Science.gov

Sample records for acoustic-to-seismic coupled signals

  1. Acoustic-to-seismic coupling variations in cold regions

    NASA Astrophysics Data System (ADS)

    Albert, Donald G.

    2002-05-01

    Experiments were conducted to investigate the variations that may occur in acoustic-to-seismic coupling arising from changes in local near-surface conditions. The emphasis of the investigations was on cold regions, where many different surface conditions exist and where conditions may change over a short time period from wind, precipitation, freezing, or thawing. The measurements were conducted by recording blank pistol shots with surface geophones and microphones. Results are presented for grassland, thin and thick seasonal snow covers, polar firn, thin grounded ice, thick glacier ice, and floating river ice. The ratio of induced ground motion to acoustic pressure ranged from 0.5 to 20 micro-meters per second per Pascal. Often two arrivals were detected on the geophones, a high-speed seismic compressional wave followed by the air wave. [Work funded by the U.S. Army.

  2. T-phase Observations in Northern California: Acoustic to Seismic Coupling at a Weakly Elastic Boundary

    NASA Astrophysics Data System (ADS)

    deGroot-Hedlin, C.; Orcutt, J.

    - Plans for a hydroacoustic network intended to monitor compliance with the CTBT call for the inclusion of five T-phase stations situated at optimal locations for the detection of seismic phases converted from ocean-borne T phases. We examine factors affecting the sensitivity of land-based stations to the seismic T phase. The acoustic to seismic coupling phenomenon is described by upslope propagation of an acoustic ray impinging at a sloping elastic wedge. We examine acoustic to seismic coupling characteristics for two cases; the first in which the shear velocity of the bottom is greater than the compressional velocity of the fluid (i.e., vp > vs > vw), the second is a weakly elastic solid in which vs<< vw< vp. The former is representative of velocities in solid rock, which might be encountered at volcanic islands; the latter is representative of marine sediments. For the case where vs > vw, we show that acoustic energy couples primarily to shear wave energy, except at very high slope angles. We show that the weakly elastic solid (i.e., vs << vw) behaves nearly like a fluid bottom, with acoustic energy coupling to both P and S waves even at low slope angles.We examine converted T-wave arrivals at northern California seismic stations for two event clusters; one a series of earthquakes near the Hawaiian Islands, the other a series of nuclear tests conducted near the Tuamoto archipelago. Each cluster yielded characteristic arrivals at each station which were consistent from event to event within a cluster, but differed between clusters. The seismic T-phases consisted of both P- and S-wave arrivals, consistent with the conversion of acoustic to seismic energy at a gently sloping sediment-covered seafloor. In general, the amplitudes of the seismic T phases were highest for stations nearest the continental slope, where seafloor slopes are greatest, however noise levels decrease rapidly with increasing distance from the coastline, so that T-wave arrivals were observable

  3. On the location of frequencies of maximum acoustic-to-seismic coupling

    SciTech Connect

    Sabatier, J.M.; Bass, H.E.; Elliott, G.R.

    1986-10-01

    Measurements of the acoustic-to-seismic transfer function (ratio of the normal soil particle velocity at a depth d to the acoustic pressure at the surface) for outdoor ground surfaces quite typically reveal a series of maxima and minima. In a publication (Sabatier et al., J. Acoust. Soc. Am. 80, 646--649 (1986)), the location and magnitude of these maxima are measured and predicted for several outdoor ground surfaces using a layered poroelastic model of the ground surface. In this paper, the seismic transfer function for a desert site is compared to the seismic transfer function for holes dug in the desert floor which were filled with pumice (volcanic rock). The hole geometry was rectangular and the hole depths varied from 0.25--2.0 m. The p- and s-wave speeds, densities, porosities, and flow resistivities for the desert floor and pumice were all measured. By varying the hole depth and the fill material, the maxima in the seismic transfer function can be shifted in frequency and the locations of the maxima compare reasonably with that of a hard-backed layer calculation. The area or extent of the acoustic-to-seismic coupling for pumice was determined to be less than 1 m/sup 2/.

  4. In situ measurements of the fragipan acoustic to seismic coupling signature

    NASA Astrophysics Data System (ADS)

    Howard, Wheeler; Hickey, Craig J.

    2002-05-01

    The phenomena of acoustic to seismic (A/S) coupling, observed and studied since the 1950s, has most recently been used to detect shallow buried objects [Sabatier and Xiang, J. Acoust. Soc. Am. 105, 1383 (1999); 106, 2143 (1999)] and monitor detonation of nuclear weapons [Orcutt, J. Acoust. Soc. Am. 105, 1038 (1999)]. At an air-surface interface airborne acoustic energy is coupled into the ground as seismic energy. The ratio of the seismic and airborne waves constitutes the A/S coupling signature, which is distinctive to the underlying structure. Seismic energy received by a geophone at the interface contains information, via reflected waves, about the underlying subsurface layer, media, and boundaries. Of particular interest in the Mississippi River Valley is the fragipan layer. The fragipan is the layer that directly affects the growth of crops, rate of soil erosion, and rate of water absorption in underlying layers. In this presentation, the A/S coupling signature data taken at an agricultural field station and forward model are discussed.

  5. An experimental study on antipersonnel landmine detection using acoustic-to-seismic coupling.

    PubMed

    Xiang, Ning; Sabatier, James M

    2003-03-01

    An acoustic-to-seismic system to detect buried antipersonnel mines exploits airborne acoustic waves penetrating the surface of the ground. Acoustic waves radiating from a sound source above the ground excite Biot type I and II compressional waves in the porous soil. The type I wave and type II waves refract toward the normal and cause air and soil particle motion. If a landmine is buried below the surface of the insonified area, these waves are scattered or reflected by the target, resulting in distinct changes to the acoustically coupled ground motion. A scanning laser Doppler vibrometer measures the motion of the ground surface. In the past, this technique has been employed with remarkable success in locating antitank mines during blind field tests [Sabatier and Xiang, IEEE Trans. Geosci. Remote Sens. 39, 1146-1154 (2001)]. The humanitarian demining mission requires an ability to locate antipersonnel mines, requiring a surmounting of additional challenges due to a plethora of shapes and smaller sizes. This paper describes an experimental study on the methods used to locate antipersonnel landmines in recent field measurements. PMID:12656368

  6. Air-ground interface: Surface waves, surface impedance and acoustic-to-seismic coupling coefficient

    NASA Technical Reports Server (NTRS)

    Daigle, Gilles; Embleton, Tony

    1990-01-01

    In atmospheric acoustics, the subject of surface waves has been an area of discussion for many years. The existence of an acoustic surface wave is now well established theoretically. The mathematical solution for spherical wave propagation above an impedance boundary includes the possibility of a contribution that possesses all the standard properties for a surface wave. Surface waves exist when the surface is sufficiently porous, relative to its acoustical resistance, that it can influence the airborne particle velocity near the surface and reduce the phase velocity of sound waves in air at the surface. This traps some of the sound energy in the air to remain near the surface as it propagates. Above porous grounds, the existence of surface waves has eluded direct experimental confirmation (pulse experiments have failed to show a separate arrival expected from the reduced phase speed) and indirect evidence for its existence has appeared contradictory. The experimental evidence for the existence of an acoustical surface wave above porous boundaries is reviewed. Recent measurements including pulse experiments are also described. A few years ago the acoustic impedance of a grass-covered surface was measured in the frequency range 30 to 300 Hz. Here, further measurements on the same site are discussed. These measurements include core samples, a shallow refractive survey to determine the seismic velocities, and measurements of the acoustic-to-seismic coupling coefficient.

  7. Investigation of the near subsurface using acoustic to seismic coupling

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Agricultural, hydrological and civil engineering applications have realized a need for information of the near subsurface over large areas. In order to obtain this spatially distributed data over such scales, the measurement technique must be highly mobile with a short acquisition time. Therefore, s...

  8. Direct coupling of haptic signals between hands

    PubMed Central

    Dupin, Lucile; Hayward, Vincent; Wexler, Mark

    2015-01-01

    Although motor actions can profoundly affect the perceptual interpretation of sensory inputs, it is not known whether the combination of sensory and movement signals occurs only for sensory surfaces undergoing movement or whether it is a more general phenomenon. In the haptic modality, the independent movement of multiple sensory surfaces poses a challenge to the nervous system when combining the tactile and kinesthetic signals into a coherent percept. When exploring a stationary object, the tactile and kinesthetic signals come from the same hand. Here we probe the internal structure of haptic combination by directing the two signal streams to separate hands: one hand moves but receives no tactile stimulation, while the other hand feels the consequences of the first hand’s movement but remains still. We find that both discrete and continuous tactile and kinesthetic signals are combined as if they came from the same hand. This combination proceeds by direct coupling or transfer of the kinesthetic signal from the moving to the feeling hand, rather than assuming the displacement of a mediating object. The combination of signals is due to perception rather than inference, because a small temporal offset between the signals significantly degrades performance. These results suggest that the brain simplifies the complex coordinate transformation task of remapping sensory inputs to take into account the movements of multiple body parts in haptic perception, and they show that the effects of action are not limited to moving sensors. PMID:25548179

  9. Direct coupling of haptic signals between hands.

    PubMed

    Dupin, Lucile; Hayward, Vincent; Wexler, Mark

    2015-01-13

    Although motor actions can profoundly affect the perceptual interpretation of sensory inputs, it is not known whether the combination of sensory and movement signals occurs only for sensory surfaces undergoing movement or whether it is a more general phenomenon. In the haptic modality, the independent movement of multiple sensory surfaces poses a challenge to the nervous system when combining the tactile and kinesthetic signals into a coherent percept. When exploring a stationary object, the tactile and kinesthetic signals come from the same hand. Here we probe the internal structure of haptic combination by directing the two signal streams to separate hands: one hand moves but receives no tactile stimulation, while the other hand feels the consequences of the first hand's movement but remains still. We find that both discrete and continuous tactile and kinesthetic signals are combined as if they came from the same hand. This combination proceeds by direct coupling or transfer of the kinesthetic signal from the moving to the feeling hand, rather than assuming the displacement of a mediating object. The combination of signals is due to perception rather than inference, because a small temporal offset between the signals significantly degrades performance. These results suggest that the brain simplifies the complex coordinate transformation task of remapping sensory inputs to take into account the movements of multiple body parts in haptic perception, and they show that the effects of action are not limited to moving sensors. PMID:25548179

  10. Signaling through G protein coupled receptors

    PubMed Central

    2009-01-01

    Heterotrimeric G proteins (Gα, Gβ/Gγ subunits) constitute one of the most important components of cell signaling cascade. G Protein Coupled Receptors (GPCRs) perceive many extracellular signals and transduce them to heterotrimeric G proteins, which further transduce these signals intracellular to appropriate downstream effectors and thereby play an important role in various signaling pathways. GPCRs exist as a superfamily of integral membrane protein receptors that contain seven transmembrane α-helical regions, which bind to a wide range of ligands. Upon activation by a ligand, the GPCR undergoes a conformational change and then activate the G proteins by promoting the exchange of GDP/GTP associated with the Gα subunit. This leads to the dissociation of Gβ/Gγ dimer from Gα. Both these moieties then become free to act upon their downstream effectors and thereby initiate unique intracellular signaling responses. After the signal propagation, the GTP of Gα-GTP is hydrolyzed to GDP and Gα becomes inactive (Gα-GDP), which leads to its re-association with the Gβ/Gγ dimer to form the inactive heterotrimeric complex. The GPCR can also transduce the signal through G protein independent pathway. GPCRs also regulate cell cycle progression. Till to date thousands of GPCRs are known from animal kingdom with little homology among them, but only single GPCR has been identified in plant system. The Arabidopsis GPCR was reported to be cell cycle regulated and also involved in ABA and in stress signaling. Here I have described a general mechanism of signal transduction through GPCR/G proteins, structure of GPCRs, family of GPCRs and plant GPCR and its role. PMID:19826234

  11. Polished Downhole Transducer Having Improved Signal Coupling

    DOEpatents

    Hall, David R.; Fox, Joe

    2006-03-28

    Apparatus and methods to improve signal coupling in downhole inductive transmission elements to reduce the dispersion of magnetic energy at the tool joints and to provide consistent impedance and contact between transmission elements located along the drill string. A transmission element for transmitting information between downhole tools is disclosed in one embodiment of the invention as including an annular core constructed of a magnetically conductive material. The annular core forms an open channel around its circumference and is configured to form a closed channel by mating with a corresponding annular core along an annular mating surface. The mating surface is polished to provide improved magnetic coupling with the corresponding annular core. An annular conductor is disposed within the open channel.

  12. Signal bi-amplification in networks of unidirectionally coupled MEMS

    NASA Astrophysics Data System (ADS)

    Tchakui, Murielle Vanessa; Woafo, Paul; Colet, Pere

    2016-01-01

    The purpose of this paper is to analyze the propagation and the amplification of an input signal in networks of unidirectionally coupled micro-electro-mechanical systems (MEMS). Two types of external excitations are considered: sinusoidal and stochastic signals. We show that sinusoidal signals are amplified up to a saturation level which depends on the transmission rate and despite MEMS being nonlinear the sinusoidal shape is well preserved if the number of MEMS is not too large. However, increasing the number of MEMS, there is an instability that leads to chaotic behavior and which is triggered by the amplification of the harmonics generated by the nonlinearities. We also show that for stochastic input signals, the MEMS array acts as a band-pass filter and after just a few elements the signal has a narrow power spectra.

  13. Heterotrimeric G Protein–Coupled Signaling in Plants

    PubMed Central

    Urano, Daisuke; Jones, Alan M.

    2016-01-01

    Investigators studying G protein–coupled signaling—often called the best-understood pathway in the world owing to intense research in medical fields—have adopted plants as a new model to explore the plasticity and evolution of G signaling. Much research on plant G signaling has not disappointed. Although plant cells have most of the core elements found in animal G signaling, differences in network architecture and intrinsic properties of plant G protein elements make G signaling in plant cells distinct from the animal paradigm. In contrast to animal G proteins, plant G proteins are self-activating, and therefore regulation of G activation in plants occurs at the deactivation step. The self-activating property also means that plant G proteins do not need and therefore do not have typical animal G protein–coupled receptors. Targets of activated plant G proteins, also known as effectors, are unlike effectors in animal cells. The simpler repertoire of G signal elements in Arabidopsis makes G signaling easier to manipulate in a multicellular context. PMID:24313842

  14. Reversible Gating of Plasmonic Coupling for Optical Signal Amplification.

    PubMed

    Khoury, Christopher G; Fales, Andrew M; Vo-Dinh, Tuan

    2016-07-20

    Amplification of optical signals is useful for a wide variety of applications, ranging from data signal transmission to chemical sensing and biomedical diagnostics. One such application in chemical sensing is surface-enhanced Raman scattering (SERS), an important technique for increasing the Raman signal using the plasmonic effect of enhanced electromagnetic fields associated with metallic nanostructures. One of the most important limitations of SERS-based amplification is the difficulty to reproducibly control the SERS signal. Here, we describe the design and implementation of a unique hybrid system capable of producing reversible gating of plasmonic coupling for Raman signal amplification. The hybrid system is composed of two subsystems: (1) colloidal magneto-plasmonic nanoparticles for SERS enhancement and (2) a micromagnet substrate with an externally applied magnetic field to modulate the colloidal nanoparticles. For this proof of concept demonstration, the nanoparticles were labeled with a Raman-active dye, and it was shown that the detected SERS signal could be reproducibly modulated by controlling the externally applied magnetic field. The developed system provides a simple, robust, inexpensive, and reusable device for SERS signal modulation. These properties will open up new possibilities for optical signal amplification and gating as well for high-throughput, reproducible SERS detection. PMID:27347606

  15. Medium effect on the characteristics of the coupled seismic and electromagnetic signals

    PubMed Central

    HUANG, Qinghua; REN, Hengxin; ZHANG, Dan; CHEN, Y. John

    2015-01-01

    Recently developed numerical simulation technique can simulate the coupled seismic and electromagnetic signals for a double couple point source or a finite fault planar source. Besides the source effect, the simulation results showed that both medium structure and medium property could affect the coupled seismic and electromagnetic signals. The waveform of coupled signals for a layered structure is more complicated than that for a simple uniform structure. Different from the seismic signals, the electromagnetic signals are sensitive to the medium properties such as fluid salinity and fluid viscosity. Therefore, the co-seismic electromagnetic signals may be more informative than seismic signals. PMID:25743062

  16. Low power, compact charge coupled device signal processing system

    NASA Technical Reports Server (NTRS)

    Bosshart, P. W.; Buss, D. D.; Eversole, W. L.; Hewes, C. R.; Mayer, D. J.

    1980-01-01

    A variety of charged coupled devices (CCDs) for performing programmable correlation for preprocessing environmental sensor data preparatory to its transmission to the ground were developed. A total of two separate ICs were developed and a third was evaluated. The first IC was a CCD chirp z transform IC capable of performing a 32 point DFT at frequencies to 1 MHz. All on chip circuitry operated as designed with the exception of the limited dynamic range caused by a fixed pattern noise due to interactions between the digital and analog circuits. The second IC developed was a 64 stage CCD analog/analog correlator for performing time domain correlation. Multiplier errors were found to be less than 1 percent at designed signal levels and less than 0.3 percent at the measured smaller levels. A prototype IC for performing time domain correlation was also evaluated.

  17. Spatio-temporal coupling of EEG signals in epilepsy

    NASA Astrophysics Data System (ADS)

    Senger, Vanessa; Müller, Jens; Tetzlaff, Ronald

    2011-05-01

    Approximately 1% of the world's population suffer from epileptic seizures throughout their lives that mostly come without sign or warning. Thus, epilepsy is the most common chronical disorder of the neurological system. In the past decades, the problem of detecting a pre-seizure state in epilepsy using EEG signals has been addressed in many contributions by various authors over the past two decades. Up to now, the goal of identifying an impending epileptic seizure with sufficient specificity and reliability has not yet been achieved. Cellular Nonlinear Networks (CNN) are characterized by local couplings of dynamical systems of comparably low complexity. Thus, they are well suited for an implementation as highly parallel analogue processors. Programmable sensor-processor realizations of CNN combine high computational power comparable to tera ops of digital processors with low power consumption. An algorithm allowing an automated and reliable detection of epileptic seizure precursors would be a"huge step" towards the vision of an implantable seizure warning device that could provide information to patients and for a time/event specific treatment directly in the brain. Recent contributions have shown that modeling of brain electrical activity by solutions of Reaction-Diffusion-CNN as well as the application of a CNN predictor taking into account values of neighboring electrodes may contribute to the realization of a seizure warning device. In this paper, a CNN based predictor corresponding to a spatio-temporal filter is applied to multi channel EEG data in order to identify mutual couplings for different channels which lead to a enhanced prediction quality. Long term EEG recordings of different patients are considered. Results calculated for these recordings with inter-ictal phases as well as phases with seizures will be discussed in detail.

  18. Dopamine Coupling to Mitochondrial Signaling: Implications for Transplantation.

    PubMed

    Stefano, George B; Ramin, Rohina; Kream, Richard M

    2016-01-01

    The persistence of major medical disorders afflicting millions of humans worldwide involves a functional pathophysiological coupling of systemic pro-inflammatory processes and tissue hypoxia. Mechanistically, reciprocal triggering of multiple ischemic/hypoxic and pro-inflammatory events, if not corrected, will promote pathophysiological amplification leading to a deleterious cascade of bio-senescent cellular and molecular signaling pathways that converge to markedly impair mitochondrial energy production. Given the level of energy production and utilization that can vary in and between cells and regionally in the same type of cells found in the body, e.g., dopamine neurons, the metabolic energy regulator, the mitochondrion, assumes a high position in the potential to maintain normal health and develop abnormal activities, resulting in chronic pathologies. The intra-mitochondrial availability of molecular oxygen as the ultimate electron acceptor drives the evolutionarily fashioned chemiosmotic production of ATP as a high-efficiency biological proton pump process. The mechanistic evolutionary bases of diabetes have demonstrated the profound alteration of normative mitochondrial function, notably deregulated respiratory processes. This same phenomenon provides evidence of mitochondrial linkages to neurological disorders, such as Parkinson's disease. To date, and despite considerable research efforts, the practical realization of advanced mitochondrial targeted therapies has not been forthcoming. PMID:26790458

  19. All-optical signal amplifier and distributor using cavity-atom coupling systems

    NASA Astrophysics Data System (ADS)

    Duan, Yafan; Lin, Gongwei; Niu, Yueping; Gong, Shangqing

    2016-05-01

    We report an all-optical signal amplifier and a signal distributor using cavity-atom coupling systems. In this system we couple atoms with an optical cavity and realize the great enhancement of a control laser by the cavity with the help of two high coupling lasers. By this effect, we can use one weak control field to control another strong target field and the intensity changes are linear with our experimental conditions. This can be used as an all-optical signal amplifier, also known as a ‘transphasor’. In our experiment, the gain of the weak field to strong field can be as high as 60. Furthermore, we can realize the distribution of optical signals, if we coordinate multiple cavity-atom coupling systems.

  20. Derailed Estrogen Signaling and Breast Cancer: An Authentic Couple

    PubMed Central

    Dey, Oindrilla; Gajulapalli, Vijay Narsihma Reddy; Bhatia, Raghavendra Singh; Bugide, Suresh; Kumar, Rakesh

    2013-01-01

    Estrogen or 17β-estradiol, a steroid hormone, plays a critical role in the development of mammary gland via acting through specific receptors. In particular, estrogen receptor-α (ERα) acts as a transcription factor and/or a signal transducer while participating in the development of mammary gland and breast cancer. Accumulating evidence suggests that the transcriptional activity of ERα is altered by the action of nuclear receptor coregulators and might be responsible, at least in part, for the development of breast cancer. In addition, this process is driven by various posttranslational modifications of ERα, implicating active participation of the upstream receptor modifying enzymes in breast cancer progression. Emerging studies suggest that the biological outcome of breast cancer cells is also influenced by the cross talk between microRNA and ERα signaling, as well as by breast cancer stem cells. Thus, multiple regulatory controls of ERα render mammary epithelium at risk for transformation upon deregulation of normal homeostasis. Given the importance that ERα signaling has in breast cancer development, here we will highlight how the activity of ERα is controlled by various regulators in a spatial and temporal manner, impacting the progression of the disease. We will also discuss the possible therapeutic value of ERα modulators as alternative drug targets to retard the progression of breast cancer. PMID:22947396

  1. Coupling Oxidative Signals to Protein Phosphorylation via Methionine Oxidation in Arabidopsis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The mechanisms involved in sensing oxidative signaling molecules such as H2O2 in plant and animal cells are not completely understood. In the present study, we tested the postulate that oxidation of methionine (Met) to Met sulfoxide (MetSO) can couple oxidative signals to changes in protein phosphor...

  2. Queueing up for enzymatic processing: correlated signaling through coupled degradation.

    PubMed

    Cookson, Natalie A; Mather, William H; Danino, Tal; Mondragón-Palomino, Octavio; Williams, Ruth J; Tsimring, Lev S; Hasty, Jeff

    2011-01-01

    High-throughput technologies have led to the generation of complex wiring diagrams as a post-sequencing paradigm for depicting the interactions between vast and diverse cellular species. While these diagrams are useful for analyzing biological systems on a large scale, a detailed understanding of the molecular mechanisms that underlie the observed network connections is critical for the further development of systems and synthetic biology. Here, we use queueing theory to investigate how 'waiting lines' can lead to correlations between protein 'customers' that are coupled solely through a downstream set of enzymatic 'servers'. Using the E. coli ClpXP degradation machine as a model processing system, we observe significant cross-talk between two networks that are indirectly coupled through a common set of processors. We further illustrate the implications of enzymatic queueing using a synthetic biology application, in which two independent synthetic networks demonstrate synchronized behavior when common ClpXP machinery is overburdened. Our results demonstrate that such post-translational processes can lead to dynamic connections in cellular networks and may provide a mechanistic understanding of existing but currently inexplicable links. PMID:22186735

  3. Spatial and Temporal Aspects of Signaling by G-Protein-Coupled Receptors.

    PubMed

    Lohse, Martin J; Hofmann, Klaus Peter

    2015-09-01

    Signaling by G-protein-coupled receptors is often considered a uniform process, whereby a homogeneously activated proportion of randomly distributed receptors are activated under equilibrium conditions and produce homogeneous, steady-state intracellular signals. While this may be the case in some biologic systems, the example of rhodopsin with its strictly local single-quantum mode of function shows that homogeneity in space and time cannot be a general property of G-protein-coupled systems. Recent work has now revealed many other systems where such simplicity does not prevail. Instead, a plethora of mechanisms allows much more complex patterns of receptor activation and signaling: different mechanisms of protein-protein interaction; temporal changes under nonequilibrium conditions; localized receptor activation; and localized second messenger generation and degradation-all of which shape receptor-generated signals and permit the creation of multiple signal types. Here, we review the evidence for such pleiotropic receptor signaling in space and time. PMID:26184590

  4. Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability.

    PubMed

    García-Cáceres, Cristina; Quarta, Carmelo; Varela, Luis; Gao, Yuanqing; Gruber, Tim; Legutko, Beata; Jastroch, Martin; Johansson, Pia; Ninkovic, Jovica; Yi, Chun-Xia; Le Thuc, Ophelia; Szigeti-Buck, Klara; Cai, Weikang; Meyer, Carola W; Pfluger, Paul T; Fernandez, Ana M; Luquet, Serge; Woods, Stephen C; Torres-Alemán, Ignacio; Kahn, C Ronald; Götz, Magdalena; Horvath, Tamas L; Tschöp, Matthias H

    2016-08-11

    We report that astrocytic insulin signaling co-regulates hypothalamic glucose sensing and systemic glucose metabolism. Postnatal ablation of insulin receptors (IRs) in glial fibrillary acidic protein (GFAP)-expressing cells affects hypothalamic astrocyte morphology, mitochondrial function, and circuit connectivity. Accordingly, astrocytic IR ablation reduces glucose-induced activation of hypothalamic pro-opio-melanocortin (POMC) neurons and impairs physiological responses to changes in glucose availability. Hypothalamus-specific knockout of astrocytic IRs, as well as postnatal ablation by targeting glutamate aspartate transporter (GLAST)-expressing cells, replicates such alterations. A normal response to altering directly CNS glucose levels in mice lacking astrocytic IRs indicates a role in glucose transport across the blood-brain barrier (BBB). This was confirmed in vivo in GFAP-IR KO mice by using positron emission tomography and glucose monitoring in cerebral spinal fluid. We conclude that insulin signaling in hypothalamic astrocytes co-controls CNS glucose sensing and systemic glucose metabolism via regulation of glucose uptake across the BBB. PMID:27518562

  5. Reservoir computing with a slowly modulated mask signal for preprocessing using a mutually coupled optoelectronic system

    NASA Astrophysics Data System (ADS)

    Tezuka, Miwa; Kanno, Kazutaka; Bunsen, Masatoshi

    2016-08-01

    Reservoir computing is a machine-learning paradigm based on information processing in the human brain. We numerically demonstrate reservoir computing with a slowly modulated mask signal for preprocessing by using a mutually coupled optoelectronic system. The performance of our system is quantitatively evaluated by a chaotic time series prediction task. Our system can produce comparable performance with reservoir computing with a single feedback system and a fast modulated mask signal. We showed that it is possible to slow down the modulation speed of the mask signal by using the mutually coupled system in reservoir computing.

  6. New direction of arrival estimation of coherent signals based on reconstructing matrix under unknown mutual coupling

    NASA Astrophysics Data System (ADS)

    Guo, Rui; Li, Weixing; Zhang, Yue; Chen, Zengping

    2016-01-01

    A direction of arrival (DOA) estimation algorithm for coherent signals in the presence of unknown mutual coupling is proposed. A group of auxiliary sensors in a uniform linear array are applied to eliminate the effects on the orthogonality of subspaces brought by mutual coupling. Then, a Toeplitz matrix, whose rank is independent of the coherency between impinging signals, is reconstructed to eliminate the rank loss of the spatial covariance matrix. Therefore, the signal and noise subspaces can be estimated properly. This method can estimate the DOAs of coherent signals under unknown mutual coupling accurately without any iteration and calibration sources. It has a low computational burden and high accuracy. Simulation results demonstrate the effectiveness of the algorithm.

  7. The Acoustic Signal of a Helicopter can be Used to Track it With Seismic Arrays

    NASA Astrophysics Data System (ADS)

    Eibl, Eva P. S.; Lokmer, Ivan; Bean, Christopher J.; Akerlie, Eggert

    2016-04-01

    We apply traditional frequency domain methods usually applied to volcanic tremor on seismic recordings of a helicopter. On a volcano the source can be repeating, closely spaced earthquakes whereas for a helicopter the source are repeating pressure pulses from the rotor blades that are converted through acoustic-to-seismic coupling. In both cases the seismic signal is referred to as tremor. As frequency gliding is in this case merely caused by the Doppler effect, not a change in the source, we can use its shape to deduce properties of the helicopter. We show in this analysis that the amount of rotor blades, rotor revolutions per minute (RPM), flight direction, height and location can be deduced. The signal was recorded by a seven station broadband array with an aperture of 1.6 km. Our spacing is close enough to record the signal at all stations and far enough to observe traveltime differences. We perform a detailed spectral and location analysis of the signal, and compare our results with the known information on the helicopter's speed, location, height, the frequency of the blades rotation and the amount of blades. This analysis is based on the characteristic shape of the curve i.e. speed of the gliding, minimum and maximum fundamental frequency, amplitudes at the inflection points at different stations and traveltimes deduced from the inflection points at different stations. The helicopter GPS track gives us a robust way of testing the method. This observation has an educative value, because the same principles can be applied to signals in different disciplines.

  8. Enhanced signal coupling in wide-field fiber-coupled imagers.

    PubMed

    Arianpour, Ashkan; Motamedi, Nojan; Agurok, Ilya P; Ford, Joseph E

    2015-02-23

    Some high-performance imaging systems, including wide angle "monocentric" lenses made of concentric spherical shells, form a deeply curved image surface coupled to focal plane sensors by optical fiber bundles with a curved input and flat output face. However, refraction at the angled input facet limits the range of input angles, even for fiber bundles with numerical aperture 1. Here we investigate using a curved beam deflector near the focal surface to increase the field of view and improve spatial resolution at the edges of the field of view. We show the field of view of such an imager can be increased from approximately 60° (full width at half maximum intensity) to over 90° using an embossed refractive microprism array, where the prism angle varies across the aperture to maintain coupling. We describe a proof-of-principle experiment using a f = 17.8mm fiber-coupled monocentric singlet lens, and show that a local region of microprisms embossed into a thin layer of SU-8 photopolymer can increase the field of view by 50%. PMID:25836560

  9. Endogenous field feedback promotes the detectability for exogenous electric signal in the hybrid coupled population

    SciTech Connect

    Wei, Xile; Zhang, Danhong; Wang, Jiang; Yu, Haitao; Lu, Meili; Che, Yanqiu

    2015-01-15

    This paper presents the endogenous electric field in chemical or electrical synaptic coupled networks, aiming to study the role of endogenous field feedback in the signal propagation in neural systems. It shows that the feedback of endogenous fields to network activities can reduce the required energy of the noise and enhance the transmission of input signals in hybrid coupled populations. As a common and important nonsynaptic interactive method among neurons, particularly, the endogenous filed feedback can not only promote the detectability of exogenous weak signal in hybrid coupled neural population but also enhance the robustness of the detectability against noise. Furthermore, with the increasing of field coupling strengths, the endogenous field feedback is conductive to the stochastic resonance by facilitating the transition of cluster activities from the no spiking to spiking regions. Distinct from synaptic coupling, the endogenous field feedback can play a role as internal driving force to boost the population activities, which is similar to the noise. Thus, it can help to transmit exogenous weak signals within the network in the absence of noise drive via the stochastic-like resonance.

  10. Axon Targeting of Olfactory Receptor Neurons is Patterned by Coupled Hedgehog Signaling at Two Distinct Steps

    PubMed Central

    Chou, Ya-Hui; Zheng, Xiaoyan; Beachy, Philip A.; Luo, Liqun

    2010-01-01

    SUMMARY We present evidence for a novel, coupled two-step action of Hedgehog signaling in patterning axon targeting of Drosophila olfactory receptor neurons (ORNs). In the first step, differential Hedgehog pathway activity in peripheral sensory organ precursors creates ORN populations with different levels of the Patched receptor. Different Patched levels in ORNs then determine axonal responsiveness to target-derived Hedgehog in the brain: only ORN axons that do not express high levels of Patched are responsive to and require a second-step of Hedgehog signaling for target selection. Hedgehog signaling in the imaginal sensory organ precursors thus confers differential ORN responsiveness to Hedgehog-mediated axon targeting in the brain. This mechanism contributes to the spatial coordination of ORN cell bodies in the periphery and their glomerular targets in the brain. Such coupled two-step signaling may be more generally used to coordinate other spatially and temporally segregated developmental events. PMID:20850015

  11. Coupling vs decoupling approaches for PDE/ODE systems modeling intercellular signaling

    NASA Astrophysics Data System (ADS)

    Carraro, Thomas; Friedmann, Elfriede; Gerecht, Daniel

    2016-06-01

    We consider PDE/ODE systems for the simulation of intercellular signaling in multicellular environments. The intracellular processes for each cell described here by ODEs determine the long-time dynamics, but the PDE part dominates the solving effort. Thus, it is not clear if commonly used decoupling methods can outperform a coupling approach. Based on a sensitivity analysis, we present a systematic comparison between coupling and decoupling approaches for this class of problems and show numerical results. For biologically relevant configurations of the model, our quantitative study shows that a coupling approach performs much better than a decoupling one.

  12. An Excitable Signal Integrator Couples to an Idling Cytoskeletal Oscillator to Drive Cell Migration

    PubMed Central

    Huang, Chuan-Hsiang; Tang, Ming; Shi, Changji; Iglesias, Pablo A.; Devreotes, Peter N.

    2013-01-01

    It is generally believed that cytoskeletal activities drive random cell migration while signal transduction events initiated by receptors regulate the cytoskeleton to guide cells. However, we find that the cytoskeletal network, involving Scar/Wave, Arp 2/3, and actin binding proteins, is only capable of generating rapid oscillations and undulations of the cell boundary. The signal transduction network, comprising multiple pathways that include Ras GTPases, PI3K, and Rac GTPases, is required to generate the sustained protrusions of migrating cells. The signal transduction network is excitable, displaying wave propagation, refractoriness, and maximal response to suprathreshold stimuli, even in the absence of the cytoskeleton. We suggest that cell motility results from coupling of “pacemaker” signal transduction and “idling motor” cytoskeletal networks, and various guidance cues that modulate the threshold for triggering signal transduction events are integrated to control the mode and direction of migration. PMID:24142103

  13. G-protein-coupled receptor kinase 2 terminates G-protein-coupled receptor function in steroid hormone 20-hydroxyecdysone signaling

    PubMed Central

    Zhao, Wen-Li; Wang, Di; Liu, Chun-Yan; Zhao, Xiao-Fan

    2016-01-01

    G-protein-coupled receptors (GPCRs) transmit extracellular signals across the cell membrane. GPCR kinases (GRKs) desensitize GPCR signals in the cell membrane. However, the role and mechanism of GRKs in the desensitization of steroid hormone signaling are unclear. In this study, we propose that GRK2 is phosphorylated by protein kinase C (PKC) in response to induction by the steroid hormone 20-hydroxyecdysone (20E), which determines its translocation to the cell membrane of the lepidopteran Helicoverpa armigera. GRK2 protein expression is increased during the metamorphic stage because of induction by 20E. Knockdown of GRK2 in larvae causes accelerated pupation, an increase in 20E-response gene expression, and advanced apoptosis and metamorphosis. 20E induces translocation of GRK2 from the cytoplasm to the cell membrane via steroid hormone ecdysone-responsive GPCR (ErGPCR-2). GRK2 is phosphorylated by PKC on serine 680 after induction by 20E, which leads to the translocation of GRK2 to the cell membrane. GRK2 interacts with ErGPCR-2. These data indicate that GRK2 terminates the ErGPCR-2 function in 20E signaling in the cell membrane by a negative feedback mechanism. PMID:27412951

  14. G-protein-coupled receptor kinase 2 terminates G-protein-coupled receptor function in steroid hormone 20-hydroxyecdysone signaling.

    PubMed

    Zhao, Wen-Li; Wang, Di; Liu, Chun-Yan; Zhao, Xiao-Fan

    2016-01-01

    G-protein-coupled receptors (GPCRs) transmit extracellular signals across the cell membrane. GPCR kinases (GRKs) desensitize GPCR signals in the cell membrane. However, the role and mechanism of GRKs in the desensitization of steroid hormone signaling are unclear. In this study, we propose that GRK2 is phosphorylated by protein kinase C (PKC) in response to induction by the steroid hormone 20-hydroxyecdysone (20E), which determines its translocation to the cell membrane of the lepidopteran Helicoverpa armigera. GRK2 protein expression is increased during the metamorphic stage because of induction by 20E. Knockdown of GRK2 in larvae causes accelerated pupation, an increase in 20E-response gene expression, and advanced apoptosis and metamorphosis. 20E induces translocation of GRK2 from the cytoplasm to the cell membrane via steroid hormone ecdysone-responsive GPCR (ErGPCR-2). GRK2 is phosphorylated by PKC on serine 680 after induction by 20E, which leads to the translocation of GRK2 to the cell membrane. GRK2 interacts with ErGPCR-2. These data indicate that GRK2 terminates the ErGPCR-2 function in 20E signaling in the cell membrane by a negative feedback mechanism. PMID:27412951

  15. Control of the neurovascular coupling by nitric oxide-dependent regulation of astrocytic Ca2+ signaling

    PubMed Central

    Muñoz, Manuel F.; Puebla, Mariela; Figueroa, Xavier F.

    2015-01-01

    Neuronal activity must be tightly coordinated with blood flow to keep proper brain function, which is achieved by a mechanism known as neurovascular coupling. Then, an increase in synaptic activity leads to a dilation of local parenchymal arterioles that matches the enhanced metabolic demand. Neurovascular coupling is orchestrated by astrocytes. These glial cells are located between neurons and the microvasculature, with the astrocytic endfeet ensheathing the vessels, which allows fine intercellular communication. The neurotransmitters released during neuronal activity reach astrocytic receptors and trigger a Ca2+ signaling that propagates to the endfeet, activating the release of vasoactive factors and arteriolar dilation. The astrocyte Ca2+ signaling is coordinated by gap junction channels and hemichannels formed by connexins (Cx43 and Cx30) and channels formed by pannexins (Panx-1). The neuronal activity-initiated Ca2+ waves are propagated among neighboring astrocytes directly via gap junctions or through ATP release via connexin hemichannels or pannexin channels. In addition, Ca2+ entry via connexin hemichannels or pannexin channels may participate in the regulation of the astrocyte signaling-mediated neurovascular coupling. Interestingly, nitric oxide (NO) can activate connexin hemichannel by S-nitrosylation and the Ca2+-dependent NO-synthesizing enzymes endothelial NO synthase (eNOS) and neuronal NOS (nNOS) are expressed in astrocytes. Therefore, the astrocytic Ca2+ signaling triggered in neurovascular coupling may activate NO production, which, in turn, may lead to Ca2+ influx through hemichannel activation. Furthermore, NO release from the hemichannels located at astrocytic endfeet may contribute to the vasodilation of parenchymal arterioles. In this review, we discuss the mechanisms involved in the regulation of the astrocytic Ca2+ signaling that mediates neurovascular coupling, with a special emphasis in the possible participation of NO in this process

  16. Engineered G protein coupled receptors reveal independent regulation of internalization, desensitization and acute signaling

    PubMed Central

    Scearce-Levie, Kimberly; Lieberman, Michael D; Elliott, Heather H; Conklin, Bruce R

    2005-01-01

    Background The physiological regulation of G protein-coupled receptors, through desensitization and internalization, modulates the length of the receptor signal and may influence the development of tolerance and dependence in response to chronic drug treatment. To explore the importance of receptor regulation, we engineered a series of Gi-coupled receptors that differ in signal length, degree of agonist-induced internalization, and ability to induce adenylyl cyclase superactivation. All of these receptors, based on the kappa opioid receptor, were modified to be receptors activated solely by synthetic ligands (RASSLs). This modification allows us to compare receptors that have the same ligands and effectors, but differ only in desensitization and internalization. Results Removal of phosphorylation sites in the C-terminus of the RASSL resulted in a mutant that was resistant to internalization and less prone to desensitization. Replacement of the C-terminus of the RASSL with the corresponding portion of the mu opioid receptor eliminated the induction of AC superactivation, without disrupting agonist-induced desensitization or internalization. Surprisingly, removal of phosphorylation sites from this chimera resulted in a receptor that is constitutively internalized, even in the absence of agonist. However, the receptor still signals and desensitizes in response to agonist, indicating normal G-protein coupling and partial membrane expression. Conclusions These studies reveal that internalization, desensitization and adenylyl cyclase superactivation, all processes that decrease chronic Gi-receptor signals, are independently regulated. Furthermore, specific mutations can radically alter superactivation or internalization without affecting the efficacy of acute Gi signaling. These mutant RASSLs will be useful for further elucidating the temporal dynamics of the signaling of G protein-coupled receptors in vitro and in vivo. PMID:15707483

  17. Loss of Gi G-Protein-Coupled Receptor Signaling in Osteoblasts Accelerates Bone Fracture Healing.

    PubMed

    Wang, Liping; Hsiao, Edward C; Lieu, Shirley; Scott, Mark; O'Carroll, Dylan; Urrutia, Ashley; Conklin, Bruce R; Colnot, Celine; Nissenson, Robert A

    2015-10-01

    G-protein-coupled receptors (GPCRs) are key regulators of skeletal homeostasis and are likely important in fracture healing. Because GPCRs can activate multiple signaling pathways simultaneously, we used targeted disruption of G(i) -GPCR or activation of G(s) -GPCR pathways to test how each pathway functions in the skeleton. We previously demonstrated that blockade of G(i) signaling by pertussis toxin (PTX) transgene expression in maturing osteoblastic cells enhanced cortical and trabecular bone formation and prevented age-related bone loss in female mice. In addition, activation of G(s) signaling by expressing the G(s) -coupled engineered receptor Rs1 in maturing osteoblastic cells induced massive trabecular bone formation but cortical bone loss. Here, we test our hypothesis that the G(i) and G(s) pathways also have distinct functions in fracture repair. We applied closed, nonstabilized tibial fractures to mice in which endogenous G(i) signaling was inhibited by PTX, or to mice with activated G(s) signaling mediated by Rs1. Blockade of endogenous G(i) resulted in a smaller callus but increased bone formation in both young and old mice. PTX treatment decreased expression of Dkk1 and increased Lef1 mRNAs during fracture healing, suggesting a role for endogenous G(i) signaling in maintaining Dkk1 expression and suppressing Wnt signaling. In contrast, adult mice with activated Gs signaling showed a slight increase in the initial callus size with increased callus bone formation. These results show that G(i) blockade and G(s) activation of the same osteoblastic lineage cell can induce different biological responses during fracture healing. Our findings also show that manipulating the GPCR/cAMP signaling pathway by selective timing of G(s) and G(i) -GPCR activation may be important for optimizing fracture repair. PMID:25917236

  18. G-Protein–Coupled Receptors Signaling Pathways in New Antiplatelet Drug Development

    PubMed Central

    Gurbel, Paul A.; Kuliopulos, Athan; Tantry, Udaya S.

    2016-01-01

    Platelet G-protein–coupled receptors influence platelet function by mediating the response to various agonists, including ADP, thromboxane A2, and thrombin. Blockade of the ADP receptor, P2Y12, in combination with cyclooxygenase-1 inhibition by aspirin has been among the most widely used pharmacological strategies to reduce cardiovascular event occurrence in high-risk patients. The latter dual pathway blockade strategy is one of the greatest advances in the field of cardiovascular medicine. In addition to P2Y12, the platelet thrombin receptor, protease activated receptor-1, has also been recently targeted for inhibition. Blockade of protease activated receptor-1 has been associated with reduced thrombotic event occurrence when added to a strategy using P2Y12 and cyclooxygenase-1 inhibition. At this time, the relative contributions of these G-protein–coupled receptor signaling pathways to in vivo thrombosis remain incompletely defined. The observation of treatment failure in ≈10% of high-risk patients treated with aspirin and potent P2Y12 inhibitors provides the rationale for targeting novel pathways mediating platelet function. Targeting intracellular signaling downstream from G-protein–coupled receptor receptors with phosphotidylionisitol 3-kinase and Gq inhibitors are among the novel strategies under investigation to prevent arterial ischemic event occurrence. Greater understanding of the mechanisms of G-protein–coupled receptor–mediated signaling may allow the tailoring of antiplatelet therapy. PMID:25633316

  19. An exonuclease-assisted amplification electrochemical aptasensor of thrombin coupling "signal on/off" strategy.

    PubMed

    Bao, Ting; Wen, Wei; Zhang, Xiuhua; Wang, Shengfu

    2015-02-20

    In this work, a dual-signaling electrochemical aptasensor based on exonuclease-catalyzed target recycling was developed for thrombin detection. The proposed aptasensor coupled "signal-on" and "signal-off" strategies. As to the construction of the aptasensor, ferrocene (Fc) labeled thrombin binding aptamer (TBA) could perfectly hybridize with the methylene blue (MB) modified thiolated capture DNA to form double-stranded structure, hence emerged two different electrochemical signals. In the presence of thrombin, TBA could form a G-quadruplex structure with thrombin, leading to the dissociation of TBA from the duplex DNA and capture DNA formed hairpin structure. Exonuclease could selectively digest single-stranded TBA in G-quadruplex structure and released thrombin to realize target recycling. As a consequence, the electrochemical signal of MB enhanced significantly, which realized "signal on" strategy, meanwhile, the deoxidization peak current of Fc decreased distinctly, which realized "signal off" strategy. The employment of exonuclease and superposition of two signals significantly improved the sensitivity of the aptasensor. In this way, an aptasensor with high sensitivity, good stability and selectivity for quantitative detection of thrombin was constructed, which exhibited a good linear range from 5 pM to 50 nM with a detection limit of 0.9 pM (defined as S/N=3). In addition, this design strategy could be applied to the detection of other proteins and small molecules. PMID:25682249

  20. Astrocyte sodium signaling and neuro-metabolic coupling in the brain.

    PubMed

    Rose, C R; Chatton, J-Y

    2016-05-26

    At tripartite synapses, astrocytes undergo calcium signaling in response to release of neurotransmitters and this calcium signaling has been proposed to play a critical role in neuron-glia interaction. Recent work has now firmly established that, in addition, neuronal activity also evokes sodium transients in astrocytes, which can be local or global depending on the number of activated synapses and the duration of activity. Furthermore, astrocyte sodium signals can be transmitted to adjacent cells through gap junctions and following release of gliotransmitters. A main pathway for activity-related sodium influx into astrocytes is via high-affinity sodium-dependent glutamate transporters. Astrocyte sodium signals differ in many respects from the well-described glial calcium signals both in terms of their temporal as well as spatial distribution. There are no known buffering systems for sodium ions, nor is there store-mediated release of sodium. Sodium signals thus seem to represent rather direct and unbiased indicators of the site and strength of neuronal inputs. As such they have an immediate influence on the activity of sodium-dependent transporters which may even reverse in response to sodium signaling, as has been shown for GABA transporters for example. Furthermore, recovery from sodium transients through Na(+)/K(+)-ATPase requires a measurable amount of ATP, resulting in an activation of glial metabolism. In this review, we present basic principles of sodium regulation and the current state of knowledge concerning the occurrence and properties of activity-related sodium transients in astrocytes. We then discuss different aspects of the relationship between sodium changes in astrocytes and neuro-metabolic coupling, putting forward the idea that indeed sodium might serve as a new type of intracellular ion signal playing an important role in neuron-glia interaction and neuro-metabolic coupling in the healthy and diseased brain. PMID:25791228

  1. Effects of chemical synapses on the enhancement of signal propagation in coupled neurons near the canard regime

    NASA Astrophysics Data System (ADS)

    Li, Xiumin; Wang, Jiang; Hu, Wuhua

    2007-10-01

    The response of three coupled FitzHugh-Nagumo neurons, under Gaussian white noise, to a subthreshold periodic signal is studied in this paper. By combining the canard dynamics, chemical coupling, and stochastic resonance together, the information transfer in this neural system is investigated. We find that chemical synaptic coupling is more efficient than the well-known linear coupling (gap junction) for local signal input, i.e., only one of the three neurons is subject to the periodic signal. This weak and local input is common in biological systems for the sake of low energy consumption.

  2. Allosteric and Biased G Protein-Coupled Receptor Signaling Regulation: Potentials for New Therapeutics

    PubMed Central

    Khoury, Etienne; Clément, Stéphanie; Laporte, Stéphane A.

    2014-01-01

    G protein-coupled receptors (GPCRs) are seven-transmembrane proteins that participate in many aspects of the endocrine function and are important targets for drug development. They transduce signals mainly, but not exclusively, via hetero-trimeric G proteins, leading to a diversity of intracellular signaling cascades. Ligands binding at the hormone orthosteric sites of receptors have been classified as agonists, antagonists, and/or inverse agonists based on their ability to mainly modulate G protein signaling. Accumulating evidence also indicates that such ligands, alone or in combination with other ones such as those acting outside the orthosteric hormone binding sites (e.g., allosteric modulators), have the ability to selectively engage subsets of signaling responses as compared to the natural endogenous ligands. Such modes of functioning have been variously referred to as “functional selectivity” or “ligand-biased signaling.” In this review, we provide an overview of the current knowledge regarding GPCR-biased signaling and their functional regulation with a focus on the evolving concept that receptor domains can also be targeted to allosterically bias signaling, and discuss the usefulness of such modes of regulation for the design of more efficient therapeutics. PMID:24847311

  3. Biased signaling through G-protein-coupled PROKR2 receptors harboring missense mutations.

    PubMed

    Sbai, Oualid; Monnier, Carine; Dodé, Catherine; Pin, Jean-Philippe; Hardelin, Jean-Pierre; Rondard, Philippe

    2014-08-01

    Various missense mutations in the gene coding for prokineticin receptor 2 (PROKR2), a G-protein-coupled receptor, have been identified in patients with Kallmann syndrome. However, the functional consequences of these mutations on the different signaling pathways of this receptor have not been studied. We first showed that the wild-type PROKR2 can activate different G-protein subtypes (Gq, Gs, and Gi/o) and recruit β-arrestins in transfected HEK-293 cells. We then examined, for each of these signaling pathways, the effects of 9 mutations that did not significantly impair cell surface targeting or ligand binding of the receptor. Four mutant receptors showing defective Gq signaling (R85C, R85H, R164Q, and V331M) could still recruit β-arrestins on ligand activation, which may cause biased signaling in vivo. Conversely, the R80C receptor could activate the 3 types of G proteins but could not recruit β-arrestins. Finally, the R268C receptor could recruit β-arrestins and activate the Gq and Gs signaling pathways but could not activate the Gi/o signaling pathway. Our results validate the concept that mutations in the genes encoding membrane receptors can bias downstream signaling in various ways, possibly leading to pathogenic and, perhaps in some cases, protective (e.g., R268C) effects. PMID:24830383

  4. A novel distributed swarm control strategy based on coupled signal oscillators.

    PubMed

    Hartbauer, Manfred; Römer, Heiner

    2007-09-01

    The miniaturization of microrobots is accompanied by limitations of signaling, sensing and agility. Control of a swarm of simple microrobots has to cope with such constraints in a way which still guarantees the accomplishment of a task. A recently proposed communication method, which is based on the coupling of signal oscillators of individual agents [13], may provide a basis for a distributed control of a simulated swarm of simple microrobots (similar to I-Swarm microrobots) engaged in a cleaning scenario. This self-organized communication method was biologically inspired from males of chorusing insects which are known for the rapid synchronization of their acoustic signals in a chorus. Signal oscillator properties were used to generate waves of synchronized signaling (s-waves) among a swarm of agents. In a simulation of a cleaning scenario, agents on the dump initiated concentrically spreading s-waves by shortening their intrinsic signal period. Dirt-carrying agents localized the dump by heading against the wave front. After optimization of certain control parameters the properties of this distributed control strategy were investigated in different variants of a cleaning scenario. These include a second dump, obstacles, different agent densities, agent drop-out and a second signal oscillator. PMID:17848790

  5. G Protein-Coupled Receptor Signaling in Stem Cells and Cancer

    PubMed Central

    Lynch, Jennifer R.; Wang, Jenny Yingzi

    2016-01-01

    G protein-coupled receptors (GPCRs) are a large superfamily of cell-surface signaling proteins that bind extracellular ligands and transduce signals into cells via heterotrimeric G proteins. GPCRs are highly tractable drug targets. Aberrant expression of GPCRs and G proteins has been observed in various cancers and their importance in cancer stem cells has begun to be appreciated. We have recently reported essential roles for G protein-coupled receptor 84 (GPR84) and G protein subunit Gαq in the maintenance of cancer stem cells in acute myeloid leukemia. This review will discuss how GPCRs and G proteins regulate stem cells with a focus on cancer stem cells, as well as their implications for the development of novel targeted cancer therapies. PMID:27187360

  6. Heterotrimeric G Protein-coupled Receptor Signaling in Yeast Mating Pheromone Response*

    PubMed Central

    Alvaro, Christopher G.; Thorner, Jeremy

    2016-01-01

    The DNAs encoding the receptors that respond to the peptide mating pheromones of the budding yeast Saccharomyces cerevisiae were isolated in 1985, and were the very first genes for agonist-binding heterotrimeric G protein-coupled receptors (GPCRs) to be cloned in any organism. Now, over 30 years later, this yeast and its receptors continue to provide a pathfinding experimental paradigm for investigating GPCR-initiated signaling and its regulation, as described in this retrospective overview. PMID:26907689

  7. G protein-coupled receptors: signalling and regulation by lipid agonists for improved glucose homoeostasis.

    PubMed

    Moran, Brian M; Flatt, Peter R; McKillop, Aine M

    2016-04-01

    G protein-coupled receptors (GPCRs) play a pivotal role in cell signalling, controlling many processes such as immunity, growth, cellular differentiation, neurological pathways and hormone secretions. Fatty acid agonists are increasingly recognised as having a key role in the regulation of glucose homoeostasis via stimulation of islet and gastrointestinal GPCRs. Downstream cell signalling results in modulation of the biosynthesis, secretion, proliferation and anti-apoptotic pathways of islet and enteroendocrine cells. GPR40 and GPR120 are activated by long-chain fatty acids (>C12) with both receptors coupling to the Gαq subunit that activates the Ca(2+)-dependent pathway. GPR41 and GPR43 are stimulated by short-chain fatty acids (C2-C5), and activation results in binding to Gαi that inhibits the adenylyl cyclase pathway attenuating cAMP production. In addition, GPR43 also couples to the Gαq subunit augmenting intracellular Ca(2+) and activating phospholipase C. GPR55 is specific for cannabinoid endogenous agonists (endocannabinoids) and non-cannabinoid fatty acids, which couples to Gα12/13 and Gαq proteins, leading to enhancing intracellular Ca(2+), extracellular signal-regulated kinase 1/2 (ERK) phosphorylation and Rho kinase. GPR119 is activated by fatty acid ethanolamides and binds to Gαs utilising the adenylate cyclase pathway, which is dependent upon protein kinase A. Current research indicates that GPCR therapies may be approved for clinical use in the near future. This review focuses on the recent advances in preclinical diabetes research in the signalling and regulation of GPCRs on islet and enteroendocrine cells involved in glucose homoeostasis. PMID:26739335

  8. Near- Source, Seismo-Acoustic Signals Accompanying a NASCAR Race at the Texas Motor Speedway

    NASA Astrophysics Data System (ADS)

    Stump, B. W.; Hayward, C.; Underwood, R.; Howard, J. E.; MacPhail, M. D.; Golden, P.; Endress, A.

    2014-12-01

    Near-source, seismo-acoustic observations provide a unique opportunity to characterize urban sources, remotely sense human activities including vehicular traffic and monitor large engineering structures. Energy separately coupled into the solid earth and atmosphere provides constraints on not only the location of these sources but also the physics of the generating process. Conditions and distances at which these observations can be made are dependent upon not only local geological conditions but also atmospheric conditions at the time of the observations. In order to address this range of topics, an empirical, seismo-acoustic study was undertaken in and around the Texas Motor Speedway in the Dallas-Ft. Worth area during the first week of April 2014 at which time a range of activities associated with a series of NASCAR races occurred. Nine, seismic sensors were deployed around the 1.5-mile track for purposes of documenting the direct-coupled seismic energy from the passage of the cars and other vehicles on the track. Six infrasound sensors were deployed on a rooftop in a rectangular array configuration designed to provide high frequency beam forming for acoustic signals. Finally, a five-element infrasound array was deployed outside the track in order to characterize how the signals propagate away from the sources in the near-source region. Signals recovered from within the track were able to track and characterize the motion of a variety of vehicles during the race weekend including individual racecars. Seismic data sampled at 1000 sps documented strong Doppler effects as the cars approached and moved away from individual sensors. There were faint seismic signals that arrived at seismic velocity but local acoustic to seismic coupling as supported by the acoustic observations generated the majority of seismic signals. Actual seismic ground motions were small as demonstrated by the dominance of regional seismic signals from a magnitude 4.0 earthquake that arrived at

  9. Motivational Salience Signal in the Basal Forebrain Is Coupled with Faster and More Precise Decision Speed

    PubMed Central

    Avila, Irene; Lin, Shih-Chieh

    2014-01-01

    The survival of animals depends critically on prioritizing responses to motivationally salient stimuli. While it is generally believed that motivational salience increases decision speed, the quantitative relationship between motivational salience and decision speed, measured by reaction time (RT), remains unclear. Here we show that the neural correlate of motivational salience in the basal forebrain (BF), defined independently of RT, is coupled with faster and also more precise decision speed. In rats performing a reward-biased simple RT task, motivational salience was encoded by BF bursting response that occurred before RT. We found that faster RTs were tightly coupled with stronger BF motivational salience signals. Furthermore, the fraction of RT variability reflecting the contribution of intrinsic noise in the decision-making process was actively suppressed in faster RT distributions with stronger BF motivational salience signals. Artificially augmenting the BF motivational salience signal via electrical stimulation led to faster and more precise RTs and supports a causal relationship. Together, these results not only describe for the first time, to our knowledge, the quantitative relationship between motivational salience and faster decision speed, they also reveal the quantitative coupling relationship between motivational salience and more precise RT. Our results further establish the existence of an early and previously unrecognized step in the decision-making process that determines both the RT speed and variability of the entire decision-making process and suggest that this novel decision step is dictated largely by the BF motivational salience signal. Finally, our study raises the hypothesis that the dysregulation of decision speed in conditions such as depression, schizophrenia, and cognitive aging may result from the functional impairment of the motivational salience signal encoded by the poorly understood noncholinergic BF neurons. PMID:24642480

  10. Motivational salience signal in the basal forebrain is coupled with faster and more precise decision speed.

    PubMed

    Avila, Irene; Lin, Shih-Chieh

    2014-03-01

    The survival of animals depends critically on prioritizing responses to motivationally salient stimuli. While it is generally believed that motivational salience increases decision speed, the quantitative relationship between motivational salience and decision speed, measured by reaction time (RT), remains unclear. Here we show that the neural correlate of motivational salience in the basal forebrain (BF), defined independently of RT, is coupled with faster and also more precise decision speed. In rats performing a reward-biased simple RT task, motivational salience was encoded by BF bursting response that occurred before RT. We found that faster RTs were tightly coupled with stronger BF motivational salience signals. Furthermore, the fraction of RT variability reflecting the contribution of intrinsic noise in the decision-making process was actively suppressed in faster RT distributions with stronger BF motivational salience signals. Artificially augmenting the BF motivational salience signal via electrical stimulation led to faster and more precise RTs and supports a causal relationship. Together, these results not only describe for the first time, to our knowledge, the quantitative relationship between motivational salience and faster decision speed, they also reveal the quantitative coupling relationship between motivational salience and more precise RT. Our results further establish the existence of an early and previously unrecognized step in the decision-making process that determines both the RT speed and variability of the entire decision-making process and suggest that this novel decision step is dictated largely by the BF motivational salience signal. Finally, our study raises the hypothesis that the dysregulation of decision speed in conditions such as depression, schizophrenia, and cognitive aging may result from the functional impairment of the motivational salience signal encoded by the poorly understood noncholinergic BF neurons. PMID:24642480

  11. Gs-coupled GPCR signalling in AgRP neurons triggers sustained increase in food intake

    PubMed Central

    Nakajima, Ken-ichiro; Cui, Zhenzhong; Li, Chia; Meister, Jaroslawna; Cui, Yinghong; Fu, Ou; Smith, Adam S.; Jain, Shalini; Lowell, Bradford B.; Krashes, Michael J.; Wess, Jürgen

    2016-01-01

    Agouti-related peptide (AgRP) neurons of the hypothalamus play a key role in regulating food intake and body weight, by releasing three different orexigenic molecules: AgRP; GABA; and neuropeptide Y. AgRP neurons express various G protein-coupled receptors (GPCRs) with different coupling properties, including Gs-linked GPCRs. At present, the potential role of Gs-coupled GPCRs in regulating the activity of AgRP neurons remains unknown. Here we show that the activation of Gs-coupled receptors expressed by AgRP neurons leads to a robust and sustained increase in food intake. We also provide detailed mechanistic data linking the stimulation of this class of receptors to the observed feeding phenotype. Moreover, we show that this pathway is clearly distinct from other GPCR signalling cascades that are operative in AgRP neurons. Our data suggest that drugs able to inhibit this signalling pathway may become useful for the treatment of obesity. PMID:26743492

  12. GTPase acceleration as the rate-limiting step in Arabidopsis G protein-coupled sugar signaling.

    PubMed

    Johnston, Christopher A; Taylor, J Philip; Gao, Yajun; Kimple, Adam J; Grigston, Jeffrey C; Chen, Jin-Gui; Siderovski, David P; Jones, Alan M; Willard, Francis S

    2007-10-30

    Heterotrimeric G protein signaling is important for cell-proliferative and glucose-sensing signal transduction pathways in the model plant organism Arabidopsis thaliana. AtRGS1 is a seven-transmembrane, RGS domain-containing protein that is a putative membrane receptor for d-glucose. Here we show, by using FRET, that d-glucose alters the interaction between the AtGPA1 and AtRGS1 in vivo. AtGPA1 is a unique heterotrimeric G protein alpha subunit that is constitutively GTP-bound given its high spontaneous nucleotide exchange coupled with slow GTP hydrolysis. Analysis of a point mutation in AtRGS1 that abrogates GTPase-accelerating activity demonstrates that the regulation of AtGPA1 GTP hydrolysis mediates sugar signal transduction during Arabidopsis development, in contrast to animals where nucleotide exchange is the limiting step in the heterotrimeric G protein nucleotide cycle. PMID:17951432

  13. Early warning signals of Atlantic Meridional Overturning Circulation collapse in a fully coupled climate model.

    PubMed

    Boulton, Chris A; Allison, Lesley C; Lenton, Timothy M

    2014-01-01

    The Atlantic Meridional Overturning Circulation (AMOC) exhibits two stable states in models of varying complexity. Shifts between alternative AMOC states are thought to have played a role in past abrupt climate changes, but the proximity of the climate system to a threshold for future AMOC collapse is unknown. Generic early warning signals of critical slowing down before AMOC collapse have been found in climate models of low and intermediate complexity. Here we show that early warning signals of AMOC collapse are present in a fully coupled atmosphere-ocean general circulation model, subject to a freshwater hosing experiment. The statistical significance of signals of increasing lag-1 autocorrelation and variance vary with latitude. They give up to 250 years warning before AMOC collapse, after ~550 years of monitoring. Future work is needed to clarify suggested dynamical mechanisms driving critical slowing down as the AMOC collapse is approached. PMID:25482065

  14. Sorting nexin 27 couples PTHR trafficking to retromer for signal regulation in osteoblasts during bone growth

    PubMed Central

    Chan, Audrey S. M.; Clairfeuille, Thomas; Landao-Bassonga, Euphemie; Kinna, Genevieve; Ng, Pei Ying; Loo, Li Shen; Cheng, Tak Sum; Zheng, Minghao; Hong, Wanjin; Teasdale, Rohan D.; Collins, Brett M.; Pavlos, Nathan J.

    2016-01-01

    The parathyroid hormone 1 receptor (PTHR) is central to the process of bone formation and remodeling. PTHR signaling requires receptor internalization into endosomes, which is then terminated by recycling or degradation. Here we show that sorting nexin 27 (SNX27) functions as an adaptor that couples PTHR to the retromer trafficking complex. SNX27 binds directly to the C-terminal PDZ-binding motif of PTHR, wiring it to retromer for endosomal sorting. The structure of SNX27 bound to the PTHR motif reveals a high-affinity interface involving conserved electrostatic interactions. Mechanistically, depletion of SNX27 or retromer augments intracellular PTHR signaling in endosomes. Osteoblasts genetically lacking SNX27 show similar disruptions in PTHR signaling and greatly reduced capacity for bone mineralization, contributing to profound skeletal deficits in SNX27-knockout mice. Taken together, our data support a critical role for SNX27-retromer mediated transport of PTHR in normal bone development. PMID:26912788

  15. Implication of Two-Coupled Differential Van der Pol Duffing Oscillator in Weak Signal Detection

    NASA Astrophysics Data System (ADS)

    Peng, Hang-hang; Xu, Xue-mei; Yang, Bing-chu; Yin, Lin-zi

    2016-04-01

    The principle of the Van der Pol Duffing oscillator for state transition and for determining critical value is described, which has been studied to indicate that the application of the Van der Pol Duffing oscillator in weak signal detection is feasible. On the basis of this principle, an improved two-coupled differential Van der Pol Duffing oscillator is proposed which can identify signals under any frequency and ameliorate signal-to-noise ratio (SNR). The analytical methods of the proposed model and the construction of the proposed oscillator are introduced in detail. Numerical experiments on the properties of the proposed oscillator compared with those of the Van der Pol Duffing oscillator are carried out. Our numerical simulations have confirmed the analytical treatment. The results demonstrate that this novel oscillator has better detection performance than the Van der Pol Duffing oscillator.

  16. Early warning signals of Atlantic Meridional Overturning Circulation collapse in a fully coupled climate model

    PubMed Central

    Boulton, Chris A.; Allison, Lesley C.; Lenton, Timothy M.

