GPR15. Thus phosphorylation signals may differentially control cell surface density of GPR15 through endocytosis. © 2017 Okamoto and Shikano. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

High resolution aquifer characterization using crosshole GPR full-waveform tomography: Comparison with direct-push and tracer test data

NASA Astrophysics Data System (ADS)

Gueting, Nils; Vienken, Thomas; Klotzsche, Anja; van der Kruk, Jan; Vanderborght, Jan; Caers, Jef; Vereecken, Harry; Englert, Andreas

2017-01-01

Limited knowledge about the spatial distribution of aquifer properties typically constrains our ability to predict subsurface flow and transport. Here we investigate the value of using high resolution full-waveform inversion of cross-borehole ground penetrating radar (GPR) data for aquifer characterization. By stitching together GPR tomograms from multiple adjacent crosshole planes, we are able to image, with a decimeter scale resolution, the dielectric permittivity and electrical conductivity of an alluvial aquifer along cross sections of 50 m length and 10 m depth. A logistic regression model is employed to predict the spatial distribution of lithological facies on the basis of the GPR results. Vertical profiles of porosity and hydraulic conductivity from direct-push, flowmeter and grain size data suggest that the GPR predicted facies classification is meaningful with regard to porosity and hydraulic conductivity, even though the distributions of individual facies show some overlap and the absolute hydraulic conductivities from the different methods (direct-push, flowmeter, grain size) differ up to approximately one order of magnitude. Comparison of the GPR predicted facies architecture with tracer test data suggests that the plume splitting observed in a tracer experiment was caused by a hydraulically low-conductive sand layer with a thickness of only a few decimeters. Because this sand layer is identified by GPR full-waveform inversion but not by conventional GPR ray-based inversion we conclude that the improvement in spatial resolution due to full-waveform inversion is crucial to detect small-scale aquifer structures that are highly relevant for solute transport.

The seven-transmembrane receptor Gpr1 governs processes relevant for the antagonistic interaction of Trichoderma atroviride with its host

PubMed Central

Omann, Markus R.; Lehner, Sylvia; Escobar Rodríguez, Carolina; Brunner, Kurt

2012-01-01

Mycoparasitic Trichoderma species are applied as biocontrol agents in agriculture to guard plants against fungal diseases. During mycoparasitism, Trichoderma directly interacts with phytopathogenic fungi, preceded by a specific recognition of the host and resulting in its disarming and killing. In various fungal pathogens, including mycoparasites, signalling via heterotrimeric G proteins plays a major role in regulating pathogenicity-related functions. However, the corresponding receptors involved in the recognition of host-derived signals are largely unknown. Functional characterization of Trichoderma atroviride Gpr1 revealed a prominent role of this seven-transmembrane protein of the cAMP-receptor-like family of fungal G-protein-coupled receptors in the antagonistic interaction with the host fungus and governing of mycoparasitism-related processes. Silencing of gpr1 led to an avirulent phenotype accompanied by an inability to attach to host hyphae. Furthermore, gpr1-silenced transformants were unable to respond to the presence of living host fungi with the expression of chitinase- and protease-encoding genes. Addition of exogenous cAMP was able to restore host attachment in gpr1-silenced transformants but could not restore mycoparasitic overgrowth. A search for downstream targets of the signalling pathway(s) involving Gpr1 resulted in the isolation of genes encoding e.g. a member of the cyclin-like superfamily and a small secreted cysteine-rich protein. Although silencing of gpr1 caused defects similar to those of mutants lacking the Tga3 Gα protein, no direct interaction between Gpr1 and Tga3 was observed in a split-ubiquitin two-hybrid assay. PMID:22075023

Angelica dahurica Extracts Improve Glucose Tolerance through the Activation of GPR119

PubMed Central

Kim, Mi-Hwi; Choung, Jin-Seung; Oh, Yoon-Sin; Moon, Hong-Sub; Jun, Hee-Sook

2016-01-01

G protein-coupled receptor (GPR) 119 is expressed in pancreatic β-cells and intestinal L cells, and is involved in glucose-stimulated insulin secretion and glucagon-like peptide-1 (GLP-1) release, respectively. Therefore, the development of GPR119 agonists is a potential treatment for type 2 diabetes. We screened 1500 natural plant extracts for GPR119 agonistic actions and investigated the most promising extract, that from Angelica dahurica (AD), for hypoglycemic actions in vitro and in vivo. Human GPR119 activation was measured in GeneBLAzer T-Rex GPR119-CRE-bla CHO-K1 cells; intracellular cAMP levels and insulin secretion were measured in INS-1 cells; and GLP-1 release was measured in GLUTag cells. Glucose tolerance tests and serum plasma insulin levels were measured in normal C57BL6 mice and diabetic db/db mice. AD extract-treated cells showed significant increases in GPR119 activation, intracellular cAMP levels, GLP-1 levels and glucose-stimulated insulin secretion as compared with controls. In normal mice, a single treatment with AD extract improved glucose tolerance and increased insulin secretion. Treatment with multiple doses of AD extract or n-hexane fraction improved glucose tolerance in diabetic db/db mice. Imperatorin, phellopterin and isoimperatorin were identified in the active fraction of AD extract. Among these, phellopterin activated GPR119 and increased active GLP-1 and insulin secretion in vitro and enhanced glucose tolerance in normal and db/db mice. We suggest that phellopterin might have a therapeutic potential for the treatment of type 2 diabetes. PMID:27391814

The G protein-coupled receptor GPR30 mediates the proliferative and invasive effects induced by hydroxytamoxifen in endometrial cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Du, Gui-Qiang; Zhou, Long; Chen, Xiao-Yue

2012-04-06

Highlights: Black-Right-Pointing-Pointer We assessed hydroxytamoxifen (OHT) effects in two endometrial cancer cell lines. Black-Right-Pointing-Pointer GPR30 mediates the proliferative effects induced by OHT. Black-Right-Pointing-Pointer GPR30 mediates the invasive effects induced by OHT. Black-Right-Pointing-Pointer GPR30 expression was up-regulated by OHT in endometrial cancer cell line. -- Abstract: The selective ER modulator tamoxifen (TAM) is the most widely used ER antagonist for treatment of women with hormone-dependent breast tumor. However, long-term treatment is associated with an increased risk of endometrial cancer. The aim of the present study was to demonstrate new insight into the role of G-protein coupled receptor 30 (GPR30) in themore » activity of TAM, which promoted endometrial cancer. In endometrial cancer cell lines ISHIKAWA and KLE, the potential of 4-hydroxytamoxifen (OHT), the active metabolite of TAM, 17{beta}-estradiol (E2) and G1, a non-steroidal GPR30-specific agonist to promote cell proliferation and invasion was evaluated. All agents above induced high proliferative and invasive effects, while the down-regulation of GPR30 or the interruption of MAPK signal pathway partly or completely prevented the action of the regent. Moreover, the RNA and protein expression of GPR30 was up-regulated by G1, E2 or OHT in both cell lines. The present study provided a new insight into the mechanism involved in the agonistic activity exerted by TAM in the uterus.« less

Sirtuin 3 (SIRT3) Regulates α-Smooth Muscle Actin (α-SMA) Production through the Succinate Dehydrogenase-G Protein-coupled Receptor 91 (GPR91) Pathway in Hepatic Stellate Cells.

PubMed

Li, Ying Hui; Choi, Dae Hee; Lee, Eun Hye; Seo, Su Ryeon; Lee, Seungkoo; Cho, Eun-Hee

2016-05-06

Sirtuin 3 (SIRT3) is an NAD(+)-dependent protein deacetylase. Recent studies have shown that SIRT3 expression is decreased in nonalcoholic fatty liver disease (NAFLD). Moreover, SIRT3 is a key regulator of succinate dehydrogenase (SDH), which catalyzes the oxidation of succinate to fumarate. Increased succinate concentrations and the specific G protein-coupled receptor 91 (GPR91) are involved in the activation of hepatic stellate cells (HSCs). In this study, we aimed to establish whether SIRT3 regulated the SDH activity, succinate, and GPR91 expression in HSCs and an animal model of NAFLD. Our goal was also to determine whether succinate released from hepatocytes regulated HSC activation. Inhibiting SIRT3 using SIRT3 siRNA exacerbated HSC activation via the SDH-succinate-GPR91 pathway, and SIRT3 overexpression or honokiol treatment attenuated HSC activation in vitro In isolated liver and HSCs from methionine- and choline-deficient (MCD) diet-induced NAFLD, the expression of SIRT3 and SDH activity was decreased, and the succinate concentrations and GPR91 expression were increased. Moreover, we found that GPR91 knockdown or resveratrol treatment improved the steatosis in MCD diet-fed mice. This investigation revealed a novel mechanism of the SIRT3-SDH-GPR91 cascade in MCD diet-induced HSC activation in NAFLD. These findings highlight the biological significance of novel strategies aimed at targeting SIRT3 and GPR91 in HSCs with the goal of improving NAFLD treatment. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Alterations in Gene and Protein Expression of Cannabinoid CB2 and GPR55 Receptors in the Dorsolateral Prefrontal Cortex of Suicide Victims.

PubMed

García-Gutiérrez, María S; Navarrete, Francisco; Navarro, Gemma; Reyes-Resina, Irene; Franco, Rafael; Lanciego, Jose Luis; Giner, Salvador; Manzanares, Jorge

2018-02-12

Recent studies point to the cannabinoid CB 2 receptors (CB 2 r) and the non-cannabinoid receptor GPR55 as potential key targets involved in the response to stress, anxiety, and depression. Considering the close relationship between neuropsychiatric disorders and suicide, the purpose of this study was to evaluate the potential alterations of CB 2 r and GPR55 in suicide victims. We analyzed gene and protein expression of both receptors by real-time PCR and western blot, respectively, in the dorsolateral prefrontal cortex (DLPFC) of 18 suicide victims with no clinical psychiatric history or treatment with anxiolytics or antidepressants, and 15 corresponding controls. We used in situ proximity ligation assay to evaluate whether the receptors formed heteromeric complexes and to determine the expression level of these heteromers, also assessing the co-expression of heteromers in neurons, astroglia, or microglia cells. CB 2 r and GPR55 gene expressions were significantly lower (by 33 and 41%, respectively) in the DLPFC of suicide cases. CB 2 r protein expression was higher, as were CB 2 -GPR55 heteroreceptor complexes. The results also revealed the presence of CB 2 -GPR55 receptor heteromers in both neurons and astrocytes, whereas microglial cells showed no expression. We did not observe any significant alterations of GPR55 protein expression. Additional studies will be necessary to evaluate if these alterations are reproducible in suicide victims diagnosed with different psychiatric disorders. Taken together, the results suggest that CB 2 r and GPR55 may play a relevant role in the neurobiology of suicide.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, Jun; Byrne, Noel; Wang, John

Clinical studies indicate that partial agonists of the G-protein-coupled, free fatty acid receptor 1 GPR40 enhance glucose-dependent insulin secretion and represent a potential mechanism for the treatment of type 2 diabetes mellitus. Full allosteric agonists (AgoPAMs) of GPR40 bind to a site distinct from partial agonists and can provide additional efficacy. We report the 3.2-Å crystal structure of human GPR40 (hGPR40) in complex with both the partial agonist MK-8666 and an AgoPAM, which exposes a novel lipid-facing AgoPAM-binding pocket outside the transmembrane helical bundle. Comparison with an additional 2.2-Å structure of the hGPR40–MK-8666 binary complex reveals an induced-fit conformational couplingmore » between the partial agonist and AgoPAM binding sites, involving rearrangements of the transmembrane helices 4 and 5 (TM4 and TM5) and transition of the intracellular loop 2 (ICL2) into a short helix. These conformational changes likely prime GPR40 to a more active-like state and explain the binding cooperativity between these ligands.« less

Structural basis for regulation of GPR56/ADGRG1 by its alternatively spliced extracellular domains

PubMed Central

Salzman, Gabriel S.; Ackerman, Sarah D.; Ding, Chen; Koide, Akiko; Leon, Katherine; Luo, Rong; Stoveken, Hannah M.; Fernandez, Celia G.; Tall, Gregory G.; Piao, Xianhua; Monk, Kelly R.; Koide, Shohei; Araç, Demet

2016-01-01

Summary Adhesion G-protein-coupled receptors (aGPCRs) play critical roles in diverse neurobiological processes including brain development, synaptogenesis, and myelination. aGPCRs have large alternatively spliced extracellular regions (ECRs) that likely mediate intercellular signaling; however, the precise roles of ECRs remain unclear. The aGPCR GPR56/ADGRG1 regulates both oligodendrocyte and cortical development. Accordingly, human GPR56 mutations cause myelination defects and brain malformations. Here, we determined the crystal structure of the GPR56 ECR, the first structure of any complete aGPCR ECR, in complex with an inverse-agonist monobody, revealing a GPCR-Autoproteolysis-Inducing domain and a previously unidentified domain that we term Pentraxin/Laminin/neurexin/sex-hormone-binding-globulin-Like (PLL). Strikingly, PLL domain deletion caused increased signaling and characterizes a GPR56 splice variant. Finally, we show that an evolutionarily conserved residue in the PLL domain is critical for oligodendrocyte development in vivo. Thus, our results suggest that the GPR56 ECR has unique and multifaceted regulatory functions, providing novel insights into aGPCR roles in neurobiology. PMID:27657451

Genistein regulates the IL-1 beta induced activation of MAPKs in human periodontal ligament cells through G protein-coupled receptor 30.

PubMed

Luo, Li-Jun; Liu, Feng; Lin, Zhi-Kai; Xie, Yu-Feng; Xu, Jia-Li; Tong, Qing-Chun; Shu, Rong

2012-06-01

Periodontal ligament (PDL) cells are fibroblasts that play key roles in tissue integrity, periodontal inflammation and tissue regeneration in the periodontium. The periodontal tissue destruction in periodontitis is mediated by host tissue-produced inflammatory cytokines, including interleukin-1β (IL-1β). Here, we report the expression of G protein-coupled receptor 30 (GPR30, also known as G protein-coupled estrogen receptor 1 GPER) in human PDL cells and its regulation by IL-1β. IL-1β-induced GPR30 expression in human PDL cells leads to the activation of multiple signaling pathways, including MAPK, NF-κB and PI3K. In contrast, genistein, an estrogen receptor ligand, postpones the activation of MAPKs induced by IL-1β. Moreover, the inhibition of GPR30 by G15, a GPR30-specific antagonist, eliminates this delay. Thus, genistein plays a role in the regulation of MAPK activation via GPR30, and GPR30 represents a novel target regulated by steroid hormones in PDL cells. Copyright © 2012 Elsevier Inc. All rights reserved.

Improving GPR image resolution in lossy ground using dispersive migration

USGS Publications Warehouse

Oden, C.P.; Powers, M.H.; Wright, D.L.; Olhoeft, G.R.

2007-01-01

As a compact wave packet travels through a dispersive medium, it becomes dilated and distorted. As a result, ground-penetrating radar (GPR) surveys over conductive and/or lossy soils often result in poor image resolution. A dispersive migration method is presented that combines an inverse dispersion filter with frequency-domain migration. The method requires a fully characterized GPR system including the antenna response, which is a function of the local soil properties for ground-coupled antennas. The GPR system response spectrum is used to stabilize the inverse dispersion filter. Dispersive migration restores attenuated spectral components when the signal-to-noise ratio is adequate. Applying the algorithm to simulated data shows that the improved spatial resolution is significant when data are acquired with a GPR system having 120 dB or more of dynamic range, and when the medium has a loss tangent of 0.3 or more. Results also show that dispersive migration provides no significant advantage over conventional migration when the loss tangent is less than 0.3, or when using a GPR system with a small dynamic range. ?? 2007 IEEE.

Gpr124 is essential for blood-brain barrier integrity in central nervous system disease.

PubMed

Chang, Junlei; Mancuso, Michael R; Maier, Carolina; Liang, Xibin; Yuki, Kanako; Yang, Lu; Kwong, Jeffrey W; Wang, Jing; Rao, Varsha; Vallon, Mario; Kosinski, Cynthia; Zhang, J J Haijing; Mah, Amanda T; Xu, Lijun; Li, Le; Gholamin, Sharareh; Reyes, Teresa F; Li, Rui; Kuhnert, Frank; Han, Xiaoyuan; Yuan, Jenny; Chiou, Shin-Heng; Brettman, Ari D; Daly, Lauren; Corney, David C; Cheshier, Samuel H; Shortliffe, Linda D; Wu, Xiwei; Snyder, Michael; Chan, Pak; Giffard, Rona G; Chang, Howard Y; Andreasson, Katrin; Kuo, Calvin J

2017-04-01

Although blood-brain barrier (BBB) compromise is central to the etiology of diverse central nervous system (CNS) disorders, endothelial receptor proteins that control BBB function are poorly defined. The endothelial G-protein-coupled receptor (GPCR) Gpr124 has been reported to be required for normal forebrain angiogenesis and BBB function in mouse embryos, but the role of this receptor in adult animals is unknown. Here Gpr124 conditional knockout (CKO) in the endothelia of adult mice did not affect homeostatic BBB integrity, but resulted in BBB disruption and microvascular hemorrhage in mouse models of both ischemic stroke and glioblastoma, accompanied by reduced cerebrovascular canonical Wnt-β-catenin signaling. Constitutive activation of Wnt-β-catenin signaling fully corrected the BBB disruption and hemorrhage defects of Gpr124-CKO mice, with rescue of the endothelial gene tight junction, pericyte coverage and extracellular-matrix deficits. We thus identify Gpr124 as an endothelial GPCR specifically required for endothelial Wnt signaling and BBB integrity under pathological conditions in adult mice. This finding implicates Gpr124 as a potential therapeutic target for human CNS disorders characterized by BBB disruption.

