Evaluating Machine Learning Regression Algorithms for Operational Retrieval of Biophysical Parameters: Opportunities for Sentinel

NASA Astrophysics Data System (ADS)

Verrelst, Jochem; Rivera, J. P.; Alonso, L.; Guanter, L.; Moreno, J.

2012-04-01

ESA’s upcoming satellites Sentinel-2 (S2) and Sentinel-3 (S3) aim to ensure continuity for Landsat 5/7, SPOT- 5, SPOT-Vegetation and Envisat MERIS observations by providing superspectral images of high spatial and temporal resolution. S2 and S3 will deliver near real-time operational products with a high accuracy for land monitoring. This unprecedented data availability leads to an urgent need for developing robust and accurate retrieval methods. Machine learning regression algorithms could be powerful candidates for the estimation of biophysical parameters from satellite reflectance measurements because of their ability to perform adaptive, nonlinear data fitting. By using data from the ESA-led field campaign SPARC (Barrax, Spain), it was recently found [1] that Gaussian processes regression (GPR) outperformed competitive machine learning algorithms such as neural networks, support vector regression) and kernel ridge regression both in terms of accuracy and computational speed. For various Sentinel configurations (S2-10m, S2- 20m, S2-60m and S3-300m) three important biophysical parameters were estimated: leaf chlorophyll content (Chl), leaf area index (LAI) and fractional vegetation cover (FVC). GPR was the only method that reached the 10% precision required by end users in the estimation of Chl. In view of implementing the regressor into operational monitoring applications, here the portability of locally trained GPR models to other images was evaluated. The associated confidence maps proved to be a good indicator for evaluating the robustness of the trained models. Consistent retrievals were obtained across the different images, particularly over agricultural sites. To make the method suitable for operational use, however, the poorer confidences over bare soil areas suggest that the training dataset should be expanded with inputs from various land cover types.

A nonlinear cointegration approach with applications to structural health monitoring

NASA Astrophysics Data System (ADS)

Shi, H.; Worden, K.; Cross, E. J.

2016-09-01

One major obstacle to the implementation of structural health monitoring (SHM) is the effect of operational and environmental variabilities, which may corrupt the signal of structural degradation. Recently, an approach inspired from the community of econometrics, called cointegration, has been employed to eliminate the adverse influence from operational and environmental changes and still maintain sensitivity to structural damage. However, the linear nature of cointegration may limit its application when confronting nonlinear relations between system responses. This paper proposes a nonlinear cointegration method based on Gaussian process regression (GPR); the method is constructed under the Engle-Granger framework, and tests for unit root processes are conducted both before and after the GPR is applied. The proposed approach is examined with real engineering data from the monitoring of the Z24 Bridge.

Estimation of the daily global solar radiation based on the Gaussian process regression methodology in the Saharan climate

NASA Astrophysics Data System (ADS)

Guermoui, Mawloud; Gairaa, Kacem; Rabehi, Abdelaziz; Djafer, Djelloul; Benkaciali, Said

2018-06-01

Accurate estimation of solar radiation is the major concern in renewable energy applications. Over the past few years, a lot of machine learning paradigms have been proposed in order to improve the estimation performances, mostly based on artificial neural networks, fuzzy logic, support vector machine and adaptive neuro-fuzzy inference system. The aim of this work is the prediction of the daily global solar radiation, received on a horizontal surface through the Gaussian process regression (GPR) methodology. A case study of Ghardaïa region (Algeria) has been used in order to validate the above methodology. In fact, several combinations have been tested; it was found that, GPR-model based on sunshine duration, minimum air temperature and relative humidity gives the best results in term of mean absolute bias error (MBE), root mean square error (RMSE), relative mean square error (rRMSE), and correlation coefficient ( r) . The obtained values of these indicators are 0.67 MJ/m2, 1.15 MJ/m2, 5.2%, and 98.42%, respectively.

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.

Modelling daily water temperature from air temperature for the Missouri River.

PubMed

Zhu, Senlin; Nyarko, Emmanuel Karlo; Hadzima-Nyarko, Marijana

2018-01-01

The bio-chemical and physical characteristics of a river are directly affected by water temperature, which thereby affects the overall health of aquatic ecosystems. It is a complex problem to accurately estimate water temperature. Modelling of river water temperature is usually based on a suitable mathematical model and field measurements of various atmospheric factors. In this article, the air-water temperature relationship of the Missouri River is investigated by developing three different machine learning models (Artificial Neural Network (ANN), Gaussian Process Regression (GPR), and Bootstrap Aggregated Decision Trees (BA-DT)). Standard models (linear regression, non-linear regression, and stochastic models) are also developed and compared to machine learning models. Analyzing the three standard models, the stochastic model clearly outperforms the standard linear model and nonlinear model. All the three machine learning models have comparable results and outperform the stochastic model, with GPR having slightly better results for stations No. 2 and 3, while BA-DT has slightly better results for station No. 1. The machine learning models are very effective tools which can be used for the prediction of daily river temperature.

Predictors of the number of under-five malnourished children in Bangladesh: application of the generalized poisson regression model

PubMed Central

2013-01-01

Background Malnutrition is one of the principal causes of child mortality in developing countries including Bangladesh. According to our knowledge, most of the available studies, that addressed the issue of malnutrition among under-five children, considered the categorical (dichotomous/polychotomous) outcome variables and applied logistic regression (binary/multinomial) to find their predictors. In this study malnutrition variable (i.e. outcome) is defined as the number of under-five malnourished children in a family, which is a non-negative count variable. The purposes of the study are (i) to demonstrate the applicability of the generalized Poisson regression (GPR) model as an alternative of other statistical methods and (ii) to find some predictors of this outcome variable. Methods The data is extracted from the Bangladesh Demographic and Health Survey (BDHS) 2007. Briefly, this survey employs a nationally representative sample which is based on a two-stage stratified sample of households. A total of 4,460 under-five children is analysed using various statistical techniques namely Chi-square test and GPR model. Results The GPR model (as compared to the standard Poisson regression and negative Binomial regression) is found to be justified to study the above-mentioned outcome variable because of its under-dispersion (variance < mean) property. Our study also identify several significant predictors of the outcome variable namely mother’s education, father’s education, wealth index, sanitation status, source of drinking water, and total number of children ever born to a woman. Conclusions Consistencies of our findings in light of many other studies suggest that the GPR model is an ideal alternative of other statistical models to analyse the number of under-five malnourished children in a family. Strategies based on significant predictors may improve the nutritional status of children in Bangladesh. PMID:23297699

Towards smart energy systems: application of kernel machine regression for medium term electricity load forecasting.

PubMed

Alamaniotis, Miltiadis; Bargiotas, Dimitrios; Tsoukalas, Lefteri H

2016-01-01

Integration of energy systems with information technologies has facilitated the realization of smart energy systems that utilize information to optimize system operation. To that end, crucial in optimizing energy system operation is the accurate, ahead-of-time forecasting of load demand. In particular, load forecasting allows planning of system expansion, and decision making for enhancing system safety and reliability. In this paper, the application of two types of kernel machines for medium term load forecasting (MTLF) is presented and their performance is recorded based on a set of historical electricity load demand data. The two kernel machine models and more specifically Gaussian process regression (GPR) and relevance vector regression (RVR) are utilized for making predictions over future load demand. Both models, i.e., GPR and RVR, are equipped with a Gaussian kernel and are tested on daily predictions for a 30-day-ahead horizon taken from the New England Area. Furthermore, their performance is compared to the ARMA(2,2) model with respect to mean average percentage error and squared correlation coefficient. Results demonstrate the superiority of RVR over the other forecasting models in performing MTLF.

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 application of feature selection to the development of Gaussian process models for percutaneous absorption.

PubMed

Lam, Lun Tak; Sun, Yi; Davey, Neil; Adams, Rod; Prapopoulou, Maria; Brown, Marc B; Moss, Gary P

2010-06-01

The aim was to employ Gaussian processes to assess mathematically the nature of a skin permeability dataset and to employ these methods, particularly feature selection, to determine the key physicochemical descriptors which exert the most significant influence on percutaneous absorption, and to compare such models with established existing models. Gaussian processes, including automatic relevance detection (GPRARD) methods, were employed to develop models of percutaneous absorption that identified key physicochemical descriptors of percutaneous absorption. Using MatLab software, the statistical performance of these models was compared with single linear networks (SLN) and quantitative structure-permeability relationships (QSPRs). Feature selection methods were used to examine in more detail the physicochemical parameters used in this study. A range of statistical measures to determine model quality were used. The inherently nonlinear nature of the skin data set was confirmed. The Gaussian process regression (GPR) methods yielded predictive models that offered statistically significant improvements over SLN and QSPR models with regard to predictivity (where the rank order was: GPR > SLN > QSPR). Feature selection analysis determined that the best GPR models were those that contained log P, melting point and the number of hydrogen bond donor groups as significant descriptors. Further statistical analysis also found that great synergy existed between certain parameters. It suggested that a number of the descriptors employed were effectively interchangeable, thus questioning the use of models where discrete variables are output, usually in the form of an equation. The use of a nonlinear GPR method produced models with significantly improved predictivity, compared with SLN or QSPR models. Feature selection methods were able to provide important mechanistic information. However, it was also shown that significant synergy existed between certain parameters, and as such it was possible to interchange certain descriptors (i.e. molecular weight and melting point) without incurring a loss of model quality. Such synergy suggested that a model constructed from discrete terms in an equation may not be the most appropriate way of representing mechanistic understandings of skin absorption.

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.

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.

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.

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.

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.

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.

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.

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.

Curriculum emphasis and resident preparation in postgraduate general dentistry programs.

PubMed

Lefever, Karen H; Atchison, Kathryn A; Mito, Ronald S; Lin, Sylvia

2002-06-01

In 1999 HRSA contracted with the UCLA School of Dentistry to evaluate the impact of federal funding on postgraduate general dentistry programs. Part of that evaluation analyzed curriculum emphasis and preparation of incoming residents in advanced general dentistry programs over a five-year period. Directors of 208 civilian AEGD and GPR programs were surveyed about the curriculum content of their programs, increased or decreased emphasis in thirty subject areas, and resident preparation and quality (GPA and National Board scores). Results indicate that curriculum changes in AEGD and GPR programs over the time period have been responsive to the changing nature of general practice. At least half of all program directors reported that their residents were less than adequately prepared in fourteen curriculum areas. Sub-analyses were conducted for AEGD/GPR programs and HRSA-funded versus nonfunded programs. Multivariate regression identified lower student quality as the most important program variable in predicting a perceived need for resident remediation. Logistic regression showed that programs with higher resident GPA and National Board Part I scores had less difficulty filling resident positions.

Work flow of signal processing data of ground penetrating radar case of rigid pavement measurements

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

Handayani, Gunawan

The signal processing of Ground Penetrating Radar (GPR) requires a certain work flow to obtain good results. Even though the Ground Penetrating Radar data looks similar with seismic reflection data, but the GPR data has particular signatures that the seismic reflection data does not have. This is something to do with coupling between antennae and the ground surface. Because of this, the GPR data should be treated differently from the seismic signal data processing work flow. Even though most of the processing steps still follow the same work flow of seismic reflection data such as: filtering, predictive deconvolution etc. Thismore » paper presents the work flow of GPR processing data on rigid pavement measurements. The processing steps start from raw data, de-Wow process, remove DC and continue with the standard process to get rid of noises i.e. filtering process. Some radargram particular features of rigid pavement along with pile foundations are presented.« less

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.

GP Workbench Manual: Technical Manual, User's Guide, and Software Guide

USGS Publications Warehouse

Oden, Charles P.; Moulton, Craig W.

2006-01-01

GP Workbench is an open-source general-purpose geophysical data processing software package written primarily for ground penetrating radar (GPR) data. It also includes support for several USGS prototype electromagnetic instruments such as the VETEM and ALLTEM. The two main programs in the package are GP Workbench and GP Wave Utilities. GP Workbench has routines for filtering, gridding, and migrating GPR data; as well as an inversion routine for characterizing UXO (unexploded ordinance) using ALLTEM data. GP Workbench provides two-dimensional (section view) and three-dimensional (plan view or time slice view) processing for GPR data. GP Workbench can produce high-quality graphics for reports when Surfer 8 or higher (Golden Software) is installed. GP Wave Utilities provides a wide range of processing algorithms for single waveforms, such as filtering, correlation, deconvolution, and calculating GPR waveforms. GP Wave Utilities is used primarily for calibrating radar systems and processing individual traces. Both programs also contain research features related to the calibration of GPR systems and calculating subsurface waveforms. The software is written to run on the Windows operating systems. GP Workbench can import GPR data file formats used by major commercial instrument manufacturers including Sensors and Software, GSSI, and Mala. The GP Workbench native file format is SU (Seismic Unix), and subsequently, files generated by GP Workbench can be read by Seismic Unix as well as many other data processing packages.

Geophysical Imaging of Sea-level Proxies in Beach-Ridge Deposits

NASA Astrophysics Data System (ADS)

Nielsen, L.; Emerich Souza, P.; Meldgaard, A.; Bendixen, M.; Kroon, A.; Clemmensen, L. B.

2017-12-01

We show ground-penetrating radar (GPR) reflection data collected over modern and fossil beach deposits from different localities along coastlines in meso-tidal regimes of Greenland and micro-tidal regimes of Denmark. The acquired reflection GPR sections show several similar characteristics but also some differences. A similar characteristic is the presence of downlapping reflections, where the downlap point is interpreted to mark the transition from upper shoreface to beachface deposits and, thus, be a marker of a level close to or at sea-level at the time of deposition. Differences in grain size of the investigated beach ridge system result in different scattering characteristics of the acquired GPR data. These differences call for tailored, careful processing of the GPR data for optimal imaging of internal beach ridge architecture. We outline elements of the GPR data processing of particular importance for optimal imaging. Moreover, we discuss advantages and challenges related to using GPR-based proxies of sea-level as compared to other methods traditionally used for establishment of curves of past sea-level variation.

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.

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.

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.

Continuous monitoring of the lunar or Martian subsurface using on-board pattern recognition and neural processing of Rover geophysical data

NASA Technical Reports Server (NTRS)

Mcgill, J. W.; Glass, C. E.; Sternberg, B. K.

1990-01-01

The ultimate goal is to create an extraterrestrial unmanned system for subsurface mapping and exploration. Neural networks are to be used to recognize anomalies in the profiles that correspond to potentially exploitable subsurface features. The ground penetrating radar (GPR) techniques are likewise identical. Hence, the preliminary research focus on GPR systems will be directly applicable to seismic systems once such systems can be designed for continuous operation. The original GPR profile may be very complex due to electrical behavior of the background, targets, and antennas, much as the seismic record is made complex by multiple reflections, ghosting, and ringing. Because the format of the GPR data is similar to the format of seismic data, seismic processing software may be applied to GPR data to help enhance the data. A neural network may then be trained to more accurately identify anomalies from the processed record than from the original record.

Ground penetrating radar: a case study for estimating root bulking rate in cassava (Manihot esculenta Crantz).

PubMed

Delgado, Alfredo; Hays, Dirk B; Bruton, Richard K; Ceballos, Hernán; Novo, Alexandre; Boi, Enrico; Selvaraj, Michael Gomez

2017-01-01

Understanding root traits is a necessary research front for selection of favorable genotypes or cultivation practices. Root and tuber crops having most of their economic potential stored below ground are favorable candidates for such studies. The ability to image and quantify subsurface root structure would allow breeders to classify root traits for rapid selection and allow agronomist the ability to derive effective cultivation practices. In spite of the huge role of Cassava ( Manihot esculenta Crantz), for food security and industrial uses, little progress has been made in understanding the onset and rate of the root-bulking process and the factors that influence it. The objective of this research was to determine the capability of ground penetrating radar (GPR) to predict root-bulking rates through the detection of total root biomass during its growth cycle. Our research provides the first application of GPR for detecting below ground biomass in cassava. Through an empirical study, linear regressions were derived to model cassava bulking rates. The linear equations derived suggest that GPR is a suitable measure of root biomass ( r  = .79). The regression analysis developed accounts for 63% of the variability in cassava biomass below ground. When modeling is performed at the variety level, it is evident that the variety models for SM 1219-9 and TMS 60444 outperform the HMC-1 variety model (r 2  = .77, .63 and .51 respectively). Using current modeling methods, it is possible to predict below ground biomass and estimate root bulking rates for selection of early root bulking in cassava. Results of this approach suggested that the general model was over predicting at early growth stages but became more precise in later root development.

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.

Adaptive Gaussian mixture models for pre-screening in GPR data

NASA Astrophysics Data System (ADS)

Torrione, Peter; Morton, Kenneth, Jr.; Besaw, Lance E.

2011-06-01

Due to the large amount of data generated by vehicle-mounted ground penetrating radar (GPR) antennae arrays, advanced feature extraction and classification can only be performed on a small subset of data during real-time operation. As a result, most GPR based landmine detection systems implement "pre-screening" algorithms to processes all of the data generated by the antennae array and identify locations with anomalous signatures for more advanced processing. These pre-screening algorithms must be computationally efficient and obtain high probability of detection, but can permit a false alarm rate which might be higher than the total system requirements. Many approaches to prescreening have previously been proposed, including linear prediction coefficients, the LMS algorithm, and CFAR-based approaches. Similar pre-screening techniques have also been developed in the field of video processing to identify anomalous behavior or anomalous objects. One such algorithm, an online k-means approximation to an adaptive Gaussian mixture model (GMM), is particularly well-suited to application for pre-screening in GPR data due to its computational efficiency, non-linear nature, and relevance of the logic underlying the algorithm to GPR processing. In this work we explore the application of an adaptive GMM-based approach for anomaly detection from the video processing literature to pre-screening in GPR data. Results with the ARA Nemesis landmine detection system demonstrate significant pre-screening performance improvements compared to alternative approaches, and indicate that the proposed algorithm is a complimentary technique to existing methods.

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

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

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.

Quantitative prediction of ionization effect on human skin permeability.

PubMed

Baba, Hiromi; Ueno, Yusuke; Hashida, Mitsuru; Yamashita, Fumiyoshi

2017-04-30

Although skin permeability of an active ingredient can be severely affected by its ionization in a dose solution, most of the existing prediction models cannot predict such impacts. To provide reliable predictors, we curated a novel large dataset of in vitro human skin permeability coefficients for 322 entries comprising chemically diverse permeants whose ionization fractions can be calculated. Subsequently, we generated thousands of computational descriptors, including LogD (octanol-water distribution coefficient at a specific pH), and analyzed the dataset using nonlinear support vector regression (SVR) and Gaussian process regression (GPR) combined with greedy descriptor selection. The SVR model was slightly superior to the GPR model, with externally validated squared correlation coefficient, root mean square error, and mean absolute error values of 0.94, 0.29, and 0.21, respectively. These models indicate that Log D is effective for a comprehensive prediction of ionization effects on skin permeability. In addition, the proposed models satisfied the statistical criteria endorsed in recent model validation studies. These models can evaluate virtually generated compounds at any pH; therefore, they can be used for high-throughput evaluations of numerous active ingredients and optimization of their skin permeability with respect to permeant ionization. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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.

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.

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.

A general procedure to generate models for urban environmental-noise pollution using feature selection and machine learning methods.

PubMed

Torija, Antonio J; Ruiz, Diego P

2015-02-01

The prediction of environmental noise in urban environments requires the solution of a complex and non-linear problem, since there are complex relationships among the multitude of variables involved in the characterization and modelling of environmental noise and environmental-noise magnitudes. Moreover, the inclusion of the great spatial heterogeneity characteristic of urban environments seems to be essential in order to achieve an accurate environmental-noise prediction in cities. This problem is addressed in this paper, where a procedure based on feature-selection techniques and machine-learning regression methods is proposed and applied to this environmental problem. Three machine-learning regression methods, which are considered very robust in solving non-linear problems, are used to estimate the energy-equivalent sound-pressure level descriptor (LAeq). These three methods are: (i) multilayer perceptron (MLP), (ii) sequential minimal optimisation (SMO), and (iii) Gaussian processes for regression (GPR). In addition, because of the high number of input variables involved in environmental-noise modelling and estimation in urban environments, which make LAeq prediction models quite complex and costly in terms of time and resources for application to real situations, three different techniques are used to approach feature selection or data reduction. The feature-selection techniques used are: (i) correlation-based feature-subset selection (CFS), (ii) wrapper for feature-subset selection (WFS), and the data reduction technique is principal-component analysis (PCA). The subsequent analysis leads to a proposal of different schemes, depending on the needs regarding data collection and accuracy. The use of WFS as the feature-selection technique with the implementation of SMO or GPR as regression algorithm provides the best LAeq estimation (R(2)=0.94 and mean absolute error (MAE)=1.14-1.16 dB(A)). Copyright © 2014 Elsevier B.V. All rights reserved.

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.

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.

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

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.

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.

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.

Estimation CODMN in Guangzhou Section of Pearl River Based on GF-1 Images

NASA Astrophysics Data System (ADS)

Feng, Y. B.; He, Y. Q.; Fu, Q. H.; Liu, C. Q.; Pan, H. Z.; Yin, B.

2018-04-01

Due to the way that remote sensing works, it has natural advantage to detect optical constituents in waters. And many kinds of inversion models were constructed based on the three main optical constituents, namely chlorophyll-a (Chl-a), suspended particulate matter (SPM), colored dissolved organic matter (CDOM). Except Chl-a used as an indicator of eutrophication, however, the public generally cares less about other two parameters and is more familiar with Grade I V scheme for utilization and protection purposes. Notice the three main optical constituents are also organic-related to some extent. It offers a possible way to estimate CODMn via remote sensing. According to field measurement conducted along the Guangzhou section of Pearl River (GPR for short), the spatial variation of CODMn in GPR shows some kinds of geographical feature, so does the correlation between CODMn and water color constituents. It indicated the complicated contribution of CODMn in GPR or some other urban rivers. Based on the band setting of GF-1 satellite, two kinds of inversion model of CODMn in GPR were finally constructed. One directly achieved CODMn from regression models of which predictors were different band combinations in different channels of GPR. To make the study more practical, the other one first provided empirical models of the three optical constituents, and then estimated CODMn of GPR based on its relationship with optical constituents. After all, Chl-a, SPM and CDOM could be distinguished optically, and remote sensing models of these three constituents in other studies may also be available.

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

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.

Statistical 21-cm Signal Separation via Gaussian Process Regression Analysis

NASA Astrophysics Data System (ADS)

Mertens, F. G.; Ghosh, A.; Koopmans, L. V. E.

2018-05-01

Detecting and characterizing the Epoch of Reionization and Cosmic Dawn via the redshifted 21-cm hyperfine line of neutral hydrogen will revolutionize the study of the formation of the first stars, galaxies, black holes and intergalactic gas in the infant Universe. The wealth of information encoded in this signal is, however, buried under foregrounds that are many orders of magnitude brighter. These must be removed accurately and precisely in order to reveal the feeble 21-cm signal. This requires not only the modeling of the Galactic and extra-galactic emission, but also of the often stochastic residuals due to imperfect calibration of the data caused by ionospheric and instrumental distortions. To stochastically model these effects, we introduce a new method based on `Gaussian Process Regression' (GPR) which is able to statistically separate the 21-cm signal from most of the foregrounds and other contaminants. Using simulated LOFAR-EoR data that include strong instrumental mode-mixing, we show that this method is capable of recovering the 21-cm signal power spectrum across the entire range k = 0.07 - 0.3 {h cMpc^{-1}}. The GPR method is most optimal, having minimal and controllable impact on the 21-cm signal, when the foregrounds are correlated on frequency scales ≳ 3 MHz and the rms of the signal has σ21cm ≳ 0.1 σnoise. This signal separation improves the 21-cm power-spectrum sensitivity by a factor ≳ 3 compared to foreground avoidance strategies and enables the sensitivity of current and future 21-cm instruments such as the Square Kilometre Array to be fully exploited.

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

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.

Rover mounted ground penetrating radar as a tool for investigating the near-surface of Mars and beyong

NASA Technical Reports Server (NTRS)

Grant, J. A.; Schultz, P. H.

1993-01-01

In spite of the highly successful nature of recent planetary missions to the terrestrial planets and outer satellites a number of questions concerning the evolution of their surfaces remain unresolved. For example, knowledge of many characteristics of the stratigraphy and soils comprising the near-surface on Mars remains largely unknown, but is crucial in order to accurately define the history of surface processes and near-surface sedimentary record. Similar statements can be made regarding our understanding of near-surface stratigraphy and processes on other extraterrestrial planetary bodies. Ground penetrating radar (GPR) is a proven and standard instrument capable of imaging the subsurface at high resolution to 10's of meters depth in a variety of terrestrial environments. Moreover, GPR is portable and easily modified for rover deployment. Data collected with a rover mounted GPR could resolve a number of issues related to planetary surface evolution by defining shallow stratigraphic records and would provide context for interpreting results of other surface analyses (e.g. elemental or mineralogical). A discussion of existing GPR capabilities is followed first by examples of how GPR might be used to better define surface evolution on Mars and then by a brief description of possible GPR applications to the Moon and other planetary surfaces.

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.

Mutations in the pH-Sensing G-protein-Coupled Receptor GPR68 Cause Amelogenesis Imperfecta.

PubMed

Parry, David A; Smith, Claire E L; El-Sayed, Walid; Poulter, James A; Shore, Roger C; Logan, Clare V; Mogi, Chihiro; Sato, Koichi; Okajima, Fumikazu; Harada, Akihiro; Zhang, Hong; Koruyucu, Mine; Seymen, Figen; Hu, Jan C-C; Simmer, James P; Ahmed, Mushtaq; Jafri, Hussain; Johnson, Colin A; Inglehearn, Chris F; Mighell, Alan J

2016-10-06

Amelogenesis is the process of dental enamel formation, leading to the deposition of the hardest tissue in the human body. This process requires the intricate regulation of ion transport and controlled changes to the pH of the developing enamel matrix. The means by which the enamel organ regulates pH during amelogenesis is largely unknown. We identified rare homozygous variants in GPR68 in three families with amelogenesis imperfecta, a genetically and phenotypically heterogeneous group of inherited conditions associated with abnormal enamel formation. Each of these homozygous variants (a large in-frame deletion, a frameshift deletion, and a missense variant) were predicted to result in loss of function. GPR68 encodes a proton-sensing G-protein-coupled receptor with sensitivity in the pH range that occurs in the developing enamel matrix during amelogenesis. Immunohistochemistry of rat mandibles confirmed localization of GPR68 in the enamel organ at all stages of amelogenesis. Our data identify a role for GPR68 as a proton sensor that is required for proper enamel formation. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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.

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.

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.

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

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.

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.

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."

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.

Role of free fatty acid receptors in the regulation of energy metabolism.

PubMed

Hara, Takafumi; Kashihara, Daiji; Ichimura, Atsuhiko; Kimura, Ikuo; Tsujimoto, Gozoh; Hirasawa, Akira

2014-09-01

Free fatty acids (FFAs) are energy-generating nutrients that act as signaling molecules in various cellular processes. Several orphan G protein-coupled receptors (GPCRs) that act as FFA receptors (FFARs) have been identified and play important physiological roles in various diseases. FFA ligands are obtained from food sources and metabolites produced during digestion and lipase degradation of triglyceride stores. FFARs can be grouped according to ligand profiles, depending on the length of carbon chains of the FFAs. Medium- and long-chain FFAs activate FFA1/GPR40 and FFA4/GPR120. Short-chain FFAs activate FFA2/GPR43 and FFA3/GPR41. However, only medium-chain FFAs, and not long-chain FFAs, activate GPR84 receptor. A number of pharmacological and physiological studies have shown that these receptors are expressed in various tissues and are primarily involved in energy metabolism. Because an impairment of these processes is a part of the pathology of obesity and type 2 diabetes, FFARs are considered as key therapeutic targets. Here, we reviewed recently published studies on the physiological functions of these receptors, primarily focusing on energy homeostasis. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

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.