    2014-01-01

    The Atlantic Meridional Overturning Circulation (AMOC) exhibits two stable states in models of varying complexity. Shifts between alternative AMOC states are thought to have played a role in past abrupt climate changes, but the proximity of the climate system to a threshold for future AMOC collapse is unknown. Generic early warning signals of critical slowing down before AMOC collapse have been found in climate models of low and intermediate complexity. Here we show that early warning signals of AMOC collapse are present in a fully coupled atmosphere-ocean general circulation model, subject to a freshwater hosing experiment. The statistical significance of signals of increasing lag-1 autocorrelation and variance vary with latitude. They give up to 250 years warning before AMOC collapse, after ~550 years of monitoring. Future work is needed to clarify suggested dynamical mechanisms driving critical slowing down as the AMOC collapse is approached. PMID:25482065

  17. Coupling Mechanism and Significance of the BOLD Signal: A Status Report

    PubMed Central

    Hillman, Elizabeth M.C.

    2014-01-01

    Functional magnetic resonance imaging (fMRI) provides a unique view of the working human mind. The blood-oxygen-level-dependent (BOLD) signal, detected in fMRI, reflects changes in deoxyhemoglobin driven by localized changes in brain blood flow and blood oxygenation, which are coupled to underlying neuronal activity by a process termed neurovascular coupling. Over the past 10 years, a range of cellular mechanisms, including astrocytes, pericytes, and interneurons, have been proposed to play a role in functional neurovascular coupling. However, the field remains conflicted over the relative importance of each process, while key spatiotemporal features of BOLD response remain unexplained. Here, we review current candidate neurovascular coupling mechanisms and propose that previously overlooked involvement of the vascular endothelium may provide a more complete picture of how blood flow is controlled in the brain. We also explore the possibility and consequences of conditions in which neurovascular coupling may be altered, including during postnatal development, pathological states, and aging, noting relevance to both stimulus-evoked and resting-state fMRI studies. PMID:25032494

  18. Astrocytic adenosine receptor A2A and Gs-coupled signaling regulate memory

    PubMed Central

    Orr, Anna G.; Hsiao, Edward C.; Wang, Max M.; Ho, Kaitlyn; Kim, Daniel H.; Wang, Xin; Guo, Weikun; Kang, Jing; Yu, Gui-Qiu; Adame, Anthony; Devidze, Nino; Dubal, Dena B.; Masliah, Eliezer; Conklin, Bruce R.; Mucke, Lennart

    2014-01-01

    Astrocytes express a variety of G protein-coupled receptors and might influence cognitive functions, such as learning and memory. However, the roles of astrocytic Gs-coupled receptors in cognitive function are not known. We found that humans with Alzheimer’s disease (AD) had increased levels of the Gs-coupled adenosine receptor A2A in astrocytes. Conditional genetic removal of these receptors enhanced long-term memory in young and aging mice, and increased the levels of Arc/Arg3.1, an immediate-early gene required for long-term memory. Chemogenetic activation of astrocytic Gs-coupled signaling reduced long-term memory in mice without affecting learning. Similar to humans with AD, aging mice expressing human amyloid precursor protein (hAPP) showed increased levels of astrocytic A2A receptors. Conditional genetic removal of these receptors enhanced memory in aging hAPP mice. Together, these findings establish a regulatory role for astrocytic Gs-coupled receptors in memory and suggest that AD-linked increases in astrocytic A2A receptor levels contribute to memory loss. PMID:25622143

  19. Structural insights into biased G protein-coupled receptor signaling revealed by fluorescence spectroscopy

    PubMed Central

    Rahmeh, Rita; Damian, Marjorie; Cottet, Martin; Orcel, Hélène; Mendre, Christiane; Durroux, Thierry; Sharma, K. Shivaji; Durand, Grégory; Pucci, Bernard; Trinquet, Eric; Zwier, Jurriaan M.; Deupi, Xavier; Bron, Patrick; Banères, Jean-Louis; Mouillac, Bernard; Granier, Sébastien

    2012-01-01

    G protein-coupled receptors (GPCRs) are seven-transmembrane proteins that mediate most cellular responses to hormones and neurotransmitters, representing the largest group of therapeutic targets. Recent studies show that some GPCRs signal through both G protein and arrestin pathways in a ligand-specific manner. Ligands that direct signaling through a specific pathway are known as biased ligands. The arginine-vasopressin type 2 receptor (V2R), a prototypical peptide-activated GPCR, is an ideal model system to investigate the structural basis of biased signaling. Although the native hormone arginine-vasopressin leads to activation of both the stimulatory G protein (Gs) for the adenylyl cyclase and arrestin pathways, synthetic ligands exhibit highly biased signaling through either Gs alone or arrestin alone. We used purified V2R stabilized in neutral amphipols and developed fluorescence-based assays to investigate the structural basis of biased signaling for the V2R. Our studies demonstrate that the Gs-biased agonist stabilizes a conformation that is distinct from that stabilized by the arrestin-biased agonists. This study provides unique insights into the structural mechanisms of GPCR activation by biased ligands that may be relevant to the design of pathway-biased drugs. PMID:22493271

  20. Current and future G protein-coupled receptor signaling targets for heart failure therapy

    PubMed Central

    Siryk-Bathgate, Ashley; Dabul, Samalia; Lymperopoulos, Anastasios

    2013-01-01

    Although there have been significant advances in the therapy of heart failure in recent decades, such as the introduction of β-blockers and antagonists of the renin–angiotensin–aldosterone system, this devastating disease still carries tremendous morbidity and mortality in the western world. G protein-coupled receptors, such as β-adrenergic and angiotensin II receptors, located in the membranes of all three major cardiac cell types, ie, myocytes, fibroblasts, and endothelial cells, play crucial roles in regulation of cardiac function in health and disease. Their importance is reflected by the fact that, collectively, they represent the direct targets of over one-third of the currently approved cardiovascular drugs used in clinical practice. Over the past few decades, advances in elucidation of the signaling pathways they elicit, specifically in the heart, have led to identification of an increasing number of new molecular targets for heart failure therapy. Here, we review these possible targets for heart failure therapy that have emerged from studies of cardiac G protein-coupled receptor signaling in health and disease, with a particular focus on the main cardiac G protein-coupled receptor types, ie, the β-adrenergic and the angiotensin II type 1 receptors. We also highlight key issues that need to be addressed to improve the chances of success of novel therapies directed against these targets. PMID:24143078

  1. G Protein Coupled Receptors in Embryonic Stem Cells: A Role for Gs-Alpha Signaling

    PubMed Central

    Layden, Brian T.; Newman, Marsha; Chen, Fei; Fisher, Amanda; Lowe, William L.

    2010-01-01

    Background Identification of receptor mediated signaling pathways in embryonic stem (ES) cells is needed to facilitate strategies for cell replacement using ES cells. One large receptor family, largely uninvestigated in ES cells, is G protein coupled receptors (GPCRs). An important role for these receptors in embryonic development has been described, but little is known about GPCR expression in ES cells. Methodology/Principal Findings We have examined the expression profile of 343 different GPCRs in mouse ES cells demonstrating for the first time that a large number of GPCRs are expressed in undifferentiated and differentiating ES cells, and in many cases at high levels. To begin to define a role for GPCR signaling in ES cells, the impact of activating Gs-alpha, one of the major alpha subunits that couples to GPCRs, was investigated. Gs-alpha activation resulted in larger embryoid bodies (EBs), due, in part, to increased cell proliferation and prevented the time-related decline in expression of transcription factors important for maintaining ES cell pluripotency. Significance/Conclusions These studies suggest that Gs-alpha signaling contributes to ES cell proliferation and pluripotency and provide a framework for further investigation of GPCRs in ES cells. PMID:20161705

  2. Neurophysiological, metabolic and cellular compartments that drive neurovascular coupling and neuroimaging signals.

    PubMed

    Moreno, Andrea; Jego, Pierrick; de la Cruz, Feliberto; Canals, Santiago

    2013-01-01

    Complete understanding of the mechanisms that coordinate work and energy supply of the brain, the so called neurovascular coupling, is fundamental to interpreting brain energetics and their influence on neuronal coding strategies, but also to interpreting signals obtained from brain imaging techniques such as functional magnetic resonance imaging. Interactions between neuronal activity and cerebral blood flow regulation are largely compartmentalized. First, there exists a functional compartmentalization in which glutamatergic peri-synaptic activity and its electrophysiological events occur in close proximity to vascular responses. Second, the metabolic processes that fuel peri-synaptic activity are partially segregated between glycolytic and oxidative compartments. Finally, there is cellular segregation between astrocytic and neuronal compartments, which has potentially important implications on neurovascular coupling. Experimental data is progressively showing a tight interaction between the products of energy consumption and neurotransmission-driven signaling molecules that regulate blood flow. Here, we review some of these issues in light of recent findings with special attention to the neuron-glia interplay on the generation of neuroimaging signals. PMID:23543907

  3. Neurophysiological, metabolic and cellular compartments that drive neurovascular coupling and neuroimaging signals

    PubMed Central

    Moreno, Andrea; Jego, Pierrick; de la Cruz, Feliberto; Canals, Santiago

    2013-01-01

    Complete understanding of the mechanisms that coordinate work and energy supply of the brain, the so called neurovascular coupling, is fundamental to interpreting brain energetics and their influence on neuronal coding strategies, but also to interpreting signals obtained from brain imaging techniques such as functional magnetic resonance imaging. Interactions between neuronal activity and cerebral blood flow regulation are largely compartmentalized. First, there exists a functional compartmentalization in which glutamatergic peri-synaptic activity and its electrophysiological events occur in close proximity to vascular responses. Second, the metabolic processes that fuel peri-synaptic activity are partially segregated between glycolytic and oxidative compartments. Finally, there is cellular segregation between astrocytic and neuronal compartments, which has potentially important implications on neurovascular coupling. Experimental data is progressively showing a tight interaction between the products of energy consumption and neurotransmission-driven signaling molecules that regulate blood flow. Here, we review some of these issues in light of recent findings with special attention to the neuron-glia interplay on the generation of neuroimaging signals. PMID:23543907

  4. Spurious cross-frequency amplitude-amplitude coupling in nonstationary, nonlinear signals

    NASA Astrophysics Data System (ADS)

    Yeh, Chien-Hung; Lo, Men-Tzung; Hu, Kun

    2016-07-01

    Recent studies of brain activities show that cross-frequency coupling (CFC) plays an important role in memory and learning. Many measures have been proposed to investigate the CFC phenomenon, including the correlation between the amplitude envelopes of two brain waves at different frequencies - cross-frequency amplitude-amplitude coupling (AAC). In this short communication, we describe how nonstationary, nonlinear oscillatory signals may produce spurious cross-frequency AAC. Utilizing the empirical mode decomposition, we also propose a new method for assessment of AAC that can potentially reduce the effects of nonlinearity and nonstationarity and, thus, help to avoid the detection of artificial AACs. We compare the performances of this new method and the traditional Fourier-based AAC method. We also discuss the strategies to identify potential spurious AACs.

  5. Modulation of cellular signaling by herpesvirus-encoded G protein-coupled receptors

    PubMed Central

    de Munnik, Sabrina M.; Smit, Martine J.; Leurs, Rob; Vischer, Henry F.

    2015-01-01

    Human herpesviruses (HHVs) are widespread infectious pathogens that have been associated with proliferative and inflammatory diseases. During viral evolution, HHVs have pirated genes encoding viral G protein-coupled receptors (vGPCRs), which are expressed on infected host cells. These vGPCRs show highest homology to human chemokine receptors, which play a key role in the immune system. Importantly, vGPCRs have acquired unique properties such as constitutive activity and the ability to bind a broad range of human chemokines. This allows vGPCRs to hijack human proteins and modulate cellular signaling for the benefit of the virus, ultimately resulting in immune evasion and viral dissemination to establish a widespread and lifelong infection. Knowledge on the mechanisms by which herpesviruses reprogram cellular signaling might provide insight in the contribution of vGPCRs to viral survival and herpesvirus-associated pathologies. PMID:25805993

  6. Direct Modulation of Heterotrimeric G Protein-coupled Signaling by a Receptor Kinase Complex.

    PubMed

    Tunc-Ozdemir, Meral; Urano, Daisuke; Jaiswal, Dinesh Kumar; Clouse, Steven D; Jones, Alan M

    2016-07-01

    Plants and some protists have heterotrimeric G protein complexes that activate spontaneously without canonical G protein-coupled receptors (GPCRs). In Arabidopsis, the sole 7-transmembrane regulator of G protein signaling 1 (AtRGS1) modulates the G protein complex by keeping it in the resting state (GDP-bound). However, it remains unknown how a myriad of biological responses is achieved with a single G protein modulator. We propose that in complete contrast to G protein activation in animals, plant leucine-rich repeat receptor-like kinases (LRR RLKs), not GPCRs, provide this discrimination through phosphorylation of AtRGS1 in a ligand-dependent manner. G protein signaling is directly activated by the pathogen-associated molecular pattern flagellin peptide 22 through its LRR RLK, FLS2, and co-receptor BAK1. PMID:27235398

  7. Transmembrane signal transduction by peptide hormones via family B G protein-coupled receptors

    PubMed Central

    Culhane, Kelly J.; Liu, Yuting; Cai, Yingying; Yan, Elsa C. Y.

    2015-01-01

    Although family B G protein-coupled receptors (GPCRs) contain only 15 members, they play key roles in transmembrane signal transduction of hormones. Family B GPCRs are drug targets for developing therapeutics for diseases ranging from metabolic to neurological disorders. Despite their importance, the molecular mechanism of activation of family B GPCRs remains largely unexplored due to the challenges in expression and purification of functional receptors to the quantity for biophysical characterization. Currently, there is no crystal structure available of a full-length family B GPCR. However, structures of key domains, including the extracellular ligand binding regions and seven-helical transmembrane regions, have been solved by X-ray crystallography and NMR, providing insights into the mechanisms of ligand recognition and selectivity, and helical arrangements within the cell membrane. Moreover, biophysical and biochemical methods have been used to explore functions, key residues for signaling, and the kinetics and dynamics of signaling processes. This review summarizes the current knowledge of the signal transduction mechanism of family B GPCRs at the molecular level and comments on the challenges and outlook for mechanistic studies of family B GPCRs. PMID:26594176

  8. G-protein-coupled receptor controls steroid hormone signaling in cell membrane

    PubMed Central

    Wang, Di; Zhao, Wen-Li; Cai, Mei-Juan; Wang, Jin-Xing; Zhao, Xiao-Fan

    2015-01-01

    G-protein-coupled receptors (GPCRs) are involved in animal steroid hormone signaling, but their mechanism is unclear. In this research, we report that a GPCR called ErGPCR-2 controls steroid hormone 20-hydroxyecdysone (20E) signaling in the cell membrane of the lepidopteran insect Helicoverpa armigera. ErGPCR-2 was highly expressed during molting and metamorphosis. 20E, via ErGPCR-2, regulated rapid intracellular calcium increase, protein phosphorylation, gene transcription, and insect metamorphosis. ErGPCR-2 was located in the cell surface and was internalized by 20E induction. GPCR kinase 2 participated in 20E-induced ErGPCR-2 phosphorylation and internalization. The internalized ErGPCR-2 was degraded by proteases to desensitize 20E signaling. ErGPCR-2 knockdown suppressed the entrance of 20E analog [3H] ponasterone A ([3H]Pon A) into the cells. ErGPCR-2 overexpression or blocking of ErGPCR-2 internalization increased the entrance of [3H]Pon A into the cells. However, ErGPCR-2 did not bind to [3H]Pon A. Results suggest that ErGPCR-2 transmits steroid hormone 20E signaling and controls 20E entrance into cells in the cell membrane. PMID:25728569

  9. Immobilized Metal Affinity Chromatography Coupled to Multiple Reaction Monitoring Enables Reproducible Quantification of Phospho-signaling.

    PubMed

    Kennedy, Jacob J; Yan, Ping; Zhao, Lei; Ivey, Richard G; Voytovich, Uliana J; Moore, Heather D; Lin, Chenwei; Pogosova-Agadjanyan, Era L; Stirewalt, Derek L; Reding, Kerryn W; Whiteaker, Jeffrey R; Paulovich, Amanda G

    2016-02-01

    A major goal in cell signaling research is the quantification of phosphorylation pharmacodynamics following perturbations. Traditional methods of studying cellular phospho-signaling measure one analyte at a time with poor standardization, rendering them inadequate for interrogating network biology and contributing to the irreproducibility of preclinical research. In this study, we test the feasibility of circumventing these issues by coupling immobilized metal affinity chromatography (IMAC)-based enrichment of phosphopeptides with targeted, multiple reaction monitoring (MRM) mass spectrometry to achieve precise, specific, standardized, multiplex quantification of phospho-signaling responses. A multiplex immobilized metal affinity chromatography- multiple reaction monitoring assay targeting phospho-analytes responsive to DNA damage was configured, analytically characterized, and deployed to generate phospho-pharmacodynamic curves from primary and immortalized human cells experiencing genotoxic stress. The multiplexed assays demonstrated linear ranges of ≥3 orders of magnitude, median lower limit of quantification of 0.64 fmol on column, median intra-assay variability of 9.3%, median inter-assay variability of 12.7%, and median total CV of 16.0%. The multiplex immobilized metal affinity chromatography- multiple reaction monitoring assay enabled robust quantification of 107 DNA damage-responsive phosphosites from human cells following DNA damage. The assays have been made publicly available as a resource to the community. The approach is generally applicable, enabling wide interrogation of signaling networks. PMID:26621847

  10. G-Protein-Coupled Lysophosphatidic Acid Receptors and Their Regulation of AKT Signaling

    PubMed Central

    Riaz, Anjum; Huang, Ying; Johansson, Staffan

    2016-01-01

    A hallmark of G-protein-coupled receptors (GPCRs) is their ability to recognize and respond to chemically diverse ligands. Lysophospholipids constitute a relatively recent addition to these ligands and carry out their biological functions by activating G-proteins coupled to a large family of cell-surface receptors. This review aims to highlight salient features of cell signaling by one class of these receptors, known as lysophosphatidic acid (LPA) receptors, in the context of phosphatidylinositol 3-kinase (PI3K)–AKT pathway activation. LPA moieties efficiently activate AKT phosphorylation and activation in a multitude of cell types. The interplay between LPA, its receptors, the associated Gαi/o subunits, PI3K and AKT contributes to the regulation of cell survival, migration, proliferation and confers chemotherapy-resistance in certain cancers. However, detailed information on the regulation of PI3K–AKT signals induced by LPA receptors is missing from the literature. Here, some urgent issues for investigation are highlighted. PMID:26861299

  11. G-Protein-Coupled Lysophosphatidic Acid Receptors and Their Regulation of AKT Signaling.

    PubMed

    Riaz, Anjum; Huang, Ying; Johansson, Staffan

    2016-01-01

    A hallmark of G-protein-coupled receptors (GPCRs) is their ability to recognize and respond to chemically diverse ligands. Lysophospholipids constitute a relatively recent addition to these ligands and carry out their biological functions by activating G-proteins coupled to a large family of cell-surface receptors. This review aims to highlight salient features of cell signaling by one class of these receptors, known as lysophosphatidic acid (LPA) receptors, in the context of phosphatidylinositol 3-kinase (PI3K)-AKT pathway activation. LPA moieties efficiently activate AKT phosphorylation and activation in a multitude of cell types. The interplay between LPA, its receptors, the associated Gαi/o subunits, PI3K and AKT contributes to the regulation of cell survival, migration, proliferation and confers chemotherapy-resistance in certain cancers. However, detailed information on the regulation of PI3K-AKT signals induced by LPA receptors is missing from the literature. Here, some urgent issues for investigation are highlighted. PMID:26861299

  12. Study on signal intensity of low field nuclear magnetic resonance via an indirect coupling measurement

    NASA Astrophysics Data System (ADS)

    Jiang, Feng-Ying; Wang, Ning; Jin, Yi-Rong; Deng, Hui; Tian, Ye; Lang, Pei-Lin; Li, Jie; Chen, Ying-Fei; Zheng, Dong-Ning

    2013-04-01

    We carry out an ultra-low-field nuclear magnetic resonance (NMR) experiment based on high-Tc superconducting quantum interference devices (SQUIDs). The measurement field is in a micro-tesla range (~10 μT-100 μT) and the experiment is conducted in a home-made magnetically-shielded-room (MSR). The measurements are performed by the indirect coupling method in which the signal of nuclei precession is indirectly coupled to the SQUID through a tuned copper coil transformer. In such an arrangement, the interferences of applied measurement and polarization field to the SQUID sensor are avoided and the performance of the SQUID is not destroyed. In order to compare the detection sensitivity obtained by using the SQUID with that achieved using a conventional low-noise-amplifier, we perform the measurements using a commercial room temperature amplifier. The results show that in a wide frequency range (~1 kHz-10 kHz) the measurements with the SQUID sensor exhibit a higher signal-to-noise ratio. Further, we discuss the dependence of NMR peak magnitude on measurement frequency. We attribute the reduction of the peak magnitude at high frequency to the increased field inhomogeneity as the measurement field increases. This is verified by compensating the field gradient using three sets of gradient coils.

  13. Active site coupling in PDE:PKA complexes promotes resetting of mammalian cAMP signaling.

    PubMed

    Krishnamurthy, Srinath; Moorthy, Balakrishnan Shenbaga; Xin Xiang, Lim; Xin Shan, Lim; Bharatham, Kavitha; Tulsian, Nikhil Kumar; Mihalek, Ivana; Anand, Ganesh S

    2014-09-16

    Cyclic 3'5' adenosine monophosphate (cAMP)-dependent-protein kinase (PKA) signaling is a fundamental regulatory pathway for mediating cellular responses to hormonal stimuli. The pathway is activated by high-affinity association of cAMP with the regulatory subunit of PKA and signal termination is achieved upon cAMP dissociation from PKA. Although steps in the activation phase are well understood, little is known on how signal termination/resetting occurs. Due to the high affinity of cAMP to PKA (KD ∼ low nM), bound cAMP does not readily dissociate from PKA, thus begging the question of how tightly bound cAMP is released from PKA to reset its signaling state to respond to subsequent stimuli. It has been recently shown that phosphodiesterases (PDEs) can catalyze dissociation of bound cAMP and thereby play an active role in cAMP signal desensitization/termination. This is achieved through direct interactions with the regulatory subunit of PKA, thereby facilitating cAMP dissociation and hydrolysis. In this study, we have mapped direct interactions between a specific cyclic nucleotide phosphodiesterase (PDE8A) and a PKA regulatory subunit (RIα isoform) in mammalian cAMP signaling, by a combination of amide hydrogen/deuterium exchange mass spectrometry, peptide array, and computational docking. The interaction interface of the PDE8A:RIα complex, probed by peptide array and hydrogen/deuterium exchange mass spectrometry, brings together regions spanning the phosphodiesterase active site and cAMP-binding sites of RIα. Computational docking combined with amide hydrogen/deuterium exchange mass spectrometry provided a model for parallel dissociation of bound cAMP from the two tandem cAMP-binding domains of RIα. Active site coupling suggests a role for substrate channeling in the PDE-dependent dissociation and hydrolysis of cAMP bound to PKA. This is the first instance, to our knowledge, of PDEs directly interacting with a cAMP-receptor protein in a mammalian system, and

  14. Digital DC-Reconstruction of AC-Coupled Electrophysiological Signals with a Single Inverting Filter

    PubMed Central

    Schmid, Ramun; Leber, Remo; Schmid, Hans-Jakob; Generali, Gianluca

    2016-01-01

    Since the introduction of digital electrocardiographs, high-pass filters have been necessary for successful analog-to-digital conversion with a reasonable amplitude resolution. On the other hand, such high-pass filters may distort the diagnostically significant ST-segment of the ECG, which can result in a misleading diagnosis. We present an inverting filter that successfully undoes the effects of a 0.05 Hz single pole high-pass filter. The inverting filter has been tested on more than 1600 clinical ECGs with one-minute durations and produces a negligible mean RMS-error of 3.1*10−8 LSB. Alternative, less strong inverting filters have also been tested, as have different applications of the filters with respect to rounding of the signals after filtering. A design scheme for the alternative inverting filters has been suggested, based on the maximum strength of the filter. With the use of the suggested filters, it is possible to recover the original DC-coupled ECGs from AC-coupled ECGs, at least when a 0.05 Hz first order digital single pole high-pass filter is used for the AC-coupling. PMID:26938769

  15. Coupled Ca2+/H+ transport by cytoplasmic buffers regulates local Ca2+ and H+ ion signaling.

    PubMed

    Swietach, Pawel; Youm, Jae-Boum; Saegusa, Noriko; Leem, Chae-Hun; Spitzer, Kenneth W; Vaughan-Jones, Richard D

    2013-05-28

    Ca(2+) signaling regulates cell function. This is subject to modulation by H(+) ions that are universal end-products of metabolism. Due to slow diffusion and common buffers, changes in cytoplasmic [Ca(2+)] ([Ca(2+)]i) or [H(+)] ([H(+)]i) can become compartmentalized, leading potentially to complex spatial Ca(2+)/H(+) coupling. This was studied by fluorescence imaging of cardiac myocytes. An increase in [H(+)]i, produced by superfusion of acetate (salt of membrane-permeant weak acid), evoked a [Ca(2+)]i rise, independent of sarcolemmal Ca(2+) influx or release from mitochondria, sarcoplasmic reticulum, or acidic stores. Photolytic H(+) uncaging from 2-nitrobenzaldehyde also raised [Ca(2+)]i, and the yield was reduced following inhibition of glycolysis or mitochondrial respiration. H(+) uncaging into buffer mixtures in vitro demonstrated that Ca(2+) unloading from proteins, histidyl dipeptides (HDPs; e.g., carnosine), and ATP can underlie the H(+)-evoked [Ca(2+)]i rise. Raising [H(+)]i tonically at one end of a myocyte evoked a local [Ca(2+)]i rise in the acidic microdomain, which did not dissipate. The result is consistent with uphill Ca(2+) transport into the acidic zone via Ca(2+)/H(+) exchange on diffusible HDPs and ATP molecules, energized by the [H(+)]i gradient. Ca(2+) recruitment to a localized acid microdomain was greatly reduced during intracellular Mg(2+) overload or by ATP depletion, maneuvers that reduce the Ca(2+)-carrying capacity of HDPs. Cytoplasmic HDPs and ATP underlie spatial Ca(2+)/H(+) coupling in the cardiac myocyte by providing ion exchange and transport on common buffer sites. Given the abundance of cellular HDPs and ATP, spatial Ca(2+)/H(+) coupling is likely to be of general importance in cell signaling. PMID:23676270

  16. Astrocyte Ca2+ Signaling Drives Inversion of Neurovascular Coupling after Subarachnoid Hemorrhage.

    PubMed

    Pappas, Anthony C; Koide, Masayo; Wellman, George C

    2015-09-30

    Physiologically, neurovascular coupling (NVC) matches focal increases in neuronal activity with local arteriolar dilation. Astrocytes participate in NVC by sensing increased neurotransmission and releasing vasoactive agents (e.g., K(+)) from perivascular endfeet surrounding parenchymal arterioles. Previously, we demonstrated an increase in the amplitude of spontaneous Ca(2+) events in astrocyte endfeet and inversion of NVC from vasodilation to vasoconstriction in brain slices obtained from subarachnoid hemorrhage (SAH) model rats. However, the role of spontaneous astrocyte Ca(2+) signaling in determining the polarity of the NVC response remains unclear. Here, we used two-photon imaging of Fluo-4-loaded rat brain slices to determine whether altered endfoot Ca(2+) signaling underlies SAH-induced inversion of NVC. We report a time-dependent emergence of endfoot high-amplitude Ca(2+) signals (eHACSs) after SAH that were not observed in endfeet from unoperated animals. Furthermore, the percentage of endfeet with eHACSs varied with time and paralleled the development of inversion of NVC. Endfeet with eHACSs were present only around arterioles exhibiting inversion of NVC. Importantly, depletion of intracellular Ca(2+) stores using cyclopiazonic acid abolished SAH-induced eHACSs and restored arteriolar dilation in SAH brain slices to two mediators of NVC (a rise in endfoot Ca(2+) and elevation of extracellular K(+)). These data indicate a causal link between SAH-induced eHACSs and inversion of NVC. Ultrastructural examination using transmission electron microscopy indicated that a similar proportion of endfeet exhibiting eHACSs also exhibited asymmetrical enlargement. Our results demonstrate that subarachnoid blood causes a delayed increase in the amplitude of spontaneous intracellular Ca(2+) release events leading to inversion of NVC. Significance statement: Aneurysmal subarachnoid hemorrhage (SAH)--strokes involving cerebral aneurysm rupture and release of blood onto the

  17. Astrocyte Ca2+ Signaling Drives Inversion of Neurovascular Coupling after Subarachnoid Hemorrhage

    PubMed Central

    Pappas, Anthony C.; Koide, Masayo

    2015-01-01

    Physiologically, neurovascular coupling (NVC) matches focal increases in neuronal activity with local arteriolar dilation. Astrocytes participate in NVC by sensing increased neurotransmission and releasing vasoactive agents (e.g., K+) from perivascular endfeet surrounding parenchymal arterioles. Previously, we demonstrated an increase in the amplitude of spontaneous Ca2+ events in astrocyte endfeet and inversion of NVC from vasodilation to vasoconstriction in brain slices obtained from subarachnoid hemorrhage (SAH) model rats. However, the role of spontaneous astrocyte Ca2+ signaling in determining the polarity of the NVC response remains unclear. Here, we used two-photon imaging of Fluo-4-loaded rat brain slices to determine whether altered endfoot Ca2+ signaling underlies SAH-induced inversion of NVC. We report a time-dependent emergence of endfoot high-amplitude Ca2+ signals (eHACSs) after SAH that were not observed in endfeet from unoperated animals. Furthermore, the percentage of endfeet with eHACSs varied with time and paralleled the development of inversion of NVC. Endfeet with eHACSs were present only around arterioles exhibiting inversion of NVC. Importantly, depletion of intracellular Ca2+ stores using cyclopiazonic acid abolished SAH-induced eHACSs and restored arteriolar dilation in SAH brain slices to two mediators of NVC (a rise in endfoot Ca2+ and elevation of extracellular K+). These data indicate a causal link between SAH-induced eHACSs and inversion of NVC. Ultrastructural examination using transmission electron microscopy indicated that a similar proportion of endfeet exhibiting eHACSs also exhibited asymmetrical enlargement. Our results demonstrate that subarachnoid blood causes a delayed increase in the amplitude of spontaneous intracellular Ca2+ release events leading to inversion of NVC. SIGNIFICANCE STATEMENT Aneurysmal subarachnoid hemorrhage (SAH)—strokes involving cerebral aneurysm rupture and release of blood onto the brain surface

  18. Competing G protein-coupled receptor kinases balance G protein and β-arrestin signaling

    PubMed Central

    Heitzler, Domitille; Durand, Guillaume; Gallay, Nathalie; Rizk, Aurélien; Ahn, Seungkirl; Kim, Jihee; Violin, Jonathan D; Dupuy, Laurence; Gauthier, Christophe; Piketty, Vincent; Crépieux, Pascale; Poupon, Anne; Clément, Frédérique; Fages, François; Lefkowitz, Robert J; Reiter, Eric

    2012-01-01

    Seven-transmembrane receptors (7TMRs) are involved in nearly all aspects of chemical communications and represent major drug targets. 7TMRs transmit their signals not only via heterotrimeric G proteins but also through β-arrestins, whose recruitment to the activated receptor is regulated by G protein-coupled receptor kinases (GRKs). In this paper, we combined experimental approaches with computational modeling to decipher the molecular mechanisms as well as the hidden dynamics governing extracellular signal-regulated kinase (ERK) activation by the angiotensin II type 1A receptor (AT1AR) in human embryonic kidney (HEK)293 cells. We built an abstracted ordinary differential equations (ODE)-based model that captured the available knowledge and experimental data. We inferred the unknown parameters by simultaneously fitting experimental data generated in both control and perturbed conditions. We demonstrate that, in addition to its well-established function in the desensitization of G-protein activation, GRK2 exerts a strong negative effect on β-arrestin-dependent signaling through its competition with GRK5 and 6 for receptor phosphorylation. Importantly, we experimentally confirmed the validity of this novel GRK2-dependent mechanism in both primary vascular smooth muscle cells naturally expressing the AT1AR, and HEK293 cells expressing other 7TMRs. PMID:22735336

  19. G protein-coupled receptors as oncogenic signals in glioma: emerging therapeutic avenues

    PubMed Central

    Cherry, Allison E; Stella, Nephi

    2014-01-01

    Gliomas are the most common malignant intracranial tumors. Newly developed targeted therapies for these cancers aim to inhibit oncogenic signals, many of which emanate from receptor tyrosine kinases, including the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptor (VEGFR). Unfortunately, the first generation treatments targeting these oncogenic signals provide little survival benefit in both mouse xenograft models and human patients. The search for new treatment options has uncovered several G protein-coupled receptor (GPCR) candidates and generated a growing interest in this class of proteins as alternative therapeutic targets for the treatment of various cancers, including GBM. GPCRs constitute a large family of membrane receptors that influence oncogenic pathways through canonical and non-canonical signaling. Accordingly, evidence indicates that GPCRs display a unique ability to crosstalk with receptor tyrosine kinases, making them important molecular components controlling tumorigenesis. This review summarizes the current research on GPCR functionality in gliomas and explores the potential of modulating these receptors to treat this devastating disease. PMID:25158675

  20. Reliability of Signal Propagation in Magnetostatically Coupled Arrays of Magnetic Nanoelements

    NASA Astrophysics Data System (ADS)

    van Mourik, Reinier; Gao, Li; Hughes, Brian; Rettner, Charles; Koopmans, Bert; Parkin, Stuart

    2013-03-01

    Nanomagnetic logic (NML) has promise as a low-power, non-volatile, and radiation resistant alternative to CMOS-based computational devices. Lines of magnetostatically coupled magnetic nano-elements (NEs) propagate information, and the intersections between lines form logic gates. We present simulations and experiments exploring the reliability of signal propagation in NML devices composed of lines of nominally rectangular permalloy NEs, typically 90 ×60 nm2 in size. An external magnetic field sets the magnetic state of an input bit and also resets each of the NEs' magnetizations along their hard axis direction. As the field is reduced to zero the input state propagates along the line of NEs as they successively relax into one of two equilibrium states. The state of the NEs is probed by (i) a magnetic tunnel junction sensing device integrated with the output NE and (ii) magnetic force microscopy imaging. We conclude that signal propagation is inherently unreliable both through variations in fabrication of the NEs and due to the innate lack of directionality of the flow of information. We demonstrate an alternative clocking method where a domain wall passing underneath an NML device clocks each NE sequentially, thereby increasing the success of signal propagation. IBM: San Jose, CA; Eindhoven University: Eindhoven, the Netherlands; Mainz Graduate school: Mainz, Germany

  1. G-protein-coupled receptor participates in 20-hydroxyecdysone signaling on the plasma membrane

    PubMed Central

    2014-01-01

    Background Animal steroid hormones are conventionally known to initiate signaling via a genomic pathway by binding to the nuclear receptors. The mechanism by which 20E initiates signaling via a nongenomic pathway is unclear. Results We illustrate that 20E triggered the nongenomic pathway through a plasma membrane G-protein-coupled receptor (named ErGPCR) in the lepidopteran insect Helicoverpa armigera. The transcript of ErGPCR was increased at the larval molting stage and metamorphic molting stage by 20E regulation. Knockdown of ErGPCR via RNA interference in vivo blocked larval–pupal transition and suppressed 20E-induced gene expression. ErGPCR overexpression in the H. armigera epidermal cell line increased the 20E-induced gene expression. Through ErGPCR, 20E modulated Calponin nuclear translocation and phosphorylation, and induced a rapid increase in cytosolic Ca2+ levels. The inhibitors of T-type voltage-gated calcium channels and canonical transient receptor potential calcium channels repressed the 20E-induced Ca2+ increase. Truncation of the N-terminal extracellular region of ErGPCR inhibited its localization on the plasma membrane and 20E-induced gene expression. ErGPCR was not detected to bind with the steroid hormone analog [3H]Pon A. Conclusion These results suggest that ErGPCR participates in 20E signaling on the plasma membrane. PMID:24507557

  2. Control of synchronization and spiking regularity by heterogenous aperiodic high-frequency signal in coupled excitable systems

    NASA Astrophysics Data System (ADS)

    Qin, Ying-Mei; Wang, Jiang; Men, Cong; Chan, Wai-Lok; Wei, Xi-Le; Deng, Bin

    2013-10-01

    This paper investigates the synchronization and spiking regularity induced by heterogenous aperiodic (HA) signal in coupled excitable FitzHugh-Nagumo systems. We found new nontrivial effects of couplings and HA signals on the firing regularity and synchronization in coupled excitable systems without a periodic external driving. The phenomenon is similar to array enhanced coherence resonance (AECR), and it is shown that AECR-type behavior is not limited to systems driven by noises. It implies that the HA signal may be beneficial for the brain function, which is similar to the role of noise. Furthermore, it is also found that the mean frequencies, the amplitudes and the heterogeneity of HA stimuli can serve as control parameters in modulating spiking regularity and synchronization in coupled excitable systems. These results may be significant for the control of the synchronized firing of the brain in neural diseases like epilepsy.

  3. SLO BK Potassium Channels Couple Gap Junctions to Inhibition of Calcium Signaling in Olfactory Neuron Diversification

    PubMed Central

    Schumacher, Jennifer A.; Wang, Xiaohong; Merrill, Sean A.; Millington, Grethel; Bayne, Brittany; Jorgensen, Erik M.; Chuang, Chiou-Fen

    2016-01-01

    The C. elegans AWC olfactory neuron pair communicates to specify asymmetric subtypes AWCOFF and AWCON in a stochastic manner. Intercellular communication between AWC and other neurons in a transient NSY-5 gap junction network antagonizes voltage-activated calcium channels, UNC-2 (CaV2) and EGL-19 (CaV1), in the AWCON cell, but how calcium signaling is downregulated by NSY-5 is only partly understood. Here, we show that voltage- and calcium-activated SLO BK potassium channels mediate gap junction signaling to inhibit calcium pathways for asymmetric AWC differentiation. Activation of vertebrate SLO-1 channels causes transient membrane hyperpolarization, which makes it an important negative feedback system for calcium entry through voltage-activated calcium channels. Consistent with the physiological roles of SLO-1, our genetic results suggest that slo-1 BK channels act downstream of NSY-5 gap junctions to inhibit calcium channel-mediated signaling in the specification of AWCON. We also show for the first time that slo-2 BK channels are important for AWC asymmetry and act redundantly with slo-1 to inhibit calcium signaling. In addition, nsy-5-dependent asymmetric expression of slo-1 and slo-2 in the AWCON neuron is necessary and sufficient for AWC asymmetry. SLO-1 and SLO-2 localize close to UNC-2 and EGL-19 in AWC, suggesting a role of possible functional coupling between SLO BK channels and voltage-activated calcium channels in AWC asymmetry. Furthermore, slo-1 and slo-2 regulate the localization of synaptic markers, UNC-2 and RAB-3, in AWC neurons to control AWC asymmetry. We also identify the requirement of bkip-1, which encodes a previously identified auxiliary subunit of SLO-1, for slo-1 and slo-2 function in AWC asymmetry. Together, these results provide an unprecedented molecular link between gap junctions and calcium pathways for terminal differentiation of olfactory neurons. PMID:26771544

  4. SLO BK Potassium Channels Couple Gap Junctions to Inhibition of Calcium Signaling in Olfactory Neuron Diversification.

    PubMed

    Alqadah, Amel; Hsieh, Yi-Wen; Schumacher, Jennifer A; Wang, Xiaohong; Merrill, Sean A; Millington, Grethel; Bayne, Brittany; Jorgensen, Erik M; Chuang, Chiou-Fen

    2016-01-01

    The C. elegans AWC olfactory neuron pair communicates to specify asymmetric subtypes AWCOFF and AWCON in a stochastic manner. Intercellular communication between AWC and other neurons in a transient NSY-5 gap junction network antagonizes voltage-activated calcium channels, UNC-2 (CaV2) and EGL-19 (CaV1), in the AWCON cell, but how calcium signaling is downregulated by NSY-5 is only partly understood. Here, we show that voltage- and calcium-activated SLO BK potassium channels mediate gap junction signaling to inhibit calcium pathways for asymmetric AWC differentiation. Activation of vertebrate SLO-1 channels causes transient membrane hyperpolarization, which makes it an important negative feedback system for calcium entry through voltage-activated calcium channels. Consistent with the physiological roles of SLO-1, our genetic results suggest that slo-1 BK channels act downstream of NSY-5 gap junctions to inhibit calcium channel-mediated signaling in the specification of AWCON. We also show for the first time that slo-2 BK channels are important for AWC asymmetry and act redundantly with slo-1 to inhibit calcium signaling. In addition, nsy-5-dependent asymmetric expression of slo-1 and slo-2 in the AWCON neuron is necessary and sufficient for AWC asymmetry. SLO-1 and SLO-2 localize close to UNC-2 and EGL-19 in AWC, suggesting a role of possible functional coupling between SLO BK channels and voltage-activated calcium channels in AWC asymmetry. Furthermore, slo-1 and slo-2 regulate the localization of synaptic markers, UNC-2 and RAB-3, in AWC neurons to control AWC asymmetry. We also identify the requirement of bkip-1, which encodes a previously identified auxiliary subunit of SLO-1, for slo-1 and slo-2 function in AWC asymmetry. Together, these results provide an unprecedented molecular link between gap junctions and calcium pathways for terminal differentiation of olfactory neurons. PMID:26771544

  5. Coupling mechanical forces to electrical signaling: molecular motors and the intracellular transport of ion channels.

    PubMed

    Barry, Joshua; Gu, Chen

    2013-04-01

    Proper localization of various ion channels is fundamental to neuronal functions, including postsynaptic potential plasticity, dendritic integration, action potential initiation and propagation, and neurotransmitter release. Microtubule-based forward transport mediated by kinesin motors plays a key role in placing ion channel proteins to correct subcellular compartments. PDZ- and coiled-coil-domain proteins function as adaptor proteins linking ionotropic glutamate and GABA receptors to various kinesin motors, respectively. Recent studies show that several voltage-gated ion channel/transporter proteins directly bind to kinesins during forward transport. Three major regulatory mechanisms underlying intracellular transport of ion channels are also revealed. These studies contribute to understanding how mechanical forces are coupled to electrical signaling and illuminating pathogenic mechanisms in neurodegenerative diseases. PMID:22910031

  6. Signal-Coupled Subthreshold Hopf-Type Systems Show a Sharpened Collective Response

    NASA Astrophysics Data System (ADS)

    Gomez, Florian; Lorimer, Tom; Stoop, Ruedi

    2016-03-01

    Astounding properties of biological sensors can often be mapped onto a dynamical system below the occurrence of a bifurcation. For mammalian hearing, a Hopf bifurcation description has been shown to work across a whole range of scales, from individual hair bundles to whole regions of the cochlea. We reveal here the origin of this scale invariance, from a general level, applicable to all dynamics in the vicinity of a Hopf bifurcation (embracing, e.g., neuronal Hodgkin-Huxley equations). When subject to natural "signal coupling," ensembles of Hopf systems below the bifurcation threshold exhibit a collective Hopf bifurcation. This collective Hopf bifurcation occurs at parameter values substantially below where the average of the individual systems would bifurcate, with a frequency profile that is sharpened if compared to the individual systems.

  7. Signal-Coupled Subthreshold Hopf-Type Systems Show a Sharpened Collective Response.

    PubMed

    Gomez, Florian; Lorimer, Tom; Stoop, Ruedi

    2016-03-11

    Astounding properties of biological sensors can often be mapped onto a dynamical system below the occurrence of a bifurcation. For mammalian hearing, a Hopf bifurcation description has been shown to work across a whole range of scales, from individual hair bundles to whole regions of the cochlea. We reveal here the origin of this scale invariance, from a general level, applicable to all dynamics in the vicinity of a Hopf bifurcation (embracing, e.g., neuronal Hodgkin-Huxley equations). When subject to natural "signal coupling," ensembles of Hopf systems below the bifurcation threshold exhibit a collective Hopf bifurcation. This collective Hopf bifurcation occurs at parameter values substantially below where the average of the individual systems would bifurcate, with a frequency profile that is sharpened if compared to the individual systems. PMID:27015509

  8. A protonation-coupled feedback mechanism controls the signalling process in bathy phytochromes

    NASA Astrophysics Data System (ADS)

    Velazquez Escobar, Francisco; Piwowarski, Patrick; Salewski, Johannes; Michael, Norbert; Fernandez Lopez, Maria; Rupp, Anna; Muhammad Qureshi, Bilal; Scheerer, Patrick; Bartl, Franz; Frankenberg-Dinkel, Nicole; Siebert, Friedrich; Andrea Mroginski, Maria; Hildebrandt, Peter

    2015-05-01

    Phytochromes are bimodal photoswitches composed of a photosensor and an output module. Photoactivation of the sensor is initiated by a double bond isomerization of the tetrapyrrole chromophore and eventually leads to protein conformational changes. Recently determined structural models of phytochromes identify differences between the inactive and the signalling state but do not reveal the mechanism of photosensor activation or deactivation. Here, we report a vibrational spectroscopic study on bathy phytochromes that demonstrates that the formation of the photoactivated state and thus (de)activation of the output module is based on proton translocations in the chromophore pocket coupling chromophore and protein structural changes. These proton transfer steps, involving the tetrapyrrole and a nearby histidine, also enable thermal back-isomerization of the chromophore via keto-enol tautomerization to afford the initial dark state. Thus, the same proton re-arrangements inducing the (de)activation of the output module simultaneously initiate the reversal of this process, corresponding to a negative feedback mechanism.

  9. Coupling Mechanical Forces to Electrical Signaling: Molecular Motors and the Intracellular Transport of Ion Channels

    PubMed Central

    Barry, Joshua; Gu, Chen

    2013-01-01

    Proper localization of various ion channels is fundamental to neuronal functions, including postsynaptic potential plasticity, dendritic integration, action potential initiation and propagation, and neurotransmitter release. Microtubule-based forward transport mediated by kinesin motors plays a key role in placing ion channel proteins to correct subcellular compartments. PDZ- and coiled-coil-domain proteins function as adaptor proteins linking ionotropic glutamate and GABA receptors to various kinesin motors, respectively. Recent studies show that several voltage-gated ion channel/transporter proteins directly bind to kinesins during forward transport. Three major regulatory mechanisms underlying intracellular transport of ion channels are also revealed. These studies contribute to understanding how mechanical forces are coupled to electrical signaling and illuminating pathogenic mechanisms in neurodegenerative diseases. PMID:22910031

  10. Mathematical modeling and application of genetic algorithm to parameter estimation in signal transduction: trafficking and promiscuous coupling of G-protein coupled receptors.

    PubMed

    Modchang, Charin; Triampo, Wannapong; Lenbury, Yongwimon

    2008-05-01

    G-protein-coupled receptors (GPCRs) constitute a large and diverse family of proteins whose primary function is to transduce extracellular stimuli into intracellular signals. These receptors play a critical role in signal transduction, and are among the most important pharmacological drug targets. Upon binding of extracellular ligands, these receptor molecules couple to one or several subtypes of G-protein which reside at the intracellular side of the plasma membrane to trigger intracellular signaling events. The question of how GPCRs select and activate a single or multiple G-protein subtype(s) has been the topic of intense investigations. Evidence is also accumulating; however, that certain GPCRs can be internalized via lipid rafts and caveolae. In many cases, the mechanisms responsible for this still remain to be elucidated. In this work, we extend the mathematical model proposed by Chen et al. [Modelling of signalling via G-protein coupled receptors: pathway-dependent agonist potency and efficacy, Bull. Math. Biol. 65 (5) (2003) 933-958] to take into account internalization, recycling, degradation and synthesis of the receptors. In constructing the model, we assume that the receptors can exist in multiple conformational states allowing for a multiple effecter pathways. As data on kinetic reaction rates in the signalling processes measured in reliable in vivo and in vitro experiments is currently limited to a small number of known values. In this paper, we also apply a genetic algorithm (GA) to estimate the parameter values in our model. PMID:18367158

  11. Metabotropic glutamate receptor 5 couples cellular prion protein to intracellular signalling in Alzheimer's disease.

    PubMed

    Haas, Laura T; Salazar, Santiago V; Kostylev, Mikhail A; Um, Ji Won; Kaufman, Adam C; Strittmatter, Stephen M

    2016-02-01

    Alzheimer's disease-related phenotypes in mice can be rescued by blockade of either cellular prion protein or metabotropic glutamate receptor 5. We sought genetic and biochemical evidence that these proteins function cooperatively as an obligate complex in the brain. We show that cellular prion protein associates via transmembrane metabotropic glutamate receptor 5 with the intracellular protein mediators Homer1b/c, calcium/calmodulin-dependent protein kinase II, and the Alzheimer's disease risk gene product protein tyrosine kinase 2 beta. Coupling of cellular prion protein to these intracellular proteins is modified by soluble amyloid-β oligomers, by mouse brain Alzheimer's disease transgenes or by human Alzheimer's disease pathology. Amyloid-β oligomer-triggered phosphorylation of intracellular protein mediators and impairment of synaptic plasticity in vitro requires Prnp-Grm5 genetic interaction, being absent in transheterozygous loss-of-function, but present in either single heterozygote. Importantly, genetic coupling between Prnp and Grm5 is also responsible for signalling, for survival and for synapse loss in Alzheimer's disease transgenic model mice. Thus, the interaction between metabotropic glutamate receptor 5 and cellular prion protein has a central role in Alzheimer's disease pathogenesis, and the complex is a potential target for disease-modifying intervention. PMID:26667279

  12. Polyglutamate directed coupling of bioactive peptides for the delivery of osteoinductive signals on allograft bone

    PubMed Central

    Culpepper, Bonnie K.; Bonvallet, Paul P.; Reddy, Michael S.; Ponnazhagan, Selvarangan; Bellis, Susan L.

    2012-01-01

    Allograft bone is commonly used as an alternative to autograft, however allograft lacks many osteoinductive factors present in autologous bone due to processing. In this study, we investigated a method to reconstitute allograft with osteoregenerative factors. Specifically, an osteoinductive peptide from collagen I, DGEA, was engineered to express a heptaglutamate (E7) domain, which binds the hydroxyapatite within bone mineral. Addition of E7 to DGEA resulted in 9× greater peptide loading on allograft, and significantly greater retention after a 5-day interval with extensive washing. When factoring together greater initial loading and retention, the E7 domain directed a 45-fold enhancement of peptide density on the allograft surface. Peptide-coated allograft was also implanted subcutaneously into rats and it was found that E7DGEA was retained in vivo for at least 3 months. Interestingly, E7DGEA peptides injected intravenously accumulated within bone tissue, implicating a potential role for E7 domains in drug delivery to bone. Finally, we determined that, as with DGEA, the E7 modification enhanced coupling of a bioactive BMP2-derived peptide on allograft. These results suggest that E7 domains are useful for coupling many types of bone-regenerative molecules to the surface of allograft to reintroduce osteoinductive signals and potentially advance allograft treatments. PMID:23182349

  13. Epigenetic regulation of G protein coupled receptor signaling and its implications in psychiatric disorders.

    PubMed

    Dogra, Shalini; Sona, Chandan; Kumar, Ajeet; Yadav, Prem N

    2016-08-01

    G protein-coupled receptors (GPCRs) act as a relay center through which extracellular signals, in the form of neurotransmitters or therapeutics, are converted into an intracellular response, which ultimately shapes the overall response at the tissue and behavioral level. Remarkably in similar ways, epigenetic mechanisms also modulate the expression pattern of a large number of genes in response to the dynamic environment inside and outside of the body, and consequently overall response. Emerging evidences from the pharmacogenomics and preclinical studies clearly suggest that these two distinct mechanisms criss-cross each other in several neurological disorders. At one hand such cross-talks between two distinct mechanisms make disease etiology more challenging to understand, while on the other hand if dealt appropriately, such situations might provide an opportunity to find novel druggable target and strategy for the treatment of complex diseases. In this review article, we have summarized and highlighted the main findings that tie epigenetic mechanisms to GPCR mediated signaling in the pathophysiology of central nervous system (CNS) disorders, including depression, addiction and pain. PMID:27046448

  14. Signal enhancement in cantilever magnetometry based on a co-resonantly coupled sensor.

    PubMed

    Körner, Julia; Reiche, Christopher F; Gemming, Thomas; Büchner, Bernd; Gerlach, Gerald; Mühl, Thomas

    2016-01-01

    Cantilever magnetometry is a measurement technique used to study magnetic nanoparticles. With decreasing sample size, the signal strength is significantly reduced, requiring advances of the technique. Ultrathin and slender cantilevers can address this challenge but lead to increased complexity of detection. We present an approach based on the co-resonant coupling of a micro- and a nanometer-sized cantilever. Via matching of the resonance frequencies of the two subsystems we induce a strong interplay between the oscillations of the two cantilevers, allowing for a detection of interactions between the sensitive nanocantilever and external influences in the amplitude response curve of the microcantilever. In our magnetometry experiment we used an iron-filled carbon nanotube acting simultaneously as nanocantilever and magnetic sample. Measurements revealed an enhancement of the commonly used frequency shift signal by five orders of magnitude compared to conventional cantilever magnetometry experiments with similar nanomagnets. With this experiment we do not only demonstrate the functionality of our sensor design but also its potential for very sensitive magnetometry measurements while maintaining a facile oscillation detection with a conventional microcantilever setup. PMID:27547621

  15. Signal enhancement in cantilever magnetometry based on a co-resonantly coupled sensor

    PubMed Central

    Körner, Julia; Reiche, Christopher F; Gemming, Thomas; Büchner, Bernd; Gerlach, Gerald

    2016-01-01

    Summary Cantilever magnetometry is a measurement technique used to study magnetic nanoparticles. With decreasing sample size, the signal strength is significantly reduced, requiring advances of the technique. Ultrathin and slender cantilevers can address this challenge but lead to increased complexity of detection. We present an approach based on the co-resonant coupling of a micro- and a nanometer-sized cantilever. Via matching of the resonance frequencies of the two subsystems we induce a strong interplay between the oscillations of the two cantilevers, allowing for a detection of interactions between the sensitive nanocantilever and external influences in the amplitude response curve of the microcantilever. In our magnetometry experiment we used an iron-filled carbon nanotube acting simultaneously as nanocantilever and magnetic sample. Measurements revealed an enhancement of the commonly used frequency shift signal by five orders of magnitude compared to conventional cantilever magnetometry experiments with similar nanomagnets. With this experiment we do not only demonstrate the functionality of our sensor design but also its potential for very sensitive magnetometry measurements while maintaining a facile oscillation detection with a conventional microcantilever setup. PMID:27547621

  16. Mitigating Oscillator Pulling Due To Magnetic Coupling in Monolithic Mixed-Signal Radio-Frequency Integrated Circuits

    SciTech Connect

    Sobering, Ian David

    2014-01-01

    An analysis of frequency pulling in a varactor-tuned LC VCO under coupling from an on-chip PA is presented. The large-signal behavior of the VCO's inversion-mode MOS varactors is outlined, and the susceptibility of the VCO to frequency pulling from PA aggressor signals with various modulation schemes is discussed. We show that if the aggressor signal is aperiodic, band-limited, or amplitude-modulated, the varactor-tuned LC VCO will experience frequency pulling due to time-modulation of the varactor capacitance. However, if the aggressor signal has constant-envelope phase modulation, VCO pulling can be eliminated, even in the presence of coupling, through careful choice of VCO frequency and divider ratio. Additional mitigation strategies, including new inductor topologies and system-level architectural choices, are also examined.

  17. COUPLING

    DOEpatents

    Hawke, B.C.

    1963-02-26

    This patent relates to a releasable coupling connecting a control rod to a control rod drive. This remotely operable coupling mechanism can connect two elements which are laterally and angviarly misaligned, and provides a means for sensing the locked condition of the elements. The coupling utilizes a spherical bayonet joint which is locked against rotation by a ball detent lock. (AEC)

  18. Evidence for Nonlinear Coupling of Solar and ENSO Signals in Indian Temperatures During the Past Century

    NASA Astrophysics Data System (ADS)

    Tiwari, R. K.; Rajesh, Rekapalli; Padmavathi, B.

    2015-02-01

    Significant fluctuations have been observed in Indian temperatures during past century. In order to identify the statistical periodicities in the maximum and minimum temperature data of different Indian zones, we have spectrally and statistically analyzed the homogeneous regional temperature series from the Western Himalayas, the Northern West, the North Central, the North East (NE), the West Coast, the East Coast, and the Interior Peninsula for the period of 107 years spanning over 1901-2007 using the multitaper method (MTM) and singular spectrum analysis (SSA) methods. The first SSA reconstructed the principal component of all the data sets representing a nonlinear trend (indicating a monotonic rise in temperature probably due to greenhouse gases and other forcing) that varies from region to region. We have reconstructed the temperature time series using the second to tenth oscillatory principal components of all the eight regions and computed their power spectral density using MTM. Our analyses indicate that there is a strong spectral power in the period range of 2-7 years and 53 years, which are matched respectively with the known El Niño-Southern oscillation (ENSO) periods and ocean circulation cycles. Further, the spectral analysis also revealed a statistically significant but riven cycle in a period range of 9.8-13 years corresponding to the Schwabe cycle in all Indiaian maximum and minimum temperature records and almost all the zonal records except in the NE data. In some of the cases, the 22 year double sunspot (Hale cycle) cycle was also identified here. Invariably the splitting of spectral peaks corresponding to solar signal indicated nonlinear characteristics of the data and; therefore, even small variations in the solar output may help in catalyzing the coupled El Niño-atmospheric ENSO cycles by altering the solar heat input to the oceans. We, therefore, conclude that the Indian temperature variability is probably driven by the nonlinear coupling of

  19. PDZ Protein Regulation of G Protein-Coupled Receptor Trafficking and Signaling Pathways.

    PubMed

    Dunn, Henry A; Ferguson, Stephen S G

    2015-10-01

    G protein-coupled receptors (GPCRs) contribute to the regulation of every aspect of human physiology and are therapeutic targets for the treatment of numerous diseases. As a consequence, understanding the myriad of mechanisms controlling GPCR signaling and trafficking is essential for the development of new pharmacological strategies for the treatment of human pathologies. Of the many GPCR-interacting proteins, postsynaptic density protein of 95 kilodaltons, disc large, zona occludens-1 (PDZ) domain-containing proteins appear most abundant and have similarly been implicated in disease mechanisms. PDZ proteins play an important role in regulating receptor and channel protein localization within synapses and tight junctions and function to scaffold intracellular signaling protein complexes. In the current study, we review the known functional interactions between PDZ domain-containing proteins and GPCRs and provide insight into the potential mechanisms of action. These PDZ domain-containing proteins include the membrane-associated guanylate-like kinases [postsynaptic density protein of 95 kilodaltons; synapse-associated protein of 97 kilodaltons; postsynaptic density protein of 93 kilodaltons; synapse-associated protein of 102 kilodaltons; discs, large homolog 5; caspase activation and recruitment domain and membrane-associated guanylate-like kinase domain-containing protein 3; membrane protein, palmitoylated 3; calcium/calmodulin-dependent serine protein kinase; membrane-associated guanylate kinase protein (MAGI)-1, MAGI-2, and MAGI-3], Na(+)/H(+) exchanger regulatory factor proteins (NHERFs) (NHERF1, NHERF2, PDZ domain-containing kidney protein 1, and PDZ domain-containing kidney protein 2), Golgi-associated PDZ proteins (Gα-binding protein interacting protein, C-terminus and CFTR-associated ligand), PDZ domain-containing guanine nucleotide exchange factors (GEFs) 1 and 2, regulator of G protein signaling (RGS)-homology-RhoGEFs (PDZ domain-containing RhoGEF and

  20. The emerging anthropogenic signal in land-atmosphere carbon-cycle coupling

    NASA Astrophysics Data System (ADS)

    Lombardozzi, Danica; Bonan, Gordon B.; Nychka, Douglas W.

    2014-09-01

    Earth system models simulate prominent terrestrial carbon-cycle responses to anthropogenically forced changes in climate and atmospheric composition over the twenty-first century. The rate and magnitude of the forced climate change is routinely evaluated relative to unforced, or natural, variability using a multi-member ensemble of simulations. However, Earth system model carbon-cycle analyses do not account for unforced variability. To investigate unforced terrestrial carbon-cycle variability, we analyse ensembles from the Coupled Model Intercomparison Project (CMIP5), focusing on the Community Climate System Model (CCSM4). The unforced variability of CCSM4 is comparable to that observed at the Harvard Forest eddy covariance flux tower site. Over the twenty-first century, unforced variability in land-atmosphere CO2 flux is larger than the forced response at decadal timescales in many areas of the world, precluding detection of the forced carbon-cycle change. Only after several decades does the forced carbon signal consistently emerge in CCSM4 and other models for the business-as-usual radiative forcing scenario (RCP8.5). Grid-cell variability in time of emergence is large, but decreases at regional scales. To attribute changes in the terrestrial carbon cycle to anthropogenic forcings, monitoring networks and model projections must consider the timescale at which the forced biogeochemical response emerges from the natural variability.

  1. Exploring phospholipase C-coupled Ca(2+) signalling networks using Boolean modelling.

    PubMed

    Bhardwaj, G; Wells, C P; Albert, R; van Rossum, D B; Patterson, R L

    2011-05-01

    In this study, the authors explored the utility of a descriptive and predictive bionetwork model for phospholipase C-coupled calcium signalling pathways, built with non-kinetic experimental information. Boolean models generated from these data yield oscillatory activity patterns for both the endoplasmic reticulum resident inositol-1,4,5-trisphosphate receptor (IP(3)R) and the plasma-membrane resident canonical transient receptor potential channel 3 (TRPC3). These results are specific as randomisation of the Boolean operators ablates oscillatory pattern formation. Furthermore, knock-out simulations of the IP(3)R, TRPC3 and multiple other proteins recapitulate experimentally derived results. The potential of this approach can be observed by its ability to predict previously undescribed cellular phenotypes using in vitro experimental data. Indeed, our cellular analysis of the developmental and calcium-regulatory protein, DANGER1a, confirms the counter-intuitive predictions from our Boolean models in two highly relevant cellular models. Based on these results, the authors theorise that with sufficient legacy knowledge and/or computational biology predictions, Boolean networks can provide a robust method for predictive modelling of any biological system. [Includes supplementary material]. PMID:21639591

  2. New functions and signaling mechanisms for the class of adhesion G protein–coupled receptors

    PubMed Central

    Liebscher, Ines; Ackley, Brian; Araç, Demet; Ariestanti, Donna M.; Aust, Gabriela; Bae, Byoung-il; Bista, Bigyan R.; Bridges, James P.; Duman, Joseph G.; Engel, Felix B.; Giera, Stefanie; Goffinet, André M.; Hall, Randy A.; Hamann, Jörg; Hartmann, Nicole; Lin, Hsi-Hsien; Liu, Mingyao; Luo, Rong; Mogha, Amit; Monk, Kelly R.; Peeters, Miriam C.; Prömel, Simone; Ressl, Susanne; Schiöth, Helgi B.; Sigoillot, Séverine M.; Song, Helen; Talbot, William S.; Tall, Gregory G.; White, James P.; Wolfrum, Uwe; Xu, Lei; Piao, Xianhua

    2014-01-01

    The class of adhesion G protein–coupled receptors (aGPCRs), with 33 human homologs, is the second largest family of GPCRs. In addition to a seven-transmembrane α-helix—a structural feature of all GPCRs—the class of aGPCRs is characterized by the presence of a large N-terminal extracellular region. In addition, all aGPCRs but one (GPR123) contain a GPCR autoproteolysis–inducing (GAIN) domain that mediates autoproteolytic cleavage at the GPCR autoproteolysis site (GPS) motif to generate N- and a C-terminal fragments (NTF and CTF, respectively) during protein maturation. Subsequently, the NTF and CTF are associated non-covalently as a heterodimer at the plasma membrane. While the biological function of the GAIN domain–mediated autocleavage is not fully understood, mounting evidence suggests that the NTF and CTF possess distinct biological activities in addition to their function as a receptor unit. We discuss recent advances in understanding the biological functions, signaling mechanisms, and disease associations of the aGPCRs. PMID:25424900

  3. A historical perspective on the lateral diffusion model of GTPase activation and related coupling of membrane signaling proteins

    PubMed Central

    Liebman, Paul A

    2014-01-01

    Aspects of our discovery of lateral diffusion of the G protein coupled receptor (GPCR) rhodopsin and that a single activated rhodopsin can non-covalently catalyze GTP binding to thousands of GTPases per second on rod disk membranes via this diffusion are summarized herein. Rapid GTPase coupling to membrane-bound phosphodiesterase (PDE) further amplifies the signal via cGMP hydrolysis, essential to visual transduction. Important generalizations from this work are that biomembranes can uniquely concentrate, orient for reaction and provide a solvent appropriate to rapid, powerful and appropriately controlled sequential interaction of signaling proteins. Of equal importance to function is timely control and termination of such powerful amplification via receptor phosphorylation (quenching) and arrestin binding. Downstream kinetic modulation by GTPase activating proteins (GAPs) and regulators of G protein signaling (RGS) and related mechanisms as well as limitations set by membrane domain fencing, structural protein binding etc. can be essential in relevant systems. PMID:25279248

  4. N-Arachidonyl glycine does not activate G protein-coupled receptor 18 signaling via canonical pathways.

    PubMed

    Lu, Van B; Puhl, Henry L; Ikeda, Stephen R

    2013-01-01

    Recent studies propose that N-arachidonyl glycine (NAGly), a carboxylic analogue of anandamide, is an endogenous ligand of the Gα(i/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 (Ca(v)2.2) 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 Gα(i/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: Gα(s), Gα(z), and Gα(15). These results suggest NAGly is not an agonist for GPR18 or that GPR18 signaling involves noncanonical pathways not examined in these studies. PMID:23104136

  5. COUPLING

    DOEpatents

    Frisch, E.; Johnson, C.G.

    1962-05-15

    A detachable coupling arrangement is described which provides for varying the length of the handle of a tool used in relatively narrow channels. The arrangement consists of mating the key and keyhole formations in the cooperating handle sections. (AEC)

  6. Fluorescence/bioluminescence resonance energy transfer techniques to study G-protein-coupled receptor activation and signaling.