Macrophage PPARγ inhibits Gpr132 to mediate the anti-tumor effects of rosiglitazone

PubMed Central

Cheng, Wing Yin; Huynh, HoangDinh; Chen, Peiwen; Peña-Llopis, Samuel; Wan, Yihong

2016-01-01

Tumor-associated macrophage (TAM) significantly contributes to cancer progression. Human cancer is enhanced by PPARγ loss-of-function mutations, but inhibited by PPARγ agonists such as TZD diabetes drugs including rosiglitazone. However, it remains enigmatic whether and how macrophage contributes to PPARγ tumor-suppressive functions. Here we report that macrophage PPARγ deletion in mice not only exacerbates mammary tumor development but also impairs the anti-tumor effects of rosiglitazone. Mechanistically, we identify Gpr132 as a novel direct PPARγ target in macrophage whose expression is enhanced by PPARγ loss but repressed by PPARγ activation. Functionally, macrophage Gpr132 is pro-inflammatory and pro-tumor. Genetic Gpr132 deletion not only retards inflammation and cancer growth but also abrogates the anti-tumor effects of PPARγ and rosiglitazone. Pharmacological Gpr132 inhibition significantly impedes mammary tumor malignancy. These findings uncover macrophage PPARγ and Gpr132 as critical TAM modulators, new cancer therapeutic targets, and essential mediators of TZD anti-cancer effects. DOI: http://dx.doi.org/10.7554/eLife.18501.001 PMID:27692066

GPR random noise reduction using BPD and EMD

NASA Astrophysics Data System (ADS)

Ostoori, Roya; Goudarzi, Alireza; Oskooi, Behrooz

2018-04-01

Ground-penetrating radar (GPR) exploration is a new high-frequency technology that explores near-surface objects and structures accurately. The high-frequency antenna of the GPR system makes it a high-resolution method compared to other geophysical methods. The frequency range of recorded GPR is so wide that random noise recording is inevitable due to acquisition. This kind of noise comes from unknown sources and its correlation to the adjacent traces is nearly zero. This characteristic of random noise along with the higher accuracy of GPR system makes denoising very important for interpretable results. The main objective of this paper is to reduce GPR random noise based on pursuing denoising using empirical mode decomposition. Our results showed that empirical mode decomposition in combination with basis pursuit denoising (BPD) provides satisfactory outputs due to the sifting process compared to the time-domain implementation of the BPD method on both synthetic and real examples. Our results demonstrate that because of the high computational costs, the BPD-empirical mode decomposition technique should only be used for heavily noisy signals.

Study of time-reversal-based signal processing applied to polarimetric GPR detection of elongated targets

NASA Astrophysics Data System (ADS)

Santos, Vinicius Rafael N.; Teixeira, Fernando L.

2017-04-01

Ground penetrating radar (GPR) is a useful sensing modality for mapping and identification of underground infrastructure networks, such as metal and concrete pipes (gas, water or sewer), phone conduits or cables, and other buried objects. Due to the polarization-dependent response of typical targets, it is of interest to investigate the optimum antenna arrangement and/or combination of arrangements that maximize the detection and classification capabilities of polarimetric GPR imaging systems. Here, we provide a preliminary study of time-reversal-based techniques applied to target detection by GPR utilizing different relative orientations of linear-polarized antenna elements (with respect to each other, as well as to the targets). We modeled three different pipe materials (metallic, plastic and concrete) and GPR systems operating at center frequencies of 100 MHz and 200 MHz. Full-wave numerical simulations are adopted to account for mutual coupling between targets. This type of assessment study may contribute to the improvement of GPR data interpretation of infrastructure networks in urban area surveys and in other engineering studies.

Mapping Subsurface Structure at Guar Kepah by using Ground Penetrating Radar

NASA Astrophysics Data System (ADS)

Mansor, Hafizuddin; Rosli, Najmiah; Ismail, N. A.; Saidin, M.; Masnan, S. S. K.

2018-04-01

A Ground Penetrating Radar (GPR) survey was conducted at Guar Kepah to detect buried object before commencement of archaeological gallery construction. The study area covered around 20 m length and 14 m width. 15 GPR lines were constructed from north to south with 20 m length, 1 m spacing and parallel to each other. The 500 MHz closed antenna had been used in this study. The surface findings were noticed before started GPR survey. The data was analysed and interpreted by using Groundvision software and several filters were applied to radargrams to enhance the data. Based on the result, several anomalies were detected. The surface findings also detected by GPR which cause hyperbolic curve in radargrams. The subsurface layer was detected by GPR survey. The anomalies are assigned to several classes based on the pattern of signals obtained in radargrams.

Relaxation of water infiltration pulses observed with GPR

NASA Astrophysics Data System (ADS)

Hantschel, Lisa; Hemmer, Benedikt; Roth, Kurt

2017-04-01

We observe the relaxation of infiltration pulses in sandy soil with ground-penetrating radar (GPR). The spatial distribution of water in the infiltration area and its temporal evolution is represented by ordinary reflections at layer boundaries as well as multiple reflections at the wetting front and the pulse boundaries. The structure of these highly resolved signals are reproduced by numerical simulations of electromagnetic wave propagation. The temporally highly resolved electrical fields reveal the origin also of complex reflection signals. The usage of these more complex signals might allow a more detailed representation of the infiltration process by direct analysis as well as in combination with inversion techniques.

GPR use and activities in the Czech Republic

NASA Astrophysics Data System (ADS)

Stryk, Josef; Matula, Radek

2014-05-01

In the field of civil engineering applications in the Czech Republic, Ground Penetrating Radar (GPR) is used particularly for the diagnostics of roads and bridges. There is no producer of GPR in the Czech Republic, sets of different producers are used, particularly Geophysical Survey Systems, Inc. (USA) and MALÅ GeoScience (Sweden). The measurement results are mostly processed by software Radan, Road Doctor Pro, ReflexW and RadEx. The only technical specification in the Czech Republic is TP 233 issued by the Ministry of Transport, which describes the diagnostics of roads by GPR. Apart from a basic description of the method and a measurement system, it mentions possible applications. The only application where accuracy is mentioned is the locating of dowels and tie bars in concrete road pavements, which states that if calibration is performed, the expected depth accuracy is up to 1.0 cm. The following R&D project is currently in progress: New diagnostics methods as a supporting decision tool for maintenance and repair of road pavements - their contribution and ways of their usage (2012-2014) The project aims to test possible non-destructive methods (particularly GPR and laser scanning), make recommendations when and how to use specific methods for individual applications and for changes in technical specifications. The following R&D projects have been recently completed: Position of dowels and tie bars in rigid pavements and importance of their correct placement to pavement performance and service life (2012-2013) The project included an analysis of individual NDT methods used for the location of dowels and tie bars and for testing of their accuracy - GPR, MIT-scan and GPR in combination with a metal detector. Multichannel ground penetrating radar as a tool for monitoring of road and bridge structures (2009-2011) The project included detection of hollow spaces under non-reinforced concrete pavements, detection of excessive amount of water in road construction layers, and measuring of crack depths in road pavements. The concrete structure diagnostics development through the use of WPR (Wall Penetrating Radar) scanner (2008-2010) The project was focused on the development of WPR for non-destructive diagnostics of concrete structures, as an accurate and reliable device for diagnostic survey, even at less easily accessible places. The results of road diagnostics by GPR are still not stored in the Road Database. In 2013, CDV designed a method how to perform assessment of the position of dowels and tie bars in concrete road pavements and the way how to register the measurement results of road layer thicknesses in the Road Database. The comparative measurements of devices used for the measurements of variable parameters of roads are performed according to technical specification of the Ministry of Transport TP 207: Accuracy Experiment. The specification deals with devices measuring surface properties and deflections of road pavements. GPR is not included there. In 2013, CDV designed a method how to perform this experiment for continual measurements of pavement layer thicknesses by GPR on reference road sections. The designed method is based on the first realized comparison measurement of pavement layer thicknesses at two-kilometre asphalt motorway section. 6 Czech companies participated in the comparative measurement. Wider use of GPR method will allow to clarify measurement accuracy for individual applications. The performance of comparative measurements together with issuing of authorization for measurement will guarantee that the measurements on Czech road network are only performed by companies with required knowledge and experience. This work is a contribution to COST Action TU1208, which is supported by the project of Technology Agency of the Czech Republic No. TE01020168: Centre for Effective and Sustainable Transport Infrastructure.

Investigation of the Binding Interaction of Fatty Acids with Human G Protein-Coupled Receptor 40 Using a Site-Specific Fluorescence Probe by Flow Cytometry.

PubMed

Ren, Xiao-Min; Cao, Lin-Ying; Zhang, Jing; Qin, Wei-Ping; Yang, Yu; Wan, Bin; Guo, Liang-Hong

2016-04-05

Human G protein-coupled receptor 40 (hGPR40), with medium- and long-chain free fatty acids (FFAs) as its natural ligands, plays an important role in the enhancement of glucose-dependent insulin secretion. To date, information about the direct binding of FFAs to hGPR40 is very limited, and how carbon-chain length affects the activities of FFAs on hGPR40 is not yet understood. In this study, a fluorescein-fasiglifam analogue (F-TAK-875A) conjugate was designed and synthesized as a site-specific fluorescence probe to study the interaction of FFAs with hGPR40. hGPR40 was expressed in human embryonic kidney 293 cells and labeled with F-TAK-875A. By using flow cytometry, competitive binding of FFA and F-TAK-875A to hGPR40-expressed cells was measured. Binding affinities of 18 saturated FFAs, with carbon-chain lengths ranging from C6 to C23, were analyzed. The results showed that the binding potencies of FFAs to hGPR40 were dependent on carbon length. There was a positive correlation between length and binding potency for seven FFAs (C9-C15), with myristic acid (C15) showing the highest potency, 0.2% relative to TAK-875. For FFAs with a length of fewer than C9 or more than C15, they had very weak or no binding. Molecular docking results showed that the binding pocket of TAK-875 in hGPR40 could enclose FFAs with lengths of C15 or fewer. However, for FFAs with lengths longer than C15, part of the alkyl chain extended out of the binding pocket. This study provided insights into the structural dependence of FFAs binding to and activation of hGPR40.

G-protein coupled receptor 56 promotes myoblast fusion through serum response factor- and nuclear factor of activated T-cell-mediated signalling but is not essential for muscle development in vivo.

PubMed

Wu, Melissa P; Doyle, Jamie R; Barry, Brenda; Beauvais, Ariane; Rozkalne, Anete; Piao, Xianhua; Lawlor, Michael W; Kopin, Alan S; Walsh, Christopher A; Gussoni, Emanuela

2013-12-01

Mammalian muscle cell differentiation is a complex process of multiple steps for which many of the factors involved have not yet been defined. In a screen to identify the regulators of myogenic cell fusion, we found that the gene for G-protein coupled receptor 56 (GPR56) was transiently up-regulated during the early fusion of human myoblasts. Human mutations in the gene for GPR56 cause the disease bilateral frontoparietal polymicrogyria; however, the consequences of receptor dysfunction on muscle development have not been explored. Using knockout mice, we defined the role of GPR56 in skeletal muscle. GPR56(-/-) myoblasts have decreased fusion and smaller myotube sizes in culture. In addition, a loss of GPR56 expression in muscle cells results in decreases or delays in the expression of myogenic differentiation 1, myogenin and nuclear factor of activated T-cell (NFAT)c2. Our data suggest that these abnormalities result from decreased GPR56-mediated serum response element and NFAT signalling. Despite these changes, no overt differences in phenotype were identified in the muscle of GPR56 knockout mice, which presented only a mild but statistically significant elevation of serum creatine kinase compared to wild-type. In agreement with these findings, clinical data from 13 bilateral frontoparietal polymicrogyria patients revealed mild serum creatine kinase increase in only two patients. In summary, targeted disruption of GPR56 in mice results in myoblast abnormalities. The absence of a severe muscle phenotype in GPR56 knockout mice and human patients suggests that other factors may compensate for the lack of this G-protein coupled receptor during muscle development and that the motor delay observed in these patients is likely not a result of primary muscle abnormalities. © 2013 FEBS.

G protein-coupled receptor 30 (GPR30) forms a plasma membrane complex with membrane-associated guanylate kinases (MAGUKs) and protein kinase A-anchoring protein 5 (AKAP5) that constitutively inhibits cAMP production.

PubMed

Broselid, Stefan; Berg, Kelly A; Chavera, Teresa A; Kahn, Robin; Clarke, William P; Olde, Björn; Leeb-Lundberg, L M Fredrik

2014-08-08

GPR30, or G protein-coupled estrogen receptor, is a G protein-coupled receptor reported to bind 17β-estradiol (E2), couple to the G proteins Gs and Gi/o, and mediate non-genomic estrogenic responses. However, controversies exist regarding the receptor pharmacological profile, effector coupling, and subcellular localization. We addressed the role of the type I PDZ motif at the receptor C terminus in receptor trafficking and coupling to cAMP production in HEK293 cells and CHO cells ectopically expressing the receptor and in Madin-Darby canine kidney cells expressing the native receptor. GPR30 was localized both intracellularly and in the plasma membrane and subject to limited basal endocytosis. E2 and G-1, reported GPR30 agonists, neither stimulated nor inhibited cAMP production through GPR30, nor did they influence receptor localization. Instead, GPR30 constitutively inhibited cAMP production stimulated by a heterologous agonist independently of Gi/o. Moreover, siRNA knockdown of native GPR30 increased cAMP production. Deletion of the receptor PDZ motif interfered with inhibition of cAMP production and increased basal receptor endocytosis. GPR30 interacted with membrane-associated guanylate kinases, including SAP97 and PSD-95, and protein kinase A-anchoring protein (AKAP) 5 in the plasma membrane in a PDZ-dependent manner. Knockdown of AKAP5 or St-Ht31 treatment, to disrupt AKAP interaction with the PKA RIIβ regulatory subunit, decreased inhibition of cAMP production, and St-Ht31 increased basal receptor endocytosis. Therefore, GPR30 forms a plasma membrane complex with a membrane-associated guanylate kinase and AKAP5, which constitutively attenuates cAMP production in response to heterologous agonists independently of Gi/o and retains receptors in the plasma membrane. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Ground-penetrating radar (GPR) responses for sub-surface salt contamination and solid waste: modeling and controlled lysimeter studies.

PubMed

Wijewardana, Y N S; Shilpadi, A T; Mowjood, M I M; Kawamoto, K; Galagedara, L W

2017-02-01

The assessment of polluted areas and municipal solid waste (MSW) sites using non-destructive geophysical methods is timely and much needed in the field of environmental monitoring and management. The objectives of this study are (i) to evaluate the ground-penetrating radar (GPR) wave responses as a result of different electrical conductivity (EC) in groundwater and (ii) to conduct MSW stratification using a controlled lysimeter and modeling approach. A GPR wave simulation was carried out using GprMax2D software, and the field test was done on two lysimeters that were filled with sand (Lysimeter-1) and MSW (Lysimeter-2). A Pulse EKKO-Pro GPR system with 200- and 500-MHz center frequency antennae was used to collect GPR field data. Amplitudes of GPR-reflected waves (sub-surface reflectors and water table) were studied under different EC levels injected to the water table. Modeling results revealed that the signal strength of the reflected wave decreases with increasing EC levels and the disappearance of the subsurface reflection and wave amplitude reaching zero at higher EC levels (when EC >0.28 S/m). Further, when the EC level was high, the plume thickness did not have a significant effect on the amplitude of the reflected wave. However, it was also found that reflected signal strength decreases with increasing plume thickness at a given EC level. 2D GPR profile images under wet conditions showed stratification of the waste layers and relative thickness, but it was difficult to resolve the waste layers under dry conditions. These results show that the GPR as a non-destructive method with a relatively larger sample volume can be used to identify highly polluted areas with inorganic contaminants in groundwater and waste stratification. The current methods of MSW dumpsite investigation are tedious, destructive, time consuming, costly, and provide only point-scale measurements. However, further research is needed to verify the results under heterogeneous aquifer conditions and complex dumpsite conditions.

Expression of fatty acid sensing G-protein coupled receptors in peripartal Holstein cows.

PubMed

Agrawal, Alea; Alharthi, Abdulrahman; Vailati-Riboni, Mario; Zhou, Zheng; Loor, Juan J

2017-01-01

G-protein coupled receptors (GPCR), also referred as Free Fatty Acid Receptors (FFAR), are widely studied within human medicine as drug targets for metabolic disorders. To combat metabolic disorders prevalent in dairy cows during the transition period, which co-occur with negative energy balance and changes to lipid and glucose metabolism, it may be helpful to identify locations and roles of FFAR and other members of the GPCR family in bovine tissues. Quantitative RT-PCR (qPCR) of subcutaneous adipose, liver, and PMNL samples during the transition period (-10, +7, and +20 or +30 d) were used for expression profiling of medium- (MCFA) and long-chain fatty acid (LCFA) receptors GPR120 and GPR40 , MCFA receptor GPR84 , and niacin receptor HCAR2/3 . Adipose samples were obtained from cows with either high (HI; BCS ≥ 3.75) or low (LO; BCS ≤ 3.25) body condition score (BCS) to examine whether FFAR expression is correlated with this indicator of health and body reserves. Supplementation of rumen-protected methionine (MET), which may improve immune function and production postpartum, was also compared with unsupplemented control (CON) cows for liver and blood polymorphonuclear leukocytes (PMNL) samples. In adipose tissue, GPR84 and GPR120 were differentially expressed over time, while GPR40 was not expressed; in PMNL, GPR40 was differentially expressed over time and between MET vs. CON, GPR84 expression differed only between dietary groups, and GPR120 was not expressed; in liver, GPCR were either not expressed or barely detectable. The data indicate that there is likely not a direct role in liver for the selected GPCR during the transition period, but they do play variable roles in adipose and PMN. In future, these receptors may prove useful targets and/or markers for peripartal metabolism and immunity.

Tapered slot antenna design for vehicular GPR applications

NASA Astrophysics Data System (ADS)

Bıçak, Emrullah; Yeǧin, Korkut; Nazlı, Hakki; Daǧ, Mahmut

2014-05-01

Vehicular applications of UWB GPR demand multiple GPR sensors operating in a harsh environment. One of the key elements of in the sensor is its UWB antenna which has minimal inter-element coupling, low group delay, high directivity and less prone to environmental conditions. Tapered slot antennas (TSA's) provide good impedance match, but they need to be modified for above specifications. Parasitic slot loaded TSA with balanced feed is proposed and a multi-channel antenna array structure is formed. Structural parameters are numerically analyzed and a prototype is built. Measurements show good performance for UWB GPR applications.