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

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.

Collaborative simulations and experiments for a novel yield model of coal devolatilization in oxy-coal combustion conditions

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

Iavarone, Salvatore; Smith, Sean T.; Smith, Philip J.

Oxy-coal combustion is an emerging low-cost “clean coal” technology for emissions reduction and Carbon Capture and Sequestration (CCS). The use of Computational Fluid Dynamics (CFD) tools is crucial for the development of cost-effective oxy-fuel technologies and the minimization of environmental concerns at industrial scale. The coupling of detailed chemistry models and CFD simulations is still challenging, especially for large-scale plants, because of the high computational efforts required. The development of scale-bridging models is therefore necessary, to find a good compromise between computational efforts and the physical-chemical modeling precision. This paper presents a procedure for scale-bridging modeling of coal devolatilization, inmore » the presence of experimental error, that puts emphasis on the thermodynamic aspect of devolatilization, namely the final volatile yield of coal, rather than kinetics. The procedure consists of an engineering approach based on dataset consistency and Bayesian methodology including Gaussian-Process Regression (GPR). Experimental data from devolatilization tests carried out in an oxy-coal entrained flow reactor were considered and CFD simulations of the reactor were performed. Jointly evaluating experiments and simulations, a novel yield model was validated against the data via consistency analysis. In parallel, a Gaussian-Process Regression was performed, to improve the understanding of the uncertainty associated to the devolatilization, based on the experimental measurements. Potential model forms that could predict yield during devolatilization were obtained. The set of model forms obtained via GPR includes the yield model that was proven to be consistent with the data. Finally, the overall procedure has resulted in a novel yield model for coal devolatilization and in a valuable evaluation of uncertainty in the data, in the model form, and in the model parameters.« less

Collaborative simulations and experiments for a novel yield model of coal devolatilization in oxy-coal combustion conditions

DOE PAGES

Iavarone, Salvatore; Smith, Sean T.; Smith, Philip J.; ...

2017-06-03

Oxy-coal combustion is an emerging low-cost “clean coal” technology for emissions reduction and Carbon Capture and Sequestration (CCS). The use of Computational Fluid Dynamics (CFD) tools is crucial for the development of cost-effective oxy-fuel technologies and the minimization of environmental concerns at industrial scale. The coupling of detailed chemistry models and CFD simulations is still challenging, especially for large-scale plants, because of the high computational efforts required. The development of scale-bridging models is therefore necessary, to find a good compromise between computational efforts and the physical-chemical modeling precision. This paper presents a procedure for scale-bridging modeling of coal devolatilization, inmore » the presence of experimental error, that puts emphasis on the thermodynamic aspect of devolatilization, namely the final volatile yield of coal, rather than kinetics. The procedure consists of an engineering approach based on dataset consistency and Bayesian methodology including Gaussian-Process Regression (GPR). Experimental data from devolatilization tests carried out in an oxy-coal entrained flow reactor were considered and CFD simulations of the reactor were performed. Jointly evaluating experiments and simulations, a novel yield model was validated against the data via consistency analysis. In parallel, a Gaussian-Process Regression was performed, to improve the understanding of the uncertainty associated to the devolatilization, based on the experimental measurements. Potential model forms that could predict yield during devolatilization were obtained. The set of model forms obtained via GPR includes the yield model that was proven to be consistent with the data. Finally, the overall procedure has resulted in a novel yield model for coal devolatilization and in a valuable evaluation of uncertainty in the data, in the model form, and in the model parameters.« less

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

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.

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.

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.

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.

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.

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.

Inverts permittivity and conductivity with structural constraint in GPR FWI based on truncated Newton method

NASA Astrophysics Data System (ADS)

Ren, Qianci

2018-04-01

Full waveform inversion (FWI) of ground penetrating radar (GPR) is a promising technique to quantitatively evaluate the permittivity and conductivity of near subsurface. However, these two parameters are simultaneously inverted in the GPR FWI, increasing the difficulty to obtain accurate inversion results for both parameters. In this study, I present a structural constrained GPR FWI procedure to jointly invert the two parameters, aiming to force a structural relationship between permittivity and conductivity in the process of model reconstruction. The structural constraint is enforced by a cross-gradient function. In this procedure, the permittivity and conductivity models are inverted alternately at each iteration and updated with hierarchical frequency components in the frequency domain. The joint inverse problem is solved by the truncated Newton method which considering the effect of Hessian operator and using the approximated solution of Newton equation to be the perturbation model in the updating process. The joint inversion procedure is tested by three synthetic examples. The results show that jointly inverting permittivity and conductivity in GPR FWI effectively increases the structural similarities between the two parameters, corrects the structures of parameter models, and significantly improves the accuracy of conductivity model, resulting in a better inversion result than the individual inversion.

Archive of ground penetrating radar data collected during USGS field activity 13BIM01—Dauphin Island, Alabama, April 2013

USGS Publications Warehouse

Forde, Arnell S.; Smith, Christopher G.; Reynolds, Billy J.

2016-03-18

From April 13 to 20, 2013, scientists from the U.S. Geological Survey St. Petersburg Coastal and Marine Science Center (USGS-SPCMSC) conducted geophysical and sediment sampling surveys on Dauphin Island, Alabama, as part of Field Activity 13BIM01. The objectives of the study were to quantify inorganic and organic accretion rates in back-barrier and mainland marsh and estuarine environments. Various field and laboratory methods were used to achieve these objectives, including subsurface imaging using Ground Penetrating Radar (GPR), sediment sampling, lithologic and microfossil analyses, and geochronology techniques to produce barrier island stratigraphic cross sections to help interpret the recent (last 2000 years) geologic evolution of the island.This data series report is an archive of GPR and associated Global Positioning System (GPS) data collected in April 2013 from Dauphin Island and adjacent barrier-island environments. In addition to GPR data, marsh core and vibracore data were also collected collected but are not reported (or included) in the current report. Data products, including elevation-corrected subsurface profile images of the processed GPR data, unprocessed digital GPR trace data, post-processed GPS data, Geographic Information System (GIS) files and accompanying Federal Geographic Data Committee (FGDC) metadata, can be downloaded from the Data Downloads page.

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

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.

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.

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

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.

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.

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.

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.

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

NASA Astrophysics Data System (ADS)

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

2016-04-01

This work aims at disseminating the ongoing research activities and third-year results of the COST (European COoperation in Science and Technology) Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar." About 350 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, Colombia, Egypt, Hong Kong, Jordan, Israel, Philippines, Russia, Rwanda, Ukraine, and United States of America. In September 2014, TU1208 has been recognised 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. For more information on COST Action TU1208, please visit www.GPRadar.eu and www.cost.eu. Acknowledgement The Authors wish to thank COST, for funding the COST Action TU1208 "Civil engineering applications of Ground Penetrating Radar."

GPR survey, as one of the best geophysical methods for social and industrial needs

NASA Astrophysics Data System (ADS)

Chernov, Anatolii

2016-04-01

This paper is about ways and methods of applying non-invasive geophysical method - Ground penetrating radar (GPR) survey in different spheres of science, industry, social life and culture. Author would like to show that geological methods could be widely used for solving great variety of industrial, human safety and other problems. In that article, we take GPR survey as an example of such useful geophysical methods. It is a fact that investigation of near surface underground medium is important process, which influence on development of different spheres of science and social life: investigation of near surface geology (layering, spreading of rock types, identification of voids, etc.), hydrogeology (depth to water horizons, their thickness), preparation step for construction of roads and buildings (civil geology, engineering geology), investigation of cultural heritage (burial places, building remains,...), ecological investigations (land slides, variation in underground water level, etc.), glaciology. These tasks can be solved by geological methods, but as usual, geophysical survey takes a lot of time and energy (especially electric current and resistivity methods, seismic survey). Author claims that GPR survey can be performed faster than other geophysical surveys and results of GPR survey are informative enough to make proper conclusions. Some problems even cannot be solved without GPR. For example, identification of burial place (one of author's research objects): results of magnetic and electric resistivity tomography survey do not contain enough information to identify burial place, but according to anomalies on GPR survey radarograms, presence of burial place can be proven. Identification of voids and non-magnetic objects also hardly can be done by another non-invasive geophysics surveys and GPR is applicable for that purpose. GPR can be applied for monitoring of dangerous processes in geological medium under roads, buildings, parks and other places of human activity. Monitoring of such hazards as landslides, underground erosion, variation in ground water level can help prevent dangerous processes with destructive consequences, which can result in peoples' injuries and even death. Moreover, GPR can be used in other spheres of life, where investigation of hidden (under or behind conductive for electromagnetic wave material) objects is needed: rescue operations (finding of people after natural and human-made disasters under snow, under debris of building material); military purpose (security systems, identification of people presence through walls, doors, ground etc.). Author work on algorithms (first of all for VIY GPRs (http://viy.ua/)), which will help more precisely find objects of interest on radarograms and even solve inverse problem of geophysics. According to information in that article, geophysical methods can be widely used to solve great variety of tasks and help to investigate humans' past (researches of cultural heritage) and provide information to create safe and comfortable future (preventing of natural hazards and better planning of construction).

The Use of Ground Penetrating Radar to Exploring Sedimentary Ore In North-Central Saudi Arabia

NASA Astrophysics Data System (ADS)

Almutairi, Yasir; Almutair, Muteb

2015-04-01

Ground Penetrating Radar (GPR) is a non-destructive geophysical method that provides a continuous subsurface profile, without drilling. This geophysical technique has great potential in delineating the extension of bauxites ore in north-central Saudi Arabia. Bauxite is from types sedimentary ores. This study aim to evaluate the effectiveness of Ground Penetrating Radar (GPR) to illustrate the subsurface feature of the Bauxite deposits at some selected mining areas north-central Saudi Arabia. Bauxite is a heterogeneous material that consists of complex metals such as alumina and aluminum. An efficient and cost-effect exploration method for bauxite mine in Saudi Arabia is required. Ground penetrating radar (GPR) measurements have been carrying out along outcrop in order to assess the potential of GPR data for imaging and characterising different lithological facies. To do so, we have tested different antenna frequencies to acquire the electromagnetic signals along a 90 m profile using the IDS system. This system equipped with a 25 MHz antenna that allows investigating the Bauxite layer at shallow depths where the clay layers may existed. Therefore, the 25 MHz frequency antenna has been used in this study insure better resolution of the subsurface and to get more penetration to image the Bauxite layer. After the GPR data acquisition, this data must be processed in order to be more easily visualized and interpreted. Data processing was done using Reflex 6.0 software. A series of tests were carried out in frequency filtering on a sample of radar sections, which was considered to better represent the entire set of data. Our results indicated that the GPR profiling has a very good agreement for mapping the bauxite layer depth at range of 7 m to 11 m. This study has emphasized that the high-resolution GPR method is the robust and cost-effect technique to map the Bauxite layer. The exploration of Bauxite resource using the GPR technique could reduce the number of holes to be strategically placed in the most promising zones.

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.

Detecting and characterizing unroofed caves by ground penetrating radar

NASA Astrophysics Data System (ADS)

Čeru, Teja; Šegina, Ela; Knez, Martin; Benac, Čedomir; Gosar, Andrej

2018-02-01

The bare karst surface in the southeastern part of Krk Island (Croatia) is characterized by different surface karst features, such as valley-like shallow linear depressions and partially or fully sediment-filled depressions of various shapes and sizes. They were noticed due to locally increased thickness of sediment and enhanced vegetation but had not yet been systematically studied and defined. Considering only the geometry of the investigated surface features and the rare traces of cave environments detected by field surveys, it was unclear which processes (surface karstification and/or speleogenesis) contributed most to their formation. The low-frequency ground penetrating radar (GPR) method using a special 50 MHz RTA antenna was applied to study and describe these karst features. Three study sites were chosen and 5 km of GPR profiles were positioned to include various surface features. The results obtained from the GPR investigation lead to the following conclusions: (1) an increased thickness of sediment was detected in all the investigated depressions indicating their considerable depth; (2) areas between different depressions expressed as attenuated zones in GPR images reveal their interconnection; (3) transitions between surface and underground features are characterized by a collapsed passage visible in the GPR data; and (4) an underground continuation of surface valley-like depressions was detected, proving the speleogenetic origin of such features. Subsurface information obtained using GPR indicates that the valley-like depressions, irregular depressions completely or partially filled with sediment, and some dolines are associated with a nearly 4 km-long unroofed cave and developed as a result of karst denudation. In the regional context, these results suggest long-lasting karstification processes in the area, in contrast to the pre-karstic fluvial phase previously assumed to have occurred here. This research is the first application of the GPR method to survey unroofed caves worldwide and the first detailed study of such karst features in Croatia. The low-frequency GPR proved to be an efficient method not only for detecting underground continuations but also for distinguishing and identifying surface features and transition zones between surface and subsurface segments of unroofed caves and can therefore be used for recognizing similar geomorphological features.

Electromagnetic modelling, inversion and data-processing techniques for GPR: ongoing activities in Working Group 3 of COST Action TU1208

NASA Astrophysics Data System (ADS)

Pajewski, Lara; Giannopoulos, Antonis; van der Kruk, Jan

2015-04-01

This work aims at presenting the ongoing research activities carried out in Working Group 3 (WG3) 'EM 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). 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. WG3 is structured in four Projects. Project 3.1 deals with 'Electromagnetic modelling for GPR applications.' Project 3.2 is concerned with 'Inversion and imaging techniques for GPR applications.' The topic of Project 3.3 is the 'Development of intrinsic models for describing near-field antenna effects, including antenna-medium coupling, for improved radar data processing using full-wave inversion.' Project 3.4 focuses on 'Advanced GPR data-processing algorithms.' Electromagnetic modeling tools that are being developed and improved include the Finite-Difference Time-Domain (FDTD) technique and the spectral domain Cylindrical-Wave Approach (CWA). One of the well-known freeware and versatile FDTD simulators is GprMax that enables an improved realistic representation of the soil/material hosting the sought structures and of the GPR antennas. Here, input/output tools are being developed to ease the definition of scenarios and the visualisation of numerical results. The CWA expresses the field scattered by subsurface two-dimensional targets with arbitrary cross-section as a sum of cylindrical waves. In this way, the interaction is taken into account of multiple scattered fields within the medium hosting the sought targets. Recently, the method has been extended to deal with through-the-wall scenarios. One of the inversion techniques currently being improved is Full-Waveform Inversion (FWI) for on-ground, off-ground, and crosshole GPR configurations. In contrast to conventional inversion tools which are often based on approximations and use only part of the available data, FWI uses the complete measured data and detailed modeling tools to obtain an improved estimation of medium properties. During the first year of the Action, information was collected and shared about state-of-the-art of the available modelling, imaging, inversion, and data-processing methods. Advancements achieved by WG3 Members were presented during the TU1208 Second General Meeting (April 30 - May 2, 2014, Vienna, Austria) and the 15th International Conference on Ground Penetrating Radar (June 30 - July 4, 2014, Brussels, Belgium). Currently, a database of numerical and experimental GPR responses from natural and manmade structures is being designed. A geometrical and physical description of the scenarios, together with the available synthetic and experimental data, will be at the disposal of the scientific community. Researchers will thus have a further opportunity of testing and validating, against reliable data, their electromagnetic forward- and inverse-scattering techniques, imaging methods and data-processing algorithms. The motivation to start this database came out during TU1208 meetings and takes inspiration by successful past initiatives carried out in different areas, as the Ipswich and Fresnel databases in the field of free-space electromagnetic scattering, and the Marmousi database in seismic science. Acknowledgement The Authors thank COST, for funding the Action TU1208 'Civil Engineering Applications of Ground Penetrating Radar.'

A Comparative Investigation of the Combined Effects of Pre-Processing, Wavelength Selection, and Regression Methods on Near-Infrared Calibration Model Performance.

PubMed

Wan, Jian; Chen, Yi-Chieh; Morris, A Julian; Thennadil, Suresh N

2017-07-01

Near-infrared (NIR) spectroscopy is being widely used in various fields ranging from pharmaceutics to the food industry for analyzing chemical and physical properties of the substances concerned. Its advantages over other analytical techniques include available physical interpretation of spectral data, nondestructive nature and high speed of measurements, and little or no need for sample preparation. The successful application of NIR spectroscopy relies on three main aspects: pre-processing of spectral data to eliminate nonlinear variations due to temperature, light scattering effects and many others, selection of those wavelengths that contribute useful information, and identification of suitable calibration models using linear/nonlinear regression . Several methods have been developed for each of these three aspects and many comparative studies of different methods exist for an individual aspect or some combinations. However, there is still a lack of comparative studies for the interactions among these three aspects, which can shed light on what role each aspect plays in the calibration and how to combine various methods of each aspect together to obtain the best calibration model. This paper aims to provide such a comparative study based on four benchmark data sets using three typical pre-processing methods, namely, orthogonal signal correction (OSC), extended multiplicative signal correction (EMSC) and optical path-length estimation and correction (OPLEC); two existing wavelength selection methods, namely, stepwise forward selection (SFS) and genetic algorithm optimization combined with partial least squares regression for spectral data (GAPLSSP); four popular regression methods, namely, partial least squares (PLS), least absolute shrinkage and selection operator (LASSO), least squares support vector machine (LS-SVM), and Gaussian process regression (GPR). The comparative study indicates that, in general, pre-processing of spectral data can play a significant role in the calibration while wavelength selection plays a marginal role and the combination of certain pre-processing, wavelength selection, and nonlinear regression methods can achieve superior performance over traditional linear regression-based calibration.

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

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.

Improving ground-penetrating radar data in sedimentary rocks using deterministic deconvolution

USGS Publications Warehouse

Xia, J.; Franseen, E.K.; Miller, R.D.; Weis, T.V.; Byrnes, A.P.

2003-01-01

Resolution is key to confidently identifying unique geologic features using ground-penetrating radar (GPR) data. Source wavelet "ringing" (related to bandwidth) in a GPR section limits resolution because of wavelet interference, and can smear reflections in time and/or space. The resultant potential for misinterpretation limits the usefulness of GPR. Deconvolution offers the ability to compress the source wavelet and improve temporal resolution. Unlike statistical deconvolution, deterministic deconvolution is mathematically simple and stable while providing the highest possible resolution because it uses the source wavelet unique to the specific radar equipment. Source wavelets generated in, transmitted through and acquired from air allow successful application of deterministic approaches to wavelet suppression. We demonstrate the validity of using a source wavelet acquired in air as the operator for deterministic deconvolution in a field application using "400-MHz" antennas at a quarry site characterized by interbedded carbonates with shale partings. We collected GPR data on a bench adjacent to cleanly exposed quarry faces in which we placed conductive rods to provide conclusive groundtruth for this approach to deconvolution. The best deconvolution results, which are confirmed by the conductive rods for the 400-MHz antenna tests, were observed for wavelets acquired when the transmitter and receiver were separated by 0.3 m. Applying deterministic deconvolution to GPR data collected in sedimentary strata at our study site resulted in an improvement in resolution (50%) and improved spatial location (0.10-0.15 m) of geologic features compared to the same data processed without deterministic deconvolution. The effectiveness of deterministic deconvolution for increased resolution and spatial accuracy of specific geologic features is further demonstrated by comparing results of deconvolved data with nondeconvolved data acquired along a 30-m transect immediately adjacent to a fresh quarry face. The results at this site support using deterministic deconvolution, which incorporates the GPR instrument's unique source wavelet, as a standard part of routine GPR data processing. ?? 2003 Elsevier B.V. All rights reserved.

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.

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

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.

Capabilities of seismic and georadar 2D/3D imaging of shallow subsurface of transport route using the Seismobile system

NASA Astrophysics Data System (ADS)

Pilecki, Zenon; Isakow, Zbigniew; Czarny, Rafał; Pilecka, Elżbieta; Harba, Paulina; Barnaś, Maciej

2017-08-01

In this work, the capabilities of the Seismobile system for shallow subsurface imaging of transport routes, such as roads, railways, and airport runways, in different geological conditions were presented. The Seismobile system combines the advantages of seismic profiling using landstreamer and georadar (GPR) profiling. It consists of up to four seismic measuring lines and carriage with a suspended GPR antenna. Shallow subsurface recognition may be achieved to a maximum width of 10.5 m for a distance of 3.5 m between the measurement lines. GPR measurement is performed in the axis of the construction. Seismobile allows the measurement time, labour and costs to be reduced due to easy technique of its installation, remote data transmission from geophones to accompanying measuring modules, automated location of the system based on GPS and a highly automated method of seismic wave excitation. In this paper, the results of field tests carried out in different geological conditions were presented. The methodologies of acquisition, processing and interpretation of seismic and GPR measurements were broadly described. Seismograms and its spectrum registered by Seismobile system were compared to the ones registered by Geode seismograph of Geometrix. Seismic data processing and interpretation software allows for the obtaining of 2D/3D models of P- and S-wave velocities. Combined seismic and GPR results achieved sufficient imaging of shallow subsurface to a depth of over a dozen metres. The obtained geophysical information correlated with geological information from the boreholes with good quality. The results of performed tests proved the efficiency of the Seismobile system in seismic and GPR imaging of a shallow subsurface of transport routes under compound conditions.

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.

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.

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.

Nondestructive Evaluation of Concrete Bridge Decks with Automated Acoustic Scanning System and Ground Penetrating Radar.

PubMed

Sun, Hongbin; Pashoutani, Sepehr; Zhu, Jinying

2018-06-16

Delamanintions and reinforcement corrosion are two common problems in concrete bridge decks. No single nondestructive testing method (NDT) is able to provide comprehensive characterization of these defects. In this work, two NDT methods, acoustic scanning and Ground Penetrating Radar (GPR), were used to image a straight concrete bridge deck and a curved intersection ramp bridge. An acoustic scanning system has been developed for rapid delamination mapping. The system consists of metal-ball excitation sources, air-coupled sensors, and a GPS positioning system. The acoustic scanning results are presented as a two-dimensional image that is based on the energy map in the frequency range of 0.5⁻5 kHz. The GPR scanning results are expressed as the GPR signal attenuation map to characterize concrete deterioration and reinforcement corrosion. Signal processing algorithms for both methods are discussed. Delamination maps from the acoustic scanning are compared with deterioration maps from the GPR scanning on both bridges. The results demonstrate that combining the acoustic and GPR scanning results will provide a complementary and comprehensive evaluation of concrete bridge decks.

Continuity of Permian Mengkareng formation through GPR interpretation in Merangin Geopark

NASA Astrophysics Data System (ADS)

Hanif, F.; Syahputra, R.; Kristyanto, T. H. W.; Tempessy, A. S.; Rokhmatuloh

2017-07-01

The Permian Mengkarang Formation was a part of the continental margin (Gondwana Land) which separated in the Devon Period. In this period, Gondwana Land experienced glaciation at the Paleo South Pole. However, the fossils found in Mengkarang Formation were tropical flora, had made the Merangin to be certified as one of the national geoparks. It also shows that the geological process (stratigraphy and tectonic) in the Merangin has occurred before the Indonesian archipelago was formed: namely the Permian to Triassic period. Ground Penetrating Radar (GPR) was chosen as an effective geophysical method to study shallow subsurface geology. GPR and seismic reflection method have the same common principle to identify the facies and sub-sequence stratigraphy but they are different in implementation. Therefore, this study aims to deliver the vertical continuity of the Permian Mengkarang Formation in high resolution unit. The GPR result showing the subsurface image is based on dielectric of the rock layers. The GPR sections show the absence of the unconformity delivered in the intercalation between mudstone, sandstone, and tuff. Thus, it can be concluded that the Permian Mengkareng Formation continues up to 20 m depth.

Lauric Acid Stimulates Mammary Gland Development of Pubertal Mice through Activation of GPR84 and PI3K/Akt Signaling Pathway.

PubMed

Meng, Yingying; Zhang, Jing; Zhang, Fenglin; Ai, Wei; Zhu, Xiaotong; Shu, Gang; Wang, Lina; Gao, Ping; Xi, Qianyun; Zhang, Yongliang; Liang, Xingwei; Jiang, Qingyan; Wang, Songbo

2017-01-11

It has been demonstrated that dietary fat affects pubertal mammary gland development. However, the role of lauric acid (LA) in this process remains unclear. Thus, this study aimed to investigate the effects of LA on mammary gland development in pubertal mice and to explore the underlying mechanism. In vitro, 100 μM LA significantly promoted proliferation of mouse mammary epithelial cell line HC11 by regulating expression of proliferative markers (cyclin D1/3, p21, PCNA). Meanwhile, LA activated the G protein-coupled receptor 84 (GPR84) and PI3K/Akt signaling pathway. In agreement, dietary 1% LA enhanced mammary duct development, increased the expression of GPR84 and cyclin D1, and activated PI3K/Akt in mammary gland of pubertal mice. Furthermore, knockdown of GPR84 or inhibition of PI3K/Akt totally abolished the promotion of HC11 proliferation induced by LA. These results showed that LA stimulated mammary gland development of pubertal mice through activation of GPR84 and PI3K/Akt signaling pathway.

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.

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.

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

Distributed Prognostic Health Management with Gaussian Process Regression

NASA Technical Reports Server (NTRS)

Saha, Sankalita; Saha, Bhaskar; Saxena, Abhinav; Goebel, Kai Frank

2010-01-01

Distributed prognostics architecture design is an enabling step for efficient implementation of health management systems. A major challenge encountered in such design is formulation of optimal distributed prognostics algorithms. In this paper. we present a distributed GPR based prognostics algorithm whose target platform is a wireless sensor network. In addition to challenges encountered in a distributed implementation, a wireless network poses constraints on communication patterns, thereby making the problem more challenging. The prognostics application that was used to demonstrate our new algorithms is battery prognostics. In order to present trade-offs within different prognostic approaches, we present comparison with the distributed implementation of a particle filter based prognostics for the same battery data.

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."