    PubMed

    Lohse, Martin J; Nuber, Susanne; Hoffmann, Carsten

    2012-04-01

    Fluorescence and bioluminescence resonance energy transfer (FRET and BRET) techniques allow the sensitive monitoring of distances between two labels at the nanometer scale. Depending on the placement of the labels, this permits the analysis of conformational changes within a single protein (for example of a receptor) or the monitoring of protein-protein interactions (for example, between receptors and G-protein subunits). Over the past decade, numerous such techniques have been developed to monitor the activation and signaling of G-protein-coupled receptors (GPCRs) in both the purified, reconstituted state and in intact cells. These techniques span the entire spectrum from ligand binding to the receptors down to intracellular second messengers. They allow the determination and the visualization of signaling processes with high temporal and spatial resolution. With these techniques, it has been demonstrated that GPCR signals may show spatial and temporal patterning. In particular, evidence has been provided for spatial compartmentalization of GPCRs and their signals in intact cells and for distinct physiological consequences of such spatial patterning. We review here the FRET and BRET technologies that have been developed for G-protein-coupled receptors and their signaling proteins (G-proteins, effectors) and the concepts that result from such experiments. PMID:22407612

  7. Light-sensitive coupling of rhodopsin and melanopsin to Gi/o and Gq signal transduction in Caenorhabditis elegans

    PubMed Central

    Cao, Pengxiu; Sun, Wenyu; Kramp, Kristopher; Zheng, Maohua; Salom, David; Jastrzebska, Beata; Jin, Hui; Palczewski, Krzysztof; Feng, Zhaoyang

    2012-01-01

    Activation of G-protein-coupled receptors (GPCRs) initiates signal transduction cascades that affect many physiological responses. The worm Caenorhabditis elegans expresses >1000 of these receptors along with their cognate heterotrimeric G proteins. Here, we report properties of 9-cis-retinal regenerated bovine opsin [(b)isoRho] and human melanopsin [(h)Mo], two light-activated, heterologously expressed GPCRs in the nervous system of C. elegans with various genetically engineered alterations. Profound transient photoactivation of Gi/o signaling by (b)isoRho led to a sudden and transient loss of worm motility dependent on cyclic adenosine monophosphate, whereas transient photoactivation of Gq signaling by (h)Mo enhanced worm locomotion dependent on phospholipase Cβ. These transgenic C. elegans models provide a unique way to study the consequences of Gi/o and Gq signaling in vivo with temporal and spatial precision and, by analogy, their relationship to human neuromotor function.—Cao, P., Sun, W., Kramp, K., Zheng, M., Salom, D., Jastrzebska, B., Jin, H., Palczewski, K., Feng, Z. Light-sensitive coupling of rhodopsin and melanopsin to Gi/o and Gq signal transduction in Caenorhabditis elegans. PMID:22090313

  8. Frontal top-down signals increase coupling of auditory low-frequency oscillations to continuous speech in human listeners.

    PubMed

    Park, Hyojin; Ince, Robin A A; Schyns, Philippe G; Thut, Gregor; Gross, Joachim

    2015-06-15

    Humans show a remarkable ability to understand continuous speech even under adverse listening conditions. This ability critically relies on dynamically updated predictions of incoming sensory information, but exactly how top-down predictions improve speech processing is still unclear. Brain oscillations are a likely mechanism for these top-down predictions [1, 2]. Quasi-rhythmic components in speech are known to entrain low-frequency oscillations in auditory areas [3, 4], and this entrainment increases with intelligibility [5]. We hypothesize that top-down signals from frontal brain areas causally modulate the phase of brain oscillations in auditory cortex. We use magnetoencephalography (MEG) to monitor brain oscillations in 22 participants during continuous speech perception. We characterize prominent spectral components of speech-brain coupling in auditory cortex and use causal connectivity analysis (transfer entropy) to identify the top-down signals driving this coupling more strongly during intelligible speech than during unintelligible speech. We report three main findings. First, frontal and motor cortices significantly modulate the phase of speech-coupled low-frequency oscillations in auditory cortex, and this effect depends on intelligibility of speech. Second, top-down signals are significantly stronger for left auditory cortex than for right auditory cortex. Third, speech-auditory cortex coupling is enhanced as a function of stronger top-down signals. Together, our results suggest that low-frequency brain oscillations play a role in implementing predictive top-down control during continuous speech perception and that top-down control is largely directed at left auditory cortex. This suggests a close relationship between (left-lateralized) speech production areas and the implementation of top-down control in continuous speech perception. PMID:26028433

  9. The G protein-coupled receptor kinase-2 is a TGFbeta-inducible antagonist of TGFbeta signal transduction.

    PubMed

    Ho, Joanne; Cocolakis, Eftihia; Dumas, Victor M; Posner, Barry I; Laporte, Stéphane A; Lebrun, Jean-Jacques

    2005-09-21

    Signaling from the activin/transforming growth factor beta (TGFbeta) family of cytokines is a tightly regulated process. Disregulation of TGFbeta signaling is often the underlying basis for various cancers, tumor metastasis, inflammatory and autoimmune diseases. In this study, we identify the protein G-coupled receptor kinase 2 (GRK2), a kinase involved in the desensitization of G protein-coupled receptors (GPCR), as a downstream target and regulator of the TGFbeta-signaling cascade. TGFbeta-induced expression of GRK2 acts in a negative feedback loop to control TGFbeta biological responses. Upon TGFbeta stimulation, GRK2 associates with the receptor-regulated Smads (R-Smads) through their MH1 and MH2 domains and phosphorylates their linker region. GRK2 phosphorylation of the R-Smads inhibits their carboxyl-terminal, activating phosphorylation by the type I receptor kinase, thus preventing nuclear translocation of the Smad complex, leading to the inhibition of TGFbeta-mediated target gene expression, cell growth inhibition and apoptosis. Furthermore, we demonstrate that GRK2 antagonizes TGFbeta-induced target gene expression and apoptosis ex vivo in primary hepatocytes, establishing a new role for GRK2 in modulating single-transmembrane serine/threonine kinase receptor-mediated signal transduction. PMID:16121194

  10. Reaction-based colorimetric signaling of Cu(2+) ions by oxidative coupling of phenols with 4-aminoantipyrine.

    PubMed

    Kim, Hong Yeong; Lee, Hyo Jin; Chang, Suk-Kyu

    2015-01-01

    A new Cu(2+)-selective chromogenic probe system based on the oxidative coupling of phenols with 4-aminoantipyrine was developed. Cu(2+) ions promoted facile coupling of phenols with 4-aminoantipyrine to yield quinoneimine dyes. Signaling with a number of phenols having no para-substituent, such as o-cresol and m-cresol, as well as p-chlorophenol having para substituent that could be expelled during the oxidation process was possible. The signaling of Cu(2+) ions was not interfered by the presence of representative metal ions except for Al(3+) ions. The possible interference from Al(3+) ions was successfully removed by using fluoride ions as a masking agent. The phenol-4-aminoantipyrine probe system showed chromogenic Cu(2+) signaling by prominent color change from colorless to pink with a detection limit of 8.5×10(-7) M. The signaling of Cu(2+) ions in practical samples using tap water and simulated semiconductor wastewater was also tested. PMID:25476354

  11. Infrasound and Seismic Observation of the Hayabusa Reentry: Burst Signals and Air-to-Ground Coupling Process

    NASA Astrophysics Data System (ADS)

    Ishihara, Y.; Hiramatsu, Y.; Yamamoto, M.; Furumoto, M.; Fujita, K.

    2012-12-01

    The Hayabusa, the world's first sample-return minor body explorer, reentered the Earth's atmosphere on June 13, 2010. This was the third direct reentry event from the interplanetary transfer orbit to the Earth at a velocity of over 11.2 km/s, and was the world's first case of a direct reentry of the spacecraft itself from the interplanetary transfer orbit. This was the very good and rare opportunity to study bolide class meteor phenomena by various aspects. Multi-site ground observations of the Hayabusa reentry were carried out in the Woomera Prohibited Area, Australia (Fujita et al., 2011). The observations were configured with optical imaging, spectroscopies, and shockwave detection with infrasound and seismic sensors. At three main stations (GOS2, GOS2A, and GOS2B), we installed small aperture infrasound/seismic arrays, as well as three single component seismic sub stations (GOS2B-sub1, to GOS2B-sub3) (Yamamoto et al., 2011; Ishihara et al., 2012). The infrasound and seismic sensors clearly recorded sonic-boom-type shockwaves from the Hayabusa sample return capsule (Ishihara et al., 2012). In addition, following capsule signal, lots of signals that probably correspond shockwave from disrupted fragments of spacecraft and energetic bursts of the spacecraft were also recorded (Yamamoto et al., 2011). In this study, we analyze signals generated by hypersonic motion of the disrupted fragments and energetic burst of the spacecraft. In addition, we examine the air-to-ground coupling process by comparing the waveforms computed by finite difference scheme with the actual ones. At all three arrayed main stations, after the capsule's shockwave arrival, we detect multiple shockwave signals by both infrasound and seismic sensors. For some of these signals arrive within 10 seconds after capsule's signal, we can identify one to one correspondence with optically tracked disrupted fragments of the spacecraft. Far after the capsule's signal, we also detect some arrivals of wave

  12. G protein-coupled receptor signalling in the cardiac nuclear membrane: evidence and possible roles in physiological and pathophysiological function

    PubMed Central

    Tadevosyan, Artavazd; Vaniotis, George; Allen, Bruce G; Hébert, Terence E; Nattel, Stanley

    2012-01-01

    G protein-coupled receptors (GPCRs) play key physiological roles in numerous tissues, including the heart, and their dysfunction influences a wide range of cardiovascular diseases. Recently, the notion of nuclear localization and action of GPCRs has become more widely accepted. Nuclear-localized receptors may regulate distinct signalling pathways, suggesting that the biological responses mediated by GPCRs are not solely initiated at the cell surface but may result from the integration of extracellular and intracellular signalling pathways. Many of the observed nuclear effects are not prevented by classical inhibitors that exclusively target cell surface receptors, presumably because of their structures, lipophilic properties, or affinity for nuclear receptors. In this topical review, we discuss specifically how angiotensin-II, endothelin, β-adrenergic and opioid receptors located on the nuclear envelope activate signalling pathways, which convert intracrine stimuli into acute responses such as generation of second messengers and direct genomic effects, and thereby participate in the development of cardiovascular disorders. PMID:22183719

  13. Low-energy signals of strongly-coupled electroweak symmetry-breaking scenarios

    NASA Astrophysics Data System (ADS)

    Pich, Antonio; Rosell, Ignasi; Santos, Joaquín; Sanz-Cillero, Juan José

    2016-03-01

    The nonobservation of new particles at the LHC suggests the existence of a mass gap above the electroweak scale. This situation is adequately described through a general electroweak effective theory with the established fields and Standard Model symmetries. Its couplings contain all information about the unknown short-distance dynamics which is accessible at low energies. We consider a generic strongly coupled scenario of electroweak symmetry breaking, with heavy states above the gap, and analyze the imprints that its lightest bosonic excitations leave on the effective Lagrangian couplings. Different quantum numbers of the heavy states imply different patterns of low-energy couplings, with characteristic correlations which could be identified in future data samples. The predictions can be sharpened with mild assumptions about the ultraviolet behaviour of the underlying fundamental theory.

  14. Toward multivalent signaling across G protein-coupled receptors from poly(amidoamine) dendrimers.

    PubMed

    Kim, Yoonkyung; Hechler, Béatrice; Klutz, Athena M; Gachet, Christian; Jacobson, Kenneth A

    2008-02-01

    Activation of the A2A receptor, a G protein-coupled receptor (GPCR), by extracellular adenosine, is antiaggregatory in platelets and anti-inflammatory. Multiple copies of an A2A agonist, the nucleoside CGS21680, were coupled covalently to PAMAM dendrimers and characterized spectroscopically. A fluorescent PAMAM-CGS21680 conjugate 5 inhibited aggregation of washed human platelets and was internalized. We envision that our multivalent dendrimer conjugates may improve overall pharmacological profiles compared to the monovalent GPCR ligands. PMID:18176997

  15. Endocytosis of Seven-Transmembrane RGS Protein Activates G- protein Coupled Signaling in Arabidopsis

    PubMed Central

    Urano, Daisuke; Phan, Nguyen; Jones, Janice C.; Yang, Jing; Huang, Jirong; Grigston, Jeffrey; Taylor, J. Philip; Jones, Alan M.

    2012-01-01

    Signal transduction typically begins by ligand-dependent activation of a concomitant partner which is otherwise in its resting state. However, in cases where signal activation is constitutive by default, the mechanism of regulation is unknown. The Arabidopsis thaliana heterotrimeric Gα protein self-activates without accessory proteins, and is kept in its resting state by the negative regulator, AtRGS1 (Regulator of G protein Signaling 1), which is the prototype of a seven transmembrane receptor fused with an RGS domain. Endocytosis of AtRGS1 by ligand-dependent endocytosis physically uncouples the GTPase accelerating activity of AtRGS1 from the Gα protein, permitting sustained activation. Phosphorylation of AtRGS1 by AtWNK8 kinase causes AtRGS1 endocytosis, required both for G protein-mediated sugar signaling and cell proliferation. In animals, receptor endocytosis results in signal desensitization, whereas in plants, endocytosis results in signal activation. These findings reveal how different organisms rearrange a regulatory system to result in opposite outcomes using similar phosphorylation-dependent endocytosis. PMID:22940907

  16. Semi-real-time monitoring of cracking on couplings by neural network analysis of acoustic emission signals

    NASA Astrophysics Data System (ADS)

    Godinez-Azcuaga, Valery F.; Shu, Fong; Finlayson, Richard D.; O'Donnell, Bruce W.

    2004-07-01

    This paper presents the results obtained during the development of a semi-real-time monitoring methodology based on Neural Network Pattern Recognition of Acoustic Emission (AE) signals for early detection of cracks in couplings used in aircraft and engine drive systems. AE signals were collected in order to establish a baseline of a gear-testing fixture background noise and its variations due to rotational speed and torque. Also, simulated cracking signals immersed in background noise were collected. EDM notches were machined in the driving gear and the load on the gearbox was increased until damaged was induced. Using these data, a Neural Network Signal Classifier (NNSC) was implemented and tested. The testing showed that the NNSC was capable of correctly identifying six different classes of AE signals corresponding to different gearbox operation conditions. Also, a semi-real-time classification software was implemented. This software includes functions that allow the user to view and classify AE data from a dynamic process as they are recorded at programmable time intervals. The software is capable of monitoring periodic statistics of AE data, which can be used as an indicator of damage presence and severity in a dynamic system. The semi-real-time classification software was successfully tested in situations where a delay of 10 seconds between data acquisition and classification was achieved with a hit rate of 50 hits/second per channel on eight active AE channels.

  17. Signal photon flux and background noise in a coupling electromagnetic detecting system for high-frequency gravitational waves

    NASA Astrophysics Data System (ADS)

    Li, Fangyu; Yang, Nan; Fang, Zhenyun; Baker, Robert M. L., Jr.; Stephenson, Gary V.; Wen, Hao

    2009-09-01

    A coupling system among Gaussian-type microwave photon flux, a static magnetic field, and fractal membranes (or other equivalent microwave lenses) can be used to detect high-frequency gravitational waves (HFGWs) in the microwave band. We study the signal photon flux, background photon flux, and the requisite minimal accumulation time of the signal in the coupling system. Unlike the pure inverse Gertsenshtein effect (G effect) caused by the HFGWs in the gigahertz band, the electromagnetic (EM) detecting scheme proposed by China and the U.S. HFGW groups is based on the composite effect of the synchroresonance effect and the inverse G effect. The key parameter in the scheme is the first-order perturbative photon flux (PPF) and not the second-order PPF; the distinguishable signal is the transverse first-order PPF and not the longitudinal PPF; the photon flux focused by the fractal membranes or other equivalent microwave lenses is not only the transverse first-order PPF but the total transverse photon flux, and these photon fluxes have different signal-to-noise ratios at the different receiving surfaces. Theoretical analysis and numerical estimation show that the requisite minimal accumulation time of the signal at the special receiving surfaces and in the background noise fluctuation would be ˜103-105 seconds for the typical laboratory condition and parameters of hrms˜10-26-10-30/Hz at 5 GHz with bandwidth ˜1Hz. In addition, we review the inverse G effect in the EM detection of the HFGWs, and it is shown that the EM detecting scheme based only on the pure inverse G effect in the laboratory condition would not be useful to detect HFGWs in the microwave band.

  18. The Novel Functions of the PLC/PKC/PKD Signaling Axis in G Protein-Coupled Receptor-Mediated Chemotaxis of Neutrophils

    PubMed Central

    Xu, Xuehua; Jin, Tian

    2015-01-01

    Chemotaxis, a directional cell migration guided by extracellular chemoattractant gradients, plays an essential role in the recruitment of neutrophils to sites of inflammation. Chemotaxis is mediated by the G protein-coupled receptor (GPCR) signaling pathway. Extracellular stimuli trigger activation of the PLC/PKC/PKD signaling axis, which controls several signaling pathways. Here, we concentrate on the novel functions of PLC/PKC/PKD signaling in GPCR-mediated chemotaxis of neutrophils. PMID:26605346

  19. Osteoclast TGF-β Receptor Signaling Induces Wnt1 Secretion and Couples Bone Resorption to Bone Formation

    PubMed Central

    Weivoda, Megan M; Ruan, Ming; Pederson, Larry; Hachfeld, Christine; Davey, Rachel A; Zajac, Jeffrey D; Westendorf, Jennifer J; Khosla, Sundeep; Oursler, Merry Jo

    2016-01-01

    Osteoblast-mediated bone formation is coupled to osteoclast-mediated bone resorption. These processes become uncoupled with age, leading to increased risk for debilitating fractures. Therefore, understanding how osteoblasts are recruited to sites of resorption is vital to treating age-related bone loss. Osteoclasts release and activate TGF-β from the bone matrix. Here we show that osteoclastspecific inhibition of TGF-β receptor signaling in mice results in osteopenia due to reduced osteoblast numbers with no significant impact on osteoclast numbers or activity. TGF-β induced osteoclast expression of Wnt1, a protein crucial to normal bone formation, and this response was blocked by impaired TGF-β receptor signaling. Osteoclasts in aged murine bones had lower TGF-β signaling and Wnt1 expression in vivo. Ex vivo stimulation of osteoclasts derived from young or old mouse bone marrow macrophages showed no difference in TGF-β–induced Wnt1 expression. However, young osteoclasts expressed reduced Wnt1 when cultured on aged mouse bone chips compared to young mouse bone chips, consistent with decreased skeletal TGF-β availability with age. Therefore, osteoclast responses to TGF-β are essential for coupling bone resorption to bone formation, and modulating this pathway may provide opportunities to treat age-related bone loss. PMID:26108893

  20. Phosphoinositides in Ca(2+) signaling and excitation-contraction coupling in skeletal muscle: an old player and newcomers.

    PubMed

    Csernoch, Laszlo; Jacquemond, Vincent

    2015-12-01

    Since the postulate, 30 years ago, that phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P 2) as the precursor of inositol 1,4,5-trisphosphate (Ins(1,4,5)P 3) would be critical for skeletal muscle excitation-contraction (EC) coupling, the issue of whether phosphoinositides (PtdInsPs) may have something to do with Ca(2+) signaling in muscle raised limited interest, if any. In recent years however, the PtdInsP world has expanded considerably with new functions for PtdIns(4,5)P 2 but also with functions for the other members of the PtdInsP family. In this context, the discovery that genetic deficiency in a PtdInsP phosphatase has dramatic consequences on Ca(2+) homeostasis in skeletal muscle came unanticipated and opened up new perspectives in regards to how PtdInsPs modulate muscle Ca(2+) signaling under normal and disease conditions. This review intends to make an update of the established, the questioned, and the unknown regarding the role of PtdInsPs in skeletal muscle Ca(2+) homeostasis and EC coupling, with very specific emphasis given to Ca(2+) signals in differentiated skeletal muscle fibers. PMID:26377756

  1. Design of a dc SQUID Phase Qubit with Controlled Coupling to the Microwave Signal

    NASA Astrophysics Data System (ADS)

    Budoyo, R. P.; Przybysz, A. J.; Cooper, B. K.; Kwon, H.; Kim, Z.; Cheng, B.; Dragt, A. J.; Anderson, J. R.; Lobb, C. J.; Wellstood, F. C.; Khalil, M.; Gladchenko, S.; Stoutimore, M.; Palmer, B. S.; Osborn, K. D.

    2011-03-01

    We have designed an Al/ Al Ox /Al dc SQUID phase qubit on a sapphire substrate with a qubit junction area of 0.3 μ m 2 to minimize loss associated with two-level systems in the junction oxide barrier. The qubit junction is shunted with a 1.5 pF interdigitated capacitor, and is isolated from the bias leads by an LC filter and an inductive isolation network using a larger Josephson junction. A previous device we built with similar parameters had its relaxation time T1 limited by coupling to the microwave line. To reduce this coupling, we adopted a transmission line design and verified the coupling strength using microwave simulations. The new design will also allow us to measure the coupling to the SQUID by throughput measurements. We will discuss our design, the microwave simulations, our estimates for the overall coherence time due to losses and noise from various sources, and our progress towards testing the device. Acknowledgement: DOD, JQI, and CNAM.

  2. A Probe of Magnetosphere-Ionosphere Coupling using the Propagation Characteristics of Very Low Frequency Signal

    NASA Astrophysics Data System (ADS)

    Nwankwo, V. U. J.; Chakrabarti, S. K.; Ogunmodimu, O. A.

    2015-12-01

    The amplitude and phase of VLF/LF radio signal are sensitive to changes in the electrical conductivity of the lower ionosphere when propagated in the Earth-ionosphere waveguide. This unique characteristic makes it useful in studying sudden ionospheric disturbances and/or anomaly especially those related to prompt X-ray flux output from solar flares and gamma ray bursts (GRBs). However, strong geomagnetic disturbances and/or storm conditions are known to produce large and global ionospheric disturbances, which can significantly affect VLF radio propagation in the D region ionosphere. Other than X-ray flux enhancement of amplitude and phase, diurnal VLF signature may convey other important information especially those related to geomagnetic disturbance/storm induced ionospheric changes. In this paper, using the data of three propagation paths (at latitudes 40-54), we performed detail analysis of the trend of variations of aspects VLF diurnal signal under varying solar and/or geomagnetic space environmental conditions for identification of possible geomagnetic footprint on the ionosphere. We found that trend of variations significantly reflected the prevailing space weather conditions of various time scales. The `dipping' of the signal diurnal amplitude have shown noteworthy consistency with significantly geomagnetic perturbed and/or storm conditions in the time scale of 1-2 days. We also found that dipping of most MDP signal occurred irrespective of the time (of the day), which an event happened, while those of MBSR, MASS, SRT and SST appear to largely depend on event occurrence time and/or duration. Pre-sunset event had more influence on the SST and MASS (dusk signal), while pre-sunrise event had more influence on the SRT and MBSR (dawn signal), and depending on the duration of the event, impact could be extended to the neighbouring point/component in succession. The induced dipping varied with geomagnetic activity/event intensity and/or duration, as well as the

  3. G-protein Coupled Receptor Signaling in Pluripotent Stem Cell-derived Cardiovascular Cells: Implications for Disease Modeling

    PubMed Central

    Dolatshad, Nazanin F.; Hellen, Nicola; Jabbour, Richard J.; Harding, Sian E.; Földes, Gabor

    2015-01-01

    Human pluripotent stem cell derivatives show promise as an in vitro platform to study a range of human cardiovascular diseases. A better understanding of the biology of stem cells and their cardiovascular derivatives will help to understand the strengths and limitations of this new model system. G-protein coupled receptors (GPCRs) are key regulators of stem cell maintenance and differentiation and have an important role in cardiovascular cell signaling. In this review, we will therefore describe the state of knowledge concerning the regulatory role of GPCRs in both the generation and function of pluripotent stem cell derived-cardiomyocytes, -endothelial, and -vascular smooth muscle cells. We will consider how far the in vitro disease models recapitulate authentic GPCR signaling and provide a useful basis for discovery of disease mechanisms or design of therapeutic strategies. PMID:26697426

  4. G Protein-Coupled Receptor Trafficking and Signalling in the Enteric Nervous System: The Past, Present and Future.

    PubMed

    Poole, Daniel P; Bunnett, Nigel W

    2016-01-01

    G protein-coupled receptors (GPCRs) enable cells to detect and respond to changes in their extracellular environment. With over 800 members, the GPCR family includes receptors for a diverse range of agonists including olfactants, neurotransmitters and hormones. Importantly, GPCRs represent a major therapeutic target, with approximately 50 % of all current drugs acting at some aspect of GPCR signalling (Audet and Bouvier 2008). GPCRs are widely expressed by all cell types in the gastrointestinal (GI) tract and are major regulators of every aspect of gut function. Many GPCRs are internalised upon activation, and this represents one of the mechanisms through which G protein-signalling is terminated. The latency between the endocytosis of GPCRs and their recycling and resensitization is a major determinant of the cell's ability to respond to subsequent exposure to agonists. PMID:27379642

  5. Self-repair in a bidirectionally coupled astrocyte-neuron (AN) system based on retrograde signaling

    PubMed Central

    Wade, John; McDaid, Liam; Harkin, Jim; Crunelli, Vincenzo; Kelso, Scott

    2012-01-01

    In this paper we demonstrate that retrograde signaling via astrocytes may underpin self-repair in the brain. Faults manifest themselves in silent or near silent neurons caused by low transmission probability (PR) synapses; the enhancement of the transmission PR of a healthy neighboring synapse by retrograde signaling can enhance the transmission PR of the “faulty” synapse (repair). Our model of self-repair is based on recent research showing that retrograde signaling via astrocytes can increase the PR of neurotransmitter release at damaged or low transmission PR synapses. The model demonstrates that astrocytes are capable of bidirectional communication with neurons which leads to modulation of synaptic activity, and that indirect signaling through retrograde messengers such as endocannabinoids leads to modulation of synaptic transmission PR. Although our model operates at the level of cells, it provides a new research direction on brain-like self-repair which can be extended to networks of astrocytes and neurons. It also provides a biologically inspired basis for developing highly adaptive, distributed computing systems that can, at fine levels of granularity, fault detect, diagnose and self-repair autonomously, without the traditional constraint of a central fault detect/repair unit. PMID:23055965

  6. Metabotropic NMDA receptor signaling couples Src family kinases to pannexin-1 during excitotoxicity.

    PubMed

    Weilinger, Nicholas L; Lohman, Alexander W; Rakai, Brooke D; Ma, Evelyn M M; Bialecki, Jennifer; Maslieieva, Valentyna; Rilea, Travis; Bandet, Mischa V; Ikuta, Nathan T; Scott, Lucas; Colicos, Michael A; Teskey, G Campbell; Winship, Ian R; Thompson, Roger J

    2016-03-01

    Overactivation of neuronal N-methyl-D-aspartate receptors (NMDARs) causes excitotoxicity and is necessary for neuronal death. In the classical view, these ligand-gated Ca(2+)-permeable ionotropic receptors require co-agonists and membrane depolarization for activation. We report that NMDARs signal during ligand binding without activation of their ion conduction pore. Pharmacological pore block with MK-801, physiological pore block with Mg(2+) or a Ca(2+)-impermeable NMDAR variant prevented NMDAR currents, but did not block excitotoxic dendritic blebbing and secondary currents induced by exogenous NMDA. NMDARs, Src kinase and Panx1 form a signaling complex, and activation of Panx1 required phosphorylation at Y308. Disruption of this NMDAR-Src-Panx1 signaling complex in vitro or in vivo by administration of an interfering peptide either before or 2 h after ischemia or stroke was neuroprotective. Our observations provide insights into a new signaling modality of NMDARs that has broad-reaching implications for brain physiology and pathology. PMID:26854804

  7. Functional MRI during hyperbaric oxygen: Effects of oxygen on neurovascular coupling and BOLD fMRI signals.

    PubMed

    Cardenas, Damon P; Muir, Eric R; Huang, Shiliang; Boley, Angela; Lodge, Daniel; Duong, Timothy Q

    2015-10-01

    Hyperbaric oxygen (HBO) therapy is used to treat a number of ailments. Improved understanding of how HBO affects neuronal activity, cerebral blood flow (CBF) and blood-oxygenation-level dependent (BOLD) changes could shed light on the role of oxygen in neurovascular coupling and help guide HBO treatments. The goal of this study was to test two hypotheses: i) activation-induced CBF fMRI response is not dependent on hemoglobin deoxygenation, and ii) activation-induced BOLD fMRI is markedly attenuated under HBO. CBF and BOLD fMRI of forepaw stimulation in anesthetized rats under HBO at 3 atmospheres absolute (ATA) were compared with normobaric air. Robust BOLD and CBF fMRI were detected under HBO. Inflow effects and spin-density changes did not contribute significantly to the BOLD fMRI signal under HBO. Analysis of the T2(⁎)-weighted signal at normobaric air and 1, 2 and 3ATA oxygen in the tissue and the superior sagittal sinus showed a strong dependence on increasing inhaled [O2]. Spontaneous electrophysiological activity and evoked local-field potentials were reduced under HBO. The differences between normobaric air and HBO in basal and evoked electrical activity could not fully account for the strong BOLD responses under HBO. We concluded that activation-induced CBF regulation in the brain does not operate through an oxygen-sensing mechanism and that stimulus-evoked BOLD responses and the venous T2(⁎)-weighted signals still have room to increase under 3ATA HBO. To our knowledge, this is the first fMRI study under HBO, providing insights into the effects of HBO on neural activity, neurovascular coupling, tissue oxygenation, and the BOLD signal. PMID:26143203

  8. Chapter Three - Ubiquitination and Protein Turnover of G-Protein-Coupled Receptor Kinases in GPCR Signaling and Cellular Regulation.

    PubMed

    Penela, P

    2016-01-01

    G-protein-coupled receptors (GPCRs) are responsible for regulating a wide variety of physiological processes, and distinct mechanisms for GPCR inactivation exist to guarantee correct receptor functionality. One of the widely used mechanisms is receptor phosphorylation by specific G-protein-coupled receptor kinases (GRKs), leading to uncoupling from G proteins (desensitization) and receptor internalization. GRKs and β-arrestins also participate in the assembly of receptor-associated multimolecular complexes, thus initiating alternative G-protein-independent signaling events. In addition, the abundant GRK2 kinase has diverse "effector" functions in cellular migration, proliferation, and metabolism homeostasis by means of the phosphorylation or interaction with non-GPCR partners. Altered expression of GRKs (particularly of GRK2 and GRK5) occurs during pathological conditions characterized by impaired GPCR signaling including inflammatory syndromes, cardiovascular disease, and tumor contexts. It is increasingly appreciated that different pathways governing GRK protein stability play a role in the modulation of kinase levels in normal and pathological conditions. Thus, enhanced GRK2 degradation by the proteasome pathway occurs upon GPCR stimulation, what allows cellular adaptation to chronic stimulation in a physiological setting. β-arrestins participate in this process by facilitating GRK2 phosphorylation by different kinases and by recruiting diverse E3 ubiquitin ligase to the receptor complex. Different proteolytic systems (ubiquitin-proteasome, calpains), chaperone activities and signaling pathways influence the stability of GRKs in different ways, thus endowing specificity to GPCR regulation as protein turnover of GRKs can be differentially affected. Therefore, modulation of protein stability of GRKs emerges as a versatile mechanism for feedback regulation of GPCR signaling and basic cellular processes. PMID:27378756

  9. Mapping physiological G protein-coupled receptor signaling pathways reveals a role for receptor phosphorylation in airway contraction

    PubMed Central

    Bradley, Sophie J.; Iglesias, Max Maza; Kong, Kok Choi; Butcher, Adrian J.; Plouffe, Bianca; Goupil, Eugénie; Bourgognon, Julie-Myrtille; Macedo-Hatch, Timothy; LeGouill, Christian; Russell, Kirsty; Laporte, Stéphane A.; König, Gabriele M.; Kostenis, Evi; Bouvier, Michel; Chung, Kian Fan; Amrani, Yassine; Tobin, Andrew B.

    2016-01-01

    G protein-coupled receptors (GPCRs) are known to initiate a plethora of signaling pathways in vitro. However, it is unclear which of these pathways are engaged to mediate physiological responses. Here, we examine the distinct roles of Gq/11-dependent signaling and receptor phosphorylation-dependent signaling in bronchial airway contraction and lung function regulated through the M3-muscarinic acetylcholine receptor (M3-mAChR). By using a genetically engineered mouse expressing a G protein-biased M3-mAChR mutant, we reveal the first evidence, to our knowledge, of a role for M3-mAChR phosphorylation in bronchial smooth muscle contraction in health and in a disease state with relevance to human asthma. Furthermore, this mouse model can be used to distinguish the physiological responses that are regulated by M3-mAChR phosphorylation (which include control of lung function) from those responses that are downstream of G protein signaling. In this way, we present an approach by which to predict the physiological/therapeutic outcome of M3-mAChR–biased ligands with important implications for drug discovery. PMID:27071102

  10. Coupled Sensing of Hunger and Thirst Signals Balances Sugar and Water Consumption.

    PubMed

    Jourjine, Nicholas; Mullaney, Brendan C; Mann, Kevin; Scott, Kristin

    2016-08-11

    Hunger and thirst are ancient homeostatic drives for food and water consumption. Although molecular and neural mechanisms underlying these drives are currently being uncovered, less is known about how hunger and thirst interact. Here, we use molecular genetic, behavioral, and anatomical studies in Drosophila to identify four neurons that modulate food and water consumption. Activation of these neurons promotes sugar consumption and restricts water consumption, whereas inactivation promotes water consumption and restricts sugar consumption. By calcium imaging studies, we show that these neurons are directly regulated by a hormone signal of nutrient levels and by osmolality. Finally, we identify a hormone receptor and an osmolality-sensitive ion channel that underlie this regulation. Thus, a small population of neurons senses internal signals of nutrient and water availability to balance sugar and water consumption. Our results suggest an elegant mechanism by which interoceptive neurons oppositely regulate homeostatic drives to eat and drink. PMID:27477513

  11. ERK signaling couples nutrient status to antiviral defense in the insect gut.

    PubMed

    Xu, Jie; Hopkins, Kaycie; Sabin, Leah; Yasunaga, Ari; Subramanian, Harry; Lamborn, Ian; Gordesky-Gold, Beth; Cherry, Sara

    2013-09-10

    A unique facet of arthropod-borne virus (arbovirus) infection is that the pathogens are orally acquired by an insect vector during the taking of a blood meal, which directly links nutrient acquisition and pathogen challenge. We show that the nutrient responsive ERK pathway is both induced by and restricts disparate arboviruses in Drosophila intestines, providing insight into the molecular determinants of the antiviral "midgut barrier." Wild-type flies are refractory to oral infection by arboviruses, including Sindbis virus and vesicular stomatitis virus, but this innate restriction can be overcome chemically by oral administration of an ERK pathway inhibitor or genetically via the specific loss of ERK in Drosophila intestinal epithelial cells. In addition, we found that vertebrate insulin, which activates ERK in the mosquito gut during a blood meal, restricts viral infection in Drosophila cells and against viral invasion of the insect gut epithelium. We find that ERK's antiviral signaling activity is likely conserved in Aedes mosquitoes, because genetic or pharmacologic manipulation of the ERK pathway affects viral infection of mosquito cells. These studies demonstrate that ERK signaling has a broadly antiviral role in insects and suggest that insects take advantage of cross-species signals in the meal to trigger antiviral immunity. PMID:23980175

  12. ERK signaling couples nutrient status to antiviral defense in the insect gut

    PubMed Central

    Xu, Jie; Hopkins, Kaycie; Sabin, Leah; Yasunaga, Ari; Subramanian, Harry; Lamborn, Ian; Gordesky-Gold, Beth; Cherry, Sara

    2013-01-01

    A unique facet of arthropod-borne virus (arbovirus) infection is that the pathogens are orally acquired by an insect vector during the taking of a blood meal, which directly links nutrient acquisition and pathogen challenge. We show that the nutrient responsive ERK pathway is both induced by and restricts disparate arboviruses in Drosophila intestines, providing insight into the molecular determinants of the antiviral “midgut barrier.” Wild-type flies are refractory to oral infection by arboviruses, including Sindbis virus and vesicular stomatitis virus, but this innate restriction can be overcome chemically by oral administration of an ERK pathway inhibitor or genetically via the specific loss of ERK in Drosophila intestinal epithelial cells. In addition, we found that vertebrate insulin, which activates ERK in the mosquito gut during a blood meal, restricts viral infection in Drosophila cells and against viral invasion of the insect gut epithelium. We find that ERK’s antiviral signaling activity is likely conserved in Aedes mosquitoes, because genetic or pharmacologic manipulation of the ERK pathway affects viral infection of mosquito cells. These studies demonstrate that ERK signaling has a broadly antiviral role in insects and suggest that insects take advantage of cross-species signals in the meal to trigger antiviral immunity. PMID:23980175

  13. Stimulation of Ca²+ signals in neurons by electrically coupled electrolyte-oxide-semiconductor capacitors.

    PubMed

    Giacomello, M; Girardi, S; Scorzeto, M; Peruffo, A; Maschietto, M; Cozzi, B; Vassanelli, S

    2011-05-15

    Electrolyte-oxide-semiconductor capacitors (EOSCs) are a class of microtransducers for extracellular electrical stimulation that have been successfully employed to activate voltage-dependent sodium channels at the neuronal soma to generate action potentials in vitro. In the present work, we report on their use to control Ca²+ signalling in cultured mammalian cells, including neurons. Evidence is provided that EOSC stimulation with voltage waveforms in the microsecond or nanosecond range activates two distinct Ca²+ pathways, either by triggering Ca²+ entry through the plasma membrane or its release from intracellular stores. Ca²+ signals were activated in non-neuronal and neuronal cell lines, CHO-K1 and SH-SY5Y. On this basis, stimulation was tailored to rat and bovine neurons to mimic physiological somatic Ca²+ transients evoked by glutamate. Being minimally invasive and easy to use, the new method represents a versatile complement to standard electrophysiology and imaging techniques for the investigation of Ca²+ signalling in dissociated primary neurons and cell lines. PMID:21345350

  14. Synchrony due to parametric averaging in neurons coupled by a shared signal

    NASA Astrophysics Data System (ADS)

    Khadra, Anmar

    2009-04-01

    Gonadotropin-releasing hormone (GnRH) is a decapeptide secreted by GnRH neurons located in the hypothalamus. It is responsible for the onset of puberty and the regulation of hormone release from the pituitary. There is a strong evidence suggesting that GnRH exerts an autocrine regulation on its own release via three types of G-proteins [L.Z. Krsmanovic, N. Mores, C.E. Navarro, K.K. Arora, K.J. Catt, An agonist-induced switch in G protein coupling of the gonadotropin-releasing hormone receptor regulates pulsatile neuropeptide secretion, Proc. Natl. Acad. Sci. 100 (2003) 2969-2974]. A mathematical model based on this proposed mechanism has been developed and extended to explain the synchrony observed in GnRH neurons by incorporating the idea of a common pool of GnRH [A. Khadra, Y.X. Li, A model for the pulsatile secretion of gonadotropin-releasing hormone from synchronized hypothalamic neurons, Biophys. J. 91 (2006) 74-83]. This type of coupling led to a very robust synchrony between these neurons. We aim in this paper to reduce the one cell model to a two-variable model using quasi-steady state (QSS) analysis, to further examine its dynamics analytically and geometrically. The concept of synchrony of a heterogeneous population will be clearly defined and established for certain cases, while, for the general case, two different types of phases are introduced to gain more insight on how the model behaves. Bifurcation diagrams for certain parameters in the one cell model are also shown to explain some of the phenomena observed in a coupled population. A comparison between the population model and an averaged two-variable model is also conducted.

  15. Malformed mdx myofibers have normal cytoskeletal architecture yet altered EC coupling and stress-induced Ca2+ signaling

    PubMed Central

    Ward, Christopher W.

    2009-01-01

    Skeletal muscle function is dependent on its highly regular structure. In studies of dystrophic (dy/dy) mice, the proportion of malformed myofibers decreases after prolonged whole muscle stimulation, suggesting that the malformed myofibers are more prone to injury. The aim of this study was to assess morphology and to measure excitation-contraction (EC) coupling (Ca2+ transients) and susceptibility to osmotic stress (Ca2+ sparks) of enzymatically isolated muscle fibers of the extensor digitorum longus (EDL) and flexor digitorum brevis (FDB) muscles from young (2–3 mo) and old (8–9 mo) mdx and age-matched control mice (C57BL10). In young mdx EDL, 6% of the myofibers had visible malformations (i.e., interfiber splitting, branched ends, midfiber appendages). In contrast, 65% of myofibers in old mdx EDL contained visible malformations. In the mdx FDB, malformation occurred in only 5% of young myofibers and 11% of old myofibers. Age-matched control mice did not display the altered morphology of mdx muscles. The membrane-associated and cytoplasmic cytoskeletal structures appeared normal in the malformed mdx myofibers. In mdx FDBs with significantly branched ends, an assessment of global, electrically evoked Ca2+ signals (indo-1PE-AM) revealed an EC coupling deficit in myofibers with significant branching. Interestingly, peak amplitude of electrically evoked Ca2+ release in the branch of the bifurcated mdx myofiber was significantly decreased compared with the trunk of the same myofiber. No alteration in the basal myoplasmic Ca2+ concentration (i.e., indo ratio) was seen in malformed vs. normal mdx myofibers. Finally, osmotic stress induced the occurrence of Ca2+ sparks to a greater extent in the malformed portions of myofibers, which is consistent with deficits in EC coupling control. In summary, our data show that aging mdx myofibers develop morphological malformations. These malformations are not associated with gross disruptions in cytoskeletal or t

  16. Shc adaptor proteins are key transducers of mitogenic signaling mediated by the G protein-coupled thrombin receptor.

    PubMed Central

    Chen, Y; Grall, D; Salcini, A E; Pelicci, P G; Pouysségur, J; Van Obberghen-Schilling, E

    1996-01-01

    The serine protease thrombin activates G protein signaling systems that lead to Ras activation and, in certain cells, proliferation. Whereas the steps leading to Ras activation by G protein-coupled receptors are not well defined, the mechanisms of Ras activation by receptor tyrosine kinases have recently been elucidated biochemically and genetically. The present study was undertaken to determine whether common signaling components are used by these two distinct classes of receptors. Here we report that the adaptor protein Shc, is phosphorylated on tyrosine residues following stimulation of the thrombin receptor in growth-responsive CCL39 fibroblasts. Shc phosphorylation by thrombin or the thrombin receptor agonist peptide is maximal by 15 min and persists for > or = 2 h. Following thrombin stimulation, phosphorylated Shc is recruited to Grb2 complexes. One or more pertussis toxin-insensitive proteins appear to mediate this effect, since (i) pertussis toxin pre-treatment of cells does not blunt the action of thrombin and (ii) Shc phosphorylation on tyrosine can be stimulated by the muscarinic m1 receptor. Shc phosphorylation does not appear to involve protein kinase C, since the addition of 4-beta-phorbol-12,13-dibutyrate has no effect. Rather, thrombin-induced Shc phosphorylation is enhanced in cells depleted of phorbol ester-sensitive protein kinase C isoforms. Expression of mutant Shc proteins defective in Grb2 binding displays a dominant-negative effect on thrombin-stimulated p44 MAP kinase activation, gene induction and cell growth. From these data, we conclude that Shc represents a crucial point of convergence between signaling pathways activated by receptor tyrosine kinases and G protein-coupled receptors. Images PMID:8605873

  17. A Perspective on Studying G-Protein-Coupled Receptor Signaling with Resonance Energy Transfer Biosensors in Living Organisms.

    PubMed

    van Unen, Jakobus; Woolard, Jeanette; Rinken, Ago; Hoffmann, Carsten; Hill, Stephen J; Goedhart, Joachim; Bruchas, Michael R; Bouvier, Michel; Adjobo-Hermans, Merel J W

    2015-09-01

    The last frontier for a complete understanding of G-protein-coupled receptor (GPCR) biology is to be able to assess GPCR activity, interactions, and signaling in vivo, in real time within biologically intact systems. This includes the ability to detect GPCR activity, trafficking, dimerization, protein-protein interactions, second messenger production, and downstream signaling events with high spatial resolution and fast kinetic readouts. Resonance energy transfer (RET)-based biosensors allow for all of these possibilities in vitro and in cell-based assays, but moving RET into intact animals has proven difficult. Here, we provide perspectives on the optimization of biosensor design, of signal detection in living organisms, and the multidisciplinary development of in vitro and cell-based assays that more appropriately reflect the physiologic situation. In short, further development of RET-based probes, optical microscopy techniques, and mouse genome editing hold great potential over the next decade to bring real-time in vivo GPCR imaging to the forefront of pharmacology. PMID:25972446

  18. Diagnostic study of coupled solar wind-magnetosphere-ionosphere dynamics in D-region ionosphere via VLF signal propagation characteristic

    NASA Astrophysics Data System (ADS)

    Nwankwo, Victor U. J.; Chakrabarti, Sandip Kumar

    2016-07-01

    Geomagnetic disturbances and storms are known to produce significant global disturbances in the ionosphere, including the middle atmosphere and troposphere. There is little understanding about the mechanism and dynamics that drive these processes in lower ionosphere. The ionosphere is also thought to be sensitive to seismic events, and it is believed that it exhibits precursory characteristics as reported in studies via characteristic anomalies in VLF signal. However, distinguishing or separating seismically induced ionospheric fluctuations from those of other origins (e.g., Solar activity, planetary and tidal waves, stratospheric warming etc.) remain vital to robust conclusion, and challenging too. The unique propagation characteristic of VLF radio signal makes it an ideal tool for the study and diagnosis of variability of D-region ionosphere. In this work, we present the analysis of solar wind-magnetosphere-ionosphere coupling dynamics in D-region ionosphere using VLF signal characteristics, and performed an investigation of previously reported 'ionospheric precursors' to understand the true origins of measured anomalies.

  19. G Protein-Coupled Receptor Signaling and Sphingosine-1-Phosphate Play a Phylogenetically Conserved Role in Endocrine Pancreas Morphogenesis ▿

    PubMed Central

    Serafimidis, Ioannis; Heximer, Scott; Beis, Dimitris; Gavalas, Anthony

    2011-01-01

    During development pancreatic endocrine cells migrate in a coordinated fashion. This migration is necessary to form fully functional islets, but the mechanisms involved remain unknown. Therapeutic strategies to restore β-cell mass and islet functionality by reprogramming endogenous exocrine cells would be strengthened from simultaneous treatments that enhance endocrine cell clustering. We found that endocrine progenitors respond to and regulate G protein-coupled receptor (GPCR) signaling in order to cluster in islets. Rgs4, a dedicated regulator of GPCR signaling, was specifically expressed in early epithelial endocrine progenitors of both zebrafish and mouse, and its expression in the mouse endocrine progenitors was strictly dependent upon Ngn3, the key specification gene of the endocrine lineage. Rgs4 loss of function resulted in defects in islet cell aggregation. By genetically inactivating Gαi-mediated GPCR signaling in endocrine progenitors, we established its role in islet cell aggregation in both mouse and zebrafish. Finally, we identified sphingosine-1-phosphate (S1P) as a ligand mediating islet cell aggregation in both species acting through distinct but closely related receptors. PMID:21911471

  20. Single cell kinase signaling assay using pinched flow coupled droplet microfluidics

    PubMed Central

    Ramji, Ramesh; Wang, Ming; Bhagat, Ali Asgar S.; Tan Shao Weng, Daniel; Thakor, Nitish V.; Teck Lim, Chwee; Chen, Chia-Hung

    2014-01-01

    Droplet-based microfluidics has shown potential in high throughput single cell assays by encapsulating individual cells in water-in-oil emulsions. Ordering cells in a micro-channel is necessary to encapsulate individual cells into droplets further enhancing the assay efficiency. This is typically limited due to the difficulty of preparing high-density cell solutions and maintaining them without cell aggregation in long channels (>5 cm). In this study, we developed a short pinched flow channel (5 mm) to separate cell aggregates and to form a uniform cell distribution in a droplet-generating platform that encapsulated single cells with >55% encapsulation efficiency beating Poisson encapsulation statistics. Using this platform and commercially available Sox substrates (8-hydroxy-5-(N,N-dimethylsulfonamido)-2-methylquinoline), we have demonstrated a high throughput dynamic single cell signaling assay to measure the activity of receptor tyrosine kinases (RTKs) in lung cancer cells triggered by cell surface ligand binding. The phosphorylation of the substrates resulted in fluorescent emission, showing a sigmoidal increase over a 12 h period. The result exhibited a heterogeneous signaling rate in individual cells and showed various levels of drug resistance when treated with the tyrosine kinase inhibitor, gefitinib. PMID:24926389

  1. Lipid signalling couples translational surveillance to systemic detoxification in Caenorhabditis elegans

    PubMed Central

    Govindan, J. Amaranath; Jayamani, Elamparithi; Zhang, Xinrui; Breen, Peter; Larkins-Ford, Jonah; Mylonakis, Eleftherios

    2015-01-01

    Translation in eukaryotes is surveilled to detect toxins and virulence factors and coupled to the induction of defense pathways. C. elegans germline-specific mutations in translation components are detected by this system to induce detoxification and immune responses in distinct somatic cells. An RNAi screen revealed gene inactivations that act at multiple steps in lipid biosynthetic and kinase pathways that act upstream of MAP kinase to mediate the systemic communication of translation-defects to induce detoxification genes. Mammalian bile acids can rescue the defect in detoxification gene induction caused by C. elegans lipid biosynthetic gene inactivations. Extracts prepared from C. elegans with translation deficits but not from wild type can also rescue detoxification gene induction in lipid biosynthetic defective strains. These eukaryotic antibacterial countermeasures are not ignored by bacteria: particular bacterial species suppress normal C. elegans detoxification responses to mutations in translation factors. PMID:26322678

  2. Embedded coupled microrings with high-finesse and close-spaced resonances for optical signal processing.

    PubMed

    Souza, Mario C M M; Barea, Luis A M; Vallini, Felipe; Rezende, Guilherme F M; Wiederhecker, Gustavo S; Frateschi, Newton C

    2014-05-01

    Single microring resonators have been used in applications such as wavelength multicasting and microwave photonics, but the dependence of the free spectral range with ring radius imposes a trade-off between the required GHz optical channel spacing, footprint and power consumption. We demonstrate four-channel all-optical wavelength multicasting using only 1 mW of control power, with converted channel spacing of 40-60 GHz. Our device is based on a compact embedded microring design fabricated on a scalable SOI platform. The coexistence of close resonance spacing and high finesse (205) in a compact footprint is possible due to enhanced quality factors (30,000) resulting from the embedded configuration and the coupling-strength dependence of resonance spacing, instead of ring size. In addition, we discuss the possibility of achieving continuously mode splitting from a single-notch resonance up to 40 GHz. PMID:24921744

  3. Acoustic-Seismic Coupling of Broadband Signals - Analysis of Potential Disturbances during CTBT On-Site Inspection Measurements

    NASA Astrophysics Data System (ADS)

    Liebsch, Mattes; Altmann, Jürgen

    2015-04-01

    For the verification of the Comprehensive Nuclear Test Ban Treaty (CTBT) the precise localisation of possible underground nuclear explosion sites is important. During an on-site inspection (OSI) sensitive seismic measurements of aftershocks can be performed, which, however, can be disturbed by other signals. To improve the quality and effectiveness of these measurements it is essential to understand those disturbances so that they can be reduced or prevented. In our work we focus on disturbing signals caused by airborne sources: When the sound of aircraft (as often used by the inspectors themselves) hits the ground, it propagates through pores in the soil. Its energy is transferred to the ground and soil vibrations are created which can mask weak aftershock signals. The understanding of the coupling of acoustic waves to the ground is still incomplete. However, it is necessary to improve the performance of an OSI, e.g. to address potential consequences for the sensor placement, the helicopter trajectories etc. We present our recent advances in this field. We performed several measurements to record sound pressure and soil velocity produced by various sources, e.g. broadband excitation by jet aircraft passing overhead and signals artificially produced by a speaker. For our experimental set-up microphones were placed close to the ground and geophones were buried in different depths in the soil. Several sensors were shielded from the directly incident acoustic signals by a box coated with acoustic damping material. While sound pressure under the box was strongly reduced, the soil velocity measured under the box was just slightly smaller than outside of it. Thus these soil vibrations were mostly created outside the box and travelled through the soil to the sensors. This information is used to estimate characteristic propagation lengths of the acoustically induced signals in the soil. In the seismic data we observed interference patterns which are likely caused by the

  4. Monodisperse magnetite nanoparticles coupled with nuclear localization signal peptide for cell-nucleus targeting.

    PubMed

    Xu, Chenjie; Xie, Jin; Kohler, Nathan; Walsh, Edward G; Chin, Y Eugene; Sun, Shouheng

    2008-03-01

    Functionalization of monodisperse superparamagnetic magnetite (Fe(3)O(4)) nanoparticles for cell specific targeting is crucial for cancer diagnostics and therapeutics. Targeted magnetic nanoparticles can be used to enhance the tissue contrast in magnetic resonance imaging (MRI), to improve the efficiency in anticancer drug delivery, and to eliminate tumor cells by magnetic fluid hyperthermia. Herein we report the nucleus-targeting Fe(3)O(4) nanoparticles functionalized with protein and nuclear localization signal (NLS) peptide. These NLS-coated nanoparticles were introduced into the HeLa cell cytoplasm and nucleus, where the particles were monodispersed and non-aggregated. The success of labeling was examined and identified by fluorescence microscopy and MRI. The work demonstrates that monodisperse magnetic nanoparticles can be readily functionalized and stabilized for potential diagnostic and therapeutic applications. PMID:18080259

  5. FAK Forms a Complex with MEF2 to Couple Biomechanical Signaling to Transcription in Cardiomyocytes.

    PubMed

    Cardoso, Alisson Campos; Pereira, Ana Helena Macedo; Ambrosio, Andre Luis Berteli; Consonni, Silvio Roberto; Rocha de Oliveira, Renata; Bajgelman, Marcio Chain; Dias, Sandra Martha Gomes; Franchini, Kleber Gomes

    2016-08-01

    Focal adhesion kinase (FAK) has emerged as a mediator of mechanotransduction in cardiomyocytes, regulating gene expression during hypertrophic remodeling. However, how FAK signaling is relayed onward to the nucleus is unclear. Here, we show that FAK interacts with and regulates myocyte enhancer factor 2 (MEF2), a master cardiac transcriptional regulator. In cardiomyocytes exposed to biomechanical stimulation, FAK accumulates in the nucleus, binds to and upregulates the transcriptional activity of MEF2 through an interaction with the FAK focal adhesion targeting (FAT) domain. In the crystal structure (2.9 Å resolution), FAT binds to a stably folded groove in the MEF2 dimer, known to interact with regulatory cofactors. FAK cooperates with MEF2 to enhance the expression of Jun in cardiomyocytes, an important component of hypertrophic response to mechanical stress. These findings underscore a connection between the mechanotransduction involving FAK and transcriptional regulation by MEF2, with potential relevance to the pathogenesis of cardiac disease. PMID:27427476

  6. A FRET based aptasensor coupled with non-enzymatic signal amplification for mercury (II) ion detection.

    PubMed

    Chu-Mong, Ketsarin; Thammakhet, Chongdee; Thavarungkul, Panote; Kanatharana, Proespichaya; Buranachai, Chittanon

    2016-08-01

    In this work, the idea of incorporating a non-enzymatic signal amplification with a regular aptasensor was tested. In this proof of principle, the sensor was designed for the detection of mercury (II) ions (Hg(2+)) based on the Förster Resonance Energy Transfer (FRET), and the catalyzed hairpin assembly (CHA) technique that was used as the signal amplification method. This sensor comprised a mercury aptamer-catalyst complex (Apt-C) and two types of hairpin DNA: H1 labeled with fluorescein and H2 labeled with tetramethylrhodamine. In the presence of Hg(2+), two facing thymine bases in the mercury aptamer strand were coordinated with one mercury ion. This caused the release of the catalyst for the catalyzed hairpin assembly (CHA) reaction that turned H1 and H2 hairpins into H1-H2 hybrids. FRET was then used to report the hairpin-duplex transformation. The sensor showed excellent specificity towards Hg(2+) over other possible interfering cations present at even a 100 fold greater concentrations. It had a linear range of 10.0-200.0nM, and a good detection limit of 7.03±0.18nM, which is lower than the regulatory mercury limit for drinking water (10nM or 2ppb). The sensor was used to detect spiked Hg(2+) in nine real surface water samples collected from three different areas. Acceptable recoveries and small standard deviations indicated that the sensor was practically applicable, and the proposed idea to incorporate a CHA amplification in a regular aptasensor was not only feasible but beneficial. The same principles can be applied to develop sensors for various different targets. PMID:27216687

  7. Metformin Disrupts Crosstalk Between G protein-Coupled Receptor and Insulin Receptor Signaling Systems and Inhibits Pancreatic Cancer Growth

    PubMed Central

    Kisfalvi, Krisztina; Eibl, Guido; Sinnett-Smith, James; Rozengurt, Enrique

    2009-01-01

    Recently we identified a novel crosstalk between insulin and G-protein-coupled receptor (GPCR) signaling pathways in human pancreatic cancer cells. Insulin enhanced GPCR signaling through a rapamycin-sensitive mTOR-dependent pathway. Metformin, the most widely used drug in the treatment of type-2 diabetes, activates AMP kinase (AMPK), which negatively regulates mTOR. Here, we determined whether metformin disrupts crosstalk between insulin receptor and GPCR signaling in pancreatic cancer cells. Treatment of human pancreatic cancer cells (PANC-1, MIAPaCa-2, BxPC-3) with insulin (10ng/ml) for 5 min markedly enhanced the increase in intracellular [Ca2+] induced by GPCR agonists (e.g. neurotensin, bradykinin, angiotensin II). Metformin pretreatment completely abrogated insulin-induced potentiation of Ca2+ signaling but did not interfere with the effect of GPCR agonists alone. Insulin also enhanced GPCR agonist-induced growth, measured by DNA synthesis, and numbers of cells cultured in adherent or non-adherent conditions. Low doses of metformin (0.1-0.5 mM) blocked stimulation of DNA synthesis, anchorage-dependent and independent growth induced by insulin and GPCR agonists. Treatment with metformin induced striking and sustained increase in the phosphorylation of AMPK at Thr172 and a selective AMPK inhibitor (compound C, at 5μM) reversed the effects of metformin on [Ca2+]i, and DNA synthesis, indicating that metformin acts through AMPK activation. In view of these results we tested whether metformin inhibits pancreatic cancer growth. Administration of metformin significantly decreased the growth of MIAPaCa-2 and PANC-1 cells xenografted on the flank of nude mice. The results raise the possibility that metformin could be a potential candidate in novel treatment strategies for human pancreatic cancer. PMID:19679549

  8. Free fatty acid G-protein coupled receptor signaling in M1 skewed white adipose tissue macrophages.

    PubMed

    Vieira, Warren Antonio; Sadie-Van Gijsen, Hanél; Ferris, William Frank

    2016-10-01

    Obesity is associated with the establishment and maintenance of a low grade, chronically inflamed state in the white adipose tissue (WAT) of the body. The WAT macrophage population is a major cellular participant in this inflammatory process that significantly contributes to the pathophysiology of the disease, with the adipose depots of obese individuals, relative to lean counterparts, having an elevated number of macrophages that are skewed towards a pro-inflammatory phenotype. Alterations in the WAT lipid micro-environment, and specifically the availability of free fatty acids, are believed to contribute towards the obesity-related quantitative and functional changes observed in these cells. This review specifically addresses the involvement of the five G-protein coupled free fatty acid receptors which bind exogenous FFAs and signal in macrophages. Particular focus is placed on the involvement of these receptors in macrophage migration and cytokine production, two important aspects that modulate inflammation. PMID:27173059

  9. TCRβ Feedback Signals Inhibit the Coupling of Recombinationally Accessible Vβ14 Segments with DJβ Complexes

    PubMed Central

    Yang-Iott, Katherine S.; Carpenter, Andrea C.; Rowh, Marta A. W.; Steinel, Natalie; Brady, Brenna L.; Hochedlinger, Konrad; Jaenisch, Rudolf; Bassing, Craig H.

    2010-01-01

    Antigen receptor allelic exclusion is thought to occur through mono-allelic initiation and subsequent feedback inhibition of recombinational accessibility. However, our previous analysis of mice containing a V(D)J recombination reporter inserted into Vβ14 (Vβ14Rep) indicated that Vβ14 chromatin accessibility is bi-allelic. To determine whether Vβ14 recombinational accessibility is subject to feedback inhibition, we analyzed TCRβ rearrangements in Vβ14Rep mice containing a pre-assembled in frame transgenic Vβ8.2Dβ1Jβ1.1 or an endogenous Vβ14Dβ1Jβ1.4 rearrangement on the homologous chromosome. Expression of either pre-assembled VβDJβCβ chain accelerated thymocyte development due to enhanced cellular selection, demonstrating that the rate-limiting step in early αβ T cell development is the assembly of an in-frame VβDJβ rearrangement. Expression of these pre-assembled VβDJβ rearrangements inhibited endogenous Vβ14-to-DJβ rearrangements as expected. However, in contrast to results predicted by the accepted model of TCRβ feedback inhibition, we found that expression of these pre-assembled TCRβ chains did not down-regulate recombinational accessibility of Vβ14 chromatin. Our findings suggest that TCRβ mediated feedback inhibition of Vβ14 rearrangements depends upon inherent properties of Vβ14, Dβ, and Jβ recombination signal sequences. PMID:20042591

  10. Discrete spatial organization of TGFβ receptors couples receptor multimerization and signaling to cellular tension

    PubMed Central

    Rys, Joanna P; DuFort, Christopher C; Monteiro, David A; Baird, Michelle A; Oses-Prieto, Juan A; Chand, Shreya; Burlingame, Alma L; Davidson, Michael W; Alliston, Tamara N

    2015-01-01

    Cell surface receptors are central to the cell's ability to generate coordinated responses to the multitude of biochemical and physical cues in the microenvironment. However, the mechanisms by which receptors enable this concerted cellular response remain unclear. To investigate the effect of cellular tension on cell surface receptors, we combined novel high-resolution imaging and single particle tracking with established biochemical assays to examine TGFβ signaling. We find that TGFβ receptors are discretely organized to segregated spatial domains at the cell surface. Integrin-rich focal adhesions organize TβRII around TβRI, limiting the integration of TβRII while sequestering TβRI at these sites. Disruption of cellular tension leads to a collapse of this spatial organization and drives formation of heteromeric TβRI/TβRII complexes and Smad activation. This work details a novel mechanism by which cellular tension regulates TGFβ receptor organization, multimerization, and function, providing new insight into the mechanisms that integrate biochemical and physical cues. DOI: http://dx.doi.org/10.7554/eLife.09300.001 PMID:26652004

  11. Δ9-Tetrahydrocannabinol targeting estrogen receptor signaling: the possible mechanism of action coupled with endocrine disruption.

    PubMed

    Takeda, Shuso

    2014-01-01

    Δ(9)-Tetrahydrocannabinol (Δ(9)-THC), a biologically active constituent of marijuana, possesses a wide variety of pharmacological and toxicological effects (e.g., analgesia, hypotension, reduction of inflammation, and anti-cancer effects). Among Δ(9)-THC's biological activities, its recognized anti-estrogenic activity has been the subject of investigations. Since Δ(9)-THC is used as both a drug of abuse (marijuana) and as a preventive therapeutic to treat pain and nausea in cancer patients undergoing chemotherapy in the United States and other countries (synthesized Δ(9)-THC; dronabinol), it is important to investigate the mechanistic basis underlying the anti-estrogenic activity of Δ(9)-THC. Since Δ(9)-THC has "no" binding potential for estrogen receptor α (ERα) which can be activated by estrogen (E2), the question of how Δ(9)-THC exerts its inhibitory effect on ERα is not resolved. We have recently reported that ERβ, a second type of ER, is involved in the Δ(9)-THC abrogation of E2/ERα-mediated transcriptional activity. Here we discuss the possible mechanism(s) of the Δ(9)-THC-mediated disruption of E2/ERα signaling by presenting our recent findings as well. PMID:25177025

  12. Coupling Physiology and Gene Regulation in Bacteria: The Phosphotransferase Sugar Uptake System Delivers the Signals

    NASA Astrophysics Data System (ADS)

    Stülke, Jörg; Hillen, Wolfgang

    In many bacteria a crucial link between metabolism and regulation of catabolic genes is based on the phosphotransferase sugar uptake system (PTS). We summarize the mechanisms of the signaling pathways originating from PTS and leading to regulation of transcription. A protein domain, called PTS regulation domain (PRD), is linked to many antiterminators and transcriptional activators and regulates their activity depending on its state of phosphorylation. Two sites can be phosphorylated in most PRDs: HPr-dependent modification at one site leads to activation while enzyme II dependent phosphorylation of the other site renders it inactive. In addition, PTS components are used to generate cofactors for regulators of transcription. The paradigm is the enzyme II dependent activity of adenylate cyclase determining the cyclic AMP level in Escherichia coli and thereby the activity of the catabolite activator protein. In many gram-positive bacteria catabolite repression is mediated by the catabolite control protein CcpA, which requires HPr Ser-46 phosphate as a cofactor to regulate transcription of catabolic genes. HPr Ser-46 phosphate is produced by HPr kinase, the activity of which is under metabolic control via the concentrations of glycolytic intermediates. These recent results establish a multifaceted regulatory role for PTS in addition to its well-established function in active sugar uptake.

  13. Posttranslational modifications of cardiac ryanodine receptors: Ca2+ signaling and EC-coupling

    PubMed Central

    Niggli, Ernst; Ullrich, Nina D.; Gutierrez, D.; Kyrychenko, Sergii; Poláková, Eva; Shirokova, Natalia

    2012-01-01

    In cardiac muscle, a number of posttranslational protein modifications can alter the function of the Ca2+ release channel of the sarcoplasmic reticulum (SR), also known as the ryanodine receptor (RyR). During every heartbeat RyRs are activated by the Ca2+-induced Ca2+ release mechanism and contribute a large fraction of the Ca2+ required for contraction. Some of the posttranslational modifications of the RyR are known to affect its gating and Ca2+ sensitivity. Presently, research in a number of laboratories is focussed on RyR phosphorylation, both by PKA and CaMKII, or on RyR modifications caused by reactive oxygen and nitrogen species (ROS / RNS). Both classes of posttranslational modifications are thought to play important roles in the physiological regulation of channel activity, but are also known to provoke abnormal alterations during various diseases. Only recently it was realized that several types of posttranslational modifications are tightly connected and form synergistic (or antagonistic) feed-back loops resulting in additive and potentially detrimental downstream effects. This review summarizes recent findings on such posttranslational modifications, attempts to bridge molecular with cellular findings, and opens a perspective for future work trying to understand the ramifications of crosstalk in these multiple signaling pathways. Clarifying these complex interactions will be important in the development of novel therapeutic approaches, since this may form the foundation for the implementation of multi-pronged treatment regimes in the future. PMID:22960642

  14. The VLF Transmitter Signal as a Diagnostic of Thunderstorm-Ionosphere Coupling

    NASA Astrophysics Data System (ADS)

    Cohen, M.