Assessment of waterfront location in hardened concrete by GPR within COST Action TU1208

NASA Astrophysics Data System (ADS)

Rodríguez-Abad, Isabel; Klysz, Gilles; Balayssac, Jean Paul; Pajewski, Lara

2016-04-01

This work focuses on the analysis of the capability of Ground-Penetrating radar (GPR) technique for evaluating how the water penetrates into concrete samples by means of the assessment of the waterfront advance. Research activities have been carried out during a Short-Term Scientific Missions (STSMs) funded by the COST (European Cooperation in Science and Technology) Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar" in November 2015. The evaluation of water penetrability is crucial in most building materials, such us concrete, since, water and aggressive chemical agents dissolved therein contribute to the deterioration of the material. A number of techniques have been developed to measure their advance in concrete. Although the most common method for measuring water content is the gravimetric method by observing the change in mass, this method has a large number of disadvantages. In this context, non-destructive techniques as GPR play an interesting role. In particular, the application of GPR in the building materials area is providing very promising and interesting results regarding the building materials characterization and especially concrete deterioration evaluation [1-3]. In addition, recent experimental studies highlight the strong relation between wave propagation parameters (velocity and energy level) and water content advance [4-5]. Water content has a decisive influence on dielectric properties and those might be assessed by the study of the wave properties that are derived by using GPR. Therefore, the waterfront advance will result in a change on wave parameters. In line with this, this research is focused on the development of specific processing algorithms necessary to understand how the water penetrates and how the wave parameters will be affected regarding the location of the antenna in reference to the water absorption direction. For this purpose, concrete samples were manufactured, which after curing (90 days) and oven drying were immersed into water for a certain time. Then, GPR measurements, with a 2 GHz central frequency antenna, were performed at specific time intervals, placing the antenna on the same side of the concrete samples that was immersed into water. After conducting GPR measurements, concrete samples were broken in two pieces to perform the visual analysis of the waterfront advance. After processing the GPR records velocity increments ware calculated and analyzed. Very accurate adjustments were found between the velocity increments and the waterfront depth, regardless the wave peaks of the direct and reflected wave used to calculate velocity increments. These results are of quite importance, because even if we are not able to locate the waterfront reflection or if it is overlapped with the direct wave signal, we might predict the waterfront position with high reliability. Acknowledgement The Authors are grateful to COST - European Cooperation in Science and Technology (www.cost.eu) for funding the Action TU1208 "Civil engineering applications of Ground Penetrating Radar" (www.GPRadar.eu). References 1. W. Lai, S. Kou, W. Tsang, C. Poon, "Characterization of concrete properties from dielectric properties using ground penetrating radar," Cement and Concrete Research, Vol. 39, pp. 687-695, 2009. 2. W. Chen, P. Shen, Z. Shui, "Determination of water content in fresh concrete mix based on relative dielectric constant measurement," Construction and Building Materials, Vol. 34, pp. 306-312, 2012. 3. S. Senin, R. Hamid, "Ground penetrating radar wave attenuation models for estimation of moisture and chloride content in concrete slab," Construction and Building Materials, Vol. 106, pp. 659-669, 2016. 4.I. Rodríguez-Abad , R. Martínez-Sala, J. Mené Aparicio, G. Klysz, "Water penetrability in hardened concrete by GPR," Proceedings of the 15th International Conference on Ground Penetrating Radar, Brussels, Belgium, 2014. 5.I. Rodríguez-Abad, G. Klysz, R. Martínez-Sala, J.P. Balayssac, J. Mené Aparicio, "Waterfront depth analysis in hardened concrete by means of the nondestructive Ground-penetrating radar technique," IEEE Journal of Selected Topics In Applied Earth Observations and Remote Sensing. Digital Object Identifier 10.1109/JSTARS.2015.2449737, 2015.

An observational retrospective/horizontal study to compare oxygen-ozone therapy and/or global postural re-education in complicated chronic low back pain

PubMed Central

Apuzzo, Dario; Giotti, Chiara; Pasqualetti, Patrizio; Ferrazza, Paolo; Soldati, Paola; Zucco, Gesualdo M.

2014-01-01

Summary Acute low back pain (LBP) is the fifth most common reason for physician visits and about nine out of ten adults experience back pain at some point in their life. In a large number of patients LBP is associated with disc herniation (DH). Recently, oxygen-ozone (O2O3) therapy has been used successfully in the treatment of LBP, reducing pain after the failure of other conservative treatments. The aim of this study was to assess the effects of O2O3 therapy in back pain rehabilitation, comparing three groups of patients suffering from chronic back pain associated with DH submitted to three different treatments: intramuscular O2O3 infiltrations, global postural re-education (GPR), or a combination of the two (O2O3+GPR). The data show that pain severity before treatment was significantly lower in the patients treated with GPR alone (VAS score 7.4) than in the O2O3+GPR patients (VAS score 8.5) and the O2O3 patients (VAS score 8.6). At the end of treatment, pain severity was lower in the O2O3 patients than in the GPR-alone patients. After some years of follow-up only the difference between O2O3+GPR and GPR-alone remained significant. PMID:25014047

A critical review of fundamental controversies in the field of GPR30 research.

PubMed

Langer, Gernot; Bader, Benjamin; Meoli, Luca; Isensee, Jörg; Delbeck, Martina; Noppinger, Patricia Ruiz; Otto, Christiane

2010-01-01

The female sex hormone estradiol plays an important role in reproduction, mammary gland development, bone turnover, metabolism, and cardiovascular function. The effects of estradiol are mediated by two classical nuclear receptors, estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta). In 2005, G-protein-coupled receptor 30 (GPR30) was claimed to act as a non-classical estrogen receptor that was also activated by the ERalpha and ERbeta antagonists tamoxifen and fulvestrant (ICI 182780). Despite many conflicting results regarding the potential role of GPR30 as an estrogen receptor, the official nomenclature was changed to GPER (G-protein-coupled estrogen receptor). This review revisits the inconsistencies that still exist in the literature and focuses on selected publications that basically address the following two questions: what is the evidence for and against the hypothesis that GPR30 acts as an estrogen receptor? What is the potential in vivo role of GPR30? Thus, in the first part we focus on conflicting results from in vitro studies analysing the subcellular localization of GPR30, its ability to bind (or not to bind) estradiol and to signal (or not to signal) in response to estradiol. In the second part, we discuss the strengths and limitations of four available GPR30 mouse models. We elucidate the potential impact of different targeting strategies on phenotypic diversity. Copyright 2010 Elsevier Inc. All rights reserved.

GPR30 mediates anorectic estrogen-induced STAT3 signaling in the hypothalamus.

PubMed

Kwon, Obin; Kang, Eun Seok; Kim, Insook; Shin, Sora; Kim, Mijung; Kwon, Somin; Oh, So Ra; Ahn, Young Soo; Kim, Chul Hoon

2014-11-01

Estrogen plays an important role in the control of energy balance in the hypothalamus. Leptin-independent STAT3 activation (i.e., tyrosine(705)-phosphorylation of STAT3, pSTAT3) in the hypothalamus is hypothesized as the primary mechanism of the estrogen-induced anorexic response. However, the type of estrogen receptor that mediates this regulation is unknown. We investigated the role of the G protein-coupled receptor 30 (GPR30) in estradiol (E2)-induced STAT3 activation in the hypothalamus. Regulation of STAT3 activation by E2, G-1, a specific agonist of GPR30 and G-15, a specific antagonist of GPR30 was analyzed in vitro and in vivo. Effect of GPR30 activation on eating behavior was analyzed in vivo. E2 stimulated pSTAT3 in cells expressing GPR30, but not expressing estrogen receptor ERα and ERβ. G-1 induced pSTAT3, and G-15 inhibited E2-induced pSTAT3 in primary cultures of hypothalamic neurons. A cerebroventricular injection of G-1 increased pSTAT3 in the arcuate nucleus of mice, which was associated with a decrease in food intake and body weight gain. These results suggest that GPR30 is the estrogen receptor that mediates the anorectic effect of estrogen through the STAT3 pathway in the hypothalamus. Copyright © 2014 Elsevier Inc. All rights reserved.

Deficiency of Gpr1 improves steroid hormone abnormality in hyperandrogenized mice.

PubMed

Yang, Ya-Li; Sun, Li-Feng; Yu, Yan; Xiao, Tian-Xia; Wang, Bao-Bei; Ren, Pei-Gen; Tang, Hui-Ru; Zhang, Jian V

2018-05-24

Polycystic ovary syndrome (PCOS) is a complex genetic disease with multifarious phenotypes. Many researches use dehydroepiandrosterone (DHEA) to induce PCOS in pubertal mouse models. The aim of this study was to investigate the role of GPR1 in dehydroepiandrosterone (DHEA)-induced hyperandrogenized mice. Prepubertal C57BL/6 mice (25 days of age) and Gpr1-deficient mice were each divided into two groups and injected daily with sesame oil with or without DHEA (6 mg/100 g) for 21 consecutive days. Hematoxylin and eosin (H&E) staining was performed to determine the characteristics of the DHEA-treated ovaries. Real-time PCR was used to examine steroid synthesis enzymes gene expression. Granulosa cell was cultured to explore the mechanism of DHEA-induced, GPR1-mediated estradiol secretion. DHEA treatment induced some aspects of PCOS in wild-type mice, such as increased body weight, elevated serum testosterone, increased number of small, cystic, atretic follicles, and absence of corpus luteum in ovaries. However, Gpr1 deficiency significantly attenuated the DHEA-induced weight gain and ovarian phenotype, improving steroidogenesis in ovaries and estradiol synthesis in cultured granulosa cells, partially through mTOR signaling. In conclusion, Gpr1 deficiency leads to the improvement of steroid synthesis in mice hyperandrogenized with DHEA, indicating that GPR1 may be a therapeutic target for DHEA-induced hyperandrogenism.

Discovery and Characterization of a Novel Small-Molecule Agonist for Medium-Chain Free Fatty Acid Receptor G Protein-Coupled Receptor 84.

PubMed

Zhang, Qing; Yang, Hui; Li, Jing; Xie, Xin

2016-05-01

G protein-coupled receptor 84 (GPR84) is a free fatty acid receptor activated by medium-chain free fatty acids with 9-14 carbons. It is expressed mainly in the immune-related tissues, such as spleen, bone marrow, and peripheral blood leukocytes. GPR84 plays significant roles in inflammatory processes and may represent a novel drug target for the treatment of immune-mediated diseases. However, the lack of potent and specific ligands for GPR84 hindered the study of its functions and the development of potential clinical applications. Here, we report the screen of 160,000 small-molecule compounds with a calcium mobilization assay using a human embryonic kidney 293 cell line stably expressing GPR84 and Gα16, and the identification of 2-(hexylthio)pyrimidine-4,6-diol (ZQ-16) as a potent and selective agonist of GPR84 with a novel structure. ZQ-16 activates several GPR84-mediated signaling pathways, including calcium mobilization, inhibition of cAMP accumulation, phosphorylation of extracellular signal-regulated protein kinase 1/2, receptor desensitization and internalization, and receptor-β-arrestin interaction. This compound may be a useful tool to study the functions of GPR84 and a potential candidate for further structural optimization. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

American-Indian diabetes mortality in the Great Plains Region 2002–2010

PubMed Central

Kelley, Allyson; Giroux, Jennifer; Schulz, Mark; Aronson, Bob; Wallace, Debra; Bell, Ronny; Morrison, Sharon

2015-01-01

Objective To compare American-Indian and Caucasian mortality rates from diabetes among tribal Contract Health Service Delivery Areas (CHSDAs) in the Great Plains Region (GPR) and describe the disparities observed. Research design and methods Mortality data from the National Center for Vital Statistics and Seer*STAT were used to identify diabetes as the underlying cause of death for each decedent in the GPR from 2002 to 2010. Mortality data were abstracted and aggregated for American-Indians and Caucasians for 25 reservation CHSDAs in the GPR. Rate ratios (RR) with 95% CIs were used and SEER*Stat V.8.0.4 software calculated age-adjusted diabetes mortality rates. Results Age-adjusted mortality rates for American-Indians were significantly higher than those for Caucasians during the 8-year period. In the GPR, American-Indians were 3.44 times more likely to die from diabetes than Caucasians. South Dakota had the highest RR (5.47 times that of Caucasians), and Iowa had the lowest RR, (1.1). Reservation CHSDA RR ranged from 1.78 to 10.25. Conclusions American-Indians in the GPR have higher diabetes mortality rates than Caucasians in the GPR. Mortality rates among American-Indians persist despite special programs and initiatives aimed at reducing diabetes in these populations. Effective and immediate efforts are needed to address premature diabetes mortality among American-Indians in the GPR. PMID:25926992

Design and Simulation of Horn Antenna Using CST Software for GPR System

NASA Astrophysics Data System (ADS)

Joret, Ariffuddin; Sulong, M. S.; Abdullah, M. F. L.; Madun, Aziman; Haimi Dahlan, Samsul

2018-04-01

Detection of underground object can be made using a GPR system. This system is classified as a non-destructive technique (NDT) where the ground areas need not to be excavated. The technique used by the GPR system is by measuring the reflection of electromagnetic wave signal produced and detected by antenna which is known as the transmitter and the receiver antenna. In this study, a GPR system was studied by means of simulation using a Horn antenna as a transceiver antenna. The electromagnetic wave signal in this simulation is produced by current signal of an antenna which having a shape of modulation of Gaussian pulse which is having spectrum from 8 GHz until 12 GHz. CST and MATLAB Software are used in this GPR system simulation. A model of a Horn antenna has been designed using the CST software before the GPR’s system simulation modeled by adding a model of background in front of the Horn antenna. The simulation results show that the output signal of the Horn antenna can be used in detecting embedded object which are made from material of wood and iron. In addition, the simulation result has successfully developed a 3D model image of the GPR system using output signal of the Horn antenna. The embedded iron object in the GPR system simulation can be seen clearly by using this 3D image.

Phytonutrient genistein is a survival factor for pancreatic β-cells via GPR30-mediated mechanism.

PubMed

Luo, Jing; Wang, Aihua; Zhen, Wei; Wang, Yao; Si, Hongwei; Jia, Zhenquan; Alkhalidy, Hana; Cheng, Zhiyong; Gilbert, Elizabeth; Xu, Bin; Liu, Dongmin

2018-05-12

We previously discovered that phytonutrient genistein rapidly activates cAMP signaling in β-cells and improves islet mass in diabetic mice. However, the mechanism underlying these actions of genistein is still unclear. Here, we show that pharmacological or molecular inhibition of Gαs blocked genistein-stimulated adenylate cyclase activity in plasma membrane and intracellular cAMP production in INS1 cells and islets. Further, genistein stimulation of cAMP generation was abolished in islets exposed to a specific GPR30 inhibitor G15 or islets from GPR30 deficient (GPR30-/-) mice. In vivo, dietary provision of genistein (0.5 g/kg diet) significantly mitigated streptozotocin-induced hyperglycemia in male WT mice, which was associated with improved blood insulin levels and pancreatic islet mass and survival, whereas these effects were absent in Gpr30-/- mice. Genistein treatment promoted survival of INS1 cells and human islets chronically exposed to palmitate and high glucose. At molecular level, genistein activated CREB phosphorylation and subsequently induced Bcl-2 expression, and knockdown of CREB diminished the protective effect of genistein on β-cells induced by lipoglucotoxicity. Finally, deletion of GPR30 in β-cells or islets ablated genistein-induced CREB phosphorylation and its cytoprotective effect. These findings demonstrate that genistein is a survival factor for β-cells via GPR30-initiated, Gαs-mediated activation of CREB. Copyright © 2018 Elsevier Inc. All rights reserved.