Inverse scattering and GPR data processing: an Introduction

NASA Astrophysics Data System (ADS)

Persico, Raffaele

2014-05-01

Inverse scattering and GPR data processing: an Introduction Raffaele Persico This abstract is meant to propose a brief overview of the book "Introduction to Ground Penetrating Radar: Inverse scattering and data processing", edited by Wiley Press (ISBN 9781118305003). The reason why I propose this contribution is the fact that, in spite of the large relevant literature, to the best of my knowledge it is not very common to find a text entirely devoted to the physical-mathematical aspects (a part of them, of course) of GPR data processing. Also due to this, probably a sort of gap between the GPR practice and the underlying theory has been created, and indeed we can meet practitioners convinced that the quality of the achieved results is indefinitely improvable by making narrower the spatial step of the data, or that it is desirable to have extremely directive antennas because this would improve the resolution. In order to provide a work hopefully able to address these and other aspects and hopefully able to give a contribution to the correction of these imprecise beliefs, a dealing from the beginning has been proposed, i.e. a sequential, relatively plane, and as much as possible self consistent, dealing starting from the Maxwell's equations and reaching the most commonly exploited migration formulas and linear inversion algorithms, both within a 2D and a 3D framework. This follows the didactic aim to provide to the reader an insight about what can be reasonably achieved and what should be reasonably done in the field and during the processing phase in order to achieve satisfying results. In particular, the reader will be hopefully made aware not only of the mathematical passages, but also of the involved approximations, the needed assumptions and the physical limits of the final algorithms. The results have been also back-upped with numerical exercises and with some experimental tests, all of which conceived on purpose for this text, and some questions with the relative answers have been inserted at the end of many chapters. On the other hand, it seemed also well advised to stress the fact that, within a GPR prospecting, the main involved parameters (especially the propagation velocity of the electromagnetic waves in the soil) and the same useful datum, i.e. "the scattered field", in most cases have to be worked out from the same GPR data. In particular, usually we don't have the possibility to measure apart the "incident field" and then retrieve the scattered field by means of an immediate subtraction operation. Indeed, these aspects are an intrinsic part of the GPR data processing, and should not left out from a text on this topic. In the end, GPR data processing has its own specificities within the larger framework of the inverse scattering problems, and the book has tried to put into evidence this fact too. Finally, even if this text is not focused on electronics, it was important to account for the fact that there are two categories of GPR systems, namely those working in time domain and those working in frequency domain. This implies some consequences in terms of the parametric choices in order to gather and process correctly the data, which has been devoted some attention too. The main aim of the book is to resume and gather together things mostly already known, but usually spread within different texts and contexts, often dealt with different approaches and expressed, let say, with different languages. The book is mainly thought of for Ph.D. students, students of master courses and university students at their last year in geophysics end engineering, but it is accessible to any GPR user with some minimal basis (i.e. at university level) on electromagnetism. Some small research work has been performed too, as e.g. with regard to the calculation in closed form of the Hermitian images for stepped frequency systems, or with respect to the introduction of the effective maximum view angle, or in order to propose a new plane demonstration of the ill-posedness of the problem. Acknowledgement The author acknowledges COST for funding COST Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar", supporting this work.

Ground-penetrating radar and differential global positioning system data collected from Long Beach Island, New Jersey, April 2015

USGS Publications Warehouse

Zaremba, Nicholas J.; Smith, Kathryn E.L.; Bishop, James M.; Smith, Christopher G.

2016-08-04

Scientists from the United States Geological Survey, St. Petersburg Coastal and Marine Science Center, U.S. Geological Survey Pacific Coastal and Marine Science Center, and students from the University of Hawaii at Manoa collected sediment cores, sediment surface grab samples, ground-penetrating radar (GPR) and Differential Global Positioning System (DGPS) data from within the Edwin B. Forsythe National Wildlife Refuge–Holgate Unit located on the southern end of Long Beach Island, New Jersey, in April 2015 (FAN 2015-611-FA). The study’s objective was to identify washover deposits in the stratigraphic record to aid in understanding barrier island evolution. This report is an archive of GPR and DGPS data collected from Long Beach Island in 2015. 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.

Development of FWIGPR, an open-source package for full-waveform inversion of common-offset GPR data

NASA Astrophysics Data System (ADS)

Jazayeri, S.; Kruse, S.

2017-12-01

We introduce a package for full-waveform inversion (FWI) of Ground Penetrating Radar (GPR) data based on a combination of open-source programs. The FWI requires a good starting model, based on direct knowledge of field conditions or on traditional ray-based inversion methods. With a good starting model, the FWI can improve resolution of selected subsurface features. The package will be made available for general use in educational and research activities. The FWIGPR package consists of four main components: 3D to 2D data conversion, source wavelet estimation, forward modeling, and inversion. (These four components additionally require the development, by the user, of a good starting model.) A major challenge with GPR data is the unknown form of the waveform emitted by the transmitter held close to the ground surface. We apply a blind deconvolution method to estimate the source wavelet, based on a sparsity assumption about the reflectivity series of the subsurface model (Gholami and Sacchi 2012). The estimated wavelet is deconvolved from the data and the sparsest reflectivity series with fewest reflectors. The gprMax code (www.gprmax.com) is used as the forward modeling tool and the PEST parameter estimation package (www.pesthomepage.com) for the inversion. To reduce computation time, the field data are converted to an effective 2D equivalent, and the gprMax code can be run in 2D mode. In the first step, the user must create a good starting model of the data, presumably using ray-based methods. This estimated model will be introduced to the FWI process as an initial model. Next, the 3D data is converted to 2D, then the user estimates the source wavelet that best fits the observed data by sparsity assumption of the earth's response. Last, PEST runs gprMax with the initial model and calculates the misfit between the synthetic and observed data, and using an iterative algorithm calling gprMax several times ineach iteration, finds successive models that better fit the data. To gauge whether the iterative process has arrived at a local or global minima, the process can be repeated with a range of starting models. Tests have shown that this package can successfully improve estimates of selected subsurface model parameters for simple synthetic and real data. Ongoing research will focus on FWI of more complex scenarios.

Applications of ground penetrating radar (GPR) in bridge deck monitoring and assessment

NASA Astrophysics Data System (ADS)

Alani, Amir M.; Aboutalebi, Morteza; Kilic, Gokhan

2013-10-01

This paper presents the essence of two case studies by the authors on two major bridges in the UK. The first case study reports on the applications of GPR and associated work carried out on the Forth Road Bridge near Edinburgh, Scotland, with the main objective of identifying possible structural defects including damaged rebar and moisture ingress at specific locations of the bridge deck. The second case study focuses on a full assessment of the Pentagon Road Bridge, in Chatham, Kent, England with particular emphasis on the identification of possible defects including structural cracks within the deck structure and establishing the layout of the upper and lower rebar positions throughout the bridge. These studies present interesting results in terms of locations of rebar and an accurate estimate of concrete cover condition as well as reporting on a remarkable similarity in the processed data concerning areas affected by ingress of moisture within the deck structures of the two bridges under investigation. It is believed that this paper will be of particular interest to bridge engineers and structural engineering practitioners with enthusiasm for adopting non-destructive testing methods such as GPR in the health monitoring and assessment of bridge structures. The observed similarities in the processed data between the two reported case studies present an interesting concept within the general context of the interpretation of GPR data, with the potential for use in many other forthcoming cases. The paper also reports on the adopted method for the GPR survey with emphasis on difficulties and challenges encountered during the actual survey. The presented results benefit from advanced processing and presentation techniques.

GPR applications for geotechnical stability of transportation infrastructures

NASA Astrophysics Data System (ADS)

Benedetto, A.; Benedetto, F.; Tosti, F.

2012-09-01

Nowadays, severe meteorological events are always more frequent all over the world. This causes a strong impact on the environment such as numerous landslides, especially in rural areas. Rural roads are exposed to an increased risk for geotechnical instability. In the meantime, financial resources for maintenance are certainly decreased due to the international crisis and other different domestic factors. In this context, the best allocation of funds becomes a priority: efficiency and effectiveness of plans and actions are crucially requested. For this purpose, the correct localisation of geotechnically instable domains is strategic. In this paper, the use of Ground-Penetrating Radar (GPR) for geotechnical inspection of pavement and sub-pavement layers is proposed. A three-step protocol has been calibrated and validated to allocate efficiently and effectively the maintenance funds. In the first step, the instability is localised through an inspection at traffic speed using a 1-GHz GPR horn launched antenna. The productivity is generally about or over 300 Km/day. Data are processed offline by automatic procedures. In the second step, a GPR inspection restricted to the critical road sections is carried out using two coupled antennas. One antenna is used for top pavement inspection (1.6 GHz central frequency) and a second antenna (600 MHz central frequency) is used for sub-pavement structure diagnosis. Finally, GPR data are post-processed in the time and frequency domains to identify accurately the geometry of the instability. The case study shows the potentiality of this protocol applied to the rural roads exposed to a landslide.

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.

A Fusion of GPR- and LiDAR-Data for Surveying and Visualisation of Archaeological Structures - a case example of an archaeological site in Strettweg, District of Murtal, Austria

NASA Astrophysics Data System (ADS)

Kamp, Nicole; Russ, Stefan; Sass, Oliver; Tiefengraber, Georg; Tiefengraber, Susanne

2014-05-01

Strettweg is a small community located in Upper Styria in the valley of the Mur. It is seen as one of the most outstanding prehistoric archaeological sites in Austria. In 1851 the "Strettweger Opferwagen" (~ 600 BC) was discovered and is considered one of the most important Hallstatt find of Austria. More than 160 years later Airborne LiDAR and modern geophysical methods like Ground Penetrating Radar (GPR) and/or Magnetics have made it possible to find additional burial mounds and map the largest prehistoric settlement in the southeastern Alps (Falkenberg). These modern techniques have provided an auxiliary tool for the archaeological team's project "Hallstattzeitlicher Fürstensitz Falkenberg/Strettweg". GPR allows for a fast and non-invasive surveying of structures and anomalies of the sub surface, by using electromagnetic radiation in the microwave range. The active remote sensing technique LiDAR (Light Detection and Ranging, also known as Laser Scanning), measures the runtime of discrete light pulses in order to map objects and structures on the surface of the earth. In the course of this archaeological project GPR (Mala ProEx - 500 MHz antenna) and terrestrial LiDAR (Riegl LMS Z620) were applied by the University of Graz, Department of Geography and Regional Science, ALADYN work group (Univ.-Prof. Dr. Oliver Sass) to collect data of a testing site with 2500 m². The existence of archaeological structures was crucial for choosing this area. The area is surrounded by fine sediments, which originated by fluviatile transportation, making the remnants of these archaeological structures easier to detect. A standard GPR-processing-workflow does not allow for a 3-dimensional visualisation of the results and complicates the detection of archaeological structures. Unlike, LiDAR which does allow for a 3-dimensional visualisation. A fusion of both techniques, by using Python scripts and the software packages REFLEXW - Sandmeier Scientific Software and LASTools - rapidlasso, applies the advantages and specialities of LiDAR and GPR, and allows to get a high-resolution 3-dimensional pointcloud. This simplifies the identification of ancient man-made near-surface structures, which enables both in the field and lab quick post-processing. The LiDAR pointcloud, when coupled with the GPR pointcloud, act as reference datasets and improve the accuracy, classification, and filtering of the GPR data.

Orphan receptor GPR179 forms macromolecular complexes with components of metabotropic signaling cascade in retina ON-bipolar neurons.

PubMed

Orlandi, Cesare; Cao, Yan; Martemyanov, Kirill A

2013-10-29

In the mammalian retina, synaptic transmission between light-excited rod photoreceptors and downstream ON-bipolar neurons is indispensable for dim vision, and disruption of this process leads to congenital stationary night blindness in human patients. The ON-bipolar neurons use the metabotropic signaling cascade, initiated by the mGluR6 receptor, to generate depolarizing responses to light-induced changes in neurotransmitter glutamate release from the photoreceptor axonal terminals. Evidence for the identity of the components involved in transducing these signals is growing rapidly. Recently, the orphan receptor, GPR179, a member of the G protein-coupled receptor (GPCR) superfamily, has been shown to be indispensable for the synaptic responses of ON-bipolar cells. In our study, we investigated the interaction of GPR179 with principle components of the signal transduction cascade. We used immunoprecipitation and proximity ligation assays in transfected cells and native retinas to characterize the protein-protein interactions involving GPR179. The influence of cascade components on GPR179 localization was examined through immunohistochemical staining of the retinas from genetic mouse models. We demonstrated that, in mouse retinas, GPR179 forms physical complexes with the main components of the metabotropic cascade, recruiting mGluR6, TRPM1, and the RGS proteins. Elimination of mGluR6 or RGS proteins, but not TRPM1, detrimentally affects postsynaptic targeting or GPR179 expression. These observations suggest that the mGluR6 signaling cascade is scaffolded as a macromolecular complex in which the interactions between the components ensure the optimal spatiotemporal characteristics of signal transduction.

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...

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).

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.

GPR investigation to allocate the archaeological remains in Mut temple, Luxor, Upper Egypt

NASA Astrophysics Data System (ADS)

Atya, M. A.; AL Khateeb, S. O.; Ahmed, S. B.; Musa, M. F.; Gaballa, M.; Abbas, A. M.; Shaaban, F. F.; Hafez, M. A.

2012-06-01

GPR investigation has been conducted on Mut temple; to the south portion of Al-Karnak temple at the eastern bank of Luxor city. Within the survey, the GPR SIR system-10A has been used connected to 100/500 MHz antenna. The present work is oriented to allocate the buried Archaeological ruins at the site, and also to evaluate the archaeological significance of the artifacts in concern to the hydro-situation. The survey is composed of three data sets; the first set (A) includes three GPR profiles located inside the temple palisade at the western bank of the holy lake, the second set (B) includes four profiles distributed on the yard between Mute and Al Karnak temples, and the third set (C) includes three profiles oriented to study the EW Sphinx Avenue front of Mute temple. The measured GPR data has been processed and visualized in different ways to show the infra-content of the artifacts in the buried subsurface of the temple. Furthermore, intensive mutual work and discussion with the local inspectorate at Luxor about the results would lead to detect the zones of possible findings and, as much as possible, to define their identities. A series of sectional GPR records, time slices, maps, and 3D graphs are introduced to represent the remains of Mut temple and its infrastructure.

The Orphan G Protein-coupled Receptor Gpr175 (Tpra40) Enhances Hedgehog Signaling by Modulating cAMP Levels.

PubMed

Singh, Jaskirat; Wen, Xiaohui; Scales, Suzie J

2015-12-04

The Hedgehog (Hh) signaling pathway plays an essential role in vertebrate embryonic tissue patterning of many developing organs. Signaling occurs predominantly in primary cilia and is initiated by the entry of the G protein-coupled receptor (GPCR)-like protein Smoothened into cilia and culminates in gene transcription via the Gli family of transcription factors upon their nuclear entry. Here we identify an orphan GPCR, Gpr175 (also known as Tpra1 or Tpra40: transmembrane protein, adipocyte associated 1 or of 40 kDa), which also localizes to primary cilia upon Hh stimulation and positively regulates Hh signaling. Interaction experiments place Gpr175 at the level of PKA and upstream of the Gαi component of heterotrimeric G proteins, which itself localizes to cilia and can modulate Hh signaling. Gpr175 or Gαi1 depletion leads to increases in cellular cAMP levels and in Gli3 processing into its repressor form. Thus we propose that Gpr175 coupled to Gαi1 normally functions to inhibit the production of cAMP by adenylyl cyclase upon Hh stimulation, thus maximizing signaling by turning off PKA activity and hence Gli3 repressor formation. Taken together our data suggest that Gpr175 is a novel positive regulator of the Hh signaling pathway. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

GPR monitoring for non-uniform infiltration through a high permeable gravel layer in the test sand box

NASA Astrophysics Data System (ADS)

Kuroda, Seiichiro; Ishii, Nobuyuki; Morii, Toshihiro

2017-04-01

Recently capillary barriers have been known as a method to protect subsurface regions against infiltration from soil surface. It has essentially non-uniform structure of permeability or soil physical property. To identify the function of the capillary barrier, the site-characterization technique for non-uniform soil moisture distribution and infiltration process is needed. We built a sand box in which a thin high-permeable gravel layer was embedded and conducted a infiltration test, including non-uniform flow of soil water induced by capillary barrier effects. We monitored this process by various types of GPR measurements, including time-lapsed soundings with multi-frequency antenna and transmission measurements like one using cross-borehole radar. Finally we will discuss the applicability of GPR for monitoring the phenomena around the capillary barrier of soil. This work has partially supported by JSPS Grant-in-aid Scientific Research program, No.16H02580.

Investigation of the detection of shallow tunnels using electromagnetic and seismic waves

NASA Astrophysics Data System (ADS)

Counts, Tegan; Larson, Gregg; Gürbüz, Ali Cafer; McClellan, James H.; Scott, Waymond R., Jr.

2007-04-01

Multimodal detection of subsurface targets such as tunnels, pipes, reinforcement bars, and structures has been investigated using both ground-penetrating radar (GPR) and seismic sensors with signal processing techniques to enhance localization capabilities. Both systems have been tested in bi-static configurations but the GPR has been expanded to a multi-static configuration for improved performance. The use of two compatible sensors that sense different phenomena (GPR detects changes in electrical properties while the seismic system measures mechanical properties) increases the overall system's effectiveness in a wider range of soils and conditions. Two experimental scenarios have been investigated in a laboratory model with nearly homogeneous sand. Images formed from the raw data have been enhanced using beamforming inversion techniques and Hough Transform techniques to specifically address the detection of linear targets. The processed data clearly indicate the locations of the buried targets of various sizes at a range of depths.

Effectiveness of a 'Global Postural Reeducation' program for persistent Low Back Pain: a non-randomized controlled trial

PubMed Central

2010-01-01

Background The aim of this non-randomized controlled trial was to evaluate the effectiveness of a Global Postural Reeducation (GPR) program as compared to a Stabilization Exercise (SE) program in subjects with persistent low back pain (LBP) at short- and mid-term follow-up (ie. 3 and 6 months). Methods According to inclusion and exclusion criteria, 100 patients with a primary complaint of persistent LBP were enrolled in the study: 50 were allocated to the GPR group and 50 to the SE group. Primary outcome measures were Roland and Morris Disability Questionnaire (RMDQ) and Oswestry Disability Index (ODI). Secondary outcome measures were lumbar Visual Analogue Scale (VAS) and Fingertip-to-floor test (FFT). Data were collected at baseline and at 3/6 months by health care professionals unaware of the study. An intention to treat approach was used to analyze participants according to the group to which they were originally assigned. Results Of the 100 patients initially included in the study, 78 patients completed the study: 42 in the GPR group and 36 in the SE group. At baseline, the two groups did not differ significantly with respect to gender, age, BMI and outcome measures. Comparing the differences between groups at short- and mid-term follow-up, the GPR group revealed a significant reduction (from baseline) in all outcome measures with respect to the SE group. The ordered logistic regression model showed an increased likelihood of definitive improvement (reduction from baseline of at least 30% in RMDQ and VAS scores) for the GPR group compared to the SE group (OR 3.9, 95% CI 2.7 to 5.7). Conclusions Our findings suggest that a GPR intervention in subjects with persistent LBP induces a greater improvement on pain and disability as compared to a SE program. These results must be confirmed by further studies with higher methodological standards, including randomization, larger sample size, longer follow-up and subgrouping of the LBP subjects. Trial registration NCT00789204 PMID:21162726

Polymorphisms in Genes Involved in the NF-κB Signalling Pathway Are Associated with Bone Mineral Density, Geometry and Turnover in Men

PubMed Central

Roshandel, Delnaz; Thomson, Wendy; Pye, Stephen R.; Boonen, Steven; Borghs, Herman; Vanderschueren, Dirk; Huhtaniemi, Ilpo T.; Adams, Judith E.; Ward, Kate A.; Bartfai, Gyorgy; Casanueva, Felipe F.; Finn, Joseph D.; Forti, Gianni; Giwercman, Aleksander; Han, Thang S.; Kula, Krzysztof; Lean, Michael E.; Pendleton, Neil; Punab, Margus; Wu, Frederick C.

2011-01-01

Introduction In this study, we aimed to investigate the association between single nucleotide polymorphisms (SNPs) within two genes involved in the NF-κB cascade (GPR177 and MAP3K14) and bone mineral density (BMD) assessed at different skeletal sites, radial geometric parameters and bone turnover. Methods Ten GPR177 SNPs previously associated with BMD with genome-wide significance and twelve tag SNPs (r2≥0.8) within MAP3K14 (±10 kb) were genotyped in 2359 men aged 40–79 years recruited from 8 centres for participation in the European Male Aging Study (EMAS). Measurement of bone turnover markers (PINP and CTX-I) in the serum and quantitative ultrasound (QUS) at the calcaneus were performed in all centres. Dual energy X-ray absorptiometry (DXA), at the lumbar spine and hip, and peripheral quantitative computed tomography (pQCT), at the distal and midshaft radius, were performed in a subsample (2 centres). Linear regression was used to test for association between the SNPs and bone measures under an additive genetic model adjusting for study centre. Results We validated the associations between SNPs in GPR177 and BMDa previously reported and also observed evidence of pleiotrophic effects on density and geometry. Rs2772300 in GPR177 was associated with increased total hip and LS BMDa, increased total and cortical vBMD at the radius and increased cortical area, thickness and stress strain index. We also found evidence of association with BMDa, vBMD, geometric parameters and CTX-I for SNPs in MAP3K14. None of the GPR177 and MAP3K14 SNPs were associated with calcaneal estimated BMD measured by QUS. Conclusion Our findings suggest that SNPs in GPR177 and MAP3K14 involved in the NF-κB signalling pathway influence bone mineral density, geometry and turnover in a population-based cohort of middle aged and elderly men. This adds to the understanding of the role of genetic variation in this pathway in determining bone health. PMID:22132199

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.

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

Visual Inspection of Water Leakage from Ground Penetrating Radar Radargram

NASA Astrophysics Data System (ADS)

Halimshah, N. N.; Yusup, A.; Mat Amin, Z.; Ghazalli, M. D.

2015-10-01

Water loss in town and suburban is currently a significant issue which reflect the performance of water supply management in Malaysia. Consequently, water supply distribution system has to be maintained in order to prevent shortage of water supply in an area. Various techniques for detecting a mains water leaks are available but mostly are time-consuming, disruptive and expensive. In this paper, the potential of Ground Penetrating Radar (GPR) as a non-destructive method to correctly and efficiently detect mains water leaks has been examined. Several experiments were designed and conducted to prove that GPR can be used as tool for water leakage detection. These include instrument validation test and soil compaction test to clarify the maximum dry density (MDD) of soil and simulation studies on water leakage at a test bed consisting of PVC pipe burying in sand to a depth of 40 cm. Data from GPR detection are processed using the Reflex 2D software. Identification of water leakage was visually inspected from the anomalies in the radargram based on GPR reflection coefficients. The results have ascertained the capability and effectiveness of the GPR in detecting water leakage which could help avoiding difficulties with other leak detection methods.

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.

Three-Dimensional Characterization of Buried Metallic Targets via a Tomographic Algorithm Applied to GPR Synthetic Data

NASA Astrophysics Data System (ADS)

Comite, Davide; Galli, Alessandro; Catapano, Ilaria; Soldovieri, Francesco; Pettinelli, Elena

2013-04-01

This work is focused on the three-dimensional (3-D) imaging of buried metallic targets achievable by processing GPR (ground penetrating radar) simulation data via a tomographic inversion algorithm. The direct scattering problem has been analysed by means of a recently-developed numerical setup based on an electromagnetic time-domain CAD tool (CST Microwave Studio), which enables us to efficiently explore different GPR scenarios of interest [1]. The investigated 3D domain considers here two media, representing, e.g., an air/soil environment in which variously-shaped metallic (PEC) scatterers can be buried. The GPR system is simulated with Tx/Rx antennas placed in a bistatic configuration at the soil interface. In the implementation, the characteristics of the antennas may suitably be chosen in terms of topology, offset, radiative features, frequency ranges, etc. Arbitrary time-domain waveforms can be used as the input GPR signal (e.g., a Gaussian-like pulse having the frequency spectrum in the microwave range). The gathered signal at the output port includes the backscattered wave from the objects to be reconstructed, and the relevant data may be displayed in canonical radargram forms [1]. The GPR system sweeps along one main rectilinear direction, and the scanning process is here repeated along different close parallel lines to acquire data for a full 3-D analysis. Starting from the processing of the synthetic GPR data, a microwave tomographic approach is used to tackle the imaging, which is based on the Kirchhoff approximation to linearize the inverse scattering problem [2]. The target reconstruction is given in terms of the amplitude of the 'object function' (normalized with respect to its maximum inside the 3-D investigation domain). The data of the scattered field are collected considering a multi-frequency step process inside the fixed range of the signal spectrum, under a multi-bistatic configuration where the Tx and Rx antennas are separated by an offset distance and move at the interface over rectilinear observation domains. Analyses have been performed for some canonical scatterer shapes (e.g., sphere and cylinder, cube and parallelepiped, cone and wedge) in order to specifically highlight the influence of all the three dimensions (length, depth, and width) in the reconstruction of the targets. The roles of both size and location of the objects are also addressed in terms of the probing signal wavelengths and of the antenna offset. The results show to what extent it is possible to achieve a correct spatial localization of the targets, in conjunction with a generally satisfactory prediction of their 3-D size and shape. It should anyway be noted that the tomographic reconstructions here manage challenging cases of non-penetrable objects with data gathered under a reflection configuration, hence most of the information achievable is expected relating to the upper illuminated parts of the reflectors that give rise to the main scattering effects. The limits in the identification of fine geometrical details are discussed further in connection with the critical aspects of GPR operation, which include the adopted detection configuration and the frequency spectrum of the employed signals. [1] G. Valerio, A. Galli, P. M. Barone, S. E. Lauro, E. Mattei, and E. Pettinelli, "GPR detectability of rocks in a Martian-like shallow subsoil: a numerical approach," Planet. Space Sci., Vol. 62, pp. 31-40, 2012. [2] R. Solimene, A. Buonanno, F. Soldovieri, and R. Pierri, "Physical optics imaging of 3D PEC objects: vector and multipolarized approaches," IEEE Trans. Geosci. Remote Sens., Vol. 48, pp. 1799-1808, Apr. 2010.

Ground penetrating radar for fracture mapping in underground hazardous waste disposal sites: A case study from an underground research tunnel, South Korea

NASA Astrophysics Data System (ADS)

Baek, Seung-Ho; Kim, Seung-Sep; Kwon, Jang-Soon; Um, Evan Schankee

2017-06-01

Secure disposal or storage of nuclear waste within stable geologic environments hinges on the effectiveness of artificial and natural radiation barriers. Fractures in the bedrock are viewed as the most likely passage for the transport of radioactive waste away from a disposal site. We utilize ground penetrating radar (GPR) to map fractures in the tunnel walls of an underground research tunnel at the Korea Atomic Energy Research Institute (KAERI). GPR experiments within the KAERI Underground Research Tunnel (KURT) were carried out by using 200 MHz, 500 MHz, and 1000 MHz antennas. By using the high-frequency antennas, we were able to identify small-scale fractures, which were previously unidentified during the tunnel excavation process. Then, through 3-D visualization of the grid survey data, we reconstructed the spatial distribution and interconnectivity of the multi-scale fractures within the wall. We found that a multi-frequency GPR approach provided more details of the complex fracture network, including deep structures. Furthermore, temporal changes in reflection polarity between the GPR surveys enabled us to infer the hydraulic characteristics of the discrete fracture network developed behind the surveyed wall. We hypothesized that the fractures exhibiting polarity change may be due to a combination of air-filled and mineralogical boundaries. Simulated GPR scans for the considered case were consistent with the observed GPR data. If our assumption is correct, the groundwater flow into these near-surface fractures may form the water-filled fractures along the existing air-filled ones and hence cause the changes in reflection polarity over the given time interval (i.e., 7 days). Our results show that the GPR survey is an efficient tool to determine fractures at various scales. Time-lapse GPR data may be essential to characterize the hydraulic behavior of discrete fracture networks in underground disposal facilities.

Molecular and functional interaction between GPR18 and cannabinoid CB2 G-protein-coupled receptors. Relevance in neurodegenerative diseases.