    2015-12-01

    Very Low Frequency (VLF) transmitter remote sensing has evolved into a useful diagnostic for the D-region ionosphere, particularly in the presence of lightning-associated disturbances. All it requires is a VLF radio receiver monitoring the amplitude and/or phase of a beacon signal over time, which perturbs during ionospheric disturbances. For much of this field's history, amplitude and phase were analyzed and presented as individual data streams. A clever formulation known as scattered field analysis was recently reintroduced, which combines amplitude and phase into a single measurement, and calculates the phasor of the scattered field, providing insights that would otherwise be missed by either amplitude or phase individually. In this presentation we describe another useful formulation that goes one step further, combining the amplitude and phase of two horizontal magnetic field channels into a single measurement: polarization ellipse. This allows insights that would otherwise by missed by examining one channel at a time. Using this formulation, we take a new look at ionospheric disturbances from thunderstorms, including early/fast events and lightning-induced electron precipitation.

  15. Effects of mitochondrial uncoupling on Ca2+ signaling during excitation-contraction coupling in atrial myocytes

    PubMed Central

    Zima, Aleksey V.; Pabbidi, Malikarjuna R.; Lipsius, Stephen L.

    2013-01-01

    Mitochondria play an important role in intracellular Ca2+ concentration ([Ca2+]i) regulation in the heart. We studied sarcoplasmic reticulum (SR) Ca2+ release in cat atrial myocytes during depolarization of mitochondrial membrane potential (ΔΨm) induced by the protonophore FCCP. FCCP caused an initial decrease of action potential-induced Ca2+ transient amplitude and frequency of spontaneous Ca2+ waves followed by partial recovery despite partially depleted SR Ca2+ stores. In the presence of oligomycin, FCCP only exerted a stimulatory effect on Ca2+ transients and Ca2+ wave frequency, suggesting that the inhibitory effect of FCCP was mediated by ATP consumption through reverse-mode operation of mitochondrial F1F0-ATPase. ΔΨm depolarization was accompanied by cytosolic acidification, increases of diastolic [Ca2+]i, intracellular Na+ concentration ([Na+]i), and intracellular Mg2+ concentration ([Mg2+]i), and a decrease of intracellular ATP concentration ([ATP]i); however, glycolytic ATP production partially compensated for the exhaustion of mitochondrial ATP supplies. In conclusion, the initial inhibition of Ca2+ transients and waves resulted from suppression of ryanodine receptor SR Ca2+ release channel activity by a decrease in [ATP], an increase of [Mg2+]i, and cytoplasmic acidification. The later stimulation resulted from reduced mitochondrial Ca2+ buffering and cytosolic Na+ and Ca2+ accumulation, leading to enhanced Ca2+-induced Ca2+ release and spontaneous Ca2+ release in the form of Ca2+ waves. ΔΨm depolarization and the ensuing consequences of mitochondrial uncoupling observed here (intracellular acidification, decrease of [ATP]i, increase of [Na+]i and [Mg2+]i, and Ca2+ overload) are hallmarks of ischemia. These findings may therefore provide insight into the consequences of mitochondrial uncoupling for ion homeostasis, SR Ca2+ release, and excitation-contraction coupling in ischemia at the cellular and subcellular level. PMID:23376829

  16. Balancing Vibrations at Harmonic Frequencies by Injecting Harmonic Balancing Signals into the Armature of a Linear Motor/Alternator Coupled to a Stirling Machine

    NASA Technical Reports Server (NTRS)

    Holliday, Ezekiel S. (Inventor)

    2014-01-01

    Vibrations at harmonic frequencies are reduced by injecting harmonic balancing signals into the armature of a linear motor/alternator coupled to a Stirling machine. The vibrations are sensed to provide a signal representing the mechanical vibrations. A harmonic balancing signal is generated for selected harmonics of the operating frequency by processing the sensed vibration signal with adaptive filter algorithms of adaptive filters for each harmonic. Reference inputs for each harmonic are applied to the adaptive filter algorithms at the frequency of the selected harmonic. The harmonic balancing signals for all of the harmonics are summed with a principal control signal. The harmonic balancing signals modify the principal electrical drive voltage and drive the motor/alternator with a drive voltage component in opposition to the vibration at each harmonic.

  17. Treatment of denervation/disuse osteoporosis in the rat with a capacitively coupled electrical signal: effects on bone formation and bone resorption.

    PubMed

    Brighton, C T; Tadduni, G T; Goll, S R; Pollack, S R

    1988-01-01

    Utilizing a sciatic neurectomy model of disuse osteoporosis, the effects on rates of bone formation and bone resorption were examined when a capacitively coupled electrical signal was applied to the denervated tibia in the rat. It was found that a low-voltage, symmetrical sine wave, 60-kHz, capacitively coupled signal had no significant effect on the amount of bone resorption occurring in denervated right tibiae in rats previously labeled with [3H]tetracycline. This was true whether the signal was applied while osteoporosis was developing (prevention of osteoporosis) or after it had been established (treatment of osteoporosis). If a similar capacitively coupled signal was applied to rats in which osteoporosis was well established, and the rats were labeled with [3H]tetracycline daily during a 12-day treatment period, it was found that there was statistically significant enhancement of the amount of new bone formation (increased [3H]tetracycline incorporation) in the tibiae that received the signal as compared with that of the controls. These results indicate that prevention or amelioration of disuse osteoporosis that occurs with a capacitively coupled electrical signal is due not to a change in the rate of bone resorption, but to an increase in the rate of bone formation. PMID:3261339

  18. Expression Pattern of the Alpha-Kafirin Promoter Coupled with a Signal Peptide from Sorghum bicolor L. Moench

    PubMed Central

    Ahmad, Norazlina; Sant, Rajnesh; Bokan, Milovan; Steadman, Kathryn J.; Godwin, Ian D.

    2012-01-01

    Regulatory sequences with endosperm specificity are essential for foreign gene expression in the desired tissue for both grain quality improvement and molecular pharming. In this study, promoters of seed storage α-kafirin genes coupled with signal sequence (ss) were isolated from Sorghum bicolor L. Moench genomic DNA by PCR. The α-kafirin promoter (α-kaf) contains endosperm specificity-determining motifs, prolamin-box, the O2-box 1, CATC, and TATA boxes required for α-kafirin gene expression in sorghum seeds. The constructs pMB-Ubi-gfp and pMB-kaf-gfp were microprojectile bombarded into various sorghum and sweet corn explants. GFP expression was detected on all explants using the Ubi promoter but only in seeds for the α-kaf promoter. This shows that the α-kaf promoter isolated was functional and demonstrated seed-specific GFP expression. The constructs pMB-Ubi-ss-gfp and pMB-kaf-ss-gfp were also bombarded into the same explants. Detection of GFP expression showed that the signal peptide (SP)::GFP fusion can assemble and fold properly, preserving the fluorescent properties of GFP. PMID:22315514

  19. A Mechanism Regulating G Protein-coupled Receptor Signaling That Requires Cycles of Protein Palmitoylation and Depalmitoylation* ♦

    PubMed Central

    Jia, Lixia; Chisari, Mariangela; Maktabi, Mohammad H.; Sobieski, Courtney; Zhou, Hao; Konopko, Aaron M.; Martin, Brent R.; Mennerick, Steven J.; Blumer, Kendall J.

    2014-01-01

    Reversible attachment and removal of palmitate or other long-chain fatty acids on proteins has been hypothesized, like phosphorylation, to control diverse biological processes. Indeed, palmitate turnover regulates Ras trafficking and signaling. Beyond this example, however, the functions of palmitate turnover on specific proteins remain poorly understood. Here, we show that a mechanism regulating G protein-coupled receptor signaling in neuronal cells requires palmitate turnover. We used hexadecyl fluorophosphonate or palmostatin B to inhibit enzymes in the serine hydrolase family that depalmitoylate proteins, and we studied R7 regulator of G protein signaling (RGS)-binding protein (R7BP), a palmitoylated allosteric modulator of R7 RGS proteins that accelerate deactivation of Gi/o class G proteins. Depalmitoylation inhibition caused R7BP to redistribute from the plasma membrane to endomembrane compartments, dissociated R7BP-bound R7 RGS complexes from Gi/o-gated G protein-regulated inwardly rectifying K+ (GIRK) channels and delayed GIRK channel closure. In contrast, targeting R7BP to the plasma membrane with a polybasic domain and an irreversibly attached lipid instead of palmitate rendered GIRK channel closure insensitive to depalmitoylation inhibitors. Palmitate turnover therefore is required for localizing R7BP to the plasma membrane and facilitating Gi/o deactivation by R7 RGS proteins on GIRK channels. Our findings broaden the scope of biological processes regulated by palmitate turnover on specific target proteins. Inhibiting R7BP depalmitoylation may provide a means of enhancing GIRK activity in neurological disorders. PMID:24385443

  20. Rhodospirillum rubrum CO-dehydrogenase. Part 2: Spectroscopic investigation and assignment of spin-spin coupling signals

    SciTech Connect

    Heo, J.; Staples, C.R.; Telser, J.; Ludden, P.W.

    1999-12-08

    The carbon monoxide dehydrogenase (CODH) from Rhodospirillum rubrum was examined at several potentials. The electron paramagnetic resonance (EPR) spectrum of CODH poised at approximately {minus}295 mV exhibits a species (referred to as C{sub red1}) that was previously attributed to [Fe{sub 4}S{sub 4}]{sub C}{sup 1+} (S = 1/2) weakly exchange-coupling with Ni{sup 2+} (S = 1) to yield apparent g-values of (G{sub z,y,x} = 2.03, 1.88, 1.71). UV-visible absorption spectroscopy showed only one [Fe{sub 4}S{sub 4}] cluster to be reduced at {minus}295 mV. Based upon the assignment of S = 1/2 resonances in indigo carmine-poised C531A CODH to a [(CO{sub L})Fe{sup 3+}-Ni{sup 2+}-H{minus}]{sup 4+} cluster, a careful search for similar resonances in the EPR spectrum of the enzyme state of wild-type CODH producing C{sub red1} was undertaken. Coupled putative [(CO{sub L})Fe{sup 3+}-Ni{sup 2+}-H{minus}]{sup 4+} signals were observed in low intensity, which, in conjunction with the other assignments, prompted a reinterpretation of the redox state of the enzyme producing C{sub red1}. instead of coupling with Ni{sup 2+} (S = 1), the authors propose [Fe{sub 4}S{sub 4}]{sub C}{sup 1+} (S = 1/2) couples with [(CO{sub L})-Fe{sup 3+}-Ni{sup 2+}-H{minus}]{sup 4+} (S = 1/2). The putative [FeNi] signals were heterogeneous, but this heterogeneity could be removed by preincubation with CO prior to subsequent poising. They propose that an unreactive CO molecule (CO{sub L}) is bound to the [FeNi] cluster, possibly modulating the reduction potential and activating the [FeNi] cluster for catalysis of a substrate CO molecule (CO{sub S}). Either Zn{sup 2+} or Co{sup 2+} was incorporated into purified, Ni-deficient CODH. The EPR spectra of reduced Zn-CODH and Co-CODH contain resonances in the g = 1.73--1.76 region (which they call C{sub red2A}), and an upfield wing (shoulder) near g = 2.09. That these features are observed without a paramagnetic heterometal present indicates that they are derived

  1. Magnetically coupled signal isolator

    NASA Technical Reports Server (NTRS)

    Black, Jr., William C. (Inventor); Hermann, Theodore M. (Inventor)

    2001-01-01

    A current determiner having an output at which representations of input currents are provided having an input conductor for the input current and a current sensor supported on a substrate electrically isolated from one another but with the sensor positioned in the magnetic fields arising about the input conductor due to any input currents. The sensor extends along the substrate in a direction primarily perpendicular to the extent of the input conductor and is formed of at least a pair of thin-film ferromagnetic layers separated by a non-magnetic conductive layer. The sensor can be electrically connected to electronic circuitry formed in the substrate including a nonlinearity adaptation circuit to provide representations of the input currents of increased accuracy despite nonlinearities in the current sensor, and can include further current sensors in bridge circuits.

  2. Ligand-induced IFN gamma receptor tyrosine phosphorylation couples the receptor to its signal transduction system (p91).

    PubMed Central

    Greenlund, A C; Farrar, M A; Viviano, B L; Schreiber, R D

    1994-01-01

    Herein we report that interferon-gamma (IFN gamma) induces the rapid and reversible tyrosine phosphorylation of the IFN gamma receptor. Using a panel of receptor intracellular domain mutants, we show that a membrane-proximal LPKS sequence (residues 266-269) is required for ligand-induced tyrosine kinase activation and/or kinase-receptor association and biological responsiveness, and a functionally critical membrane-distal tyrosine residue (Y440) is a target of the activated enzyme. The biological significance of Y440 phosphorylation was demonstrated by showing that a receptor-derived nonapeptide corresponding to receptor residues 436-444 and containing phosphorylated Y440 bound specifically to p91, blocked p91 phosphorylation and inhibited the generation of an active p91-containing transcription factor complex. In contrast, nonphosphorylated wild-type, phosphorylated mutant, or phosphorylated irrelevant peptides did not. Moreover, the phosphorylated Y440-containing peptide did not interact with a related but distinct latent transcription factor (p113) which is activatible by IFN alpha but not IFN gamma. These results thus document the specific and inducible association of p91 with the phosphorylated IFN gamma receptor and thereby elucidate the mechanism by which ligand couples the IFN gamma receptor to its signal transduction system. Images PMID:8156998

  3. Structural, signalling and regulatory properties of the group I metabotropic glutamate receptors: prototypic family C G-protein-coupled receptors.

    PubMed Central

    Hermans, E; Challiss, R A

    2001-01-01

    In 1991 a new type of G-protein-coupled receptor (GPCR) was cloned, the type 1a metabotropic glutamate (mGlu) receptor, which, despite possessing the defining seven-transmembrane topology of the GPCR superfamily, bore little resemblance to the growing number of other cloned GPCRs. Subsequent studies have shown that there are eight mammalian mGlu receptors that, together with the calcium-sensing receptor, the GABA(B) receptor (where GABA is gamma-aminobutyric acid) and a subset of pheromone, olfactory and taste receptors, make up GPCR family C. Currently available data suggest that family C GPCRs share a number of structural, biochemical and regulatory characteristics, which differ markedly from those of the other GPCR families, most notably the rhodopsin/family A GPCRs that have been most widely studied to date. This review will focus on the group I mGlu receptors (mGlu1 and mGlu5). This subgroup of receptors is widely and differentially expressed in neuronal and glial cells within the brain, and receptor activation has been implicated in the control of an array of key signalling events, including roles in the adaptative changes needed for long-term depression or potentiation of neuronal synaptic connectivity. In addition to playing critical physiological roles within the brain, the mGlu receptors are also currently the focus of considerable attention because of their potential as drug targets for the treatment of a variety of neurological and psychiatric disorders. PMID:11672421

  4. Phosphorylation-Coupled Proteolysis of the Transcription Factor MYC2 Is Important for Jasmonate-Signaled Plant Immunity

    PubMed Central

    Zhai, Qingzhe; Yan, Liuhua; Tan, Dan; Chen, Rong; Sun, Jiaqiang; Gao, Liyan; Dong, Meng-Qiu; Wang, Yingchun; Li, Chuanyou

    2013-01-01

    As a master regulator of jasmonic acid (JA)–signaled plant immune responses, the basic helix-loop-helix (bHLH) Leu zipper transcription factor MYC2 differentially regulates different subsets of JA–responsive genes through distinct mechanisms. However, how MYC2 itself is regulated at the protein level remains unknown. Here, we show that proteolysis of MYC2 plays a positive role in regulating the transcription of its target genes. We discovered a 12-amino-acid element in the transcription activation domain (TAD) of MYC2 that is required for both the proteolysis and the transcriptional activity of MYC2. Interestingly, MYC2 phosphorylation at residue Thr328, which facilitates its turnover, is also required for the MYC2 function to regulate gene transcription. Together, these results reveal that phosphorylation-coupled turnover of MYC2 stimulates its transcription activity. Our results exemplify that, as with animals, plants employ an “activation by destruction” mechanism to fine-tune their transcriptome to adapt to their ever-changing environment. PMID:23593022

  5. Submicrometer Imaging by Laser Ablation-Inductively Coupled Plasma Mass Spectrometry via Signal and Image Deconvolution Approaches.

    PubMed

    Van Malderen, Stijn J M; van Elteren, Johannes T; Vanhaecke, Frank

    2015-06-16

    In this work, pre- and postacquisition procedures for enhancing the lateral resolution of laser ablation-inductively coupled plasma mass spectrometry (LA-ICPMS) in two- and three-dimensional (2D, 3D) nuclide distribution mapping beyond the laser beam waist are described. 2D images were constructed by projecting a rectangular grid of discrete LA positions, arranged at interspacings smaller than the dimensions of the laser beam waist, onto the sample surface, thus oversampling the region of interest and producing a 2D image convolved in the spatial domain. The pulse response peaks of a low-dispersion LA cell were isolated via signal deconvolution of the transient mass analyzer response. A 3D stack of 2D images was deconvolved by an iterative Richardson-Lucy algorithm with Total Variance regularization, enabling submicrometer image fidelity, demonstrated in the analysis of trace level features in corroded glass. A point spread function (PSF) could be derived from topography maps of single pulse craters from atomic force microscopy. This experimental PSF allows the approach to take into account the laser beam shape, beam aberrations, and the laser-solid interaction, which in turn enhances the spatial resolution of the reconstructed volume. PMID:25975805

  6. Sigma 1 receptor modulation of G-protein-coupled receptor signaling: potentiation of opioid transduction independent from receptor binding.

    PubMed

    Kim, Felix J; Kovalyshyn, Ivanka; Burgman, Maxim; Neilan, Claire; Chien, Chih-Cheng; Pasternak, Gavril W

    2010-04-01

    sigma Ligands modulate opioid actions in vivo, with agonists diminishing morphine analgesia and antagonists enhancing the response. Using human BE(2)-C neuroblastoma cells that natively express opioid receptors and human embryonic kidney (HEK) cells transfected with a cloned mu opioid receptor, we now demonstrate a similar modulation of opioid function, as assessed by guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTP gamma S) binding, by sigma(1) receptors. sigma Ligands do not compete opioid receptor binding. Administered alone, neither sigma agonists nor antagonists significantly stimulated [(35)S]GTP gamma S binding. Yet sigma receptor selective antagonists, but not agonists, shifted the EC(50) of opioid-induced stimulation of [(35)S]GTP gamma S binding by 3- to 10-fold to the left. This enhanced potency was seen without a change in the efficacy of the opioid, as assessed by the maximal stimulation of [(35)S]GTP gamma S binding. sigma(1) Receptors physically associate with mu opioid receptors, as shown by coimmunoprecipitation studies in transfected HEK cells, implying a direct interaction between the proteins. Thus, sigma receptors modulate opioid transduction without influencing opioid receptor binding. RNA interference knockdown of sigma(1) in BE(2)-C cells also potentiated mu opioid-induced stimulation of [(35)S]GTP gamma S binding. These modulatory actions are not limited to mu and delta opioid receptors. In mouse brain membrane preparations, sigma(1)-selective antagonists also potentiated both opioid receptor and muscarinic acetylcholine receptor-mediated stimulation of [(35)S]GTP gamma S binding, suggesting a broader role for sigma receptors in modulating G-protein-coupled receptor signaling. PMID:20089882

  7. σ1 Receptor Modulation of G-Protein-Coupled Receptor Signaling: Potentiation of Opioid Transduction Independent from Receptor Binding

    PubMed Central

    Kim, Felix J.; Kovalyshyn, Ivanka; Burgman, Maxim; Neilan, Claire; Chien, Chih-Cheng

    2010-01-01

    σ Ligands modulate opioid actions in vivo, with agonists diminishing morphine analgesia and antagonists enhancing the response. Using human BE(2)-C neuroblastoma cells that natively express opioid receptors and human embryonic kidney (HEK) cells transfected with a cloned μ opioid receptor, we now demonstrate a similar modulation of opioid function, as assessed by guanosine 5′-O-(3-[35S]thio)triphosphate ([35S]GTPγS) binding, by σ1 receptors. σ Ligands do not compete opioid receptor binding. Administered alone, neither σ agonists nor antagonists significantly stimulated [35S]GTPγS binding. Yet σ receptor selective antagonists, but not agonists, shifted the EC50 of opioid-induced stimulation of [35S]GTPγS binding by 3- to 10-fold to the left. This enhanced potency was seen without a change in the efficacy of the opioid, as assessed by the maximal stimulation of [35S]GTPγS binding. σ1 Receptors physically associate with μ opioid receptors, as shown by coimmunoprecipitation studies in transfected HEK cells, implying a direct interaction between the proteins. Thus, σ receptors modulate opioid transduction without influencing opioid receptor binding. RNA interference knockdown of σ1 in BE(2)-C cells also potentiated μ opioid-induced stimulation of [35S]GTPγS binding. These modulatory actions are not limited to μ and δ opioid receptors. In mouse brain membrane preparations, σ1-selective antagonists also potentiated both opioid receptor and muscarinic acetylcholine receptor-mediated stimulation of [35S]GTPγS binding, suggesting a broader role for σ receptors in modulating G-protein-coupled receptor signaling. PMID:20089882

  8. System and method for ultrafast optical signal detecting via a synchronously coupled anamorphic light pulse encoded laterally

    DOEpatents

    Heebner, John E.

    2010-08-03

    In one general embodiment, a method for ultrafast optical signal detecting is provided. In operation, a first optical input signal is propagated through a first wave guiding layer of a waveguide. Additionally, a second optical input signal is propagated through a second wave guiding layer of the waveguide. Furthermore, an optical control signal is applied to a top of the waveguide, the optical control signal being oriented diagonally relative to the top of the waveguide such that the application is used to influence at least a portion of the first optical input signal propagating through the first wave guiding layer of the waveguide. In addition, the first and the second optical input signals output from the waveguide are combined. Further, the combined optical signals output from the waveguide are detected. In another general embodiment, a system for ultrafast optical signal recording is provided comprising a waveguide including a plurality of wave guiding layers, an optical control source positioned to propagate an optical control signal towards the waveguide in a diagonal orientation relative to a top of the waveguide, at least one optical input source positioned to input an optical input signal into at least a first and a second wave guiding layer of the waveguide, and a detector for detecting at least one interference pattern output from the waveguide, where at least one of the interference patterns results from a combination of the optical input signals input into the first and the second wave guiding layer. Furthermore, propagation of the optical control signal is used to influence at least a portion of the optical input signal propagating through the first wave guiding layer of the waveguide.

  9. Non-Dioxin-Like Polychlorinated Biphenyls Inhibit G-Protein Coupled Receptor-Mediated Ca2+ Signaling by Blocking Store-Operated Ca2+ Entry

    PubMed Central

    Park, Yurim; Lee, Seung-Hyun; Jo, Su-Hyun; Chung, Sungkwon; Kim, Kyong-Tai

    2016-01-01

    Polychlorinated biphenyls (PCBs) are ubiquitous pollutants which accumulate in the food chain. Recently, several molecular mechanisms by which non-dioxin-like (NDL) PCBs mediate neurodevelopmental and neurobehavioral toxicity have been elucidated. However, although the G-protein coupled receptor (GPCR) is a significant target for neurobehavioral disturbance, our understanding of the effects of PCBs on GPCR signaling remains unclear. In this study, we investigated the effects of NDL-PCBs on GPCR-mediated Ca2+ signaling in PC12 cells. We found that ortho-substituted 2,2’,6-trichlorinated biphenyl (PCB19) caused a rapid decline in the Ca2+ signaling of bradykinin, a typical Gq- and phospholipase Cβ-coupled GPCR, without any effect on its inositol 1,4,5-trisphosphate production. PCB19 reduced thapsigargin-induced sustained cytosolic Ca2+ levels, suggesting that PCB19 inhibits SOCE. The abilities of other NDL-PCBs to inhibit store-operated Ca2+ entry (SOCE) were also examined and found to be of similar potencies to that of PCB19. PCB19 also showed a manner equivalent to that of known SOCE inhibitors. PCB19-mediated SOCE inhibition was confirmed by demonstrating the ability of PCB19 to inhibit the SOCE current and thapsigargin-induced Mn2+ influx. These results imply that one of the molecular mechanism by which NDL-PCBs cause neurobehavioral disturbances involves NDL-PCB-mediated inhibition of SOCE, thereby interfering with GPCR-mediated Ca2+ signaling. PMID:26963511

  10. Sensing Positive versus Negative Reward Signals through Adenylyl Cyclase-Coupled GPCRs in Direct and Indirect Pathway Striatal Medium Spiny Neurons

    PubMed Central

    Nair, Anu G.; Eriksson, Olivia; Vincent, Pierre

    2015-01-01

    Transient changes in striatal dopamine (DA) concentration are considered to encode a reward prediction error (RPE) in reinforcement learning tasks. Often, a phasic DA change occurs concomitantly with a dip in striatal acetylcholine (ACh), whereas other neuromodulators, such as adenosine (Adn), change slowly. There are abundant adenylyl cyclase (AC) coupled GPCRs for these neuromodulators in striatal medium spiny neurons (MSNs), which play important roles in plasticity. However, little is known about the interaction between these neuromodulators via GPCRs. The interaction between these transient neuromodulator changes and the effect on cAMP/PKA signaling via Golf- and Gi/o-coupled GPCR are studied here using quantitative kinetic modeling. The simulations suggest that, under basal conditions, cAMP/PKA signaling could be significantly inhibited in D1R+ MSNs via ACh/M4R/Gi/o and an ACh dip is required to gate a subset of D1R/Golf-dependent PKA activation. Furthermore, the interaction between ACh dip and DA peak, via D1R and M4R, is synergistic. In a similar fashion, PKA signaling in D2+ MSNs is under basal inhibition via D2R/Gi/o and a DA dip leads to a PKA increase by disinhibiting A2aR/Golf, but D2+ MSNs could also respond to the DA peak via other intracellular pathways. This study highlights the similarity between the two types of MSNs in terms of high basal AC inhibition by Gi/o and the importance of interactions between Gi/o and Golf signaling, but at the same time predicts differences between them with regard to the sign of RPE responsible for PKA activation. SIGNIFICANCE STATEMENT Dopamine transients are considered to carry reward-related signal in reinforcement learning. An increase in dopamine concentration is associated with an unexpected reward or salient stimuli, whereas a decrease is produced by omission of an expected reward. Often dopamine transients are accompanied by other neuromodulatory signals, such as acetylcholine and adenosine. We highlight the

  11. Differential pathway coupling efficiency of the activated insulin receptor drives signaling selectivity by xmeta, an allosteric partial agonist antibody

    Technology Transfer Automated Retrieval System (TEKTRAN)

    XMetA, an anti-insulin receptor (IR) monoclonal antibody, is an allosteric partial agonist of the IR. We have previously reported that XMetA activates the “metabolic-biased” Akt kinase signaling pathway while having little or no effect on the “mitogenic” MAPK signaling pathwayof ERK 1/2. To inves...

  12. DAF-18/PTEN locally antagonizes insulin signalling to couple germline stem cell proliferation to oocyte needs in C. elegans.

    PubMed

    Narbonne, Patrick; Maddox, Paul S; Labbé, Jean-Claude

    2015-12-15

    During development, stem cell populations rapidly proliferate to populate the expanding tissues and organs. During this phase, nutrient status, by systemically affecting insulin/IGF-1 signalling, largely dictates stem cell proliferation rates. In adults, however, differentiated stem cell progeny requirements are generally reduced and vary according to the spatiotemporal needs of each tissue. We demonstrate here that differential regulation of germline stem cell proliferation rates in Caenorhabditis elegans adults is accomplished through localized neutralization of insulin/IGF-1 signalling, requiring DAF-18/PTEN, but not DAF-16/FOXO. Indeed, the specific accumulation of oocytes, the terminally differentiated stem cell progeny, triggers a feedback signal that locally antagonizes insulin/IGF-1 signalling outputs in the germ line, regardless of their systemic levels, to block germline stem cell proliferation. Thus, during adulthood, stem cells can differentially respond within tissues to otherwise equal insulin/IGF-1 signalling inputs, according to the needs for production of their immediate terminally differentiated progeny. PMID:26552888

  13. Bacillus bombysepticus α-Toxin Binding to G Protein-Coupled Receptor Kinase 2 Regulates cAMP/PKA Signaling Pathway to Induce Host Death

    PubMed Central

    Lin, Ping; Cheng, Tingcai; Ma, Sanyuan; Gao, Junping; Jin, Shengkai; Jiang, Liang; Xia, Qingyou

    2016-01-01

    Bacterial pathogens and their toxins target host receptors, leading to aberrant behavior or host death by changing signaling events through subversion of host intracellular cAMP level. This is an efficient and widespread mechanism of microbial pathogenesis. Previous studies describe toxins that increase cAMP in host cells, resulting in death through G protein-coupled receptor (GPCR) signaling pathways by influencing adenylyl cyclase or G protein activity. G protein-coupled receptor kinase 2 (GRK2) has a central role in regulation of GPCR desensitization. However, little information is available about the pathogenic mechanisms of toxins associated with GRK2. Here, we reported a new bacterial toxin-Bacillus bombysepticus (Bb) α-toxin that was lethal to host. We showed that Bb α-toxin interacted with BmGRK2. The data demonstrated that Bb α-toxin directly bound to BmGRK2 to promote death by affecting GPCR signaling pathways. This mechanism involved stimulation of Gαs, increase level of cAMP and activation of protein kinase A (PKA). Activated cAMP/PKA signal transduction altered downstream effectors that affected homeostasis and fundamental biological processes, disturbing the structural and functional integrity of cells, resulting in death. Preventing cAMP/PKA signaling transduction by inhibitions (NF449 or H-89) substantially reduced the pathogenicity of Bb α-toxin. The discovery of a toxin-induced host death specifically linked to GRK2 mediated signaling pathway suggested a new model for bacterial toxin action. Characterization of host genes whose expression and function are regulated by Bb α-toxin and GRK2 will offer a deeper understanding of the pathogenesis of infectious diseases caused by pathogens that elevate cAMP. PMID:27022742

  14. Generation of multi-channel high-speed physical random numbers originated from two chaotic signals of mutually coupled semiconductor lasers

    NASA Astrophysics Data System (ADS)

    Tang, X.; Wu, Z. M.; Wu, J. G.; Deng, T.; Fan, L.; Zhong, Z. Q.; Chen, J. J.; Xia, G. Q.

    2015-01-01

    We propose and experimentally demonstrate a novel technique to generate multi-channel high-speed physical random numbers (PRNs) by taking two chaotic signal outputs from mutually coupled semiconductor lasers (MC-SLs) as entropy sources. First, through controlling the operation parameters of the MC-SL system, two time-delay signature (TDS) suppressed chaotic signals can be obtained. Next, each of these two chaotic signals is sampled by an 8 bit analog-to-digital converter (ADC) with a sampling rate of 10 GHz, and then a bitwise exclusive-OR (XOR) operation on the corresponding bits in samples of the chaotic signal and its time delayed signal is implemented to obtain 8 bit XOR data. Furthermore, through selecting the five least significant bits (LSBs) of 8 bit XOR data to form 5 bit Boolean sequences, two sets of PRN streams with a rate up to 50 Gbits s-1 are generated and successfully pass the NIST statistical tests. Finally, merging these two sets of 50 Gbits s-1 PRN streams by an interleaving operation, another set of the 100 Gbits s-1 PRN stream, which meets all the quality criteria of NIST statistical tests, is also acquired.

  15. Mixed Quantum-Classical Simulations of Transient Absorption Pump-Probe Signals for a Photo-Induced Electron Transfer Reaction Coupled to an Inner-Sphere Vibrational Mode.

    PubMed

    Martinez, Franz; Hanna, Gabriel

    2016-05-19

    In a previous study (Martinez, F.; Hanna, G. Chem. Phys. Lett. 2013, 573, 77-83), we demonstrated the ability of two approximate solutions of the quantum-classical Liouville equation (QCLE) for qualitatively capturing the electronic dynamics in the pump-probe transient absorption (TA) signal of a model of a condensed phase photoinduced electron transfer reaction whose ground and excited donor states have the same equilibrium geometry. However, the question remained as to the ability of these solutions to treat the more complex situation in which the electronic states are coupled to a low-frequency inner-sphere harmonic vibrational mode (representing an intramolecular mode of the donor-acceptor complex) that shifts their equilibrium geometries with respect to each other and thereby gives rise to signatures of vibrational dynamics in the TA signal. Thus, in this study, we investigated this situation by treating the vibrational mode both quantum mechanically and classically within the context of the approximate Poisson bracket mapping equation (PBME) and forward-backward trajectory solutions (FBTS) of the QCLE. Depending on the definition of the quantum subsystem, both PBME and FBTS are capable of qualitatively capturing several of the main features in the exact TA signal and quantitatively capturing the characteristic time scale of the vibrational dynamics, despite the moderately strong subsystem-bath coupling in this model. Particularly, we found that treating the vibrational mode quantum mechanically using either PBME or FBTS better captures the signatures of the vibrational dynamics, while treating it classically using FBTS better captures the decay in the signal. These findings underscore the utility of the PBME and FBTS approaches for efficiently modeling and interpreting TA signals. PMID:26766568

  16. Signalling of sphingosine-1-phosphate in Müller glial cells via the S1P/EDG-family of G-protein-coupled receptors.

    PubMed

    Esche, Mirko; Hirrlinger, Petra G; Rillich, Katja; Yafai, Yousef; Pannicke, Thomas; Reichenbach, Andreas; Weick, Michael

    2010-08-16

    Signalling of sphingosine-1-phosphate (S1P) via G-protein-coupled receptors of the Endothelial Differentiation Gene family differentially regulates cellular processes such as migration, proliferation and morphogenesis in a variety of cell types. Proliferation and migration of retinal Müller glial cells are involved in pathological events such as proliferative vitreoretinopathy and proliferative diabetic retinopathy. Investigation of possible functional roles of S1P receptors might thus open new insights into Müller cell pathophysiology. Here we show that cultured Müller cells from the guinea pig retina respond to application of S1P with an increase in the intracellular calcium content in a concentration-dependent manner (EC(50) 11nM). This calcium increase consists of two components; an initial fast peak and a slow plateau component. The initial transient is caused by a release of calcium from intracellular stores and is suppressed by U-73122, a selective phospholipase C inhibitor. The slow plateau component is caused by a calcium influx. These results suggest that the S1P-induced calcium response in Müller cells partially involves signalling via G-protein-coupled receptors. Moreover, S1P slightly induced Müller cell migration but no proliferation. Thus, the data indicate that Müller cells might be involved in S1P signalling in the retina. PMID:20540988

  17. Antibody-directed coupling of endoglin and MMP-14 is a key mechanism for endoglin shedding and deregulation of TGF-β signaling.

    PubMed

    Kumar, S; Pan, C C; Bloodworth, J C; Nixon, A B; Theuer, C; Hoyt, D G; Lee, N Y

    2014-07-24

    Endoglin is a transforming growth factor β (TGF-β) coreceptor that serves as a prognostic, diagnostic and therapeutic vascular target in human cancer. A number of endoglin ectodomain-targeting antibodies (Abs) can effectively suppress both normal and tumor-associated angiogenesis, but their molecular actions remain poorly characterized. Here we define a key mechanism for TRACON105 (TRC105), a humanized monoclonal Ab in clinical trials for treatment of advanced or metastatic tumors. TRC105, along with several other endoglin Abs tested, enhance endoglin shedding through direct coupling of endoglin and the membrane-type 1 matrix metalloproteinase (MMP)-14 at the cell surface to release the antiangiogenic factor, soluble endoglin (sEng). In addition to this coupling process, endoglin shedding is further amplified by increased MMP-14 expression that requires TRC105 concentration-dependent c-Jun N-terminal kinase (JNK) activation. There were also notable counterbalancing effects on canonical Smad signaling in which TRC105 abrogated both the steady-state and TGF-β-induced Smad1/5/8 activation while augmenting Smad2/3 activation. Interestingly, TRC105-induced sEng and aberrant Smad signaling resulted in an excessive migratory response through enhanced stress fiber formation and disruption of endothelial cell-cell junctions. Collectively, our study defines endoglin shedding and deregulated TGF-β signaling during migration as major mechanisms by which TRC105 inhibits angiogenesis. PMID:24077288

  18. Antibody-directed coupling of endoglin and MMP-14 is a key mechanism for endoglin shedding and deregulation of TGF-β signaling

    PubMed Central

    Kumar, S; Pan, C C; Bloodworth, J C; Nixon, A B; Theuer, C; Hoyt, D G; Lee, N Y

    2014-01-01

    Endoglin is a transforming growth factor β (TGF-β) coreceptor that serves as a prognostic, diagnostic and therapeutic vascular target in human cancer. A number of endoglin ectodomain-targeting antibodies (Abs) can effectively suppress both normal and tumor-associated angiogenesis, but their molecular actions remain poorly characterized. Here we define a key mechanism for TRACON105 (TRC105), a humanized monoclonal Ab in clinical trials for treatment of advanced or metastatic tumors. TRC105, along with several other endoglin Abs tested, enhance endoglin shedding through direct coupling of endoglin and the membrane-type 1 matrix metalloproteinase (MMP)-14 at the cell surface to release the antiangiogenic factor, soluble endoglin (sEng). In addition to this coupling process, endoglin shedding is further amplified by increased MMP-14 expression that requires TRC105 concentration-dependent c-Jun N-terminal kinase (JNK) activation. There were also notable counterbalancing effects on canonical Smad signaling in which TRC105 abrogated both the steady-state and TGF-β-induced Smad1/5/8 activation while augmenting Smad2/3 activation. Interestingly, TRC105-induced sEng and aberrant Smad signaling resulted in an excessive migratory response through enhanced stress fiber formation and disruption of endothelial cell–cell junctions. Collectively, our study defines endoglin shedding and deregulated TGF-β signaling during migration as major mechanisms by which TRC105 inhibits angiogenesis. PMID:24077288

  19. Target-induced formation of gold amalgamation on DNA-based sensing platform for electrochemical monitoring of mercury ion coupling with cycling signal amplification strategy.

    PubMed

    Chen, Jinfeng; Tang, Juan; Zhou, Jun; Zhang, Lan; Chen, Guonan; Tang, Dianping

    2014-01-31

    Heavy metal ion pollution poses severe risks in human health and environmental pollutant, because of the likelihood of bioaccumulation and toxicity. Driven by the requirement to monitor trace-level mercury ion (Hg(2+)), herein we construct a new DNA-based sensor for sensitive electrochemical monitoring of Hg(2+) by coupling target-induced formation of gold amalgamation on DNA-based sensing platform with gold amalgamation-catalyzed cycling signal amplification strategy. The sensor was simply prepared by covalent conjugation of aminated poly-T(25) oligonucleotide onto the glassy carbon electrode by typical carbodiimide coupling. Upon introduction of target analyte, Hg(2+) ion was intercalated into the DNA polyion complex membrane based on T-Hg(2+)-T coordination chemistry. The chelated Hg(2+) ion could induce the formation of gold amalgamation, which could catalyze the p-nitrophenol with the aid of NaBH4 and Ru(NH3)6(3+) for cycling signal amplification. Experimental results indicated that the electronic signal of our system increased with the increasing Hg(2+) level in the sample, and has a detection limit of 0.02nM with a dynamic range of up to 1000nM Hg(2+). The strategy afforded exquisite selectivity for Hg(2+) against other environmentally related metal ions. In addition, the methodology was evaluated for the analysis of Hg(2+) in spiked tap-water samples, and the recovery was 87.9-113.8%. PMID:24439499

  20. Enhanced thj signal at the LHC with h → γγ decay and CP-violating top-Higgs coupling

    NASA Astrophysics Data System (ADS)

    Yue, Jason

    2015-05-01

    We study the observability of non-standard top Yukawa couplings in the pp → t (→ ℓνℓ b) h (→ γγ) j channel at 14 TeV high-luminosity LHC (HL-LHC). The small diphoton branching ratio is enhanced when the CP-violating phase, ξ, of the top-Higgs interaction is non-zero. When the modulus of the top-Higgs interaction assumes the SM value, yt = ytSM, we find that the signal significance reaches 2.7σ (7.7 σ) when ξ = 0.25 π (0.5 π). Furthermore, the different couplings modify the polarisation of the top quark, and can subsequently be distinguished via asymmetries in spin correlations with the final state leptons. The diphoton decay mode is found to be significantly more promising than the previously considered pp → t (→ ℓνℓ b) h (→ bbbar) j channel.

  1. The observation at Chofu of Doppler-shifts of subionospheric LF signal transmitted from Saga, and the mechanism of lithosphere- atmosphere-ionosphere coupling

    NASA Astrophysics Data System (ADS)

    Hayakawa, M.; Kasahara, Y.; Endoh, T.; Hobara, Y.; Asai, S.

    2012-04-01

    This paper is based on the measurement at Chofu(CHF) of subionospheric signals from an LF transmitter, JJY (frequency=60kHz) (transmitted from Saga, Kyushu). The data analysis was done for the 6-month period from January 1, 2009 to June 30, 2009, during which several earthquakes happened near the propagation path of JJY-CHF. The Doppler-shifts of subionospheric LF signals are considered to provide the significant direct information in the lower ionosphere. It is found that we could detect the significant increase in the AGW and AW components of Doppler-shifts several days before each earthquake. This fact provides a definite strong support to the AGW channel of the lithosphere-atmosphere-ionosphere-coupling.

  2. Oncogenic CARMA1 couples NF-κB and β-catenin signaling in diffuse large B-cell lymphomas

    PubMed Central

    Bognar, M K; Vincendeau, M; Erdmann, T; Seeholzer, T; Grau, M; Linnemann, J R; Ruland, J; Scheel, C H; Lenz, P; Ott, G; Lenz, G; Hauck, S M; Krappmann, D

    2016-01-01

    Constitutive activation of the antiapoptotic nuclear factor-κB (NF-κB) signaling pathway is a hallmark of the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphomas (DLBCL). Recurrent oncogenic mutations are found in the scaffold protein CARMA1 (CARD11) that connects B-cell receptor (BCR) signaling to the canonical NF-κB pathway. We asked how far additional downstream processes are activated and contribute to the oncogenic potential of DLBCL-derived CARMA1 mutants. To this end, we expressed oncogenic CARMA1 in the NF-κB negative DLBCL lymphoma cell line BJAB. By a proteomic approach we identified recruitment of β-catenin and its destruction complex consisting of APC, AXIN1, CK1α and GSK3β to oncogenic CARMA1. Recruitment of the β-catenin destruction complex was independent of CARMA1-BCL10-MALT1 complex formation or constitutive NF-κB activation and promoted the stabilization of β-catenin. The β-catenin destruction complex was also recruited to CARMA1 in ABC DLBCL cell lines, which coincided with elevated β-catenin expression. In line, β-catenin was frequently detected in non-GCB DLBCL biopsies that rely on chronic BCR signaling. Increased β-catenin amounts alone were not sufficient to induce classical WNT target gene signatures, but could augment TCF/LEF-dependent transcriptional activation in response to WNT signaling. In conjunction with NF-κB, β-catenin enhanced expression of immunosuppressive interleukin-10 and suppressed antitumoral CCL3, indicating that β-catenin can induce a favorable tumor microenvironment. Thus, parallel activation of NF-κB and β-catenin signaling by gain-of-function mutations in CARMA1 augments WNT stimulation and is required for regulating the expression of distinct NF-κB target genes to trigger cell-intrinsic and extrinsic processes that promote DLBCL lymphomagenesis. PMID:26776161

  3. Tumor necrosis factor receptor superfamily costimulation couples T cell receptor signal strength to thymic regulatory T cell differentiation

    PubMed Central

    Mahmud, Shawn A.; Manlove, Luke S.; Schmitz, Heather M.; Xing, Yan; Wang, Yanyan; Owen, David L.; Schenkel, Jason M.; Boomer, Jonathan S.; Green, Jonathan M.; Yagita, Hideo; Chi, Hongbo; Hogquist, Kristin A.; Farrar, Michael A.

    2014-01-01

    Regulatory T (Treg) cells express tumor necrosis factor receptor superfamily (TNFRSF) members, but their role in thymic Treg development is undefined. We demonstrate that Treg progenitors highly express the TNFRSF members GITR, OX40, and TNFR2. Expression of these receptors correlates directly with T cell receptor (TCR) signal strength, and requires CD28 and the kinase TAK1. Neutralizing TNFSF ligands markedly reduced Treg development. Conversely, TNFRSF agonists enhanced Treg differentiation by augmenting IL-2R/STAT5 responsiveness. GITR-ligand costimulation elicited a dose-dependent enrichment of lower-affinity cells within the Treg repertoire. In vivo, combined inhibition of GITR, OX40 and TNFR2 abrogated Treg development. Thus TNFRSF expression on Treg progenitors translates strong TCR signals into molecular parameters that specifically promote Treg differentiation and shape the Treg repertoire. PMID:24633226

  4. Ultraspecific electrochemical DNA biosensor by coupling spontaneous cascade DNA branch migration and dual-signaling sensing strategy.

    PubMed

    Wang, Ting; Zhou, Lili; Bai, Shulian; Zhang, Zhang; Li, Junlong; Jing, Xiaoying; Xie, Guoming

    2016-04-15

    Using spontaneous cascade DNA branch migration and dual-signaling sensing strategy, we developed a novel universal electrochemical biosensor for the highly specific and sensitive detection of nucleic acids. A target strand (Ts) competitively hybridized with a ferrocene (Fc)-labeled signal probe (Fc-S1), which was blocked by a protector strand (Ps), after strand displacement to form the Ts/Fc-S1 duplex. A methylene blue (MB)-modified signal probe (MB-S2) was immobilized on the Au electrode surface by hybridizing with a thiolated capture probe (Cp). Then, the obtained reactants (Ts/Fc-S1 and MB-S2/Cp) suffered spontaneous DNA branch migration and produced two hybridization products (Fc-S1/Cp and MB-S2/Ts). These reactions led to the dissociation of MB molecules and the collection of Fc molecules. The detection mechanism of this DNA biosensor involved distance variation between the redox tags and the Au electrode, which was associated with target-induced cascade DNA branch migration. Moreover, we rationally designed the cascade DNA branch migration to occur spontaneously with ΔG° ≈ 0, at which slight thermodynamic changes caused by base mismatch exerted a disproportionately large effect on the hybridization yield. This "signal-on/off" sensing system exhibited a remarkable analytical performance and an ultrahigh discrimination capability even against a single-base mismatch. The maximum discrimination factor (DF) of base mutations or alterations can reach 17.9. Therefore, our electrochemical biosensor might hold a great potential for further applications in biomedical research and early clinical diagnosis. PMID:26657589

  5. Specific Activation of the G Protein-coupled Receptor BNGR-A21 by the Neuropeptide Corazonin from the Silkworm, Bombyx mori, Dually Couples to the Gq and Gs Signaling Cascades*

    PubMed Central

    Yang, Jingwen; Huang, Haishan; Yang, Huipeng; He, Xiaobai; Jiang, Xue; Shi, Ying; Alatangaole, Damirin; Shi, Liangen; Zhou, Naiming

    2013-01-01

    Corazonin, an undecapeptide neurohormone sharing a highly conserved amino acid sequence across Insecta, plays different physiological roles in the regulation of heart contraction rates, silk spinning rates, the induction of dark color and morphometric phase changes, and ecdysis. Corazonin receptors have been identified in Drosophila melanogaster, Manduca sexta, and Musca domestica. However, detailed information on the signaling and major physiological functions of corazonin and its receptor is largely unknown. In the current study, using both the mammalian cell line HEK293 and insect cell lines BmN and Sf21, we paired the Bombyx corazonin neuropeptide as a specific endogenous ligand for the Bombyx neuropeptide G protein-coupled receptor A21 (BNGR-A21), and we therefore designated this receptor as BmCrzR. Further characterization indicated that synthetic BmCrz demonstrated a high affinity for and activated BmCrzR, resulting in intracellular cAMP accumulation, Ca2+ mobilization, and ERK1/2 phosphorylation via the Gq- and Gs-coupled signaling pathways. The direct interaction of BmCrzR with BmCrz was confirmed by a rhodamine-labeled BmCrz peptide. Moreover, experiments with double-stranded RNA and synthetic peptide injection suggested a possible role of BmCrz/BmCrzR in the regulation of larval growth and spinning rate. Our present results provide the first in-depth information on BmCrzR-mediated signaling for further elucidation of the BmCrz/BmCrzR system in the regulation of fundamental physiological processes. PMID:23457297

  6. Intercellular calcium signaling in a gap junction-coupled cell network establishes asymmetric neuronal fates in C. elegans

    PubMed Central

    Schumacher, Jennifer A.; Hsieh, Yi-Wen; Chen, Shiuhwei; Pirri, Jennifer K.; Alkema, Mark J.; Li, Wen-Hong; Chang, Chieh; Chuang, Chiou-Fen

    2012-01-01

    The C. elegans left and right AWC olfactory neurons specify asymmetric subtypes, one default AWCOFF and one induced AWCON, through a stochastic, coordinated cell signaling event. Intercellular communication between AWCs and non-AWC neurons via a NSY-5 gap junction network coordinates AWC asymmetry. However, the nature of intercellular signaling across the network and how individual non-AWC cells in the network influence AWC asymmetry is not known. Here, we demonstrate that intercellular calcium signaling through the NSY-5 gap junction neural network coordinates a precise 1AWCON/1AWCOFF decision. We show that NSY-5 gap junctions in C. elegans cells mediate small molecule passage. We expressed vertebrate calcium-buffer proteins in groups of cells in the network to reduce intracellular calcium levels, thereby disrupting intercellular communication. We find that calcium in non-AWC cells of the network promotes the AWCON fate, in contrast to the autonomous role of calcium in AWCs to promote the AWCOFF fate. In addition, calcium in specific non-AWCs promotes AWCON side biases through NSY-5 gap junctions. Our results suggest a novel model in which calcium has dual roles within the NSY-5 network: autonomously promoting AWCOFF and non-autonomously promoting AWCON. PMID:23093425

  7. Intraflagellar Transport/Hedgehog-Related Signaling Components Couple Sensory Cilium Morphology and Serotonin Biosynthesis in Caenorhabditis elegans

    PubMed Central

    Moussaif, Mustapha; Sze, Ji Ying

    2009-01-01

    Intraflagellar transport in cilia has been proposed as a crucial mediator of Hedgehog signal transduction during embryonic pattern formation in both vertebrates and invertebrates. Here, we show that the Hh receptor Patched-related factor DAF-6 and intraflagellar transport modulate serotonin production in Caenorhabditis elegans animals, by remodeling the architecture of dendritic cilia of a pair of ADF serotonergic chemosensory neurons. Wild-type animals under aversive environment drastically reduce DAF-6 expression in glia-like cells surrounding the cilia of chemosensory neurons, resulting in cilium structural remodeling and upregulation of the serotonin-biosynthesis enzyme tryptophan hydroxylase tph-1 in the ADF neurons. These cellular and molecular modifications are reversed when the environment improves. Mutants of daf-6 or intraflagellar transport constitutively upregulate tph-1 expression. Epistasis analyses indicate that DAF-6/intraflagellar transport and the OCR-2/OSM-9 TRPV channel act in concert, regulating two layers of activation of tph-1 in the ADF neurons. The TRPV signaling turns on tph-1 expression under favorable and aversive conditions, whereas inactivation of DAF-6 by stress results in further upregulation of tph-1 independently of OCR-2/OSM-9 activity. Behavioral analyses suggest that serotonin facilitates larval animals resuming development when the environment improves. Our study revealed the cilium structure of serotonergic neurons as a trigger of regulated serotonin production, and demonstrated that a Hedgehog-related signaling component is dynamically regulated by environment and underscores neuroplasticity of serotonergic neurons in C. elegans under stress and stress recovery. PMID:19339602

  8. RDGBα, a PtdIns-PtdOH transfer protein, regulates G-protein-coupled PtdIns(4,5)P2 signalling during Drosophila phototransduction

    PubMed Central

    Yadav, Shweta; Garner, Kathryn; Georgiev, Plamen; Li, Michelle; Gomez-Espinosa, Evelyn; Panda, Aniruddha; Mathre, Swarna; Okkenhaug, Hanneke; Cockcroft, Shamshad; Raghu, Padinjat

    2015-01-01

    ABSTRACT Many membrane receptors activate phospholipase C (PLC) during signalling, triggering changes in the levels of several plasma membrane lipids including phosphatidylinositol (PtdIns), phosphatidic acid (PtdOH) and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2]. It is widely believed that exchange of lipids between the plasma membrane and endoplasmic reticulum (ER) is required to restore lipid homeostasis during PLC signalling, yet the mechanism remains unresolved. RDGBα (hereafter RDGB) is a multi-domain protein with a PtdIns transfer protein (PITP) domain (RDGB-PITPd). We find that, in vitro, the RDGB-PITPd binds and transfers both PtdOH and PtdIns. In Drosophila photoreceptors, which experience high rates of PLC activity, RDGB function is essential for phototransduction. We show that binding of PtdIns to RDGB-PITPd is essential for normal phototransduction; however, this property is insufficient to explain the in vivo function because another Drosophila PITP (encoded by vib) that also binds PtdIns cannot rescue the phenotypes of RDGB deletion. In RDGB mutants, PtdIns(4,5)P2 resynthesis at the plasma membrane following PLC activation is delayed and PtdOH levels elevate. Thus RDGB couples the turnover of both PtdIns and PtdOH, key lipid intermediates during G-protein-coupled PtdIns(4,5)P2 turnover. PMID:26203165

  9. An Adaptive Low-Cost GNSS/MEMS-IMU Tightly-Coupled Integration System with Aiding Measurement in a GNSS Signal-Challenged Environment

    PubMed Central

    Zhou, Qifan; Zhang, Hai; Li, You; Li, Zheng

    2015-01-01

    The main aim of this paper is to develop a low-cost GNSS/MEMS-IMU tightly-coupled integration system with aiding information that can provide reliable position solutions when the GNSS signal is challenged such that less than four satellites are visible in a harsh environment. To achieve this goal, we introduce an adaptive tightly-coupled integration system with height and heading aiding (ATCA). This approach adopts a novel redundant measurement noise estimation method for an adaptive Kalman filter application and also augments external measurements in the filter to aid the position solutions, as well as uses different filters to deal with various situations. On the one hand, the adaptive Kalman filter makes use of the redundant measurement system’s difference sequence to estimate and tune noise variance instead of employing a traditional innovation sequence to avoid coupling with the state vector error. On the other hand, this method uses the external height and heading angle as auxiliary references and establishes a model for the measurement equation in the filter. In the meantime, it also changes the effective filter online based on the number of tracked satellites. These measures have increasingly enhanced the position constraints and the system observability, improved the computational efficiency and have led to a good result. Both simulated and practical experiments have been carried out, and the results demonstrate that the proposed method is effective at limiting the system errors when there are less than four visible satellites, providing a satisfactory navigation solution. PMID:26393605

  10. An Adaptive Low-Cost GNSS/MEMS-IMU Tightly-Coupled Integration System with Aiding Measurement in a GNSS Signal-Challenged Environment.

    PubMed

    Zhou, Qifan; Zhang, Hai; Li, You; Li, Zheng

    2015-01-01

    The main aim of this paper is to develop a low-cost GNSS/MEMS-IMU tightly-coupled integration system with aiding information that can provide reliable position solutions when the GNSS signal is challenged such that less than four satellites are visible in a harsh environment. To achieve this goal, we introduce an adaptive tightly-coupled integration system with height and heading aiding (ATCA). This approach adopts a novel redundant measurement noise estimation method for an adaptive Kalman filter application and also augments external measurements in the filter to aid the position solutions, as well as uses different filters to deal with various situations. On the one hand, the adaptive Kalman filter makes use of the redundant measurement system's difference sequence to estimate and tune noise variance instead of employing a traditional innovation sequence to avoid coupling with the state vector error. On the other hand, this method uses the external height and heading angle as auxiliary references and establishes a model for the measurement equation in the filter. In the meantime, it also changes the effective filter online based on the number of tracked satellites. These measures have increasingly enhanced the position constraints and the system observability, improved the computational efficiency and have led to a good result. Both simulated and practical experiments have been carried out, and the results demonstrate that the proposed method is effective at limiting the system errors when there are less than four visible satellites, providing a satisfactory navigation solution. PMID:26393605

  11. A Fluorescent Live Imaging Screening Assay Based on Translocation Criteria Identifies Novel Cytoplasmic Proteins Implicated in G Protein-coupled Receptor Signaling Pathways.

    PubMed

    Lecat, Sandra; Matthes, Hans W D; Pepperkok, Rainer; Simpson, Jeremy C; Galzi, Jean-Luc

    2015-05-01

    Several cytoplasmic proteins that are involved in G protein-coupled receptor signaling cascades are known to translocate to the plasma membrane upon receptor activation, such as beta-arrestin2. Based on this example and in order to identify new cytoplasmic proteins implicated in the ON-and-OFF cycle of G protein-coupled receptor, a live-imaging screen of fluorescently labeled cytoplasmic proteins was performed using translocation criteria. The screening of 193 fluorescently tagged human proteins identified eight proteins that responded to activation of the tachykinin NK2 receptor by a change in their intracellular localization. Previously we have presented the functional characterization of one of these proteins, REDD1, that translocates to the plasma membrane. Here we report the results of the entire screening. The process of cell activation was recorded on videos at different time points and all the videos can be visualized on a dedicated website. The proteins BAIAP3 and BIN1, partially translocated to the plasma membrane upon activation of NK2 receptors. Proteins ARHGAP12 and PKM2 translocated toward membrane blebs. Three proteins that associate with the cytoskeleton were of particular interest : PLEKHH2 rearranged from individual dots located near the cell-substrate adhesion surface into lines of dots. The speriolin-like protein, SPATC1L, redistributed to cell-cell junctions. The Chloride intracellular Channel protein, CLIC2, translocated from actin-enriched plasma membrane bundles to cell-cell junctions upon activation of NK2 receptors. CLIC2, and one of its close paralogs, CLIC4, were further shown to respond with the same translocation pattern to muscarinic M3 and lysophosphatidic LPA receptors. This screen allowed us to identify potential actors in signaling pathways downstream of G protein-coupled receptors and could be scaled-up for high-content screening. PMID:25759509

  12. Angiotensin II receptor subtypes are coupled with distinct signal-transduction mechanisms in neurons and astrocytes from rat brain

    SciTech Connect

    Sumners, C.; Wei Tang; Zelezna, B.; Raizada, M.K. )

    1991-09-01

    Both neurons and astrocytes contain specific receptors for angiotensin II (AII). The authors used selective ligands for the AT{sub 1} and AT{sub 2} types of AII receptors to investigate the expression of functional receptor subtypes in astrocyte cultures and neuron cultures from 1-day-old (neonatal) rat brain. In astrocyte cultures, competition of {sup 125}I-labeled AII ({sup 125}I-AII) specific binding with AT{sub 1} (DuP753) or AT{sub 2} {l brace}PD123177, CGP42112A, (Phe(p-NH{sub 2}){sup 6})AII{r brace} selective receptor ligands revealed a potency series of AII > DuP753 > > > CGP42112A > (Phe(p-NH{sub 2}){sup 6})AII > PD123177. These results suggest a predominance of the AT{sub 1} receptor subtype in neonatal astrocytes. {sup 125}I-AII specific binding to neonate neuronal cultures was reduced 73-84% by 1 {mu} MPD123177, and the residual {sup 125}I-AII specific binding was eliminated by DuP753. The results suggest that astrocyte cultures from neonatal rat brains contain predominantly AT{sub 1} receptors that are coupled to a stimulation of inositophospholipid hydrolysis. In contrast, neuron cultures from neonatal rat brain contain mostly AT{sub 2} receptors that are coupled to a reduction in basal cGMP levels, but a smaller population of AT{sub 1} receptors is also present in these neurons.

  13. Coincident signalling between the Gi/Go-coupled delta-opioid receptor and the Gq-coupled m3 muscarinic receptor at the level of intracellular free calcium in SH-SY5Y cells.

    PubMed

    Yeo, A; Samways, D S; Fowler, C E; Gunn-Moore, F; Henderson, G

    2001-03-01

    In SH-SY5Y cells, activation of delta-opioid receptors with [D-Pen(2,5)]-enkephalin (DPDPE; 1 microM) did not alter the intracellular free Ca(2+) concentration [Ca(2+)](i). However, when DPDPE was applied during concomitant Gq-coupled m3 muscarinic receptor stimulation by carbachol or oxotremorine-M, it produced an elevation of [Ca(2+)](i). The DPDPE-evoked increase in [Ca(2+)](i) was abolished when the carbachol-sensitive intracellular Ca(2+) store was emptied. There was a marked difference between the concentration-response relationship for the elevation of [Ca(2+)](i) by carbachol (EC(50) 13 microM, Hill slope 1) and the concentration-response relationship for carbachol's permissive action in revealing the delta-opioid receptor-mediated elevation of [Ca(2+)] (EC(50) 0.7 mM; Hill slope 1.8). Sequestration of free G protein beta gamma dimers by transient transfection of cells with a beta gamma binding protein (residues 495-689 of the C terminal tail of G protein-coupled receptor kinase 2) reduced the ability of delta opioid receptor activation to elevate [Ca(2+)](i). However, DPDPE did not elevate either basal or oxotremorine-M-evoked inositol phosphate production indicating that delta-opioid receptor activation did not stimulate phospholipase C. Furthermore, delta-opioid receptor activation did not result in the reversal of muscarinic receptor desensitization, membrane hyperpolarization or stimulation of sphingosine kinase. There was no coincident signalling between the delta-opioid receptor and the lysophosphatidic acid receptor which couples to elevation of [Ca(2+)](i) in SH-SY5Y cells by a PLC-independent mechanism. In SH-SY5Y cells the coincident signalling between the endogenously expressed delta-opioid and m3 muscarinic receptors appears to occur in the receptor activation-Ca(2+) release signalling pathway at a step after the activation of phospholipase C. PMID:11259487

  14. Novel reciprocal regulation of cAMP signaling and apoptosis by orphan G-protein-coupled receptor GPRC5A gene expression

    SciTech Connect

    Hirano, Minoru; Zang, Liqing; Oka, Takehiko; Ito, Yoshiyuki; Shimada, Yasuhito; Nishimura, Yuhei; Tanaka, Toshio . E-mail: tanaka@doc.medic.mie-u.ac.jp

    2006-12-08

    GPRC5A is a member of G-protein-coupled receptors, which was originally identified as an all-trans-retinoic acid-induced gene. Although recent studies reported that this gene was highly expressed in the cancer cell lines and that GPRC5A might positively regulate cell proliferation, its mechanism remains unknown. We investigated the upstream and downstream signaling of GPRC5A and its biological function, and found that cAMP signaling is the novel GPRC5A induction pathway. When GPRC5A gene was overexpressed, intracellular cAMP concentration was decreased, and Gs{alpha} gene expression was downregulated. On the other hand, RNA interference of GPRC5A increased mRNA levels of Gs{alpha} and intracellular cAMP, reduced cell number, and induced apoptosis. Conversely, cell number was increased by GPRC5A overexpression. We first report the novel negative feedback model of cAMP signaling through GPRC5A gene expression. This evidence explains one of the mechanisms of the GPRC5A-regulated cell growth in some cancer cell lines.

  15. Bright Fluorescence Monitoring System Utilizing Zoanthus sp. Green Fluorescent Protein (ZsGreen) for Human G-Protein-Coupled Receptor Signaling in Microbial Yeast Cells

    PubMed Central

    Nakamura, Yasuyuki; Ishii, Jun; Kondo, Akihiko

    2013-01-01

    G-protein-coupled receptors (GPCRs) are currently the most important pharmaceutical targets for drug discovery because they regulate a wide variety of physiological processes. Consequently, simple and convenient detection systems for ligands that regulate the function of GPCR have attracted attention as powerful tools for new drug development. We previously developed a yeast-based fluorescence reporter ligand detection system using flow cytometry. However, using this conventional detection system, fluorescence from a cell expressing GFP and responding to a ligand is weak, making detection of these cells by fluorescence microscopy difficult. We here report improvements to the conventional yeast fluorescence reporter assay system resulting in the development of a new highly-sensitive fluorescence reporter assay system with extremely bright fluorescence and high signal-to-noise (S/N) ratio. This new system allowed the easy detection of GPCR signaling in yeast using fluorescence microscopy. Somatostatin receptor and neurotensin receptor (implicated in Alzheimer’s disease and Parkinson’s disease, respectively) were chosen as human GPCR(s). The facile detection of binding to these receptors by cognate peptide ligands was demonstrated. In addition, we established a highly sensitive ligand detection system using yeast cell surface display technology that is applicable to peptide screening, and demonstrate that the display of various peptide analogs of neurotensin can activate signaling through the neurotensin receptor in yeast cells. Our system could be useful for identifying lead peptides with agonistic activity towards targeted human GPCR(s). PMID:24340008

  16. Quantitative phosphoproteomic analysis of signaling downstream of the prostaglandin e2/g-protein coupled receptor in human synovial fibroblasts: potential antifibrotic networks.