Overview and comparative study of GPR international standards and guidelines - COST Action TU1208

NASA Astrophysics Data System (ADS)

Pajewski, Lara; Marciniak, Marian; Benedetto, Andrea; Tosti, Fabio

2016-04-01

Ground Penetrating Radar (GPR) can be effectively used for non-destructive testing of composite structures and diagnostics affecting the whole life-cycle of civil engineering works. Nevertheless, few recognised international standards exist in this field and inhomogeneous recommendations are present in different countries. Moreover, the levels of knowledge, awareness and experience regarding the use of GPR in civil engineering vary strongly across different European areas. The COST Action TU1208 is working hard on leveraging these differences, by sharing and disseminating knowledge and experience, as well as by developing guidelines and protocols for a safe and effective use of GPR in civil engineering. GPR users need to know which is the best way to conduct GPR measurements and what the quality level for the results should be. The TU1208 guidelines will ensure a higher efficiency and quality of GPR services and they will constitute a scientific basis for the introduction of European Standards on the application of GPR in civil engineering. The aim of this contribution is to present an in-depth overview and critical analysis of the existing GPR international and national standards and guidelines. The main documents considered in our work are listed and briefly described in the following. Three standards are provided by the American Society for Testing and Materials (ASTM), to guide the GPR use for subsurface investigation, evaluation of asphalt-covered concrete bridge decks, and determination of pavement-layer thickness: 1. ASTM D6432-11, Standard Guide for Using the Surface Ground Penetrating Radar Method for Subsurface Investigation, ASTM International, West Conshohocken, PA, 2011, www.astm.org, DOI: 10.1520/D6432-11. 2. ASTM D6087-08, Standard Test Method for Evaluating Asphalt-Covered Concrete Bridge Decks Using Ground Penetrating Radar, ASTM International, West Conshohocken, PA, 2008, www.astm.org, DOI: 10.1520/D6087-08. 3. ASTM D4748-10, Standard Test Method for Determining the Thickness of Bound Pavement Layers Using Short-Pulse Radar, ASTM International, West Conshohocken, PA, 2010, www.astm.org, DOI: 10.1520/D4748-10. Further ASTM standards exist, not focused on GPR but including useful information (details are not provided here, for brevity reasons). There are no standards in Europe, instead, guiding the GPR use for subsurface prospecting and regulating the numerous applications of this non-destructive technique. The following Radio and Telecommunications Terminal Equipment (R&TTE) directive applies to GPR equipment and allows the placing of a GPR product on the European (EU) market for sale: Directive 1999/5/EC of the European Parliament and of the Council of 9 March 1999, on radio equipment and telecommunications terminal equipment and the mutual recognition of their conformity. Official Journal of the European Union, L 91, 7.4.1999, open access on ec.europa.eu. This document will be repealed, since 13 June 2016, by the following R&TTE directive: Directive 2014/53/EU of the European Parliament and of the Council of 16 April 2014, on the harmonisation of the laws of the Member States relating to the making available on the market of radio equipment, repealing Directive 1999/5/EC. Official Journal of the European Union, L 153, 22.5.2014, open access on ec.europa. Although conformance to the R&TTE directive allows the placing of a GPR product on the market for sale, it does not give authority for its use. In order to use the equipment, in the majority of EU member countries, a license is required. The license is controlled and issued by the radio administration in each of the member countries. The Electronic Communications Committee (ECC) of the European Conference of Postal and Telecommunications Administrations (CEPT) considers and develops policies on electronic communications activities in European context, taking account of European and international legislations and regulations. There are 48 European countries involved in the CEPT, which cooperate to regulate posts, radio spectrum and communications networks in Europe. The ECC agreed to the decision ECC/DEC/(06)08, specifically referred to GPR and Wall Penetrating Radar (WPR) systems: ECC Decision of 1 December 2006 on the conditions for use of the radio spectrum by Ground- and Wall- Probing Radar (GPR/WPR) imaging systems, 14 December 2006, open access on www.cept.org. This is not legally binding on member countries. It is currently implemented by 25 and partly implemented by 2 of the 48 administrations; 5 further administration are considering and studying the decision. Outside Europe, different approaches exist, ranging from very formal technical approval and licensing conditions to no specific rules. A series of standards and codes, introduced by the European Telecommunications Standards Institute (ETSI), regulate the GPR use and its emissions of electromagnetic radiation in Europe: 1. ETSI EN 301 489-1 v1.9.2, Electromagnetic compatibility and Radio spectrum Matters (ERM); ElectroMagnetic Compatibility (EMC) standard for radio equipment and services; Part 1: Common technical requirements, Sept. 2011, open access on www.etsi.org, Ref. DEN/ERM-EMC-230-32, 45 pp. [7]. This document is a Harmonized European Standard. 2. ETSI EN 301 489-32 v1.1.1, Electromagnetic compatibility and Radio spectrum Matters (ERM); ElectroMagnetic Compatibility (EMC) standard for radio equipment and services; Part 32: Specific conditions for Ground and Wall Probing Radar applications, Sept. 2009, open access on www.etsi.org, Ref. DEN/ERM-EMC-230-32, 12 pp. [8]. This document is currently (May 2015) a Candidate Harmonized European Standard (Telecommunication Series). 3. ETSI EN 302/066-1 v1.2.1, Electromagnetic compatibility and Radio spectrum Matters (ERM); Ground- and Wall- Probing Radar applications (GPR/WPR) imaging systems; Part 1: Technical characteristics and test methods, Dec. 2007, open access on www.etsi.org, Ref. REN/ERM-TG31A-0113-1, 25 pp. [9]. This document is a Harmonized European Standard (Telecommunications series). 4. ETSI EN 302/066-2 v1.2.1, Electromagnetic compatibility and Radio spectrum Matters (ERM); Ground- and Wall- Probing Radar applications (GPR/WPR) imaging systems; Part 2: Harmonized EN covering essential requirements of article 3.2 of the R&TTE Directive, Dec. 2007, open access on www.etsi.org, Ref. REN/ERM-TG31A-0113-2, 12 pp. [10]. This document is a Harmonized European Standard (Telecommunications series). 5. ETSI EG 202 730 v1.1.1, Electromagnetic compatibility and Radio spectrum Matters (ERM); Code of Practice in respect of the control, use and application of Ground Probing Radar (GPR) and Wall Probing Radar (WPR) systems and equipment, Sept. 2009, open access on www.etsi.org, Ref. DEG/ERM-TGUWB-010, 11 pp. [11]. This document is currently (May 2015) an ETSI guide. Few National GPR Guidelines and Standards exist in Europe. In France, the National standard NF S 70-003, Parts 1-3, is concerned with the use of GPR to detect buried utilities. Still in France, Cerema/Ifsttar produced protocols for road inspection. In Germany, the DGZfP e.V. (German Society for Non-Destructive Testing) published a fact sheet called "Merkblatt B10" on the radar method for non-destructive testing in civil engineering (2008). Still in Germany, there is a BASt (Federal Highway Administration) instruction sheet on the use of GPR to gain inventory data of road structure (2003). In Poland, the national regulation of September 24, 1998 (Dz.U. Nr 126 poz. 839) cites 'georadar testing' as a method to investigate the soil structure. In Scandinavia, recommendations for guidelines were developed during the MARA NORD Project (2010-2012) on the use of GPR in asphalt air voids content measurements, in road construction quality control, in bridge deck surveys, in road rehabilitation projects and in site investigations. Acknowledgement This work stems from the research activities of COST (European COoperation in Science and Technology) Action TU1208 "Civil engineering applications of Ground Penetrating Radar." The Authors thank COST (www.cost.eu) for funding the Action TU1208 (www.GPRadar.eu). Part of this work was carried out during the Short-Term Scientific Mission STSM-TU1208-24656 "Comparative study of GPR international standards and guidelines" (Dr Lara Pajewski, Italy, visiting Prof Marian Marciniak, Poland).

Raw and processed ground-penetrating radar and postprocessed differential global positioning system data collected from Assateague Island, Maryland, October 2014

USGS Publications Warehouse

Zaremba, Nicholas J.; Bernier, Julie C.; Forde, Arnell S.; Smith, Christopher G.

2016-06-08

This report serves as an archive of GPR and DGPS data collected from Assateague Island in October 2014. Data products, including raw GPR and processed DGPS data, elevation corrected GPR profiles, and accompanying Federal Geographic Data Committee metadata can be downloaded from the Data Downloads page.

Ground penetrating radar (GPR) detects fine roots of agricultural crops in the field

Treesearch

Xiuwei Liu; Xuejun Dong; Qingwu Xue; Daniel I. Leskovar; John Jifon; John R. Butnor; Thomas Marek

2018-01-01

Aim Ground penetrating radar (GPR) as a non-invasive technique is widely used in coarse root detection. However, the applicability of the technique to detect fine roots of agricultural crops is unknown. The objective of this study was to assess the feasibility of utilizing GPR to detect fine roots in the field.

Effective implementation of ground penetrating radar (GPR) for condition assessment and monitoring phase 2 : research summary.

DOT National Transportation Integrated Search

2016-10-01

This University of Maryland (UMD) project, in cooperation with Starodub Inc, : had the following objectives: : 1) Provide data analysis support for 40 bridge decks; : 2) Develop the analysis pipeline for producing structural reports according to the ...

Advancing Understanding of the Role of Belowground Processes in Terrestrial Carbon Sinks trhrough Ground-Penetrating Radar. Final Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Day, Frank P.

2015-02-06

Coarse roots play a significant role in belowground carbon cycling and will likely play an increasingly crucial role in belowground carbon sequestration as atmospheric CO 2 levels continue to rise, yet they are one of the most difficult ecosystem parameters to quantify. Despite promising results with ground-penetrating radar (GPR) as a nondestructive method of quantifying biomass of coarse roots, this application of GPR is in its infancy and neither the complete potential nor limitations of the technology have been fully evaluated. The primary goals and questions of this study fell into four groups: (1) GPR methods: Can GPR detect changemore » in root biomass over time, differentiate live roots from dead roots, differentiate between coarse roots, fine roots bundled together, and a fine root mat, remain effective with varied soil moisture, and detect shadowed roots (roots hidden below larger roots); (2) CO 2 enrichment study at Kennedy Space Center in Brevard County, Florida: Are there post-fire legacy effects of CO 2 fertilization on plant carbon pools following the end of CO 2application ? (3) Disney Wilderness Study: What is the overall coarse root biomass and potential for belowground carbon storage in a restored longleaf pine flatwoods system? Can GPR effectively quantify coarse roots in soils that are wetter than the previous sites and that have a high percentage of saw palmetto rhizomes present? (4) Can GPR accurately represent root architecture in a three-dimensional model? When the user is familiar with the equipment and software in a setting that minimizes unsuitable conditions, GPR is a relatively precise, non-destructive, useful tool for estimating coarse root biomass. However, there are a number of cautions and guidelines that should be followed to minimize inaccuracies or situations that are untenable for GPR use. GPR appears to be precise as it routinely predicts highly similar values for a given area across multiple scanning events; however, it appears to lack sufficient accuracy at small scales. Knowledge of soil conditions and their effects on GPR wave propagation and reception are paramount for the collection of useful data. Strong familiarity with the software and equipment is both important and necessary for GPR use in estimating coarse root biomass. GPR must be utilized at low soil moisture levels in order to accurately represent existing coarse root structures. Our results from Disney Wilderness Preserve highlight the need for a strong understanding of the limitations of GPR, specifically knowledge of root structures (saw palmetto rhizomes) or environmental factors (low moisture content) that may hinder its application within a given system. The 3D modeling of course roots with GPR appears quite promising, as it has become more accurate and precise as the software has advanced and become more robust, but there is still a need for more precision before it will likely be able to model anything more than simple root systems comprised mostly of large diameter roots. Our results from Kennedy Space Center suggest that there are legacy effects from CO 2 fertilization in the form of more root mass providing a greater capacity for aboveground plant regrowth following fire, even 7 years after treatment ended.« less

Low concentration of BPA induces mice spermatocytes apoptosis via GPR30.

PubMed

Wang, Chaoliang; Zhang, Jianxiang; Li, Qi; Zhang, Tianbiao; Deng, Zishi; Lian, Jing; Jia, Donghui; Li, Rui; Zheng, Tao; Ding, Xiaoju; Yang, Fan; Ma, Chao; Wang, Rui; Zhang, Weixing; Guo Wen, Jian

2017-07-25

Bisphenol A (BPA) acts as xenoestrogen and has a great impact on disorders of human reproductive system. However, the mechanism through which BPA can affect human testicular function remains to be identified. GPR30 is a novel membrane estrogen receptor with high-affinity and low-capacity binding to estrogens. We demonstrated that estrogen receptor α (ERα), estrogen receptor β (ERβ) as well as GPR30 are expressed in mouse spermatocyte-derived GC-2 cells using Real-time PCR. We treated the cells with different doses of BPA and found that even low doses of BPA can inhibit GC-2 cell growth using MTT assay. To make sure which receptor is responsible for the biological function of BPA, we used ER down-regulator ICI and indicated that BPA could bind to GPR30. We also observed that BPA was able to induce Erk1/2 phosphorylation in GC-2 cells and proved that this process was mediated by GPR30-related EGFR-MAPK pathway using western blot. By Real-time PCR, we found that the expression of c-Fos was up-regulated and Cyclin D1 gene was down-regulated, in the presence of BPA and ICI. The results of MTT assay, comet assay and flow cytometry indicated that the activation of GPR30 induced by BPA inhibited the cell growth and induced cell apoptosis and ICI, GPR30 siRNA, EGFR inhibitor (AG), and MAPK (PD) inhibitor could partially reverse this effect. Immunohistochemistry on the testis of BPA -damaged mice showed that BPA induced spermatocyte apoptosis without affecting the seminiferous tubules and spermatocyte. In conclusion, BPA triggered spermatocyte apoptosis via GPR30.

Insulinotropic and antidiabetic effects of 17β-estradiol and the GPR30 agonist G-1 on human pancreatic islets.

PubMed

Kumar, Rajesh; Balhuizen, Alexander; Amisten, Stefan; Lundquist, Ingmar; Salehi, Albert

2011-07-01

We have recently shown that 17β-estradiol (E2) and the synthetic G protein-coupled receptor 30 (GPR30) ligand G-1 have antiapoptotic actions in mouse pancreatic islets, raising the prospect that they might exert beneficial effects also in human islets. The objective of the present study was to identify the expression of GPR30 in human islets and clarify the role of GPR30 in islet hormone secretion and β-cell survival. GPR30 expression was analyzed by confocal microscopy, Western blot, and quantitative PCR in islets from female and male donors. Hormone secretion, phosphatidylinositol hydrolysis, cAMP content, and caspase-3 activity in female islets were determined with conventional methods and apoptosis with the annexin-V method. Confocal microscopy revealed GPR30 expression in islet insulin, glucagon, and somatostatin cells. GPR30 mRNA and protein expression was markedly higher in female vs. male islets. An amplifying effect of G-1 or E2 on cAMP content and insulin secretion from isolated female islets was not influenced by the E2 genomic receptor (ERα and ERβ) antagonists ICI 182,780 and EM-652. Cytokine-induced (IL-1β plus TNFα plus interferon-γ) apoptosis in islets cultured for 24 h at 5 mmol/liter glucose was almost abolished by G-1 or E2 treatment and was not affected by the nuclear estrogen receptor antagonists. Concentration-response studies on female islets from healthy controls and type 2 diabetic subjects showed that both E2 and G-1 displayed important antidiabetic actions by improving glucose-stimulated insulin release while suppressing glucagon and somatostatin secretion. In view of these findings, we propose that small molecules activating GPR30 could be promising in the therapy of diabetes mellitus.

Quantitative, nondestructive estimates of coarse root biomass in a temperate pine forest using 3-D ground-penetrating radar (GPR)

NASA Astrophysics Data System (ADS)

Molon, Michelle; Boyce, Joseph I.; Arain, M. Altaf

2017-01-01

Coarse root biomass was estimated in a temperate pine forest using high-resolution (1 GHz) 3-D ground-penetrating radar (GPR). GPR survey grids were acquired across a 400 m2 area with varying line spacing (12.5 and 25 cm). Root volume and biomass were estimated directly from the 3-D radar volume by using isometric surfaces calculated with the marching cubes algorithm. Empirical relations between GPR reflection amplitude and root diameter were determined for 14 root segments (0.1-10 cm diameter) reburied in a 6 m2 experimental test plot and surveyed at 5-25 cm line spacing under dry and wet soil conditions. Reburied roots >1.4 cm diameter were detectable as continuous root structures with 5 cm line separation. Reflection amplitudes were strongly controlled by soil moisture and decreased by 40% with a twofold increase in soil moisture. GPR line intervals of 12.5 and 25 cm produced discontinuous mapping of roots, and GPR coarse root biomass estimates (0.92 kgC m-2) were lower than those obtained previously with a site-specific allometric equation due to nondetection of vertical roots and roots <1.5 cm diameter. The results show that coarse root volume and biomass can be estimated directly from interpolated 3-D GPR volumes by using a marching cubes approach, but mapping of roots as continuous structures requires high inline sampling and line density (<5 cm). The results demonstrate that 3-D GPR is viable approach for estimating belowground carbon and for mapping tree root architecture. This methodology can be applied more broadly in other disciplines (e.g., archaeology and civil engineering) for imaging buried structures.

4-Hydroxytamoxifen-stimulated processing of cyclin E is mediated via G protein-coupled receptor 30 (GPR30) and accompanied by enhanced migration in MCF-7 breast cancer cells.

PubMed

Li, Yang; Chen, Yan; Zhu, Zhu-Xia; Liu, Xiao-Hong; Yang, Li; Wan, Lei; Lei, Ting-Wen; Wang, Xu-Dong

2013-07-05

Over-expression of cleaved cyclin E in breast tumors is closely associated with tumor progression and resistance to antiestrogens. 17β-Estradiol (E2) has been recently shown to induce cyclin E processing in breast cancer cells. Tamoxifen has been used in patients with estrogen-sensitive breast cancer, yet resistance to antiestrogens and recurrence will appear in some of the patients after its continued use. We therefore addressed possible effects of tamoxifen on the generation of cleaved cyclin E and its signal mechanism(s) in estrogen-responsive MCF-7 breast cancer cells that express both G protein-coupled protein (GPR) 30 and estrogen receptor α (ERα). 4-Hydroxytamoxifen (OHT, tamoxifen's active form) failed to prevent E2-induced proteolysis of cyclin E and migration, but rather triggered cyclin E cleavage coincident with augmented migration. OHT-induced cyclin E truncation also occurred in SK-BR-3 cells that express GPR30 and lack ERα, but not in MDA-MB-231 cells that express neither GPR30 nor ERα. G1, a specific GPR 30 agonist, caused dramatic proteolysis of cyclin E and enhanced migration. Furthermore, OHT-stimulated cleavage of cyclin E and migration were tremendously attenuated by G15, a GPR30 antagonist, or siRNA against GPR30. In addition, inhibitors for EGFR or ERK1/2 remarkably suppressed OHT-induced truncation of cyclin E, suggesting involvement of EGFR signaling. Collectively, our data indicate that OHT contributes to the production of proteolyzed cyclin E via GPR30 with augmented migration in MCF-7 cells. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

G protein-coupled receptor 30 expression is up-regulated by EGF and TGF alpha in estrogen receptor alpha-positive cancer cells.