PubMed

Reyes-Resina, Irene; Navarro, Gemma; Aguinaga, David; Canela, Enric I; Schoeder, Clara T; Zaluski, Michal; Kiec-Kononowicz, Katarzyna; Saura, Carlos A; Müller, Christa E; Franco, Rafael

2018-06-02

GPR18, still considered an orphan receptor, may respond to endocannabinoids, whose canonical receptors are CB 1 and CB 2 . GPR18 and CB 2 receptors share a role in peripheral immune response regulation and are co-expressed in microglia, which are immunocompetent cells in the central nervous system (CNS). We aimed at identifying heteroreceptor complexes formed by GPR18 and CB 1 R or CB 2 R in resting and activated microglia. Receptor-receptor interaction was assessed using energy-transfer approaches, and receptor function by determining cAMP levels and ERK1/2 phosphorylation in heterologous cells and primary cultures of microglia. Heteroreceptor identification in primary cultures of microglia was achieved by in situ proximity ligation assays. Energy transfer results showed interaction of GPR18 with CB 2 R but not with CB 1 R. CB 2 -GPR18 heteroreceptor complexes displayed particular functional properties (heteromer prints) often consisting of negative cross-talk (activation of one receptor reduces signaling arising from the partner receptor) and cross-antagonism (the response of one of the receptors is blocked by a selective antagonist of the partner receptor). Activated microglia showed the heteromer print (negative cross-talk and bidirectional cross-antagonism) and increased expression of CB 2 R and GPR18. Due to the important role of CB 2 R in neuroprotection, we further investigated heteroreceptor occurrence in primary cultures of microglia from transgenic mice overexpressing human APP Sw,Ind , an Alzheimer's disease model. Microglial cells from transgenic mice showed the heteromer print and functional interactions that were similar to those found in cells from wild-type animals that were activated by treatment with lipopolysaccharide and interferon-ɤ. Our results show that GPR18 and its heteromers may play important roles in neurodegenerative processes. Copyright © 2018. Published by Elsevier Inc.

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.

Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets.

PubMed

Ulven, Trond

2012-01-01

The deorphanization of the free fatty acid (FFA) receptors FFA1 (GPR40), FFA2 (GPR43), FFA3 (GPR41), GPR84, and GPR120 has made clear that the body is capable of recognizing and responding directly to nonesterified fatty acid of virtually any chain length. Colonic fermentation of dietary fiber produces high concentrations of the short-chain fatty acids (SCFAs) acetate, propionate and butyrate, a process which is important to health. The phylogenetically related 7-transmembrane (7TM) receptors free fatty acid receptor 2 (FFA2) and FFA3 are activated by these SCFAs, and several lines of evidence indicate that FFA2 and FFA3 mediate beneficial effects associated with a fiber-rich diet, and that they may be of interest as targets for treatment of inflammatory and metabolic diseases. FFA2 is highly expressed on immune cells, in particular neutrophils, and several studies suggest that the receptor plays a role in diseases involving a dysfunctional neutrophil response, such as inflammatory bowel disease (IBD). Both FFA2 and FFA3 have been implicated in metabolic diseases such as type 2 diabetes and in regulation of appetite. More research is however required to clarify the potential of the receptors as drug targets and establish if activation or inhibition would be the preferred mode of action. The availability of potent and selective receptor modulators is a prerequisite for these studies. The few modulators of FFA2 or FFA3 that have been published hitherto in the peer-reviewed literature in general have properties that make them less than ideal as such tools, but published patent applications indicate that better tool compounds might soon become available which should enable studies critical to validate the receptors as new drug targets.

Two collateral problems in the framework of ground-penetrating radar data inversion: influence of the emitted waveform outline and radargram comparison.

NASA Astrophysics Data System (ADS)

Oliveira, Rui Jorge; Caldeira, Bento; Borges, José Fernando

2017-04-01

Obtain three-dimensional models of the physical properties of buried structures in the subsurface by inversion of GPR data is an appeal to Archaeology and a challenge to Geophysics. Along the research of solutions to resolve this issue stand out two major problems that need to be solved: 1) Establishment the basis of the computation that allows assign numerically in the synthetic radargrams, the physical conditions at which the GPR wave were generated; and 2) automatic comparison of the computed synthetic radargrams with the correspondent observed ones. The influence of the pulse shape in GPR data processing was a studied topic. The pulse outline emitted by GPR antennas was experimentally acquired and this information has been used in the deconvolution operation, carried out by iterative process, similarly the approach used in seismology to obtain the receiver functions. In order to establish the comparison between real and synthetic radargrams, were tested automatic image adjustment algorithms, which search the best fit between two radargramas and quantify their differences through the calculation of Normalized Root Mean Square Deviation (NRMSD). After the implementation of the last tests, the NRMSD between the synthetic and real data is about 19% (initially it was 29%). These procedures are essential to be able to perform an inversion of GPR data obtained in the field. Acknowledgment: This work is co-funded by the European Union through the European Regional Development Fund, included in the COMPETE 2020 (Operational Program Competitiveness and Internationalization) through the ICT project (UID/GEO/04683/2013) with the reference POCI-01-0145-FEDER-007690.

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.

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.

GPR Mapping of a Buried Paleolithic Landscape Near Kathu, South Africa

NASA Astrophysics Data System (ADS)

Papadimitrios, K. S.; Balduino-Sollaci, C.; Vaughn, S.; Edwards, S.; Bank, C. G.; Chazan, M.

2014-12-01

he Bestwood site located near Kathu, South Africa is a 30 Ha sand-filled valley where tens of thousands of artifacts (hand axes and stone tools) dating from 700Kya to 1Mya mark a previously inhabited Stone Age site. By running close to 10 km of GPR lines and two 20mX20m grids with a 200 MHz antenna we were effectively able to sample the subsurface of the area and thus recreate the paleolandscape. Raw radargrams were viewed and processed through the MATLAB and GPR-SLICE programs. Both the raw and processed radargrams showed a distinct boundary as the GPR was moved from gravel hill conditions to sandy valley conditions. This boundary was interpreted to be an interface in the subsurface between sand on top and gravel layers below. A sinuous, meandering depression within that boundary that progressed down valley was interpreted as a paleochannel incised into the local gravels. Within the 20mx20m grids two 1mx1m test pits were dug on the assumed banks of the paleochannel. The pits served both to ground truth the inferred transition from sand to gravel and to help define a precise velocity of radar propagation for the sand layer. Our results aid archaeologists in understanding the interactions of early humans with the local landscape.

Ground-penetrating radar: A tool for monitoring bridge scour

USGS Publications Warehouse

Anderson, N.L.; Ismael, A.M.; Thitimakorn, T.

2007-01-01

Ground-penetrating radar (GPR) data were acquired across shallow streams and/or drainage ditches at 10 bridge sites in Missouri by maneuvering the antennae across the surface of the water and riverbank from the bridge deck, manually or by boat. The acquired two-dimensional and three-dimensional data sets accurately image the channel bottom, demonstrating that the GPR tool can be used to estimate and/or monitor water depths in shallow fluvial environments. The study results demonstrate that the GPR tool is a safe and effective tool for measuring and/or monitoring scour in proximity to bridges. The technique can be used to safely monitor scour at assigned time intervals during peak flood stages, thereby enabling owners to take preventative action prior to potential failure. The GPR tool can also be used to investigate depositional and erosional patterns over time, thereby elucidating these processes on a local scale. In certain instances, in-filled scour features can also be imaged and mapped. This information may be critically important to those engaged in bridge design. GPR has advantages over other tools commonly employed for monitoring bridge scour (reflection seismic profiling, echo sounding, and electrical conductivity probing). The tool doesn't need to be coupled to the water, can be moved rapidly across (or above) the surface of a stream, and provides an accurate depth-structure model of the channel bottom and subchannel bottom sediments. The GPR profiles can be extended across emerged sand bars or onto the shore.

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.

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.

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.

Ground penetrating radar applied to rebar corrosion inspection

NASA Astrophysics Data System (ADS)

Eisenmann, David; Margetan, Frank; Chiou, Chien-Ping T.; Roberts, Ron; Wendt, Scott

2013-01-01

In this paper we investigate the use of ground penetrating radar (GPR) to detect corrosion-induced thinning of rebar in concrete bridge structures. We consider a simple pulse/echo amplitude-based inspection, positing that the backscattered response from a thinned rebar will be smaller than the similar response from a fully-intact rebar. Using a commercial 1600-MHz GPR system we demonstrate that, for laboratory specimens, backscattered amplitude measurements can detect a thinning loss of 50% in rebar diameter over a short length. GPR inspections on a highway bridge then identify several rebar with unexpectedly low amplitudes, possibly signaling thinning. To field a practical amplitude-based system for detecting thinned rebar, one must be able to quantify and assess the many factors that can potentially contribute to GPR signal amplitude variations. These include variability arising from the rebar itself (e.g., thinning) and from other factors (concrete properties, antenna orientation and liftoff, etc.). We report on early efforts to model the GPR instrument and the inspection process so as to assess such variability and to optimize inspections. This includes efforts to map the antenna radiation pattern, to predict how backscattered responses will vary with rebar size and location, and to assess detectability improvements via synthetic aperture focusing techniques (SAFT).

Ground-penetrating radar exploration for ancient monuments at the Valley of Mummies -Kilo 6, Bahariya Oasis, Egypt

NASA Astrophysics Data System (ADS)

Shaaban, Fathy A.; Abbas, Abbas M.; Atya, Magdy A.; Hafez, Mahfouz A.

2009-06-01

A Valley of Mummies was discovered recently by an Egyptian team at Bahariya Oasis, located about 380 km west of the pyramids. Four tombs were excavated, and inside them were found one hundred and five mummies (105), many of them beautifully gilded. These mummies, many sumptuously decorated with religious scenes, are the very best Roman-Period mummies ever found in Egypt. These remains are around 2000 years old, but they are in remarkable condition. A Ground-Penetrating Radar (GPR) had proved successful in detecting the cavities in resistive soil in which the mummies were found. The GPR survey conducted near the earlier-discovered tombs at Kilo-6 El-Bahariya to Farafra Oasis road is the focus of this paper. The GPR survey was conducted using the SIR-2000 attached to a 200 MHz monostatic antenna. The two areas to be surveyed were selected by the archaeologists in situ. Area one was 40 m × 40 m and Area two was 30 m × 15 m. A grid pattern survey in one direction; with one-meter profile spacing was done to both areas. In addition, a focusing survey was undertaken over the entire Area one. In addition, twenty long GPR profiles were conducted in an attempt to determine the outer, expected limits of the burial area. After the data acquisition, Reflex software was used for data processing and presentation. The final results of the radar survey: in the form of 2D radar records, time slices and 3D block diagrams; were used to guide the archaeologists during the excavation process. The excavation processes have been completed by the archaeologists, and many tombs and mummies were discovered. It is worthy to mention that, the excavations and location of tombs and cavities matched strongly with the GPR results.

Accounting for Hydrologic State in Ground-Penetrating Radar Classification Systems

DTIC Science & Technology

2014-04-22

water content as a result of infiltration processes. • Demonstrated that effective medium approximations (one-dimensional flow and ray theory...280 290 300 310 320 330 340 -5 0 5 10 15 20 (a) (b) (c) Page 8 of 32 Figure 6: a) Conceptual model of flow experiment and GPR rays showing... ray theory for GPR) for characterizing the hydrologic state of the subsurface under arbitrary water content conditions. Figure 7: Comparison of

Wideband radar for airborne minefield detection

NASA Astrophysics Data System (ADS)

Clark, William W.; Burns, Brian; Dorff, Gary; Plasky, Brian; Moussally, George; Soumekh, Mehrdad

2006-05-01

Ground Penetrating Radar (GPR) has been applied for several years to the problem of detecting both antipersonnel and anti-tank landmines. RDECOM CERDEC NVESD is developing an airborne wideband GPR sensor for the detection of minefields including surface and buried mines. In this paper, we describe the as-built system, data and image processing techniques to generate imagery, and current issues with this type of radar. Further, we will display images from a recent field test.

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

Reconstruction of Vertical Profile of Permittivity of Layered Media which is Probed Using Vertical Differential Antenna

NASA Astrophysics Data System (ADS)

Pochanin, Gennadiy P.; Poyedinchuk, Anatoliy Y.; Varianytsia-Roshchupkina, Liudmyla A.; Pochanina, Iryna Ye.

2016-04-01

Results of this research are intended to use at GPR investigations of layered media (for example, at roads' inspection) for the processing of collected data and reconstruction of dependence of permittivity on the depth. Recently, an antenna system with a vertical differential configuration of receiving module (Patent UA81652) for GPR was suggested and developed The main advantage of the differential antennas in comparison with bistatic antennas is a high electromagnetic decoupling between the transmitting and receiving modules. The new vertical differential configuration has an additional advantage because it allows collecting GPR data reflected by layered media without any losses of information about these layers [1] and, potentially, it is a more accurate instrument for the layers thickness measurements [2]. The developed antenna system is tested in practice with the GPR at asphalt thickness measurements [3] and shown an accuracy which is better than 0.5 cm. Since this antenna system is good for sounding from above the surface (air coupled technique), the mobile laboratory was equipped with the developed GPR [3]. In order to process big set of GPR data that collected during probing at long routes of the roads, for the data processing it was tested new algorithm of the inverse problem solution. It uses a fast algorithm for calculation of electromagnetic wave diffraction by non-uniform anisotropic layers [4]. The algorithm is based on constructing a special case solution to the Riccati equation for the Cauchy problem and enables a qualitative description of the wave diffraction by the electromagnetic structure of the type within a unitary framework. At this stage as initial data we used synthetic GPR data that were obtained as results of the FDTD simulation of the problem of UWB electromagnetic impulse diffraction on layered media. Differential and bistatic antenna configurations were tested at several different profiles of permittivity. Meanings of permittivity of each of layers were reconstructed successfully. Corresponding results are given in the presentation. Acknowledgement The authors acknowledge COST for funding Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar", supporting this work. References 1. L. Gurel, and U. Oguz, "Three-Dimensional FDTD modeling of a ground penetrating radar" IEEE Trans. Geosci. Remote Sensing, vol. 38, no. 4, pp. 1513-1521, 2000. 2. L. Varianytsia-Roshchupkina, Pochanin G., Pochanina I., Masalov Proc. of the 8th Int. Workshop on Advanced Ground Penetrating Radar (IWAGPR 15), Florence, Italy, July 2015. 3. Pochanin, G. P., Ruban, V. P., Kholod, P. V., Shuba, A. A., Pochanin, A. G., Orlenko, A.A., Batrakov, D. O., and Batrakova, A. G. GPR for pavement monitoring., Journal of Radio Electronics. No.1. 2013, Moscow, http://jre.cplire.ru/alt/jan13/8/text.pdf. 4. A. V. Brovenko, P. N. Melezhik, A. Y. Poyedinchuk A numerical analytical method for solving problems of electromagnetic wave diffraction by non-uniform anisotropic layers. Radiophysics and Electronics, Vol.19, No. 4. 2014. pp.12-20.

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.

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.

Field Trial Results of a 14-channel GPR Integrated with a U.S. Program for 3-D Utility Mapping

NASA Astrophysics Data System (ADS)

Anspach, James H.

2013-04-01

Existing underground utilities continue to be a leading cause of highway construction delay claims in the United States. Although 80-90% of existing utilities can typically be discovered and mapped using a wide range of geophysical tools, there is a recognizable need to improve the process. Existing shortcomings to the utility mapping process include a lack of viable depth attributes, long field occupation times, low experience level of the field technicians, and separate survey / geophysics functions. The U.S. National Academies and its Transportation Research Board recently concluded a project on alleviating the existing utility mapping shortcomings through the development of enhanced GPR. An existing commercial 400MHz 14-channel towed array was enhanced with positioning and interpretation hardware and software over a 3-year US 2M program. Field trials for effectiveness were conducted in a city suburb commercialized environment where the relative permittivity values averaged 9.4. The effectiveness of enhanced GPR was compared to traditional utility mapping techniques (Single Channel GPR, FDEM, Acoustic, Sondes, Gradiometric Magnetometers) during the project. The project area utilities included natural gas, water, electric, telephone, cable, storm, sanitary, traffic control, and several unknown function lines. Depths for these utilities were mostly unknown. 81% of known (from records and field appurtenance visual observation) utilities were detected via traditional geophysical means. These traditional geophysical means also detected 14% additional and previously "unknown" utilities. The enhanced GPR detected approximately 40% of the known and unknown utilities, and found an additional 6% of utilities that were previously undetected. These additional utilities were subsequently determined to be small diameter abandoned water and gas systems in very poor and broken condition. Although it did well with metallic water and gas lines, communication and electric utilities were mostly undetectable. Through a ground-truthing program of test holes to expose utilities, the depth values derived from the enhanced GPR were fairly consistent and within 15 cm of actual depth. The incomplete underground picture determined by the enhanced GPR reinforces previous studies that show that the mapping of existing underground utilities is a multi-tool effort that takes highly trained and skilled field technicians and data interpreters. The addition of a new GPR tool is valuable in determining continuous depth profiles of imaged utilities. A second and significant benefit is the interpretation of other geotechnical data that benefit project designers. This might include showing geometry, location, intensity, and depths of either areas of anomalies, or of known structures, such as paving thickness, substrate thickness, voids, water table, soil lenses, boulders, bedrock, and so forth. The Florida Department of Transportation has decided to take advantage of this new technology and has entered into an experimental contract with Cardno TBE to incorporate several enhanced GPR arrays with traditional utility detection tools. The goal of this contract will be to provide a 3-D model of existing underground utilities for use in automated construction. The GPR 3-D data model will be melded with conventional subsurface utility engineering and mapping practices and will be required to follow the ASCE 38 standard for utility data reliability.

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

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...

Does Nonlinear Modeling Play a Role in Plasmid Bioprocess Monitoring Using Fourier Transform Infrared Spectra?

PubMed

Lopes, Marta B; Calado, Cecília R C; Figueiredo, Mário A T; Bioucas-Dias, José M

2017-06-01

The monitoring of biopharmaceutical products using Fourier transform infrared (FT-IR) spectroscopy relies on calibration techniques involving the acquisition of spectra of bioprocess samples along the process. The most commonly used method for that purpose is partial least squares (PLS) regression, under the assumption that a linear model is valid. Despite being successful in the presence of small nonlinearities, linear methods may fail in the presence of strong nonlinearities. This paper studies the potential usefulness of nonlinear regression methods for predicting, from in situ near-infrared (NIR) and mid-infrared (MIR) spectra acquired in high-throughput mode, biomass and plasmid concentrations in Escherichia coli DH5-α cultures producing the plasmid model pVAX-LacZ. The linear methods PLS and ridge regression (RR) are compared with their kernel (nonlinear) versions, kPLS and kRR, as well as with the (also nonlinear) relevance vector machine (RVM) and Gaussian process regression (GPR). For the systems studied, RR provided better predictive performances compared to the remaining methods. Moreover, the results point to further investigation based on larger data sets whenever differences in predictive accuracy between a linear method and its kernelized version could not be found. The use of nonlinear methods, however, shall be judged regarding the additional computational cost required to tune their additional parameters, especially when the less computationally demanding linear methods herein studied are able to successfully monitor the variables under study.

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.

Applying 2-D resistivity imaging and ground penetrating radar (GPR) methods to identify infiltration of water in the ground surface

NASA Astrophysics Data System (ADS)

Yusof, Azim Hilmy Mohamad; Azman, Muhamad Iqbal Mubarak Faharul; Ismail, Nur Azwin; Ismail, Noer El Hidayah

2017-07-01

Infiltration of water into the soil mostly happens in area near to the ocean or area where rain occurred frequently. This paper explains about the water infiltration process that occurred vertically and horizontally at the subsurface layer. Infiltration act as an indicator of the soil's ability to allow water movement into and through the soil profile. This research takes place at Teluk Kumbar, Pulau Pinang, area that located near to the sea. Thus, infiltration process occurs actively. The study area consists of unconsolidated marine clay, sand and gravel deposits. Furthermore, the methods used for this research is 2-D Resistivity Imaging by using Wenner-Schlumberger array with 2.5 m minimum electrode spacing, and the second method is Ground Penetrating Radar (GPR) with antenna frequency of 250MHz. 2-D Resistivity Imaging is used to investigate the subsurface layer of the soil. Other than that, this method can also be used to investigate the water infiltration that happens horizontally. GPR is used to investigate shallow subsurface layer and to investigate the water infiltration from above. The results of inversion model of 2-D Resistivity Imaging shows that the subsurface layer at distance of 0 m to 20 m are suspected to be salt water intrusion zone due to the resistivity value of 0 Ω.m to 1 Ω.m. As for the radargram results from the GPR, the anomaly seems to be blurry and unclear, and EM waves signal can only penetrate up to 1.5 m depth. This feature shows that the subsurface layer is saturated with salt water. Applying 2-D resistivity imaging and GPR method were implemented to each other in identifying infiltration of water in the ground surface.

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).

Multiscale Geophysical Characterization of Weathering Fronts Along a Climate and Vegetation Gradient in Chile

NASA Astrophysics Data System (ADS)

Dal Bo, I.; Klotzsche, A.; Schaller, M.; Ehlers, T. A.; Vereecken, H.; Van Der Kruk, J.

2017-12-01

Understanding how weathering processes act is non-trivial. Direct methods are spatially restricted, time consuming, and expensive. Here, we show how to upscale and extend the point-scale layering information from dug pits deploying a multi-scale geophysical approach. Many studies have recently shown the potential of geophysics in bridging the gap between scales, although limited to specific environments. We applied Electromagnetic Induction (EMI), Ground Penetrating Radar (GPR), and Electrical Resistivity Tomography (ERT) in four study areas separated by 1600 km in the Chilean Coastal Cordillera, and ranging from the arid Atacama Desert in the north and temperate forests in the south. The main goals were to understand how the soil profile and the weathering front vary: 1) from north to south along these gradients, 2) in north- and south-facing hillslopes, and 3) within a single hillslope. We measured at the large-scale (EMI), at the profile scale (EMI, ERT, and GPR), and at the point-scale (GPR). The total length of the EMI, GPR and ERT measurements was 28.95 km, 3.67 km, and 0.27 km. GPR wide angle reflection and refraction measurements were the link between ground-truth data and geophysics. The low electrical conductivity (EC) regime limited the applicability of the EMI and ERT. However, still relative patterns of apparent electrical conductivity (ECa) from EMI could be used. Generally, ECa increased moving uphill and from north to south. Due to the low EC values in the study areas, GPR could image several reflections up to 8 m depth partially confirmed by the pit layering. Thicker layers on GPR profiles were present going from north to south and in the bottom-mid part of the hillslopes, as confirmed by ground-truth data. The main recognizable feature in the GPR profiles was the transition between B and C horizon. Here, hyperbolic-shape signatures were observed that probably were related to the presence of heterogeneities. The soil pits showed deeper layers in more vegetated south-facing hillslopes, which could be correlated with increased signal penetration and reflection depths in the GPR profiles. Soil depths and their interaction with biota in soil-mantled landscapes will be better characterized by combining geophysics with more environmental parameters within the interdisciplinary EarthShape project.

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

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.

Zinc Supplementation, via GPR39, Upregulates PKCζ to Protect Intestinal Barrier Integrity in Caco-2 Cells Challenged by Salmonella enterica Serovar Typhimurium.

PubMed

Shao, Yu-Xin; Lei, Zhao; Wolf, Patricia G; Gao, Yan; Guo, Yu-Ming; Zhang, Bing-Kun

2017-07-01

Background: Zinc has been shown to improve intestinal barrier function against Salmonella enterica serovar Typhimurium ( S. typhimurium ) infection, but the mechanisms involved in this process remain undefined. Objective: We aimed to explore the roles of G protein-coupled receptor (GPR)39 and protein kinase Cζ (PKCζ) in the regulation by zinc of intestinal barrier function. Methods: A Transwell Caco-2 monolayer was pretreated with 0, 50, or 100 μM Zn and then incubated with S. typhimurium for 0-6 h. Afterward, cells silenced by the small interfering RNA for GPR39 or PKCζ were pretreated with 100 μM Zn and incubated with S. typhimurium for 3 h. Finally, transepithelial electrical resistance (TEER), permeability, tight junction (TJ) proteins, and signaling molecules GPR39 and PKCζ were measured. Results: Compared with controls, S. typhimurium decreased TEER by 62.3-96.2% at 4-6 h ( P < 0.001), increased ( P < 0.001) permeability at 6 h, and downregulated ( P < 0.05) TJ protein zonula occludens (ZO)-1 and occludin by 104-123%, as well as Toll-like receptor 2 and PKCζ by 35.1% and 75.2%, respectively. Compared with S. typhimurium- challenged cells, 50 and 100 μM Zn improved TEER by 26.3-60.9% at 4-6 h ( P < 0.001) and decreased ( P < 0.001) permeability and bacterial invasion at 6 h. A total of 100 μM Zn increased ZO-1, occludin, GPR39, and PKCζ 0.72- to 1.34-fold ( P < 0.05); however, 50 μM Zn did not affect ZO-1 or occludin ( P > 0.1). Silencing GPR39 decreased ( P < 0.05) zinc-activated PKCζ and blocked ( P < 0.05) the promotion of zinc on epithelial integrity. Furthermore, silencing PKCζ counteracted the protective effect of zinc on epithelial integrity but did not inhibit GPR39 ( P = 0.138). Conclusion: We demonstrated that zinc upregulates PKCζ by activating GPR39 to enhance the abundance of ZO-1, thereby improving epithelial integrity in S. typhimurium- infected Caco-2 cells. © 2017 American Society for Nutrition.

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.

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

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.

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.

GPR30: a novel therapeutic target in estrogen-related disease.

PubMed

Prossnitz, Eric R; Sklar, Larry A; Oprea, Tudor I; Arterburn, Jeffrey B

2008-03-01

Estrogen is a crucial hormone in human physiology that regulates a multitude of biological processes. It is also an important target in many diseases such as cancer and skeletal, neurological and immunological conditions. The actions of estrogen have traditionally been ascribed to one of two closely related classical nuclear hormone receptors, ERalpha and ERbeta, which are best characterized for regulating gene expression. Recent studies have revealed the contribution of a novel estrogen receptor GPR30, which belongs to the family of seven-transmembrane G-protein-coupled receptors, to many of the rapid biological responses to estrogen. Many drugs, such as tamoxifen and fulvestrant, which seem to selectively inhibit the activities of the classical estrogen receptors, are in widespread clinical use. However, recent results indicate that these same drugs activate multiple cellular-signaling pathways via GPR30. Unraveling the pharmacological profiles and specificities of ERalpha, ERbeta and GPR30 will be vital for understanding not only the physiological roles of each receptor but also for the development of the next generation of receptor-specific drugs.

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.

A user friendly interface for microwave tomography enhanced GPR surveys

NASA Astrophysics Data System (ADS)

Catapano, Ilaria; Affinito, Antonio; Soldovieri, Francesco

2013-04-01

Ground Penetrating Radar (GPR) systems are nowadays widely used in civil applications among which structural monitoring is one of the most critical issues due to its importance in terms of risks prevents and cost effective management of the structure itself. Despite GPR systems are assessed devices, there is a continuous interest towards their optimization, which involves both hardware and software aspects, with the common final goal to achieve accurate and highly informative images while keeping as low as possible difficulties and times involved in on field surveys. As far as data processing is concerned, one of the key aims is the development of imaging approaches capable of providing images easily interpretable by not expert users while keeping feasible the requirements in terms of computational resources. To satisfy this request or at least improve the reconstruction capabilities of data processing tools actually available in commercial GPR systems, microwave tomographic approaches based on the Born approximation have been developed and tested in several practical conditions, such as civil and archeological investigations, sub-service monitoring, security surveys and so on [1-3]. However, the adoption of these approaches is subjected to the involvement of expert workers, which have to be capable of properly managing the gathered data and their processing, which involves the solution of a linear inverse scattering problem. In order to overcome this drawback, aim of this contribution is to present an end-user friendly software interface that makes possible a simple management of the microwave tomographic approaches. In particular, the proposed interface allows us to upload both synthetic and experimental data sets saved in .txt, .dt and .dt1 formats, to perform all the steps needed to obtain tomographic images and to display raw-radargrams, intermediate and final results. By means of the interface, the users can apply time gating, back-ground removal or both to extract from the gathered data the meaningful signal, they can process the full set of the gathered A-scans or select a their portion as well as they can choose to account for an arbitrary time window inside that adopted during the measurement stage. Finally, the interface allows us to perform the imaging according to two different tomographic approaches, both modeling the scattering phenomenon according to the Born approximation and looking for cylindrical objects of arbitrary cross section (2D geometry) probed by an incident field polarized along the invariance axis (scalar case). One approach is based on the assumption that the scattering phenomenon arises in a homogeneous medium, while the second one accounts for the presence of a flat air-medium interface. 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] R. Persico, F. Soldovieri, E. Utsi, "Microwave tomography for processing of GPR data at Ballachulish, J. Geophys. and Eng., vol.7, pp.164-173, 2010. [3] 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.