    PubMed

    Gerarduzzi, Casimiro; He, QingWen; Antoniou, John; Di Battista, John A

    2014-11-01

    The Prostaglandin E2 (PGE2) signaling mechanism within fibroblasts is of growing interest as it has been shown to prevent numerous fibrotic features of fibroblast activation with limited evidence of downstream pathways. To understand the mechanisms of fibroblasts producing tremendous amounts of PGE2 with autocrine effects, we apply a strategy of combining a wide-screening of PGE2-induced kinases with quantitative phosphoproteomics. Our large-scale proteomic approach identified a PKA signal transmitted through phosphorylation of its substrates harboring the R(R/X)X(S*/T*) motif. We documented 115 substrates, of which 72 had 89 sites with a 2.5-fold phosphorylation difference in PGE2-treated cells than in untreated cells, where approximately half of such sites were defined as being novel. They were compiled by networking software to focus on highlighted activities and to associate them with a functional readout of fibroblasts. The substrates were associated with a variety of cellular functions including cytoskeletal structures (migration/motility), regulators of G-protein coupled receptor function, protein kinases, and transcriptional/translational regulators. For the first time, we extended the PGE2 pathway into an elaborate network of interconnecting phosphoproteins, providing vital information to a once restricted signalosome. These data provide new insights into eicosanoid-initiated cell signaling with regards to the regulation of fibroblast activation and the identification of new targets for evidenced-based pharmacotherapy against fibrosis. PMID:25223752

  17. Ccr4-Not Regulates RNA Polymerase I Transcription and Couples Nutrient Signaling to the Control of Ribosomal RNA Biogenesis

    PubMed Central

    Laribee, R. Nicholas; Hosni-Ahmed, Amira; Workman, Jason J.; Chen, Hongfeng

    2015-01-01

    Ribosomal RNA synthesis is controlled by nutrient signaling through the mechanistic target of rapamycin complex 1 (mTORC1) pathway. mTORC1 regulates ribosomal RNA expression by affecting RNA Polymerase I (Pol I)-dependent transcription of the ribosomal DNA (rDNA) but the mechanisms involved remain obscure. This study provides evidence that the Ccr4-Not complex, which regulates RNA Polymerase II (Pol II) transcription, also functions downstream of mTORC1 to control Pol I activity. Ccr4-Not localizes to the rDNA and physically associates with the Pol I holoenzyme while Ccr4-Not disruption perturbs rDNA binding of multiple Pol I transcriptional regulators including core factor, the high mobility group protein Hmo1, and the SSU processome. Under nutrient rich conditions, Ccr4-Not suppresses Pol I initiation by regulating interactions with the essential transcription factor Rrn3. Additionally, Ccr4-Not disruption prevents reduced Pol I transcription when mTORC1 is inhibited suggesting Ccr4-Not bridges mTORC1 signaling with Pol I regulation. Analysis of the non-essential Pol I subunits demonstrated that the A34.5 subunit promotes, while the A12.2 and A14 subunits repress, Ccr4-Not interactions with Pol I. Furthermore, ccr4Δ is synthetically sick when paired with rpa12Δ and the double mutant has enhanced sensitivity to transcription elongation inhibition suggesting that Ccr4-Not functions to promote Pol I elongation. Intriguingly, while low concentrations of mTORC1 inhibitors completely inhibit growth of ccr4Δ, a ccr4Δ rpa12Δ rescues this growth defect suggesting that the sensitivity of Ccr4-Not mutants to mTORC1 inhibition is at least partially due to Pol I deregulation. Collectively, these data demonstrate a novel role for Ccr4-Not in Pol I transcriptional regulation that is required for bridging mTORC1 signaling to ribosomal RNA synthesis. PMID:25815716

  18. Nicotine, alcohol and cocaine coupling to reward processes via endogenous morphine signaling: the dopamine-morphine hypothesis.

    PubMed

    Stefano, George B; Bianchi, Enrica; Guarna, Massimo; Fricchione, Gregory L; Zhu, Wei; Cadet, Patrick; Mantione, Kirk J; Casares, Federico M; Kream, Richard M; Esch, Tobias

    2007-06-01

    Pleasure is described as a state or feeling of happiness and satisfaction resulting from an experience that one enjoys. We examine the neurobiological factors underlying reward processes and pleasure phenomena. With regard to possible negative effects of pleasure, we focus on addiction and motivational toxicity. Pleasure can serve cognition, productivity and health, but simultaneously promotes addiction and other negative behaviors. It is a complex neurobiological phenomenon, relying on reward circuitry or limbic activity. These processes involve dopaminergic signaling. Moreover, nicotine, cocaine and alcohol appear to exert their pleasure providing action via endogenous morphinergic mechanisms. Natural rewarding activities are necessary for survival and appetitive motivation, usually governing beneficial biological behaviors like eating, sex and reproduction. Social contacts can further facilitate the positive effects exerted by pleasurable experiences. However, artificial stimulants can be detrimental, since flexibility and normal control of behavior are deteriorated. Additionally, addictive drugs are capable of directly acting on reward pathways, now, in part, via endogenous morphine processes. PMID:17534245

  19. Activator-inhibitor coupling between Rho signaling and actin assembly make the cell cortex an excitable medium

    PubMed Central

    Bement, William M.; Leda, Marcin; Moe, Alison M.; Kita, Angela M.; Larson, Matthew E.; Golding, Adriana E.; Pfeuti, Courtney; Su, Kuan-Chung; Miller, Ann L.; Goryachev, Andrew B.; von Dassow, George

    2016-01-01

    Animal cell cytokinesis results from patterned activation of the small GTPase Rho, which directs assembly of actomyosin in the equatorial cortex. Cytokinesis is restricted to a portion of the cell cycle following anaphase onset in which the cortex is responsive to signals from the spindle. We show that shortly after anaphase onset oocytes and embryonic cells of frogs and echinoderms exhibit cortical waves of Rho activity and F-actin polymerization. The waves are modulated by cyclin-dependent kinase 1 (Cdk1) activity and require the Rho GEF (guanine nucleotide exchange factor), Ect2. Surprisingly, during wave propagation, while Rho activity elicits F-actin assembly, F-actin subsequently inactivates Rho. Experimental and modeling results show that waves represent excitable dynamics of a reaction diffusion system with Rho as the activator and F-actin the inhibitor. We propose that cortical excitability explains fundamental features of cytokinesis including its cell cycle regulation. PMID:26479320

  20. Activator-inhibitor coupling between Rho signalling and actin assembly makes the cell cortex an excitable medium.

    PubMed

    Bement, William M; Leda, Marcin; Moe, Alison M; Kita, Angela M; Larson, Matthew E; Golding, Adriana E; Pfeuti, Courtney; Su, Kuan-Chung; Miller, Ann L; Goryachev, Andrew B; von Dassow, George

    2015-11-01

    Animal cell cytokinesis results from patterned activation of the small GTPase Rho, which directs assembly of actomyosin in the equatorial cortex. Cytokinesis is restricted to a portion of the cell cycle following anaphase onset in which the cortex is responsive to signals from the spindle. We show that shortly after anaphase onset oocytes and embryonic cells of frogs and echinoderms exhibit cortical waves of Rho activity and F-actin polymerization. The waves are modulated by cyclin-dependent kinase 1 (Cdk1) activity and require the Rho GEF (guanine nucleotide exchange factor), Ect2. Surprisingly, during wave propagation, although Rho activity elicits F-actin assembly, F-actin subsequently inactivates Rho. Experimental and modelling results show that waves represent excitable dynamics of a reaction-diffusion system with Rho as the activator and F-actin the inhibitor. We propose that cortical excitability explains fundamental features of cytokinesis including its cell cycle regulation. PMID:26479320

  1. Coupling of a signal response domain in I kappa B alpha to multiple pathways for NF-kappa B activation.

    PubMed Central

    Brockman, J A; Scherer, D C; McKinsey, T A; Hall, S M; Qi, X; Lee, W Y; Ballard, D W

    1995-01-01

    The eukaryotic transcription factor NF-kappa B plays a central role in the induced expression of human immunodeficiency virus type 1 and in many aspects of the genetic program mediating normal T-cell activation and growth. The nuclear activity of NF-kappa B is tightly regulated from the cytoplasmic compartment by an inhibitory subunit called I kappa B alpha. This cytoplasmic inhibitor is rapidly phosphorylated and degraded in response to a diverse set of NF-kappa B-inducing agents, including T-cell mitogens, proinflammatory cytokines, and viral transactivators such as the Tax protein of human T-cell leukemia virus type 1. To explore these I kappa B alpha-dependent mechanisms for NF-kappa B induction, we identified novel mutants of I kappa B alpha that uncouple its inhibitory and signal-transducing functions in human T lymphocytes. Specifically, removal of the N-terminal 36 amino acids of I kappa B alpha failed to disrupt its ability to form latent complexes with NF-kappa B in the cytoplasm. However, this deletion mutation prevented the induced phosphorylation, degradative loss, and functional release of I kappa B alpha from NF-kappa B in Tax-expressing cells. Alanine substitutions introduced at two serine residues positioned within this N-terminal regulatory region of I kappa B alpha also yielded constitutive repressors that escaped from Tax-induced turnover and that potently inhibited immune activation pathways for NF-kappa B induction, including those initiated from antigen and cytokine receptors. In contrast, introduction of a phosphoserine mimetic at these sites rectified this functional defect, a finding consistent with a causal linkage between the phosphorylation status and proteolytic stability of this cytoplasmic inhibitor. Together, these in vivo studies define a critical signal response domain in I kappa B alpha that coordinately controls the biologic activities of I kappa B alpha and NF-kappa B in response to viral and immune stimuli. PMID:7739562

  2. A new optical method coupling light polarization and Vis-NIR spectroscopy to improve the measured absorbance signal's quality of soil samples.

    NASA Astrophysics Data System (ADS)

    Gobrecht, Alexia; Bendoula, Ryad; Roger, Jean-Michel; Bellon-Maurel, Véronique

    2014-05-01

    Visible - Near-infrared spectroscopy (Vis-NIRS) is now commonly used to measure different physical and chemical parameters of soils, including carbon content. However, prediction model accuracy is insufficient for Vis-NIRS to replace routine laboratory analysis. One of the biggest issues this technique is facing up to is light scattering due to soil particles. It causes departure in the assumed linear relationship between the Absorbance spectrum and the concentration of the chemicals of interest as stated by Beer-Lambert's Law, which underpins the calibration models. Therefore it becomes essential to improve the metrological quality of the measured signal in order to optimize calibration as light/matter interactions are at the basis of the resulting linear modeling. Optics can help to mitigate scattering effect on the signal. We put forward a new optical setup coupling linearly polarized light with a Vis-NIR spectrometer to free the measured spectra from multi-scattering effect. The corrected measured spectrum was then used to compute an Absorbance spectrum of the sample, using Dahm's Equation in the frame of the Representative Layer Theory. This method has been previously tested and validated on liquid (milk+ dye) and powdered (sand + dye) samples showing scattering (and absorbing) properties. The obtained Absorbance was a very good approximation of the Beer-Lambert's law absorbance. Here, we tested the method on a set of 54 soil samples to predict Soil Organic Carbon content. In order to assess the signal quality improvement by this method, we built and compared calibration models using Partial Least Square (PLS) algorithm. The prediction model built from new Absorbance spectrum outperformed the model built with the classical Absorbance traditionally obtained with Vis-NIR diffuse reflectance. This study is a good illustration of the high influence of signal quality on prediction model's performances.

  3. Serum Response Factor-GATA Ternary Complex Required for Nuclear Signaling by a G-Protein-Coupled Receptor

    PubMed Central

    Morin, Steves; Paradis, Pierre; Aries, Anne; Nemer, Mona

    2001-01-01

    Endothelins are a family of biologically active peptides that are critical for development and function of neural crest-derived and cardiovascular cells. These effects are mediated by two G-protein-coupled receptors and involve transcriptional regulation of growth-responsive and/or tissue-specific genes. We have used the cardiac ANF promoter, which represents the best-studied tissue-specific endothelin target, to elucidate the nuclear pathways responsible for the transcriptional effects of endothelins. We found that cardiac-specific response to endothelin 1 (ET-1) requires the combined action of the serum response factor (SRF) and the tissue-restricted GATA proteins which bind over their adjacent sites, within a 30-bp ET-1 response element. We show that SRF and GATA proteins form a novel ternary complex reminiscent of the well-characterized SRF-ternary complex factor interaction required for transcriptional induction of c-fos in response to growth factors. In transient cotransfections, GATA factors and SRF synergistically activate atrial natriuretic factor and other ET-1-inducible promoters that contain both GATA and SRF binding sites. Thus, GATA factors may represent a new class of tissue-specific SRF accessory factors that account for muscle- and other cell-specific SRF actions. PMID:11158291

  4. Actions of translocator protein ligands on neutrophil adhesion and motility induced by G-protein coupled receptor signaling.

    PubMed

    de Lima, Camila Bento; Tamura, Eduardo K; Montero-Melendez, Trindad; Palermo-Neto, João; Perretti, Mauro; Markus, Regina P; Farsky, Sandra Helena Poliselli

    2012-01-13

    The 18 kDa translocator protein (TSPO) also known as the peripheral benzodiazepine receptor (PBR), mediates the transportation of cholesterol and anions from the outer to the inner mitochondrial membrane in different cells types. Although recent evidences indicate a potential role for TSPO in the development of inflammatory processes, the mechanisms involved have not been elucidated. The present study investigated the ability of the specific TSPO ligands, the isoquinoline carboxamide PK11195 and benzodiazepine Ro5-4864, on neutrophil recruitment promoted by the N-formylmethionyl-leucyl-phenylalanine peptide (fMLP), an agonist of G-protein coupled receptor (GPCR). Pre-treatment with Ro5-4864 abrograted fMLP-induced leukocyte-endothelial interactions in mesenteric postcapillary venules in vivo. Moreover, in vitro Ro5-4864 treatment prevented fMLP-induced: (i) L-selectin shedding and overexpression of PECAM-1 on the neutrophil cell surface; (ii) neutrophil chemotaxis and (iii) enhancement of intracellular calcium cations (iCa(+2)). Intriguingly, the two latter effects were augmented by cell treatment with PK11195. An allosteric agonist/antagonist relation may be suggested, as the effects of Ro5-4864 on fMLP-stimulated neutrophils were reverted by simultaneous treatment with PK11195. Taken together, these data highlight TSPO as a modulator of pathways of neutrophil adhesion and locomotion induced by GPCR, connecting TSPO actions and the onset of an innate inflammatory response. PMID:22209795

  5. A G protein-coupled receptor with low density lipoprotein-binding motifs suggests a role for lipoproteins in G-linked signal transduction.

    PubMed Central

    Tensen, C P; Van Kesteren, E R; Planta, R J; Cox, K J; Burke, J F; van Heerikhuizen, H; Vreugdenhil, E

    1994-01-01

    We have isolated and analyzed a cDNA from the central nervous system of the mollusc Lymnaea stagnalis encoding a putative receptor, which might be a natural hybrid between two different classes of receptor proteins. Preceded by a signal peptide, two types of repeated sequences are present in the N-terminal part of the protein. The first repeat displays a high sequence similarity to the extracellular binding domains of the low density lipoprotein receptor, which binds and internalizes cholesterol-containing apolipoproteins. The second repeat and the C-terminal part of the Lymnaea receptor are very similar to regions of a specific class of guanine nucleotide-binding protein-coupled receptors, the mammalian glycoprotein hormone receptors. The mRNA encoding the receptor is predominantly expressed in a small number of neurons within the central nervous system and to a lesser extent in the heart. Images PMID:8197140

  6. Evidence that phospholipid turnover is the signal transducing system coupled to serotonin-S2 receptor sites

    SciTech Connect

    de Chaffoy de Courcelles, D.; Leysen, J.E.; De Clerck, F.; Van Belle, H.; Janssen, P.A.

    1985-06-25

    Upon stimulation with serotonin of washed human platelets prelabeled with (/sup 32/P)orthophosphate, the authors found an approximately 250% increase in (/sup 32/P)phosphatidic acid (PA) formation, a small decrease in (/sup 32/P)phosphatidylinositol 4,5-bisphosphate, and a concomitant increase in (/sup 32/P)phosphatidylinositol 4-phosphate. Using (/sup 3/H)arachidonate for prelabeling, (/sup 3/H)diacylglycerol accumulated transiently at 10 s after addition of the agonist, (/sup 3/H)PA increased but to a lower extent compared to /sup 32/P-labeled lipid, and the formation of both (/sup 3/H)polyphosphoinositides increased. The serotonin-induced dose-dependent changes in (/sup 32/P)PA correlate with its effect on the changes in slope of aggregation of platelets. The potency of 13 drugs to antagonize the serotonin-induced PA formation closely corresponds to both their potency to inhibit platelet aggregation and their binding affinity for serotonin-S2 receptor sites. It is suggested that at least part of the signal transducing system following activation of the serotonin-S2 receptors involves phospholipase C catalyzed inositol lipid breakdown yielding diacylglycerol which is subsequently phosphorylated to PA.

  7. Butyl benzyl phthalate blocks Ca{sup 2+} signaling coupled with purinoceptor in rat PC12 cells

    SciTech Connect

    Liu, P.-S. . E-mail: psliu@mail.scu.edu.tw; Chen, Y.-Y.

    2006-01-15

    Butyl benzyl phthalate (BBP) is a plasticizer and causes public concern because of its genomic estrogenic effects via estrogen receptors. We previously found that BBP has non-genomic effects, exerting inhibitory effects on the functional activities of nicotinic acetylcholine receptors (nAChR) in bovine adrenal chromaffin cells. nAChR belongs to the superfamily of neurotransmitter-gated channels, so does P2X purinoceptor that is widely distributed in the nervous system and play a role in pain reactions. In this study, we investigated the effects of BBP on the change of [Ca{sup 2+}]{sub c} (cytosolic calcium ion concentration) under the stimulation of purinoceptors in PC12 cells and found that BBP inhibited ATP-induced [Ca{sup 2+}]{sub c} rise (IC{sub 5} = 8.3 {mu}M). The inhibitory rate of BBP remained under the increase of ATP concentration; therefore, the possibility of competitive inhibition was excluded. The inhibition of BBP on P2Y was excluded because its inhibition on ATP-induced [Ca{sup 2+}]{sub c} rise was not found in the absence of extracellular Ca{sup 2+}. BBP might have some actions on voltage-operated Ca{sup 2+} channels (VOCCs) since BBP inhibited the Ca{sup 2+} signaling responding to high K{sup +} stimulation (IC{sub 5} = 1.2 {mu}M). We suggest that BBP inhibits the ATP-induced [Ca{sup 2+}]{sub c} rise via its non-competitive inhibition on P2X purinoceptors and VOCCs in the plasma membrane.

  8. Wnt/β-catenin coupled with HIF-1α/VEGF signaling pathways involved in galangin neurovascular unit protection from focal cerebral ischemia

    PubMed Central

    Wu, Chuanhong; Chen, Jianxin; Chen, Chang; Wang, Wei; Wen, Limei; Gao, Kuo; Chen, Xiuping; Xiong, Sihuai; Zhao, Huihui; Li, Shaojing

    2015-01-01

    Microenvironmental regulation has become a promising strategy for complex disease treatment. The neurovascular unit (NVU), as the key structural basis to maintain an optimal brain microenvironment, has emerged as a new paradigm to understand the pathology of stroke. In this study, we investigated the effects of galangin, a natural flavonoid isolated from the rhizome of Alpina officinarum Hance, on NVU microenvironment improvement and associated signal pathways in rats impaired by middle cerebral artery occlusion (MCAO). Galangin ameliorated neurological scores, cerebral infarct volume and cerebral edema and reduced the concentration of Evans blue (EB) in brain tissue. NVU ultrastructural changes were also improved by galangin. RT-PCR and western blot revealed that galangin protected NVUs through the Wnt/β-catenin pathway coupled with HIF-1α and vascular endothelial growth factor (VEGF). VEGF and β-catenin could be the key nodes of these two coupled pathways. In conclusion, Galangin might function as an anti-ischemic stroke drug by improving the microenvironment of NVUs. PMID:26537366

  9. Sex differences in the activity of signalling pathways and expression of G-protein-coupled receptor kinases in the neonatal ventral hippocampal lesion model of schizophrenia

    PubMed Central

    Bychkov, Evgeny; Ahmed, M. Rafiuddin; Gurevich, Eugenia V.

    2010-01-01

    Animals with the neonatal ventral hippocampal lesion (NVHL) demonstrate altered responsiveness to stress and various drugs reminiscent of that in schizophrenia. Post-pubertal onset of abnormalities suggests the possibility of sex differences in NVHL effects that may model sex differences in schizophrenia. Here we demonstrate that novelty- and MK-801-induced hyperactivity is evident in both male and female NVHL rats, whereas only NVHL males were hyperactive in response to apomorphine. Next, we examined the sex- and NVHL-dependent differences in the activity of the ERK and Akt pathways. The basal activity of both pathways was higher in females than in males. NVHL reduces the level of phosphorylation of ERK1/2, Akt, and GSK-3 in both sexes, although males show more consistent downregulation. Females had higher levels of G-protein-coupled kinases [G-protein-coupled receptor kinase (GRK)] 3 and 5, whereas the concentrations of other GRKs and arrestins were the same. In the nucleus accumbens, the concentration of GRK5 in females was elevated by NVHL to the male level. The data demonstrate profound sex differences in the expression and activity of signalling molecules that may underlie differential susceptibility to schizophrenia. PMID:20158934

  10. Cilostazol Modulates Autophagic Degradation of β-Amyloid Peptide via SIRT1-Coupled LKB1/AMPKα Signaling in Neuronal Cells

    PubMed Central

    Lee, Won Suk; Shin, Hwa Kyoung; Kim, Hye Young; Hong, Ki Whan; Kim, Chi Dae

    2016-01-01

    A neuroprotective role of autophagy mediates the degradation of β-amyloid peptide (Aβ) in Alzheimer’s disease (AD). The previous study showed cilostazol modulates autophagy by increasing beclin1, Atg5 and LC3-II expressions, and depletes intracellular Aβ accumulation. This study elucidated the mechanisms through which cilostazol modulates the autophagic degradation of Aβ in neurons. In N2a cells, cilostazol (10–30 μM), significantly increased the expression of P-AMPKα (Thr 172) and downstream P-ACC (acetyl-CoA carboxylase) (Ser 79) as did resveratrol (SIRT1 activator), or AICAR (AMPK activator), which were blocked by KT5720, compound C (AMPK inhibitor), or sirtinol. Furthermore, phosphorylated-mTOR (Ser 2448) and phosphorylated-P70S6K (Thr 389) expressions were suppressed, and LC3-II levels were elevated in association with decreased P62/Sqstm1 by cilostazol. Cilostazol increased cathepsin B activity and decreased p62/SQSTM 1, consequently decreased accumulation of Aβ1–42 in the activated N2aSwe cells, and these results were blocked by sirtinol, compound C and bafilomycin A1 (autophagosome blocker), suggesting enhanced autophagosome formation by cilostazol. In SIRT1 gene-silenced N2a cells, cilostazol failed to increase the expressions of P-LKB1 (Ser 428) and P-AMPKα, which contrasted with its effect in negative control cells transfected with scrambled siRNA duplex. Further, N2a cells transfected with expression vectors encoding pcDNA SIRT1 showed increased P-AMPKα expression, which mimicked the effect of cilostazol in N2a cells; suggesting cilostazol-stimulated expressions of P-LKB1 and P-AMPKα were SIRT1-dependent. Unlike their effects in N2a cells, in HeLa cells, which lack LKB1, cilostazol and resveratrol did not elevate SIRT1 or P-AMPKα expression, indicating cilostazol and resveratrol-stimulated expressions of SIRT1 and P-AMPKα are LKB1-dependent. In conclusion, cilostazol upregulates autophagy by activating SIRT1-coupled P-LKB1/P-AMPKα and

  11. Cilostazol Modulates Autophagic Degradation of β-Amyloid Peptide via SIRT1-Coupled LKB1/AMPKα Signaling in Neuronal Cells.

    PubMed

    Park, So Youn; Lee, Hye Rin; Lee, Won Suk; Shin, Hwa Kyoung; Kim, Hye Young; Hong, Ki Whan; Kim, Chi Dae

    2016-01-01

    A neuroprotective role of autophagy mediates the degradation of β-amyloid peptide (Aβ) in Alzheimer's disease (AD). The previous study showed cilostazol modulates autophagy by increasing beclin1, Atg5 and LC3-II expressions, and depletes intracellular Aβ accumulation. This study elucidated the mechanisms through which cilostazol modulates the autophagic degradation of Aβ in neurons. In N2a cells, cilostazol (10-30 μM), significantly increased the expression of P-AMPKα (Thr 172) and downstream P-ACC (acetyl-CoA carboxylase) (Ser 79) as did resveratrol (SIRT1 activator), or AICAR (AMPK activator), which were blocked by KT5720, compound C (AMPK inhibitor), or sirtinol. Furthermore, phosphorylated-mTOR (Ser 2448) and phosphorylated-P70S6K (Thr 389) expressions were suppressed, and LC3-II levels were elevated in association with decreased P62/Sqstm1 by cilostazol. Cilostazol increased cathepsin B activity and decreased p62/SQSTM 1, consequently decreased accumulation of Aβ1-42 in the activated N2aSwe cells, and these results were blocked by sirtinol, compound C and bafilomycin A1 (autophagosome blocker), suggesting enhanced autophagosome formation by cilostazol. In SIRT1 gene-silenced N2a cells, cilostazol failed to increase the expressions of P-LKB1 (Ser 428) and P-AMPKα, which contrasted with its effect in negative control cells transfected with scrambled siRNA duplex. Further, N2a cells transfected with expression vectors encoding pcDNA SIRT1 showed increased P-AMPKα expression, which mimicked the effect of cilostazol in N2a cells; suggesting cilostazol-stimulated expressions of P-LKB1 and P-AMPKα were SIRT1-dependent. Unlike their effects in N2a cells, in HeLa cells, which lack LKB1, cilostazol and resveratrol did not elevate SIRT1 or P-AMPKα expression, indicating cilostazol and resveratrol-stimulated expressions of SIRT1 and P-AMPKα are LKB1-dependent. In conclusion, cilostazol upregulates autophagy by activating SIRT1-coupled P-LKB1/P-AMPKα and

  12. Diffuse light reflectance signals as potential indicators of loss of viability in brain tissue due to hypoxia: charge-coupled-device-based imaging and fiber-based measurement

    NASA Astrophysics Data System (ADS)

    Kawauchi, Satoko; Nishidate, Izumi; Uozumi, Yoichi; Nawashiro, Hiroshi; Ashida, Hiroshi; Sato, Shunichi

    2013-01-01

    Brain tissue is highly vulnerable to ischemia/hypoxia, and real-time monitoring of its viability is important. By fiber-based measurements for rat brain, we previously observed a unique triphasic reflectance change (TRC) after a certain period of time after hypoxia. After TRC, rats could not be rescued, suggesting that TRC can be used as an indicator of loss of brain tissue viability. In this study, we investigated this diffuse-reflectance change due to hypoxia in three parts. First, we developed and validated a theoretical method to quantify changes in the absorption and reduced scattering coefficients involved in TRC. Second, we performed charge-coupled-device-based reflectance imaging of the rat brain during hypoxia followed by reoxygenation to examine spatiotemporal characteristics of the reflectance and its correlation with reversibility of brain tissue damage. Third, we made simultaneous imaging and fiber-based measurement of the reflectance for the rat to compare signals obtained by these two modalities. We observed a nontriphasic reflectance change by the imaging, and it was associated with brain tissue viability. We found that TRC measured by the fibers preceded the reflectance-signal change captured by the imaging. This time difference is attributable to the different observation depths in the brain with these two methods.

  13. Signalling couples hair follicle stem cell quiescence with reduced histone H3 K4/K9/K27me3 for proper tissue homeostasis

    PubMed Central

    Lee, Jayhun; Kang, Sangjo; Lilja, Karin C.; Colletier, Keegan J.; Scheitz, Cornelia Johanna Franziska; Zhang, Ying V.; Tumbar, Tudorita

    2016-01-01

    Mechanisms of plasticity to acquire different cell fates are critical for adult stem cell (SC) potential, yet are poorly understood. Reduced global histone methylation is an epigenetic state known to mediate plasticity in cultured embryonic SCs and T-cell progenitors. Here we find histone H3 K4/K9/K27me3 levels actively reduced in adult mouse skin and hair follicle stem cells (HFSCs) during G0 quiescence. The level of marks over specific gene promoters did not correlate to mRNA level changes in quiescent HFSCs. Skin hypomethylation during quiescence was necessary for subsequent progression of hair homeostasis (cycle). Inhibiting BMP signal, a known HFSC anti-proliferative factor, elevated HFSC methylation in vivo during quiescence prior to proliferation onset. Furthermore, removal of proliferation factors and addition of BMP4 reduced histone methylases and increased demethylases mRNAs in cultured skin epithelial cells. We conclude that signalling couples hair follicle stem cell quiescence with reduced H3 K4/K9/K27me3 levels for proper tissue homeostasis. PMID:27080563

  14. Recruitment of the adaptor protein Nck to PECAM-1 couples oxidative stress to canonical NF-κB signaling and inflammation.

    PubMed

    Chen, Jie; Leskov, Igor L; Yurdagul, Arif; Thiel, Bonnie; Kevil, Christopher G; Stokes, Karen Y; Orr, A Wayne

    2015-02-24

    Oxidative stress stimulates nuclear factor κB (NF-κB) activation and NF-κB-dependent proinflammatory gene expression in endothelial cells during several pathological conditions, including ischemia/reperfusion injury. We found that the Nck family of adaptor proteins linked tyrosine kinase signaling to oxidative stress-induced activation of NF-κB through the classic IκB kinase-dependent pathway. Depletion of Nck prevented oxidative stress induced by exogenous hydrogen peroxide or hypoxia/reoxygenation injury from activating NF-κB in endothelial cells, increasing the abundance of the proinflammatory molecules ICAM-1 (intracellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule-1) and recruiting leukocytes. Nck depletion also attenuated endothelial cell expression of genes encoding proinflammatory factors but not those encoding antioxidants. Nck promoted oxidative stress-induced activation of NF-κB by coupling the tyrosine phosphorylation of PECAM-1 (platelet endothelial cell adhesion molecule-1) to the activation of p21-activated kinase, which mediates oxidative stress-induced NF-κB signaling. Consistent with this mechanism, treatment of mice subjected to ischemia/reperfusion injury in the cremaster muscle with a Nck inhibitory peptide blocked leukocyte adhesion and emigration and the accompanying vascular leak. Together, these data identify Nck as an important mediator of oxidative stress-induced inflammation and a potential therapeutic target for ischemia/reperfusion injury. PMID:25714462

  15. Coupled High Speed Imaging and Seismo-Acoustic Recordings of Strombolian Explosions at Etna, July 2014: Implications for Source Processes and Signal Inversions.

    NASA Astrophysics Data System (ADS)

    Taddeucci, J.; Del Bello, E.; Scarlato, P.; Ricci, T.; Andronico, D.; Kueppers, U.; Cannata, A.; Sesterhenn, J.; Spina, L.

    2015-12-01

    Seismic and acoustic surveillance is routinely performed at several persistent activity volcanoes worldwide. However, interpretation of the signals associated with explosive activity is still equivocal, due to both source variability and the intrinsically limited information carried by the waves. Comparison and cross-correlation of the geophysical quantities with other information in general and visual recording in particular is therefore actively sought. At Etna (Italy) in July 2014, short-lived Strombolian explosions ejected bomb- to lapilli-sized, molten pyroclasts at a remarkably repeatable time interval of about two seconds, offering a rare occasion to systematically investigate the seismic and acoustic fields radiated by this common volcanic source. We deployed FAMoUS (FAst, MUltiparametric Setup for the study of explosive activity) at 260 meters from the vents, recording more than 60 explosions in thermal and visible high-speed videos (50 to 500 frames per second) and broadband seismic and acoustic instruments (1 to 10000 Hz for the acoustic and from 0.01 to 30 Hz for the seismic). Analysis of this dataset highlights nonlinear relationships between the exit velocity and mass of ejecta and the amplitude and frequency of the acoustic signals. It also allows comparing different methods to estimate source depth, and to validate existing theory on the coupling of airwaves with ground motion.

  16. Diffuse light reflectance signals as potential indicators of loss of viability in brain tissue due to hypoxia: charge-coupled-device-based imaging and fiber-based measurement.

    PubMed

    Kawauchi, Satoko; Nishidate, Izumi; Uozumi, Yoichi; Nawashiro, Hiroshi; Ashida, Hiroshi; Sato, Shunichi

    2013-01-01

    Brain tissue is highly vulnerable to ischemia/hypoxia, and real-time monitoring of its viability is important. By fiber-based measurements for rat brain, we previously observed a unique triphasic reflectance change (TRC) after a certain period of time after hypoxia. After TRC, rats could not be rescued, suggesting that TRC can be used as an indicator of loss of brain tissue viability. In this study, we investigated this diffuse-reflectance change due to hypoxia in three parts. First, we developed and validated a theoretical method to quantify changes in the absorption and reduced scattering coefficients involved in TRC. Second, we performed charge-coupled-device-based reflectance imaging of the rat brain during hypoxia followed by reoxygenation to examine spatiotemporal characteristics of the reflectance and its correlation with reversibility of brain tissue damage. Third, we made simultaneous imaging and fiber-based measurement of the reflectance for the rat to compare signals obtained by these two modalities. We observed a nontriphasic reflectance change by the imaging, and it was associated with brain tissue viability. We found that TRC measured by the fibers preceded the reflectance-signal change captured by the imaging. This time difference is attributable to the different observation depths in the brain with these two methods. PMID:23291715

  17. Indole-3-acetic acid biosensor based on G-rich DNA labeled AuNPs as chemiluminescence probe coupling the DNA signal amplification

    NASA Astrophysics Data System (ADS)

    Hun, Xu; Mei, Zhenghua; Wang, Zhouping; He, Yunhua

    2012-09-01

    A highly sensitive chemiluminescence (CL) method for detection of phytohormone indole-3-acetic acid (IAA) was developed by using G-rich DNA labeled gold nanoparticles (AuNPs) as CL probe coupling the DNA signal amplification technology. The IAA antibody was immobilized on carboxyl terminated magnetic beads (MBs). In the presence of IAA, antibody labeled AuNPs were captured by antibody functionalized MBs. The DNA on AuNPs is released by a ligand exchange process induced by the addition of DTT. The released DNA is then acted as the linker and hybridized with the capture DNA on MBs and probe DNA on AuNPs CL probe. The CL signal is obtained via the instantaneous derivatization reaction between a specific CL reagent, 3,4,5-trimethoxyl-phenylglyoxal (TMPG), and the G-rich DNA on AuNPs CL probe. IAA can be detected in the concentration range from 0.02 ng/mL to 30 ng/mL, and the limit of detection is 0.01 ng/mL.

  18. Improving Precision and Accuracy of Isotope Ratios from Short Transient Laser Ablation-Multicollector-Inductively Coupled Plasma Mass Spectrometry Signals: Application to Micrometer-Size Uranium Particles.

    PubMed

    Claverie, Fanny; Hubert, Amélie; Berail, Sylvain; Donard, Ariane; Pointurier, Fabien; Pécheyran, Christophe

    2016-04-19

    The isotope drift encountered on short transient signals measured by multicollector inductively coupled plasma mass spectrometry (MC-ICPMS) is related to differences in detector time responses. Faraday to Faraday and Faraday to ion counter time lags were determined and corrected using VBA data processing based on the synchronization of the isotope signals. The coefficient of determination of the linear fit between the two isotopes was selected as the best criterion to obtain accurate detector time lag. The procedure was applied to the analysis by laser ablation-MC-ICPMS of micrometer sized uranium particles (1-3.5 μm). Linear regression slope (LRS) (one isotope plotted over the other), point-by-point, and integration methods were tested to calculate the (235)U/(238)U and (234)U/(238)U ratios. Relative internal precisions of 0.86 to 1.7% and 1.2 to 2.4% were obtained for (235)U/(238)U and (234)U/(238)U, respectively, using LRS calculation, time lag, and mass bias corrections. A relative external precision of 2.1% was obtained for (235)U/(238)U ratios with good accuracy (relative difference with respect to the reference value below 1%). PMID:27031645

  19. Recruitment of the adaptor protein Nck to PECAM-1 couples oxidant stress to canonical NF-κB signaling and inflammation

    PubMed Central

    Chen, Jie; Leskov, Igor L.; Yurdagul, Arif; Thiel, Bonnie; Kevil, Christopher G.; Stokes, Karen Y.; Orr, A. Wayne

    2015-01-01

    Oxidant stress drives nuclear factor κB (NF-κB) activation and NF-κB-dependent proinflammatory gene expression in endothelial cells during several pathological conditions, including ischemia/reperfusion injury. We showed that the Nck family of adaptor proteins linked tyrosine kinase signaling to oxidant stress-induced activation of NF-κB through the classic IκB kinase (IKK)-dependent pathway. Depletion of Nck prevented oxidant stress induced by exogenous peroxide or hypoxia/reoxygenation injury from triggering the activation of NF-κB in endothelial cells, increases in the abundance of the pro-inflammatory molecules ICAM-1 (intracellular adhesion molecule 1) and VCAM-1 (vascular cell adhesion molecule 1), and leukocyte recruitment. Nck depletion also attenuated endothelial cell expression of genes encoding proinflammatory factors, but not those encoding antioxidants. We further showed that Nck promoted oxidant stress-induced activation of NF-κB by coupling the tyrosine phosphorylation of platelet-endothelial cell adhesion molecule-1 (PECAM-1) to the activation of p21 activated kinase, which mediates oxidant stress-induced NF-κB signaling. Consistent with this model, treatment of mice subjected to ischemia/reperfusion injury in the cremaster muscle with a Nck inhibitory peptide inhibited leukocyte adhesion and emigration and the accompanying vascular leak. Together, these data identify Nck as an important mediator of oxidant stress-induced inflammation and a potential therapeutic target for ischemia/reperfusion injury. PMID:25714462

  20. Signalling couples hair follicle stem cell quiescence with reduced histone H3 K4/K9/K27me3 for proper tissue homeostasis.

    PubMed

    Lee, Jayhun; Kang, Sangjo; Lilja, Karin C; Colletier, Keegan J; Scheitz, Cornelia Johanna Franziska; Zhang, Ying V; Tumbar, Tudorita

    2016-01-01

    Mechanisms of plasticity to acquire different cell fates are critical for adult stem cell (SC) potential, yet are poorly understood. Reduced global histone methylation is an epigenetic state known to mediate plasticity in cultured embryonic SCs and T-cell progenitors. Here we find histone H3 K4/K9/K27me3 levels actively reduced in adult mouse skin and hair follicle stem cells (HFSCs) during G0 quiescence. The level of marks over specific gene promoters did not correlate to mRNA level changes in quiescent HFSCs. Skin hypomethylation during quiescence was necessary for subsequent progression of hair homeostasis (cycle). Inhibiting BMP signal, a known HFSC anti-proliferative factor, elevated HFSC methylation in vivo during quiescence prior to proliferation onset. Furthermore, removal of proliferation factors and addition of BMP4 reduced histone methylases and increased demethylases mRNAs in cultured skin epithelial cells. We conclude that signalling couples hair follicle stem cell quiescence with reduced H3 K4/K9/K27me3 levels for proper tissue homeostasis. PMID:27080563

  1. The viral G protein-coupled receptor ORF74 unmasks phospholipase C signaling of the receptor tyrosine kinase IGF-1R.

    PubMed

    de Munnik, Sabrina M; van der Lee, Rosan; Velders, Daniëlle M; van Offenbeek, Jody; Smits-de Vries, Laura; Leurs, Rob; Smit, Martine J; Vischer, Henry F

    2016-06-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) encodes the constitutively active G protein-coupled receptor ORF74, which is expressed on the surface of infected host cells and has been linked to the development of the angioproliferative tumor Kaposi's sarcoma. Furthermore, the insulin-like growth factor (IGF)-1 receptor, a receptor tyrosine kinase, also plays an essential role in Kaposi's sarcoma growth and survival. In this study we examined the effect of the constitutively active viral receptor ORF74 on human IGF-1R signaling. Constitutive and CXCL1-induced ORF74 signaling did not transactivate IGF-1R. In contrast, IGF-1 stimulated phospholipase C (PLC) activation in an ORF74-dependent manner without affecting chemokine binding to ORF74. Inhibition of constitutive ORF74 activity by mutagenesis or the inverse agonist CXCL10, or neutralizing IGF-1R with an antibody or silencing IGF-1R expression using siRNA inhibited PLC activation by IGF-1. Transactivation of ORF74 in response to IGF-1 occurred independently of Src, PI3K, and secreted ORF74 ligands. Furthermore, tyrosine residues in the carboxyl-terminus and intracellular loop 2 of ORF74 are not essential for IGF-1-induced PLC activation. Interestingly, PLC activation in response to IGF-1 is specific for ORF74 as IGF-1 was unable to activate PLC in cells expressing the constitutively active human cytomegalovirus (HCMV)-encoded GPCR US28. Interestingly, IGF-1 does not induce β-arrestin recruitment to ORF74. The proximity ligation assay revealed close proximity between ORF74 and IGF-1R on the cell surface, but a physical interaction was not confirmed by co-immunoprecipitation. Unmasking IGF-1R signaling to PLC in response to IGF-1 is a previously unrecognized action of ORF74. PMID:26931381

  2. Protease-activated receptor 2 (PAR2) protein and transient receptor potential vanilloid 4 (TRPV4) protein coupling is required for sustained inflammatory signaling.

    PubMed

    Poole, Daniel P; Amadesi, Silvia; Veldhuis, Nicholas A; Abogadie, Fe C; Lieu, TinaMarie; Darby, William; Liedtke, Wolfgang; Lew, Michael J; McIntyre, Peter; Bunnett, Nigel W

    2013-02-22

    G protein-coupled receptors of nociceptive neurons can sensitize transient receptor potential (TRP) ion channels, which amplify neurogenic inflammation and pain. Protease-activated receptor 2 (PAR(2)), a receptor for inflammatory proteases, is a major mediator of neurogenic inflammation and pain. We investigated the signaling mechanisms by which PAR(2) regulates TRPV4 and determined the importance of tyrosine phosphorylation in this process. Human TRPV4 was expressed in HEK293 cells under control of a tetracycline-inducible promoter, allowing controlled and graded channel expression. In cells lacking TRPV4, the PAR(2) agonist stimulated a transient increase in [Ca(2+)](i). TRPV4 expression led to a markedly sustained increase in [Ca(2+)](i). Removal of extracellular Ca(2+) and treatment with the TRPV4 antagonists Ruthenium Red or HC067047 prevented the sustained response. Inhibitors of phospholipase A(2) and cytochrome P450 epoxygenase attenuated the sustained response, suggesting that PAR(2) generates arachidonic acid-derived lipid mediators, such as 5',6'-EET, that activate TRPV4. Src inhibitor 1 suppressed PAR(2)-induced activation of TRPV4, indicating the importance of tyrosine phosphorylation. The TRPV4 tyrosine mutants Y110F, Y805F, and Y110F/Y805F were expressed normally at the cell surface. However, PAR(2) was unable to activate TRPV4 with the Y110F mutation. TRPV4 antagonism suppressed PAR(2) signaling to primary nociceptive neurons, and TRPV4 deletion attenuated PAR(2)-stimulated neurogenic inflammation. Thus, PAR(2) activation generates a signal that induces sustained activation of TRPV4, which requires a key tyrosine residue (TRPV4-Tyr-110). This mechanism partly mediates the proinflammatory actions of PAR(2). PMID:23288842

  3. The ETS domain transcriptional repressor Anterior open inhibits MAP kinase and Wingless signaling to couple tracheal cell fate with branch identity.

    PubMed

    Caviglia, Sara; Luschnig, Stefan

    2013-03-01

    Cells at the tips of budding branches in the Drosophila tracheal system generate two morphologically different types of seamless tubes. Terminal cells (TCs) form branched lumenized extensions that mediate gas exchange at target tissues, whereas fusion cells (FCs) form ring-like connections between adjacent tracheal metameres. Each tracheal branch contains a specific set of TCs, FCs, or both, but the mechanisms that select between the two tip cell types in a branch-specific fashion are not clear. Here, we show that the ETS domain transcriptional repressor anterior open (aop) is dispensable for directed tracheal cell migration, but plays a key role in tracheal tip cell fate specification. Whereas aop globally inhibits TC and FC specification, MAPK signaling overcomes this inhibition by triggering degradation of Aop in tip cells. Loss of aop function causes excessive FC and TC specification, indicating that without Aop-mediated inhibition, all tracheal cells are competent to adopt a specialized fate. We demonstrate that Aop plays a dual role by inhibiting both MAPK and Wingless signaling, which induce TC and FC fate, respectively. In addition, the branch-specific choice between the two seamless tube types depends on the tracheal branch identity gene spalt major, which is sufficient to inhibit TC specification. Thus, a single repressor, Aop, integrates two different signals to couple tip cell fate selection with branch identity. The switch from a branching towards an anastomosing tip cell type may have evolved with the acquisition of a main tube that connects separate tracheal primordia to generate a tubular network. PMID:23444354

  4. Prunetin signals via G-protein-coupled receptor, GPR30(GPER1): Stimulation of adenylyl cyclase and cAMP-mediated activation of MAPK signaling induces Runx2 expression in osteoblasts to promote bone regeneration.

    PubMed

    Khan, Kainat; Pal, Subhashis; Yadav, Manisha; Maurya, Rakesh; Trivedi, Arun Kumar; Sanyal, Sabyasachi; Chattopadhyay, Naibedya

    2015-12-01

    Prunetin is found in red clover and fruit of Prunus avium (red cherry). The effect of prunetin on osteoblast function, its mode of action and bone regeneration in vivo were investigated. Cultures of primary osteoblasts, osteoblastic cell line and HEK293T cells were used for various in vitro studies. Adult female rats received drill-hole injury at the femur diaphysis to assess the bone regenerative effect of prunetin. Prunetin at 10nM significantly (a) increased proliferation and differentiation of primary cultures of osteoblasts harvested from rats and (b) promoted formation of mineralized nodules by bone marrow stromal/osteoprogenitor cells. At this concentration, prunetin did not activate any of the two nuclear estrogen receptors (α and β). However, prunetin triggered signaling via a G-protein-coupled receptor, GPR30/GPER1, and enhanced cAMP levels in osteoblasts. G15, a selective GPR30 antagonist, abolished prunetin-induced increases in osteoblast proliferation, differentiation and intracellular cAMP. In osteoblasts, prunetin up-regulated runt-related transcription factor 2 (Runx2) protein through cAMP-dependent Erk/MAP kinase activation that ultimately resulted in the up-regulation of GPR30. Administration of prunetin at 0.25mg/kg given to rats stimulated bone regeneration at the site of drill hole and up-regulated Runx2 expression in the fractured callus and the effect was comparable to human parathyroid hormone, the only clinically used osteogenic therapy. We conclude that prunetin promotes osteoinduction in vivo and the mechanism is defined by signaling through GPR30 resulting in the up-regulation of the key osteogenic gene Runx2 that in turn up-regulates GPR30. PMID:26345541

  5. Adenosine A1 receptors heterodimerize with β1- and β2-adrenergic receptors creating novel receptor complexes with altered G protein coupling and signaling.

    PubMed

    Chandrasekera, P Charukeshi; Wan, Tina C; Gizewski, Elizabeth T; Auchampach, John A; Lasley, Robert D

    2013-04-01

    G protein coupled receptors play crucial roles in mediating cellular responses to external stimuli, and increasing evidence suggests that they function as multiple units comprising homo/heterodimers and hetero-oligomers. Adenosine and β-adrenergic receptors are co-expressed in numerous tissues and mediate important cellular responses to the autocoid adenosine and sympathetic stimulation, respectively. The present study was undertaken to examine whether adenosine A1ARs heterodimerize with β1- and/or β2-adrenergic receptors (β1R and β2R), and whether such interactions lead to functional consequences. Co-immunoprecipitation and co-localization studies with differentially epitope-tagged A1, β1, and β2 receptors transiently co-expressed in HEK-293 cells indicate that A1AR forms constitutive heterodimers with both β1R and β2R. This heterodimerization significantly influenced orthosteric ligand binding affinity of both β1R and β2R without altering ligand binding properties of A1AR. Receptor-mediated ERK1/2 phosphorylation significantly increased in cells expressing A1AR/β1R and A1AR/β2R heteromers. β-Receptor-mediated cAMP production was not altered in A1AR/β1R expressing cells, but was significantly reduced in the A1AR/β2R cells. The inhibitory effect of the A1AR on cAMP production was abrogated in both A1AR/β1R and A1AR/β2R expressing cells in response to the A1AR agonist CCPA. Co-immunoprecipitation studies conducted with human heart tissue lysates indicate that endogenous A1AR, β1R, and β2R also form heterodimers. Taken together, our data suggest that heterodimerization between A1 and β receptors leads to altered receptor pharmacology, functional coupling, and intracellular signaling pathways. Unique and differential receptor cross-talk between these two important receptor families may offer the opportunity to fine-tune crucial signaling responses and development of more specific therapeutic interventions. PMID:23291003

  6. Arsenite and Cadmium Activate MAPK/ERK via Membrane Estrogen Receptors and G-Protein Coupled Estrogen Receptor Signaling in Human Lung Adenocarcinoma Cells.

    PubMed

    Huff, Mary O; Todd, Sarah L; Smith, Aaron L; Elpers, Julie T; Smith, Alexander P; Murphy, Robert D; Bleser-Shartzer, Allison S; Hoerter, Jacob E; Radde, Brandie N; Klinge, Carolyn M

    2016-07-01

    Epidemiological evidence indicates that cadmium and arsenic exposure increase lung cancer risk. Cadmium and arsenic are environmental contaminants that act as endocrine disruptors (EDs) by activating estrogen receptors (ERs) in breast and other cancer cell lines but their activity as EDs in lung cancer is untested. Here, we examined the effect of cadmium chloride (CdCl2) and sodium arsenite (NaAsO2) on the proliferation of human lung adenocarcinoma cell lines. Results demonstrated that both CdCl2 and NaAsO2 stimulated cell proliferation at environmentally relevant nM concentrations in a similar manner to 17β-estradiol (E2) in H1793, H2073, and H1944 cells but not in H1792 or H1299 cells. Further studies in H1793 cells showed that 100 nM CdCl2 and NaAsO2 rapidly stimulated mitogen-activated protein kinase (MAPK, extracellular-signal-regulated kinases) phosphorylation with a peak detected at 15 min. Inhibitor studies suggest that rapid MAPK phosphorylation by NaAsO2, CdCl2, and E2 involves ER, Src, epidermal growth factor receptor, and G-protein coupled ER (GPER) in a pertussis toxin-sensitive pathway. CdCl2 and E2 activation of MAPK may also involve ERβ. This study supports the involvement of membrane ER and GPER signaling in mediating cellular responses to environmentally relevant nM concentrations of CdCl2 and NaAsO2 in lung adenocarcinoma cells. PMID:27071941

  7. δ-Opioid receptors stimulate the metabolic sensor AMP-activated protein kinase through coincident signaling with G(q/11)-coupled receptors.

    PubMed

    Olianas, Maria C; Dedoni, Simona; Olianas, Alessandra; Onali, Pierluigi

    2012-02-01

    AMP-activated protein kinase (AMPK) and δ-opioid receptors (DORs) are both involved in controlling cell survival, energy metabolism, and food intake, but little is known on the interaction between these two signaling molecules. Here we show that activation of human DORs stably expressed in Chinese hamster ovary (CHO) cells increased AMPK activity and AMPK phosphorylation on Thr172. DOR-induced AMPK phosphorylation was prevented by pertussis toxin, reduced by protein kinase A (PKA) activators, and unaffected by PKA, transforming growth factor-β-activated kinase 1, mitogen-activated protein kinase, and protein kinase C inhibitors. Conversely, the DOR effect was reduced by Ca(2+)/calmodulin-dependent protein kinase kinase (CaMKK) inhibition, apyrase treatment, G(q/11) antagonism, and blockade of P2 purinergic receptors. Apyrase treatment also depressed DOR stimulation of intracellular Ca(2+) concentration, whereas P2 receptor antagonism blocked DOR stimulation of inositol phosphate accumulation. In SH-SY5Y neuroblastoma cells and primary olfactory bulb neurons, DOR activation failed to affect AMPK phosphorylation per se but potentiated the stimulation by either muscarinic agonists or 2-methyl-thio-ADP. Sequestration of G protein βγ subunits (Gβγ) blocked the DOR potentiation of AMPK phosphorylation induced by oxotremorine-M. In CHO cells, the AMPK activator 5-aminoimidazole-4-carboxamide1-β-D-ribonucleoside stimulated AMPK phosphorylation and glucose uptake, whereas pharmacological inhibition of AMPK, expression of a dominant-negative mutant of AMPKα1, and P2Y receptor blockade reduced DOR-stimulated glucose uptake. The data indicate that in different cell systems, DOR activation up-regulates AMPK through a Gβγ-dependent synergistic interaction with G(q/11)-coupled receptors, potentiating Ca(2+) release and CaMKKβ-dependent AMPK phosphorylation. In CHO cells, this coincident signaling mechanism is involved in DOR-induced glucose uptake. PMID:22031472

  8. Specificity of g protein-coupled receptor kinase 6-mediated phosphorylation and regulation of single-cell m3 muscarinic acetylcholine receptor signaling.

    PubMed

    Willets, Jonathon M; Mistry, Rajendra; Nahorski, Stefan R; Challiss, R A John

    2003-11-01

    Previously we have shown that G protein-coupled receptor kinase (GRK) 6 plays a major role in the regulation of the human M3 muscarinic acetylcholine receptor (M3 mAChR) in the human neuroblastoma SH-SY5Y. However, 30-fold overexpression of the catalytically inactive, dominant-negative K215RGRK6 produced only a 50% suppression of M3 mAChR phosphorylation and desensitization. Here, we have attempted to determine whether other endogenous kinases play a role in the regulation of M3 mAChR signaling. In contrast to the clear attenuating effect of K215RGRK6 expression on M3 mAChR regulation, dominant-negative forms of GRKs (K220RGRK2, K220RGRK3, K215RGRK5) and casein kinase 1alpha (K46RCK1alpha) were without effect. In addition, inhibition of a variety of second-messenger-regulated kinases and the tyrosine kinase Src also had no effect upon agonist-stimulated M3 mAChR regulation. To investigate further the desensitization process we have followed changes in inositol 1,4,5-trisphosphate in single SHSY5Y cells using the pleckstrin homology domain of PLCdelta1 tagged with green fluorescent protein (eGFP-PHPLCdelta1). Stimulation of cells with approximate EC50 concentrations of agonist before and after a desensitizing period of agonist exposure resulted in a marked attenuation of the latter response. Altered GRK6 activity, through overexpression of wild-type GRK6 or K215RGRK6, enhanced or reduced the degree of M3 mAChR desensitization, respectively. Taken together, our data indicate that M3 mAChR desensitization is mediated by GRK6 in human SH-SY5Y cells, and we show that receptor desensitization of phospholipase C signaling can be monitored in 'real-time' in single, living cells. PMID:14573754

  9. Highly Sensitive and Selective Photoelectrochemical Biosensor for Hg(2+) Detection Based on Dual Signal Amplification by Exciton Energy Transfer Coupled with Sensitization Effect.

    PubMed

    Zhao, Ming; Fan, Gao-Chao; Chen, Jing-Jia; Shi, Jian-Jun; Zhu, Jun-Jie

    2015-12-15

    A highly sensitive and selective photoelectrochemical (PEC) biosensor for Hg(2+) detection was developed on the basis of the synergistic effect of exciton energy transfer (EET) between CdS quantum dots (QDs) and Au nanoparticles (NPs) coupled with sensitization of rhodamine 123 (Rh123) for signal amplification. First, the TiO2/CdS hybrid structure obtained by depositing CdS QDs on TiO2 film was employed as a matrix for immobilizing probe DNA (pDNA). Next, Rh123 was introduced into the pDNA terminal, and then Au NP labeled target DNA (Au-tDNA) was hybridized with pDNA to form a rod-like double helix structure. The detection of Hg(2+) was based on a conformational change of the pDNA after incubating with Hg(2+). In the absence of Hg(2+), Rh123 was located away from the electrode surface due to the DNA hybridization, leading to inhibition of the sensitization effect, and meanwhile, the occurrence of EET between CdS QDs and Au NPs resulted in a photocurrent decrease. However, after incubating with Hg(2+), the rod-like double helix was disrupted, and the energy transfer was broken. In this case, the photocurrent recovered, and meanwhile, the folded pDNA made the labeled Rh123 move closer to the electrode surface, leading to the formation of the sensitization structure, which evidently increased the photocurrent intensity. The sensitivity of the biosensor for Hg(2+) detection was greatly enhanced for the dual signal amplification strategy. The linear range was 10 fM to 200 nM, with a detection limit of 3.3 fM. This biosensor provides a promising new platform for detecting various heavy metal ions at ultralow levels. PMID:26599580

  10. G protein-coupled receptor 30 mediates estrogen-induced proliferation of primordial germ cells via EGFR/Akt/β-catenin signaling pathway.

    PubMed

    Ge, Chutian; Yu, Minli; Zhang, Caiqiao

    2012-07-01

    In vertebrates, estrogens are required for the normal development and function of postnatal gonads. However, it remains unclear whether estrogens are able to modulate development of the fetal germ cells. Here, we show that, unexpectedly, chicken primordial germ cells (PGC) lacking estrogen receptor α/β still proliferate in response to 17β-estradiol (E(2)). This is due to the capacity of G protein-coupled receptor 30 (GPR30), existing on PGC, to directly bind E(2). Knockdown experiments suggest that GPR30 is required for E(2)-stimulated PGC proliferation. Furthermore, this estrogen-induced activation of GPR30 is revealed to occur through the Gβγ-subunit protein-dependent and through the matrix metalloproteinase-dependent transactivation of the epidermal growth factor receptor. Epidermal growth factor receptor activation results in a series of intracellular events, including activation of the phosphatidylinositol 3-kinase/serine-threonine kinase/β-catenin pathway, which are followed by the induction of c-fos, c-myc, cyclin D1/E, and B-cell lymphoma 2 expression, and the inhibition of B-cell lymphoma 2-associated X protein expression and caspase3/9 activity. This eventually leads to decreased apoptosis and increased PGC proliferation. Collectively, these findings offer novel insights into the dynamic mechanism of estrogen action on PGC proliferation and suggest that E(2)/GPR30 signaling might play an important role in regulating fetal germ cell development, particularly at the stage before sexual differentiation. PMID:22635679

  11. G-protein-coupled receptor cell signaling pathways mediating embryonic chick retinal growth cone collapse induced by lysophosphatidic acid and sphingosine-1-phosphate.

    PubMed

    Fincher, Jarod; Whiteneck, Canaan; Birgbauer, Eric

    2014-01-01

    In the development of the nervous system, one of the critical aspects is the proper navigation of axons to their targets, i.e. the problem of axonal guidance. We used the chick visual system as a model to investigate the role of the lysophospholipids lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) as potential axon guidance cues. We showed that both LPA and S1P cause a specific, dose-dependent growth cone collapse of retinal neurons in vitro in the chick model system, with slight differences compared to the mouse but very similar to observations in Xenopus. Because LPA and S1P receptors are G-protein-coupled receptors, we analyzed the intracellular signaling pathways using pharmacological inhibitors in chick retinal neurons. Blocking rho kinase (ROCK) prevented growth cone collapse by LPA and S1P, while blocking PLC or chelating calcium had no effect on growth cone collapse. Inhibition of Gi/o with pertussis toxin resulted in a partial reduction of growth cone collapse, both with LPA and with S1P. Inhibition of p38 blocked growth cone collapse mediated by LPA but not S1P. Thus, in addition to the involvement of the G12/13-ROCK pathway, LPA- and S1P-induced collapse of chick retinal growth cones has a partial requirement for Gi/o. PMID:25138637

  12. G protein-coupled receptor 30 ligand G-1 increases aryl hydrocarbon receptor signalling by inhibition of tubulin assembly and cell cycle arrest in human MCF-7 cells.

    PubMed

    Tarnow, Patrick; Tralau, Tewes; Luch, Andreas

    2016-08-01

    Regulatory crosstalk between the aryl hydrocarbon receptor (AHR) and oestrogen receptor α (ERα) is well established. Apart from the nuclear receptors ERα and ERβ, oestrogen signalling further involves an unrelated G protein-coupled receptor termed GPR30. In order to investigate potential regulatory crosstalk, this study investigated the influence of G-1 as one of the few GPR30-specific ligands on the AHR regulon in MCF-7 cells. As a well-characterised model system, these human mammary carcinoma cells co-express all three receptors (AHR, ERα and GPR30) and are thus ideally suited to study corresponding regulatory pathway interactions on transcript level. Indeed, treatment with micromolar concentrations of the GPR30-specific agonist G-1 resulted in up-regulation of AHR as well as the transcripts for cytochromes P450 1A1 and 1B1, two well-known targets of the AHR regulon. While this was partly attributable to G-1-mediated inhibition of tubulin assembly and subsequent cell cycle arrest in the G2/M phase, the effects nevertheless required functional AHR. However, G-1-induced up-regulation of CYP 1A1 was not mediated by GPR30, as G15 antagonist treatment as well as a knockdown of GPR30 and AHR failed to inhibit this effect. PMID:26475489

  13. Signaling through the G-protein-coupled receptor Rickets is important for polarity, detachment, and migration of the border cells in Drosophila.

    PubMed

    Anllo, Lauren; Schüpbach, Trudi

    2016-06-15

    Cell migration plays crucial roles during development. An excellent model to study coordinated cell movements is provided by the migration of border cell clusters within a developing Drosophila egg chamber. In a mutagenesis screen, we isolated two alleles of the gene rickets (rk) encoding a G-protein-coupled receptor. The rk alleles result in border cell migration defects in a significant fraction of egg chambers. In rk mutants, border cells are properly specified and express the marker Slbo. Yet, analysis of both fixed as well as live samples revealed that some single border cells lag behind the main border cell cluster during migration, or, in other cases, the entire border cell cluster can remain tethered to the anterior epithelium as it migrates. These defects are observed significantly more often in mosaic border cell clusters, than in full mutant clusters. Reduction of the Rk ligand, Bursicon, in the border cell cluster also resulted in migration defects, strongly suggesting that Rk signaling is utilized for communication within the border cell cluster itself. The mutant border cell clusters show defects in localization of the adhesion protein E-cadherin, and apical polarity proteins during migration. E-cadherin mislocalization occurs in mosaic clusters, but not in full mutant clusters, correlating well with the rk border cell migration phenotype. Our work has identified a receptor with a previously unknown role in border cell migration that appears to regulate detachment and polarity of the border cell cluster coordinating processes within the cells of the cluster themselves. PMID:27130192

  14. G protein-coupled estrogen receptor inhibits the P2Y receptor-mediated Ca(2+) signaling pathway in human airway epithelia.

    PubMed

    Hao, Yuan; Chow, Alison W; Yip, Wallace C; Li, Chi H; Wan, Tai F; Tong, Benjamin C; Cheung, King H; Chan, Wood Y; Chen, Yangchao; Cheng, Christopher H; Ko, Wing H

    2016-08-01

    P2Y receptor activation causes the release of inflammatory cytokines in the bronchial epithelium, whereas G protein-coupled estrogen receptor (GPER), a novel estrogen (E2) receptor, may play an anti-inflammatory role in this process. We investigated the cellular mechanisms underlying the inhibitory effect of GPER activation on the P2Y receptor-mediated Ca(2+) signaling pathway and cytokine production in airway epithelia. Expression of GPER in primary human bronchial epithelial (HBE) or 16HBE14o- cells was confirmed on both the mRNA and protein levels. Stimulation of HBE or 16HBE14o- cells with E2 or G1, a specific agonist of GPER, attenuated the nucleotide-evoked increases in [Ca(2+)]i, whereas this effect was reversed by G15, a GPER-specific antagonist. G1 inhibited the secretion of two proinflammatory cytokines, interleukin (IL)-6 and IL-8, in cells stimulated by adenosine 5'-(γ-thio)triphosphate (ATPγS). G1 stimulated a real-time increase in cAMP levels in 16HBE14o- cells, which could be inhibited by adenylyl cyclase inhibitors. The inhibitory effects of E2 or G1 on P2Y receptor-induced increases in Ca(2+) were reversed by treating the cells with a protein kinase A (PKA) inhibitor. These results demonstrated that the inhibitory effects of G1 or E2 on P2Y receptor-mediated Ca(2+) mobilization and cytokine secretion were due to GPER-mediated activation of a cAMP-dependent PKA pathway. This study has reported, for the first time, the expression and function of GPER as an anti-inflammatory component in human bronchial epithelia, which may mediate through its opposing effects on the pro-inflammatory pathway activated by the P2Y receptors in inflamed airway epithelia. PMID:27271044

  15. Quantitative analysis of trace elements in environmental powders with laser ablation inductively coupled mass spectrometry using non-sample-corresponding reference materials for signal evaluation

    NASA Astrophysics Data System (ADS)

    Bauer, Gerald; Limbeck, Andreas

    2015-11-01

    Laser ablation inductively coupled plasma-mass spectrometry (LA-ICP-MS) is an attractive alternative to traditional procedures for the analysis of environmental samples (i.e., conventional liquid measurement after sample digestion). However, for accurate quantification, certified reference materials (CRM) are necessary which match the composition of the sample and include all elements of interest at the required concentration levels. The limited availability of appropriate CRMs hampers therefore substantial application. In this work, an LA-ICP-MS procedure allowing for accurate determination of trace element contents in powdered environmental samples is presented. For LA-ICP-MS analysis, the samples are mixed with an internal standard (silver oxide) and a binder (sodium tetra borate) and subsequently pressed to pellets. Quantification is accomplished using a calibration function determined using CRMs with varying matrix composition and analyte content, pre-treated and measured in the same way as the samples. With this approach, matrix-induced ablation differences resulting from varying physical/chemical properties of the individual CRMs could be compensated. Furthermore, ICP-related matrix-effects could be minimized using collision/reaction cell technology. Applicability of the procedure has been demonstrated by assessment of Cd, Cu, Ni, and Zn in four different environmental CRMs (NIST SRM1648a (urban particulate matter), NIST SRM2709 (San Joaquin Soil), BCR144 (sewage sludge), and BCR723 (road dust)). Signal evaluation was performed by alternative use of three CRMs for calculation of the calibration function whereas the remaining fourth CRM acted as unknown sample, resulting in a good agreement between measured and certified values for all elements and reference materials.