PubMed

Vivacqua, Adele; Lappano, Rosamaria; De Marco, Paola; Sisci, Diego; Aquila, Saveria; De Amicis, Francesca; Fuqua, Suzanne A W; Andò, Sebastiano; Maggiolini, Marcello

2009-11-01

In the present study, we evaluated the regulation of G protein-coupled receptor (GPR)30 expression in estrogen receptor (ER)-positive endometrial, ovarian, and estrogen-sensitive, as well as tamoxifen-resistant breast cancer cells. We demonstrate that epidermal growth factor (EGF) and TGF alpha transactivate the GPR30 promoter and accordingly up-regulate GPR30 mRNA and protein levels only in endometrial and tamoxifen-resistant breast cancer cells. These effects exerted by EGF and TGF alpha were dependent on EGF receptor (EGFR) expression and activation and involved phosphorylation of the Tyr(1045) and Tyr(1173) EGFR sites. Using gene-silencing experiments and specific pharmacological inhibitors, we have ascertained that EGF and TGF alpha induce GPR30 expression through the EGFR/ERK transduction pathway, and the recruitment of c-fos to the activator protein-1 site located within GPR30 promoter sequence. Interestingly, we show that functional cross talk of GPR30 with both activated EGFR and ER alpha relies on a physical interaction among these receptors, further extending the potential of estrogen to trigger a complex stimulatory signaling network in hormone-sensitive tumors. Given that EGFR/HER2 overexpression is associated with tamoxifen resistance, our data may suggest that ligand-activated EGFR could contribute to the failure of tamoxifen therapy also by up-regulating GPR30, which in turn could facilitates the action of estrogen. In addition, important for resistance is the ability of tamoxifen to bind to and activate GPR30, the expression of which is up-regulated by EGFR activation. Our results emphasize the need for new endocrine agents able to block widespread actions of estrogen without exerting any stimulatory activity on transduction pathways shared by the steroid and growth factor-signaling networks.

Stimulating the GPR30 estrogen receptor with a novel tamoxifen analogue activates SF-1 and promotes endometrial cell proliferation.

PubMed

Lin, Benjamin C; Suzawa, Miyuki; Blind, Raymond D; Tobias, Sandra C; Bulun, Serdar E; Scanlan, Thomas S; Ingraham, Holly A

2009-07-01

Estrogens and selective estrogen receptor (ER) modulators such as tamoxifen are known to increase uterine cell proliferation. Mounting evidence suggests that estrogen signaling is mediated not only by ERalpha and ERbeta nuclear receptors, but also by GPR30 (GPER), a seven transmembrane (7TM) receptor. Here, we report that primary human endometriotic H-38 cells express high levels of GPR30 with no detectable ERalpha or ERbeta. Using a novel tamoxifen analogue, STX, which activates GPR30 but not ERs, significant stimulation of the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways was observed in H-38 cells and in Ishikawa endometrial cancer cells expressing GPR30; a similar effect was observed in JEG3 choriocarcinoma cells. STX treatment also increased cellular pools of phosphatidylinositol (3,4,5) triphosphate, a proposed ligand for the nuclear hormone receptor SF-1 (NR5A1). Consistent with these findings, STX, tamoxifen, and the phytoestrogen genistein were able to increase SF-1 transcription, promote Ishikawa cell proliferation, and induce the SF-1 target gene aromatase in a GPR30-dependent manner. Our findings suggest a novel signaling paradigm that is initiated by estrogen activation of the 7TM receptor GPR30, with signal transduction cascades (PI3K and MAPK) converging on nuclear hormone receptors (SF-1/LRH-1) to modulate their transcriptional output. We propose that this novel GPR30/SF-1 pathway increases local concentrations of estrogen, and together with classic ER signaling, mediate the proliferative effects of synthetic estrogens such as tamoxifen, in promoting endometriosis and endometrial cancers.

Activation of GPR30 attenuates chronic pain-related anxiety in ovariectomized mice.

PubMed

Liu, Shui-bing; Tian, Zhen; Guo, Yan-yan; Zhang, Nan; Feng, Bin; Zhao, Ming-gao

2015-03-01

Estrogen regulates neuroendocrine and inflammatory processes that play critical roles in neuroinflammation, anxiety, and chronic pain. Patients suffering from chronic pain often complain of anxiety. However, limited information is available regarding the neural circuitry of chronic pain-related anxiety and the related function of estrogen. Hindpaw injection of complete Freund's adjuvant (CFA) and chronic constriction injury (CCI) of the sciatic nerve induced notable pain sensitization and anxiety-like behavior in ovariectomized (OVX) mice. We found that the level of G-protein-coupled receptor 30 (GPR30), a membrane estrogen receptor, was significantly increased in the basolateral amygdala (BLA) of ovariectomized (OVX) mice suffering from chronic inflammatory and neuropathic pain. Subcutaneous injection or BLA local infusion of the GPR30 agonist G1 significantly reduced anxiety-like behavior in CFA-injected and CCI-OVX mice; however, this treatment did not alter the nociceptive threshold. GPR30 knock down by shRNA in the BLA of OVX mice inhibited the anxiolytic effects of GPR30 activation. G1 administration reversed the upregulation of GluR1 subunit in AMPA and NR2A-containing NMDA receptors and the downregulation of GABAA receptors in the BLA of CFA-injected and CCI-OVX mice. Electrophysiological recording revealed that GPR30 activation could prevent imbalance between excitatory and inhibitory transmissions in the BLA synapses of CFA-injected OVX mice. In conclusion, GPR30 activation induced anxiolytic effects but did not affect the nociceptive threshold of mice under chronic pain. The anxiolytic effects of GPR30 were partially due to maintaining the balance between excitatory and inhibitory transmissions in the BLA. Copyright © 2015 Elsevier Ltd. All rights reserved.

Soil Moisture Content Estimation using GPR Reflection Travel Time

NASA Astrophysics Data System (ADS)

Lunt, I. A.; Hubbard, S. S.; Rubin, Y.

2003-12-01

Ground-penetrating radar (GPR) reflection travel time data were used to estimate changes in soil water content under a range of soil saturation conditions throughout the growing season at a California winery. Data were collected during four data acquisition campaigns over an 80 by 180 m area using 100 MHz surface GPR antennae. GPR reflections were associated with a thin, low permeability clay layer located between 0.8 to 1.3 m below the ground surface that was calibrated with borehole information and mapped across the study area. Field infiltration tests and neutron probe logs suggest that the thin clay layer inhibited vertical water flow, and was coincident with high volumetric water content (VWC) values. The GPR reflection two-way travel time and the depth of the reflector at borehole locations were used to calculate an average dielectric constant for soils above the reflector. A site-specific relationship between the dielectric constant and VWC was then used to estimate the depth-averaged VWC of the soils above the reflector. Compared to average VWC measurements from calibrated neutron probe logs over the same depth interval, the average VWC estimates obtained from GPR reflections had an RMS error of 2 percent. We also investigated the estimation of VWC using reflections associated with an advancing water front, and found that estimates of average VWC to the water front could be obtained with similar accuracy. These results suggested that the two-way travel time to a GPR reflection associated with a geological surface or wetting front can be used under natural conditions to obtain estimates of average water content when borehole control is available. The GPR reflection method therefore has potential for monitoring soil water content over large areas and under variable hydrological conditions.

Coordinate regulation of estrogen-mediated fibronectin matrix assembly and epidermal growth factor receptor transactivation by the G protein-coupled receptor, GPR30.

PubMed

Quinn, Jeffrey A; Graeber, C Thomas; Frackelton, A Raymond; Kim, Minsoo; Schwarzbauer, Jean E; Filardo, Edward J

2009-07-01

Estrogen promotes changes in cytoskeletal architecture not easily attributed to the biological action of estrogen receptors, ERalpha and ERbeta. The Gs protein-coupled transmembrane receptor, GPR30, is linked to specific estrogen binding and rapid estrogen-mediated release of heparin-bound epidermal growth factor. Using marker rescue and dominant interfering mutant strategies, we show that estrogen action via GPR30 promotes fibronectin (FN) matrix assembly by human breast cancer cells. Stimulation with 17beta-estradiol or the ER antagonist, ICI 182, 780, results in the recruitment of FN-engaged integrin alpha5beta1 conformers to fibrillar adhesions and the synthesis of FN fibrils. Concurrent with this cellular response, GPR30 promotes the formation of Src-dependent, Shc-integrin alpha5beta1 complexes. Function-blocking antibodies directed against integrin alpha5beta1 or soluble Arg-Gly-Asp peptide fragments derived from FN specifically inhibited GPR30-mediated epidermal growth factor receptor transactivation. Estrogen-mediated FN matrix assembly and epidermal growth factor receptor transactivation were similarly disrupted in integrin beta1-deficient GE11 cells, whereas reintroduction of integrin beta1 into GE11 cells restored these responses. Mutant Shc (317Y/F) blocked GPR30-induced FN matrix assembly and tyrosyl phosphorylation of erbB1. Interestingly, relative to recombinant wild-type Shc, 317Y/F Shc was more readily retained in GPR30-induced integrin alpha5beta1 complexes, yet this mutant did not prevent endogenous Shc-integrin alpha5beta1 complex formation. Our results suggest that GPR30 coordinates estrogen-mediated FN matrix assembly and growth factor release in human breast cancer cells via a Shc-dependent signaling mechanism that activates integrin alpha5beta1.

Examination of soil effect upon GPR detectability of landmine with different orientations

NASA Astrophysics Data System (ADS)

Ebrahim, Shereen M.; Medhat, N. I.; Mansour, Khamis K.; Gaber, A.

2018-06-01

Landmines represent a serious environmental problem for several countries as it causes severe injured and many victims. In this paper, the response of GPR from different parameters of the landmine targets has been shown and the data is correlated with observed field experiment made in 2012 at Miami Crandon Park test site. The ability of GPR for detecting non-metallic mines with different orientations was revealed and soil effect upon the GPR signal was examined putting into consideration the soil parameters in different locations in Egypt such as in Sinai and El Alamein. The simulation results showed that PMN-2 landmine was detected at 5 cm and 15 cm depths, even at the minimum radar cross section vertical orientation. The B-Scan (2D GPR profiles) of PMN-2 target at 15 cm depth figured out high reflectivity for Wadi deposits due to large contrast between PMN-2 landmine material and soil of sand dunes.

Gpr124 controls CNS angiogenesis and blood-brain barrier integrity by promoting ligand-specific canonical wnt signaling.

PubMed

Zhou, Yulian; Nathans, Jeremy

2014-10-27

Canonical Wnt signaling in endothelial cells (ECs) is required for vascularization of the central nervous system (CNS) and for formation and maintenance of barrier properties unique to CNS vasculature. Gpr124 is an orphan member of the adhesion G protein-coupled receptor family that is expressed in ECs and is essential for CNS angiogenesis and barrier formation via an unknown mechanism. Using canonical Wnt signaling assays in cell culture and genetic loss- and gain-of-function experiments in mice, we show that Gpr124 functions as a coactivator of Wnt7a- and Wnt7b-stimulated canonical Wnt signaling via a Frizzled receptor and Lrp coreceptor and that Gpr124-stimulated signaling functions in concert with Norrin/Frizzled4 signaling to control CNS vascular development. These experiments identify Gpr124 as a ligand-specific coactivator of canonical Wnt signaling.

Lack of GPR88 enhances medium spiny neuron activity and alters motor- and cue-dependent behaviors.

PubMed

Quintana, Albert; Sanz, Elisenda; Wang, Wengang; Storey, Granville P; Güler, Ali D; Wanat, Matthew J; Roller, Bryan A; La Torre, Anna; Amieux, Paul S; McKnight, G Stanley; Bamford, Nigel S; Palmiter, Richard D

2012-11-01

The striatum regulates motor control, reward and learning. Abnormal function of striatal GABAergic medium spiny neurons (MSNs) is believed to contribute to the deficits in these processes that are observed in many neuropsychiatric diseases. The orphan G protein-coupled receptor GPR88 is robustly expressed in MSNs and is regulated by neuropharmacological drugs, but its contribution to MSN physiology and behavior is unclear. We found that, in the absence of GPR88, MSNs showed increased glutamatergic excitation and reduced GABAergic inhibition, which promoted enhanced firing rates in vivo, resulting in hyperactivity, poor motor coordination and impaired cue-based learning in mice. Targeted viral expression of GPR88 in MSNs rescued the molecular and electrophysiological properties and normalized behavior, suggesting that aberrant MSN activation in the absence of GPR88 underlies behavioral deficits and its dysfunction may contribute to behaviors observed in neuropsychiatric disease.

Molecular genetic analysis of patients with sporadic and X-linked infantile nystagmus

PubMed Central

Zhao, Hui; Huang, Xiu-Feng; Zheng, Zhi-Li; Deng, Wen-Li; Lei, Xin-Lan; Xing, Dong-Jun; Ye, Liang; Xu, Su-Zhong; Chen, Jie; Zhang, Fang; Yu, Xin-Ping; Jin, Zi-Bing

2016-01-01

Objectives Infantile nystagmus (IN) is a genetically heterogeneous condition characterised by involuntary rhythmic oscillations of the eyes accompanied by different degrees of vision impairment. Two genes have been identified as mainly causing IN: FRMD7 and GPR143. The aim of our study was to identify the genetic basis of both sporadic IN and X-linked IN. Design Prospective analysis. Patients Twenty Chinese patients, including 15 sporadic IN cases and 5 from X-linked IN families, were recruited and underwent molecular genetic analysis. We first performed PCR-based DNA sequencing of the entire coding region and the splice junctions of the FRMD7 and GPR143 genes in participants. Mutational analysis and co-segregation confirmation were then performed. Setting All clinical examinations and genetic experiments were performed in the Eye Hospital of Wenzhou Medical University. Results Two mutations in the FRMD7 gene, including one novel nonsense mutation (c.1090C>T, p.Q364X) and one reported missense mutation (c.781C>G, p.R261G), were identified in two of the five (40%) X-linked IN families. However, none of putative mutations were identified in FRMD7 or GPR143 in any of the sporadic cases. Conclusions The results suggest that mutations in FRMD7 appeared to be the major genetic cause of X-linked IN, but not of sporadic IN. Our findings provide further insights into FRMD7 mutations, which could be helpful for future genetic diagnosis and genetic counselling of Chinese patients with nystagmus. PMID:27036142

GPR55: Metabolic Help or Hindrance?

PubMed

Henstridge, Christopher M; Brown, Andrew J; Waldhoer, Maria

2016-09-01

Since the discovery of the lysophospholipid-sensitive receptor GPR55, hopes have been raised that targeting this G protein-coupled receptor (GPCR) may represent a novel approach for the treatment of metabolic disorders. We discuss conflicting evidence surrounding GPR55 physiology and highlight its potential as a novel target for the treatment of obesity and diabetes. Copyright © 2016 Elsevier Ltd. All rights reserved.

GPR30: A G protein-coupled receptor for estrogen.

PubMed

Prossnitz, Eric R; Arterburn, Jeffrey B; Sklar, Larry A

2007-02-01

Estrogen is a critical steroid in human physiology exerting its effect both at the transcriptional level as well as at the level of rapid intracellular signaling through second messengers. Many of estrogen's transcriptional effects have long been known to be mediated through classical nuclear steroid receptors but recent studies also demonstrate the existence of a 7-transmembrane G protein-coupled receptor, GPR30 that responds to estrogen with rapid cellular signaling. There is currently controversy over the ability of classical estrogen receptors to recapitulate GPR30-mediated signaling mechanisms and vice versa. This article will summarize recent literature and address the relationship between GPR30 and conventional estrogen receptor signaling.

The ubiquitin ligase Mdm2 controls oligodendrocyte maturation by intertwining mTOR with G protein-coupled receptor kinase 2 in the regulation of GPR17 receptor desensitization.

PubMed

Fumagalli, Marta; Bonfanti, Elisabetta; Daniele, Simona; Zappelli, Elisa; Lecca, Davide; Martini, Claudia; Trincavelli, Maria L; Abbracchio, Maria P

2015-12-01

During oligodendrocyte precursor cell (OPC) differentiation, defective control of the membrane receptor GPR17 has been suggested to block cell maturation and impair remyelination under demyelinating conditions. After the immature oligodendrocyte stage, to enable cells to complete maturation, GPR17 is physiologically down-regulated via phosphorylation/desensitization by G protein-coupled receptor kinases (GRKs); conversely, GRKs are regulated by the "mammalian target of rapamycin" mTOR. However, how GRKs and mTOR are connected to each other in modulating GPR17 function and oligodendrogenesis has remained elusive. Here we show, for the first time, a role for Murine double minute 2 (Mdm2), a ligase previously involved in ubiquitination/degradation of the onco-suppressor p53 protein. In maturing OPCs, both rapamycin and Nutlin-3, a small molecule inhibitor of Mdm2-p53 interactions, increased GRK2 sequestration by Mdm2, leading to impaired GPR17 down-regulation and OPC maturation block. Thus, Mdm2 intertwines mTOR with GRK2 in regulating GPR17 and oligodendrogenesis and represents a novel actor in myelination. © 2015 Wiley Periodicals, Inc.

Activation of G-protein-coupled receptor 30 increases T-type calcium currents in trigeminal ganglion neurons via the cholera toxin-sensitive protein kinase A pathway.

PubMed

Yue, Jingxia; Zhang, Yi; Li, Xuemin; Gong, Shan; Tao, Jin; Jiang, Xinghong

2014-11-01

G protein-coupled receptor 30 (GPR30) is a seven transmembrane domain G protein coupled receptor. In our study, GPR30 expression was found in trigeminal ganglia (TG) in mice, detected by RT-PCR and western blotting. We examined the effects of GPR30 activation on T-type calcium channels using GPR30-specific compound 1 (G-1), a GPR30-selective agonist, in TG neurons and demonstrated that G-1 induced an increase in T-type calcium channel currents (T-currents) in TGs. Intracellular infusion of GDP-β-S and pre-treatment of the neurons with cholera toxin (CTX) blocked the effects of G-1, suggesting that the G(s)-protein was involved. Intracellular application of the protein kinase A (PKA) inhibitor PKI 6-22 or pretreatment of the neurons with H89 abolished G-1 -induced enhancement of T-currents in TG neurons. However, incubation with PKC inhibitor elicited no such effects. In conclusion, our study shows that activation of GPR30 by G-1 increases T-currents via the CTX-sensitive and PKA-dependent pathway.

G protein-coupled receptor 84, a microglia-associated protein expressed in neuroinflammatory conditions.