Cloning, Phylogenetic Analysis, and Distribution of Free Fatty Acid Receptor GPR120 Expression along the Gastrointestinal Tract of Housing versus Grazing Kid Goats.

PubMed

Ran, Tao; Li, Hengzhi; Liu, Yong; Zhou, Chuanshe; Tang, Shaoxun; Han, Xuefeng; Wang, Min; He, Zhixiong; Kang, Jinghe; Yan, Qiongxian; Tan, Zhiliang; Beauchemin, Karen A

2016-03-23

G-protein-coupled receptor 120 (GPR120) is reported as a long-chain fatty acid (LCFA) receptor that elicits free fatty acid (FFA) regulation on metabolism homeostasis. The study aimed to clone the gpr120 gene of goats (g-GPR120) and subsequently investigate phylogenetic analysis and tissue distribution throughout the digestive tracts of kid goats, as well as the effect of housing versus grazing (H vs G) feeding systems on GPR120 expression. Partial coding sequence (CDS) of g-GPR120 was cloned and submitted to NCBI (accession no. KU161270 ). Phylogenetic analysis revealed that g-GPR120 shared higher homology in both mRNA and amino acid sequences for ruminants than nonruminants. Immunochemistry, real-time PCR, and Western blot analysis showed that g-GPR120 was expressed throughout the digestive tracts of goats. The expression of g-GPR120 was affected by feeding system and age, with greater expression of g-GPR120 in the G group. It was concluded that the g-GPR120-mediated LCFA chemosensing mechanism is widely present in the tongue and gastrointestinal tract of goats and that its expression can be affected by feeding system and age.

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

A ground penetrating radar investigation of a glacial-marine ice- contact delta, Pineo Ridge, eastern coastal Maine

USGS Publications Warehouse

Tary, A.K.; Duncan, M. FitzGerald; Weddle, T.K.

2007-01-01

In eastern coastal Maine, many flat-topped landforms, often identified as glacial-marine deltas, are cultivated for blueberry production. These agriculturally valuable features are not exploited for aggregate resources, severely limiting stratigraphic exposure. Coring is often forbidden; where permissible, coarse-grained surficial sediments make coring and sediment retrieval difficult. Ground penetrating radar (GPR) has become an invaluable tool in an ongoing study of the otherwise inaccessible subsurface morphology in this region and provides a means of detailing the large-scale sedimentary structures comprising these features. GPR studies allow us to reassess previous depositional interpretations and to develop alternative developmental models. The work presented here focuses on Pineo Ridge, a large, flat-topped ice-marginal glacial-marine delta complex with a strong linear trend and two distinct landform zones, informally termed East Pineo and West Pineo. Previous workers have described each zone separately due to local morphological variation. Our GPR work further substantiates this geomorphic differentiation. East Pineo developed as a series of deltaic lobes prograding southward from an ice-contact margin during the local marine highstand. GPR data do not suggest postdepositional modification by ice-margin re-advance. We suggest that West Pineo has a more complex, two-stage depositional history. The southern section of the feature consists of southward-prograding deltaic lobes deposited during retreat of the Laurentide ice margin, with later erosional modification during marine regression. The northern section of West Pineo formed as a series of northward-prograd- ing deltaic lobes as sediment-laden meltwater may have been diverted by the existing deposits of the southern section of West Pineo. ?? 2007 The Geological Society of America. All rights reserved.

Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets

PubMed Central

Ulven, Trond

2012-01-01

The deorphanization of the free fatty acid (FFA) receptors FFA1 (GPR40), FFA2 (GPR43), FFA3 (GPR41), GPR84, and GPR120 has made clear that the body is capable of recognizing and responding directly to nonesterified fatty acid of virtually any chain length. Colonic fermentation of dietary fiber produces high concentrations of the short-chain fatty acids (SCFAs) acetate, propionate and butyrate, a process which is important to health. The phylogenetically related 7-transmembrane (7TM) receptors free fatty acid receptor 2 (FFA2) and FFA3 are activated by these SCFAs, and several lines of evidence indicate that FFA2 and FFA3 mediate beneficial effects associated with a fiber-rich diet, and that they may be of interest as targets for treatment of inflammatory and metabolic diseases. FFA2 is highly expressed on immune cells, in particular neutrophils, and several studies suggest that the receptor plays a role in diseases involving a dysfunctional neutrophil response, such as inflammatory bowel disease (IBD). Both FFA2 and FFA3 have been implicated in metabolic diseases such as type 2 diabetes and in regulation of appetite. More research is however required to clarify the potential of the receptors as drug targets and establish if activation or inhibition would be the preferred mode of action. The availability of potent and selective receptor modulators is a prerequisite for these studies. The few modulators of FFA2 or FFA3 that have been published hitherto in the peer-reviewed literature in general have properties that make them less than ideal as such tools, but published patent applications indicate that better tool compounds might soon become available which should enable studies critical to validate the receptors as new drug targets. PMID:23060857

The potentialities of ground-penetrating radar in the engineering geology using the radars GROT-12 and GROT-12E

NASA Astrophysics Data System (ADS)

Volkomirskaya, Liudmila; Gulevich, Oxana; Musalev, Dmitri

2013-04-01

The potentialities of ground-penetrating radar in the engineering geology using the radars GROT-12 and GROT-12E L.B. Volkomirskaya(1,2), O.A. Gulevich(1,2), D.N. Musalev(3) 1. IZMIRAN, 142190, Russia, Moscow, Troitsk, Kalugskoe 4 2. ZAO Timer, 142190, Russia, Moscow, Troitsk, Lesnaya str. 4B 3. OAO Belgorchemprom, Republic of Belarus, Minsk, Masherov str. 17 The article presents the potentialities of ground-penetrating radar in the engineering geology on the basis of the latest modifications of the GPR "GROT": the low-frequency GPR GROT-12 and the high-frequency GPR GROT-12E. The article gives technical specifications of the GPRs GROT-12 and GROT-12E and their particular characteristics that define them from analogues. The solutions of direct problems of ground penetrating radar on the basis of Maxwell's equations in general formulation with given wide-band signal source are confronted to experimental data received from different fields of the engineering geology, for example: 1. To secure mining in salt mines the method was adapted to locate in the working layers the investigating boreholes, fault lines, borders of displacement and blowout of productive layers, as well as working pits without access. 2. To monitor the reinforced concrete structures of airport runways the technology was worked out to collect and process GPR data so as to locate communications under the runways and examine basement condition. 3. To carry out the reconstruction of buildings and pre-project engineering geological works the GPR shooting technology was improved to process the examinations of the bearing capacity of soils and to locate lost communications. 4. To perform ecological monitoring of abandoned mines the technology of the GPR data collecting and processing was developed to assess the conditions of stowage materials in mouths of destroyed vertical mine shafts, the location of inclined mine shafts, the determination of hollow spaces and thinning zones, the localization of ground and mining waters, as well as the state of dumps (spoil tips). The dependence was investigated between the resolution, the exploration depth and the characteristics of GPR: the power and pulse length of transmitter, the digit capacity and frequency of the receiver, the construction of antennas. The article includes examples of usage of GROT-12 and GROT-12E in research at the depth 100 m and deeper in the salt mines in Starobinsk deposit, in the Sheremetyevo airport in Moscow, in the mining fields of Kuznetsk Basin, Donets Basin and Australia. The article presents a study of the required characteristics of ground-penetrating radars considering the given parameters of the exploration depth and digit capacity.

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

Exploring the Martian Highlands using a Rover-Deployed Ground Penetrating Radar

NASA Technical Reports Server (NTRS)

Grant, J. A.; Schutz, A. E.; Campbell, B. A.

2001-01-01

The Martian highlands record a long and often complex history of geologic activity that has shaped the planet over time. Results of geologic mapping and new data from the Mars Global Surveyor spacecraft reveal layered surfaces created by multiple processes that are often mantled by eolian deposits. Knowledge of the near-surface stratigraphy as it relates to evolution of surface morphology will provide critical context for interpreting rover/lander remote sensing data and for defining the geologic setting of a highland lander. Rover-deployed ground penetrating radar (GPR) can directly measure the range and character of in situ radar properties, thereby helping to constrain near-surface geology and structure. As is the case for most remote sensing instruments, a GPR may not detect water unambiguously on Mars. Nevertheless, any local, near-surface occurrence of liquid water will lead to large, easily detected dielectric contrasts. Moreover, definition of stratigraphy and setting will help in evaluating the history of aqueous activity and where any water might occur and be accessible. GPR data can also be used to infer the degree of any post-depositional pedogenic alteration or weathering, thereby enabling assessment of pristine versus secondary morphology. Most importantly perhaps, GPR can provide critical context for other rover and orbital instruments/data sets. Hence, rover-deployment of a GPR deployment should enable 3-D mapping of local stratigraphy and could guide subsurface sampling.

Trichoderma G protein-coupled receptors: functional characterisation of a cAMP receptor-like protein from Trichoderma atroviride.

PubMed

Brunner, Kurt; Omann, Markus; Pucher, Marion E; Delic, Marizela; Lehner, Sylvia M; Domnanich, Patrick; Kratochwill, Klaus; Druzhinina, Irina; Denk, Dagmar; Zeilinger, Susanne

2008-12-01

Galpha subunits act to regulate vegetative growth, conidiation, and the mycoparasitic response in Trichoderma atroviride. To extend our knowledge on G protein signalling, we analysed G protein-coupled receptors (GPCRs). As the genome sequence of T. atroviride is not publicly available yet, we carried out an in silico exploration of the genome database of the close relative T. reesei. Twenty genes encoding putative GPCRs distributed over eight classes and additional 35 proteins similar to the Magnaporthe grisea PTH11 receptor were identified. Subsequently, four T. atroviride GPCR-encoding genes were isolated and affiliated to the cAMP receptor-like family by phylogenetic and topological analyses. All four genes showed lowest expression on glycerol and highest mRNA levels upon carbon starvation. Transcription of gpr3 and gpr4 responded to exogenously added cAMP and the shift from liquid to solid media. gpr3 mRNA levels also responded to the presence of fungal hyphae or cellulose membranes. Further characterisation of mutants bearing a gpr1-silencing construct revealed that Gpr1 is essential for vegetative growth, conidiation and conidial germination. Four genes encoding the first GPCRs described in Trichoderma were isolated and their expression characterized. At least one of these GPCRs is important for several cellular processes, supporting the fundamental role of G protein signalling in this fungus.

Soft sensor modeling based on variable partition ensemble method for nonlinear batch processes

NASA Astrophysics Data System (ADS)

Wang, Li; Chen, Xiangguang; Yang, Kai; Jin, Huaiping

2017-01-01

Batch processes are always characterized by nonlinear and system uncertain properties, therefore, the conventional single model may be ill-suited. A local learning strategy soft sensor based on variable partition ensemble method is developed for the quality prediction of nonlinear and non-Gaussian batch processes. A set of input variable sets are obtained by bootstrapping and PMI criterion. Then, multiple local GPR models are developed based on each local input variable set. When a new test data is coming, the posterior probability of each best performance local model is estimated based on Bayesian inference and used to combine these local GPR models to get the final prediction result. The proposed soft sensor is demonstrated by applying to an industrial fed-batch chlortetracycline fermentation process.

Subsurface Hydrologic Processes Revealed by Time-lapse GPR in Two Contrasting Soils in the Shale Hills CZO

NASA Astrophysics Data System (ADS)

Guo, L.; Lin, H.; Nyquist, J.; Toran, L.; Mount, G.

2017-12-01

Linking subsurface structures to their functions in determining hydrologic processes, such as soil moisture dynamics, subsurface flow patterns, and discharge behaviours, is a key to understanding and modelling hydrological systems. Geophysical techniques provide a non-invasive approach to investigate this form-function dualism of subsurface hydrology at the field scale, because they are effective in visualizing subsurface structure and monitoring the distribution of water. In this study, we used time-lapse ground-penetrating radar (GPR) to compare the hydrologic responses of two contrasting soils in the Shale Hills Critical Zone Observatory. By integrating time-lapse GPR with artificial water injection, we observed distinct flow patterns in the two soils: 1) in the deep Rushtown soil (over 1.5 m depth to bedrock) located in a concave hillslope, a lateral preferential flow network extending as far as 2 m downslope was identified above a less permeable layer and via a series of connected macropores; whereas 2) in the shallow Weikert soil ( 0.3 m depth to saprock) located in a planar hillslope, vertical infiltration into the permeable fractured shale dominated the flow field, while the development of lateral preferential flow along the hillslope was restrained. At the Weikert soil site, the addition of brilliant blue dye to the water injection followed by in situ excavation supported GPR interpretation that only limited lateral preferential flow formed along the soil-saprock interface. Moreover, seasonally repeated GPR surveys indicated different patterns of profile moisture distribution in the two soils that in comparison with the dry season, a dense layer within the BC horizon in the deep Rushtown soil prevented vertical infiltration in the wet season, leading to the accumulation of soil moisture above this layer; whereas, in the shallow Weikert soil, water infiltrated into saprock in wet seasons, building up water storage within the fractured bedrock (i.e., the rock moisture). Results of this study demonstrated the strong interplay between soil structures and subsurface hydrologic behaviors, and time-lapse GPR is an effective method to establish such a relationship under the field conditions.

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

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.

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

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.

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.

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.

Sedimentological and geophysical studies of clastic reservoir analogs: Methods, applications and developments of ground-penetrating radar for determination of reservoir geometries in near-surface settings. Final report

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

McMechan, G.A.; Soegaard, K.

1998-05-25

An integrated sedimentologic and GPR investigation has been carried out on a fluvial channel sandstone in the mid-Cretaceous Ferron Sandstone at Coyote Basin along the southwestern flank of the San Rafael Uplift in east-central Utah. This near-surface study, which covers a area of 40 {times} 16.5 meters to a depth of 15 meters, integrates detailed stratigraphic data from outcrop sections and facies maps with multi-frequency 3-D GPR surveys. The objectives of this investigation are two-fold: (1) to develop new ground-penetrating radar (GPR) technology for imaging shallow subsurface sandstone bodies, and (2) to construct an empirical three-dimensional sandstone reservoir model suitablemore » for hydrocarbon flow-simulation by imaging near-surface sandstone reservoir analogs with the use of GPR. The sedimentological data base consists of a geologic map of the survey area and a detailed facies map of the cliff face immediately adjacent to the survey area. Five vertical sections were measured along the cliff face adjacent to the survey area. In addition, four wells were cored within the survey area from which logs were recorded. In the sections and well logs primary sedimentary structures were documented along with textural information and permeability data. Gamma-ray profiles were also obtained for all sections and core logs. The sedimentologic and stratigraphic information serves as the basis from which much of the processing and interpretation of the GPR data was made. Three 3-D GPR data sets were collected over the survey area at frequencies of 50 MHZ, 100 MHZ, and 200 MHZ.« less

Proton receptor GPR68 expression in dendritic-cell-like S100β-positive cells of rat anterior pituitary gland: GPR68 induces interleukin-6 gene expression in extracellular acidification.

PubMed

Horiguchi, Kotaro; Higuchi, Masashi; Yoshida, Saishu; Nakakura, Takashi; Tateno, Kozue; Hasegawa, Rumi; Takigami, Shu; Ohsako, Shunji; Kato, Takako; Kato, Yukio

2014-11-01

S100β-positive cells, which do not express the classical pituitary hormones, appear to possess multifunctional properties and are assumed to be heterogeneous in the anterior pituitary gland. The presence of several protein markers has shown that S100β-positive cells are composed of populations such as stem/progenitor cells, epithelial cells, astrocytes and dendritic cells. Recently, we succeeded in separating S100β-positive cells into round-cell (dendritic-cell-like) and process-cell types. We also found the characteristic expression of anti-inflammatory factors (interleukin-6, Il-6) and membrane receptors (integrin β-6) in the round type. Here, we further investigate the function of the subpopulation of S100β-positive cells. Since IL-6 is also a paracrine factor that regulates hormone producing-cells, we examine whether a correlation exists among extracellular acid stress, IL-6 and hormone production by using primary cultures of anterior pituitary cells. Dendritic-cell-like S100β-positive cells notably expressed Gpr68 (proton receptor) and Il-6. Furthermore, the expression of Il-6 and proopiomelanocortin (Pomc) was up-regulated by extracellular acidification. The functional role of IL-6 and GPR68 in the gene expression of Pomc during extracellular acidification was also examined. Small interfering RNA for Il-6 up-regulated Pomc expression and that for Gpr68 reversed the down-regulation of Il-6 and up-regulated Pomc expression by extracellular acidification. Thus, S100β-positive dendritic-like cells can sense an increase in extracellular protons via GPR68 and respond by the production of IL-6 in order to suppress the up-regulation of Pomc expression.

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.

Application of GPR Method for Detection of Loose Zones in Flood Levee

NASA Astrophysics Data System (ADS)

Gołębiowski, Tomisław; Małysa, Tomasz

2018-02-01

In the paper the results of non-invasive georadar (GPR) surveys carried out for detection of loose zones located in the flood levee was presented. Terrain measurements were performed on the Vistula river flood levee in the village of Wawrzeńczyce near Cracow. In the investigation site, during the flood in 2010, leakages of levee were observed, so detection of inner water filtration paths was an important matter taking into account the stability of the levee during the next flood. GPR surveys had reconnaissance character, so they were carried out with the use of short-offset reflection profiling (SORP) technique and radargrams were subjected to standard signal processing. The results of surveys allowed to outline main loose zone in the levee which were the reason of leakages in 2010. Additionally gravel interbeddings in sand were detected which had an important influence, due to higher porosity of such zones, to water filtration inside of the levee. In the paper three solutions which allow to increase quality and resolution of radargrams were presented, i.e. changeable-polarisation surveys, advanced signal processing and DHA procedure.

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.

Using ground-penetrating radar and sidescan sonar to compare lake bottom geology in New England

NASA Astrophysics Data System (ADS)

Nesbitt, I. M.; Campbell, S. W.; Arcone, S. A.; Smith, S. M.

2017-12-01

Post-Laurentide Ice Sheet erosion and re-deposition has had a significant influence on the geomorphology of New England. Anthropogenic activities such as forestry, farming, and construction of infrastructure such as dams and associated lake reservoirs, has further contributed to near surface changes. Unfortunately, these surface dynamics are difficult to constrain, both in space and time. One analog that can be used to estimate erosion and deposition, lake basin sedimentation, is typically derived from lake bottom sediment core samples. Reliance on core records assumes that derived sedimentation rates are representative of the broader watershed, despite being only a single point measurement. Geophysical surveys suggest that this assumption can be highly erroneous and unrepresentative of an entire lake basin. Herein, we conducted ground-penetrating radar (GPR) and side-scan sonar (SSS) surveys of multiple lakes in Maine, New Hampshire, and Vermont which are representative of different basin types to estimate sedimentation rates since Laurentide retreat. Subsequent age constraints from cores on multiple GPR-imaged horizons could be used to refine estimates of sedimentation rate change caused by evolving physical, biological, and chemical processes that control erosion, transport, and re-deposition. This presentation will provide a summary of GPR and SSS data collection methods, assumptions and limitations, structural and surficial interpretations, and key findings from multiple lake basins in New England. Results show that GPR and SSS are efficient, cost effective, and relatively accurate tools for helping to constrain lake erosion and deposition processes.

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.

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.

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

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.

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.

Adapting Ground Penetrating Radar for Non-Destructive In-Situ Root and Tuber Assessment

NASA Astrophysics Data System (ADS)

Teare, B. L.; Hays, D. B.; Delgado, A.; Dobreva, I. D.; Bishop, M. P.; Lacey, R.; Huo, D.; Wang, X.

2017-12-01

Ground penetrating radar (GPR) is a rapidly evolving technology extensively used in geoscience, civil science, archeology, and military, and has become a novel application in agricultural systems. One promising application of GPR is for root and tuber detection and measurement. Current commercial GPR systems have been used for detection of large roots, but few studies have attempted to detect agronomic roots, and even fewer have attempted to measure and quantify the total root mass. The ability to monitor and measure root and tuber mass and architecture in an agricultural setting would have far-reaching effects. A few of these include the potential for breeding higher yielding root and tuber crops, rapid bulking roots, discovery of crops with greater carbon sequestration, discovery of plant varieties which have greater ability to stabilize slopes against erosion and slope failure, and drought tolerant varieties. Despite the possible benefits and the current maturity of GPR technology, several challenges remain in the attempt to optimize its use for root and tuber detection. These challenges center on three categories: spatial resolution, data processing, and field-deployable hardware configuration. This study is centered around tuber measurement and its objectives are to i) identify ideal antenna array configurations, frequency, and pulse density; ii) develop novel processing techniques which leverage powerful computer technologies to provide highly accurate measurements of detected features; and iii) develop a cart system which is appropriate for agricultural fields and non-destructive sampling. Already, a 2 GHz multiarray antenna has been identified as an optimal system for tuber detection. Software and processing algorithm development is ongoing, but has already shown improvement over current software offerings. Recent field activity suggest that carts should be width adjustable and sport independent suspension systems to maintain antenna orientation.

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.

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.

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

Integrating auxiliary data and geophysical techniques for the estimation of soil clay content using CHAID algorithm

NASA Astrophysics Data System (ADS)

Abbaszadeh Afshar, Farideh; Ayoubi, Shamsollah; Besalatpour, Ali Asghar; Khademi, Hossein; Castrignano, Annamaria

2016-03-01

This study was conducted to estimate soil clay content in two depths using geophysical techniques (Ground Penetration Radar-GPR and Electromagnetic Induction-EMI) and ancillary variables (remote sensing and topographic data) in an arid region of the southeastern Iran. GPR measurements were performed throughout ten transects of 100 m length with the line spacing of 10 m, and the EMI measurements were done every 10 m on the same transect in six sites. Ten soil cores were sampled randomly in each site and soil samples were taken from the depth of 0-20 and 20-40 cm, and then the clay fraction of each of sixty soil samples was measured in the laboratory. Clay content was predicted using three different sets of properties including geophysical data, ancillary data, and a combination of both as inputs to multiple linear regressions (MLR) and decision tree-based algorithm of Chi-Squared Automatic Interaction Detection (CHAID) models. The results of the CHAID and MLR models with all combined data showed that geophysical data were the most important variables for the prediction of clay content in two depths in the study area. The proposed MLR model, using the combined data, could explain only 0.44 and 0.31% of the total variability of clay content in 0-20 and 20-40 cm depths, respectively. Also, the coefficient of determination (R2) values for the clay content prediction, using the constructed CHAID model with the combined data, was 0.82 and 0.76 in 0-20 and 20-40 cm depths, respectively. CHAID models, therefore, showed a greater potential in predicting soil clay content from geophysical and ancillary data, while traditional regression methods (i.e. the MLR models) did not perform as well. Overall, the results may encourage researchers in using georeferenced GPR and EMI data as ancillary variables and CHAID algorithm to improve the estimation of soil clay content.

The Application of Depth Migration for Processing GPR Data

NASA Astrophysics Data System (ADS)

Hoai Trung, Dang; Van Giang, Nguyen; Thanh Van, Nguyen

2018-03-01

Migration methods play a significant role in processing ground penetrating radar data. Beside recovering the true image of subsurface structures from the prior designed velocity model and the raw GPR data, the migration algorithm could be an effective tool in bulding real environmental velocity model. In this paper, we have proposed one technique using energy diagram extracted from migrated data as a criterion of looking for the correct velocity. Split Step Fourier migration, a depth migration, is chosen for facing the challenge where the velocity varies laterally and vertically. Some results verified on field data on Vietnam show that migrated sections with calculated velocity from energy diagram have the best quality.

Sensor fusion approaches for EMI and GPR-based subsurface threat identification

NASA Astrophysics Data System (ADS)

Torrione, Peter; Morton, Kenneth, Jr.; Besaw, Lance E.

2011-06-01

Despite advances in both electromagnetic induction (EMI) and ground penetrating radar (GPR) sensing and related signal processing, neither sensor alone provides a perfect tool for detecting the myriad of possible buried objects that threaten the lives of Soldiers and civilians. However, while neither GPR nor EMI sensing alone can provide optimal detection across all target types, the two approaches are highly complementary. As a result, many landmine systems seek to make use of both sensing modalities simultaneously and fuse the results from both sensors to improve detection performance for targets with widely varying metal content and GPR responses. Despite this, little work has focused on large-scale comparisons of different approaches to sensor fusion and machine learning for combining data from these highly orthogonal phenomenologies. In this work we explore a wide array of pattern recognition techniques for algorithm development and sensor fusion. Results with the ARA Nemesis landmine detection system suggest that nonlinear and non-parametric classification algorithms provide significant performance benefits for single-sensor algorithm development, and that fusion of multiple algorithms can be performed satisfactorily using basic parametric approaches, such as logistic discriminant classification, for the targets under consideration in our data sets.

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.

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.

Attenuation of CXCR4 responses by CCL18 in acute lymphocytic leukemia B cells.

PubMed

Catusse, J; Wollner, S; Leick, M; Schröttner, P; Schraufstätter, I; Burger, M

2010-11-01

CCL18 and CXCL12 are homeostatic chemokines with high constitutive concentrations in serum. Elevated levels of CCL18 have been described in various diseases including childhood acute lymphocytic leukemia (ALL) but its functions remain poorly characterized. Its receptor has not been identified, but functional cellular responses like lymphocyte chemotaxis have been described. CXCL12 is a pivotal chemokine for hematopoiesis and B cell homing processes. We demonstrate that CCL18 interferes with CXCL12-mediated pre-B ALL cell activation. CXCL12-induced calcium mobilization, chemotaxis, pseudo-emperipolesis and cellular proliferation could be significantly reduced by CCL18 in pre-B ALL cell lines. The results could be observed in primary cells from patients suffering from pre-B ALL, but not in cells from patients suffering from common ALL. Direct effects of CCL18 on the receptor for CXCL12, CXCR4, could be excluded. Moreover, we found that CCL18 modulations of CXCL12-induced responses are mediated through the chemokine-like receptor GPR30. CCL18 bound to GPR30 expressing cells, and antibodies against GPR30 abolished this binding as well as CCL18-mediated functional effects. We also observed that, CCL18 interferes with the activation of GPR30 by previously identified ligands (17β-estradiol and chemical agonists). We therefore suggest that CCL18 is an important modulator of CXCR4-dependent responses in pre-B ALL cells via interactions with GPR30. © 2010 Wiley-Liss, Inc.