  16. Defects in muscarinic receptor-coupled signal transduction in isolated parotid gland cells after in vivo irradiation: evidence for a non-DNA target of radiation

    PubMed Central

    Coppes, R P; Meter, A; Latumalea, S P; Roffel, A F; Kampinga, H H

    2005-01-01

    Radiation-induced dysfunction of normal tissue, an unwanted side effect of radiotherapeutic treatment of cancer, is usually considered to be caused by impaired loss of cell renewal due to sterilisation of stem cells. This implies that the onset of normal tissue damage is usually determined by tissue turnover rate. Salivary glands are a clear exception to this rule: they have slow turnover rates (>60 days), yet develop radiation-induced dysfunction within hours to days. We showed that this could not be explained by a hypersensitivity to radiation-induced apoptosis or necrosis of the differentiated cells. In fact, salivary cells are still capable of amylase secretion shortly after irradiation while at the same time water secretion seems specifically and severely impaired. Here, we demonstrate that salivary gland cells isolated after in vivo irradiation are impaired in their ability to mobilise calcium from intracellular stores (Ca2+i), the driving force for water secretion, after exposure to muscarinic acetylcholine receptor agonists. Using radioligand-receptor-binding assays it is shown that radiation caused no changes in receptor density, receptor affinity nor in receptor-G-protein coupling. However, muscarinic acetylcholine agonist-induced activation of protein kinase C alpha (PKCα), measured as translocation to the plasma membrane, was severely affected in irradiated cells. Also, the phorbol ester PMA could no longer induce PKCα translocation in irradiated cells. Our data hence indicate that irradiation specifically interferes with PKCα association with membranes, leading to impairment of intracellular signalling. To the best of our knowledge, these data for the first time suggest that, the cells' capacity to respond to a receptor agonist is impaired after irradiation. PMID:15668705

  17. From land use to land cover: Restoring the afforestation signal in a coupled integrated assessment - earth system model and the implications for CMIP5 RCP simulations

    SciTech Connect

    Di Vittorio, Alan V.; Chini, Louise M.; Bond-Lamberty, Benjamin; Mao, Jiafu; Shi, Xiaoying; Truesdale, John E.; Craig, Anthony P.; Calvin, Katherine V.; Jones, Andrew D.; Collins, William D.; Edmonds, James A.; Hurtt, George; Thornton, Peter E.; Thomson, Allison M.

    2014-11-27

    Climate projections depend on scenarios of fossil fuel emissions and land use change, and the IPCC AR5 parallel process assumes consistent climate scenarios across Integrated Assessment and Earth System Models (IAMs and ESMs). To facilitate consistency, CMIP5 used a novel land use harmonization to provide ESMs with seamless, 1500-2100 land use trajectories generated by historical data and four IAMs. However, we have identified and partially addressed a major gap in the CMIP5 land coupling design. The CMIP5 Community ESM (CESM) global afforestation is only 22% of RCP4.5 afforestation from 2005 to 2100. Likewise, only 17% of the Global Change Assessment Model’s (GCAM’s) 2040 RCP4.5 afforestation signal, and none of the pasture loss, were transmitted to CESM within a newly integrated model. This is a critical problem because afforestation is necessary for achieving the RCP4.5 climate stabilization. We attempted to rectify this problem by modifying only the ESM component of the integrated model, enabling CESM to simulate 66% of GCAM’s afforestation in 2040, and 94% of GCAM’s pasture loss as grassland and shrubland losses. This additional afforestation increases vegetation carbon gain by 19 PgC and decreases atmospheric CO2 gain by 8 ppmv from 2005 to 2040, implying different climate scenarios between CMIP5 GCAM and CESM. Similar inconsistencies likely exist in other CMIP5 model results, primarily because land cover information is not shared between models, with possible contributions from afforestation exceeding model-specific, potentially viable forest area. Further work to harmonize land cover among models will be required to adequately rectify this problem.

  18. JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma

    PubMed Central

    Nairismägi, M-L; Tan, J; Lim, J Q; Nagarajan, S; Ng, C C Y; Rajasegaran, V; Huang, D; Lim, W K; Laurensia, Y; Wijaya, G C; Li, Z M; Cutcutache, I; Pang, W L; Thangaraju, S; Ha, J; Khoo, L P; Chin, S T; Dey, S; Poore, G; Tan, L H C; Koh, H K M; Sabai, K; Rao, H-L; Chuah, K L; Ho, Y-H; Ng, S-B; Chuang, S-S; Zhang, F; Liu, Y-H; Pongpruttipan, T; Ko, Y H; Cheah, P-L; Karim, N; Chng, W-J; Tang, T; Tao, M; Tay, K; Farid, M; Quek, R; Rozen, S G; Tan, P; Teh, B T; Lim, S T; Tan, S-Y; Ong, C K

    2016-01-01

    Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK-STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available. PMID:26854024

  19. Galanin stimulates cortisol secretion from human adrenocortical cells through the activation of galanin receptor subtype 1 coupled to the adenylate cyclase-dependent signaling cascade.

    PubMed

    Belloni, Anna S; Malendowicz, Ludwik K; Rucinski, Marcin; Guidolin, Diego; Nussdorfer, Gastone G

    2007-12-01

    Previous studies showed that galanin receptors are expressed in the rat adrenal, and galanin modulates glucocorticoid secretion in this species. Hence, we investigated the expression of the various galanin receptor subtypes (GAL-R1, GAL-R2 and GAL-R3) in the human adrenocortical cells, and the possible involvement of galanin in the control of cortisol secretion. Reverse transcription-polymerase chain reaction detected the expression of GAL-R1 (but not GAL-R2 and GAL-R3) in the inner zones of the human adrenal cortex. The galanin concentration dependently enhanced basal, but not ACTH-stimulated secretion of cortisol from dispersed inner adrenocortical cells (maximal effective concentration, 10(-8) M). The cortisol response to 10(-8) M galanin was abrogated by GAL-R1 immunoneutralization, and unaffected by GAL-R2 or GAL-R3 immunoneutralization. Galanin (10(-8) M) and ACTH (10(-9) M) enhanced cyclic-AMP production from dispersed cells, and the response was suppressed by the adenylate cyclase inhibitor SQ-22536 (10(-4) M). Galanin did not affect inositol triphosphate release, which, in contrast, was raised by angiotensin-II (10(-8) M). SQ-22536 and the protein kinase (PK)A inhibitor H-89 (10(-5) M) abolished the cortisol response to 10(-8) M galanin, while the phospholipase C inhibitor U-73122 and the PKC inhibitor calphostin-C were ineffective. Preincubation with pertussis toxin (Ptx) (0.5 microg/ml) partially inhibited the cortisol response to galanin. We conclude that galanin stimulates cortisol secretion from human inner adrenocortical cells, acting through GAL-R1 coupled to the adenylate cyclase/PKA-dependent signaling cascade via a Ptx-sensitive Galpha protein. PMID:17982695

  20. JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma.

    PubMed

    Nairismägi, M-L; Tan, J; Lim, J Q; Nagarajan, S; Ng, C C Y; Rajasegaran, V; Huang, D; Lim, W K; Laurensia, Y; Wijaya, G C; Li, Z M; Cutcutache, I; Pang, W L; Thangaraju, S; Ha, J; Khoo, L P; Chin, S T; Dey, S; Poore, G; Tan, L H C; Koh, H K M; Sabai, K; Rao, H-L; Chuah, K L; Ho, Y-H; Ng, S-B; Chuang, S-S; Zhang, F; Liu, Y-H; Pongpruttipan, T; Ko, Y H; Cheah, P-L; Karim, N; Chng, W-J; Tang, T; Tao, M; Tay, K; Farid, M; Quek, R; Rozen, S G; Tan, P; Teh, B T; Lim, S T; Tan, S-Y; Ong, C K

    2016-06-01

    Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK-STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available. PMID:26854024

  1. Gq Protein-Coupled Membrane-Initiated Estrogen Signaling Rapidly Excites Corticotropin-Releasing Hormone Neurons in the Hypothalamic Paraventricular Nucleus in Female Mice.

    PubMed

    Hu, Pu; Liu, Ji; Yasrebi, Ali; Gotthardt, Juliet D; Bello, Nicholas T; Pang, Zhiping P; Roepke, Troy A

    2016-09-01

    CRH neurons in the hypothalamic paraventricular nucleus (PVN) play a central role in regulating the hypothalamus-pituitary-adrenal (HPA) axis and are directly influenced by 17β-estradiol (E2). Although compelling evidence has suggested the existence of membrane-associated estrogen receptors (mERs) in hypothalamic and other central nervous system neurons, it remains unknown whether E2 impacts CRH neuronal excitability through this mechanism. The purpose of the current study is to examine the existence and function of mER signaling in PVN CRH neurons. Whole-cell recordings were made from CRH neurons identified by Alexa Fluor 594 labeling and post hoc immunostaining in ovariectomized female mice. E2 (100nM) rapidly suppressed the M-current (a voltage-dependent K(+) current) and potentiated glutamatergic excitatory postsynaptic currents. The putative Gq-coupled mER (Gq-mER) characterized in hypothalamic proopiomelanocortin neurons initiates a phospholipase C-protein kinase C-protein kinase A pathway; therefore, we examined the involvement of this pathway using selective inhibitors. Indeed, the ER antagonist ICI 182780 and inhibitors of Gq-phospholipase C-protein kinase C-protein kinase A blocked E2's actions, suggesting dependence on the Gq-mER. Furthermore, STX, a selective ligand for the Gq-mER, mimicked E2's actions. Finally, to examine the in vivo effect of Gq-mER activation, E2 or STX injection increased c-fos expression in CRH neurons in the PVN, suggesting CRH neuronal activation. This corresponded to an increase in plasma corticosterone. We conclude that the Gq-mER plays a critical role in the rapid regulation of CRH neuronal activity and the HPA axis. Our findings provide a potential underlying mechanism for E2's involvement in the pathophysiology of HPA-associated mood disorders. PMID:27387482

  2. PDE5A suppression of acute β-adrenergic activation requires modulation of myocyte beta-3 signaling coupled to PKG-mediated troponin I phosphorylation

    PubMed Central

    Lee, Dong I.; Vahebi, Susan; Tocchetti, Carlo Gabriele; Barouch, Lili A.; Solaro, R. John; Takimoto, Eiki

    2010-01-01

    Phosphodiesterase type 5A (PDE5A) inhibitors acutely suppress beta-adrenergic receptor (β-AR) stimulation in left ventricular myocytes and hearts. This modulation requires cyclic GMP synthesis via nitric oxide synthase (NOS)-NO stimulation, but upstream and downstream mechanisms remain un-defined. To determine this, adult cardiac myocytes from genetically engineered mice and controls were studied by video microscopy to assess sarcomere shortening (SS) and fura2-AM fluorescence to measure calcium transients (CaT). Enhanced SS from isoproterenol (ISO, 10 nM) was suppressed ≥50% by the PDE5A inhibitor sildenafil (SIL, 1 µM), without altering CaT. This regulation was unaltered despite co-inhibition of either the cGMP-stimulated cAMP-esterase PDE2 (Bay 60-7550), or cGMP-inhibited cAMP-esterase PDE3 (cilostamide). Thus, the SIL response could not be ascribed to cGMP interaction with alternative PDEs. However, genetic deletion (or pharmacologic blockade) of β3-ARs, which couple to NOS signaling, fully prevented SIL modulation of ISO-stimulated SS. Importantly, both PDE5A protein expression and activity were similar in β3-AR knockout (β3-AR−/−) myocytes as in controls. Downstream, cGMP stimulates protein kinase G (PKG), and we found contractile modulation by SIL required PKG activation and enhanced TnI phosphorylation at S23, S24. Myocytes expressing the slow skeletal TnI isoform which lacks these sites displayed no modulation of ISO responses by SIL. Non-equilibrium isoelectric focusing gel electrophoresis showed SIL increased TnI phosphorylation above that from concomitant ISO in control but not β3-AR−/− myocytes. These data support a cascade involving β3-AR stimulation, and subsequent PKG-dependent TnI S23, S24 phosphorylation as primary factors underlying the capacity of acute PDE5A inhibition to blunt myocardial β-adrenergic stimulation. PMID:20107996

  3. Magnetoelectric coupling study in multiferroic Pb(Fe{sub 0.5}Nb{sub 0.5})O{sub 3} ceramics through small and large electric signal standard measurements

    SciTech Connect

    Raymond, Oscar; Siqueiros, Jesus M.; Font, Reynaldo; Portelles, Jorge

    2011-05-01

    Multifunctional multiferroic materials such as the single phase compound Pb(Fe{sub 0.5}Nb{sub 0.5})O{sub 3} (PFN), where ferroelectric and antiferromagnetic order coexist, are very promising and have great interest from the academic and technological points of view. In this work, coupling of the ferroelectric and magnetic moments is reported. For this study, a combination of the small signal response using the impedance spectroscopy technique and the electromechanical resonance method with the large signal response through standard ferroelectric hysteresis measurement, has been used with and without an applied magnetic field. The measurements to determine the electrical properties of the ceramic were performed as functions of the bias and poling electric fields. A simultaneous analysis of the complex dielectric constant {epsilon}-tilde, impedance Z-tilde, electric modulus M-tilde, admittance Y-tilde, and the electromechanical parameters and coupling factors is presented. The results are correlated with a previous study of structural, morphological, small signal dielectric frequency-temperature response, and the ferroelectric hysteretic, magnetic and magnetodielectric behaviors. The observed shifts of the resonance and antiresonance frequency values can be associated with change of the ferroelectric domain size favored by the readjustment of the oxygen octahedron when the magnetic field is applied. From P-E hysteresis loops obtained without and with an external applied magnetic field, a dc magnetoelectric coupling effect with maximum value of 4 kV/cm T (400 mV/cm Oe) was obtained.

  4. Differential pathway coupling efficiency of the activated insulin receptor drives signaling selectivity by XMetA, an allosteric partial agonist antibody

    Technology Transfer Automated Retrieval System (TEKTRAN)

    XMetA, an anti-insulin receptor (IR) monoclonal antibody, is an allosteric partial agonist of the IR. We have previously reported that XMetA activates the “metabolic-biased” Akt kinase signaling pathway while having little or no effect on the “mitogenic” MAPK signaling pathwayof ERK 1/2. To inves...

  5. The role of PLDα1 in providing specificity to signal-response coupling by heterotrimeric G-protein components in Arabidopsis.

    PubMed

    Roy Choudhury, Swarup; Pandey, Sona

    2016-04-01

    Heterotrimeric G-proteins comprised of Gα, Gβ and Gγ subunits are important signal transducers in all eukaryotes. In plants, G-proteins affect multiple biotic and abiotic stress responses, as well as many developmental processes, even though their repertoire is significantly limited compared with that in metazoan systems. One canonical and three extra-large Gα, 1 Gβ and 3 Gγ proteins represent the heterotrimeric G-protein complex in Arabidopsis, and a single regulatory protein, RGS1, is one of the few known biochemical regulators of this signaling complex. This quantitative disparity between the number of signaling components and the range of processes they influence is rather intriguing. We now present evidence that the phospholipase Dα1 protein is a key component and modulator of the G-protein complex in affecting a subset of signaling pathways. We also show that the same G-protein subunits and their modulators exhibit distinct physiological and genetic interactions depending on specific signaling and developmental pathways. Such developmental plasticity and interaction specificity likely compensates for the lack of multiplicity of individual subunits, and helps to fine tune the plants' responses to constantly changing environments. PMID:26935351

  6. The G-protein-coupled bile acid receptor Gpbar1 (TGR5) suppresses gastric cancer cell proliferation and migration through antagonizing STAT3 signaling pathway

    PubMed Central

    Guo, Cong; Su, Jia; Li, Zhijun; Xiao, Rui; Wen, Jianxun; Li, Yanyan; Zhang, Meng; Zhang, Xueting; Yu, Donna; Huang, Wendong

    2015-01-01

    Gpbar1 (TGR5), a membrane-bound bile acid receptor, is well known for its roles in regulation of energy homeostasis and glucose metabolism. Here we show that TGR5 is a suppressor of gastric cancer cell proliferation and migration through antagonizing STAT3 signaling pathway. We firstly show that TGR5 activation greatly inhibited proliferation and migration of human gastric cancer cells and strongly induced gastric cancer cell apoptosis. We then found that TGR5 activation antagonized STAT3 signaling pathway through suppressing the phosphorylation of STAT3 and its transcription activity induced by lipopolysaccharide (LPS) or interleukin-6. TGR5 overexpression with ligand treatment inhibited gene expression mediated by STAT3. It suggests that TGR5 antagonizes gastric cancer proliferation and migration at least in part by inhibiting STAT3 signaling. These findings identify TGR5 as a suppressor of gastric cancer cell proliferation and migration that may serve as an attractive therapeutic tool for human gastric cancer. PMID:26417930

  7. Effect of J coupling on 1.3-ppm lipid methylene signal acquired with localised proton MRS at 3 T.

    PubMed

    Breitkreutz, Dylan Y; Fallone, B Gino; Yahya, Atiyah

    2015-10-01

    The purpose of this work was to investigate the effect of J-coupling interactions on the quantification and T2 determination of 1.3-ppm lipid methylene protons at 3 T. The response of the 1.3-ppm protons of hexanoic, heptanoic, octanoic, linoleic and oleic acid was measured as a function of point-resolved spectroscopy (PRESS) and stimulated echo acquisition mode (STEAM) TE. In addition, a narrow-bandwidth refocusing PRESS sequence designed to rewind J-coupling evolution of the 1.3-ppm protons was applied to the five fatty acids, to corn oil and to tibial bone marrow of six healthy volunteers. Peak areas were plotted as a function of TE, and data were fitted to monoexponentially decaying functions to determine Mo (the extrapolated area for TE = 0 ms) and T2 values. In phantoms, rewinding J-coupling evolution resulted in 198%, 64%, 44%, 20% and 15% higher T2 values for heptanoic, octanoic, linoleic and oleic acid, and corn oil, respectively, compared with those obtained with standard PRESS. The narrow-bandwidth PRESS sequence also resulted in significant changes in Mo , namely -77%, -22%, 28%, 23% and 28% for heptanoic, octanoic, linoleic and oleic acid, and corn oil, respectively. T2 values obtained with STEAM were closer to the values measured with narrow-bandwidth PRESS. On average, in tibial bone marrow (six volunteers) rewinding J-coupling evolution resulted in 21% ± 3% and 9 % ± 1% higher Mo and T2 values, respectively. This work demonstrates that the consequence of neglecting to consider scalar coupling effects on the quantification of 1.3-ppm lipid methylene protons and their T2 values is not negligible. The linoleic and oleic acid T2 results indicate that T2 measures of lipids with standard MRS techniques are dependent on lipid composition. PMID:26314546

  8. From land use to land cover: restoring the afforestation signal in a coupled integrated assessment-earth system model and the implications for CMIP5 RCP simulations

    NASA Astrophysics Data System (ADS)

    Di Vittorio, A. V.; Chini, L. P.; Bond-Lamberty, B.; Mao, J.; Shi, X.; Truesdale, J.; Craig, A.; Calvin, K.; Jones, A.; Collins, W. D.; Edmonds, J.; Hurtt, G. C.; Thornton, P.; Thomson, A.

    2014-11-01

    Climate projections depend on scenarios of fossil fuel emissions and land use change, and the Intergovernmental Panel on Climate Change (IPCC) AR5 parallel process assumes consistent climate scenarios across integrated assessment and earth system models (IAMs and ESMs). The CMIP5 (Coupled Model Intercomparison Project Phase 5) project used a novel "land use harmonization" based on the Global Land use Model (GLM) to provide ESMs with consistent 1500-2100 land use trajectories generated by historical data and four IAMs. A direct coupling of the Global Change Assessment Model (GCAM), GLM, and the Community ESM (CESM) has allowed us to characterize and partially address a major gap in the CMIP5 land coupling design: the lack of a corresponding land cover harmonization. For RCP4.5, CESM global afforestation is only 22% of GCAM's 2005 to 2100 afforestation. Likewise, only 17% of GCAM's 2040 afforestation, and zero pasture loss, were transmitted to CESM within the directly coupled model. This is a problem because GCAM relied on afforestation to achieve RCP4.5 climate stabilization. GLM modifications and sharing forest area between GCAM and GLM within the directly coupled model did not increase CESM afforestation. Modifying the land use translator in addition to GLM, however, enabled CESM to include 66% of GCAM's afforestation in 2040, and 94% of GCAM's pasture loss as grassland and shrubland losses. This additional afforestation increases CESM vegetation carbon gain by 19 PgC and decreases atmospheric CO2 gain by 8 ppmv from 2005 to 2040, which demonstrates that CESM without additional afforestation simulates a different RCP4.5 scenario than prescribed by GCAM. Similar land cover inconsistencies exist in other CMIP5 model results, primarily because land cover information is not shared between models. Further work to harmonize land cover among models will be required to increase fidelity between IAM scenarios and ESM simulations and realize the full potential of scenario

  9. The Complex of Ciliary Neurotrophic Factor-Ciliary Neurotrophic Factor Receptor α Up-Regulates Connexin43 and Intercellular Coupling in Astrocytes via the Janus Tyrosine Kinase/Signal Transducer and Activator of Transcription PathwayD⃞

    PubMed Central

    Ozog, Mark A.; Bernier, Suzanne M.; Bates, Dave C.; Chatterjee, Bishwanath; Lo, Cecilia W.; Naus, Christian C.G.

    2004-01-01

    Cytokines regulate numerous cell processes, including connexin expression and gap junctional coupling. In this study, we examined the effect of ciliary neurotrophic factor (CNTF) on connexin43 (Cx43) expression and intercellular coupling in astrocytes. Murine cortical astrocytes matured in vitro were treated with CNTF (20 ng/ml), soluble ciliary neurotrophic factor receptor α (CNTFRα) (200 ng/ml), or CNTF-CNTFRα. Although CNTF and CNTFRα alone had no effect on Cx43 expression, the heterodimer CNTF-CNTFRα significantly increased both Cx43 mRNA and protein levels. Cx43 immunostaining correlated with increased intercellular coupling as determined by dye transfer analysis. By using the pharmacological inhibitor α-cyano-(3,4-dihydroxy)-N-benzylcinnamide (AG490), the increase in Cx43 was found to be dependent on the Janus tyrosine kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Immunocytochemical analysis revealed that CNTF-CNTFRα treatment produced nuclear localization of phosphorylated STAT3, whereas CNTF treatment alone did not. Transient transfection of constructs containing various sequences of the Cx43 promoter tagged to a LacZ reporter into ROS 17/2.8 cells confirmed that the promoter region between -838 to -1693 was deemed necessary for CNTF-CNTFRα to induce heightened expression. CNTF-CNTFRα did not alter Cx30 mRNA levels, suggesting selectivity of CNTF-CNTFRα for connexin signaling. Together in the presence of soluble receptor, CNTF activates the JAK/STAT pathway leading to enhanced Cx43 expression and intercellular coupling. PMID:15342787

  10. The G-Protein-Coupled Bile Acid Receptor Gpbar1 (TGR5) Inhibits Gastric Inflammation Through Antagonizing NF-κB Signaling Pathway

    PubMed Central

    Guo, Cong; Qi, Hui; Yu, Yingjie; Zhang, Qiqi; Su, Jia; Yu, Donna; Huang, Wendong; Chen, Wei-Dong; Wang, Yan-Dong

    2015-01-01

    Gpbar1 (TGR5), a membrane-bound bile acid receptor, is well-known for its roles in regulation of energy homeostasis and glucose metabolism. Here, we show that mice lacking TGR5 were much more susceptible to lipopolysaccharide (LPS)-induced acute gastric inflammation than wild-type (WT) mice and TGR5 is a negative regulator of gastric inflammation through antagonizing NF-κB signaling pathway. We found that the treatment of TGR5 ligands 23(S)-mCDCA and GPBARA (3-(2-Chlorophenyl)-N-(4-chlorophenyl)-N,5-dimethylisoxazole-4-carboxamide) suppressed gene and protein expression mediated by NF-κB signaling. TGR5 overexpression with ligand treatment inhibited gene expression of interferon-inducible protein 10 (IP-10), TNF-α, and chemoattractant protein-1 (MCP-1) induced by LPS. Furthermore, we revealed that TGR5 activation antagonized NF-κB signaling pathway through suppressing its transcription activity, the phosphorylation of IκBα and p65 translocation, which suggests that TGR5 antagonizes gastric inflammation at least in part by inhibiting NF-κB signaling. These findings identify TGR5 as a negative mediator of gastric inflammation that may serve as an attractive therapeutic tool for human gastric inflammation and cancer. PMID:26696888

  11. Coupling calcium/calmodulin-mediated signaling and herbivore-induced plant response calmodulin-binding transcription factor AtSR1/CAMTA3

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Calcium/calmodulin (Ca2+/CaM) has long been considered a crucial component in wound signaling pathway. However, no functional significance of Ca2+/CaM-binding proteins has been identified in plant responses to herbivore attack/wounding stress. We have reported earlier that a family of Ca2+/CaM-bindi...

  12. From land use to land cover: Restoring the afforestation signal in a coupled integrated assessment - earth system model and the implications for CMIP5 RCP simulations

    NASA Astrophysics Data System (ADS)

    Di Vittorio, Alan; Chini, Louise; Bond-Lamberty, Ben; Mao, Jiafu; Shi, Xiaoying; Truesdale, John; Craig, Anthony; Calvin, Kate; Jones, Andrew; Collins, William; Edmonds, Jae; Hurtt, George; Thornton, Peter; Thomson, Allison

    2015-04-01

    Climate projections depend on scenarios of fossil fuel emissions and land use change, and the IPCC AR5 parallel process assumes consistent climate scenarios across Integrated Assessment and Earth System Models (IAMs and ESMs). The CMIP5 project used a novel "land use harmonization" based on the Global Land use Model (GLM) to provide ESMs with consistent 1500-2100 land use trajectories generated by historical data and four IAMs. A direct coupling of the Global Change Assessment Model (GCAM), GLM, and the Community ESM (CESM) has allowed us to characterize and partially address a major gap in the CMIP5 land coupling design: the lack of a corresponding land cover harmonization. For RCP4.5, CESM global afforestation is only 22% of GCAM's 2005 to 2100 afforestation. Likewise, only 17% of GCAM's 2040 afforestation, and zero pasture loss, were transmitted to CESM within the directly coupled model. This is a problem because GCAM relied on afforestation to achieve RCP4.5 climate stabilization. GLM modifications and sharing forest area between GCAM and GLM within the directly coupled model did not increase CESM afforestation. Modifying the land use translator in addition to GLM, however, enabled CESM to include 66% of GCAM's afforestation in 2040, and 94% of GCAM's pasture loss as grassland and shrubland losses. This additional afforestation increases CESM vegetation carbon gain by 19 PgC and decreases atmospheric CO2 gain by 8 ppmv from 2005 to 2040, which demonstrates that CESM without additional afforestation simulates a different RCP4.5 scenario than prescribed by GCAM. Similar land cover inconsistencies exist in other CMIP5 model results, primarily because land cover information is not shared between models. Further work to harmonize land cover among models will be required to increase fidelity between IAM scenarios and ESM simulations and realize the full potential of scenario-based earth system simulations.

  13. Microgravity and Signaling Molecules in Rat Osteoblasts: Downstream of Receptor Tyrosine Kinase, G-Protein-Coupled Receptor, and Small GTP-Binding Proteins

    NASA Technical Reports Server (NTRS)

    Kumel, Yasuhiro; Shimokawa, Hitoyata; Morita, Sadao; Katano, Hisako; Akiyama, Hideo; Hirano, Masahiko; Ohya, Keiichi; Sams, Clarence F.; Whitson, Peggy A.

    2005-01-01

    Rat osteoblasts were cultured for 4 and 5 days aboard Space Shuttle and solubilized on board. The mRNA levels of the post-receptor signaling molecules were analyzed by quantitative RT-PCR. The G-protein alpha subunit G(alpha)q mRNA levels were elevated 3-fold by microgravity. G(alpha)q stimulates PLC(beta), and then PKC. PKC(delta) and PKC(theta) mRNA levels were increased 2- to 5-fold by microgravity The mRNA levels of SOS and Ras GRF were increased 4 to 5-fold by microgravity, while Ras GAP was not altered. Spaceflight-induced bone loss might be attributed to microgravity modulation of the signaling pathway in osteoblasts.

  14. A microRNA program in the C. elegans hypodermis couples to intestinal mTORC2/PQM-1 signaling to modulate fat transport.

    PubMed

    Dowen, Robert H; Breen, Peter C; Tullius, Thomas; Conery, Annie L; Ruvkun, Gary

    2016-07-01

    Animals integrate metabolic, developmental, and environmental information before committing key resources to reproduction. In Caenorhabditis elegans, adult animals transport fat from intestinal cells to the germline to promote reproduction. We identified a microRNA (miRNA)-regulated developmental timing pathway that functions in the hypodermis to nonautonomously coordinate the mobilization of intestinal fat stores to the germline upon initiation of adulthood. This developmental timing pathway, which is controlled by the lin-4 and let-7 miRNAs, engages mTOR signaling in the intestine. The intestinal signaling component is specific to mTORC2 and functions in parallel to the insulin pathway to modulate the activity of the serum/glucocorticoid-regulated kinase (SGK-1). Surprisingly, SGK-1 functions independently of DAF-16/FoxO; instead, SGK-1 promotes the cytoplasmic localization of the PQM-1 transcription factor, which antagonizes intestinal fat mobilization at the transcriptional level when localized to the nucleus. These results revealed that a non-cell-autonomous developmental input regulates intestinal fat metabolism by engaging mTORC2 signaling to promote the intertissue transport of fat reserves from the soma to the germline. PMID:27401555

  15. Mitogen-Activated Protein Kinase 8 (MAP3K8) Mediates the Signaling Pathway of Estradiol Stimulating Progesterone Production Through G Protein-Coupled Receptor 30 (GPR30) in Mouse Corpus Luteum.

    PubMed

    Liu, Ying; Li, Yueqin; Zhang, Di; Liu, Jiali; Gou, Kemian; Cui, Sheng

    2015-05-01

    The corpus luteum (CL) is a transient endocrine gland developed from the ovulated follicles, and the most important function is to synthesize and secrete progesterone (P(4)), a key hormone to maintain normal pregnancy and estrous cycle in most mammals. It is known that estrogen has a vital role in stimulating P(4) synthesis in CL, but it still remains unclear about the mechanism of estradiol (E(2)) regulating P(4) production in CL. Our results here first show that all of the CL cells express MAPK 8 (MAP3K8), and the MAP3K8 level is much higher at the midstage than at the early and late stages during CL development. The further functional studies show that the forced inhibition of endogenous MAP3K8 by using MAP3K8 small interfering RNA and MAP3K8 signaling inhibitor (MAP3K8i) in the luteal cells significantly block the P(4) synthesis and neutralize the enhancing effect of E(2) on P(4) production in the CL. In addition, our results here demonstrate that the stimulating effect of E(2) on P(4) synthesis relies on the estrogen no-classical protein-coupled receptor 30, and MAP3K8 is involved in mediating the protein-coupled receptor 30signaling of E(2) affecting P(4) synthesis via stimulating ERK phosphorylation. These novel findings are critical for our understanding the ovary physiology and pathological mechanism. PMID:25763610

  16. From Land Use to Land Cover: Restoring the Afforestation Signal in a Coupled Integrated Assessment - Earth System Model and the Implications for CMIP5 RCP Simulations

    NASA Astrophysics Data System (ADS)

    Di Vittorio, A. V.; Chini, L. P.; Bond-Lamberty, B. P.; Mao, J.; Shi, X.; Truesdale, J. E.; Craig, A.; Calvin, K. V.; Jones, A. D.; Collins, W.; Edmonds, J.; Hurtt, G. C.; Thornton, P. E.; Thomson, A. M.

    2014-12-01

    Climate projections depend on scenarios of fossil fuel emissions and land use change, and the IPCC AR5 parallel process assumes consistent climate scenarios across Integrated Assessment and Earth System Models (IAMs and ESMs). The CMIP5 project used a novel "land use harmonization" based on the Global Land use Model (GLM) to provide ESMs with consistent 1500-2100 land use trajectories generated by historical data and four IAM projections. A direct coupling of the Global Change Assessment Model (GCAM), GLM, and the Community ESM (CESM) has allowed us to characterize and partially address a major gap in the CMIP5 land coupling design: the lack of a corresponding land cover harmonization. The CMIP5 CESM global afforestation is only 22% of GCAM's 2005 to 2100 RCP4.5 afforestation. Likewise, only 17% of GCAM's 2040 RCP4.5 afforestation, and zero pasture loss, were transmitted to CESM within the directly coupled model. This is a problem because afforestation was relied upon to achieve RCP4.5 climate stabilization. GLM modifications within the directly coupled model did not increase CESM afforestation. Modifying the CESM land use translator in addition to GLM, however, enabled CESM to simulate 66% of GCAM's afforestation in 2040, and 94% of GCAM's pasture loss as grassland and shrubland losses. This additional afforestation increases vegetation carbon gain by 19 PgC and decreases atmospheric CO2 gain by 8 ppmv from 2005 to 2040, implying different RCP4.5 climate scenarios between CMIP5 GCAM and CESM. Although the IAMs and ESMs were not expected to have exactly the same climate forcing, due in part to different terrestrial carbon cycles and atmospheric radiation algorithms, the ESMs were expected to project climates representative of the RCP scenarios. Similar land cover inconsistencies exist in other CMIP5 model results, primarily because land cover information is not shared between IAM and ESM models. High RCP4.5 afforestation might also contribute to inconsistencies as

  17. From land use to land cover: restoring the afforestation signal in a coupled integrated assessment - earth system model and the implications for CMIP5 RCP simulations

    NASA Astrophysics Data System (ADS)

    Di Vittorio, A. V.; Chini, L. P.; Bond-Lamberty, B.; Mao, J.; Shi, X.; Truesdale, J.; Craig, A.; Calvin, K.; Jones, A.; Collins, W. D.; Edmonds, J.; Hurtt, G. C.; Thornton, P.; Thomson, A.

    2014-05-01

    Climate projections depend on scenarios of fossil fuel emissions and land use change, and the IPCC AR5 parallel process assumes consistent climate scenarios across Integrated Assessment and Earth System Models (IAMs and ESMs). The CMIP5 project used a novel "land use harmonization" based on the Global Land use Model (GLM) to provide ESMs with consistent 1500-2100 land use trajectories generated by historical data and four IAM projections. A direct coupling of the Global Change Assessment Model (GCAM), GLM, and the Community ESM (CESM) has allowed us to characterize and partially address a major gap in the CMIP5 land coupling design: the lack of a corresponding land cover harmonization. The CMIP5 CESM global afforestation is only 22% of GCAM's 2005 to 2100 RCP4.5 afforestation. Likewise, only 17% of GCAM's 2040 RCP4.5 afforestation, and zero pasture loss, were transmitted to CESM within the directly coupled model. This is a problem because afforestation was relied upon to achieve RCP4.5 climate stabilization. GLM modifications within the directly coupled model did not increase CESM afforestation. Modifying the land use translator in addition to GLM, however, enabled CESM to simulate 66% of GCAM's afforestation in 2040, and 94% of GCAM's pasture loss as grassland and shrubland losses. This additional afforestation increases vegetation carbon gain by 19 PgC and decreases atmospheric CO2 gain by 8 ppmv from 2005 to 2040, implying different RCP4.5 climate scenarios between CMIP5 GCAM and CESM. Although the IAMs and ESMs were not expected to have exactly the same climate forcing, due in part to different terrestrial carbon cycles and atmospheric radiation algorithms, the ESMs were expected to project climates representative of the RCP scenarios. Similar land cover inconsistencies exist in other CMIP5 model results, primarily because land cover information is not shared between models. High RCP4.5 afforestation might also contribute to inconsistencies as some ESMs might

  18. MicroRNA-mediated signal amplification coupled with GNP/dendrimers on a mass-sensitive biosensor and its applications in intracellular microRNA quantification.

    PubMed

    Guo, Yingshu; Wang, Yujie; Yang, Guangxu; Xu, Jing-Juan; Chen, Hong-Yuan

    2016-11-15

    Here, a mass-sensitive microRNA sensing surface is developed by utilizing a probe DNA/gold nanoparticles (GNP)/dendrimer composite coupling with an enzymatic amplification process. The probe DNA/GNP/dendrimer composite is prepared via the covalent coupling between the NH2 groups in PAMAM or DNA and the COOH group on GNP. Target microRNA binds to a stem-loop-structured DNA on maganatic NPs, forming a heteroduplex. By enzyme recycling amplification, a large number of linker sequences are produced on MNPs. Via the combination of probe DNA, the linker DNA on MNPs and a capture DNA on gold chip, the DNA/GNP/dendrimer probe could be assembled on the surface of gold chip inducing a sensitive frequency response. It presents an excellent performance in microRNA-203 quantification with a detection linear range of 1.0×10(-11)-1.0×10(-9)M. Both the success in discriminating expressing miroRNA-203 in MCF-7 cell and the well agreement with the commercial qRT-PCR detection method implied its potential application in early cancer diagnosis for future. PMID:27311115

  19. Induction of Cyclin D2 in Rat Granulosa Cells Requires FSH-dependent Relief from FOXO1 Repression Coupled with Positive Signals from Smad*

    PubMed Central

    Park, Youngkyu; Maizels, Evelyn T.; Feiger, Zachary J.; Alam, Hena; Peters, Carl A.; Woodruff, Teresa K.; Unterman, Terry G.; Lee, Eun Jig; Jameson, J. Larry; Hunzicker-Dunn, Mary

    2006-01-01

    Ovarian follicles undergo exponential growth in response to follicle-stimulating hormone (FSH), largely as a result of the proliferation of granulosa cells (GCs). In vitro under serum-free conditions, rat GCs differentiate in response to FSH but do not proliferate unless activin is also present. In the presence of FSH plus activin, GCs exhibit enhanced expression of cyclin D2 as well as inhibin-α, aromatase, steroidogenic factor-1 (SF-1), cholesterol side chain (SCC), and epiregulin. In this report we sought to identify the signaling pathways by which FSH and activin promote GC proliferation and differentiation. Our results show that these responses are associated with prolonged Akt phosphorylation relative to time-matched controls and are dependent on phosphati-dylinositol 3-kinase (PI 3-kinase) and Smad2/3 signaling, based on the ability of the PI 3-kinase inhibitor LY294002 or infection with adenoviral dominant negative Smad3 (DN-Smad3) mutant to attenuate induction of cyclin D2, inhibin-α, aromatase, SCC, SF-1, and epiregulin. The DN-Smad3 mutant also abolished prolonged Akt phosphorylation stimulated by FSH plus activin 24 h post-treatment. Infection with the adenoviral constitutively active forkhead box-containing protein, O subfamily (FOXO)1 mutant suppressed induction of cyclin D2, aromatase, inhibin-α, SF-1, and epiregulin. Transient transfections of GCs with constitutively active FOXO1 mutant also suppressed cyclin D2, inhibin-α, and epiregulin promoter-reporter activities. Chromatin immunoprecipitation results demonstrate in vivo the association of FOXO1 with the cyclin D2 promoter in untreated GCs and release of FOXO1 from the cyclin D2 promoter upon addition of FSH plus activin. These results suggest that proliferation and differentiation of GCs in response to FSH plus activin requires both removal of FOXO1-dependent repression and positive signaling from Smad2/3. PMID:15613482

  20. Coupling calcium/calmodulin-mediated signaling and herbivore-induced plant response through calmodulin-binding transcription factor AtSR1/CAMTA3.

    PubMed

    Qiu, Yongjian; Xi, Jing; Du, Liqun; Suttle, Jeffrey C; Poovaiah, B W

    2012-05-01

    Calcium/calmodulin (Ca(2+)/CaM) has long been considered a crucial component in wound signaling pathway. However, very few Ca(2+)/CaM-binding proteins have been identified which regulate plant responses to herbivore attack/wounding stress. We have reported earlier that a family of Ca(2+)/CaM-binding transcription factors designated as AtSRs (also known as AtCAMTAs) can respond differentially to wounding stress. Further studies revealed that AtSR1/CAMTA3 is a negative regulator of plant defense, and Ca(2+)/CaM-binding to AtSR1 is indispensable for the suppression of salicylic acid (SA) accumulation and disease resistance. Here we report that Ca(2+)/CaM-binding is also critical for AtSR1-mediated herbivore-induced wound response. Interestingly, atsr1 mutant plants are more susceptible to herbivore attack than wild-type plants. Complementation of atsr1 mutant plants by overexpressing wild-type AtSR1 protein can effectively restore plant resistance to herbivore attack. However, when mutants of AtSR1 with impaired CaM-binding ability were overexpressed in atsr1 mutant plants, plant resistance to herbivore attack was not restored, suggesting a key role for Ca(2+)/CaM-binding in wound signaling. Furthermore, it was observed that elevated SA levels in atsr1 mutant plants have a negative impact on both basal and induced biosynthesis of jasmonates (JA). These results revealed that Ca(2+)/CaM-mediated signaling regulates plant response to herbivore attack/wounding by modulating the SA-JA crosstalk through AtSR1. PMID:22371088

  1. Highly sensitive fluorescence assay of DNA methyltransferase activity via methylation-sensitive cleavage coupled with nicking enzyme-assisted signal amplification.

    PubMed

    Zhao, Yongxi; Chen, Feng; Wu, Yayan; Dong, Yanhua; Fan, Chunhai

    2013-04-15

    Herein, using DNA adenine methylation (Dam) methyltransferase (MTase) as a model analyte, a simple, rapid, and highly sensitive fluorescence sensing platform for monitoring the activity and inhibition of DNA MTase was developed on the basis of methylation-sensitive cleavage and nicking enzyme-assisted signal amplification. In the presence of Dam MTase, an elaborately designed hairpin probe was methylated. With the help of methylation-sensitive restriction endonuclease DpnI, the methylated hairpin probe could be cleaved to release a single-stranded DNA (ssDNA). Subsequently, this released ssDNA would hybridize with the molecular beacon (MB) to open its hairpin structure, resulting in the restoration of fluorescence signal as well as formation of the double-stranded recognition site for nicking enzyme Nt.BbvCI. Eventually, an amplified fluorescence signal was observed through the enzymatic recycling cleavage of MBs. Based on this unique strategy, a very low detection limit down to 0.06 U/mL was achieved within a short assay time (60 min) in one step, which is superior to those of most existing approaches. Owing to the specific site recognition of MTase toward its substrate, the proposed sensing system was able to readily discriminate Dam MTase from other MTase such as M.SssI and even detect the target in complex biological matrix. Furthermore, the application of the proposed sensing strategy for screening Dam MTase inhibitors was also demonstrated with satisfactory results. This novel method not only provides a promising platform for monitoring activity and inhibition of DNA MTases, but also shows great potentials in biological process researches, drugs discovery and clinical diagnostics. PMID:23202331

  2. H2O2 and cytosolic Ca2+ signals triggered by the PM H-coupled transport system mediate K+/Na+ homeostasis in NaCl-stressed Populus euphratica cells.

    PubMed

    Sun, Jian; Wang, Mei-Juan; Ding, Ming-Quan; Deng, Shu-Rong; Liu, Mei-Qin; Lu, Cun-Fu; Zhou, Xiao-Yang; Shen, Xin; Zheng, Xiao-Jiang; Zhang, Zeng-Kai; Song, Jin; Hu, Zan-Min; Xu, Yue; Chen, Shao-Liang

    2010-06-01

    Using confocal microscopy, X-ray microanalysis and the scanning ion-selective electrode technique, we investigated the signalling of H(2)O(2), cytosolic Ca(2+) ([Ca(2+)](cyt)) and the PM H(+)-coupled transport system in K(+)/Na(+) homeostasis control in NaCl-stressed calluses of Populus euphratica. An obvious Na(+)/H(+) antiport was seen in salinized cells; however, NaCl stress caused a net K(+) efflux, because of the salt-induced membrane depolarization. H(2)O(2) levels, regulated upwards by salinity, contributed to ionic homeostasis, because H(2)O(2) restrictions by DPI or DMTU caused enhanced K(+) efflux and decreased Na(+)/H(+) antiport activity. NaCl induced a net Ca(2+) influx and a subsequent rise of [Ca(2+)](cyt), which is involved in H(2)O(2)-mediated K(+)/Na(+) homeostasis in salinized P. euphratica cells. When callus cells were pretreated with inhibitors of the Na(+)/H(+) antiport system, the NaCl-induced elevation of H(2)O(2) and [Ca(2+)](cyt) was correspondingly restricted, leading to a greater K(+) efflux and a more pronounced reduction in Na(+)/H(+) antiport activity. Results suggest that the PM H(+)-coupled transport system mediates H(+) translocation and triggers the stress signalling of H(2)O(2) and Ca(2+), which results in a K(+)/Na(+) homeostasis via mediations of K(+) channels and the Na(+)/H(+) antiport system in the PM of NaCl-stressed cells. Accordingly, a salt stress signalling pathway of P. euphratica cells is proposed. PMID:20082667

  3. Estrogen stimulated migration and invasion of estrogen receptor-negative breast cancer cells involves an ezrin-dependent crosstalk between G protein-coupled receptor 30 and estrogen receptor beta signaling.

    PubMed

    Zhou, Kewen; Sun, Peng; Zhang, Yaxing; You, Xinchao; Li, Ping; Wang, Tinghuai

    2016-07-01

    Estrogen mediates important cellular activities in estrogen receptor negative (ER-) breast cancer cells via membrane associated G protein-coupled receptor 30 (GPR30). However, the biological role and mechanism of estrogen action on cell motility and invasion in this aggressive kind of tumors remains poorly understood. We showed here that treatment with 17β-estradiol (E2) in ER-negative cancer cells resulted in ezrin-dependent cytoskeleton rearrangement and elicited a stimulatory effect on cell migration and invasion. Mechanistically, E2 induced ezrin activation was mediated by distinct mechanisms in different cell contexts. In SK-BR-3 cells with a high GPR30/ERβ ratio, silencing of GPR30 was able to abolish E2 induced ERK1/2, AKT phosphorylation and ezrin activation, whereas in MDA-MB-231 cells with low GPR30/ERβ ratio, E2 stimulated ezrin activation was mediated by the ERβ/PI3K/AKT signaling pathway. Importantly, we showed that activation of GPR30 signaling significantly prevents ERβ activation induced ezrin phosphorylation, cell migration and invasion, indicating an antagonist effect between GPR30 and ERβ signaling in MDA-MB-231 cells. These findings highlight the important interplay between different estrogen receptors in estrogen induced cell motility and invasiveness in ER-negative breast cancer cells. PMID:26850467

  4. NOX3 NADPH Oxidase Couples Transient Receptor Potential Vanilloid 1 to Signal Transducer and Activator of Transcription 1-Mediated Inflammation and Hearing Loss

    PubMed Central

    Mukherjea, Debashree; Jajoo, Sarvesh; Sheehan, Kelly; Kaur, Tejbeer; Sheth, Sandeep; Bunch, Jennifer; Perro, Christopher; Rybak, Leonard P.

    2011-01-01

    Abstract Transient receptor potential vanilloid 1 (TRPV1) is implicated in cisplatin ototoxicity. Activation of this channel by cisplatin increases reactive oxygen species generation, which contribute to loss of outer hair cells in the cochlea. Knockdown of TRPV1 by short interfering RNA protected against cisplatin ototoxicity. In this study, we examined the mechanism underlying TRPV1-mediated ototoxicity using cultured organ of Corti transformed cells (UB/OC-1) and rats. Trans-tympanic injections of capsaicin produced transient hearing loss within 24 h, which recovered by 72 h. In UB/OC-1 cells, capsaicin increased NOX3 NADPH oxidase activity and activation of signal transducer and activator of transcription 1 (STAT1). Intratympanic administration of capsaicin transiently increased STAT1 activity and expression of downstream proinflammatory molecules. Capsaicin produced a transient increase in CD14-positive inflammatory cells into the cochlea, which mimicked the temporal course of STAT1 activation but did not alter the expression of apoptotic genes or damage to outer hair cells. In addition, trans-tympanic administration of STAT1 short interfering RNA protected against capsaicin-induced hearing loss. These data suggest that activation of TRPV1 mediates temporary hearing loss by initiating an inflammatory process in the cochlea via activation of NOX3 and STAT1. Thus, these proteins represent reasonable targets for ameliorating hearing loss. Antioxid. Redox Signal. 14, 999–1010. PMID:20712533

  5. Momordin Ic couples apoptosis with autophagy in human hepatoblastoma cancer cells by reactive oxygen species (ROS)-mediated PI3K/Akt and MAPK signaling pathways.

    PubMed

    Mi, Yashi; Xiao, Chunxia; Du, Qingwei; Wu, Wanqiang; Qi, Guoyuan; Liu, Xuebo

    2016-01-01

    Momordin Ic is a principal saponin constituent of Fructus Kochiae, which acts as an edible and pharmaceutical product more than 2000 years in China. Our previous research found momordin Ic induced apoptosis by PI3K/Akt and MAPK signaling pathways in HepG2 cells. While the role of autophagy in momordin Ic induced cell death has not been discussed, and the connection between the apoptosis and autophagy is not clear yet. In this work, we reported momordin Ic promoted the formation of autophagic vacuole and expression of Beclin 1 and LC-3 in a dose- and time-dependent manner. Compared with momordin Ic treatment alone, the autophagy inhibitor 3-methyladenine (3-MA) also can inhibit apoptosis, while autophagy activator rapamycin (RAP) has the opposite effect, and the apoptosis inhibitor ZVAD-fmk also inhibited autophagy induced by momordin Ic. Momordin Ic simultaneously induces autophagy and apoptosis by suppressing the ROS-mediated PI3K/Akt and activating the ROS-related JNK and P38 pathways. Additionally, momordin Ic induces apoptosis by suppressing PI3K/Akt-dependent NF-κB pathways and promotes autophagy by ROS-mediated Erk signaling pathway. Those results suggest that momordin Ic has great potential as a nutritional preventive strategy in cancer therapy. PMID:26593748

  6. Nrf2-Mediated HO-1 Induction Coupled with the ERK Signaling Pathway Contributes to Indirect Antioxidant Capacity of Caffeic Acid Phenethyl Ester in HepG2 Cells

    PubMed Central

    Kim, Jin-Kyoung; Jang, Hae-Dong

    2014-01-01

    The objective of this study is to investigate the contributing effect of the nuclear transcription factor-erythroid 2-related factor 2 (Nrf2)-mediated signaling pathway on the indirect antioxidant capacity of caffeic acid phenethyl ester (CAPE) against oxidative stress in HepG2 cells. The result of an antioxidant response element (ARE)-luciferase assay showed that CAPE stimulated ARE promoter activity resulting in increased transcriptional and translational activities of heme oxygenase-1 (HO-1). In addition, CAPE treatment enhanced Nrf2 accumulation in the nucleus and the post-translational phosphorylation level of extracellular signal-regulated kinase (ERK) among several protein kinases tested. Treatment with ERK inhibitor U126 completely suppressed CAPE-induced ERK phosphorylation and HO-1 expression, but it only partly inhibited CAPE-induced Nrf2 accumulation and ARE promoter. Using the 2',7'-dichlorofluorescein-diacetate (DCFH-DA) method, the cellular antioxidant capacity of CAPE against 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH)- or H2O2-induced oxidative stress also was shown to be partially suppressed by the ERK inhibitor. From the overall results it is proposed that the indirect antioxidant activity of CAPE against oxidative stress in HepG2 cells is partially attributed to induction of HO-1, which is regulated by Kelch-like erythroid-cell-derived protein with CNC homology (ECH)-associated protein 1 (Keap1)-independent Nrf2 activation relying on post-translational phosphorylation of ERK. PMID:25007817

  7. Polymerase chain reaction coupling with magnetic nanoparticles-based biotin-avidin system for amplification of chemiluminescent detection signals of nucleic acid.

    PubMed

    Li, Zhiyang; He, Lei; He, Nongyue; Deng, Yan; Shi, Zhiyang; Wang, Hua; Li, Song; Liu, Hongna; Wang, Zhifei; Wang, Daxin

    2011-02-01

    A novel method was established through the detection of chemiluminescent signals of nucleic acid hybridization based on magnetic nanoparticles (MNPs) and PCR. 5' amino- modified specific probes were immobilized on the surface of silanized MNPs by Schiff reaction between amino and aldehyde group. The probes were used to capture the synthetic biotin-dUTP-labeled DNA fragments which were obtained by polymerase chain reaction (PCR). Then these complexes were bonded with streptavidin-modified alkaline phosphatase (SA-AP). Finally the chemiluminescent signals were detected by adding 3-(2'-spiroadamantane)- 4-methoxy -4-(3"-phosphoryloxy) phenyl-1, 2-dioxetane (AMPPD) which was the substrate reagent of AP. The concentration of probes which were immobilized on the surface of MNPs was studied, how to reduce the adsorption of SA-AP on the surface of MNPs was also researched. It was shown that 12.5 pmol of probes were immobilized on 1 mg of MNPs. Aldehyde-MNPs modified with probes could adsorb SA-AP, affecting the sensitivity of chemiluminescene consequently. Reduction of aldehyde group by sodium borohydride and blocking the bare position of MNPs with bovine serum albumin (BSA) could decrease the background of chemiluminescence, and this method has good specificity in detection of chloramphenicol acetyltransferase (CAT) gene. PMID:21456141

  8. Kinetic and mechanistic analyses of new classes of inhibitors of two-component signal transduction systems using a coupled assay containing HpkA-DrrA from Thermotoga maritima.

    PubMed

    Foster, J Estelle; Sheng, Qin; McClain, Jonathan R; Bures, Mark; Nicas, Thalia I; Henry, Kenneth; Winkler, Malcolm E; Gilmour, Raymond

    2004-04-01

    Two-component signal transduction systems (TCSs) play fundamental roles in bacterial survival and pathogenesis and have been proposed as targets for the development of novel classes of antibiotics. A new coupled assay was developed and applied to analyse the kinetic mechanisms of three new kinds of inhibitors of TCS function. The assay exploits the biochemical properties of the cognate HpkA-DrrA histidine kinase-response regulator pair from Thermotoga maritima and allows multiple turnovers of HpkA, linear formation of phosphorylated DrrA, and Michaelis-Menten analysis of inhibitors. The assay was validated in several ways, including confirmation of competitive inhibition by adenosine 5'-beta,gamma-imidotriphosphate (AMP-PNP). The coupled assay, autophosphorylation and chemical cross-linking were used to determine the mechanisms by which several compounds inhibit TCS function. A cyanoacetoacetamide showed non-competitive inhibition with respect to ATP concentration in the coupled assay. The cyanoacetoacetamide also inhibited autophosphorylation of histidine kinases from other bacteria, indicating that the coupled assay could detect general inhibitors of histidine kinase function. Inhibition of HpkA autophosphorylation by this compound was probably caused by aggregation of HpkA, consistent with a previous model for other hydrophobic compounds. In contrast, ethodin was a potent inhibitor of the combined assay, did not inhibit HpkA autophosphorylation, but still led to aggregation of HpkA. These data suggest that ethodin bound to the HpkA kinase and inhibited transfer of the phosphoryl group to DrrA. A peptide corresponding to the phosphorylation site of DrrA appeared to inhibit TCS function by a mechanism similar to that of ethodin, except that autophosphorylation was inhibited at high peptide concentrations. The latter mechanism of inhibition of TCS function is unusual and its analysis demonstrates the utility of these approaches to the kinetic analyses of additional

  9. Serelaxin-mediated signal transduction in human vascular cells: bell-shaped concentration–response curves reflect differential coupling to G proteins

    PubMed Central

    Sarwar, M; Samuel, C S; Bathgate, R A; Stewart, D R; Summers, R J

    2015-01-01

    Background and Purpose In a recently conducted phase III clinical trial, RELAX-AHF, serelaxin infusion over 48 h improved short- and long-term clinical outcomes in patients with acute heart failure. In this study we used human primary cells from the umbilical vasculature to better understand the signalling mechanisms activated by serelaxin. Experimental Approach We examined the acute effects of serelaxin on signal transduction mechanisms in primary human umbilical vascular cells and its chronic actions on markers of cardiovascular function and disease. Key Results The RXFP1 receptor, the cognate serelaxin receptor, was expressed at the cell surface in HUVECs and human umbilical vein smooth muscle cells (HUVSMCs), human umbilical artery smooth muscle cells (HUASMCs) and human cardiac fibroblasts (HCFs), but not human umbilical artery endothelial cells. In HUVECs and HUVSMCs, serelaxin increased cAMP, cGMP accumulation and pERK1/2, and the concentration–response curves (CRCs) were bell-shaped. Similar bell-shaped CRCs for cGMP and pERK1/2 were observed in HCFs, whereas in HUASMCs, serelaxin increased cAMP, cGMP and pERK1/2 with sigmoidal CRCs. Gαi/o and lipid raft disruption, but not Gαs inhibition, altered the serelaxin CRC for cAMP and cGMP accumulation in HUVSMC but not HUASMC. Longer term serelaxin exposure increased the expression of neuronal NOS, VEGF, ETβ receptors and MMPs (gelatinases) in RXFP1 receptor-expressing cells. Conclusions and Implications Serelaxin caused acute and chronic changes in human umbilical vascular cells that were cell background dependent. Bell-shaped CRCs that were observed only in venous cells and fibroblasts involved Gαi/o located within membrane lipid rafts. PMID:25297987

  10. Berberine attenuates high glucose-induced fibrosis by activating the G protein-coupled bile acid receptor TGR5 and repressing the S1P2/MAPK signaling pathway in glomerular mesangial cells.

    PubMed

    Yang, Zhiying; Li, Jie; Xiong, Fengxiao; Huang, Junying; Chen, Cheng; Liu, Peiqing; Huang, Heqing

    2016-08-15

    Berberine (BBR) exerts powerful renoprotective effects on diabetic nephropathy (DN), but the underlying mechanisms remain unclear. We previously demonstrated that activation of the G protein-coupled bile acid receptor TGR5 ameliorates diabetic nephropathy by inhibiting the activation of the sphingosine 1-phosphate (S1P)/sphingosine 1-phosphate receptor 2 (S1P2) signaling pathway. In this study, we explored the role of TGR5 in the BBR-induced downregulation of sphingosine 1-phosphate receptor 2 (S1P2)/mitogen-activated protein kinase (MAPK)-mediated fibrosis in glomerular mesangial cells (GMCs). Results showed that, BBR suppressed the expression of FN, ICAM-1, and TGF-β1 in high-glucose cultures of GMCs, and the phosphorylation level of c-Jun/c-Fos was downregulated. The high glucose lowered TGR5 expression in a time-dependent manner; this effect was reversed by BBR in a dose-dependent manner. The TGR5 agonist INT-777 decreased the high glucose-induced FN, ICAM-1, and TGF-β1 protein contents. In addition, TGR5 siRNA blocked S1P2 degradation by BBR. And MAPK signaling, which plays important regulatory roles in the pathological progression of DN, was activated by TGR5 siRNA. Apart from this, MAPK signaling as well as FN, ICAM-1, and TGF-β1 suppressed by BBR under high glucose conditions were limited by TGR5 depletion. Thus, BBR decreases FN, ICAM-1, and TGF-β1 levels under high glucose conditions in GMCs possibly by activating TGR5 and inhibiting S1P2/MAPK signaling. PMID:27292312

  11. Microcontrollers Generate Timing Signals For CCD Arrays

    NASA Technical Reports Server (NTRS)

    Hostetter, Marilyn K.; Mccloskey, John C.; Reed, Kenneth V.

    1992-01-01

    Microcontrollers generate timing signals for charge-coupled-device array detectors in electronic system developed to test such detectors. With microcontroller, one changes timing signals via software, without changes in wiring. Approach more flexible, timing signals changed easier and quicker.

  12. Acidosis promotes Bcl-2 family-mediated evasion of apoptosis: involvement of acid-sensing G protein-coupled receptor Gpr65 signaling to Mek/Erk.

    PubMed

    Ryder, Christopher; McColl, Karen; Zhong, Fei; Distelhorst, Clark W

    2012-08-10

    Acidosis arises in solid and lymphoid malignancies secondary to altered nutrient supply and utilization. Tumor acidosis correlates with therapeutic resistance, although the mechanism behind this effect is not fully understood. Here we show that incubation of lymphoma cell lines in acidic conditions (pH 6.5) blocks apoptosis induced by multiple cytotoxic metabolic stresses, including deprivation of glucose or glutamine and treatment with dexamethasone. We sought to examine the role of the Bcl-2 family of apoptosis regulators in this process. Interestingly, we found that acidic culture causes elevation of both Bcl-2 and Bcl-xL, while also attenuating glutamine starvation-induced elevation of p53-up-regulated modulator of apoptosis (PUMA) and Bim. We confirmed with knockdown studies that these shifts direct survival decisions during starvation and acidosis. Importantly, the promotion of a high anti- to pro-apoptotic Bcl-2 family member ratio by acidosis renders cells exquisitely sensitive to the Bcl-2/Bcl-xL antagonist ABT-737, suggesting that acidosis causes Bcl-2 family dependence. This dependence appears to be mediated, in part, by the acid-sensing G protein-coupled receptor, GPR65, via a MEK/ERK pathway. PMID:22685289

  13. A dPIP5K Dependent Pool of Phosphatidylinositol 4,5 Bisphosphate (PIP2) Is Required for G-Protein Coupled Signal Transduction in Drosophila Photoreceptors

    PubMed Central

    Yadav, Shweta; Kumari, Kamalesh; Nair, Amit; Trivedi, Deepti; Raghu, Padinjat

    2015-01-01

    Multiple PIP2 dependent molecular processes including receptor activated phospholipase C activity occur at the neuronal plasma membranes, yet levels of this lipid at the plasma membrane are remarkably stable. Although the existence of unique pools of PIP2 supporting these events has been proposed, the mechanism by which they are generated is unclear. In Drosophila photoreceptors, the hydrolysis of PIP2 by G-protein coupled phospholipase C activity is essential for sensory transduction of photons. We identify dPIP5K as an enzyme essential for PIP2 re-synthesis in photoreceptors. Loss of dPIP5K causes profound defects in the electrical response to light and light-induced PIP2 dynamics at the photoreceptor membrane. Overexpression of dPIP5K was able to accelerate the rate of PIP2 synthesis following light induced PIP2 depletion. Other PIP2 dependent processes such as endocytosis and cytoskeletal function were unaffected in photoreceptors lacking dPIP5K function. These results provide evidence for the existence of a unique dPIP5K dependent pool of PIP2 required for normal Drosophila phototransduction. Our results define the existence of multiple pools of PIP2 in photoreceptors generated by distinct lipid kinases and supporting specific molecular processes at neuronal membranes. PMID:25633995

  14. NOX3 NADPH oxidase couples transient receptor potential vanilloid 1 to signal transducer and activator of transcription 1-mediated inflammation and hearing loss.

    PubMed

    Mukherjea, Debashree; Jajoo, Sarvesh; Sheehan, Kelly; Kaur, Tejbeer; Sheth, Sandeep; Bunch, Jennifer; Perro, Christopher; Rybak, Leonard P; Ramkumar, Vickram

    2011-03-15

    Transient receptor potential vanilloid 1 (TRPV1) is implicated in cisplatin ototoxicity. Activation of this channel by cisplatin increases reactive oxygen species generation, which contribute to loss of outer hair cells in the cochlea. Knockdown of TRPV1 by short interfering RNA protected against cisplatin ototoxicity. In this study, we examined the mechanism underlying TRPV1-mediated ototoxicity using cultured organ of Corti transformed cells (UB/OC-1) and rats. Trans-tympanic injections of capsaicin produced transient hearing loss within 24 h, which recovered by 72 h. In UB/OC-1 cells, capsaicin increased NOX3 NADPH oxidase activity and activation of signal transducer and activator of transcription 1 (STAT1). Intratympanic administration of capsaicin transiently increased STAT1 activity and expression of downstream proinflammatory molecules. Capsaicin produced a transient increase in CD14-positive inflammatory cells into the cochlea, which mimicked the temporal course of STAT1 activation but did not alter the expression of apoptotic genes or damage to outer hair cells. In addition, trans-tympanic administration of STAT1 short interfering RNA protected against capsaicin-induced hearing loss. These data suggest that activation of TRPV1 mediates temporary hearing loss by initiating an inflammatory process in the cochlea via activation of NOX3 and STAT1. Thus, these proteins represent reasonable targets for ameliorating hearing loss. PMID:20712533

  15. Marginal zone B cells exacerbate endotoxic shock via interleukin-6 secretion induced by Fcα/μR-coupled TLR4 signalling.

    PubMed

    Honda, Shin-Ichiro; Sato, Kazuki; Totsuka, Naoya; Fujiyama, Satoshi; Fujimoto, Manabu; Miyake, Kensuke; Nakahashi-Oda, Chigusa; Tahara-Hanaoka, Satoko; Shibuya, Kazuko; Shibuya, Akira

    2016-01-01

    Marginal zone (MZ) B cells produce a first wave of antibodies for protection from blood-borne pathogens. However, the role of MZ B cells in inflammatory responses has not been elucidated. Here we show that MZ B cells produce pro-inflammatory cytokines, such as interleukin-6 (IL-6), and exacerbate systemic inflammatory responses to lipopolysaccharide (LPS). After intravenous injection of LPS or E. coli, mice deficient in MZ B cells or IL-6 only in MZ B cells have attenuated systemic inflammatory responses and prolonged survival compared with wild-type mice. LPS directly stimulates MZ B cells via Toll-like receptor 4 (TLR4) and MyD88 pathways for IL-6 production. Furthermore, TLR4 requires physical and functional association with Fcα/μR (CD351) for its oligomer formation, NF-κB signalling and IL-6 production from MZ B cells; this association is responsible for systemic inflammatory responses and endotoxic shock. These results reveal a pro-inflammatory role of MZ B cells in endotoxic shock. PMID:27146354

  16. The MDM2-p53-pyruvate carboxylase signalling axis couples mitochondrial metabolism to glucose-stimulated insulin secretion in pancreatic β-cells.