PubMed

Bouchard, Caroline; Pagé, Julie; Bédard, Andréanne; Tremblay, Pierrot; Vallières, Luc

2007-06-01

G protein-coupled receptor 84 (GPR84) is a recently discovered member of the seven transmembrane receptor superfamily whose function and regulation are unknown. Here, we report that in mice suffering from endotoxemia, microglia express GPR84 in a strong and sustained manner. This property is shared by subpopulations of peripheral macrophages and, to a much lesser extent, monocytes. The induction of GPR84 expression by endotoxin is mediated, at least in part, by proinflammatory cytokines, notably tumor necrosis factor (TNF) and interleukin-1 (IL-1), because mice lacking either one or both of these molecules have fewer GPR84-expressing cells in their cerebral cortex than wild-type mice during the early phase of endotoxemia. Moreover, when injected intracerebrally or added to microglial cultures, recombinant TNF stimulates GPR84 expression through a dexamethasone-insensitive mechanism. Finally, we show that microglia produce GPR84 not only during endotoxemia, but also during experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. In conclusion, this study reports the identification of a new sensitive marker of microglial activation, which may play an important regulatory role in neuroimmunological processes, acting downstream to the effects of proinflammatory mediators.

GPR107, a G-protein-coupled receptor essential for intoxication by Pseudomonas aeruginosa exotoxin A, localizes to the Golgi and is cleaved by furin.

PubMed

Tafesse, Fikadu G; Guimaraes, Carla P; Maruyama, Takeshi; Carette, Jan E; Lory, Stephen; Brummelkamp, Thijn R; Ploegh, Hidde L

2014-08-29

A number of toxins, including exotoxin A (PE) of Pseudomonas aeruginosa, kill cells by inhibiting protein synthesis. PE kills by ADP-ribosylation of the translation elongation factor 2, but many of the host factors required for entry, membrane translocation, and intracellular transport remain to be elucidated. A genome-wide genetic screen in human KBM7 cells was performed to uncover host factors used by PE, several of which were confirmed by CRISPR/Cas9-gene editing in a different cell type. Several proteins not previously implicated in the PE intoxication pathway were identified, including GPR107, an orphan G-protein-coupled receptor. GPR107 localizes to the trans-Golgi network and is essential for retrograde transport. It is cleaved by the endoprotease furin, and a disulfide bond connects the two cleaved fragments. Compromising this association affects the function of GPR107. The N-terminal region of GPR107 is critical for its biological function. GPR107 might be one of the long-sought receptors that associates with G-proteins to regulate intracellular vesicular transport. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Annual layers revealed by GPR in the subsurface of a prograding coastal barrier, southwest Washington, U.S.A

USGS Publications Warehouse

Moore, L.J.; Jol, H.M.; Kruse, S.; Vanderburgh, S.; Kaminsky, G.M.

2004-01-01

The southwest Washington coastline has experienced extremely high rates of progradation during the late Holocene. Subsurface stratigraphy, preserved because of progradation and interpreted using ground-penetrating radar (GPR), has previously been used successfully to document coastal response to prehistoric storm and earthquake events. New GPR data collected at Ocean Shores, Washington, suggest that the historic stratigraphy of the coastal barrier in this area represents a higher resolution record of coastal behavior than previously thought. GPR records for this location at 200 MHz reveal a series of gently sloping, seaward-dipping reflections with slopes similar to the modern beach and spacings on the order of 20-45 cm. Field evidence and model results suggest that thin (1-10 cm), possibly magnetite-rich, heavy-mineral lags or low-porosity layers left by winter storms and separated by thick (20-40 cm) summer progradational sequences are responsible for generating the GPR reflections. These results indicate that a record of annual progradation is preserved in the subsurface of the prograding barrier and can be quantified using GPR. Such records of annual coastal behavior, where available, will be invaluable in understanding past coastal response to climatic and tectonic forcing. ?? 2004.

Long-term ground penetrating radar monitoring of a small volume DNAPL release in a natural groundwater flow field.

PubMed

Hwang, Yong Keun; Endres, Anthony L; Piggott, Scott D; Parker, Beth L

2008-04-04

An earlier field experiment at Canadian Forces Base Borden by Brewster and Annan [Geophysics 59 (1994) 1211] clearly demonstrated the capability of ground penetrating radar (GPR) reflection profiling to detect and monitor the formation of DNAPL layers in the subsurface. Their experiment involved a large volume release (770 L) of tetrachloroethylene into a portion of the sand aquifer that was hydraulically isolated from groundwater flow by sheet pile walls. In this study, we evaluated the ability of GPR profiling to detect and monitor much smaller volume releases (50 L). No subsurface confining structure was used in this experiment; hence, the DNAPL impacted zone was subjected to the natural groundwater flow regime. This condition allowed us to geophysically monitor the DNAPL mass loss over a 66 month period. Reflectivity variations on the GPR profiles were used to infer the presence and evolution of the solvent layers. GPR imaging found significant reflectivity increases due to solvent layer formation during the two week period immediately after the release. These results demonstrated the capacity of GPR profiling for the detection and monitoring of lesser volume DNAPL releases that are more representative of small-scale industrial spills. The GPR imaged solvent layers subsequently reduced in both areal extent and reflectivity after 29 months and almost completely disappeared by the end of the 66 month monitoring period. Total DNAPL mass estimates based on GPR profiling data indicated that the solvent mass was reduced to 34%-36% of its maximum value after 29 months; only 4%-9% of the solvent mass remained in the study area after 66 months. These results are consistent with independent hydrogeological estimates of remaining DNAPL mass based on the downgradient monitoring of the dissolved solvent phase. Hence, we have concluded that the long-term GPR reflectivity changes of the DNAPL layers are likely the result from the dissolution of chlorinated solvents residing in those layers. The long-term monitoring results demonstrated that GPR profiling is a promising non-invasive method for use at DNAPL contaminated sites in sandy aquifers where temporal information about immiscible contaminant mass depletion due to either natural flow or remediation is needed. However, our results also indicated that the GPR signature of older DNAPL impacted zones may not differ greatly from the uncontaminated background if significant mass reduction due to dissolution has occurred.

Regulation of neuronal pH by the metabotropic Zn(2+)-sensing Gq-coupled receptor, mZnR/GPR39.

PubMed

Ganay, Thibault; Asraf, Hila; Aizenman, Elias; Bogdanovic, Milos; Sekler, Israel; Hershfinkel, Michal

2015-12-01

Synaptically released Zn(2+) acts as a neurotransmitter, in part, by activating the postsynaptic metabotropic Zn(2+)-sensing Gq protein-coupled receptor (mZnR/GPR39). In previous work using epithelial cells, we described crosstalk between Zn(2+) signaling and changes in intracellular pH and/or extracellular pH (pHe). As pH changes accompany neuronal activity under physiological and pathological conditions, we tested whether Zn(2+) signaling is involved in regulation of neuronal pH. Here, we report that up-regulation of a major H(+) extrusion pathway, the Na(+)/H(+) exchanger (NHE), is induced by mZnR/GPR39 activation in an extracellular-regulated kinase 1/2-dependent manner in hippocampal neurons in vitro. We also observed that changes in pHe can modulate neuronal mZnR/GPR39-dependent signaling, resulting in reduced activity at pHe 8 or 6.5. Similarly, Zn(2+)-dependent extracellular-regulated kinase 1/2 phosphorylation and up-regulation of NHE activity were absent at acidic pHe. Thus, our results suggest that when pHe is maintained within the physiological range, mZnR/GPR39 activation can up-regulate NHE-dependent recovery from intracellular acidification. During acidosis, as pHe drops, mZnR/GPR39-dependent NHE activation is inhibited, thereby attenuating further H(+) extrusion. This mechanism may serve to protect neurons from excessive decreases in pHe. Thus, mZnR/GPR39 signaling provides a homeostatic adaptive process for regulation of intracellular and extracellular pH changes in the brain. We show that the postsynaptic metabotropic Zn(2+)-sensing Gq protein-coupled receptor (mZnR/GPR39) activation induces up-regulation of a major neuronal H(+) extrusion pathway, the Na(+)/H(+) exchanger (NHE), thereby enhancing neuronal recovery from intracellular acidification. Changes in extracellular pH (pHe), however, modulate neuronal mZnR/GPR39-dependent signaling, resulting in reduced activity at pHe 8 or 6.5. This mechanism may serve to protect neurons from excessive decreases in pHe during acidosis. Hence, mZnR/GPR39 signaling provides a homeostatic adaptive process for regulation of intracellular and extracellular pH changes in the brain. © 2015 International Society for Neurochemistry.

GPR17: molecular modeling and dynamics studies of the 3-D structure and purinergic ligand binding features in comparison with P2Y receptors.

PubMed

Parravicini, Chiara; Ranghino, Graziella; Abbracchio, Maria P; Fantucci, Piercarlo

2008-06-04

GPR17 is a G-protein-coupled receptor located at intermediate phylogenetic position between two distinct receptor families: the P2Y and CysLT receptors for extracellular nucleotides and cysteinyl-LTs, respectively. We previously showed that GPR17 can indeed respond to both classes of endogenous ligands and to synthetic compounds active at the above receptor families, thus representing the first fully characterized non-peptide "hybrid" GPCR. In a rat brain focal ischemia model, the selective in vivo knock down of GPR17 by anti-sense technology or P2Y/CysLT antagonists reduced progression of ischemic damage, thus highlighting GPR17 as a novel therapeutic target for stroke. Elucidation of the structure of GPR17 and of ligand binding mechanisms are the necessary steps to obtain selective and potent drugs for this new potential target. On this basis, a 3-D molecular model of GPR17 embedded in a solvated phospholipid bilayer and refined by molecular dynamics simulations has been the first aim of this study. To explore the binding mode of the "purinergic" component of the receptor, the endogenous agonist UDP and two P2Y receptor antagonists demonstrated to be active on GPR17 (MRS2179 and cangrelor) were then modeled on the receptor. Molecular dynamics simulations suggest that GPR17 nucleotide binding pocket is similar to that described for the other P2Y receptors, although only one of the three basic residues that have been typically involved in ligand recognition is conserved (Arg255). The binding pocket is enclosed between the helical bundle and covered at the top by EL2. Driving interactions are H-bonds and salt bridges between the 6.55 and 6.52 residues and the phosphate moieties of the ligands. An "accessory" binding site in a region formed by the EL2, EL3 and the Nt was also found. Nucleotide binding to GPR17 occurs on the same receptor regions identified for already known P2Y receptors. Agonist/antagonist binding mode are similar, but not identical. An accessory external binding site could guide small ligands to the deeper principal binding site in a multi-step mechanism of activation. The nucleotide binding pocket appears to be unable to allocate the leukotrienic type ligands in the same effective way.

Volumetric-modulated Arc Therapy Lung Stereotactic Body Radiation Therapy Dosimetric Quality Assurance: A Comparison between Radiochromic Film and Chamber Array.

PubMed

Colodro, Juan Fernando Mata; Berná, Alfredo Serna; Puchades, Vicente Puchades; Amores, David Ramos; Baños, Miguel Alcaraz

2017-01-01

The aim of this work is to verify the use of radiochromic film in the quality assurance (QA) of volumetric-modulated arc therapy (VMAT) lung stereotactic body radiation therapy (SBRT) plans and compare the results with those obtained using an ion chamber array. QA was performed for 14 plans using a two-dimensional-array seven29 and EBT3 film. Dose values per session ranged between 7.5 Gy and 18 Gy. The multichannel method was used to obtain a dose map for film. The results obtained were compared with treatment planning system calculated profiles through gamma analysis. Passing criteria were 3%/3 mm, 2%/2 mm and 3%/1.5 mm with maximum and local dose (LD) normalization. Mean gamma passing rate (GPR) (percentage of points presenting a gamma function value of <1) was obtained and compared. Calibration curves were obtained for each color channel within the dose range 0-16 Gy. Mean GPR values for film were >98.9% for all criteria when normalizing per maximum dose. When using LD, normalization was >92.7%. GPR values for the array were lower for all criteria; this difference being statistically significant when normalizing at LD, reaching 12% for the 3%/1.5 mm criterion. Both detectors provide satisfactory results for the QA of plans for VMAT lung SBRT. The film provided greater mean GPR values, afforded greater spatial resolution and was more efficient overall.

Evidence for a GPR18 Role in Diurnal Regulation of Intraocular Pressure

PubMed Central

Miller, Sally; Leishman, Emma; Oehler, Olivia; Daily, Laura; Murataeva, Natalia; Wager-Miller, Jim; Bradshaw, Heather; Straiker, Alex

2016-01-01

Purpose The diurnal cycling of intraocular pressure (IOP) was first described in humans more than a century ago. This cycling is preserved in other species. The physiologic underpinning of this diurnal variation in IOP remains a mystery, even though elevated pressure is indicated in most forms of glaucoma, a common cause of blindness. Once identified, the system that underlies diurnal variation would represent a natural target for therapeutic intervention. Methods Using normotensive mice, we measured the regulation of ocular lipid species by the enzymes fatty acid amide hydrolase (FAAH) and N-arachidonoyl phosphatidylethanolamine phospholipase (NAPE-PLD), mRNA expression of these enzymes, and their functional role in diurnal regulation of IOP. Results We now report that NAPE-PLD and FAAH mice do not exhibit a diurnal cycling of IOP. These enzymes produce and break down acylethanolamines, including the endogenous cannabinoid anandamide. The diurnal lipid profile in mice shows that levels of most N-acyl ethanolamines and, intriguingly, N-arachidonoyl glycine (NAGly), decline at night: NAGly is a metabolite of arachidonoyl ethanolamine and a potent agonist at GPR18 that lowers intraocular pressure. The GPR18 blocker O1918 raises IOP during the day when pressure is low, but not at night. Quantitative PCR analysis shows that FAAH mRNA levels rise with pressure, suggesting that FAAH mediates the changes in pressure. Conclusions Our results support FAAH-dependent NAGly action at GPR18 as the physiologic basis of the diurnal variation of intraocular pressure in mice. PMID:27893106

Time-frequency analysis of GPR data to investigate the damage of monumental buildings

NASA Astrophysics Data System (ADS)

Leucci, Giovanni; Masini, Nicola; Persico, Raffaele

2012-08-01

The presence of particular microclimatic conditions inside monumental buildings is responsible for bio-deterioration processes. In many cases, efflorescence and moulds are visible on the facades of several monuments of historical importance. In many other cases, the effects of decay processes are not visible, thus making difficult the diagnosis and the consequent setup of effective rehabilitation and preservation interventions, especially in the presence of a complex geometry and/or a large variability of construction materials. In such cases, a valuable contribution could be provided by geophysical methods (such as electrical resistivity, electromagnetic conductivity, ground-penetrating radar (GPR), etc), which have been proved to be successful tools for sub-surface investigation and characterization of historical buildings. In old monumental buildings, the masonry structures frequently exhibit cracks, voids, detachments and high moisture contrasts that can give rise to reflection events in radar signals. However, the complexity of the geometry and the structural heterogeneity that characterize these old structures often make the GPR results difficult to analyse and interpret. In particular, the spatial variation in GPR signal attenuation can provide important information about the electrical properties of the investigated materials that, in turn, can be used to assess the physical parameters associated with damage. In this paper, we propose an approach that analyses the data in the form of ‘frequency maps’ to evidence absorption losses probably linked to higher moisture content. Two real case histories back up the proposed method.

Characteristics of the GPR field pattern antennas

NASA Astrophysics Data System (ADS)

Pérez-Gracia, V.; González-Drigo, R.; Di Capua, D.; Pujades, L. G.

2007-10-01

Ground-Penetrating Radar has become a popular non-destructive and non-invasive tool in different kind of applications: civil engineering, archaeology, concrete and masonry analysis, etc. The selection of the antenna frequencies depends on the application, but each antenna has a radiation pattern and some characteristics that have influence in the final interpretation and in the model obtained for the studied medium. The knowledge of these features and its coupling effects with the medium could improve the results of the GPR prospecting studies. In this work, some experimental procedures were carried out in order to obtain the 1.6 GHz centre frequency antenna characteristics in the air and in one material medium and to compare them. First, the study of the attenuation due to geometrical spreading was performed. This result was compared with the amplitude attenuation in a material medium, deduced from the GPR experimental data. Second, the shape of the radiation pattern was estimated in laboratory for different distances between the target and the antenna. Near field and far field were considered during the experimental data acquisition. Third, the relative amplitude of the reflected wave (in dB) was obtained depending on the relative position of the antenna over the target. The shape of the radiation pattern and the relative amplitudes obtained in the air were compared with those obtained in a slow medium (water). This slow medium was characterized with the wave velocity and the attenuation factor of the GPR signal.

Volumetric-modulated Arc Therapy Lung Stereotactic Body Radiation Therapy Dosimetric Quality Assurance: A Comparison between Radiochromic Film and Chamber Array

PubMed Central

Colodro, Juan Fernando Mata; Berná, Alfredo Serna; Puchades, Vicente Puchades; Amores, David Ramos; Baños, Miguel Alcaraz

2017-01-01

Introduction: The aim of this work is to verify the use of radiochromic film in the quality assurance (QA) of volumetric-modulated arc therapy (VMAT) lung stereotactic body radiation therapy (SBRT) plans and compare the results with those obtained using an ion chamber array. Materials and Methods: QA was performed for 14 plans using a two-dimensional-array seven29 and EBT3 film. Dose values per session ranged between 7.5 Gy and 18 Gy. The multichannel method was used to obtain a dose map for film. Results: The results obtained were compared with treatment planning system calculated profiles through gamma analysis. Passing criteria were 3%/3 mm, 2%/2 mm and 3%/1.5 mm with maximum and local dose (LD) normalization. Mean gamma passing rate (GPR) (percentage of points presenting a gamma function value of <1) was obtained and compared. Calibration curves were obtained for each color channel within the dose range 0–16 Gy. Mean GPR values for film were >98.9% for all criteria when normalizing per maximum dose. When using LD, normalization was >92.7%. GPR values for the array were lower for all criteria; this difference being statistically significant when normalizing at LD, reaching 12% for the 3%/1.5 mm criterion. Conclusion: Both detectors provide satisfactory results for the QA of plans for VMAT lung SBRT. The film provided greater mean GPR values, afforded greater spatial resolution and was more efficient overall. PMID:28974858

Surface geophysical methods for characterising frozen ground in transitional permafrost landscapes

USGS Publications Warehouse

Briggs, Martin A.; Campbell, Seth; Nolan, Jay; Walvoord, Michelle Ann; Ntarlagiannis, Dimitrios; Day-Lewis, Frederick D.; Lane, John W.