Artificial intelligence and signal processing for infrastructure assessment

NASA Astrophysics Data System (ADS)

Assaleh, Khaled; Shanableh, Tamer; Yehia, Sherif

2015-04-01

The Ground Penetrating Radar (GPR) is being recognized as an effective nondestructive evaluation technique to improve the inspection process. However, data interpretation and complexity of the results impose some limitations on the practicality of using this technique. This is mainly due to the need of a trained experienced person to interpret images obtained by the GPR system. In this paper, an algorithm to classify and assess the condition of infrastructures utilizing image processing and pattern recognition techniques is discussed. Features extracted form a dataset of images of defected and healthy slabs are used to train a computer vision based system while another dataset is used to evaluate the proposed algorithm. Initial results show that the proposed algorithm is able to detect the existence of defects with about 77% success rate.

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.

Inertial and GPS data integration for positioning and tracking of GPR

NASA Astrophysics Data System (ADS)

Chicarella, Simone; D'Alvano, Alessandro; Ferrara, Vincenzo; Frezza, Fabrizio; Pajewski, Lara

2015-04-01

Nowadays many applications and studies use a Global Positioning System (GPS) to integrate Ground-Penetrating Radar (GPR) data [1-2]. The aim is the production of detailed detection maps that are geo-referenced and superimposable on geographic maps themes. GPS provides data to determine static positioning, and to track the mobile detection system path on the land. A low-cost standard GPS, like GPS-622R by RF Solutions Ltd, allows accuracy around 2.5 m CEP (Circular Error Probability), and a maximum update rate of 10 Hz. These accuracy and update rate are satisfying values when we evaluate positioning datum, but they are unsuitable for precision tracking of a speedy-mobile GPR system. In order to determine the relative displacements with respect to an initial position on the territory, an Inertial Measurement Unit (IMU) can be used. Some inertial-system applications for GPR tracking have been presented in recent studies [3-4]. The integration of both GPS and IMU systems is the aim of our work, in order to increase GPR applicability, e.g. the case of a GPR mounted on an unmanned aerial vehicle for the detection of people buried under avalanches [5]. In this work, we will present the design, realization and experimental characterization of our electronic board that includes GPS-622R and AltIMU-10 v3 by Pololu. The latter comprises an inertial-measurement unit and an altimeter. In particular, the IMU adopts L3GD20 gyro and LSM303D accelerometer and magnetometer; the digital barometer LPS331AP provides data for altitude evaluation. The prototype of our system for GPR positioning and tracking is based on an Arduino microcontroller board. Acknowledgement This work benefited from networking activities carried out within the EU funded COST Action TU1208 'Civil Engineering Applications of Ground Penetrating Radar. ' References [1] M. Solla, X. Núñez-Nieto, M. Varela-González, J. Martínez-Sánchez, and P. Arias, 'GPR for Road Inspection: georeferencing and efficient approach to data processing and visualization,' Proceedings of 15th IEEE International Conference on Ground Penetrating Radar - GPR 2014, Brussels, Belgium, June 30 - July 4, 2014, pp. 913-918. [2] S. Urbini, L. Vittuari, and S. Gandolfi, 'GPR and GPS data integration: examples of application in Antarctica,' Annali di Geofisica, Vol. 44, No. 4, August 2001, pp. 687-702. [3] V. Prokhorenko, V. Ivashchuk, S. Korsun, and O. Dykovska, 'An Inertial Measurement Unit Application for a GPR Tracking and Positioning,' Proceedings of the 12th International Conference on Ground Penetrating Radar, June 15-19, 2008, Birmingham, UK, pp. 19-24. [4] M. Pasternak, W. Miluski, W. Czarnecki, and J. Pietrasinski, 'An optoelectronic-inertial system for handheld GPR positioning,' Proceedings of the 15th IEEE International Radar Symposium (IRS), Gdansk, Poland, June 16-18, 2014, pp. 1-4. [5] L. Crocco and V. Ferrara, 'A Review on Ground Penetrating Radar Technology for the Detection of Buried or Trapped Victims,' Proceedings of the IEEE 2nd International Workshop on Collaborations in Emergency Response and Disaster Management (ERDM 2014) as part of 2014 International Conference on Collaboration Technologies and Systems (CTS 2014) - Minneapolis (Minnesota, USA), May 19-23, 2014, pp. 535-540.

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.

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.

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.

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.

Geophysical characterization of peatlands using crosshole GPR full-waveform inversion: Case study from a bog in northwestern Germany

NASA Astrophysics Data System (ADS)

Schmäck, J.; Klotzsche, A.; Van Der Kruk, J.; Vereecken, H.; Bechtold, M.

2017-12-01

The characterization of peatlands is of particular interest, since areas with peat soils represent global hotspots for the exchange of greenhouse gases. Their effect on global warming depends on several parameters, like mean annual water level and land use. Models of greenhouse gas emissions and carbon accumulation in peatlands can be improved by including small-scale soil properties that e.g. act as gas traps and periodically release gases to the atmosphere during ebullition events. Ground penetrating radar (GPR) is well suited to non- or minimal invasively characterize and improve our understanding of dynamic processes that take place in the critical zone. It uses high frequency electromagnetic waves to image and characterize the dielectric permittivity and electrical conductivity of the critical zone, which can be related to hydrogeological properties like porosity, soil water content, salinity and clay content. In the last decade, the full-waveform inversion of crosshole GPR data has proved to be a powerful tool to improve the image resolution compared to standard ray-based methods. This approach was successfully applied to several different aquifers and was able to provide decimeter-scale resolution images including small-scale high contrast layers that can be related to zones of high porosity, zones of preferential flow or clay lenses. The comparison to independently measured e.g. logging data proved the reliability of the method. Here, for the first time crosshole GPR full-waveform inversion is used to image three peatland plots with different land use that are part of the "Ahlen-Falkenberger Moor peat bog complex" in northwestern Germany. The full-waveform inversion of the acquired data returned higher resolution images than standard ray-based GPR methods, and, is able to improve our understanding of subsurface structures. The comparison of the different plots is expected to provide new insights into gas content and gas trapping structures across different land uses. Additionally, season-related changes of peatland soil properties are investigated. The crosshole GPR full-waveform inversion was successfully applied to several datasets and the results show the utility and credibility of GPR FWI to analyze peatland properties.

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.

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.

The Impact of Fire on Active Layer Thicknes

NASA Astrophysics Data System (ADS)

Schaefer, K. M.; Parsekian, A.; Natali, S.; Ludwig, S.; Michaelides, R. J.; Zebker, H. A.; Chen, J.

2016-12-01

Fire influences permafrost thermodynamics by darkening the surface to increase solar absorption and removing insulating moss and organic soil, resulting in an increase in Active Layer Thickness (ALT). The summer of 2015 was one of the worst fire years on record in Alaska with multiple fires in the Yukon-Kuskokwim (YK) Delta. To understand the impacts of fire on permafrost, we need large-scale, extensive measurements of ALT both within and outside the fire zones. In August 2016, we surveyed ALT across multiple fire zones in the YK Delta using Ground Penetrating Radar (GPR) and mechanical probing. GPR uses pulsed, radio-frequency electromagnetic waves to noninvasively image the subsurface and is an effective tool to quickly map ALT over large areas. We supplemented this ALT data with measurements of Volumetric Water Content (VWC), Organic Layer Thickness (OLT), and burn severity. We quantified the impacts of fire by statistically comparing the measurements inside and outside the fire zones and statistically regressing ALT against VWC, change in OLT, and burn severity.

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

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.

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

Deposits related to supercritical flows in glacifluvial deltas and subaqueous ice-contact fans: Integrating facies analysis and ground-penetrating radar

NASA Astrophysics Data System (ADS)

Lang, Joerg; Sievers, Julian; Loewer, Markus; Igel, Jan; Winsemann, Jutta

2017-04-01

Bedforms related to supercritical flows have recently received much interest and the understanding of flow morphodynamics and depositional processes has been greatly advanced. However, outcrop studies of these bedforms are commonly hampered by their long wavelengths. Therefore, we combined outcrop-based facies analysis with extensive ground-penetrating radar (GPR) measurements. Different GPR antennas (200, 400 and 1500 MHz) were utilised to measure both long profiles and densely spaced grids in order to map the large-scale facies architecture and image the three-dimensional geometry of the deposits. The studied delta and subaqueous ice-contact fan successions were deposited within ice-dammed lakes, which formed along the margins of the Middle Pleistocene Scandinavian ice sheets across Northern Germany. These glacilacustrine depositional systems are characterised by high aggradation rates due to the rapid expansion and deceleration of high-energy sediment-laden flows, favouring the preservation of bedforms related to supercritical flows. In flow direction, delta foresets commonly display lenticular scours, which are 2 to 6 m wide and 0.15 to 0.5 m deep. Characteristically, scours are filled by upslope dipping backsets, consisting of pebbly sand. In a few cases, massive and deformed strata were observed, passing upflow into backsets. Across flow, scours are 2 to 3 m wide and typically display a concentric infill. The scour fills are commonly associated with subhorizontally or sinusoidal stratified pebbly sand. These facies types are interpreted as deposits of cyclic steps and antidunes, respectively, representing deposition from supercritical density flows, which formed during high meltwater discharge events or regressive slope failures (Winsemann et al., in review). The GPR-sections show that the scour fills form trains along the delta foresets, which can be traced for up to 15 m. The studied subaqueous ice-contact fan succession relates to the zone of flow transition of a supercritical plane-wall efflux-jet and is characterised by deposits of chutes-and-pools, antidunes and humpback dunes (Lang & Winsemann, 2013). In the GPR-sections, long wavelength (2 to 40 m) sinusoidal reflectors with lateral extents of up to 175 m represent the dominant radar facies, which is interpreted as deposits of stationary aggrading antidunes. This radar facies is associated with lenses (2 to 15 m wide, 0.5 to 1.5 m thick) filled with planar upflow-dipping reflectors, and sheet-like sigmoidal downflow-dipping reflectors, which are interpreted as deposits of chutes-and-pools and humpback dunes, respectively. Facies transitions occur from cyclic steps or chutes-and-pools to antidunes and from antidunes to humpback dunes, and are interpreted as related to the evolution of bedforms under spatially and temporarily changing flow conditions. References: Lang, J. & Winsemann, J. (2013) Lateral and vertical facies relationships of bedforms deposited by aggrading supercritical flows: from cyclic steps to humpback dunes. Sedimentary Geology 296, 36-54. Winsemann, J., Lang, J., Loewer, M., Polom, U., Pollok, L., Igel, J. & Brandes, C. (in review) Forced regressive ice-marginal deltas in glacial lake basins: geomorphology, facies variability and large-scale depositional architecture.

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

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.

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

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.

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.

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

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.

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.

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.

SNARE-dependent upregulation of KCC2 activity following metabotropic zinc receptor (mZnR/GPR39) activation in rat cortical neurons in vitro

PubMed Central

Saadi, Robert A.; He, Kai; Hartnett, Karen A.; Kandler, Karl; Hershfinkel, Michal; Aizenman, Elias

2012-01-01

The major outward chloride transporter in neurons is the potassium chloride co-transporter 2 (KCC2), critical for maintaining an inhibitory reversal potential for GABAA receptor channels. In a recent study, we showed that Zn2+ regulates GABAA reversal potentials in the hippocampus by enhancing the activity of KCC2 via an increase in its surface expression. Zn2+ initiates this process by activating the Gq-coupled metabotropic Zn2+ receptor mZnR/GPR39. Here, we first demonstrated that mZnR/GPR39 is functional in cortical neurons in culture and then tested the hypothesis that the increase in KCC2 activity is mediated through a SNARE-dependent process. We established the presence of functional mZnR in rat cultured cortical neurons by loading cells with a Ca2+ indicator and exposing cells to Zn2+, which triggered consistent Ca2+ responses that were blocked by the Gq antagonist YM-254890, but not by the metabotropic glutamate receptor antagonist MCPG. Importantly, Zn2+ treatment under these conditions did not increase the intracellular concentrations of Zn2+ itself. We then measured KCC2 activity by monitoring both the rate and relative amount of furosemide-sensitive NH4+ influx via the co-transporter using an intracellular pH sensitive fluorescent indicator. We observed that Zn2+ pretreatment induced a Ca2+-dependent increase in KCC2 activity. The effects of Zn2+ on KCC2 activity were also observed in wild-type mouse cortical neurons in culture, but not in neurons obtained from mZnR/GPR39−/− mice, suggesting that Zn2+ acts via mZnR/GPR39 activation to upregulate KCC2 activity. We next transfected rat cortical neurons with a plasmid encoding botulinum toxin C1 (Botox C1), which cleaves the SNARE proteins syntaxin 1 and SNAP-25. Basal KCC2 activity was similar in both transfected and non-transfected neurons. Non-transfected cells, or cells transfected with marker vector alone, showed a Zn2+-dependent increase in KCC2 activity. In contrast, KCC2 activity in neurons expressing Botox C1 was unchanged by Zn2+. These results suggest that SNARE proteins are necessary for the increased activity of KCC2 following Zn2+ stimulation of mZnR/GPR39. PMID:22441041

GPR technique as a tool for decision-making regarding timber beam inner reinforcement: The Lonja de la Seda de Valencia, Spain

NASA Astrophysics Data System (ADS)

García, Francisco; Ramirez, Manuel; Benlloch, Javier; Valls, Ana

2015-04-01

This paper describes the decision-making process for the timber beam inner reinforcement of the building The Lonja de la Seda de Valencia (15th c.), Spain. This research was based on the study of 13 timber beams for their diagnosis and the characterization before decision-making in structural reinforcement. For this purpose, we integrated the results of analysis of historical documentation, in situ visual inspection and ground penetrating radar (GPR). The rehabilitation project considered the substitution of the upper-storey floor (The Consulate of the Sea Hall) for another one that complied with the original. This room was closed due to the instability of the timber beams. For the flooring renovation it was necessary to increase the rigidity of the timber floor framing. Preliminary conclusions, which derived from the historical documentation and in situ visual inspection of the timber coffered ceiling were: (a) timber beams supported inside masonry walls could suffer moisture and xylophage attacks, (b) timber beams were significantly damaged (splits, ring shakes, failure of beam section that reduced its bearing capacity), (c) substantial timber beam warping. So the main objectives of this GPR study were: to detect splits, to identify failure of section due to biological attacks, to pinpoint epoxy resin reconstructions and to assess the severity of the damages observed on surface. A GPR survey was carried out in timber coffered-ceiling beams of The Consulate of the Sea Hall. Radar measurements were carried out using a SIR-10H system (GSSI) and a 1.6 GHz ground coupled antenna, due to the timber beam dimensions (0.45 x 0.45 x 8.75 m. A total of 37 longitudinal profiles were collected in the centre of all the beam accessible sides. After radragram processing steps, a number of anomalies were detected in the records, which were analysed. The outcomes derived from this GPR study were taken into account when it came to make decisions in the final restoration project of the timber coffered ceiling elements: timber beams, wooden latticework and floor. The results obtained in this survey are a good example of GPR application in Civil Engineering for timber beam inner reinforcement of a building, establishing technical criteria.

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.

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.

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.

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.

Ground-penetrating radar evidence of refrozen meltwater in the firn column of Larsen C Ice Shelf

NASA Astrophysics Data System (ADS)

Hubbard, B. P.; Booth, A. D.; Sevestre, H.; Kulessa, B.; Bevan, S. L.; Luckman, A. J.; Kuipers Munneke, P.; Buzzard, S. C.; Ashmore, D. W.; O'Leary, M.

2017-12-01

Firn densification, which has been strongly implicated in ice shelf collapse, can occur rapidly by the percolation and refreezing of surface meltwater. This process reduces the permeability of the firn column, potentially establishing a positive feedback between densification and the occurrence of surface meltwater ponds, and may ultimately facilitate fracturing associated with shelf collapse. Meltwater ponds on Larsen C's Cabinet (CI) and Whirlwind (WI) inlets form where foehn winds reach and influence the shelf surface. While associated zones of refrozen meltwater are strongly evidenced in borehole optical televiewing (OPTV) and seismic refraction data, the sparsity of these observations limits insight into the dimensions of these zones. Here, we present highlights from an 800-km archive of ground-penetrating radar (GPR) profiles acquired by the MIDAS project on CI and WI during November-December 2015. In the upstream reaches of CI and WI, stratified firn layers are abruptly truncated by zones of diminished GPR reflectivity. These initiate 5 m beneath the surface and extend to a depth of 30 m. Volumes appear to exceed 6 km3 (CI) and 1 km3 (WI); these are underestimates, established only where there is GPR control. The horizontal distribution of these zones correlates with the pattern of reduced backscatter in SAR images, supporting their association with meltwater ponds. GPR reflectivity models, derived from OPTV density trends, suggest reduced GPR wavespeeds (as do GPR velocity analyses) and dielectric contrasts consistent with homogenised and densified firn. A firn density model supports the ability of meltwater ponds to form periodically in Cabinet Inlet and subsequently homogenise the density of the firn column. Our observations suggest that ice shelves affected by surface melt and ponding can contain spatially extensive bodies of ice that are warmer and denser than assumed so far, with significant implications for ice shelf flow and fracturing.

Lysophosphatidylinositol-induced activation of the cation channel TRPV2 triggers glucagon-like peptide-1 secretion in enteroendocrine L cells.

PubMed

Harada, Kazuki; Kitaguchi, Tetsuya; Kamiya, Taichi; Aung, Kyaw Htet; Nakamura, Kazuaki; Ohta, Kunihiro; Tsuboi, Takashi

2017-06-30

The lysophosphatidylinositol (LPI) has crucial roles in multiple physiological processes, including insulin exocytosis from pancreatic islets. However, the role of LPI in secretion of glucagon-like peptide-1 (GLP-1), a hormone that enhances glucose-induced insulin secretion, is unclear. Here, we used the murine enteroendocrine L cell line GLUTag and primary murine small intestinal cells to elucidate the mechanism of LPI-induced GLP-1 secretion. Exogenous LPI addition increased intracellular Ca 2+ concentrations ([Ca 2+ ] i ) in GLUTag cells and induced GLP-1 secretion from both GLUTag and acutely prepared primary intestinal cells. The [Ca 2+ ] i increase was suppressed by an antagonist for G protein-coupled receptor 55 (GPR55) and by silencing of GPR55 expression, indicating involvement of G q and G 12/13 signaling pathways in the LPI-induced increased [Ca 2+ ] i levels and GLP-1 secretion. However, GPR55 agonists did not mimic many of the effects of LPI. We also found that phospholipase C inhibitor and Rho-associated kinase inhibitor suppressed the [Ca 2+ ] i increase and that LPI increased the number of focal adhesions, indicating actin reorganization. Of note, blockage or silencing of transient receptor potential cation channel subfamily V member 2 (TRPV2) channels suppressed both the LPI-induced [Ca 2+ ] i increase and GLP-1 secretion. Furthermore, LPI accelerated TRPV2 translocation to the plasma membrane, which was significantly suppressed by a GPR55 antagonist. These findings suggest that TRPV2 activation via actin reorganization induced by G q and G 12/13 signaling is involved in LPI-stimulated GLP-1 secretion in enteroendocrine L cells. Because GPR55 agonists largely failed to mimic the effects of LPI, its actions on L cells are at least partially independent of GPR55 activation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

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.

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.

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.

Advances in 3D soil mapping and water content estimation using multi-channel ground-penetrating radar

NASA Astrophysics Data System (ADS)

Moysey, S. M.

2011-12-01

Multi-channel ground-penetrating radar systems have recently become widely available, thereby opening new possibilities for shallow imaging of the subsurface. One advantage of these systems is that they can significantly reduce survey times by simultaneously collecting multiple lines of GPR reflection data. As a result, it is becoming more practical to complete 3D surveys - particularly in situations where the subsurface undergoes rapid changes, e.g., when monitoring infiltration and redistribution of water in soils. While 3D and 4D surveys can provide a degree of clarity that significantly improves interpretation of the subsurface, an even more powerful feature of the new multi-channel systems for hydrologists is their ability to collect data using multiple antenna offsets. Central mid-point (CMP) surveys have been widely used to estimate radar wave velocities, which can be related to water contents, by sequentially increasing the distance, i.e., offset, between the source and receiver antennas. This process is highly labor intensive using single-channel systems and therefore such surveys are often only performed at a few locations at any given site. In contrast, with multi-channel GPR systems it is possible to physically arrange an array of antennas at different offsets, such that a CMP-style survey is performed at every point along a radar transect. It is then possible to process this data to obtain detailed maps of wave velocity with a horizontal resolution on the order of centimeters. In this talk I review concepts underlying multi-channel GPR imaging with an emphasis on multi-offset profiling for water content estimation. Numerical simulations are used to provide examples that illustrate situations where multi-offset GPR profiling is likely to be successful, with an emphasis on considering how issues like noise, soil heterogeneity, vertical variations in water content and weak reflection returns affect algorithms for automated analysis of the data. Overall, the ideal situation occurs when distinct, strong reflections are obtained from flat lying interfaces. To evaluate this idea in the field, data were collected from an agricultural field in the Clemson Experimental Forest in South Carolina and a restored floodplain at the East Branch Pecatonica River Restoration Observatory in Wisconsin using a pulseEKKO Pro GPR with 12 channels containing 500MHz antennas with offsets between 0.2-1.5m. The GPR data collection was found to be extremely efficient, allowing for an equivalent of over 12km of data to be collected within a day. While the two sites are significantly different, with contrasts ranging from soil structure to attenuation characteristics, the results illustrate that it is possible to obtain meaningful information about soil variability using multi-offset GPR profiling even at sites with non-ideal conditions.

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.

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.

Ground Penetrating Radar as a Contextual Sensor for Multi-Sensor Radiological Characterisation

PubMed Central

Ukaegbu, Ikechukwu K.; Gamage, Kelum A. A.

2017-01-01

Radioactive sources exist in environments or contexts that influence how they are detected and localised. For instance, the context of a moving source is different from a stationary source because of the effects of motion. The need to incorporate this contextual information in the radiation detection and localisation process has necessitated the integration of radiological and contextual sensors. The benefits of the successful integration of both types of sensors is well known and widely reported in fields such as medical imaging. However, the integration of both types of sensors has also led to innovative solutions to challenges in characterising radioactive sources in non-medical applications. This paper presents a review of such recent applications. It also identifies that these applications mostly use visual sensors as contextual sensors for characterising radiation sources. However, visual sensors cannot retrieve contextual information about radioactive wastes located in opaque environments encountered at nuclear sites, e.g., underground contamination. Consequently, this paper also examines ground-penetrating radar (GPR) as a contextual sensor for characterising this category of wastes and proposes several ways of integrating data from GPR and radiological sensors. Finally, it demonstrates combined GPR and radiation imaging for three-dimensional localisation of contamination in underground pipes using radiation transport and GPR simulations. PMID:28387706

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.

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.

GPR investigations along the North Anatolian Fault near Izmit (Turkey): Constraints on the right-lateral movement and slip history

NASA Astrophysics Data System (ADS)

Ferry, M.; Meghraoui, M.; Rockwell, T. K.; Kozaci, Ö.; Akyuz, S.; Girard, J.-F.; Barka, A.

2003-04-01

The 1999 Ms 7.4 Izmit earthquake produced more than 110 km of surface rupture along the North Anatolian fault. We present here ground-penetrating radar (GPR) profiles surveyed across and parallel to the 1999 Izmit earthquake ruptures at two sites along the Izmit-Sapanca segment. Fine sandy and coarse gravels favor the penetration depth and processed radar profiles image clearly visible reflectors within the uppermost 10 m. In Köseköy, they document cumulative right-lateral offset of a stream channel by the fault. Old fluvial channel deposits also visible in trenches show a maximum 13.5 to 14 m lateral displacement. Younger channel units display 4 m of right-lateral displacement at 2.5 m depth and correlation with dated trench units yields an average slip rate of 15 mm/yr. At site 2, GPR profiles display the successive faulting of a medieval Ottoman Canal which excavation probably took place in 1591 A.D.. GPR profiles image the corresponding surface as well as numerous faults that affect it. A following trench study confirmed these results as they provide consistent results with the occurrence of three faulting events post-1591 A.D., one of which probably as large as the 1999 Izmit earthquake.

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.

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 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.

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.

Predicting Short Term Runoff Efficiency Using Antecedent Soil Moisture Estimates From Ground Penetrating Radar Data

NASA Astrophysics Data System (ADS)

Hermance, J. F.; Bohidar, R. N.

2002-05-01

Hydrologists universally recognize the importance of antecedent soil moisture conditions for predicting the response of catchments to storm events. We describe a pilot study involving a series of repeat geophysical measurements over a 5 month period to determine the water content of the subsurface immediately before a sequence of precipitation events. We correlate the resultant streamflow "response" of the local catchment to each event with the antecedent soil moisture at our reference site using a metric commonly employed by hydrologists: the ratio Qef/W, referred to here as the "short term runoff efficiency", which is simply the time-integrated volume of event flow (Qef) at the catchment's outflow point normalized by the volume of total precipitation (W) over its area. To determine the volumetric water content (Cw) of soils, past studies suggest the effectiveness of pulsed radio frequency methods, such as time domain reflectometry (TDR), or ground-penetrating radar (GPR). To first order, for typical field conditions and procedures, the velocity of a radio pulse in the subsurface is inversely proportional to the square root of the bulk dielectric constant, which in turn is proportional to the soil's water content. For this study, the advantage of GPR over conventional TDR measurements is that the GPR procedure determines average velocities from two-way traveltimes to an interface at depth, resulting in estimates of average physical properties over much larger volumes of the subsurface than would TDR. Our hydrologic data are USGS daily averaged discharges from the Ten Mile River (watershed area = 138 km2; 53.2 mi2) in southern New England. Daily values of precipitation were provided by personnel from the Seekonk Water District Office (MA) adjacent to the field site. Our hydrograph separation was facilitated by the observation that the event flow seems to be adequately represented by a simple composite cascaded linear reservoir model. The GPR data involved a series of repeated wide-angle reflection "soundings" on a typical stratified glacial drift deposit, with velocities determined using both hand-picks and normal moveout velocity scans. In addition, on each day soil samples were collected and analyzed in the lab for volumetric water. GPR velocities were reduced to estimates of soil water concentrations using published mixing relations; of these we elected the conventional Topp relation as our provisional standard. A preliminary comparison of soil water content derived from our GPR data with analyses of field samples in the lab using the gravimetric method yields a correlation coefficient of R2 ~ 0.97. Selecting 5 cases during the early spring and summer of 2000, when storm events occurred within a few days following each respective measurement, a simple regression provides a relation whereby short term runoff efficiencies over the range of 0.03 (3%) to 0.25 (25%), respectively, appear to be linearly related to soil moisture contents over the range of 0.13 (13%) to 0.22 (22%) through a relation of the form Qef/W = 2.42Cw - 0.284, with a correlation coefficient of R2 ~ 0.95. Thus, estimates of soil moisture based on estimates from GPR velocities is promising for predicting runoff from small catchments - it is imperative, however, that such studies be paralleled by careful attention to the acquisition, conditioning and analysis of GPR data, as well as by knowledge of the subsurface stratigraphy of the field area.

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

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

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

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

Laser Scanner Technology, Ground-Penetrating Radar and Augmented Reality for the Survey and Recovery of Artistic, Archaeological and Cultural Heritage

NASA Astrophysics Data System (ADS)

Barrile, V.; Bilotta, G.; Meduri, G. M.; De Carlo, D.; Nunnari, A.