    PubMed

    Li, Xiaomu; Cheng, Kenneth K Y; Liu, Zhuohao; Yang, Jin-Kui; Wang, Baile; Jiang, Xue; Zhou, Yawen; Hallenborg, Philip; Hoo, Ruby L C; Lam, Karen S L; Ikeda, Yasuhiro; Gao, Xin; Xu, Aimin

    2016-01-01

    Mitochondrial metabolism is pivotal for glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells. However, little is known about the molecular machinery that controls the homeostasis of intermediary metabolites in mitochondria. Here we show that the activation of p53 in β-cells, by genetic deletion or pharmacological inhibition of its negative regulator MDM2, impairs GSIS, leading to glucose intolerance in mice. Mechanistically, p53 activation represses the expression of the mitochondrial enzyme pyruvate carboxylase (PC), resulting in diminished production of the TCA cycle intermediates oxaloacetate and NADPH, and impaired oxygen consumption. The defective GSIS and mitochondrial metabolism in MDM2-null islets can be rescued by restoring PC expression. Under diabetogenic conditions, MDM2 and p53 are upregulated, whereas PC is reduced in mouse β-cells. Pharmacological inhibition of p53 alleviates defective GSIS in diabetic islets by restoring PC expression. Thus, the MDM2-p53-PC signalling axis links mitochondrial metabolism to insulin secretion and glucose homeostasis, and could represent a therapeutic target in diabetes. PMID:27265727

  17. The Staphylococcus aureus KdpDE Two-Component System Couples Extracellular K+ Sensing and Agr Signaling to Infection Programming ▿ † ‡

    PubMed Central

    Xue, Ting; You, Yibo; Hong, De; Sun, Haipeng; Sun, Baolin

    2011-01-01

    The Kdp system is widely distributed among bacteria. In Escherichia coli, the Kdp-ATPase is a high-affinity K+ uptake system and its expression is activated by the KdpDE two-component system in response to K+ limitation or salt stress. However, information about the role of this system in many bacteria still remains obscure. Here we demonstrate that KdpFABC in Staphylococcus aureus is not a major K+ transporter and that the main function of KdpDE is not associated with K+ transport but that instead it regulates transcription for a series of virulence factors through sensing external K+ concentrations, indicating that this bacterium might modulate its infectious status through sensing specific external K+ stimuli in different environments. Our results further reveal that S. aureus KdpDE is upregulated by the Agr/RNAIII system, which suggests that KdpDE may be an important virulence regulator coordinating the external K+ sensing and Agr signaling during pathogenesis in this bacterium. PMID:21422185

  18. Marginal zone B cells exacerbate endotoxic shock via interleukin-6 secretion induced by Fcα/μR-coupled TLR4 signalling

    PubMed Central

    Honda, Shin-ichiro; Sato, Kazuki; Totsuka, Naoya; Fujiyama, Satoshi; Fujimoto, Manabu; Miyake, Kensuke; Nakahashi-Oda, Chigusa; Tahara-Hanaoka, Satoko; Shibuya, Kazuko; Shibuya, Akira

    2016-01-01

    Marginal zone (MZ) B cells produce a first wave of antibodies for protection from blood-borne pathogens. However, the role of MZ B cells in inflammatory responses has not been elucidated. Here we show that MZ B cells produce pro-inflammatory cytokines, such as interleukin-6 (IL-6), and exacerbate systemic inflammatory responses to lipopolysaccharide (LPS). After intravenous injection of LPS or E. coli, mice deficient in MZ B cells or IL-6 only in MZ B cells have attenuated systemic inflammatory responses and prolonged survival compared with wild-type mice. LPS directly stimulates MZ B cells via Toll-like receptor 4 (TLR4) and MyD88 pathways for IL-6 production. Furthermore, TLR4 requires physical and functional association with Fcα/μR (CD351) for its oligomer formation, NF-κB signalling and IL-6 production from MZ B cells; this association is responsible for systemic inflammatory responses and endotoxic shock. These results reveal a pro-inflammatory role of MZ B cells in endotoxic shock. PMID:27146354

  19. The MDM2–p53–pyruvate carboxylase signalling axis couples mitochondrial metabolism to glucose-stimulated insulin secretion in pancreatic β-cells

    PubMed Central

    Li, Xiaomu; Cheng, Kenneth K. Y.; Liu, Zhuohao; Yang, Jin-Kui; Wang, Baile; Jiang, Xue; Zhou, Yawen; Hallenborg, Philip; Hoo, Ruby L. C.; Lam, Karen S. L.; Ikeda, Yasuhiro; Gao, Xin; Xu, Aimin

    2016-01-01

    Mitochondrial metabolism is pivotal for glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells. However, little is known about the molecular machinery that controls the homeostasis of intermediary metabolites in mitochondria. Here we show that the activation of p53 in β-cells, by genetic deletion or pharmacological inhibition of its negative regulator MDM2, impairs GSIS, leading to glucose intolerance in mice. Mechanistically, p53 activation represses the expression of the mitochondrial enzyme pyruvate carboxylase (PC), resulting in diminished production of the TCA cycle intermediates oxaloacetate and NADPH, and impaired oxygen consumption. The defective GSIS and mitochondrial metabolism in MDM2-null islets can be rescued by restoring PC expression. Under diabetogenic conditions, MDM2 and p53 are upregulated, whereas PC is reduced in mouse β-cells. Pharmacological inhibition of p53 alleviates defective GSIS in diabetic islets by restoring PC expression. Thus, the MDM2–p53–PC signalling axis links mitochondrial metabolism to insulin secretion and glucose homeostasis, and could represent a therapeutic target in diabetes. PMID:27265727

  20. Structural Elements in the Gαs and Gαq C Termini That Mediate Selective G Protein-coupled Receptor (GPCR) Signaling.

    PubMed

    Semack, Ansley; Sandhu, Manbir; Malik, Rabia U; Vaidehi, Nagarajan; Sivaramakrishnan, Sivaraj

    2016-08-19

    Although the importance of the C terminus of the α subunit of the heterotrimeric G protein in G protein-coupled receptor (GPCR)-G protein pairing is well established, the structural basis of selective interactions remains unknown. Here, we combine live cell FRET-based measurements and molecular dynamics simulations of the interaction between the GPCR and a peptide derived from the C terminus of the Gα subunit (Gα peptide) to dissect the molecular mechanisms of G protein selectivity. We observe a direct link between Gα peptide binding and stabilization of the GPCR conformational ensemble. We find that cognate and non-cognate Gα peptides show deep and shallow binding, respectively, and in distinct orientations within the GPCR. Binding of the cognate Gα peptide stabilizes the agonist-bound GPCR conformational ensemble resulting in favorable binding energy and lower flexibility of the agonist-GPCR pair. We identify three hot spot residues (Gαs/Gαq-Gln-384/Leu-349, Gln-390/Glu-355, and Glu-392/Asn-357) that contribute to selective interactions between the β2-adrenergic receptor (β2-AR)-Gαs and V1A receptor (V1AR)-Gαq The Gαs and Gαq peptides adopt different orientations in β2-AR and V1AR, respectively. The β2-AR/Gαs peptide interface is dominated by electrostatic interactions, whereas the V1AR/Gαq peptide interactions are predominantly hydrophobic. Interestingly, our study reveals a role for both favorable and unfavorable interactions in G protein selection. Residue Glu-355 in Gαq prevents this peptide from interacting strongly with β2-AR. Mutagenesis to the Gαs counterpart (E355Q) imparts a cognate-like interaction. Overall, our study highlights the synergy in molecular dynamics and FRET-based approaches to dissect the structural basis of selective G protein interactions. PMID:27330078

  1. The Selective Estrogen Receptor Modulator Raloxifene Regulates Arginine-Vasopressin Gene Expression in Human Female Neuroblastoma Cells Through G Protein-Coupled Estrogen Receptor and ERK Signaling.

    PubMed

    Grassi, Daniela; Ghorbanpoor, Samar; Acaz-Fonseca, Estefania; Ruiz-Palmero, Isabel; Garcia-Segura, Luis M

    2015-10-01

    The selective estrogen receptor modulator raloxifene reduces blood pressure in hypertensive postmenopausal women. In the present study we have explored whether raloxifene regulates gene expression of arginine vasopressin (AVP), which is involved in the pathogenesis of hypertension. The effect of raloxifene was assessed in human female SH-SY5Y neuroblastoma cells, which have been recently identified as a suitable cellular model to study the estrogenic regulation of AVP. Raloxifene, within a concentration ranging from 10(-10) M to 10(-6) M, decreased the mRNA levels of AVP in SH-SY5Y cells with maximal effect at 10(-7) M. This effect of raloxifene was imitated by an agonist (±)-1-[(3aR*,4S*,9bS*)-4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-8-yl]-ethanone of G protein-coupled estrogen receptor-1 (GPER) and blocked by an antagonist (3aS*,4R*,9bR*)-4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-3H-cyclopenta[c]quinoline of GPER and by GPER silencing. Raloxifene induced a time-dependent increase in the level of phosphorylated ERK1 and ERK2, by a mechanism blocked by the GPER antagonist. The treatment of SH-SY5Y cells with either a MAPK/ERK kinase 1/2-specific inhibitor (1,4-diamino-2, 3-dicyano-1,4-bis(2-aminophenylthio)butadine) or a protein kinase C inhibitor (sotrastaurin) blocked the effects of raloxifene on the phosphorylation of ERK1/2 and the regulation of AVP mRNA levels. These results reveal a mechanism mediating the regulation of AVP expression by raloxifene, involving the activation of GPER, which in turn activates protein kinase C, MAPK/ERK kinase, and ERK. The regulation of AVP by raloxifene and GPER may have implications for the treatment of blood hypertension(.). PMID:26200092

  2. Signal voter

    DOEpatents

    Goodwin, Roy L.

    1981-01-01

    A voter for providing a single accurate output signal that is derived from the closest two signal levels of three input signals, each of which signals represents a measurement of the same phenomena. By means of the voting circuit, the signals are first sorted by level of amplitude and then ranked as highest, middle or lowest. The highest or lowest signal that is furthest from the middle signal is rejected, while the other highest or lowest signal is selected for processing. The selected high or low signal is then averaged with the middle signal to provide the output signal.

  3. H2O2-Activated Mitochondrial Phospholipase iPLA2γ Prevents Lipotoxic Oxidative Stress in Synergy with UCP2, Amplifies Signaling via G-Protein–Coupled Receptor GPR40, and Regulates Insulin Secretion in Pancreatic β-Cells

    PubMed Central

    Ježek, Jan; Dlasková, Andrea; Zelenka, Jaroslav; Jabůrek, Martin

    2015-01-01

    Abstract Aims: Pancreatic β-cell chronic lipotoxicity evolves from acute free fatty acid (FA)–mediated oxidative stress, unprotected by antioxidant mechanisms. Since mitochondrial uncoupling protein-2 (UCP2) plays antioxidant and insulin-regulating roles in pancreatic β-cells, we tested our hypothesis, that UCP2-mediated uncoupling attenuating mitochondrial superoxide production is initiated by FA release due to a direct H2O2-induced activation of mitochondrial phospholipase iPLA2γ. Results: Pro-oxidant tert-butylhydroperoxide increased respiration, decreased membrane potential and mitochondrial matrix superoxide release rates of control but not UCP2- or iPLA2γ-silenced INS-1E cells. iPLA2γ/UCP2-mediated uncoupling was alternatively activated by an H2O2 burst, resulting from palmitic acid (PA) β-oxidation, and it was prevented by antioxidants or catalase overexpression. Exclusively, nascent FAs that cleaved off phospholipids by iPLA2γ were capable of activating UCP2, indicating that the previously reported direct redox UCP2 activation is actually indirect. Glucose-stimulated insulin release was not affected by UCP2 or iPLA2γ silencing, unless pro-oxidant activation had taken place. PA augmented insulin secretion via G-protein–coupled receptor 40 (GPR40), stimulated by iPLA2γ-cleaved FAs (absent after GPR40 silencing). Innovation and Conclusion: The iPLA2γ/UCP2 synergy provides a feedback antioxidant mechanism preventing oxidative stress by physiological FA intake in pancreatic β-cells, regulating glucose-, FA-, and redox-stimulated insulin secretion. iPLA2γ is regulated by exogenous FA via β-oxidation causing H2O2 signaling, while FAs are cleaved off phospholipids, subsequently acting as amplifying messengers for GPR40. Hence, iPLA2γ acts in eminent physiological redox signaling, the impairment of which results in the lack of antilipotoxic defense and contributes to chronic lipotoxicity. Antioxid. Redox Signal. 23, 958–972. PMID:25925080

  4. New perspectives in signaling mediated by receptors coupled to stimulatory G protein: the emerging significance of cAMP efflux and extracellular cAMP-adenosine pathway

    PubMed Central

    Godinho, Rosely O.; Duarte, Thiago; Pacini, Enio S. A.

    2015-01-01

    G protein-coupled receptors (GPCRs) linked to stimulatory G (Gs) proteins (GsPCRs) mediate increases in intracellular cyclic AMP as consequence of activation of nine adenylyl cyclases , which differ considerably in their cellular distribution and activation mechanisms. Once produced, cyclic AMP may act via distinct intracellular signaling effectors such as protein kinase A and the exchange proteins activated by cAMP (Epacs). More recently, attention has been focused on the efflux of cAMP through a specific transport system named multidrug resistance proteins that belongs to the ATP-binding cassette transporter superfamily. Outside the cell, cAMP is metabolized into adenosine, which is able to activate four distinct subtypes of adenosine receptors, members of the GPCR family: A1, A2A, A2B, and A3. Taking into account that this phenomenon occurs in numerous cell types, as consequence of GsPCR activation and increment in intracellular cAMP levels, in this review, we will discuss the impact of cAMP efflux and the extracellular cAMP-adenosine pathway on the regulation of GsPCR-induced cell response. PMID:25859216

  5. Measurand transient signal suppressor

    NASA Technical Reports Server (NTRS)

    Bozeman, Richard J., Jr. (Inventor)

    1994-01-01

    A transient signal suppressor for use in a controls system which is adapted to respond to a change in a physical parameter whenever it crosses a predetermined threshold value in a selected direction of increasing or decreasing values with respect to the threshold value and is sustained for a selected discrete time interval is presented. The suppressor includes a sensor transducer for sensing the physical parameter and generating an electrical input signal whenever the sensed physical parameter crosses the threshold level in the selected direction. A manually operated switch is provided for adapting the suppressor to produce an output drive signal whenever the physical parameter crosses the threshold value in the selected direction of increasing or decreasing values. A time delay circuit is selectively adjustable for suppressing the transducer input signal for a preselected one of a plurality of available discrete suppression time and producing an output signal only if the input signal is sustained for a time greater than the selected suppression time. An electronic gate is coupled to receive the transducer input signal and the timer output signal and produce an output drive signal for energizing a control relay whenever the transducer input is a non-transient signal which is sustained beyond the selected time interval.

  6. DC coupled Doppler radar physiological monitor.

    PubMed

    Zhao, Xi; Song, Chenyan; Lubecke, Victor; Boric-Lubecke, Olga

    2011-01-01

    One of the challenges in Doppler radar systems for physiological monitoring is a large DC offset in baseband outputs. Typically, AC coupling is used to eliminate this DC offset. Since the physiological signals of interest include frequency content near DC, it is not desirable to simply use AC coupling on the radar outputs. While AC coupling effectively removes DC offset, it also introduces a large time delay and distortion. This paper presents the first DC coupled IQ demodulator printed circuit board (PCB) design and measurements. The DC coupling is achieved by using a mixer with high LO to RF port isolation, resulting in a very low radar DC offset on the order of mV. The DC coupled signals from the PCB radar system were successfully detected with significant LNA gain without saturation. Compared to the AC coupled results, the DC coupled results show great advantages of less signal distortion and more accurate rate estimation. PMID:22254704

  7. Helix coupling

    DOEpatents

    Ginell, W.S.

    1982-03-17

    A coupling for connecting helix members in series, which consists of a pair of U-shaped elements, one of which is attached to each helix end with the U sections of the elements interlocked. The coupling is particularly beneficial for interconnecting helical Nitinol elements utilized in thermal actuators or engines. Each coupling half is attached to the associated helix at two points, thereby providing axial load while being easily removed from the helix, and reusable.

  8. Helix coupling

    DOEpatents

    Ginell, William S.

    1989-04-25

    A coupling for connecting helix members in series, which consists of a pair of U-shaped elements, one of which is attached to each helix end with the "U" sections of the elements interlocked. The coupling is particularly beneficial for interconnecting helical Nitinol elements utilized in thermal actuators or engines. Each coupling half is attached to the associated helix at two points, thereby providing axial load while being easily removed from the helix, and reusable.

  9. Planar slot coupled microwave hybrid

    DOEpatents

    Petter, Jeffrey K.

    1991-01-01

    A symmetrical 180.degree. microwave hybrid is constructed by opening a slot line in a ground plane below a conducting strip disposed on a dielectric substrate, creating a slot coupled conductor. Difference signals propagating on the slot coupled conductor are isolated on the slot line leaving sum signals to propagate on the microstrip. The difference signal is coupled from the slot line onto a second microstrip line for transmission to a desired location. The microstrip branches in a symmetrical fashion to provide the input/output ports of the 180.degree. hybrid. The symmetry of the device provides for balance and isolation between sum and difference signals, and provides an advantageous balance between the power handling capabilities and the bandwidth of the device.

  10. Estrogen and pure antiestrogen fulvestrant (ICI 182 780) augment cell–matrigel adhesion of MCF-7 breast cancer cells through a novel G protein coupled estrogen receptor (GPR30)-to-calpain signaling axis

    SciTech Connect

    Chen, Yan; Li, Zheng; He, Yan; Shang, Dandan; Pan, Jigang; Wang, Hongmei; Chen, Huamei; Zhu, Zhuxia; Wang, Xudong

    2014-03-01

    Fulvestrant (ICI 182 780, ICI) has been used in treating patients with hormone-sensitive breast cancer, yet initial or acquired resistance to endocrine therapies frequently arises and, in particular, cancer recurs as metastasis. We demonstrate here that both 17-beta-estradiol (E2) and ICI enhance cell adhesion to matrigel in MCF-7 breast cancer cells, with increased autolysis of calpain 1 (large subunit) and proteolysis of focal adhesion kinase (FAK), indicating calpain activation. Additionally, either E2 or ICI induced down-regulation of estrogen receptor α without affecting G protein coupled estrogen receptor 30 (GPR30) expression. Interestingly, GPR30 agonist G1 triggered calpain 1 autolysis but not calpain 2, whereas ER agonist diethylstilbestrol caused no apparent calpain autolysis. Furthermore, the actions of E2 and ICI on calpain and cell adhesion were tremendously suppressed by G15, or knockdown of GPR30. E2 and ICI also induced phosphorylation of extracellular regulated protein kinases 1 and 2 (ERK1/2), and suppression of ERK1/2 phosphorylation by U0126 profoundly impeded calpain activation triggered by estrogenic and antiestrogenic stimulations indicating implication of ERK1/2 in the GPR30-mediated action. Lastly, the E2- or ICI-induced cell adhesion was dramatically impaired by calpain-specific inhibitors, ALLN or calpeptin, suggesting requirement of calpain in the GPR30-associated action. These data show that enhanced cell adhesion by E2 and ICI occurs via a novel GPR30-ERK1/2-calpain pathway. Our results indicate that targeting the GPR30 signaling may be a potential strategy to reduce metastasis and improve the efficacy of antiestrogens in treatment of advanced breast cancer. - Highlights: • Estrogen and ICI augment adhesion to matrigel with calpain activation in MCF-7 cells. • GPR30 mediates cell–matrigel adhesion and calpain activation via ERK1/2. • Calpain is required in the cell–matrigel adhesion induced by E2 and ICI.

  11. Inhibitory effects of omega-3 fatty acids on early brain injury after subarachnoid hemorrhage in rats: Possible involvement of G protein-coupled receptor 120/β-arrestin2/TGF-β activated kinase-1 binding protein-1 signaling pathway.

    PubMed

    Yin, Jia; Li, Haiying; Meng, Chengjie; Chen, Dongdong; Chen, Zhouqing; Wang, Yibin; Wang, Zhong; Chen, Gang

    2016-06-01

    Omega-3 fatty acids have been reported to improve neuron functions during aging and in patients affected by mild cognitive impairment, and mediate potent anti-inflammatory via G protein-coupled receptor 120 (GPR120) signal pathway. Neuron dysfunction and inflammatory response also contributed to the progression of subarachnoid hemorrhage (SAH)-induced early brain injury (EBI). This study was to examine the effects of omega-3 fatty acids on SAH-induced EBI. Two weeks before SAH, 30% Omega-3 fatty acids was administered by oral gavage at 1g/kg body weight once every 24h. Specific siRNA for GPR120 was exploited. Terminal deoxynucleotidyl transferase dUTP nick end labeling, fluoro-Jade B staining, and neurobehavioral scores and brain water content test showed that omega-3 fatty acids effectively suppressed SAH-induced brain cell apoptosis and neuronal degradation, behavioral impairment, and brain edema. Western blot, immunoprecipitation, and electrophoretic mobility shift assays results showed that omega-3 fatty acids effectively suppressed SAH-induced elevation of inflammatory factors, including cyclooxygenase-2, monocyte chemoattractant protein-1, and inducible nitric oxide synthase. In addition, omega-3 fatty acids could inhibit phosphorylation of transforming growth factor β activated kinase-1 (TAK1), MEK4, c-Jun N-terminal kinase, and IkappaB kinase as well as activation of nuclear factor kappa B through regulating GPR120/β-arrestin2/TAK1 binding protein-1 pathway. Furthermore, siRNA-induced GPR120 silencing blocked the protective effects of omega-3 fatty acids. Here, we show that stimulation of GPR120 with omega-3 fatty acids pretreatment causes anti-apoptosis and anti-inflammatory effects via β-arrestin2/TAK1 binding protein-1/TAK1 pathway in the brains of SAH rats. Fish omega-3 fatty acids as part of a daily diet may reduce EBI in an experimental rat model of SAH. PMID:27000704

  12. A KSHV microRNA Directly Targets G Protein-Coupled Receptor Kinase 2 to Promote the Migration and Invasion of Endothelial Cells by Inducing CXCR2 and Activating AKT Signaling

    PubMed Central

    Bai, Zhiqiang; Qin, Di; Yan, Qin; Zhu, Jianzhong; Krueger, Brian J.; Renne, Rolf; Gao, Shou-Jiang; Lu, Chun

    2015-01-01

    Kaposi's sarcoma (KS) is a highly disseminated angiogenic tumor of endothelial cells linked to infection by Kaposi's sarcoma-associated herpesvirus (KSHV). KSHV encodes more than two dozens of miRNAs but their roles in KSHV-induced tumor dissemination and metastasis remain unknown. Here, we found that ectopic expression of miR-K12-3 (miR-K3) promoted endothelial cell migration and invasion. Bioinformatics and luciferase reporter analyses showed that miR-K3 directly targeted G protein-coupled receptor (GPCR) kinase 2 (GRK2, official gene symbol ADRBK1). Importantly, overexpression of GRK2 reversed miR-K3 induction of cell migration and invasion. Furthermore, the chemokine receptor CXCR2, which was negatively regulated by GRK2, was upregulated in miR-K3-transduced endothelial cells. Knock down of CXCR2 abolished miR-K3-induced cell migration and invasion. Moreover, miR-K3 downregulation of GRK2 relieved its direct inhibitory effect on AKT. Both CXCR2 induction and the release of AKT from GRK2 were required for miR-K3 maximum activation of AKT and induction of cell migration and invasion. Finally, deletion of miR-K3 from the KSHV genome abrogated its effect on the GRK2/CXCR2/AKT pathway and KSHV-induced migration and invasion. Our data provide the first-line evidence that, by repressing GRK2, miR-K3 facilitates cell migration and invasion via activation of CXCR2/AKT signaling, which likely contribute to the dissemination of KSHV-induced tumors. PMID:26402907

  13. Structure of the ternary complex formed by a chemotaxis receptor signaling domain, the CheA histidine kinase and the coupling protein CheW as determined by pulsed dipolar ESR spectroscopy†

    PubMed Central

    Bhatnagar, Jaya; Borbat, Peter P.; Pollard, Abiola M.; Bilwes, Alexandrine M.; Freed, Jack H.; Crane, Brian R.

    2010-01-01

    The signaling apparatus that controls bacterial chemotaxis is composed of a core complex containing chemoreceptors, the histidine auto-kinase CheA, and the coupling protein CheW. Site-specific spin labeling and pulsed-dipolar ESR spectroscopy (PDS) have been applied to investigate the structure of a soluble ternary complex formed by T. maritima CheA (TmCheA), CheW, and receptor signaling domains. Thirty-five symmetric spin-labels sites (SLSs) were engineered into the five domains of the CheA dimer and CheW to provide distance restraints within the CheA:CheW complex in the absence and presence of a soluble receptor that inhibits kinase activity (Tm14). Additional PDS restraints between spin-labeled CheA, CheW and an engineered single-chain receptor labeled at six different sites allows docking of the receptor structure relative to the CheA:CheW complex. Disulfide cross-linking between selectively incorporated Cys residues finds two pairs of positions that provide further constraints within the ternary complex: one involving Tm14 and CheW, and another involving Tm14 and CheA. The derived structure of the ternary complex indicates a primary site of interaction between CheW and Tm14 that agrees well with previous biochemical and genetic data on transmembrane chemoreceptors. The PDS distance distributions are most consistent with only one CheW directly engaging one dimeric Tm14. The CheA dimerization domain (P3) aligns roughly antiparallel to the receptor conserved signaling tip, but does not interact strongly with it. The angle of the receptor axis with respect to P3 and the CheW-binding P5 domains is bound by two limits differing by ~20°. In one limit, Tm14 aligns roughly along P3 and may interact to some extent with the hinge region near the P3 hairpin loop. In the other limit, Tm14 tilts to interact with the P5 domain of the opposite subunit in an interface that mimics that observed with the P5 homolog CheW. The time-domain ESR data can be simulated from the model

  14. Signal conditioning system

    NASA Technical Reports Server (NTRS)

    Zahzah, Mohamad (Inventor); Korkosz, Gregory J. (Inventor); Bohr, Gerald (Inventor)

    2000-01-01

    A current-driven signal conditioning system comprising a first terminal, a second terminal, a strain gauge, and an instrumentation amplifier is disclosed. The strain gauge is adapted to measure a deformation of a structure and to generate a resistance which corresponds to the measured deformation. The instrumentation amplifier is adapted to be connected between the first terminal and the second terminal. The instrumentation amplifier is further adapted to be connected to the strain gauge and to place an output current on the second terminal. The output current is proportional to the resistance generated by the strain gauge. An output resister is coupled between the strain gauge and the second terminal, and a capacitor is coupled between the resister and the first terminal. A zenor diode is coupled between the first terminal and the strain gauge, and a diode is also coupled between the first terminal and the strain gauge.

  15. A novel algorithm for buried target detection evaluated on a collection of seismo-acoustic data

    NASA Astrophysics Data System (ADS)

    Malof, Jordan M.; Knox, Mary; Torrione, Peter A.; Collins, Leslie M.; Morton, Kenneth D.

    2014-06-01

    A recently validated technique for buried target detection relies on applying an acoustic stimulus signal to a patch of earth and then measuring its seismic (vibrational) response using a laser Doppler vibrometer (LDV). Target detection in this modality often relies on estimating the acoustic-to-seismic coupling ratio (A/S ratio) of the ground, which is altered by the presence of a buried target. For this study, LDV measurements were collected over patches of earth under varying environmental conditions using a known stimulus. These observations are then used to estimate the performance of several methods to discriminate between target and non-target patches. The first part of the study compares the performance of human observers against a set of established seismo-acoustic features from the literature. The simple features are based on previous studies where statistics on the Fourier transform of the acoustic-to-seismic transfer function estimate are measured. The human observers generally offered much better detection performance than any established feature. One weakness of the Fourier features is their inability to utilize local spatiotemporal target cues. To address these weaknesses, a novel automatic detection algorithm is proposed which uses a multi-scale blob detector to identify suspicious regions in time and space. These suspicious spatiotemporal locations are then clustered and assigned a decision statistic based on the confidence and number of cluster members. This method is shown to improve performance over the established Fourier statistics, resulting in performance much closer to the human observers.

  16. Optical coupling

    NASA Astrophysics Data System (ADS)

    Bock, J. J.; Gundersen, J.; Lee, A. T.; Richards, P. L.; Wollack, E.

    2009-03-01

    This paper describes contributions to the CMBpol Technology Study Workshop concerning optical coupling structures. These are structures in or near the focal plane which convert the free space wave to a superconducting microstrip on a SI wafer, or to the waveguide input to a HEMT receiver. In addition to an introduction and conclusions by the editor, this paper includes independent contributions by Bock on 'Planar Antenna-Coupled Bolometers for CMB Polarimetry', by Gunderson and Wollack on 'Millimeter-Wave Platlet Feeds', and by Lee on 'Multi-band Dual-Polarization Lens-coupled Planar Antennas for Bolometric CMB polarimetry.'

  17. Signal Words

    MedlinePlus

    ... Signal Words? Signal words are found on pesticide product labels, and they describe the acute (short-term) toxicity ... red letters on the front panel of the product label. 2,4 Acute Oral LD 50 Inhalation LC ...

  18. Prosthesis coupling

    NASA Technical Reports Server (NTRS)

    Reswick, J. B.; Mooney, V.; Bright, C. W.; Owens, L. J. (Inventor)

    1979-01-01

    A coupling for use in an apparatus for connecting a prosthesis to the bone of a stump of an amputated limb is described which permits a bio-compatible carbon sleeve forming a part of the prosthesis connector to float so as to prevent disturbing the skin seal around the carbon sleeve. The coupling includes a flexible member interposed between a socket that is inserted within an intermedullary cavity of the bone and the sleeve. A lock pin is carried by the prosthesis and has a stem portion which is adapted to be coaxially disposed and slideably within the tubular female socket for securing the prosthesis to the stump. The skin around the percutaneous carbon sleeve is able to move as a result of the flexing coupling so as to reduce stresses caused by changes in the stump shape and/or movement between the bone and the flesh portion of the stump.

  19. FLEXIBLE COUPLING

    DOEpatents

    Babelay, E.F.

    1962-02-13

    A flexible shaft coupling for operation at speeds in excess of 14,000 rpm is designed which requires no lubrication. A driving sleeve member and a driven sleeve member are placed in concentric spaced relationship. A torque force is transmitted to the driven member from the driving member through a plurality of nylon balls symmetrically disposed between the spaced sleeves. The balls extend into races and recesses within the respective sleeve members. The sleeve members have a suitable clearance therebetween and the balls have a suitable radial clearance during operation of the coupling to provide a relatively loose coupling. These clearances accommodate for both parallel and/or angular misalignments and avoid metal-tometal contact between the sleeve members during operation. Thus, no lubrication is needed, and a minimum of vibrations is transmitted between the sleeve members. (AEC)

  20. Signaling on the endocytic pathway.

    PubMed

    McPherson, P S; Kay, B K; Hussain, N K

    2001-06-01

    Ligand binding to receptor tyrosine kinases and G-protein-coupled receptors initiates signal transduction events and induces receptor endocytosis via clathrin-coated pits and vesicles. While receptor-mediated endocytosis has been traditionally considered an effective mechanism to attenuate ligand-activated responses, more recent studies demonstrate that signaling continues on the endocytic pathway. In fact, certain signaling events, such as the activation of the extracellular signal-regulated kinases, appear to require endocytosis. Protein components of signal transduction cascades can assemble at clathrin coated pits and remain associated with endocytic vesicles following their dynamin-dependent release from the plasma membrane. Thus, endocytic vesicles can function as a signaling compartment distinct from the plasma membrane. These observations demonstrate that endocytosis plays an important role in the activation and propagation of signaling pathways. PMID:11389765

  1. Capacitively-coupled inductive sensor

    DOEpatents

    Ekdahl, Carl A.

    1984-01-01

    A capacitively coupled inductive shunt current sensor which utilizes capacitive coupling between flanges having an annular inductive channel formed therein. A voltage dividing capacitor is connected between the coupling capacitor and ground to provide immediate capacitive division of the output signal so as to provide a high frequency response of the current pulse to be detected. The present invention can be used in any desired outer conductor such as the outer conductor of a coaxial transmission line, the outer conductor of an electron beam transmission line, etc.

  2. Sphingosine 1-phosphate signalling.

    PubMed

    Mendelson, Karen; Evans, Todd; Hla, Timothy

    2014-01-01

    Sphingosine 1-phosphate (S1P) is a lipid mediator formed by the metabolism of sphingomyelin. In vertebrates, S1P is secreted into the extracellular environment and signals via G protein-coupled S1P receptors to regulate cell-cell and cell-matrix adhesion, and thereby influence cell migration, differentiation and survival. The expression and localization of S1P receptors is dynamically regulated and controls vascular development, vessel stability and immune cell trafficking. In addition, crucial events during embryogenesis, such as angiogenesis, cardiogenesis, limb development and neurogenesis, are regulated by S1P signalling. Here, and in the accompanying poster, we provide an overview of S1P signalling in development and in disease. PMID:24346695

  3. Vibrational Coupling

    SciTech Connect

    2011-01-01

    By homing in on the distribution patterns of electrons around an atom, a team of scientists team with Berkeley Lab's Molecular Foundry showed how certain vibrations from benzene thiol cause electrical charge to "slosh" onto a gold surface (left), while others do not (right). The vibrations that cause this "sloshing" behavior yield a stronger SERS signal.

  4. Nonlinear interaction of meta-atoms through optical coupling

    SciTech Connect

    Slobozhanyuk, A. P.; Kapitanova, P. V.; Filonov, D. S.; Belov, P. A.; Powell, D. A.; Shadrivov, I. V.; Kivshar, Yu. S.; Lapine, M.; McPhedran, R. C.

    2014-01-06

    We propose and experimentally demonstrate a multi-frequency nonlinear coupling mechanism between split-ring resonators. We engineer the coupling between two microwave resonators through optical interaction, whilst suppressing the direct electromagnetic coupling. This allows for a power-dependent interaction between the otherwise independent resonators, opening interesting opportunities to address applications in signal processing, filtering, directional coupling, and electromagnetic compatibility.

  5. Magic-T-Coupled Magnetrons

    NASA Technical Reports Server (NTRS)

    Dickinson, R. M.

    1985-01-01

    Outputs of two magnetrons added coherently in scheme based on resonant waveguide coupling and injection phase locking. In addition, filaments are turned off after starting. Overall effect is relatively-inexpensive, lowpower, noisy magnetrons generate clean carrier signals of higher power that ordinarily require more expensive klystrons.

  6. Phosphoinositide signaling.

    PubMed

    Boss, Wendy F; Im, Yang Ju

    2012-01-01

    "All things flow and change…even in the stillest matter there is unseen flux and movement." Attributed to Heraclitus (530-470 BC), from The Story of Philosophy by Will Durant. Heraclitus, a Greek philosopher, was thinking on a much larger scale than molecular signaling; however, his visionary comments are an important reminder for those studying signaling today. Even in unstimulated cells, signaling pathways are in constant metabolic flux and provide basal signals that travel throughout the organism. In addition, negatively charged phospholipids, such as the polyphosphorylated inositol phospholipids, provide a circuit board of on/off switches for attracting or repelling proteins that define the membranes of the cell. This template of charged phospholipids is sensitive to discrete changes and metabolic fluxes-e.g., in pH and cations-which contribute to the oscillating signals in the cell. The inherent complexities of a constantly fluctuating system make understanding how plants integrate and process signals challenging. In this review we discuss one aspect of lipid signaling: the inositol family of negatively charged phospholipids and their functions as molecular sensors and regulators of metabolic flux in plants. PMID:22404474

  7. Hedgehog signalling.

    PubMed

    Lee, Raymond Teck Ho; Zhao, Zhonghua; Ingham, Philip W

    2016-02-01

    The Hedgehog (Hh) signalling pathway is one of the key regulators of metazoan development. Hh proteins have been shown to play roles in many developmental processes and have become paradigms for classical morphogens. Dysfunction of the Hh pathway underlies a number of human developmental abnormalities and diseases, making it an important therapeutic target. Interest in Hh signalling thus extends across many fields, from evo-devo to cancer research and regenerative medicine. Here, and in the accompanying poster, we provide an outline of the current understanding of Hh signalling mechanisms, highlighting the similarities and differences between species. PMID:26839340

  8. Contactless Coupling For Power And Data

    NASA Technical Reports Server (NTRS)

    Moody, John C.; Foley, Joseph W.

    1988-01-01

    Experimental flat-plate coupling transmits digital data signals and electrical power across small gap between two modules. Split transformer and optoelectronic components transmit electrical power and digital signals across small gap. Coupling concept useful substitute for electrical connectors in equipment assembled by robots, remote manipulators, or humans working in protective clothing or otherwise restricted in dexterity. Offers higher reliability due to one overall alignment mechanism as opposed to multiple pin/socket alignment requirements.

  9. Tubular Coupling

    NASA Technical Reports Server (NTRS)

    Rosenbaum, Bernard J. (Inventor)

    2000-01-01

    A system for coupling a vascular overflow graft or cannula to a heart pump. A pump pipe outlet is provided with an external tapered surface which receives the end of a compressible connula. An annular compression ring with a tapered internal bore surface is arranged about the cannula with the tapered internal surface in a facing relationship to the external tapered surface. The angle of inclination of the tapered surfaces is converging such that the spacing between the tapered surfaces decreases from one end of the external tapered surface to the other end thereby providing a clamping action of the tapered surface on a cannula which increases as a function of the length of cannula segment between the tapered surfaces. The annular compression ring is disposed within a tubular locking nut which threadedly couples to the pump and provides a compression force for urging the annular ring onto the cannula between the tapered surfaces. The nut has a threaded connection to the pump body. The threaded coupling to the pump body provides a compression force for the annular ring. The annular ring has an annular enclosure space in which excess cannula material from the compression between the tapered surfaces to "bunch up" in the space and serve as an enlarged annular ring segment to assist holding the cannula in place. The clamped cannula provides a seamless joint connection to the pump pipe outlet where the clamping force is uniformly applied to the cannula because of self alignment of the tapered surfaces. The nut can be easily disconnected to replace the pump if necessary.

  10. High temperature pressure coupled ultrasonic waveguide

    SciTech Connect

    Caines, M.J.

    1983-07-12

    A pressure coupled ultrasonic waveguide is provided to which one end may be attached a transducer and at the other end a high temperature material for continuous ultrasonic testing of the material. The ultrasonic signal is coupled from the waveguide into the material through a thin, dry copper foil.

  11. High temperature pressure coupled ultrasonic waveguide

    DOEpatents

    Caines, Michael J.

    1983-01-01

    A pressure coupled ultrasonic waveguide is provided to which one end may be attached a transducer and at the other end a high temperature material for continuous ultrasonic testing of the material. The ultrasonic signal is coupled from the waveguide into the material through a thin, dry copper foil.

  12. Analysis of capacitive coupling within microelectrode array.

    PubMed

    Hu, Z; Troyk, P R; Detlefsen, D E

    2006-01-01

    Capacitive coupling within high-density microelectrode arrays can degrade neural recording signal or disperse neural stimulation current. Material deterioration in a chronically implanted neural stimulation/recording system can cause such an undesired effect. We present a simple method with an iterative algorithm to quantify the cross-coupling capacitance, in-situ. PMID:17947024

  13. Calcium signaling and cytotoxicity.

    PubMed Central

    Kass, G E; Orrenius, S

    1999-01-01

    The divalent calcium cation Ca(2+) is used as a major signaling molecule during cell signal transduction to regulate energy output, cellular metabolism, and phenotype. The basis to the signaling role of Ca(2+) is an intricate network of cellular channels and transporters that allow a low resting concentration of Ca(2+) in the cytosol of the cell ([Ca(2+)]i) but that are also coupled to major dynamic and rapidly exchanging stores. This enables extracellular signals from hormones and growth factors to be transduced as [Ca(2+)]i spikes that are amplitude and frequency encoded. There is considerable evidence that a number of toxic environmental chemicals target these Ca(2+) signaling processes, alter them, and induce cell death by apoptosis. Two major pathways for apoptosis will be considered. The first one involves Ca(2+)-mediated expression of ligands that bind to and activate death receptors such as CD95 (Fas, APO-1). In the second pathway, Ca(2+) has a direct toxic effect and its primary targets include the mitochondria and the endoplasmic reticulum (ER). Mitochondria may respond to an apoptotic Ca(2+) signal by the selective release of cytochrome c or through enhanced production of reactive oxygen species and opening of an inner mitochondrial membrane pore. Toxic agents such as the environmental pollutant tributyltin or the natural plant product thapsigargin, which deplete the ER Ca(2+) stores, will induce as a direct result of this effect the opening of plasma membrane Ca(2+) channels and an ER stress response. In contrast, under some conditions, Ca(2+) signals may be cytoprotective and antagonize the apoptotic machinery. Images Figure 1 Figure 2 Figure 3 PMID:10229704

  14. Lysophosphatidic acid signalling in development.

    PubMed

    Sheng, Xiaoyan; Yung, Yun C; Chen, Allison; Chun, Jerold

    2015-04-15

    Lysophosphatidic acid (LPA) is a bioactive phospholipid that is present in all tissues examined to date. LPA signals extracellularly via cognate G protein-coupled receptors to mediate cellular processes such as survival, proliferation, differentiation, migration, adhesion and morphology. These LPA-influenced processes impact many aspects of organismal development. In particular, LPA signalling has been shown to affect fertility and reproduction, formation of the nervous system, and development of the vasculature. Here and in the accompanying poster, we review the developmentally related features of LPA signalling. PMID:25852197

  15. Dark coupling

    SciTech Connect

    Gavela, M.B.; Hernández, D.; Honorez, L. Lopez; Mena, O.; Rigolin, S. E-mail: d.hernandez@uam.es E-mail: omena@ific.uv.es

    2009-07-01

    The two dark sectors of the universe—dark matter and dark energy—may interact with each other. Background and linear density perturbation evolution equations are developed for a generic coupling. We then establish the general conditions necessary to obtain models free from non-adiabatic instabilities. As an application, we consider a viable universe in which the interaction strength is proportional to the dark energy density. The scenario does not exhibit ''phantom crossing'' and is free from instabilities, including early ones. A sizeable interaction strength is compatible with combined WMAP, HST, SN, LSS and H(z) data. Neutrino mass and/or cosmic curvature are allowed to be larger than in non-interacting models. Our analysis sheds light as well on unstable scenarios previously proposed.

  16. Thermoacoustic couple

    DOEpatents

    Wheatley, J.C.; Swift, G.W.; Migliori, A.

    1983-10-04

    An apparatus and method for determining acoustic power density level and its direction in a fluid using a single sensor are disclosed. The preferred embodiment of the apparatus, which is termed a thermoacoustic couple, consists of a stack of thin, spaced apart polymeric plates, selected ones of which include multiple bimetallic thermocouple junctions positioned along opposite end edges thereof. The thermocouple junctions are connected in series in the nature of a thermopile, and are arranged so as to be responsive to small temperature differences between the opposite edges of the plates. The magnitude of the temperature difference, as represented by the magnitude of the electrical potential difference generated by the thermopile, is found to be directly related to the level of acoustic power density in the gas.

  17. Gibberellin signaling.

    PubMed

    Hartweck, Lynn M

    2008-12-01

    This review covers recent advances in gibberellin (GA) signaling. GA signaling is now understood to hinge on DELLA proteins. DELLAs negatively regulate GA response by activating the promoters of several genes including Xerico, which upregulates the abscisic acid pathway which is antagonistic to GA. DELLAs also promote transcription of the GA receptor, GIBBERELLIN INSENSITIVE DWARF 1 (GID1) and indirectly regulate GA biosynthesis genes enhancing GA responsiveness and feedback control. A structural analysis of GID1 provides a model for understanding GA signaling. GA binds within a pocket of GID1, changes GID1 conformation and increases the affinity of GID1 for DELLA proteins. GA/GID1/DELLA has increased affinity for an F-Box protein and DELLAs are subsequently degraded via the proteasome. Therefore, GA induces growth through degradation of the DELLAs. The binding of DELLA proteins to three of the PHYTOCHROME INTERACTING FACTOR (PIF) proteins integrates light and GA signaling pathways. This binding prevents PIFs 3, 4, and 5 from functioning as positive transcriptional regulators of growth in the dark. Since PIFs are degraded in light, these PIFs can only function in the combined absence of light and presence of GA. New analyses suggest that GA signaling evolved at the same time or just after the plant vascular system and before plants acquired the capacity for seed reproduction. An analysis of sequences cloned from Physcomitrella suggests that GID1 and DELLAs were the first to evolve but did not initially interact. The more recently diverging spike moss Selaginella has all the genes required for GA biosynthesis and signaling, but the role of GA response in Selaginella physiology remains a mystery. PMID:18936962

  18. Digital Fluoroscopy with AN Optically Coupled Charge-Coupled Device

    NASA Astrophysics Data System (ADS)

    Liu, Hong

    1992-01-01

    This research was aimed at investigating the potential of developing an optically coupled charge-coupled device (CCD) imaging system for some digital fluoroscopic applications. The viability of this concept for fluoroscopic imaging was studied with respect to image intensifier-television (II -TV) techniques. The anticipated advantages of the optically coupled CCD, compared with II-TV, include higher contrast sensitivity, larger dynamic range, moderate spatial resolution and clinically acceptable dose. Following an investigation of some theoretical and practical issues concerning the optical coupling efficiency between the intensifying screen and the CCD imager, mathematical methods were developed to relate the signal, signal-to -noise ratio, and x-ray quantum efficiency of the optically coupled CCD imaging chain. The spatial resolution of the system was also analyzed. Using an ultra-sensitive CCD, as well as improved scintillating and optical coupling techniques, we built a laboratory system for experiments. We conducted measurements of the modulation transfer function (MTF), contrast sensitivity, contrast-detail detectability and detector contrast. The results suggest that the lesion detectability of our sub-optimal system was comparable to that of a screen-film technique under the same radiation dose, and was significantly better than II-TV fluoroscopy. Potential clinical applications of our system include mammography, pre-operational localization, pediatric chest radiography, and single tracer autoradiography. Images of selected phantoms, pathological specimens and small animals were acquired to demonstrate the radiologic quality attainable for such procedures. We conclude that developing an x-ray quantum limited, pseudo-real time, digital fluoroscopic imaging system (for some applications) without an II appears to be theoretically and technically feasible. The successful development of optically coupled CCD fluoroscopy has the potential for improving the

  19. Digital fluoroscopy with an optically coupled charge-coupled device

    NASA Astrophysics Data System (ADS)

    Liu, Hong

    1992-07-01

    This research was aimed at investigating the potential of developing an optically coupled charge-coupled device (CCD) imaging system for some digital fluoroscopic applications. The viability of this concept for fluoroscopic imaging was studied with respect to image intensifier-television (II-TV) techniques. The anticipated advantages of the optically coupled CCD, compared with II-TV, include higher contrast sensitivity, larger dynamic range, moderate spatial resolution and clinically acceptable dose. Following an investigation of some theoretical and practical issues concerning the optical coupling efficiency between the intensifying screen and the CCD imager, mathematical methods were developed to relate the signal, signal-to-noise ratio, and x-ray quantum efficiency of the optically coupled CCD imaging chain. The spatial resolution of the system was also analyzed. Using an ultra-sensitive CCD, as well as improved scintillating and optical coupling techniques, we built a laboratory system for experiments. We conducted measurements of the modulation transfer function (MTF), contrast sensitivity, contrast-detail detectability and detector contrast. The results suggest that the lesion detectability of our sub-optimal system was comparable to that of a screen-film technique under the same radiation dose, and was significantly better than II-TV fluoroscopy. Potential clinical applications of our system include mammography, pre-operational localization, pediatric chest radiography, and single tracer autoradiography. Images of selected phantoms, pathological specimens and small animals were acquired to demonstrate the radiologic quality attainable for such procedures. We conclude that developing an x-ray quantum limited, pseudo-real time, digital fluoroscopic imaging system (for some applications) without an II appears to be theoretically and technically feasible. The successful development of optically coupled CCD fluoroscopy has the potential for improving the quality

  20. Signaling by Sensory Receptors

    PubMed Central

    Julius, David; Nathans, Jeremy

    2012-01-01

    Sensory systems detect small molecules, mechanical perturbations, or radiation via the activation of receptor proteins and downstream signaling cascades in specialized sensory cells. In vertebrates, the two principal categories of sensory receptors are ion channels, which mediate mechanosensation, thermosensation, and acid and salt taste; and G-protein-coupled receptors (GPCRs), which mediate vision, olfaction, and sweet, bitter, and umami tastes. GPCR-based signaling in rods and cones illustrates the fundamental principles of rapid activation and inactivation, signal amplification, and gain control. Channel-based sensory systems illustrate the integration of diverse modulatory signals at the receptor, as seen in the thermosensory/pain system, and the rapid response kinetics that are possible with direct mechanical gating of a channel. Comparisons of sensory receptor gene sequences reveal numerous examples in which gene duplication and sequence divergence have created novel sensory specificities. This is the evolutionary basis for the observed diversity in temperature- and ligand-dependent gating among thermosensory channels, spectral tuning among visual pigments, and odorant binding among olfactory receptors. The coding of complex external stimuli by a limited number of sensory receptor types has led to the evolution of modality-specific and species-specific patterns of retention or loss of sensory information, a filtering operation that selectively emphasizes features in the stimulus that enhance survival in a particular ecological niche. The many specialized anatomic structures, such as the eye and ear, that house primary sensory neurons further enhance the detection of relevant stimuli. PMID:22110046

  1. Symbolic transfer entropy-based premature signal analysis

    NASA Astrophysics Data System (ADS)

    Wang, Jun; Yu, Zheng-Feng

    2012-01-01

    In this paper, we use symbolic transfer entropy to study the coupling strength between premature signals. Numerical experiments show that three types of signal couplings are in the same direction. Among them, normal signal coupling is the strongest, followed by that of premature ventricular contractions, and that of atrial premature beats is the weakest. The T test shows that the entropies of the three signals are distinct. Symbolic transfer entropy requires less data, can distinguish the three types of signals and has very good computational efficiency.

  2. 49 CFR 236.509 - Two or more locomotives coupled.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Two or more locomotives coupled. 236.509 Section... Train Stop, Train Control and Cab Signal Systems Standards § 236.509 Two or more locomotives coupled. The automatic train stop, train control or cab signal apparatus shall be arranged so that when two...

  3. Wavelet approach to artifact noise removal from Capacitive coupled Electrocardiograph.

    PubMed

    Lee, Seung Min; Kim, Ko Keun; Park, Kwang Suk

    2008-01-01

    Capacitive coupled Electrocardiography (ECG) is introduced as non-invasive measurement technology for ubiquitous health care and appliance are spread out widely. Although it has many merits, however, capacitive coupled ECG is very weak for motion artifacts for its non-skin-contact property. There are many studies for artifact problems which treats all artifact signals below 0.8Hz. In our capacitive coupled ECG measurement system, artifacts exist not only below 0.8Hz but also over than 10Hz. Therefore, artifact noise removal algorithm using wavelet method is tested to reject artifact-wandered signal from measured signals. It is observed that using power calculation each decimation step, artifact-wandered signal is removed as low frequency artifacts as high frequency artifacts. Although some original ECG signal is removed with artifact signal, we could level the signal quality for long term measure which shows the best quality ECG signals as we can get. PMID:19163323

  4. Signal prediction by anticipatory relaxation dynamics

    NASA Astrophysics Data System (ADS)

    Voss, Henning U.

    2016-03-01

    Real-time prediction of signals is a task often encountered in control problems as well as by living systems. Here, a parsimonious prediction approach based on the coupling of a linear relaxation-delay system to a smooth, stationary signal is described. The resulting anticipatory relaxation dynamics (ARD) is a frequency-dependent predictor of future signal values. ARD not only approximately predicts signals on average but can anticipate the occurrence of signal peaks, too. This can be explained by recognizing ARD as an input-output system with negative group delay. It is characterized, including its prediction horizon, by its analytically given frequency response function.

  5. Phosphoinositide signaling in somatosensory neurons.

    PubMed

    Rohacs, Tibor

    2016-05-01

    Somatosensory neurons of the dorsal root ganglia (DRG) and trigeminal ganglia (TG) are responsible for detecting thermal and tactile stimuli. They are also the primary neurons mediating pain and itch. A large number of cell surface receptors in these neurons couple to phospholipase C (PLC) enzymes leading to the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and the generation of downstream signaling molecules. These neurons also express many different ion channels, several of which are regulated by phosphoinositides. This review will summarize the knowledge on phosphoinositide signaling in DRG neurons, with special focus on effects on sensory and other ion channels. PMID:26724974

  6. Pharmacology of intracellular signalling pathways

    PubMed Central

    Nahorski, Stefan R

    2006-01-01

    This article provides a brief and somewhat personalized review of the dramatic developments that have occurred over the last 45 years in our understanding of intracellular signalling pathways associated with G-protein-coupled receptor activation. Signalling via cyclic AMP, the phosphoinositides and Ca2+ is emphasized and these systems have already been revealed as new pharmacological targets. The therapeutic benefits of most of such targets are, however, yet to be realized, but it is certain that the discipline of pharmacology needs to widen its boundaries to meet these challenges in the future. PMID:16402119

  7. Bradykinin-activated transmembrane signals are coupled via N/sub o/ or N/sub i/ to production of inositol 1,4,5-trisphosphate, a second messenger in NG108-15 neuroblastoma-glioma hybrid cells

    SciTech Connect

    Higashida, H.; Streaty, R.A.; Klee, W.; Nirenberg, M.

    1986-02-01

    The addition of bradykinin to NG108-15 cells results in a transient hyperpolarization followed by prolonged cell depolarization. Injection of inositol 1,4,5-trisphosphate or CaS into the cytoplasm of NG108-15 cells also elicits cell hyperpolarization followed by depolarization. Tetraethylammonium ions inhibit the hyperpolarizing response of cells to bradykinin or inositol 1,4,5-trisphosphate. Thus, the hyperpolarizing phase of the cell response may be due to inositol 1,4,5-trisphosphate-dependent release of stored UVCa-labelled CaS into the cytoplasm, which activates CaS -dependent K channels. The depolarizing phase of the cell response to bradykinin is due largely to inhibition of M channels, thereby decreasing the rate of K efflux from cells and, to a lesser extent, to activation of CaS -dependent ion channels and CaS channels. In contrast, injection of inositol 1,4,5-trisphosphate or CaS into the cytosol did not alter M channel activity. Incubation of NG108-15 cells with pertussis toxin inhibits bradykinin-dependent cell hyperpolarization and depolarization. Bradykinin stimulates low K/sub m/ GTPase activity and inhibits adenylate cyclase in NG108-15 membrane preparations but not in membranes prepared from cells treated with pertussis toxin. These results show that (bradykinin-receptor) complexes interact with N/sub o/ or N/sub i/ and suggest that N/sub o/ and/or N/sub i/ mediate the transduction of signals from bradykinin receptors to phospholipase C and adenylate cyclase.

  8. Systemic silencing signal(s).

    PubMed

    Fagard, M; Vaucheret, H

    2000-06-01

    Grafting experiments have revealed that transgenic plants that undergo co-suppression of homologous transgenes and endogenous genes or PTGS of exogenous transgenes produce a sequence-specific systemic silencing signal that is able to propagate from cell to cell and at long distance. Similarly, infection of transgenic plants by viruses that carry (part of) a transgene sequence results in global silencing (VIGS) of the integrated transgenes although viral infection is localized. Systemic PTGS and VIGS strongly resemble recovery from virus infection in non-transgenic plants, leading to protection against secondary infection in newly emerging leaves and PTGS of transiently expressed homologous transgenes. The sequence-specific PTGS signal is probably a transgene product (for example, aberrant RNA) or a secondary product (for example, RNA molecules produced by an RNA-dependent RNA polymerase with transgene RNA as a matrix) that mimics the type of viral RNA that is targeted for degradation by cellular defence. Whether some particular cases of transgene TGS could also rely on the production of such a mobile molecule is discussed. PMID:10999411

  9. The selectivity of noise and coupling for coherence biresonance and array-enhanced coherence biresonance in coupled neural systems.

    PubMed

    Shi, JianCheng; Luo, Min; Dong, Tao

    2009-11-01

    The selectivity of noise and coupling for coherence biresonance (CBR) and array-enhanced coherence biresonance (AECBR) in coupled neural systems has been investigated. It is shown that, depending on the coupling strength and noise intensity, various coherence behaviors and phenomena are exhibited, including CBR, coherence resonance without tuning, AECBR and undamped signal transmission. There exist optimal coupling and noise regions for the occurrence of CBR and AECBR in the transmission of noise-induced oscillations (NIOs). PMID:19615426

  10. Collider Signal I :. Resonance

    NASA Astrophysics Data System (ADS)

    Tait, Tim M. P.

    2010-08-01

    These TASI lectures were part of the summer school in 2008 and cover the collider signal associated with resonances in models of physics beyond the Standard Model. I begin with a review of the Z boson, one of the best-studied resonances in particle physics, and review how the Breit-Wigner form of the propagator emerges in perturbation theory and discuss the narrow width approximation. I review how the LEP and SLAC experiments could use the kinematics of Z events to learn about fermion couplings to the Z. I then make a brief survey of models of physics beyond the Standard Model which predict resonances, and discuss some of the LHC observables which we can use to discover and identify the nature of the BSM physics. I finish up with a discussion of the linear moose that one can use for an effective theory description of a massive color octet vector particle.

  11. Olfactory receptor signaling.

    PubMed

    Antunes, Gabriela; Simoes de Souza, Fabio Marques

    2016-01-01

    The guanine nucleotide protein (G protein)-coupled receptors (GPCRs) superfamily represents the largest class of membrane protein in the human genome. More than a half of all GPCRs are dedicated to interact with odorants and are termed odorant-receptors (ORs). Linda Buck and Richard Axel, the Nobel Prize laureates in physiology or medicine in 2004, first cloned and characterized the gene family that encode ORs, establishing the foundations to the understanding of the molecular basis for odor recognition. In the last decades, a lot of progress has been done to unravel the functioning of the sense of smell. This chapter gives a general overview of the topic of olfactory receptor signaling and reviews recent advances in this field. PMID:26928542

  12. Electrical coupling in multi-array charge coupled devices

    NASA Astrophysics Data System (ADS)

    Singh, Parul; Sakarvadiya, Vishal; Dubey, Neeraj; Kirkire, Shweta; Thapa, Nitesh; Banerjee, Arup

    2016-05-01

    Silicon based charge coupled device (CCD) performances have improved immensely over the years. Scientific community across the globe target challenging remote sensing applications with CCD as optical imaging detector. Over the years, both pixel count (from few hundreds to few tens of thousands) and line readout rate (from few kHz to few tens of kHz) have increased considerably. Pixels are readout using a large number of output ports driven up to few tens of MHz Moreover, for multi-spectral applications, same Si die contains multiple arrays sharing input stimuli. This is usually done to optimize package pin count. Si die as well as package level layout of clock and bias lines become critical for closely spaced multi-array devices. The inter-array separation may go down to few hundreds of microns when filter coating is laid on top of the die. Die level layout becomes quite critical for devices with such architecture. The inter-array (consecutive arrays) separation is optimized to reduce optical coupling / stray light in devices integrated multi-band strip filter. Layout constraints along with shared bias/clock lines are known to produce electrical cross-talk or coupling. Effect of this (within one array or between two arrays) cross-talk is more pronounced in systems having low noise floor. Video signal dependent coupling in a multi-port system becomes quite complex and leads to a relatively noisier system (post correction). The paper presents results of simulations and tests (pre and post correction) addressing this type of electrical coupling. The paper presents cause, impact and possible remedial measures to minimize such coupling in a multi-array, multi-port TDI CCD from 1.3% to below 0.06%.

  13. Signal processing in magnetoencephalography.

    PubMed

    Vrba, J; Robinson, S E

    2001-10-01

    The subject of this article is detection of brain magnetic fields, or magnetoencephalography (MEG). The brain fields are many orders of magnitude smaller than the environmental magnetic noise and their measurement represent a significant metrological challenge. The only detectors capable of resolving such small fields and at the same time handling the large dynamic range of the environmental noise are superconducting quantum interference devices (or SQUIDs). The SQUIDs are coupled to the brain magnetic fields using combinations of superconducting coils called flux transformers (primary sensors). The environmental noise is attenuated by a combination of shielding, primary sensor geometry, and synthetic methods. One of the most successful synthetic methods for noise elimination is synthetic higher-order gradiometers. How the gradiometers can be synthesized is shown and examples of their noise cancellation effectiveness are given. The MEG signals measured on the scalp surface must be interpreted and converted into information about the distribution of currents within the brain. This task is complicated by the fact that such inversion is nonunique. Additional mathematical simplifications, constraints, or assumptions must be employed to obtain useful source images. Methods for the interpretation of the MEG signals include the popular point current dipole, minimum norm methods, spatial filtering, beamformers, MUSIC, and Bayesian techniques. The use of synthetic aperture magnetometry (a class of beamformers) is illustrated in examples of interictal epileptic spiking and voluntary hand-motor activity. PMID:11812209

  14. Acquisition signal transmitter

    NASA Technical Reports Server (NTRS)

    Friedman, Morton L. (Inventor)

    1989-01-01

    An encoded information transmitter which transmits a radio frequency carrier that is amplitude modulated by a constant frequency waveform and thereafter amplitude modulated by a predetermined encoded waveform, the constant frequency waveform modulated carrier constituting an acquisition signal and the encoded waveform modulated carrier constituting an information bearing signal, the acquisition signal providing enhanced signal acquisition and interference rejection favoring the information bearing signal. One specific application for this transmitter is as a distress transmitter where a conventional, legislated audio tone modulated signal is transmitted followed first by the acquisition signal and then the information bearing signal, the information bearing signal being encoded with, among other things, vehicle identification data. The acquistion signal enables a receiver to acquire the information bearing signal where the received signal is low and/or where the received signal has a low signal-to-noise ratio in an environment where there are multiple signals in the same frequency band as the information bearing signal.

  15. Neurovascular coupling: a parallel implementation

    PubMed Central

    Dormanns, Katharina; Brown, Richard G.; David, Tim

    2015-01-01

    A numerical model of neurovascular coupling (NVC) is presented based on neuronal activity coupled to vasodilation/contraction models via the astrocytic mediated perivascular K+ and the smooth muscle cell (SMC) Ca2+ pathway termed a neurovascular unit (NVU). Luminal agonists acting on P2Y receptors on the endothelial cell (EC) surface provide a flux of inositol trisphosphate (IP3) into the endothelial cytosol. This concentration of IP3 is transported via gap junctions between EC and SMC providing a source of sarcoplasmic derived Ca2+ in the SMC. The model is able to relate a neuronal input signal to the corresponding vessel reaction (contraction or dilation). A tissue slice consisting of blocks, each of which contain an NVU is connected to a space filling H-tree, simulating a perfusing arterial tree (vasculature) The model couples the NVUs to the vascular tree via a stretch mediated Ca2+ channel on both the EC and SMC. The SMC is induced to oscillate by increasing an agonist flux in the EC and hence increased IP3 induced Ca2+ from the SMC stores with the resulting calcium-induced calcium release (CICR) oscillation inhibiting NVC thereby relating blood flow to vessel contraction and dilation following neuronal activation. The coupling between the vasculature and the set of NVUs is relatively weak for the case with agonist induced where only the Ca2+ in cells inside the activated area becomes oscillatory however, the radii of vessels both inside and outside the activated area oscillate (albeit small for those outside). In addition the oscillation profile differs between coupled and decoupled states with the time required to refill the cytosol with decreasing Ca2+ and increasing frequency with coupling. The solution algorithm is shown to have excellent weak and strong scaling. Results have been generated for tissue slices containing up to 4096 blocks. PMID:26441619

  16. Neurovascular coupling: a parallel implementation.

    PubMed

    Dormanns, Katharina; Brown, Richard G; David, Tim

    2015-01-01

    A numerical model of neurovascular coupling (NVC) is presented based on neuronal activity coupled to vasodilation/contraction models via the astrocytic mediated perivascular K(+) and the smooth muscle cell (SMC) Ca(2+) pathway termed a neurovascular unit (NVU). Luminal agonists acting on P2Y receptors on the endothelial cell (EC) surface provide a flux of inositol trisphosphate (IP3) into the endothelial cytosol. This concentration of IP3 is transported via gap junctions between EC and SMC providing a source of sarcoplasmic derived Ca(2+) in the SMC. The model is able to relate a neuronal input signal to the corresponding vessel reaction (contraction or dilation). A tissue slice consisting of blocks, each of which contain an NVU is connected to a space filling H-tree, simulating a perfusing arterial tree (vasculature) The model couples the NVUs to the vascular tree via a stretch mediated Ca(2+) channel on both the EC and SMC. The SMC is induced to oscillate by increasing an agonist flux in the EC and hence increased IP3 induced Ca(2+) from the SMC stores with the resulting calcium-induced calcium release (CICR) oscillation inhibiting NVC thereby relating blood flow to vessel contraction and dilation following neuronal activation. The coupling between the vasculature and the set of NVUs is relatively weak for the case with agonist induced where only the Ca(2+) in cells inside the activated area becomes oscillatory however, the radii of vessels both inside and outside the activated area oscillate (albeit small for those outside). In addition the oscillation profile differs between coupled and decoupled states with the time required to refill the cytosol with decreasing Ca(2+) and increasing frequency with coupling. The solution algorithm is shown to have excellent weak and strong scaling. Results have been generated for tissue slices containing up to 4096 blocks. PMID:26441619

  17. Coupled optical resonance laser locking.

    PubMed

    Burd, S C; du Toit, P J W; Uys, H

    2014-10-20

    We have demonstrated simultaneous laser frequency stabilization of a UV and IR laser, to coupled transitions of ions in the same spectroscopic sample, by detecting only the absorption of the UV laser. Separate signals for locking the different lasers are obtained by modulating each laser at a different frequency and using lock-in detection of a single photodiode signal. Experimentally, we simultaneously lock a 369 nm and a 935 nm laser to the (2)S(1/2) → (2)(P(1/2) and (2)D(3/2) → (3)D([3/2]1/2) transitions, respectively, of Yb(+) ions generated in a hollow cathode discharge lamp. Stabilized lasers at these frequencies are required for cooling and trapping Yb(+) ions, used in quantum information and in high precision metrology experiments. This technique should be readily applicable to other ion and neutral atom systems requiring multiple stabilized lasers. PMID:25401537

  18. Orbiter CCTV video signal noise analysis

    NASA Technical Reports Server (NTRS)

    Lawton, R. M.; Blanke, L. R.; Pannett, R. F.

    1977-01-01

    The amount of steady state and transient noise which will couple to orbiter CCTV video signal wiring is predicted. The primary emphasis is on the interim system, however, some predictions are made concerning the operational system wiring in the cabin area. Noise sources considered are RF fields from on board transmitters, precipitation static, induced lightning currents, and induced noise from adjacent wiring. The most significant source is noise coupled to video circuits from associated circuits in common connectors. Video signal crosstalk is the primary cause of steady state interference, and mechanically switched control functions cause the largest induced transients.