2017-01-01

The distribution of shallow frozen ground is paramount to research in cold regions, and is subject to temporal and spatial changes influenced by climate, landscape disturbance and ecosystem succession. Remote sensing from airborne and satellite platforms is increasing our understanding of landscape-scale permafrost distribution, but typically lacks the resolution to characterise finer-scale processes and phenomena, which are better captured by integrated surface geophysical methods. Here, we demonstrate the use of electrical resistivity imaging (ERI), electromagnetic induction (EMI), ground penetrating radar (GPR) and infrared imaging over multiple summer field seasons around the highly dynamic Twelvemile Lake, Yukon Flats, central Alaska, USA. Twelvemile Lake has generally receded in the past 30 yr, allowing permafrost aggradation in the receded margins, resulting in a mosaic of transient frozen ground adjacent to thick, older permafrost outside the original lakebed. ERI and EMI best evaluated the thickness of shallow, thin permafrost aggradation, which was not clear from frost probing or GPR surveys. GPR most precisely estimated the depth of the active layer, which forward electrical resistivity modelling indicated to be a difficult target for electrical methods, but could be more tractable in time-lapse mode. Infrared imaging of freshly dug soil pit walls captured active-layer thermal gradients at unprecedented resolution, which may be useful in calibrating emerging numerical models. GPR and EMI were able to cover landscape scales (several kilometres) efficiently, and new analysis software showcased here yields calibrated EMI data that reveal the complicated distribution of shallow permafrost in a transitional landscape.

The utility of ground-penetrating radar and its time-dependence in the discovery of clandestine burials.

PubMed

Salsarola, Dominic; Poppa, Pasquale; Amadasi, Alberto; Mazzarelli, Debora; Gibelli, Daniele; Zanotti, Emma; Porta, Davide; Cattaneo, Cristina

2015-08-01

In the field of forensic investigation burial is a relatively common method of hiding a corpse. The location of clandestine graves is, however, a particularly difficult task in which multiple forensic disciplines such as anthropology, botany or archaeology can provide valuable assistance. The use of GPR (ground-penetrating radar) has recently been introduced as a method in the detection of these graves, but what is the true potential of this tool in an operative search scenario? In this study a total of 11 pig carcasses were buried in two wooded areas, each presenting a similar soil composition. The animals were subsequently exhumed at regular intervals, ranging from 2 to 111 weeks, using systematic GPR analysis of the burial sites and archaeological recovery of the subjects that were then autopsied. GPR proved to be useful in recognizing anomalies at the chosen depths of burial and appeared to be dependent on the state of decay of the samples, producing only slight anomalous readings in the presence of skeletal remains: at 92 weeks from burial the difference in signal was weak and at 111 weeks GPR survey offered no helpful information as to burial location. The experiment, in this particular context, determined the technique as being successful in the presence of recent burials, highlighting the need for a multidisciplinary approach in the operative search for buried human remains. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Evaluation of grout behind the lining of shield tunnels using ground-penetrating radar in the Shanghai Metro Line, China

NASA Astrophysics Data System (ADS)

Xie, Xiongyao; Liu, Yujian; Huang, Hongwei; Du, Jun; Zhang, Fengshou; Liu, Lanbo

2007-09-01

For shield tunnelling construction in soft soil areas, the coverage uniformity and quality of consolidation of the injected grout mortar behind the prefabricated tunnel segment is the main concern for tunnel safety and ground settlement. In this paper, ground-penetrating radar (GPR) was applied to evaluate the grout behind the tunnel lining segments in Shanghai, China. The dielectric permittivity of the grout material in Shanghai Metro tunnelling construction was measured in the laboratory. Combining physical modelling results with finite different time domain numerical modelling results, we suggest that the antenna with frequency 200 MHz is well suited to penetrate the reinforced steel bar network of the tunnel lining segment and testing grout patterns behind the segment. The electromagnetic velocity of the grout behind the segment of the tunnel is 0.1 m ns-1 by the analysis of field common-middle point data. A wave-translated method was put forward to process the GPR images. Furthermore, combining the information acquired by GPR with experience data, a GPR non-destructive test standard for the grout mortar evaluation in Shanghai Metro tunnel construction was brought forward. The grout behind the tunnel lining segment is classified into three types: uncompensated grout mortar with a thickness less than 10 cm, normal grout mortar with a thickness between 10 cm and 30 cm and overcompensated grout mortar, which is more than 30 cm thick. The classified method is easily put into practice.

Short communication: identification of the conformational requirement for the specificities of coreceptors for human and simian immunodeficiency viruses.

PubMed

Shimizu, Nobuaki; Tanaka, Atsushi; Jinno-Oue, Atsushi; Mori, Takahisa; Ohtsuki, Takahiro; Hoshino, Hiroo

2010-03-01

More than 10 G protein-coupled receptors (GPCRs) work as coreceptors for human and simian immunodeficiency viruses (HIVs/SIVs); however, structural features critical for coreceptor activity have not been identified. Our objective was to elucidate the structural requirement of coreceptor activities. Amino-terminal regions (NTRs), extracellular loops (ECLs), and the undecapeptidyl arch (UPA) in the second ECL have been shown to be important for coreceptor function. We made chimeric coreceptors for these regions between CCR5 and GPR1, which is genetically distant from CCR5, and analyzed their activities. The coreceptor activity and specificity of CCR5 were maintained when its NTR or UPA was replaced with GPR1. In contrast, the GPR1 chimera with CCR5 NTR was used by HIV-1 strains that can use only CCR5, but not both CCR5 and CXCR4, or GPR1. GPR1 chimera with CCR5 UPA almost lost activity. All ECL chimeras could hardly maintain activity. Thus, CCR5 is more flexibly acceptable to heterologous NTR and UPA than GPR1, suggesting the existence of conformational differences made by the integration of multiple extracellular regions. This conformation may specifically interact with HIV-1 in a strain-dependent manner. Identification of a factor that is critical to make this conformation will contribute to understanding the mechanism of coreceptor function of GPCRs. For this, the coreceptor activity of GPR1, which is genetically distant from CCR5, will be a useful tool.

GPR40 partial agonist MK-2305 lower fasting glucose in the Goto Kakizaki rat via suppression of endogenous glucose production

PubMed Central

Kirkland, Melissa E.; Kosinski, Daniel T.; Mane, Joel; Bunzel, Michelle; Cao, Jin; Souza, Sarah; Thomas-Fowlkes, Brande; Di Salvo, Jerry; Weinglass, Adam B.; Li, Xiaoyan; Myers, Robert W.; Knagge, Kevin; Carrington, Paul E.; Hagmann, William K.

2017-01-01

GPR40 (FFA1) is a fatty acid receptor whose activation results in potent glucose lowering and insulinotropic effects in vivo. Several reports illustrate that GPR40 agonists exert glucose lowering in diabetic humans. To assess the mechanisms by which GPR40 partial agonists improve glucose homeostasis, we evaluated the effects of MK-2305, a potent and selective partial GPR40 agonist, in diabetic Goto Kakizaki rats. MK-2305 decreased fasting glucose after acute and chronic treatment. MK-2305-mediated changes in glucose were coupled with increases in plasma insulin during hyperglycemia and glucose challenges but not during fasting, when glucose was normalized. To determine the mechanism(s) mediating these changes in glucose metabolism, we measured the absolute contribution of precursors to glucose production in the presence or absence of MK-2305. MK-2305 treatment resulted in decreased endogenous glucose production (EGP) driven primarily through changes in gluconeogenesis from substrates entering at the TCA cycle. The decrease in EGP was not likely due to a direct effect on the liver, as isolated perfused liver studies showed no effect of MK-2305 ex vivo and GPR40 is not expressed in the liver. Taken together, our results suggest MK-2305 treatment increases glucose stimulated insulin secretion (GSIS), resulting in changes to hepatic substrate handling that improve glucose homeostasis in the diabetic state. Importantly, these data extend our understanding of the underlying mechanisms by which GPR40 partial agonists reduce hyperglycemia. PMID:28542610

Genetic variants of the unsaturated fatty acid receptor GPR120 relating to obesity in dogs.

PubMed

Miyabe, Masahiro; Gin, Azusa; Onozawa, Eri; Daimon, Mana; Yamada, Hana; Oda, Hitomi; Mori, Akihiro; Momota, Yutaka; Azakami, Daigo; Yamamoto, Ichiro; Mochizuki, Mariko; Sako, Toshinori; Tamura, Katsutoshi; Ishioka, Katsumi

2015-10-01

G protein-coupled receptor (GPR) 120 is an unsaturated fatty acid receptor, which is associated with various physiological functions. It is reported that the genetic variant of GPR120, p.Arg270His, is detected more in obese people, and this genetic variation functionally relates to obesity in humans. Obesity is a common nutritional disorder also in dogs, but the genetic factors have not ever been identified in dogs. In this study, we investigated the molecular structure of canine GPR120 and searched for candidate genetic variants which may relate to obesity in dogs. Canine GPR120 was highly homologous to those of other species, and seven transmembrane domains and two N-glycosylation sites were conserved. GPR120 mRNA was expressed in lung, jejunum, ileum, colon, hypothalamus, hippocampus, spinal cord, bone marrow, dermis and white adipose tissues in dogs, as those in mice and humans. Genetic variants of GPR120 were explored in client-owned 141 dogs, resulting in that 5 synonymous and 4 non-synonymous variants were found. The variant c.595C>A (p.Pro199Thr) was found in 40 dogs, and the gene frequency was significantly higher in dogs with higher body condition scores, i.e. 0.320 in BCS4-5 dogs, 0.175 in BCS3 dogs and 0.000 in BCS2 dogs. We conclude that c.595C>A (p.Pro199Thr) is a candidate variant relating to obesity, which may be helpful for nutritional management of dogs.

Mice Lacking Free Fatty Acid Receptor 1 (GPR40/FFAR1) are Protected Against Conjugated Linoleic Acid-Induced Fatty Liver but Develop Inflammation and Insulin Resistance in the Brain.

PubMed

Sartorius, Tina; Drescher, Andrea; Panse, Madhura; Lastovicka, Petr; Peter, Andreas; Weigert, Cora; Kostenis, Evi; Ullrich, Susanne; Häring, Hans-Ulrich

2015-01-01

Conjugated linoleic acids (CLAs) affect body fat distribution, induce insulin resistance and stimulate insulin secretion. The latter effect is mediated through the free fatty acid receptor-1 (GPR40/FFAR1). This study examines whether GPR40/FFAR1 interacts with tissue specific metabolic changes induced by CLAs. After chronic application of CLAs C57BL/6J wild type (WT) and GPR40/FFAR1 (Ffar1(-/-)) knockout mice developed insulin resistance. Although CLAs accumulated in liver up to 46-fold genotype-independently, hepatic triglycerides augmented only in WT mice. This triglyceride deposition was not associated with increased inflammation. In contrast, in brain of CLA fed Ffar1(-/-) mice mRNA levels of TNF-α were 2-fold higher than in brain of WT mice although CLAs accumulated genotype-independently in brain up to 4-fold. Concomitantly, Ffar1(-/-) mice did not respond to intracerebroventricular (i.c.v.) insulin injection with an increase in cortical activity while WT mice reacted as assessed by radiotelemetric electrocorticography (ECoG) measurements. In vitro incubation of primary murine astrocytes confirmed that CLAs stimulate neuronal inflammation independent of GPR40/FFAR1. This study discloses that GPR40/FFAR1 indirectly modulates organ-specific effects of CLAs: the expression of functional GPR40/FFAR1 counteracts CLA-induced inflammation and insulin resistance in the brain, but favors the development of fatty liver. © 2015 S. Karger AG, Basel.

The Metabolic Sensor GPR43 Receptor Plays a Role in the Control of Klebsiella pneumoniae Infection in the Lung

PubMed Central

Galvão, Izabela; Tavares, Luciana P.; Corrêa, Renan O.; Fachi, José Luís; Rocha, Vitor Melo; Rungue, Marcela; Garcia, Cristiana C.; Cassali, Geovanni; Ferreira, Caroline M.; Martins, Flaviano S.; Oliveira, Sergio C.; Mackay, Charles R.; Teixeira, Mauro M.; Vinolo, Marco Aurélio R.; Vieira, Angélica T.

2018-01-01

Pneumonia is one of the leading causes of death and mortality worldwide. The inflammatory responses that follow respiratory infections are protective leading to pathogen clearance but can also be deleterious if unregulated. The microbiota is known to be an important protective barrier against infections, mediating both direct inhibitory effects against the potential pathogen and also regulating the immune responses contributing to a proper clearance of the pathogen and return to homeostasis. GPR43 is one receptor for acetate, a microbiota metabolite shown to induce and to regulate important immune functions. Here, we addressed the role of GPR43 signaling during pulmonary bacterial infections. We have shown for the first time that the absence of GPR43 leads to increased susceptibility to Klebsiella pneumoniae infection, which was associated to both uncontrolled proliferation of bacteria and to increased inflammatory response. Mechanistically, we showed that GPR43 expression especially in neutrophils and alveolar macrophages is important for bacterial phagocytosis and killing. In addition, treatment with the GPR43 ligand, acetate, is protective during bacterial lung infection. This was associated to reduction in the number of bacteria in the airways and to the control of the inflammatory responses. Altogether, GPR43 plays an important role in the “gut–lung axis” as a sensor of the host gut microbiota activity through acetate binding promoting a proper immune response in the lungs. PMID:29515566

GPR40/FFAR1 deficient mice increase noradrenaline levels in the brain and exhibit abnormal behavior.

PubMed

Aizawa, Fuka; Nishinaka, Takashi; Yamashita, Takuya; Nakamoto, Kazuo; Kurihara, Takashi; Hirasawa, Akira; Kasuya, Fumiyo; Miyata, Atsuro; Tokuyama, Shogo

2016-12-01

The free fatty acid receptor 1 (GPR40/FFAR1) is a G protein-coupled receptor, which is activated by long chain fatty acids. We have previously demonstrated that activation of brain GPR40/FFAR1 exerts an antinociceptive effect that is mediated by the modulation of the descending pain control system. However, it is unclear whether brain GPR40/FFAR1 contributes to emotional function. In this study, we investigated the involvement of GPR40/FFAR1 in emotional behavior using GPR40/FFAR1 deficient (knockout, KO) mice. The emotional behavior in wild and KO male mice was evaluated at 9-10 weeks of age by the elevated plus-maze test, open field test, social interaction test, and sucrose preference test. Brain monoamines levels were measured using LC-MS/MS. The elevated plus-maze test and open field tests revealed that the KO mice reduced anxiety-like behavior. There were no differences in locomotor activity or social behavior between the wild and KO mice. In the sucrose preference test, the KO mice showed reduction in sucrose preference and intake. The level of noradrenaline was higher in the hippocampus, medulla oblongata, hypothalamus and midbrain of KO mice. Therefore, these results suggest that brain GPR40/FFAR1 is associated with anxiety- and depression-related behavior regulated by the increment of noradrenaline in the brain. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Assessment of highway condition using combined geophysical surveys

NASA Astrophysics Data System (ADS)

Dera, Abdallah Alhadi

Four pavement sections were investigated using ground penetrating radar (GPR) and Ultrasonic Surface Wave (USW). The objective of this research was to compare the effectiveness of two non-destructive geophysical tools, GPR and the PSPA, in assessing the condition of the pavements, composed of different construction materials. The GPR data were acquired using a 1.5 GHz antenna along five traverses spaced at two ft. intervals approximately 1000 ft. long. On the other hand, the PSPA data were acquired at the stations spaced at 1000 ft. along the five GPR traverses. Core samples were collected at each site to constrain the interpretation of the acquired geophysical data. The sites include section US 63 about three miles north of Rolla, US 54 in Camdenton County, MO 179 in Jefferson City, and HWY U in Dent County. The types of pavement in these sites were, asphalt concrete overlaying portland cement concrete (AC/PCC), and full-depth asphalt concrete (AC) pavements or full depth bituminous mix (BM). Based on the acquired and analyzed data of the GPR and PSPA, the data of both tools correlated reasonably well. The PSPA technique successfully measured the elastic modulus and the thickness of pavement and detected horizontal flaws (e.g. debonding and delaminations). Similarly, the GPR technique successfully measured the thickness of pavement and detected horizontal flaws (e.g. debonding and delaminations) within the pavement. The research demonstrated that both non-destructive geophysical tools (GPR and PSPA) are effective in assessing the condition of different types of pavement.

Gamma-glutamyl-transpeptidase to platelet ratio is not superior to APRI,FIB-4 and RPR for diagnosing liver fibrosis in CHB patients in China.

PubMed

Huang, Rui; Wang, Guiyang; Tian, Chen; Liu, Yong; Jia, Bei; Wang, Jian; Yang, Yue; Li, Yang; Sun, Zhenhua; Yan, Xiaomin; Xia, Juan; Xiong, Yali; Song, Peixin; Zhang, Zhaoping; Ding, Weimao; Wu, Chao

2017-08-17

The gamma-glutamyl transpeptidase to platelet ratio (GPR) is a novel index to estimate liver fibrosis in chronic hepatitis B (CHB). Few studies compared diagnostic accuracy of GPR with other non-invasive fibrosis tests based on blood parameters. We analyzed diagnostic values of GPR for detecting liver fibrosis and compared diagnostic performances of GPR with APRI (aspartate aminotransferase-to-platelet ratio index), FIB-4 (fibrosis index based on the four factors), NLR (neutrophil-to-lymphocyte ratio), AAR (aspartate aminotransferase/alanine aminotransferase ratio) and RPR (red cell distribution width-to-platelet ratio) in HBeAg positive CHB and HBeAg negative CHB. We found AUROCs of GPR in predicting significant liver fibrosis, advanced liver fibrosis and liver cirrhosis were 0.732 (95% CI 0.663 to 0.801), 0.788 (95% CI 0.729 to 0.847) and 0.753 (95% CI 0.692 to 0.814), respectively. Further comparisons showed the diagnostic performance of GPR was not significantly different with APRI, FIB-4 and RPR in identifying significant fibrosis, advanced fibrosis and cirrhosis, but it was significantly superior to AAR and NLR in both HBeAg positive CHB and HBeAg negative CHB. In conclusion, GPR does not show advantages than APRI, FIB-4 and RPR in identifying significant liver fibrosis, advanced liver fibrosis and liver cirrhosis in both HBeAg positive CHB and HBeAg negative CHB in China.