2017-11-01

In this study, using technologies such as laser scanner and GPR it was desired to see their potential in the cultural heritage. Also with regard to the processing part we are compared the results obtained by the various commercial software and algorithms developed and implemented in Matlab. Moreover, Virtual Reality and Augmented Reality allow integrating the real world with historical-artistic information, laser scanners and georadar (GPR) data and virtual objects, virtually enriching it with multimedia elements, graphic and textual information accessible through smartphones and tablets.

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

Retrieval of Shape Characteristics for Buried Objects with GPR Monitoring

NASA Astrophysics Data System (ADS)

Soldovieri, F.; Comite, D.; Galli, A.; Valerio, G.; Barone, P. M.; Lauro, S. E.; Mattei, E.; Pettinelli, E.

2012-04-01

Information retrieval on the location and the geometrical features (dimensions and shape) of buried objects is of fundamental importance in geosciences areas involving environmental protection, mine clearance, archaeological investigations, space and planetary exploration, and so forth. Among the different non-invasive sensing techniques usually employed to achieve this kind of information, those based on ground-penetrating-radar (GPR) instruments are well-established and suitable to the mentioned purposes [1]. In this context, our interest in the present work is specifically focused on testing the potential performance of typical GPR instruments by means of appropriate data processing. It will be shown in particular to what extent the use of a suitable "microwave tomographic approach" [2] is able to furnish a shape estimation of the targets, possibly recognizing different kinds of canonical geometries, even having reduced cross sections and in critical conditions, where the scatterer size is comparable with resolution limits imposed by the usual measurement configurations. Our study starts by obtaining the typical "direct" information from the GPR techniques that is the scattered field in subsurface environments under the form of radargrams. In order to get a wide variety of scenarios for the operating conditions, this goal is achieved by means of two different and independent approaches [3]. One approach is based on direct measurements through an experimental laboratory setup: commercial GPR instruments (typically bistatic configurations operating around 1 GHz frequency range) are used to collect radargram profiles by investigating an artificial basin filled of liquid and/or granular materials (sand, etc.), in which targets (having different constitutive parameters, shape, and dimensions) can be buried. The other approach is based on numerical GPR simulations by means of a commercial CAD electromagnetic tool (CST), whose suitable implementation and data processing allow us to retrieve results again in the form of radargrams for the scattering features of arbitrarily-composed subsurfaces. Once these types of "direct" (measured and/or simulated) radargram data are obtained, the "inverse" problem is then handled, based on a Born approximation to linearize the scattering problem. The targets are represented in terms of anomalies ("contrast function") of dielectric permittivity and conductivity with respect to the properties of a background environment. The analysis of the relevant results for the spatial distribution of the magnitude of the contrast function shows that, in various even-challenging practical cases, this kind of approach is able to properly locate buried objects, also identifying the relevant shape features. [1] D. J. Daniels (Ed.), Ground penetrating radar. IEE Press, 2004. [2] E. Pettinelli, A. Di Matteo, E. Mattei, L. Crocco, F. Soldovieri, J. D. Redman, and A. P. Annan, "GPR response from buried pipes: measurement on field site and tomographic reconstructions," IEEE Trans. Geosci. Remote Sensing, vol. 47, pp. 2639-2645, Aug. 2009. [3] G. Valerio, A. Galli, P. M. Barone, S. E. Lauro, E. Mattei, and E. Pettinelli, "GPR detectability of rocks in a Martian-like shallow subsoil: a numerical approach," Planet. Space Sci., 10 pp., doi: 10.1016/j.pss.2011.12.003, 2011.

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.

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.

Robust Foregrounds Removal for 21-cm Experiments

NASA Astrophysics Data System (ADS)

Mertens, F.; Ghosh, A.; Koopmans, L. V. E.

2018-05-01

Direct detection of the Epoch of Reionization via the redshifted 21-cm line will have unprecedented implications on the study of structure formation in the early Universe. To fulfill this promise current and future 21-cm experiments will need to detect the weak 21-cm signal over foregrounds several order of magnitude greater. This requires accurate modeling of the galactic and extragalactic emission and of its contaminants due to instrument chromaticity, ionosphere and imperfect calibration. To solve for this complex modeling, we propose a new method based on Gaussian Process Regression (GPR) which is able to cleanly separate the cosmological signal from most of the foregrounds contaminants. We also propose a new imaging method based on a maximum likelihood framework which solves for the interferometric equation directly on the sphere. Using this method, chromatic effects causing the so-called ``wedge'' are effectively eliminated (i.e. deconvolved) in the cylindrical (k⊥, k∥) power spectrum.

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

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

Detection and delineation of underground septic tanks in sandy terrain using ground penetrating radar

NASA Astrophysics Data System (ADS)

Omolaiye, Gabriel Efomeh; Ayolabi, Elijah A.

2010-09-01

A ground penetrating radar (GPR) survey was conducted on the Lekki Peninsula, Lagos State, Nigeria. The primary target of the survey was the delineation of underground septic tanks (ST). A total of four GPR profiles were acquired on the survey site using Ramac X3M GPR equipment with a 250MHz antenna, chosen based on the depth of interest and resolution. An interpretable depth of penetration of 4.5m below the surface was achieved after processing. The method accurately delineated five underground ST. The tops of the ST were easily identified on the radargram based on the strong-amplitude anomalies, the length and the depths to the base of the ST were estimated with 99 and 73 percent confidence respectively. The continuous vertical profiles provide uninterrupted subsurface data along the lines of traverse, while the non-intrusive nature makes it an ideal tool for the accurate mapping and delineation of underground utilities.

Multi-offset GPR methods for hyporheic zone investigations

USGS Publications Warehouse

Brosten, T.R.; Bradford, J.H.; McNamara, J.P.; Gooseff, M.N.; Zarnetske, J.P.; Bowden, W.B.; Johnston, M.E.

2009-01-01

Porosity of stream sediments has a direct effect on hyporheic exchange patterns and rates. Improved estimates of porosity heterogeneity will yield enhanced simulation of hyporheic exchange processes. Ground-penetrating radar (GPR) velocity measurements are strongly controlled by water content thus accurate measures of GPR velocity in saturated sediments provides estimates of porosity beneath stream channels using petrophysical relationships. Imaging the substream system using surface based reflection measurements is particularly challenging due to large velocity gradients that occur at the transition from open water to saturated sediments. The continuous multi-offset method improves the quality of subsurface images through stacking and provides measurements of vertical and lateral velocity distributions. We applied the continuous multi-offset method to stream sites on the North Slope, Alaska and the Sawtooth Mountains near Boise, Idaho, USA. From the continuous multi-offset data, we measure velocity using reflection tomography then estimate water content and porosity using the Topp equation. These values provide detailed measurements for improved stream channel hydraulic and thermal modelling. ?? 2009 European Association of Geoscientists & Engineers.

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.

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

The detectability of archaeological structures beneath the soil using the ground penetrating radar technique

NASA Astrophysics Data System (ADS)

Ferrara, C.; Barone, P. M.; Pajewski, L.; Pettinelli, E.; Rossi, G.

2012-04-01

The traditional excavation tools applied to Archaeology (i.e. trowels, shovels, bulldozers, etc.) produce, generally, a fast and invasive reconstruction of the ancient past. The geophysical instruments, instead, seem to go in the opposite direction giving, rapidly and non-destructively, geo-archaeological information. Moreover, the economic aspect should not be underestimated: where the former invest a lot of money in order to carry out an excavation or restoration, the latter spend much less to manage a geophysical survey, locating precisely the targets. Survey information gathered using non-invasive methods contributes to the creation of site strategies, conservation, preservation and, if necessary, accurate location of excavation and restoration units, without destructive testing methods, also in well-known archaeological sites [1]-[3]. In particular, Ground Penetrating Radar (GPR) has, recently, become the most important physical technique in archaeological investigations, allowing the detection of targets with both very high vertical and horizontal resolution, and has been successfully applied both to archaeological and diagnostic purposes in historical and monumental sites [4]. GPR configuration, antenna frequency and survey modality can be different, depending on the scope of the measurements, the nature of the site or the type of targets. Two-dimensional (2D) time/depth slices and radargrams should be generated and integrated with information obtained from other buried or similar artifacts to provide age, structure and context of the surveyed sites. In the present work, we present three case-histories on well-known Roman archaeological sites in Rome, in which GPR technique has been successfully used. To obtain 2D maps of the explored area, a bistatic GPR (250MHz and 500MHz antennas) was applied, acquiring data along several parallel profiles. The GPR results reveal the presence of similar circular anomalies in all the investigated archaeological sites. In particular, in the Domus Aurea, in the Domitian Stadium, and in the San Cesario in Palatio church, the processing of the GPR data highlights not only the presence of Roman circular bases/insoles of pillars not yet brought to the light, but also their structural disposition and geometry. These three examples show that GPR technique is a valid support which, in exhaustive way, can underline the unexpected presence of ancient structures beneath the soil, also in well-known archaeological sites.

Reconstruction of the inner structure of small scale mining waste dumps by combining GPR and ERTdata.

NASA Astrophysics Data System (ADS)

Kniess, Rudolf; Martin, Tina

2015-04-01

Two abandoned small waste dumps in the west of the Harz mountains (Germany) were analysed using ground penetrating radar (GPR) and electrical resistivity tomography (ERT). Aim of the project (ROBEHA, funded by the German Federal Ministry of Education and Research (033R105)) is the assessment of the recycling potential of the mining residues taking into account environmental risks of reworking the dump site. One task of the geophysical prospection is the investigation of the inner structure of the mining dump. This is important for the estimation of the approximate volume of potentially reusable mining deposits within the waste dump. The two investigated dump sites are different in age and therefore differ in their structure. The older residues (< 1930) consist of ore processing waste from density separation (stamp mill sand). The younger dump site descends from comprises slag dump waste. The layer of fine grained residues at the first dump site is less than 6 m thick and the slag layer is less than 2 m thick. Both sites are partially overlain by forest or grassland vegetation and characterized by topographical irregularities. Due to the inhomogeneity of the sites we applied electrical resistivity tomography (ERT) and ground penetrating radar (GPR) for detailed investigation. Using ERT we could distinguish various layers within the mining dumps. The resistivities of the dumped material differ from the bedrock resistivities at both sites. The GPR measurements show near surface layer boundaries down to 3 - 4 m. In consecutive campaigns 100 MHz and 200 MHz antennas were used. The GPR results (layer boundaries) were included into the ERT inversion algorithm to enable more precise and stable resistivity models. This needs some special preprocessing steps. The 3D-Position of every electrode from ERT measurement and the GPR antenna position on the surface require an accuracy of less than 1cm. At some points, the layer boundaries and radar wave velocities can be calibrated with borehole stratigraphic data from a mineralogical drilling campaign. This is important for a precise time-depth conversion of reflectors from GPR measurement. This reflectors were taken from radargram and have been adopted as resistivity boundary in the start model of the geoelectric inversion algorithm.

An Experimental Study in Determining Energy Expenditure from Treadmill Walking using Hip-Worn Inertial Sensors

PubMed Central

Vathsangam, Harshvardhan; Emken, Adar; Schroeder, E. Todd; Spruijt-Metz, Donna; Sukhatme, Gaurav S.

2011-01-01

This paper describes an experimental study in estimating energy expenditure from treadmill walking using a single hip-mounted triaxial inertial sensor comprised of a triaxial accelerometer and a triaxial gyroscope. Typical physical activity characterization using accelerometer generated counts suffers from two drawbacks - imprecison (due to proprietary counts) and incompleteness (due to incomplete movement description). We address these problems in the context of steady state walking by directly estimating energy expenditure with data from a hip-mounted inertial sensor. We represent the cyclic nature of walking with a Fourier transform of sensor streams and show how one can map this representation to energy expenditure (as measured by V O2 consumption, mL/min) using three regression techniques - Least Squares Regression (LSR), Bayesian Linear Regression (BLR) and Gaussian Process Regression (GPR). We perform a comparative analysis of the accuracy of sensor streams in predicting energy expenditure (measured by RMS prediction accuracy). Triaxial information is more accurate than uniaxial information. LSR based approaches are prone to outlier sensitivity and overfitting. Gyroscopic information showed equivalent if not better prediction accuracy as compared to accelerometers. Combining accelerometer and gyroscopic information provided better accuracy than using either sensor alone. We also analyze the best algorithmic approach among linear and nonlinear methods as measured by RMS prediction accuracy and run time. Nonlinear regression methods showed better prediction accuracy but required an order of magnitude of run time. This paper emphasizes the role of probabilistic techniques in conjunction with joint modeling of triaxial accelerations and rotational rates to improve energy expenditure prediction for steady-state treadmill walking. PMID:21690001

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...

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.

An Update on Non-CB1, Non-CB2 Cannabinoid Related G-Protein-Coupled Receptors

PubMed Central

Morales, Paula; Reggio, Patricia H.

2017-01-01

Abstract The endocannabinoid system (ECS) has been shown to be of great importance in the regulation of numerous physiological and pathological processes. To date, two Class A G-protein-coupled receptors (GPCRs) have been discovered and validated as the main therapeutic targets of this system: the cannabinoid receptor type 1 (CB1), which is the most abundant neuromodulatory receptor in the brain, and the cannabinoid receptor type 2 (CB2), predominantly found in the immune system among other organs and tissues. Endogenous cannabinoid receptor ligands (endocannabinoids) and the enzymes involved in their synthesis, cell uptake, and degradation have also been identified as part of the ECS. However, its complex pharmacology suggests that other GPCRs may also play physiologically relevant roles in this therapeutically promising system. In the last years, GPCRs such as GPR18 and GPR55 have emerged as possible missing members of the cannabinoid family. This categorization still stimulates strong debate due to the lack of pharmacological tools to validate it. Because of their close phylogenetic relationship, the Class A orphan GPCRs, GPR3, GPR6, and GPR12, have also been associated with the cannabinoids. Moreover, certain endo-, phyto-, and synthetic cannabinoid ligands have displayed activity at other well-established GPCRs, including the opioid, adenosine, serotonin, and dopamine receptor families. In addition, the cannabinoid receptors have also been shown to form dimers with other GPCRs triggering cross-talk signaling under specific conditions. In this mini review, we aim to provide insight into the non-CB1, non-CB2 cannabinoid-related GPCRs that have been reported thus far. We consider the physiological relevance of these molecular targets in modulating the ECS. PMID:29098189

Kisspeptin-13 enhances memory and mitigates memory impairment induced by Aβ1-42 in mice novel object and object location recognition tasks.

PubMed

Jiang, J H; He, Z; Peng, Y L; Jin, W D; Wang, Z; Han, R W; Chang, M; Wang, R

2015-09-01

Kisspeptin (KP), the endogenous ligand of GPR54, is a recently discovered neuropeptide shown to be involved in regulating reproductive system, anxiety-related behavior, locomotion, food intake, and suppression of metastasis across a range of cancers. KP is transcribed within the hippocampus, and GPR54 has been found in the amygdala and hippocampus, suggesting that KP might be involved in mediating learning and memory. However, the role of KP in cognition was largely unclear. Here, we investigated the role of KP-13, one of the endogenous active isoforms, in memory processes, and determined whether KP-13 could mitigate memory impairment induced by Aβ1-42 in mice, using novel object recognition (NOR) and object location recognition (OLR) tasks. Intracerebroventricular (i.c.v.) infusion of KP-13 (2μg) immediately after training not only facilitated memory formation, but also prolonged memory retention in both tasks. The memory-improving effects of KP-13 could be blocked by the GPR54 receptor antagonist, kisspeptin-234 (234), and GnRH receptors antagonist, Cetrorelix, suggesting pharmacological specificity. Then the memory-enhancing effects were also presented after infusion of KP-13 into the hippocampus. Moreover, we found that i.c.v. injection of KP-13 was able to reverse the memory impairment induced by Aβ1-42, which was inhibited by 234. To sum up, the results of our work indicate that KP-13 could facilitate memory formation and prolong memory retention through activation of the GPR54 and GnRH receptors, and suppress memory-impairing effect of Aβ1-42 through activation of the GPR54, suggesting that KP-13 may be a potential drug for enhancing memory and treating Alzheimer's disease. Copyright © 2015 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.

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.

GPR-derived architecture of a lahar-generated fan at Cotopaxi volcano, Ecuador

NASA Astrophysics Data System (ADS)

Ettinger, Susanne; Manville, Vern; Kruse, Sarah; Paris, Raphaël

2014-05-01

The internal geometry of volcaniclastic fans produced by aggradation during lahar events is difficult to examine in modern settings because of the frequent lack of three-dimensional exposures. This makes it challenging to (i) reconstruct the spatial and temporal evolution of such fans; and (ii) interpret observed facies stratigraphy in the context of lahar flow dynamics from proximal to distal fan reaches. This research therefore presents the results of a ground penetrating radar (GPR) survey of the Rumipamba fan at the mouth of the Burrohuaycu quebrada on the southwestern flank of Cotopaxi volcano. A survey grid consisting of 50 individual GPR profiles representing a total length of 19.4 km was constructed covering most of the 4-km2 large fan surface. All GPR profiles were collected using a PulseEKKO 100 with a 400 V transmitter. Fan sediments consist of sandy and gravelly lahar deposits, alternating with volcanic fallout including ash and pumice lapilli, at times reworked by fluvial processes. Deposits could be ground-truthed to a depth of ~3 m, whereas GPR penetration depth reaches 15 m. Data interpretation was based on classification into 15 distinct radar facies characterized by the nature of their bounding surfaces and/or internal features, cross-referenced where possible with shallow exposures. Three main facies were identified: parallel, irregular, and clinoform. Erosional contacts were distinguished from aggradational ones (vertical, channel fill, and lateral accretion). Flow parallel versus flow transverse and proximal-distal variations in deposit architecture were featured. The results of this study confirm the existence of two major channel systems in the northern and southern extremities of the fan and the more recent formation of a smaller central fan channel system. Deposit architecture is complex and facies chronologies illustrate that lahars have affected the entire survey area.

Anatomical and histological profiling of orphan G-protein-coupled receptor expression in gastrointestinal tract of C57BL/6J mice.

PubMed

Ito, Junko; Ito, Masahiko; Nambu, Hirohide; Fujikawa, Toru; Tanaka, Kenichi; Iwaasa, Hisashi; Tokita, Shigeru

2009-11-01

G-protein-coupled receptors (GPCRs) constitute the largest family of transmembrane receptors and regulate a variety of physiological and disease processes. Although the roles of many non-odorant GPCRs have been identified in vivo, several GPCRs remain orphans (oGPCRs). The gastrointestinal (GI) tract is the largest endocrine organ and is a promising target for drug discovery. Given their close link to physiological function, the anatomical and histological expression profiles of benchmark GI-related GPCRs, such as the cholecystokinin-1 receptor and GPR120, and 106 oGPCRs were investigated in the mucosal and muscle-myenteric nerve layers in the GI tract of C57BL/6J mice by quantitative real-time polymerase chain reaction. The mRNA expression patterns of these benchmark molecules were consistent with previous in situ hybridization and immunohistochemical studies, validating the experimental protocols in this study. Of 96 oGPCRs with significant mRNA expression in the GI tract, several oGPCRs showed unique expression patterns. GPR85, GPR37, GPR37L1, brain-specific angiogenesis inhibitor (BAI) 1, BAI2, BAI3, and GPRC5B mRNAs were preferentially expressed in the muscle-myenteric nerve layer, similar to GPCRs that are expressed in both the central and enteric nerve systems and that play multiple regulatory roles throughout the gut-brain axis. In contrast, GPR112, trace amine-associated receptor (TAAR) 1, TAAR2, and GPRC5A mRNAs were preferentially expressed in the mucosal layer, suggesting their potential roles in the regulation of secretion, immunity, and epithelial homeostasis. These anatomical and histological mRNA expression profiles of oGPCRs provide useful clues about the physiological roles of oGPCRs in the GI tract.

Soil hydraulic material properties and layered architecture from time-lapse GPR

NASA Astrophysics Data System (ADS)

Jaumann, Stefan; Roth, Kurt

2018-04-01

Quantitative knowledge of the subsurface material distribution and its effective soil hydraulic material properties is essential to predict soil water movement. Ground-penetrating radar (GPR) is a noninvasive and nondestructive geophysical measurement method that is suitable to monitor hydraulic processes. Previous studies showed that the GPR signal from a fluctuating groundwater table is sensitive to the soil water characteristic and the hydraulic conductivity function. In this work, we show that the GPR signal originating from both the subsurface architecture and the fluctuating groundwater table is suitable to estimate the position of layers within the subsurface architecture together with the associated effective soil hydraulic material properties with inversion methods. To that end, we parameterize the subsurface architecture, solve the Richards equation, convert the resulting water content to relative permittivity with the complex refractive index model (CRIM), and solve Maxwell's equations numerically. In order to analyze the GPR signal, we implemented a new heuristic algorithm that detects relevant signals in the radargram (events) and extracts the corresponding signal travel time and amplitude. This algorithm is applied to simulated as well as measured radargrams and the detected events are associated automatically. Using events instead of the full wave regularizes the inversion focussing on the relevant measurement signal. For optimization, we use a global-local approach with preconditioning. Starting from an ensemble of initial parameter sets drawn with a Latin hypercube algorithm, we sequentially couple a simulated annealing algorithm with a Levenberg-Marquardt algorithm. The method is applied to synthetic as well as measured data from the ASSESS test site. We show that the method yields reasonable estimates for the position of the layers as well as for the soil hydraulic material properties by comparing the results to references derived from ground truth data as well as from time domain reflectometry (TDR).

Nested polynomial trends for the improvement of Gaussian process-based predictors

NASA Astrophysics Data System (ADS)

Perrin, G.; Soize, C.; Marque-Pucheu, S.; Garnier, J.

2017-10-01

The role of simulation keeps increasing for the sensitivity analysis and the uncertainty quantification of complex systems. Such numerical procedures are generally based on the processing of a huge amount of code evaluations. When the computational cost associated with one particular evaluation of the code is high, such direct approaches based on the computer code only, are not affordable. Surrogate models have therefore to be introduced to interpolate the information given by a fixed set of code evaluations to the whole input space. When confronted to deterministic mappings, the Gaussian process regression (GPR), or kriging, presents a good compromise between complexity, efficiency and error control. Such a method considers the quantity of interest of the system as a particular realization of a Gaussian stochastic process, whose mean and covariance functions have to be identified from the available code evaluations. In this context, this work proposes an innovative parametrization of this mean function, which is based on the composition of two polynomials. This approach is particularly relevant for the approximation of strongly non linear quantities of interest from very little information. After presenting the theoretical basis of this method, this work compares its efficiency to alternative approaches on a series of examples.

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.

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.

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.

Non-destructive testing for the structures and civil infrastructures characterization

NASA Astrophysics Data System (ADS)

Capozzoli, L.; Rizzo, E.

2012-04-01

This work evaluates the ability of non-conventional NDT techniques such as GPR, geoelectrical method and conventional ones such as infrared thermography (IRT) and sonic test for the characterization of building structures in laboratory and in-situ. Moreover, the integration of the different techniques were evaluated in order to reduce the degree of uncertainties associated. The presence of electromagnetic, resistivity or thermal anomalies in the behavior may be related to the presence of defects, crack, decay or moisture. The research was conducted in two phases: the first phase was performed in laboratory and the second one mainly in the field work. The laboratory experiments proceeded to calibrate the geophysical techniques GPR and geoelectrical method on building structures. A multi-layer structure was reconstructed in laboratory, in order to simulate a back-bridge: asphalt, reinforced concrete, sand and gravel layers. In the deep sandy layer, PVC, aluminum and steel pipes were introduced. This structure has also been brought to crack in a predetermined area and hidden internal fractures were investigated. GPR has allowed to characterize the panel in a non-invasive mode; radar maps were developed using various algorithms during post-process about 2D maps and 3D models with aerial acquisition of 400 MHz, 900MHz, 1500MHz, 2000MHz. Geoelectrical testing was performed with a network of 25 electrodes spaced at mutual distance of 5 cm. Two different configurations were used dipole-dipole and pole-dipole approaches. In the second phase, we proceeded to the analysis of pre-tensioned concrete in order to detect the possible presence of criticality in the structure. For this purpose by GPR 2GHz antenna, a '70 years precast bridge characterized by a high state of decay was studied; then were also analyzed a pillar and a beam of recent production directly into the processing plant. Moreover, results obtained using GPR were compared with those obtained through the use of infrared thermography and sonic testing. Finally, we investigated a radiant floor by GPR (900 MHz to 2000 MHz antennas) and long-wave infrared camera. Non-destructive diagnostic techniques allow to investigate a building structure in reinforced concrete or masonry without altering the characteristics of the element investigated. For this reason, geo-electrical and electromagnetic surveys of masonry are a suitable non-destructive tool for the diagnosis of a deteriorated concrete structure. Moreover, the integration of different NDT techniques (conventional and no-conventional) is a very powerful to maximize the capabilities and to compensate for the limitations of each method.

Empirical prediction of mechanical properties of flexible pavement through GPR

NASA Astrophysics Data System (ADS)

Bianchini Ciampoli, Luca; Benedetto, Andrea

2017-04-01

To date, it is well known that the frequency of accidental events recorded on a road, is related to the deterioration rate of its pavement. In this sense, the monitoring of the pavement health over a road network is a crucial task for the administrations, to define a priority scale for maintenance works, and accordingly to lower the risk of accidents. Several studies suggest the possibility to employ Ground-penetrating Radar (GPR) to overcome the limits of traditional bearing tests, which due to their low productivity and high costs, can only give a discrete knowledge about the strength of the pavement. This work presents a GPR-based empirical model for the prediction of the bearing capacity of a road pavement, expressed as Young's Modulus. The model exploits the GPR to extract information on the thickness of the base course and the clay content, by referring to the signal velocity and attenuation, respectively. To test the effectiveness of the model, experimental activities have been accounted for. In particular, multi-frequency GPR tests have been performed along road sections of rural roads, composed of a flexible pavement, for a total of 45 Km. As ground-truth, light falling weight deflectometer (LFWD) and Curviameter have been employed. Both the electromagnetic and the mechanical datasets have been properly processed, in order to reduce misinterpretations and to raise the statistical significance of the procedure. Hence, the calibration of the parameters composing the model was run in a subsection, equal to 8% of the total length, randomly selected within the surveyed track. Finally, as validation, the model has been applied to the whole analysed dataset. As a result, the empirical model showed a good effectiveness in predicting the mechanical response of the pavement, with a normalised root mean squared deviation equal to 0.27. Finally, by averaging the measured and predicted mechanical data every 50 m and sorting the results into strength classes, a qualitative approach useful for a visual detection of low-resistance areas has been also proposed. This study demonstrates the efficiency and reliability of GPR in mechanical assessment of flexible pavements. This empirical approach can represent a useful tool for administrations and companies managing road assets, for a non-destructive detection of the areas interested by early stage deterioration processes, and the definition of a priority-based scheduling of maintenance works. Acknowledgements The Authors thank COST, for funding the Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar."

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.