Design and testing of Ground Penetrating Radar equipment dedicated for civil engineering applications: ongoing activities in Working Group 1 of COST Action TU1208

NASA Astrophysics Data System (ADS)

Pajewski, Lara; Manacorda, Guido; Persico, Raffaele

2015-04-01

This work aims at presenting the ongoing research activities carried out in Working Group 1 'Novel GPR instrumentation' of the COST (European COoperation in Science and Technology) Action TU1208 'Civil Engineering Applications of Ground Penetrating Radar' (www.GPRadar.eu). The principal goal of the COST Action TU1208 is to exchange and increase scientific-technical knowledge and experience of GPR techniques in civil engineering, simultaneously promoting throughout Europe the effective use of this safe and non-destructive technique in the monitoring of infrastructures and structures. Working Group 1 (WG1) of the Action focuses on the development of innovative GPR equipment dedicated for civil engineering applications. It includes three Projects. Project 1.1 is focused on the 'Design, realisation and optimisation of innovative GPR equipment for the monitoring of critical transport infrastructures and buildings, and for the sensing of underground utilities and voids.' Project 1.2 is concerned with the 'Development and definition of advanced testing, calibration and stability procedures and protocols, for GPR equipment.' Project 1.3 deals with the 'Design, modelling and optimisation of GPR antennas.' During the first year of the Action, WG1 Members coordinated between themselves to address the state of the art and open problems in the scientific fields identified by the above-mentioned Projects [1, 2]. In carrying our this work, the WG1 strongly benefited from the participation of IDS Ingegneria dei Sistemi, one of the biggest GPR manufacturers, as well as from the contribution of external experts as David J. Daniels and Erica Utsi, sharing with the Action Members their wide experience on GPR technology and methodology (First General Meeting, July 2013). The synergy with WG2 and WG4 of the Action was useful for a deep understanding of the problems, merits and limits of available GPR equipment, as well as to discuss how to quantify the reliability of GPR results. An innovative reconfigurable ground-coupled stepped-frequency GPR is being studied and optimised by a group of WG1 Members; it was designed in Italy and is equipped with two bow-tie antennas, with a series of switches along their arms, so that their size can be varied. The system was tested in several sites, both indoor and outdoor, in comparison with a commercial ground-coupled pulsed system [1, 3, 4]. Subsequently, within a COST Short-Term Scientific Mission (STSM), the prototype device was sent to Norway and compared with a commercial ground-coupled stepped-frequency radar [5]. These experimental activities were fundamental to gain a deepen knowledge of the reconfigurable GPR prototype and to plan its improvement. Another innovative system being designed within the Action and proposed by Italian Members, will allow investigating the mechanical properties of pavement, in addition to its geometrical and electromagnetic properties. Cooperation with the COST Action IC1102 'Versatile, Integrated, and Signal-aware Technologies for Antennas (VISTA)' has been established, concerning the design of GPR antennas. At least two more WG1 activities need to be mentioned, as they are very interesting and promising. The first one, coordinated by Italy and involving Members and external experts from Germany, United Kingdom, Japan and United States, is the development of a protocol providing recommendations for the safety of people and instruments in near surface geophysical prospecting, with a particular focus to the use of GPR. The second initiative is called GPR4Everyone, it was proposed by Italy and consists in creating a virtual store of GPR equipment at the disposal of Members from inclusiveness Countries: some Institutes have GPR systems and complementary NDT equipment no longer used, while there are Institutes who cannot afford to buy a GPR; thus, the idea is to cense the unused equipment and make it available to be given for free to researchers from less research-intensive countries, as a small step to counterbalance research communities' unequal access to funding and resources distribution. Acknowledgement The Authors thank COST, for funding the COST Action TU1208 'Civil Engineering Applications of Ground Penetrating Radar.' References [1] Proceedings of the First Action's General Meeting (Rome, Italy, 22-24 July 2013), 1st edition, COST Action TU1208, L. Pajewski, A. Benedetto, Eds., ISBN 978-88-548-6191-6 (Aracne, 2013). [2] Civil Engineering Applications of Ground Penetrating Radar, A. Benedetto, L. Pajewski, Eds., ISBN 978-3-319-04812-3 (Springer, 2015, in press). [3] Proceedings of the 15th International Conference on Ground Penetrating Radar - GPR 2014, S. Lambot, A. Giannopoulos, L. Pajewski, F. De André, E. Slob, C. Craeye, Eds., IEEE Conf. Number 35163 (IEEE, 2014). [4] Proceedings of the Second Action's General Meeting (Vienna, Austria, 30 April-2 May 2014), COST Action TU1208, L. Pajewski, A. Benedetto, Eds., ISBN 978-88-548-7224-0 (Aracne, 2014).

Automated pavement analysis in Missouri using ground penetrating radar

DOT National Transportation Integrated Search

2003-02-01

Current geotechnical procedures for monitoring the condition of roadways are time consuming and can be disruptive to traffic, often requiring extensive invasive procedures (e.g., coring). Ground penetrating radar (GPR) technology offers a methodology...

Zhenbao pill protects against acute spinal cord injury via miR-146a-5p regulating the expression of GPR17

PubMed Central

Lv, Bokang; Huan, Yanqiang; Liu, Bin; Li, Yutang; Jia, Lizhou; Qu, Chenhui; Wang, Dongsheng; Yu, Hai

2018-01-01

The aim of the present study was to observe the effect of zhenbao pill on the motor function of acute spinal cord injury (ASCI) rats and the molecular mechanisms involving miR-146a-5p and G-protein-coupled receptor 17 (GPR17). ASCI rat model was established by modified Allen method, and then the rats were divided into three groups. SH-SY5Y cells were cultured overnight in hypoxia condition and transfected with miR-146a-5p mimic or miR-146a-5p inhibitor. The hind limb motor function of the rats was evaluated by Basso, Beattie, Bresnahan (BBB) scoring system. Quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the expression of miR-146a-5p, GPR17, inducible nitric oxide synthase (iNOS), interleukin 1β (IL-1β), and tumor necrosis factor α (TNF-α). Neuronal apoptosis was measured using flow cytometry assay. Luciferase reporter assay was performed to determine the regulation of miR-146a-5p on GPR17. Zhenbao pill could enhance hind limb motor function and attenuate the inflammatory response caused by ASCI. Moreover, zhenbao pill increased the level of miR-146a-5p and decreased GPR17 expression in vivo and in vitro. Bioinformatics software predicted that GPR17 3′-UTR had a binding site with miR-146a-5p. Luciferase reporter assay showed that miR-146a-5p had a negative regulatory effect on GPR17 expression. Knockdown of miR-146a-5p could reverse the effect of zhenbao pill on the up-regulation of GPR17 induced by hypoxia, reversed the inhibitory effect of zhenbao pill on the cell apoptosis induced by hypoxia and the recovery of zhenbao pill on hind limb motor function in ASCI rats. Zhenbao pill could inhibit neuronal apoptosis by regulating miR-146a-5p/GPR17 expression, and then promoting the recovery of spinal cord function. PMID:29187582

GPR30 activation improves memory and facilitates DHPG-induced LTD in the hippocampal CA3 of middle-aged mice.

PubMed

Xu, Wen; Cao, Jian; Zhou, Yan; Wang, Lina; Zhu, Guoqi

2018-03-01

Reduced estrogen levels and decreased expression of related receptors are typical cerebral features of aging. The G protein-coupled estrogen receptor 1 (GPER1, also known as GPR30) is considered a novel therapeutic target for neurodegenerative diseases. In this study, we demonstrated that hippocampal GPR30 expression was reduced in middle-aged mice compared with young adult mice. GPR30 agonist G1 improved both fear and spatial memory in both male and female middle-aged mice, but not in young adult mice, which were blocked by the GPR30 antagonist G15. Interestingly, a group I metabotropic glutamate receptor (mGluR) agonist, 3,5-dihydroxyphenylglycine (DHPG)-induced long-term depression (LTD) in mossy fiber-cornu ammonis 3 (MF-CA3) synapses but not Schaffer collateral-CA1 (SC-CA1) synapses was facilitated in brain slices from G1-treated middle-aged mice. Long-term potentiation (LTP) in SC-CA1 synapses was not affected in slices from G1-treated mice. The effects of GPR30 activation on memory and DHPG-LTD in MF-CA3 synapses were further confirmed by viral expression of GPR30 in the CA3. The regulation of hippocampal synaptic plasticity by G1 treatment might be related to brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) signaling, as G15 also blocked G1-induced activation of the BDNF-TrkB pathway. Moreover, we found that DHPG triggered GluA internalization in slices from G1-treated mice but not control mice. Pharmacological experiments showed that G1-mediated facilitation of DHPG-induced LTD in MF-CA3 synapses was dependent on protein kinase B (Akt), mammalian target of rapamycin (mTor), and TrkB signaling. In conclusion, our results indicate that GPR30 activation improves memory in middle-aged mice, likely through facilitating synaptic plasticity in the CA3. This study provides novel evidence that GPR30 activation can improve memory in middle-aged animals. Copyright © 2018 Elsevier Inc. All rights reserved.

ERK1/2/COX-2/PGE2 signaling pathway mediates GPR91-dependent VEGF release in streptozotocin-induced diabetes

PubMed Central

Li, Tingting; Hu, Jianyan; Du, Shanshan; Chen, Yongdong; Wang, Shuai

2014-01-01

Purpose Retinal vascular dysfunction caused by vascular endothelial growth factor (VEGF) is the major pathological change that occurs in diabetic retinopathy (DR). It has recently been demonstrated that G protein-coupled receptor 91 (GPR91) plays a major role in both vasculature development and retinal angiogenesis. In this study, we examined the signaling pathways involved in GPR91-dependent VEGF release during the early stages of retinal vascular change in streptozotocin-induced diabetes. Methods Diabetic rats were assigned randomly to receive intravitreal injections of shRNA lentiviral particles targeting GPR91 (LV.shGPR91) or control particles (LV.shScrambled). Accumulation of succinate was assessed by gas chromatography-mass spectrometry (GC-MS). At 14 weeks, the ultrastructure and function of the retinal vessels of diabetic retinas with or without shRNA treatment were assessed using hematoxylin and eosin (HE) staining, transmission electron microscopy (TEM), and Evans blue dye permeability. The expression of GPR91, extracellular signal-regulated kinases 1 and 2 (ERK1/2) and cyclooxygenase-2 (COX-2) were measured using immunofluorescence and western blotting. COX-2 and VEGF mRNA were determined by quantitative RT–PCR. Prostaglandin E2 (PGE2) and VEGF secretion were detected using an enzyme-linked immunosorbent assay. Results Succinate exhibited abundant accumulation in diabetic rat retinas. The retinal telangiectatic vessels, basement membrane thickness, and Evans blue dye permeability were attenuated by treatment with GPR91 shRNA. In diabetic rats, knockdown of GPR91 inhibited the activities of ERK1/2 and COX-2 as well as the expression of PGE2 and VEGF. Meanwhile, COX-2, PGE2, and VEGF expression was inhibited by ERK1/2 inhibitor U0126 and COX-2 inhibitor NS-398. Conclusions Our data suggest that hyperglycemia causes succinate accumulation and GPR91 activity in retinal ganglion cells, which mediate VEGF-induced retinal vascular change via the ERK1/2/COX-2/PGE2 pathway. This study highlights the signaling pathway as a potential target for intervention in DR. PMID:25324681

Estrogen and pure antiestrogen fulvestrant (ICI 182 780) augment cell–matrigel adhesion of MCF-7 breast cancer cells through a novel G protein coupled estrogen receptor (GPR30)-to-calpain signaling axis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Yan; Li, Zheng; He, Yan

2014-03-01

Fulvestrant (ICI 182 780, ICI) has been used in treating patients with hormone-sensitive breast cancer, yet initial or acquired resistance to endocrine therapies frequently arises and, in particular, cancer recurs as metastasis. We demonstrate here that both 17-beta-estradiol (E2) and ICI enhance cell adhesion to matrigel in MCF-7 breast cancer cells, with increased autolysis of calpain 1 (large subunit) and proteolysis of focal adhesion kinase (FAK), indicating calpain activation. Additionally, either E2 or ICI induced down-regulation of estrogen receptor α without affecting G protein coupled estrogen receptor 30 (GPR30) expression. Interestingly, GPR30 agonist G1 triggered calpain 1 autolysis but notmore » calpain 2, whereas ER agonist diethylstilbestrol caused no apparent calpain autolysis. Furthermore, the actions of E2 and ICI on calpain and cell adhesion were tremendously suppressed by G15, or knockdown of GPR30. E2 and ICI also induced phosphorylation of extracellular regulated protein kinases 1 and 2 (ERK1/2), and suppression of ERK1/2 phosphorylation by U0126 profoundly impeded calpain activation triggered by estrogenic and antiestrogenic stimulations indicating implication of ERK1/2 in the GPR30-mediated action. Lastly, the E2- or ICI-induced cell adhesion was dramatically impaired by calpain-specific inhibitors, ALLN or calpeptin, suggesting requirement of calpain in the GPR30-associated action. These data show that enhanced cell adhesion by E2 and ICI occurs via a novel GPR30-ERK1/2-calpain pathway. Our results indicate that targeting the GPR30 signaling may be a potential strategy to reduce metastasis and improve the efficacy of antiestrogens in treatment of advanced breast cancer. - Highlights: • Estrogen and ICI augment adhesion to matrigel with calpain activation in MCF-7 cells. • GPR30 mediates cell–matrigel adhesion and calpain activation via ERK1/2. • Calpain is required in the cell–matrigel adhesion induced by E2 and ICI.« less

Differential effects of α4β7 and GPR15 on homing of effector and regulatory T cells from patients with UC to the inflamed gut in vivo.

PubMed

Fischer, Anika; Zundler, Sebastian; Atreya, Raja; Rath, Timo; Voskens, Caroline; Hirschmann, Simon; López-Posadas, Rocío; Watson, Alastair; Becker, Christoph; Schuler, Gerold; Neufert, Clemens; Atreya, Imke; Neurath, Markus F

2016-10-01

Gut homing of lymphocytes via adhesion molecules has recently emerged as new target for therapy in IBDs. We aimed to analyse the in vivo homing of effector (Teff) and regulatory (Treg) T cells to the inflamed gut via α4β7 and G protein receptor GPR15. We assessed the expression of homing receptors on T cells in peripheral blood and inflamed mucosa. We studied the migration pattern and homing of Teff and Treg cells to the inflamed gut using intravital confocal microscopy and FACS in a humanised mouse model in dextran sodium sulfate-treated NSG (NOD.Cg-Prkdcscid-Il2rgtm1Wjl/SzJ) mice. Expression of GPR15 and α4β7 was significantly increased on Treg rather than Teff cells in peripheral blood of patients with UC as compared with Crohn's disease and controls. In vivo analysis in a humanised mouse model showed augmented gut homing of UC Treg cells as compared with controls. Moreover, suppression of UC (but not control) Teff and Treg cell homing was noted upon treatment with the α4β7 antibody vedolizumab. In contrast, siRNA blockade of GPR15 had only effects on homing of Teff cells but did not affect Treg homing in UC. Clinical vedolizumab treatment was associated with marked expansion of UC Treg cells in peripheral blood. α4β7 rather than GPR15 is crucial for increased colonic homing of UC Treg cells in vivo, while both receptors control UC Teff cell homing. Vedolizumab treatment impairs homing of UC Treg cells leading to their accumulation in peripheral blood with subsequent suppression of systemic Teff cell expansion. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Use of high-resolution ground-penetrating radar in kimberlite delineation

USGS Publications Warehouse

Kruger, J.M.; Martinez, A.; Berendsen, P.

1997-01-01

High-resolution ground-penetrating radar (GPR) was used to image the near-surface extent of two exposed Late Cretaceous kimberlites intruded into lower Permian limestone and dolomite host rocks in northeast Kansas. Six parallel GPR profiles identify the margin of the Randolph 1 kimberlite by the up-bending and termination of limestone reflectors. Five radially-intersecting GPR profiles identify the elliptical margin of the Randolph 2 kimberlite by the termination of dolomite reflectors near or below the kimberlite's mushroom-shaped cap. These results suggest GPR may augment magnetic methods for the delineation of kimberlites or other forceful intrusions in a layered host rock where thick, conductive soil or shale is not present at the surface.

Discovery of an Isothiazole-Based Phenylpropanoic Acid GPR120 Agonist as a Development Candidate for Type 2 Diabetes.

PubMed

Zhang, Xuqing; Cai, Chaozhong; Sui, Zhihua; Macielag, Mark; Wang, Yuanping; Yan, Wen; Suckow, Arthur; Hua, Hong; Bell, Austin; Haug, Peter; Clapper, Wilma; Jenkinson, Celia; Gunnet, Joseph; Leonard, James; Murray, William V

2017-09-14

We have discovered a novel series of isothiazole-based phenylpropanoic acids as GPR120 agonists. Extensive structure-activity relationship studies led to the discovery of a potent GPR120 agonist 4x , which displayed good EC 50 values in both calcium and β-arrestin assays. It also presented good pharmaceutical properties and a favorable PK profile. Moreover, it demonstrated in vivo antidiabetic activity in C57BL/6 DIO mice. Studies in WT and knockout DIO mice showed that it improved glucose handling during an OGTT via GPR120. Overall, 4x possessed promising antidiabetic effect and good safety profile to be a development candidate.