Evaluating Algorithm Performance Metrics Tailored for Prognostics

NASA Technical Reports Server (NTRS)

Saxena, Abhinav; Celaya, Jose; Saha, Bhaskar; Saha, Sankalita; Goebel, Kai

2009-01-01

Prognostics has taken a center stage in Condition Based Maintenance (CBM) where it is desired to estimate Remaining Useful Life (RUL) of the system so that remedial measures may be taken in advance to avoid catastrophic events or unwanted downtimes. Validation of such predictions is an important but difficult proposition and a lack of appropriate evaluation methods renders prognostics meaningless. Evaluation methods currently used in the research community are not standardized and in many cases do not sufficiently assess key performance aspects expected out of a prognostics algorithm. In this paper we introduce several new evaluation metrics tailored for prognostics and show that they can effectively evaluate various algorithms as compared to other conventional metrics. Specifically four algorithms namely; Relevance Vector Machine (RVM), Gaussian Process Regression (GPR), Artificial Neural Network (ANN), and Polynomial Regression (PR) are compared. These algorithms vary in complexity and their ability to manage uncertainty around predicted estimates. Results show that the new metrics rank these algorithms in different manner and depending on the requirements and constraints suitable metrics may be chosen. Beyond these results, these metrics offer ideas about how metrics suitable to prognostics may be designed so that the evaluation procedure can be standardized. 1

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.

Acute effect of Vagus nerve stimulation parameters on cardiac chronotropic, inotropic, and dromotropic responses

NASA Astrophysics Data System (ADS)

Ojeda, David; Le Rolle, Virginie; Romero-Ugalde, Hector M.; Gallet, Clément; Bonnet, Jean-Luc; Henry, Christine; Bel, Alain; Mabo, Philippe; Carrault, Guy; Hernández, Alfredo I.

2017-11-01

Vagus nerve stimulation (VNS) is an established therapy for drug-resistant epilepsy and depression, and is considered as a potential therapy for other pathologies, including Heart Failure (HF) or inflammatory diseases. In the case of HF, several experimental studies on animals have shown an improvement in the cardiac function and a reverse remodeling of the cardiac cavity when VNS is applied. However, recent clinical trials have not been able to reproduce the same response in humans. One of the hypothesis to explain this lack of response is related to the way in which stimulation parameters are defined. The combined effect of VNS parameters is still poorly-known, especially in the case of VNS synchronously delivered with cardiac activity. In this paper, we propose a methodology to analyze the acute cardiovascular effects of VNS parameters individually, as well as their interactive effects. A Latin hypercube sampling method was applied to design a uniform experimental plan. Data gathered from this experimental plan was used to produce a Gaussian process regression (GPR) model in order to estimate unobserved VNS sequences. Finally, a Morris screening sensitivity analysis method was applied to each obtained GPR model. Results highlight dominant effects of pulse current, pulse width and number of pulses over frequency and delay and, more importantly, the degree of interactions between these parameters on the most important acute cardiovascular responses. In particular, high interacting effects between current and pulse width were found. Similar sensitivity profiles were observed for chronotropic, dromotropic and inotropic effects. These findings are of primary importance for the future development of closed-loop, personalized neuromodulator technologies.

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.

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.

Structural monitoring via microwave tomography-enhanced GPR: the Montagnole test site

NASA Astrophysics Data System (ADS)

Catapano, Ilaria; Di Napoli, Rosario; Soldovieri, Francesco; Bavusi, Massimo; Loperte, Antonio; Dumoulin, Jean

2012-08-01

Structural integrity assessment and monitoring of infrastructures are key factors to prevent and manage crisis events (natural disasters, terrorist attacks and so on) and ensure urban safety. This necessity motivates huge interest towards design, optimization and integration of non-invasive remote and in situ diagnostic techniques. In this framework, ground penetrating radar (GPR) is a well-assessed instrumentation, which allows one to attain information on the inner status of man-made structures while avoiding invasive tests. However, despite its potential, a more widespread use of GPR is actually affected by the difficulties in providing highly informative and easily interpretable images as an outcome of the overall diagnostics procedure. This drawback can be mitigated thanks to the use of microwave tomography (MT) as a data processing tool able to enhance the achievable reconstruction capabilities, and several proofs of its effectiveness have been already shown. In this paper, the potential of the MT approach is investigated in the framework of structural monitoring by an experiment carried out in the Montagnole test site in the French Alps, where the progressive damage of a one-scale concrete beam has been monitored thanks to the integration of several electromagnetic sensing techniques. In this framework, the capability of the MT-enhanced GPR strategy is examined with respect to the possibility of providing information about the damage of the rebar grid of the beam.

Targeting orphan G protein-coupled receptors for the treatment of diabetes and its complications: C-peptide and GPR146.

PubMed

Kolar, G R; Grote, S M; Yosten, G L C

2017-01-01

G protein-coupled receptors (GPCRs) are the most abundant receptor family encoded by the human genome and are the targets of a high percentage of drugs currently in use or in clinical trials for the treatment of diseases such as diabetes and its associated complications. Thus, orphan GPCRs, for which the ligand is unknown, represent an important untapped source of therapeutic potential for the treatment of many diseases. We have identified the previously orphan GPCR, GPR146, as the putative receptor of proinsulin C-peptide, which may prove to be an effective treatment for diabetes-associated complications. For example, we have found a potential role of C-peptide and GPR146 in regulating the function of the retinal pigment epithelium, a monolayer of cells in the retina that serves as part of the blood-retinal barrier and is disrupted in diabetic macular oedema. However, C-peptide signalling in this cell type appears to depend at least in part on extracellular glucose concentration and its interaction with insulin. In this review, we discuss the therapeutic potential of orphan GPCRs with a special focus on C-peptide and GPR146, including past and current strategies used to 'deorphanize' this diverse family of receptors, past successes and the inherent difficulties of this process. © 2016 The Association for the Publication of the Journal of Internal Medicine.

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.

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

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.

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.

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).

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.

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

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

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

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.

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.

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

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

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.

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

In-situ GPR test for three-dimensional mapping of the dielectric constant in a rock mass

NASA Astrophysics Data System (ADS)

Elkarmoty, Mohamed; Colla, Camilla; Gabrielli, Elena; Papeschi, Paolo; Bonduà, Stefano; Bruno, Roberto

2017-11-01

The Ground Penetrating Radar (GPR) is used to detect subsurface anomalies in several applications. The more the velocity of propagation or the dielectric constant is estimated accurately, the more the detection of anomalies at true subsurface depth can be accurately obtained. Since many GPR applications are performed in rock mass with non-homogeneous discontinuous nature, errors in estimating a bulk velocity of propagation or dielectric constant are possible. This paper presents a new in-situ GPR test for mapping the dielectric constant variability in a rock mass. The main aim is to investigate to what extent the dielectric constant is variable in the micro and macro scale of a typical rock mass and to give attention to GPR users in rock mass mediums. The methodology of this research is based on the insertion of steel rods in a rock mass, thus acting as reflectors. The velocity of propagation can be then modeled, from hyperbolic reflections, in the form of velocity pathways from antenna positions to a buried rod. Each pathway is characterized by discrete points which are assumed in three dimensions as centers of micro cubic rock mass. This allows converting the velocity of propagation into a dielectric constant for mapping and modeling the dielectric constant in a volumetric rock mass using a volumetric data visualization software program (Voxler). In a case study, 6 steel drilling rods were diagonally inserted in a vertical face of a bench in a sandstone quarry. Five equally spaced parallel lines, almost perpendicular to the orientations of the rods, were surveyed by a dual frequency GPR antenna of 200 and 600 MHz. The results show that the dielectric constant is randomly varied within the micro and macro scale either in single radargrams or in the volumetric rock mass. The proposed method can be useful if considered in signal processing software programs, particularly in presence of subsurface utilities with known geometry and dimension, allowing converting double travel time, through portions of a radargram, into more reliable depths using discrete dielectric constant values instead of one value for a whole radargram.

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.

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.

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

Use of Ground Penetrating Radar for Site Investigation of Low-Volume Roadways and Design Recommendations

NASA Astrophysics Data System (ADS)

Scullion, T.; Saarenketo, T.

2002-07-01

This report will present several case studies describing the use of ground penetrating radar (GPR) technology for site investigations. Two types of GPR will be described-the air-launched and ground-coupled systems. The use of air-launched radar is well established within the Texas Department of Transportation (TxDOT). The limitation of this technology is its depth of penetration. While providing very useful information on the surface and base layers, it provides little information on the sub-grade soils. The use of low-frequency ground-coupled radar systems will provide little useful near-surface information but it can provide data on sub-grade properties and how they vary along a project. Combining both radar types can potentially provide a comprehensive subsurface investigative tool for both new pavement construction and for major pavement rehabilitation projects. In this report a brief description will be provided of the different systems together with the software used to process the GPR signals. Air-launched data are processed with the COLORMAP system developed by the Texas Transportation Institute. The ground-coupled data are processed using the Road Doctor system developed by Roadscanners, Inc. of Finland. The case studies presented were collected on actual TxDOT evaluation projects mainly in the Bryan District. They range from near-surface applications where the goal was to identify changes in pavement structure which were not available in construction records to identifying the areas beneath the pavement subsidence associated with strip mining activities.

Who is going to rescue the rescuers? Post-traumatic stress disorder among rescue workers operating in Greece during the European refugee crisis.

PubMed

Sifaki-Pistolla, Dimitra; Chatzea, Vasiliki-Eirini; Vlachaki, Sofia-Aikaterini; Melidoniotis, Evangelos; Pistolla, Georgia

2017-01-01

During the European refugee crisis, numerous Greek and international rescue workers are operating in Lesvos, offering search, rescue, and first aid services. Exposure to stressful life events while engaging in this rescue work can result in developing Post-Traumatic Stress Disorder (PTSD). The study aimed to assess the prevalence of PTSD and explore potential differences between different categories of rescuers. A cross-sectional study was conducted among 217 rescue workers. Participants were grouped according to affiliation: "Greek Professionals Rescuers/GPR", "International Professionals Rescuers/IPR" and "Volunteer Rescuers/VR". The PTSD Checklist-Civilian Version (PCL-C) was utilized. All tests were two-tailed (a = 0.05). Mann-Whitney, Kruskal-Wallis, and multivariate logistic regression were performed. Overall probable PTSD prevalence found was 17.1%. Rates varied significantly per rescuer's category; 23.1% in GPR, 11.8% in IPR, and 14.6% in VR (p = 0.02). GPR demonstrated the highest risk compared to IPR and VR (p < 0.001). Females had approximately two times higher risk. Other significant risk factors included marital status, age, and number of children. Lack of previous experience, longer operation period, longer shift hours, and handling dead refugees and dead children were also considered major risk factors. Rescue workers providing substantial aid to the refugees and migrants at Lesvos experience significant psychological distress. The present findings indicate the urgent need for targeted interventions. Further studies are needed to address long-term effects of the refugee crisis on rescuers, and explore effective measures to prevent PTSD.

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".

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.

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.

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.

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).

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.

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 ...

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.

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.

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.

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

Geo-statistical model of Rainfall erosivity by using high temporal resolution precipitation data in Europe

NASA Astrophysics Data System (ADS)

Panagos, Panos; Ballabio, Cristiano; Borrelli, Pasquale; Meusburger, Katrin; Alewell, Christine

2015-04-01

Rainfall erosivity (R-factor) is among the 6 input factors in estimating soil erosion risk by using the empirical Revised Universal Soil Loss Equation (RUSLE). R-factor is a driving force for soil erosion modelling and potentially can be used in flood risk assessments, landslides susceptibility, post-fire damage assessment, application of agricultural management practices and climate change modelling. The rainfall erosivity is extremely difficult to model at large scale (national, European) due to lack of high temporal resolution precipitation data which cover long-time series. In most cases, R-factor is estimated based on empirical equations which take into account precipitation volume. The Rainfall Erosivity Database on the European Scale (REDES) is the output of an extensive data collection of high resolution precipitation data in the 28 Member States of the European Union plus Switzerland taking place during 2013-2014 in collaboration with national meteorological/environmental services. Due to different temporal resolutions of the data (5, 10, 15, 30, 60 minutes), conversion equations have been applied in order to homogenise the database at 30-minutes interval. The 1,541 stations included in REDES have been interpolated using the Gaussian Process Regression (GPR) model using as covariates the climatic data (monthly precipitation, monthly temperature, wettest/driest month) from WorldClim Database, Digital Elevation Model and latitude/longitude. GPR has been selected among other candidate models (GAM, Regression Kriging) due the best performance both in cross validation (R2=0.63) and in fitting dataset (R2=0.72). The highest uncertainty has been noticed in North-western Scotland, North Sweden and Finland due to limited number of stations in REDES. Also, in highlands such as Alpine arch and Pyrenees the diversity of environmental features forced relatively high uncertainty. The rainfall erosivity map of Europe available at 500m resolution plus the standard error and the erosivity density (Rainfall erosivity per mm of precipitation) are available in the European Soil Data Centre (ESDAC). The highest erosivity has been found in the mediterrean countries (Italy, Western Greece, Spain, Northern Portugal), South Austria, Slovenia, Croatia and Western United Kingdom.

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.

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.

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

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).

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.

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.

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).

Interaction between GPR120 p.R270H loss-of-function variant and dietary fat intake on incident type 2 diabetes risk in the D.E.S.I.R. study.

PubMed

Lamri, A; Bonnefond, A; Meyre, D; Balkau, B; Roussel, R; Marre, M; Froguel, P; Fumeron, F

2016-10-01

GPR120 (encoded by FFAR4) is a lipid sensor that plays an important role in the control of energy balance. GPR120 is activated by long chain fatty acids (FAs) including omega-3 FAs. In humans, the loss of function p.R270H variant of the gene FFAR4 has been associated with a lower protein activity, an increased risk of obesity and higher fasting plasma glucose levels. The aim of this study was to investigate whether p.R270H interacts with dietary fat intake to modulate the risk of type 2 diabetes (T2D, 198 incident; 368 prevalent cases) and overweight (787 incident and 2891 prevalent cases) in the prospective D.E.S.I.R. study (n = 5,212, 9 years follow-up). The association of p.R270H with dietary fat and total calories was assessed by linear mixed models. The interaction between p.R270H and dietary fat on T2D and overweight was assessed by logistic regression analysis. The p.R270H variant had a minor allele frequency of 1.45% and was not significantly associated with total calories intake, fat intake or the total calories derived from fat (%). However, there was a significant interaction between p.R270H and dietary fat modulating the incidence of T2D (Pinteraction = 0.02) where the H-carriers had a higher risk of T2D than RR homozygotes in the low fat intake category only. The interaction between p.R270H and fat intake modulating the incidence and prevalence of overweight was not significant. The p.R270H variant of GPR120 modulates the risk of T2D in interaction with dietary fat intake in the D.E.S.I.R. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Association analysis of the chromosome 4p-located G protein-coupled receptor 78 (GPR78) gene in bipolar affective disorder and schizophrenia.

PubMed

Underwood, S L; Christoforou, A; Thomson, P A; Wray, N R; Tenesa, A; Whittaker, J; Adams, R A; Le Hellard, S; Morris, S W; Blackwood, D H R; Muir, W J; Porteous, D J; Evans, K L

2006-04-01

The orphan G protein-coupled receptor 78 (GPR78) gene lies within a region of chromosome 4p where we have previously shown linkage to bipolar affective disorder (BPAD) in a large Scottish family. GPR78 was screened for single-nucleotide polymorphisms (SNPs) and a linkage disequilibrium map was constructed. Six tagging SNPs were selected and tested for association on a sample of 377 BPAD, 392 schizophrenia (SCZ) and 470 control individuals. Using standard chi(2) statistics and a backwards logistic regression approach to adjust for the effect of sex, SNP rs1282, located approximately 3 kb upstream of the coding region, was identified as a potentially important variant in SCZ (chi(2) P=0.044; LRT P=0.065). When the analysis was restricted to females, the strength of association increased to an uncorrected allele P-value of 0.015 (odds ratios (OR)=1.688, 95% confidence intervals (CI): 1.104-2.581) and uncorrected genotype P-value of 0.015 (OR=5.991, 95% CI: 1.545-23.232). Under the recessive model, the genotype P-value improved further to 0.005 (OR=5.618, 95% CI: 1.460-21.617) and remained significant after correcting for multiple testing (P=0.017). No single-marker association was detected in the SCZ males, in the BPAD individuals or with any other SNP. Haplotype analysis of the case-control samples revealed several global and individual haplotypes, with P-values <0.05, all but one of which contained SNP rs1282. After correcting for multiple testing, two haplotypes remained significant in both the female BPAD individuals (P=0.038 and 0.032) and in the full sample of affected female individuals (P=0.044 and 0.033). Our results provide preliminary evidence for the involvement of GPR78 in susceptibility to BPAD and SCZ in the Scottish population. Molecular Psychiatry (2006) 11, 384-394. doi:10.1038/sj.mp.4001786; published online 3 January 2006.

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

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.

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.

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.

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

Estrogens Induce Rapid Cytoskeleton Re-Organization in Human Dermal Fibroblasts via the Non-Classical Receptor GPR30

PubMed Central

Carnesecchi, Julie; Malbouyres, Marilyne; de Mets, Richard; Balland, Martial; Beauchef, Gallic; Vié, Katell; Chamot, Christophe; Lionnet, Claire; Ruggiero, Florence; Vanacker, Jean-Marc

2015-01-01

The post-menopausal decrease in estrogen circulating levels results in rapid skin deterioration pointing out to a protective effect exerted by these hormones. The identity of the skin cell type responding to estrogens is unclear as are the cellular and molecular processes they elicit. Here, we reported that lack of estrogens induces rapid re-organization of the human dermal fibroblast cytoskeleton resulting in striking cell shape change. This morphological change was accompanied by a spatial re-organization of focal adhesion and a substantial reduction of their number as evidenced by vinculin and actin co-staining. Cell morphology and cytoskeleton organization was fully restored upon 17β-estradiol (E2) addition. Treatment with specific ER antagonists and cycloheximide respectively showed that the E2 acts independently of the classical Estrogen Receptors and that cell shape change is mediated by non-genomic mechanisms. E2 treatment resulted in a rapid and transient activation of ERK1/2 but not Src or PI3K. We show that human fibroblasts express the non-classical E2 receptor GPR30 and that its agonist G-1 phenocopies the effect of E2. Inhibiting GPR30 through treatment with the G-15 antagonist or specific shRNA impaired E2 effects. Altogether, our data reveal a novel mechanism by which estrogens act on skin fibroblast by regulating cell shape through the non-classical G protein-coupled receptor GPR30 and ERK1/2 activation. PMID:25781607

Estrogens induce rapid cytoskeleton re-organization in human dermal fibroblasts via the non-classical receptor GPR30.

PubMed

Carnesecchi, Julie; Malbouyres, Marilyne; de Mets, Richard; Balland, Martial; Beauchef, Gallic; Vié, Katell; Chamot, Christophe; Lionnet, Claire; Ruggiero, Florence; Vanacker, Jean-Marc

2015-01-01

The post-menopausal decrease in estrogen circulating levels results in rapid skin deterioration pointing out to a protective effect exerted by these hormones. The identity of the skin cell type responding to estrogens is unclear as are the cellular and molecular processes they elicit. Here, we reported that lack of estrogens induces rapid re-organization of the human dermal fibroblast cytoskeleton resulting in striking cell shape change. This morphological change was accompanied by a spatial re-organization of focal adhesion and a substantial reduction of their number as evidenced by vinculin and actin co-staining. Cell morphology and cytoskeleton organization was fully restored upon 17β-estradiol (E2) addition. Treatment with specific ER antagonists and cycloheximide respectively showed that the E2 acts independently of the classical Estrogen Receptors and that cell shape change is mediated by non-genomic mechanisms. E2 treatment resulted in a rapid and transient activation of ERK1/2 but not Src or PI3K. We show that human fibroblasts express the non-classical E2 receptor GPR30 and that its agonist G-1 phenocopies the effect of E2. Inhibiting GPR30 through treatment with the G-15 antagonist or specific shRNA impaired E2 effects. Altogether, our data reveal a novel mechanism by which estrogens act on skin fibroblast by regulating cell shape through the non-classical G protein-coupled receptor GPR30 and ERK1/2 activation.

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.

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.

Preprocessing of A-scan GPR data based on energy features

NASA Astrophysics Data System (ADS)

Dogan, Mesut; Turhan-Sayan, Gonul

2016-05-01

There is an increasing demand for noninvasive real-time detection and classification of buried objects in various civil and military applications. The problem of detection and annihilation of landmines is particularly important due to strong safety concerns. The requirement for a fast real-time decision process is as important as the requirements for high detection rates and low false alarm rates. In this paper, we introduce and demonstrate a computationally simple, timeefficient, energy-based preprocessing approach that can be used in ground penetrating radar (GPR) applications to eliminate reflections from the air-ground boundary and to locate the buried objects, simultaneously, at one easy step. The instantaneous power signals, the total energy values and the cumulative energy curves are extracted from the A-scan GPR data. The cumulative energy curves, in particular, are shown to be useful to detect the presence and location of buried objects in a fast and simple way while preserving the spectral content of the original A-scan data for further steps of physics-based target classification. The proposed method is demonstrated using the GPR data collected at the facilities of IPA Defense, Ankara at outdoor test lanes. Cylindrically shaped plastic containers were buried in fine-medium sand to simulate buried landmines. These plastic containers were half-filled by ammonium nitrate including metal pins. Results of this pilot study are demonstrated to be highly promising to motivate further research for the use of energy-based preprocessing features in landmine detection problem.

State-of-the-art and trends of Ground-Penetrating Radar antenna arrays

NASA Astrophysics Data System (ADS)

Vescovo, Roberto; Pajewski, Lara; Tosti, Fabio

2016-04-01

The aim of this contribution is to offer an overview on the antenna arrays for GPR systems, current trends and open issues. Antennas are a critical hardware component of a radar system, dictating its performance in terms of capability to detect targets. Nevertheless, most of the research efforts in the Ground-Penetrating Radar (GPR) area focus on the use of this imaging technique in a plethora of different applications and on the improvement of modelling/inversion/processing techniques, whereas a limited number of studies deal with technological issues related to the design of novel systems, including the synthesis, optimisation and characterisation of advanced antennas. Even fewer are the research activities carried out to develop innovative antenna arrays. GPR antennas operate in a strongly demanding environment and should satisfy a number of requirements, somehow unique and very different than those of conventional radar antennas. The same applies to GPR antenna arrays. The first requirement is an ultra-wide frequency band: the radar has to transmit and receive short-duration time-domain waveforms, in the order of a few nanoseconds, the time-duration of the emitted pulses being a trade-off between the desired radar resolution and penetration depth. Furthermore, GPR antennas should have a linear phase characteristic over the whole operational frequency range, predictable polarisation and gain. Due to the fact that a subsurface imaging system is essentially a short-range radar, the coupling between transmitting and receiving antennas has to be low and short in time. GPR antennas should have quick ring-down characteristics, in order to prevent masking of targets and guarantee a good resolution. The radiation patterns should ensure minimal interference with unwanted objects, usually present in the complex operational environment; to this aim, antennas should provide high directivity and concentrate the electromagnetic energy into a narrow solid angle. As GPR antennas work very close to the matter or even in contact with it, changes in electrical properties of the matter should not affect strongly the antenna performance, so that a wide applicability of the radar system can be achieved. Moreover, antennas should provide stable performance at different elevation levels. For an efficient coupling of electromagnetic waves into the ground/investigated structure, good impedance matching is necessary at the antenna/matter interface. Another important requirement concerns the weight and size of the antennas: for ease of utilisation and to allow a wide applicability, the antennas shall be light and compact. Array of antennas can be used in GPR systems to enable a faster data collection by increasing the extension of investigated area per time unit. This can be a significant advantage in archaeological prospection, road and bridge inspection, mine detection, as well as in several other civil-engineering and geoscience applications where the collection of data requires the execution of a large number of profiles. Moreover, antenna arrays allow collecting multi-offset measurements simultaneously, thereby providing additional information for a more effective imaging and characterisation of the natural or manmade scenario under test. Two approaches are possible to GPR array design. The simplest and most common is to conceive the array as a multi-channel radar system composed of single-channel radars. Much more can be achieved, if array-design techniques are employed to synthesise the whole system. This second approach is just beginning in the GPR field and is definitely promising, as it gives the possibility to fully exploit the potentiality of arrays. Another important issue, when using GPR systems on irregular surfaces, is that the position of array elements has to be recorded during the surveys, by using suitable high-precision positioning systems. Current research activities on the design of GPR arrays are progressing in various directions, including the synthesis of arrays with a high directivity achieved by using simple elements, arrays with the capability of a steerable beam as in smart antennas, arrays composed of adaptive antennas with electronic control of characteristics to adapt to different soils and materials, and application-specific arrays. Acknowledgement This abstract is a contribution to COST (European COoperation in Science and Technology) Action TU1208 "Civil engineering applications of Ground Penetrating Radar" (www.GPRadar.eu). The Authors thank COST for funding the Action TU1208.

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.

Depositional and erosional architectures of gravelly braid bar formed by a flood in the Abe River, central Japan, inferred from a three-dimensional ground-penetrating radar analysis

NASA Astrophysics Data System (ADS)

Okazaki, Hiroko; Kwak, Youngjoo; Tamura, Toru

2015-07-01

We conducted a ground-penetrating radar (GPR) survey of gravelly braid bars in the Abe River, central Japan, to clarify the three-dimensional (3D) variations in their depositional facies under various geomorphologic conditions. In September 2011, a ten-year return-period flood in the study area reworked and deposited braid bars. After the flood, we surveyed three bars with different geomorphologies using a GPR system with a 250-MHz antenna and identified seven fundamental radar depositional facies: Inclined reflections (facies Ia and Ib), horizontal to subhorizontal reflections (facies IIa and IIb), discontinuous reflections (facies IIIa and IIIb), and facies assemblage with a large-scale channel-shaped lower boundary (facies IV). Combinations of these facies indicate bar formation processes: channel filling, lateral aggradation, and lateral and downstream accretion. In the Abe River, aerial photographs and airborne laser scanning data were obtained before and after the flood. The observed changes of the surface topography are consistent with the subsurface results seen in the GPR sections. This study demonstrated that the erosional and depositional architecture observed among bars with different channel styles was related to river width and represented depositional processes for high-sediment discharge. The quantitative characterizations of the sedimentary architecture will be useful for interpreting gravelly fluvial deposits in the rock record.

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 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.

4D ground penetrating radar measurements as non-invasive means for hydrological process investigation

NASA Astrophysics Data System (ADS)

Jackisch, Conrad; Allroggen, Niklas

2017-04-01

The missing vision into the subsurface appears to be a major limiting factor for our hydrological process understanding and theory development. Today, hydrology-related sciences have collected tremendous evidence for soils acting as drainage network and retention stores simultaneously in structured and self-organising domains. However, our present observation technology relies mainly on point-scale sensors, which integrate over a volume of unknown structures and is blind for their distribution. Although heterogeneity is acknowledged at all scales, it is rarely seen as inherent system property. At small scales (soil moisture probe) and at large scales (neutron probe) our measurements leave quite some ambiguity. Consequently, spatially and temporally continuous measurement of soil water states is essential for advancing our understanding and development of subsurface process theories. We present results from several irrigation experiments accompanied by 2D and 3D time-lapse GPR for the development of a novel technique to visualise and quantify water dynamics in the subsurface. Through the comparison of TDR, tracer and gravimetric measurement of soil moisture it becomes apparent that all sensor-based techniques are capable to record temporal dynamics, but are challenged to precisely quantify the measurements and to extrapolate them in space. At the same time excavative methods are very limited in temporal and spatial resolution. The application of non-invasive 4D GPR measurements complements the existing techniques and reveals structural and temporal dynamics simultaneously. By consequently increasing the density of the GPR data recordings in time and space, we find means to process the data also in the time-dimension. This opens ways to quantitatively analyse soil water dynamics in complex settings.

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.

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.