  19. Device and method for redirecting electromagnetic signals

    DOEpatents

    Garcia, Ernest J.

    1999-01-01

    A device fabricated to redirect electromagnetic signals, the device including a primary driver adapted to provide a predetermined force, a linkage system coupled to the primary driver, a pusher rod rotationally coupled to the linkage system, a flexible rod element attached to the pusher rod and adapted to buckle upon the application of the predetermined force, and a mirror structure attached to the flexible rod element at one end and to the substrate at another end. When the predetermined force buckles the flexible rod element, the mirror structure and the flexible rod element both move to thereby allow a remotely-located electromagnetic signal directed towards the device to be redirected.

  20. Electronic pictures from charged-coupled devices

    NASA Technical Reports Server (NTRS)

    Mccann, D. H.; Turly, A. P.; White, M.

    1979-01-01

    Imaging system uses charge-coupled devices (CCD's) to generate TV-like pictures with high resolution, sensitivity, and signal-to-noise ratio. It combines detectors for five spectral bands as well as processing and control circuitry all on single silicon chip.

  1. Inductively coupled wireless RF coil arrays.

    PubMed

    Bulumulla, S B; Fiveland, E; Park, K J; Foo, T K; Hardy, C J

    2015-04-01

    As the number of coils increases in multi-channel MRI receiver-coil arrays, RF cables and connectors become increasingly bulky and heavy, degrading patient comfort and slowing workflow. Inductive coupling of signals provides an attractive "wireless" approach, with the potential to reduce coil weight and cost while simplifying patient setup. In this work, multi-channel inductively coupled anterior arrays were developed and characterized for 1.5T imaging. These comprised MR receiver coils inductively (or "wirelessly") linked to secondary or "sniffer" coils whose outputs were transmitted via preamps to the MR system cabinet. The induced currents in the imaging coils were blocked by passive diode circuits during RF transmit. The imaging arrays were totally passive, obviating the need to deliver power to the coils, and providing lightweight, untethered signal reception with easily positioned coils. Single-shot fast spin echo images were acquired from 5 volunteers using a 7-element inductively coupled coil array and a conventionally cabled 7-element coil array of identical geometry, with the inductively-coupled array showing a relative signal-to-noise ratio of 0.86 +/- 0.07. The concept was extended to a larger 9-element coil array to demonstrate the effect of coil element size on signal transfer and RF-transmit blocking. PMID:25523607

  2. Neurons from rat brain coupled to transistors

    NASA Astrophysics Data System (ADS)

    Vassanelli, S.; Fromherz, P.

    Field-effect transistors form spontaneously capacitive junctions with cultured nerve cells from rat brains. The transfer of ac signals from neurons to silicon is studied and used to parametrize an equivalent circuit. The coupling is distinctly weaker than in junctions assembled with leech nerve cells. The implications with respect to the recording and stimulation of neuronal activity by silicon devices are considered.

  3. Decoding Ca2+ signals in plants

    NASA Technical Reports Server (NTRS)

    Sathyanarayanan, P. V.; Poovaiah, B. W.

    2004-01-01

    Different input signals create their own characteristic Ca2+ fingerprints. These fingerprints are distinguished by frequency, amplitude, duration, and number of Ca2+ oscillations. Ca(2+)-binding proteins and protein kinases decode these complex Ca2+ fingerprints through conformational coupling and covalent modifications of proteins. This decoding of signals can lead to a physiological response with or without changes in gene expression. In plants, Ca(2+)-dependent protein kinases and Ca2+/calmodulin-dependent protein kinases are involved in decoding Ca2+ signals into phosphorylation signals. This review summarizes the elements of conformational coupling and molecular mechanisms of regulation of the two groups of protein kinases by Ca2+ and Ca2+/calmodulin in plants.

  4. Decoding Ca2+ signals in plants.

    PubMed

    Sathyanarayanan, P V; Poovaiah, B W

    2004-01-01

    Different input signals create their own characteristic Ca2+ fingerprints. These fingerprints are distinguished by frequency, amplitude, duration, and number of Ca2+ oscillations. Ca(2+)-binding proteins and protein kinases decode these complex Ca2+ fingerprints through conformational coupling and covalent modifications of proteins. This decoding of signals can lead to a physiological response with or without changes in gene expression. In plants, Ca(2+)-dependent protein kinases and Ca2+/calmodulin-dependent protein kinases are involved in decoding Ca2+ signals into phosphorylation signals. This review summarizes the elements of conformational coupling and molecular mechanisms of regulation of the two groups of protein kinases by Ca2+ and Ca2+/calmodulin in plants. PMID:16044584

  5. G-protein-coupled receptor heteromer dynamics

    PubMed Central

    Vilardaga, Jean-Pierre; Agnati, Luigi F.; Fuxe, Kjell; Ciruela, Francisco

    2010-01-01

    G-protein-coupled receptors (GPCRs) represent the largest family of cell surface receptors, and have evolved to detect and transmit a large palette of extracellular chemical and sensory signals into cells. Activated receptors catalyze the activation of heterotrimeric G proteins, which modulate the propagation of second messenger molecules and the activity of ion channels. Classically thought to signal as monomers, different GPCRs often pair up with each other as homo- and heterodimers, which have been shown to modulate signaling to G proteins. Here, we discuss recent advances in GPCR heteromer systems involving the kinetics of the early steps in GPCR signal transduction, the dynamic property of receptor–receptor interactions, and how the formation of receptor heteromers modulate the kinetics of G-protein signaling. PMID:21123619

  6. Effect of chemical synapse on vibrational resonance in coupled neurons

    NASA Astrophysics Data System (ADS)

    Deng, Bin; Wang, Jiang; Wei, Xile

    2009-03-01

    The response of three coupled FitzHugh-Nagumo neurons, under high-frequency driving, to a subthreshold low-frequency signal is investigated. We show that an optimal amplitude of the high-frequency driving enhances the response of coupled excited neurons to a subthreshold low-frequency input, and the chemical synaptic coupling is more efficient than the well-known electrical coupling (gap junction), especially when the coupled neurons are near the canard regime, for local signal input, i.e., only one of the three neurons is subject to a low-frequency signal. The influence of additive noise and the interplay between vibrational and stochastic resonance are also analyzed.

  7. Gq-Coupled Receptors in Autoimmunity

    PubMed Central

    Zhang, Lu; Shi, Guixiu

    2016-01-01

    Heterotrimeric G proteins can be divided into Gi, Gs, Gq/11, and G12/13 subfamilies according to their α subunits. The main function of G proteins is transducing signals from G protein coupled receptors (GPCRs), a family of seven transmembrane receptors. In recent years, studies have demonstrated that GPCRs interact with Gq, a member of the Gq/11 subfamily of G proteins. This interaction facilitates the vital role of this family of proteins in immune regulation and autoimmunity, particularly for Gαq, which is considered the functional α subunit of Gq protein. Therefore, understanding the mechanisms through which Gq-coupled receptors control autoreactive lymphocytes is critical and may provide insights into the treatment of autoimmune disorders. In this review, we summarize recent advances in studies of the role of Gq-coupled receptors in autoimmunity, with a focus on their pathologic role and downstream signaling. PMID:26885533

  8. DREADD: A Chemogenetic GPCR Signaling Platform

    PubMed Central

    Zhu, Hu

    2015-01-01

    Recently, we created a family of engineered G protein-coupled receptors (GPCRs) called DREADD (designer receptors exclusively activated by designer drugs) which can precisely control three major GPCR signaling pathways (Gq, Gi, and Gs). DREADD technology has been successfully applied in a variety of in vivo studies to control GPCR signaling, and here we describe recent advances of DREADD technology and discuss its potential application in drug discovery, gene therapy, and tissue engineering. PMID:25522378

  9. GPCR signaling along the endocytic pathway

    PubMed Central

    Irannejad, Roshanak; von Zastrow, Mark

    2016-01-01

    Many G protein-coupled receptors (GPCRs) internalize after agonist-induced activation. While endocytosis has long been associated with homeostatic attenuation of cellular responsiveness, accumulating evidence from study of a wide range of eukaryotes reveals that the endocytic pathway also contributes to generating receptor-initiated signals themselves. Here we review recent progress in this area, discussing primarily but not exclusively GPCR signaling in mammalian cells. PMID:24680436

  10. Signalling drought in guard cells.

    PubMed

    Luan, S.

    2002-02-01

    A number of environmental conditions including drought, low humidity, cold and salinity subject plants to osmotic stress. A rapid plant response to such stress conditions is stomatal closure to reduce water loss from plants. From an external stress signal to stomatal closure, many molecular components constitute a signal transduction network that couples the stimulus to the response. Numerous studies have been directed to resolving the framework and molecular details of stress signalling pathways in plants. In guard cells, studies focus on the regulation of ion channels by abscisic acid (ABA), a chemical messenger for osmotic stress. Calcium, protein kinases and phosphatases, and membrane trafficking components have been shown to play a role in ABA signalling process in guard cells. Studies also implicate ABA-independent regulation of ion channels by osmotic stress. In particular, a direct osmosensing pathway for ion channel regulation in guard cells has been identified. These pathways form a complex signalling web that monitors water status in the environment and initiates responses in stomatal movements. PMID:11841666

  11. Synchronization of coupled Boolean phase oscillators

    NASA Astrophysics Data System (ADS)

    Rosin, David P.; Rontani, Damien; Gauthier, Daniel J.

    2014-04-01

    We design, characterize, and couple Boolean phase oscillators that include state-dependent feedback delay. The state-dependent delay allows us to realize an adjustable coupling strength, even though only Boolean signals are exchanged. Specifically, increasing the coupling strength via the range of state-dependent delay leads to larger locking ranges in uni- and bidirectional coupling of oscillators in both experiment and numerical simulation with a piecewise switching model. In the unidirectional coupling scheme, we unveil asymmetric triangular-shaped locking regions (Arnold tongues) that appear at multiples of the natural frequency of the oscillators. This extends observations of a single locking region reported in previous studies. In the bidirectional coupling scheme, we map out a symmetric locking region in the parameter space of frequency detuning and coupling strength. Because of the large scalability of our setup, our observations constitute a first step towards realizing large-scale networks of coupled oscillators to address fundamental questions on the dynamical properties of networks in a new experimental setting.

  12. Biorhythm in Couple Counseling

    ERIC Educational Resources Information Center

    Araoz, Daniel L.

    1977-01-01

    Twelve couples in marital counseling were studied during 12 months on the basis of their biorhythms. For each couple a compatibility percentage was obtained. It was found that difficulties in their interaction correlated highly with dissonance in their biorhythms. (Author)

  13. Adenylate Kinase and AMP Signaling Networks: Metabolic Monitoring, Signal Communication and Body Energy Sensing

    PubMed Central

    Dzeja, Petras; Terzic, Andre

    2009-01-01

    Adenylate kinase and downstream AMP signaling is an integrated metabolic monitoring system which reads the cellular energy state in order to tune and report signals to metabolic sensors. A network of adenylate kinase isoforms (AK1-AK7) are distributed throughout intracellular compartments, interstitial space and body fluids to regulate energetic and metabolic signaling circuits, securing efficient cell energy economy, signal communication and stress response. The dynamics of adenylate kinase-catalyzed phosphotransfer regulates multiple intracellular and extracellular energy-dependent and nucleotide signaling processes, including excitation-contraction coupling, hormone secretion, cell and ciliary motility, nuclear transport, energetics of cell cycle, DNA synthesis and repair, and developmental programming. Metabolomic analyses indicate that cellular, interstitial and blood AMP levels are potential metabolic signals associated with vital functions including body energy sensing, sleep, hibernation and food intake. Either low or excess AMP signaling has been linked to human disease such as diabetes, obesity and hypertrophic cardiomyopathy. Recent studies indicate that derangements in adenylate kinase-mediated energetic signaling due to mutations in AK1, AK2 or AK7 isoforms are associated with hemolytic anemia, reticular dysgenesis and ciliary dyskinesia. Moreover, hormonal, food and antidiabetic drug actions are frequently coupled to alterations of cellular AMP levels and associated signaling. Thus, by monitoring energy state and generating and distributing AMP metabolic signals adenylate kinase represents a unique hub within the cellular homeostatic network. PMID:19468337

  14. Adaptive coupling of inferior olive neurons in cerebellar learning.

    PubMed

    Tokuda, Isao T; Hoang, Huu; Schweighofer, Nicolas; Kawato, Mitsuo

    2013-11-01

    In the cerebellar learning hypothesis, inferior olive neurons are presumed to transmit high fidelity error signals, despite their low firing rates. The idea of chaotic resonance has been proposed to realize efficient error transmission by desynchronized spiking activities induced by moderate electrical coupling between inferior olive neurons. A recent study suggests that the coupling strength between inferior olive neurons can be adaptive and may decrease during the learning process. We show that such a decrease in coupling strength can be beneficial for motor learning, since efficient coupling strength depends upon the magnitude of the error signals. We introduce a scheme of adaptive coupling that enhances the learning of a neural controller for fast arm movements. Our numerical study supports the view that the controlling strategy of the coupling strength provides an additional degree of freedom to optimize the actual learning in the cerebellum. PMID:23337637

  15. Optical filter having coupled whispering-gallery-mode resonators

    NASA Technical Reports Server (NTRS)

    Savchenkov, Anatoliy (Inventor); Ilchenko, Vladimir (Inventor); Maleki, Lutfollah (Inventor); Handley, Timothy A. (Inventor)

    2006-01-01

    Optical filters having at least two coupled whispering-gallery-mode (WGM) optical resonators to produce a second order or higher order filter function with a desired spectral profile. At least one of the coupled WGM optical resonators may be tunable by a control signal to adjust the filtering function.

  16. High-temperature pressure-coupled ultrasonic waveguide

    DOEpatents

    Caines, M.J.

    1981-02-11

    A pressure coupled ultrasonic waveguide is provided to which one end may be attached a transducer and at the other end a high temperature material for continuous ultrasonic testing of the material. The ultrasonic signal is coupled from the waveguide into the material through a thin, dry copper foil.

  17. Toroid Joining Gun For Fittings And Couplings

    NASA Technical Reports Server (NTRS)

    Fox, Robert L.; Swaim, Robert J.; Johnson, Samuel D.; Buckley, John D.; Copeland, Carl E.; Coultrip, Robert H.; Johnston, David F.; Phillips, William M.

    1992-01-01

    Hand-held gun used to join metal heat-to-shrink couplings. Uses magnetic induction (eddy currents) to produce heat in metal coupling, and thermocouple to measure temperature and signals end of process. Gun, called "toroid joining gun" concentrates high levels of heat in localized areas. Reconfigured for use on metal heat-to-shrink fitting and coupling applications. Provides rapid heating, operates on low power, lightweight and portable. Safe for use around aircraft fuel and has no detrimental effects on surrounding surfaces or objects. Reliable in any environment and under all weather conditions. Gun logical device for taking full advantage of capabilities of new metal heat-to-shrink couplings and fittings.

  18. Radio frequency coupling apparatus and method for measuring minority carrier lifetimes in semiconductor materials

    DOEpatents

    Johnston, Steven W.; Ahrenkiel, Richard K.

    2002-01-01

    An apparatus for measuring the minority carrier lifetime of a semiconductor sample using radio-frequency coupling. The measuring apparatus includes an antenna that is positioned a coupling distance from a semiconductor sample which is exposed to light pulses from a laser during sampling operations. A signal generator is included to generate high frequency, such as 900 MHz or higher, sinusoidal waveform signals that are split into a reference signal and a sample signal. The sample signal is transmitted into a sample branch circuit where it passes through a tuning capacitor and a coaxial cable prior to reaching the antenna. The antenna is radio-frequency coupled with the adjacent sample and transmits the sample signal, or electromagnetic radiation corresponding to the sample signal, to the sample and receives reflected power or a sample-coupled-photoconductivity signal back. To lower impedance and speed system response, the impedance is controlled by limiting impedance in the coaxial cable and the antenna reactance. In one embodiment, the antenna is a waveguide/aperture hybrid antenna having a central transmission line and an adjacent ground flange. The sample-coupled-photoconductivity signal is then transmitted to a mixer which also receives the reference signal. To enhance the sensitivity of the measuring apparatus, the mixer is operated to phase match the reference signal and the sample-coupled-photoconductivity signal.

  19. Conduction-coupled Tesla transformer

    NASA Astrophysics Data System (ADS)

    Reed, J. L.

    2015-03-01

    A proof-of-principle Tesla transformer circuit is introduced. The new transformer exhibits the high voltage-high power output signal of shock-excited transformers. The circuit, with specification of proper circuit element values, is capable of obtaining extreme oscillatory voltages. The primary and secondary portions of the circuit communicate solely by conduction. The destructive arcing between the primary and secondary inductors in electromagnetically coupled transformers is ubiquitous. Flashover is eliminated in the new transformer as the high-voltage inductors do not interpenetrate and so do not possess an annular volume of electric field. The inductors are remote from one another. The high voltage secondary inductor is isolated in space, except for a base feed conductor, and obtains earth by its self-capacitance to the surroundings. Governing equations, for the ideal case of no damping, are developed from first principles. Experimental, theoretical, and circuit simulator data are presented for the new transformer. Commercial high-temperature superconductors are discussed as a means to eliminate the counter-intuitive damping due to small primary inductances in both the electromagnetic-coupled and new conduction-coupled transformers.

  20. Conduction-coupled Tesla transformer.

    PubMed

    Reed, J L

    2015-03-01

    A proof-of-principle Tesla transformer circuit is introduced. The new transformer exhibits the high voltage-high power output signal of shock-excited transformers. The circuit, with specification of proper circuit element values, is capable of obtaining extreme oscillatory voltages. The primary and secondary portions of the circuit communicate solely by conduction. The destructive arcing between the primary and secondary inductors in electromagnetically coupled transformers is ubiquitous. Flashover is eliminated in the new transformer as the high-voltage inductors do not interpenetrate and so do not possess an annular volume of electric field. The inductors are remote from one another. The high voltage secondary inductor is isolated in space, except for a base feed conductor, and obtains earth by its self-capacitance to the surroundings. Governing equations, for the ideal case of no damping, are developed from first principles. Experimental, theoretical, and circuit simulator data are presented for the new transformer. Commercial high-temperature superconductors are discussed as a means to eliminate the counter-intuitive damping due to small primary inductances in both the electromagnetic-coupled and new conduction-coupled transformers. PMID:25832281

  1. Distributed coupling complexity in a weakly coupled oscillatory network with associative properties

    NASA Astrophysics Data System (ADS)

    Kostorz, Kathrin; Hölzel, Robert W.; Krischer, Katharina

    2013-08-01

    We present a novel architecture of an oscillatory neural network capable of performing pattern recognition tasks. Two established strategies for obtaining associative properties in oscillatory networks invoke either a physical, time constant or a global, dynamical all-to-all coupling. Our network distributes the complexity of the coupling between the spatial and the temporal domain. Instead of {O}(N^2) physical connections or a global connection with {O}(N^2) frequency components, each of the N oscillators receives an individual coupling signal which is composed of N - 1 frequency components. We demonstrate that such a network can be built with analog electronic oscillators and possesses reliable pattern recognition properties. Theoretical analysis shows that the scalability is in fact superior to the dynamic global coupling approach, while its physical complexity is greatly reduced compared to the individual time constant coupling.

  2. A Simple Structure for Signal Amplification

    NASA Astrophysics Data System (ADS)

    Ding, Wan-Xiang; Gu, Chang-Gui; Liang, Xiao-Ming

    2016-02-01

    It has been found that a triple-node feed-forward motif has a function of signal amplification, where two input nodes receive the external weak signal and jointly modulate the response of the third output node [Liang et al., Phys. Rev. E 88 (2013) 012910]. We here show that the signal amplification can be further enhanced by adding a link between the two input nodes in the feed-forward motif. We further reveal that the coupling strength of the link regulates the enhancement of signal amplification in the modified feed-forward motif. We finally analyze the mechanism of signal amplification of such simple structure. Supported by the Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning under Grant No. QD2015016, the National Natural Science Foundation of China under Grant Nos. 11505114 and 11305078

  3. Coupled modes, frequencies and fields of a dielectric resonator and a cavity using coupled mode theory

    NASA Astrophysics Data System (ADS)

    Elnaggar, Sameh Y.; Tervo, Richard; Mattar, Saba M.

    2014-01-01

    Probes consisting of a dielectric resonator (DR) inserted in a cavity are important integral components of electron paramagnetic resonance (EPR) spectrometers because of their high signal-to-noise ratio. This article studies the behavior of this system, based on the coupling between its dielectric and cavity modes. Coupled-mode theory (CMT) is used to determine the frequencies and electromagnetic fields of this coupled system. General expressions for the frequencies and field distributions are derived for both the resulting symmetric and anti-symmetric modes. These expressions are applicable to a wide range of frequencies (from MHz to THz). The coupling of cavities and DRs of various sizes and their resonant frequencies are studied in detail. Since the DR is situated within the cavity then the coupling between them is strong. In some cases the coupling coefficient, κ, is found to be as high as 0.4 even though the frequency difference between the uncoupled modes is large. This is directly attributed to the strong overlap between the fields of the uncoupled DR and cavity modes. In most cases, this improves the signal to noise ratio of the spectrometer. When the DR and the cavity have the same frequency, the coupled electromagnetic fields are found to contain equal contributions from the fields of the two uncoupled modes. This situation is ideal for the excitation of the probe through an iris on the cavity wall. To verify and validate the results, finite element simulations are carried out. This is achieved by simulating the coupling between a cylindrical cavity's TE011 and the dielectric insert's TE01δ modes. Coupling between the modes of higher order is also investigated and discussed. Based on CMT, closed form expressions for the fields of the coupled system are proposed. These expressions are crucial in the analysis of the probe's performance.

  4. Coupled modes, frequencies and fields of a dielectric resonator and a cavity using coupled mode theory.

    PubMed

    Elnaggar, Sameh Y; Tervo, Richard; Mattar, Saba M

    2014-01-01

    Probes consisting of a dielectric resonator (DR) inserted in a cavity are important integral components of electron paramagnetic resonance (EPR) spectrometers because of their high signal-to-noise ratio. This article studies the behavior of this system, based on the coupling between its dielectric and cavity modes. Coupled-mode theory (CMT) is used to determine the frequencies and electromagnetic fields of this coupled system. General expressions for the frequencies and field distributions are derived for both the resulting symmetric and anti-symmetric modes. These expressions are applicable to a wide range of frequencies (from MHz to THz). The coupling of cavities and DRs of various sizes and their resonant frequencies are studied in detail. Since the DR is situated within the cavity then the coupling between them is strong. In some cases the coupling coefficient, κ, is found to be as high as 0.4 even though the frequency difference between the uncoupled modes is large. This is directly attributed to the strong overlap between the fields of the uncoupled DR and cavity modes. In most cases, this improves the signal to noise ratio of the spectrometer. When the DR and the cavity have the same frequency, the coupled electromagnetic fields are found to contain equal contributions from the fields of the two uncoupled modes. This situation is ideal for the excitation of the probe through an iris on the cavity wall. To verify and validate the results, finite element simulations are carried out. This is achieved by simulating the coupling between a cylindrical cavity's TE011 and the dielectric insert's TE01δ modes. Coupling between the modes of higher order is also investigated and discussed. Based on CMT, closed form expressions for the fields of the coupled system are proposed. These expressions are crucial in the analysis of the probe's performance. PMID:24246950

  5. Array enhanced stochastic resonance: Implications for signal processing

    SciTech Connect

    Inchiosa, M.E.; Bulsara, A.R.; Lindner, J.F.; Meadows, B.K.; Ditto, W.L.

    1996-06-01

    In computer simulations, we enhance the response of a {open_quote}{open_quote}stochastic resonator{close_quote}{close_quote} by coupling it into an array of identical resonators. We relate this array enhanced stochastic resonance (AESR) to the global spatiotemporal dynamics of the array and show how noise and coupling cooperate to organize spatial order, temporal periodicity, and peak output signal-to-noise ratio. We consider the application of AESR to signal processing. {copyright} {ital 1996 American Institute of Physics.}

  6. Classical and quantum distinctions between weak and strong coupling

    NASA Astrophysics Data System (ADS)

    Rahimzadeh-Kalaleh Rodriguez, Said

    2016-03-01

    Coupled systems subject to dissipation exhibit two different regimes known as weak coupling and strong coupling. Two damped coupled harmonic oscillators (CHOs) constitute a model system where the key features of weak and strong coupling can be identified. Several of these features are common to classical and quantum systems, as a number of quantum-classical correspondences have shown. However, the condition defining the boundary between weak and strong coupling is distinct in classical and quantum formalisms. Here we describe the origin of two widely used definitions of strong coupling. Using a classical CHO model, we show that energy exchange cycles and avoided resonance crossings signal the onset of strong coupling according to one criterion. From the classical CHO model we derive a non-Hermitian Hamiltonian describing open quantum systems. Based on the analytic properties of the Hamiltonian, we identify the boundary between weak and strong coupling with a different feature: a non-Hermitian degeneracy known as the exceptional point. For certain parameter ranges the classical and quantum criterion for strong coupling coincide; for other ranges they do not. Examples of systems in strong coupling according to one or another criterion, but not both, are illustrated. The framework here presented is suitable for introducing graduate or advanced undegraduate students to the basic properties of strongly coupled systems, as well as to the similarities and subtle differences between classical and quantum descriptions of coupled dissipative systems.

  7. Signal processor for processing ultrasonic receiver signals

    DOEpatents

    Fasching, George E.

    1980-01-01

    A signal processor is provided which uses an analog integrating circuit in conjunction with a set of digital counters controlled by a precision clock for sampling timing to provide an improved presentation of an ultrasonic transmitter/receiver signal. The signal is sampled relative to the transmitter trigger signal timing at precise times, the selected number of samples are integrated and the integrated samples are transferred and held for recording on a strip chart recorder or converted to digital form for storage. By integrating multiple samples taken at precisely the same time with respect to the trigger for the ultrasonic transmitter, random noise, which is contained in the ultrasonic receiver signal, is reduced relative to the desired useful signal.

  8. A study of coupling two thermoacoustic lasers

    NASA Astrophysics Data System (ADS)

    Surathu, Rohit

    Thermoacoustics is a field studying the effects of applying heat to particular resonator geometries, resulting in the oscillations of gas and thereby producing sound waves. This field is a rich blend of many other scientific fields: acoustics, thermodynamics, and fluid mechanics. Thermoacoustic engines work on a similar principle as traditional heat engines. The main difference between a traditional heat engine and a thermoacoustic engine is that an acoustic wave drives the thermodynamic process in the latter. These engines are easy to construct, and there are no moving parts, which reduces the mechanical wear and tear. In our case, we fabricated the simpler thermoacoustic lasers to conduct the analysis. In most previous work within this field, different designs were tested and studied for a single laser operation from which extensive experimental data sets were collected and analyzed. Design and operation of a thermoacoustic laser pair is more complicated. Even though there have been a few coupling studies, detailed information about the acoustic field of multiple thermoacoustic lasers is lacking. Hence, an effort was made to study the interaction between the sound waves by acoustically coupling two thermoacoustic lasers. The acoustic coupling was varied using 4 different configurations. First, the lasers were placed parallel to each other, with their open ends separated by a 1 m distance (0° crossing angle). Next, the sound waves of the two lasers were focused at a particular point, with their openings in proximity at a fixed crossing angle (30 or 90°). Finally, the spatial distance between the openings of the 30 and 90° crossing lasers was increased in their own respective angles. The signals were read using three different measuring devices: a sound pressure level meter, a unidirectional microphone or an omnidirectional miniature microphone. The signals read using both microphones were collected, measured, and analyzed. The results proved that coupling

  9. Three tooth kinematic coupling

    DOEpatents

    Hale, Layton C.

    2000-01-01

    A three tooth kinematic coupling based on having three theoretical line contacts formed by mating teeth rather than six theoretical point contacts. The geometry requires one coupling half to have curved teeth and the other coupling half to have flat teeth. Each coupling half has a relieved center portion which does not effect the kinematics, but in the limit as the face width approaches zero, three line contacts become six point contacts. As a result of having line contact, a three tooth coupling has greater load capacity and stiffness. The kinematic coupling has application for use in precision fixturing for tools or workpieces, and as a registration device for a work or tool changer or for optics in various products.

  10. Three tooth kinematic coupling

    SciTech Connect

    Hale, L.C.

    2000-05-23

    A three tooth kinematic coupling is disclosed based on having three theoretical line contacts formed by mating teeth rather than six theoretical point contacts. The geometry requires one coupling half to have curved teeth and the other coupling half to have flat teeth. Each coupling half has a relieved center portion which does not effect the kinematics, but in the limit as the face width approaches zero, three line contacts become six point contacts. As a result of having line contact, a three tooth coupling has greater load capacity and stiffness. The kinematic coupling has application for use in precision fixturing for tools or workpieces, and as a registration device for a work or tool changer or for optics in various products.

  11. Signal verification can promote reliable signalling.

    PubMed

    Broom, Mark; Ruxton, Graeme D; Schaefer, H Martin

    2013-11-22

    The central question in communication theory is whether communication is reliable, and if so, which mechanisms select for reliability. The primary approach in the past has been to attribute reliability to strategic costs associated with signalling as predicted by the handicap principle. Yet, reliability can arise through other mechanisms, such as signal verification; but the theoretical understanding of such mechanisms has received relatively little attention. Here, we model whether verification can lead to reliability in repeated interactions that typically characterize mutualisms. Specifically, we model whether fruit consumers that discriminate among poor- and good-quality fruits within a population can select for reliable fruit signals. In our model, plants either signal or they do not; costs associated with signalling are fixed and independent of plant quality. We find parameter combinations where discriminating fruit consumers can select for signal reliability by abandoning unprofitable plants more quickly. This self-serving behaviour imposes costs upon plants as a by-product, rendering it unprofitable for unrewarding plants to signal. Thus, strategic costs to signalling are not a prerequisite for reliable communication. We expect verification to more generally explain signal reliability in repeated consumer-resource interactions that typify mutualisms but also in antagonistic interactions such as mimicry and aposematism. PMID:24068354

  12. Signal verification can promote reliable signalling

    PubMed Central

    Broom, Mark; Ruxton, Graeme D.; Schaefer, H. Martin

    2013-01-01

    The central question in communication theory is whether communication is reliable, and if so, which mechanisms select for reliability. The primary approach in the past has been to attribute reliability to strategic costs associated with signalling as predicted by the handicap principle. Yet, reliability can arise through other mechanisms, such as signal verification; but the theoretical understanding of such mechanisms has received relatively little attention. Here, we model whether verification can lead to reliability in repeated interactions that typically characterize mutualisms. Specifically, we model whether fruit consumers that discriminate among poor- and good-quality fruits within a population can select for reliable fruit signals. In our model, plants either signal or they do not; costs associated with signalling are fixed and independent of plant quality. We find parameter combinations where discriminating fruit consumers can select for signal reliability by abandoning unprofitable plants more quickly. This self-serving behaviour imposes costs upon plants as a by-product, rendering it unprofitable for unrewarding plants to signal. Thus, strategic costs to signalling are not a prerequisite for reliable communication. We expect verification to more generally explain signal reliability in repeated consumer–resource interactions that typify mutualisms but also in antagonistic interactions such as mimicry and aposematism. PMID:24068354

  13. Retroactive Signaling in Short Signaling Pathways

    PubMed Central

    Sepulchre, Jacques-Alexandre; Merajver, Sofía D.; Ventura, Alejandra C.

    2012-01-01

    In biochemical signaling pathways without explicit feedback connections, the core signal transduction is usually described as a one-way communication, going from upstream to downstream in a feedforward chain or network of covalent modification cycles. In this paper we explore the possibility of a new type of signaling called retroactive signaling, offered by the recently demonstrated property of retroactivity in signaling cascades. The possibility of retroactive signaling is analysed in the simplest case of the stationary states of a bicyclic cascade of signaling cycles. In this case, we work out the conditions for which variables of the upstream cycle are affected by a change of the total amount of protein in the downstream cycle, or by a variation of the phosphatase deactivating the same protein. Particularly, we predict the characteristic ranges of the downstream protein, or of the downstream phosphatase, for which a retroactive effect can be observed on the upstream cycle variables. Next, we extend the possibility of retroactive signaling in short but nonlinear signaling pathways involving a few covalent modification cycles. PMID:22848403

  14. Statistical physics approaches to understanding physiological signals

    NASA Astrophysics Data System (ADS)

    Chen, Zhi

    This thesis applies novel statistical physics approaches to investigate complex mechanisms underlying some physiological signals related to human motor activity and stroke. The scale-invariant properties of motor activity fluctuations and the phase coupling between blood flow (BF) in the brain and blood pressure (BP) at the finger are studied. Both BF and BP signals are controlled by cerebral autoregulation, the impairment of which is relevant to stroke. Part I of this thesis introduces experimental methods of assessing human activity fluctuations, BF and BP signals. These signals are often nonstationary, i.e., the mean and the standard deviation of signals are not invariant under time shifts. This fact imposes challenges in correctly analyzing properties of such signals. A review of conventional methods and the methods from statistical physics in quantifying long-range power-law correlations (an important scale-invariant property) and phase coupling in nonstationary signals is provided. Part II investigates the effects of trends, nonstationarities and applying certain nonlinear filters on the scale-invariant properties of signals. Nonlinear logarithmic filters are shown to change correlation properties of anti-correlated signals and strongly positively-correlated signals. It is also shown that different types of trends may change correlation properties and thus mask true correlations in the original signal. A "superposition rule" is established to quantitatively describe the relationship among correlation properties of any two signals and the sum of these two signals. Based on this rule, simulations are conducted to show how to distinguish the correlations due to trends and nonstationaries from the true correlations in the real world signals. Part III investigates dynamics of human activity fluctuations. Results suggest that apparently random forearm motion possesses previously unrecognized dynamic patterns characterized by common distribution forms, scale

  15. The spatiotemporal order of signaling events unveils the logic of development signaling

    PubMed Central

    Zhu, Hao; Owen, Markus R.; Mao, Yanlan

    2016-01-01

    Motivation: Animals from worms and insects to birds and mammals show distinct body plans; however, the embryonic development of diverse body plans with tissues and organs within is controlled by a surprisingly few signaling pathways. It is well recognized that combinatorial use of and dynamic interactions among signaling pathways follow specific logic to control complex and accurate developmental signaling and patterning, but it remains elusive what such logic is, or even, what it looks like. Results: We have developed a computational model for Drosophila eye development with innovated methods to reveal how interactions among multiple pathways control the dynamically generated hexagonal array of R8 cells. We obtained two novel findings. First, the coupling between the long-range inductive signals produced by the proneural Hh signaling and the short-range restrictive signals produced by the antineural Notch and EGFR signaling is essential for generating accurately spaced R8s. Second, the spatiotemporal orders of key signaling events reveal a robust pattern of lateral inhibition conducted by Ato-coordinated Notch and EGFR signaling to collectively determine R8 patterning. This pattern, stipulating the orders of signaling and comparable to the protocols of communication, may help decipher the well-appreciated but poorly defined logic of developmental signaling. Availability and implementation: The model is available upon request. Contact: hao.zhu@ymail.com Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27153573

  16. Evaluation of Air Coupled Ultrasound for Composite Aerospace Structure

    NASA Astrophysics Data System (ADS)

    Tat, H.; Georgeson, G.; Bossi, R.

    2009-03-01

    Non-contact air coupled ultrasound suffers from the high acoustic impedance mismatch characteristics of air to solid interfaces. Advances in transducer technology, particularly MEMS, have improved the acoustic impedance match at the transmission stage and the signal to noise at the reception stage. Comparisons of through transmission (TTU) scanning of laminate and honeycomb test samples using conventional piezoelectric air coupled transducers, new MEMS air coupled transducers, and standard water coupled inspections have been performed to assess the capability. An additional issue for air coupled UT inspection is the need for a lean implementation for both manufacturing and in-service operations. Concepts and applications utilizing magnetic coupling of transducers have been developed that allows air coupled inspection operations in compact low cost configurations.

  17. Multiplexing oscillatory biochemical signals.

    PubMed

    de Ronde, Wiet; ten Wolde, Pieter Rein

    2014-04-01

    In recent years it has been increasingly recognized that biochemical signals are not necessarily constant in time and that the temporal dynamics of a signal can be the information carrier. Moreover, it is now well established that the protein signaling network of living cells has a bow-tie structure and that components are often shared between different signaling pathways. Here we show by mathematical modeling that living cells can multiplex a constant and an oscillatory signal: they can transmit these two signals simultaneously through a common signaling pathway, and yet respond to them specifically and reliably. We find that information transmission is reduced not only by noise arising from the intrinsic stochasticity of biochemical reactions, but also by crosstalk between the different channels. Yet, under biologically relevant conditions more than 2 bits of information can be transmitted per channel, even when the two signals are transmitted simultaneously. These observations suggest that oscillatory signals are ideal for multiplexing signals. PMID:24685537

  18. Study of digital charge coupled devices

    NASA Technical Reports Server (NTRS)

    Wilson, D. D.; Young, V. F.

    1980-01-01

    Charge coupled devices represent unique usage of the metal oxide semiconductor concept. These devices can sample an AC signal at the input, transfer charge proportional to this signal through the CCD shift register and then provide an output of the same frequency and shape as the input. The delay time between input and output is controlled by the CCD operating frequency and the number of stages in the shift resistor. This work is a reliability evaluation of the buried channel and surface channel CCD technologies. The constructions are analyzed, failure modes are described, and test results are reported.

  19. Slab coupled optical fiber sensor calibration

    NASA Astrophysics Data System (ADS)

    Whitaker, B.; Noren, J.; Chadderdon, S.; Wang, W.; Forber, R.; Selfridge, R.; Schultz, S.

    2013-02-01

    This paper presents a method for calibrating slab coupled optical fiber sensors (SCOS). An automated system is presented for selecting the optimal laser wavelength for use in SCOS interrogation. The wavelength calibration technique uses a computer sound card for both the creation of the applied electric field and the signal detection. The method used to determine the ratio between the measured SCOS signal and the applied electric field is also described along with a demonstration of the calibrated SCOS involving measuring the dielectric breakdown of air.

  20. Bibliographic Coupling: A Review

    ERIC Educational Resources Information Center

    Weinberg, Bella Hass

    1974-01-01

    The theory and practical applications of bibliographic coupling are reviewed. The reviewer takes issue with the use of bibliographic coupling for information retrieval and automatic classification on logical grounds, and for reasons relating to uncontrolled citation practices. The usefulness of the procedure for the study of the science of science…

  1. Gear Spline Coupling Program

    2013-08-29

    An analytical model is developed to evaluate the design of a spline coupling. For a given torque and shaft misalignment, the model calculates the number of teeth in contact, tooth loads, stiffnesses, stresses, and safety factors. The analytic model provides essential spline coupling design and modeling information and could be easily integrated into gearbox design and simulation tools.

  2. Translation-coupling systems

    DOEpatents

    Pfleger, Brian; Mendez-Perez, Daniel

    2015-05-19

    Disclosed are systems and methods for coupling translation of a target gene to a detectable response gene. A version of the invention includes a translation-coupling cassette. The translation-coupling cassette includes a target gene, a response gene, a response-gene translation control element, and a secondary structure-forming sequence that reversibly forms a secondary structure masking the response-gene translation control element. Masking of the response-gene translation control element inhibits translation of the response gene. Full translation of the target gene results in unfolding of the secondary structure and consequent translation of the response gene. Translation of the target gene is determined by detecting presence of the response-gene protein product. The invention further includes RNA transcripts of the translation-coupling cassettes, vectors comprising the translation-coupling cassettes, hosts comprising the translation-coupling cassettes, methods of using the translation-coupling cassettes, and gene products produced with the translation-coupling cassettes.

  3. Translation-coupling systems

    DOEpatents

    Pfleger, Brian; Mendez-Perez, Daniel

    2013-11-05

    Disclosed are systems and methods for coupling translation of a target gene to a detectable response gene. A version of the invention includes a translation-coupling cassette. The translation-coupling cassette includes a target gene, a response gene, a response-gene translation control element, and a secondary structure-forming sequence that reversibly forms a secondary structure masking the response-gene translation control element. Masking of the response-gene translation control element inhibits translation of the response gene. Full translation of the target gene results in unfolding of the secondary structure and consequent translation of the response gene. Translation of the target gene is determined by detecting presence of the response-gene protein product. The invention further includes RNA transcripts of the translation-coupling cassettes, vectors comprising the translation-coupling cassettes, hosts comprising the translation-coupling cassettes, methods of using the translation-coupling cassettes, and gene products produced with the translation-coupling cassettes.

  4. Nonlinear spin wave coupling in adjacent magnonic crystals

    NASA Astrophysics Data System (ADS)

    Sadovnikov, A. V.; Beginin, E. N.; Morozova, M. A.; Sharaevskii, Yu. P.; Grishin, S. V.; Sheshukova, S. E.; Nikitov, S. A.

    2016-07-01

    We have experimentally studied the coupling of spin waves in the adjacent magnonic crystals. Space- and time-resolved Brillouin light-scattering spectroscopy is used to demonstrate the frequency and intensity dependent spin-wave energy exchange between the side-coupled magnonic crystals. The experiments and the numerical simulation of spin wave propagation in the coupled periodic structures show that the nonlinear phase shift of spin wave in the adjacent magnonic crystals leads to the nonlinear switching regime at the frequencies near the forbidden magnonic gap. The proposed side-coupled magnonic crystals represent a significant advance towards the all-magnonic signal processing in the integrated magnonic circuits.

  5. Non-Invasive Optical Biosensor for Probing Cell Signaling

    PubMed Central

    Fang, Ye

    2007-01-01

    Cell signaling mediated through a cellular target is encoded by spatial and temporal dynamics of downstream signaling networks. The coupling of temporal dynamics with spatial gradients of signaling activities guides cellular responses upon stimulation. Monitoring the integration of cell signaling in real time, if realized, would provide a new dimension for understanding cell biology and physiology. Optical biosensors including resonant waveguide grating (RWG) biosensor manifest a physiologically relevant and integrated cellular response related to dynamic redistribution of cellular matters, thus providing a non-invasive means for cell signaling study. This paper reviews recent progresses in biosensor instrumentation, and theoretical considerations and potential applications of optical biosensors for whole cell sensing.

  6. ERK Signals: Scaffolding Scaffolds?

    PubMed Central

    Casar, Berta; Crespo, Piero

    2016-01-01

    ERK1/2 MAP Kinases become activated in response to multiple intra- and extra-cellular stimuli through a signaling module composed of sequential tiers of cytoplasmic kinases. Scaffold proteins regulate ERK signals by connecting the different components of the module into a multi-enzymatic complex by which signal amplitude and duration are fine-tuned, and also provide signal fidelity by isolating this complex from external interferences. In addition, scaffold proteins play a central role as spatial regulators of ERKs signals. In this respect, depending on the subcellular localization from which the activating signals emanate, defined scaffolds specify which substrates are amenable to be phosphorylated. Recent evidence has unveiled direct interactions among different scaffold protein species. These scaffold-scaffold macro-complexes could constitute an additional level of regulation for ERK signals and may serve as nodes for the integration of incoming signals and the subsequent diversification of the outgoing signals with respect to substrate engagement. PMID:27303664

  7. Sending Signals Dynamically

    PubMed Central

    Smock, Robert G.; Gierasch, Lila M.

    2010-01-01

    Proteins mediate transmission of signals along intercellular and intracellular pathways and between the exterior and the interior of a cell. The dynamic properties of signaling proteins are crucial to their functions. We discuss emerging paradigms for the role of protein dynamics in signaling. A central tenet is that proteins fluctuate among many states on evolutionarily selected energy landscapes. Upstream signals remodel this landscape, causing signaling proteins to transmit information to downstream partners. New methods provide insight into the dynamic properties of signaling proteins at the atomic scale. The next stages in the signaling hierarchy—how multiple signals are integrated and how cellular signaling pathways are organized in space and time—present exciting challenges for the future, requiring bold multidisciplinary approaches. PMID:19359576

  8. Exponentially modified QCD coupling

    SciTech Connect

    Cvetic, Gorazd; Valenzuela, Cristian

    2008-04-01

    We present a specific class of models for an infrared-finite analytic QCD coupling, such that at large spacelike energy scales the coupling differs from the perturbative one by less than any inverse power of the energy scale. This condition is motivated by the Institute for Theoretical and Experimental Physics operator product expansion philosophy. Allowed by the ambiguity in the analytization of the perturbative coupling, the proposed class of couplings has three parameters. In the intermediate energy region, the proposed coupling has low loop-level and renormalization scheme dependence. The present modification of perturbative QCD must be considered as a phenomenological attempt, with the aim of enlarging the applicability range of the theory of the strong interactions at low energies.

  9. Ground energy coupling

    NASA Astrophysics Data System (ADS)

    Metz, P. D.

    The feasibility of ground coupling for various heat pump systems was investigated. Analytical heat flow models were developed to approximate design ground coupling devices for use in solar heat pump space conditioning systems. A digital computer program called GROCS (GRound Coupled Systems) was written to model 3-dimensional underground heat flow in order to simulate the behavior of ground coupling experiments and to provide performance predictions which have been compared to experimental results. GROCS also has been integrated with TRNSYS. Soil thermal property and ground coupling device experiments are described. Buried tanks, serpentine earth coils in various configurations, lengths and depths, and sealed vertical wells are being investigated. An earth coil used to heat a house without use of resistance heating is described.

  10. Signals for supersymmetry at HERA

    NASA Astrophysics Data System (ADS)

    Dreiner, Herbert; Morawitz, Peter

    1994-10-01

    We consider the baryon parity signals at HERA for the case of the MSSM production mechanisms and the decays via the lepton number violating couplings L iQ overlineD. We can probe very small Yukawa couplings λ' ⪆ 3 · 10 -6, limited only by the decay length of the LSP. We assume the LSP to be the lightest neutralino and study its decays in detail. We present the matrix element squared for the tree-level decay amplitude of a generally mixed neutralino explicitly. We find that the braching fraction to charged leptons strongly depends on the SUSY parameters and can differ significantly from the naively expected 50%. The SUSY mass reaches of the studied processes in the ZEUS detector at HERA were found to be : ( m(≈ e, ≈ v) + m ( t˜ q)) ⩽ 170 GeV, 195 GeV and 205 GeV for the L τQ overlineD, L μQ overlineDand L eQ overlineD couplings respectively. These are well above existing limits on R-parity violating ? SUSY from previous experiments. We conclude that HERA offers a very promising discovery potential for ? SUSY.

  11. Algorithm for astronomical, point source, signal to noise ratio calculations

    NASA Technical Reports Server (NTRS)

    Jayroe, R. R.; Schroeder, D. J.

    1984-01-01

    An algorithm was developed to simulate the expected signal to noise ratios as a function of observation time in the charge coupled device detector plane of an optical telescope located outside the Earth's atmosphere for a signal star, and an optional secondary star, embedded in a uniform cosmic background. By choosing the appropriate input values, the expected point source signal to noise ratio can be computed for the Hubble Space Telescope using the Wide Field/Planetary Camera science instrument.

  12. Lysophosphatidic Acid (LPA) Signaling in Vertebrate Reproduction

    PubMed Central

    Ye, Xiaoqin; Chun, Jerold

    2009-01-01

    Lysophosphatidic acid (LPA) is a cell membrane phospholipid metabolite that can act as an extracellular signal. Its effects are mediated through at least five G protein-coupled receptors (GPCRs), LPA1-5, and likely others as well. Studies in multiple species including LPA receptor-deficient mice and humans have identified or implicated important roles for receptor-mediated LPA signaling in multiple aspects of vertebrate reproduction. These include ovarian function, spermatogenesis, fertilization, early embryo development, embryo implantation, embryo spacing, decidualization, pregnancy maintenance, and parturition. LPA signaling may also have pathological consequences, influencing aspects of endometriosis and ovarian cancer. Here we review recent progress in LPA signaling research relevant to female and male reproduction. PMID:19836970

  13. Depression: The Differing Narratives of Couples in Couple Therapy

    ERIC Educational Resources Information Center

    Rautiainen, Eija-Liisa; Aaltonen, Jukka

    2010-01-01

    How does the spouse of a person with depression take part in constructing narratives of depression in couple therapy? In this study we examined couples' ways of co-constructing narratives of depression in couple therapy. Three couple therapy processes were chosen for the study, one spouse in each couple having been referred to an outpatient clinic…

  14. Subcellular optogenetics – controlling signaling and single-cell behavior

    PubMed Central

    Karunarathne, W. K. Ajith; O'Neill, Patrick R.; Gautam, Narasimhan

    2015-01-01

    ABSTRACT Variation in signaling activity across a cell plays a crucial role in processes such as cell migration. Signaling activity specific to organelles within a cell also likely plays a key role in regulating cellular functions. To understand how such spatially confined signaling within a cell regulates cell behavior, tools that exert experimental control over subcellular signaling activity are required. Here, we discuss the advantages of using optogenetic approaches to achieve this control. We focus on a set of optical triggers that allow subcellular control over signaling through the activation of G-protein-coupled receptors (GPCRs), receptor tyrosine kinases and downstream signaling proteins, as well as those that inhibit endogenous signaling proteins. We also discuss the specific insights with regard to signaling and cell behavior that these subcellular optogenetic approaches can provide. PMID:25433038

  15. Signal sciences workshop proceedings

    SciTech Connect

    Candy, J.V.

    1997-05-01

    This meeting is aimed primarily at signal processing and controls. The technical program for the 1997 Workshop includes a variety of efforts in the Signal Sciences with applications in the Microtechnology Area a new program at LLNL and a future area of application for both Signal/Image Sciences. Special sessions organized by various individuals in Seismic and Optical Signal Processing as well as Micro-Impulse Radar Processing highlight the program, while the speakers at the Signal Processing Applications session discuss various applications of signal processing/control to real world problems. For the more theoretical, a session on Signal Processing Algorithms was organized as well as for the more pragmatic, featuring a session on Real-Time Signal Processing.

  16. Signal Processing, Analysis, & Display

    SciTech Connect

    Lager, Darrell; Azevado, Stephen

    1986-06-01

    SIG is a general-purpose signal processing, analysis, and display program. Its main purpose is to perform manipulations on time- and frequency-domain signals. However, it has been designed to ultimately accommodate other representations for data such as multiplexed signals and complex matrices. Two user interfaces are provided in SIG - a menu mode for the unfamiliar user and a command mode for more experienced users. In both modes errors are detected as early as possible and are indicated by friendly, meaningful messages. An on-line HELP package is also included. A variety of operations can be performed on time- and frequency-domain signals including operations on the samples of a signal, operations on the entire signal, and operations on two or more signals. Signal processing operations that can be performed are digital filtering (median, Bessel, Butterworth, and Chebychev), ensemble average, resample, auto and cross spectral density, transfer function and impulse response, trend removal, convolution, Fourier transform and inverse window functions (Hamming, Kaiser-Bessel), simulation (ramp, sine, pulsetrain, random), and read/write signals. User definable signal processing algorithms are also featured. SIG has many options including multiple commands per line, command files with arguments,commenting lines, defining commands, and automatic execution for each item in a repeat sequence. Graphical operations on signals and spectra include: x-y plots of time signals; real, imaginary, magnitude, and phase plots of spectra; scaling of spectra for continuous or discrete domain; cursor zoom; families of curves; and multiple viewports.

  17. Coupling in the Tevatron

    SciTech Connect

    Gelfand, N.M.

    1994-12-01

    The performance of the Fermilab Tevatron Collider at the commencement of run Ib was far below expectations. After a frustrating period of several months, a low-{beta} quad downstream of the interaction point at B0 was found to be rolled. This rolled quadrupole coupled the horizontal and vertical motion of the Tevatron beams. It also made matching the beam from the Main Ring to the Tevatron impossible, resulting in emittance blow up on injection. The net result of the roll was a significant reduction in the Tevatron luminosity. When the roll in the quadrupole was corrected the performance of the Tevatron improved dramatically. This note will discuss the experimental data indicating the presence of coupling and subsequent calculations which show how coupling an affect the luminosity. It is not intended to exhaust a discussion of coupling, which hopefully will be understood well enough to be discussed in a subsequent note.

  18. The subfertile couple.

    PubMed

    McCusker, M P

    1982-01-01

    When pregnancy is achieved through fertility awareness, there are further long-range benefits to the couple: information which will permit them the choice to avoid, delay or achieve subsequent pregnancies. Thus, the opportunity for responsible parenthood continues. The goal of nursing in subfertility care is to identify factors which may contribute to lowered fertility, and to teach and/or refer appropriately. The most comprehensive single intervention may be to teach the couple awareness of their own fertility through the Billings Method of natural family planning. If conception does not occur, the couple may progress to infertility investigation, knowing that the expense, inconvenience, and possible trauma are justified. Whether pregnancy occurs or not, it is likely that the couple will have had the benefit of clarifying their relationship, further understanding their bodies, and generally growing toward fuller personhood. PMID:6920464

  19. Coupled gating between cardiac calcium release channels (ryanodine receptors).

    PubMed

    Marx, S O; Gaburjakova, J; Gaburjakova, M; Henrikson, C; Ondrias, K; Marks, A R

    2001-06-01

    Excitation-contraction coupling in heart muscle requires the activation of Ca(2+)-release channels/type 2 ryanodine receptors (RyR2s) by Ca(2+) influx. RyR2s are arranged on the sarcoplasmic reticular membrane in closely packed arrays such that their large cytoplasmic domains contact one another. We now show that multiple RyR2s can be isolated under conditions such that they remain physically coupled to one another. When these coupled channels are examined in planar lipid bilayers, multiple channels exhibit simultaneous gating, termed "coupled gating." Removal of the regulatory subunit, the FK506 binding protein (FKBP12.6), functionally but not physically uncouples multiple RyR2 channels. Coupled gating between RyR2 channels may be an important regulatory mechanism in excitation-contraction coupling as well as in other signaling pathways involving intracellular Ca(2+) release. PMID:11397781

  20. A FIELD CANCELATION SIGNAL EXTRACTION METHOD FOR MAGNETIC PARTICLE IMAGING

    PubMed Central

    Mahlke, Max; Hubertus, Simon; Lammers, Twan; Kiessling, Fabian

    2014-01-01

    In nowadays Magnetic Particle Imaging (MPI) signal detection and excitation happens at the same time. This concept, however, leads to strong coupling of the drive (excitation) field (DF) with the receive chain. As the induced DF signal is several orders of magnitude higher, special measures have to be taken to suppress this signal portion within the receive signal to keep the required dynamic range of the subsequent analog to digital conversion in a technically feasible range. For “frequency space MPI” high-order band-stop-filters have been successfully used to remove the DF signals, which unfortunately as well removes the fundamental harmonic components of the signal of the magnetic nanoparticles (MNP). According to the Langevin theory the fundamental harmonic component has a large signal contribution and is important for direct reconstruction of the particle concentration. In order to separate the fundamental harmonic component of the MNP from the induced DF signal, different concepts have been proposed using signal cancelation based on additional DF signals, also in combination with additional filtering. In this paper, we propose a field-cancelation (FC) concept in which a receive coil (RC) consists of a series connection of a primary coil in combination with an additional cancelation coil. The geometry of the primary coil was chosen to be sensitive for the MNP signal while the cancelation coil was chosen to minimize the overall inductive coupling of the FC-RC with the DF. Sensitivity plots and mutual coupling coefficients were calculated using a thin-wire approximation. A prototype FC-RC was manufactured and effectiveness of the reduction of the mutual inductive coupling (d) was tested in an existing mouse MPI scanner. The difference between simulations (ds=70 dB) and the measurements (dms=55 dB) indicated the feasibility as well as the need for further investigations. PMID:25892745

  1. Module coupling and predictability

    NASA Astrophysics Data System (ADS)

    Knopf, B.; Held, H.

    2003-04-01

    Successive coupling of several nonlinear submodules seems to be the implicit master strategy of the current world-wide modelling endeavour. The process of coupling is investigated by using different methods of examining low order coupled atmosphere-ocean systems. As a first step, a coupled atmosphere-ocean system, based on the Lorenz84 atmosphere is considered, operated in a forced versus the truly coupled mode. In [1] it is shown that forcing cannot emulate the fully coupled system, yet quite the contrary, generates time series of intermittently high predictability ("locking"). Standard linear stability analysis is incapable to explain the locking phenomenon. While regions of linear asymptotic stability can be evaluated, it turns out that this criterion is too conservative and does not explain the standard locking situation, as the trajectory periodically leaves the region of stability during a locking phase. We therefore propose that the locking phenomenon needs to be analysed in the framework of non-linear dynamics. Preliminary analysis of the statistic of locking-periods displays a similarity to type III intermittency. Bifurcation diagrams obtained from the continuation software AUTO indicate a rich phase space structure which makes the interpretation of the locking phenomenon intricate. Systematic variation of coupling constants appears to be a promising task as the key effects could be followed into parameter regimes of more transparent phase space structure. begin{thebibliography}{0} bibitem{Wittenberg98}A. T. Wittenberg, J. L. Anderson. Dynamical implications of prescribing part of a coupled system: Results from a low order model. Nonlinear Processes in Geophysics, 5: 167-179, 1998.

  2. Coupled transverse motion

    SciTech Connect

    Teng, L.C.

    1989-01-01

    The magnetic field in an accelerator or a storage ring is usually so designed that the horizontal (x) and the vertical (y) motions of an ion are uncoupled. However, because of imperfections in construction and alignment, some small coupling is unavoidable. In this lecture, we discuss in a general way what is known about the behaviors of coupled motions in two degrees-of-freedom. 11 refs., 6 figs.

  3. Apparatus for millimeter-wave signal generation

    DOEpatents

    Vawter, G. Allen; Hietala, Vincent M.; Zolper, John C.; Mar, Alan; Hohimer, John P.

    1999-01-01

    An opto-electronic integrated circuit (OEIC) apparatus is disclosed for generating an electrical signal at a frequency .gtoreq.10 GHz. The apparatus, formed on a single substrate, includes a semiconductor ring laser for generating a continuous train of mode-locked lasing pulses and a high-speed photodetector for detecting the train of lasing pulses and generating the electrical signal therefrom. Embodiments of the invention are disclosed with an active waveguide amplifier coupling the semiconductor ring laser and the high-speed photodetector. The invention has applications for use in OEICs and millimeter-wave monolithic integrated circuits (MMICs).

  4. Regulator of G-protein signaling - 5 (RGS5) is a novel repressor of hedgehog signaling.

    PubMed

    Mahoney, William M; Gunaje, Jagadambika; Daum, Guenter; Dong, Xiu Rong; Majesky, Mark W

    2013-01-01

    Hedgehog (Hh) signaling plays fundamental roles in morphogenesis, tissue repair, and human disease. Initiation of Hh signaling is controlled by the interaction of two multipass membrane proteins, patched (Ptc) and smoothened (Smo). Recent studies identify Smo as a G-protein coupled receptor (GPCR)-like protein that signals through large G-protein complexes which contain the Gαi subunit. We hypothesize Regulator of G-Protein Signaling (RGS) proteins, and specifically RGS5, are endogenous repressors of Hh signaling via their ability to act as GTPase activating proteins (GAPs) for GTP-bound Gαi, downstream of Smo. In support of this hypothesis, we demonstrate that RGS5 over-expression inhibits sonic hedgehog (Shh)-mediated signaling and osteogenesis in C3H10T1/2 cells. Conversely, signaling is potentiated by siRNA-mediated knock-down of RGS5 expression, but not RGS4 expression. Furthermore, using immuohistochemical analysis and co-immunoprecipitation (Co-IP), we demonstrate that RGS5 is present with Smo in primary cilia. This organelle is required for canonical Hh signaling in mammalian cells, and RGS5 is found in a physical complex with Smo in these cells. We therefore conclude that RGS5 is an endogenous regulator of Hh-mediated signaling and that RGS proteins are potential targets for novel therapeutics in Hh-mediated diseases. PMID:23637832

  5. Reliable Signal Transduction

    NASA Astrophysics Data System (ADS)

    Wollman, Roy

    Stochasticity inherent to biochemical reactions (intrinsic noise) and variability in cellular states (extrinsic noise) degrade information transmitted through signaling networks. We analyzed the ability of temporal signal modulation - that is dynamics - to reduce noise-induced information loss. In the extracellular signal-regulated kinase (ERK), calcium (Ca(2 +)) , and nuclear factor kappa-B (NF- κB) pathways, response dynamics resulted in significantly greater information transmission capacities compared to nondynamic responses. Theoretical analysis demonstrated that signaling dynamics has a key role in overcoming extrinsic noise. Experimental measurements of information transmission in the ERK network under varying signal-to-noise levels confirmed our predictions and showed that signaling dynamics mitigate, and can potentially eliminate, extrinsic noise-induced information loss. By curbing the information-degrading effects of cell-to-cell variability, dynamic responses substantially increase the accuracy of biochemical signaling networks.

  6. Mitochondria and cell signalling

    PubMed Central

    Tait, Stephen W. G.; Green, Douglas R.

    2012-01-01

    Mitochondria have long been considered as crucial organelles, primarily for their roles in biosynthetic reactions such as ATP synthesis. However, it is becoming increasingly apparent that mitochondria are intimately involved in cell signalling pathways. Mitochondria perform various signalling functions, serving as platforms to initiate cell signalling, as well as acting as transducers and effectors in multiple processes. Here, we discuss the active roles that mitochondria have in cell death signalling, innate immunity and autophagy. Common themes of mitochondrial regulation emerge from these diverse but interconnected processes. These include: the outer mitochondrial membrane serving as a major signalling platform, and regulation of cell signalling through mitochondrial dynamics and by mitochondrial metabolites, including ATP and reactive oxygen species. Importantly, defects in mitochondrial control of cell signalling and in the regulation of mitochondrial homeostasis might underpin many diseases, in particular age-related pathologies. PMID:22448037

  7. Coupling Correction Study at NSRRC

    SciTech Connect

    Safranek, James

    2003-07-29

    Emittance coupling between vertical and horizontal planes at TLS has been investigated. Using a set of skew quadrupoles, the coupling can be corrected to an acceptable value. The coupling sources are studied and possible errors are reduced.

  8. Seismic signals from asymmetric underground nuclear explosions

    SciTech Connect

    Davis, C.G.

    1993-09-01

    The methods discussed to estimate the effect on the seismic signals from asymmetric underground nuclear explosions, depends on the use of large-scale numerical codes and high-speed computers. The use of a two-dimensional (2D) radiation diffusion coupled Eulerian hydrodynamic code (SOIL) for the early time phenomenology is discussed. The results from this calculation are then coupled into a 2D Lagrangian code that treats the strength of the materials and the effects of fractures, ground reflections and spells. The final step in the simulation is the use of a seismic code (which uses the representation theory) to develop the actual far field seismic signals. These calculations were run on the CRAY YMP computers at the Los Alamos National Laboratory.

  9. Low-voltage differentially-signaled modulators

    SciTech Connect

    Zortman, William A.; Lentine, Anthony L.; Hsia, Alexander H.; Watts, Michael R.

    2015-09-08

    Photonic modulators and methods of modulating an input optical signal are provided. A photonic modulator includes at least one modulator section and differential drive circuitry. The at least one modulator section includes a P-type layer and an N-type layer forming a PN junction in the modulator section. The differential drive circuitry is electrically coupled to the P-type layer and the N-type layer of the at least one modulator section.

  10. Roles for lipid heterogeneity in immunoreceptor signaling.

    PubMed

    Holowka, David; Baird, Barbara

    2016-08-01

    Immune receptors that specifically recognize foreign antigens to activate leukocytes in adaptive immune responses belong to a family of multichain cell surface proteins. All of these contain immunoreceptor tyrosine-based activation motifs in one or more subunits that initiate signaling cascades following stimulated tyrosine phosphorylation by Src-family kinases. As highlighted in this review, lipids participate in this initial activation step, as well as in more downstream signaling steps. We summarize evidence for cholesterol-dependent ordered lipids serving to regulate the store-operated Ca(2+) channel, Orai1, and we describe the sensitivity of Orai1 coupling to the ER Ca(2+) sensor, STIM1, to inhibition by polyunsaturated fatty acids. Phosphoinositides play key roles in regulating STIM1-Orai1 coupling, as well as in the stimulated Ca(2+) oscillations that are a consequence of IgE receptor signaling in mast cells. They also participate in the coupling between the plasma membrane and the actin cytoskeleton, which regulates immune receptor responses in T cells, B cells, and mast cells, both positively and negatively, depending on the cellular context. Recent studies show that other phospholipids with mostly saturated acylation also participate in coupling between receptors and the actin cytoskeleton. Lipid heterogeneity is a central feature of the intimate relationship between the plasma membrane and the actin cytoskeleton. The detailed nature of these interactions and how they are dynamically regulated to initiate and propagate receptor-mediated cell signaling are challenging questions for further investigation. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon. PMID:26995463

  11. Inductively coupled stent antennas in MRI.

    PubMed

    Quick, Harald H; Kuehl, Hilmar; Kaiser, Gernot; Bosk, Silke; Debatin, Jörg F; Ladd, Mark E

    2002-11-01

    The development of intimal hyperplasia following stent deployment can lead to narrowing or even occlusion of the stent lumen. The underlying mechanisms leading to neointimal proliferation within stents remain largely unknown. Long-term evaluation of stent patency requires a noninvasive means for assessing the stent lumen. MR angiography (MRA) has shown potential to provide noninvasive assessment of the vascular system. However, a detailed assessment of the stent lumen with MRI is often hampered by material-dependent susceptibility artifacts, as well as by radiofrequency (RF) eddy currents generated inside the electrically conducting stent mesh. In this study, stent prototypes were designed to act as active resonant structures at the Larmor frequency of the MR system. Employing the principle of inductive coupling, the B(1) fields of the stents were coupled to that of an outside surface coil. The stents thus acted as local RF signal amplifiers. Various stent designs were investigated regarding their coupling to an external coil, signal homogeneity, and suitability for mechanical expansion for implantation purposes. The dependency of flip angle amplification on the quality factor Q of the stents was systematically investigated. Phantom experiments revealed signal amplification in all stent prototypes. Signal enhancement inside and close to the surface of the stents enabled their localization with high contrast in MR images. In vivo imaging experiments in the iliac, renal, and splenic arteries of two pigs confirmed the in vitro findings. Wireless active visualization of stents allows for detailed analysis of the stent lumen with high contrast and spatial resolution. The proposed method could thus provide a powerful diagnostic means for the noninvasive long-term follow-up of stent patency, thereby enhancing our understanding of the mechanisms of restenosis. PMID:12417992

  12. Telephone multiline signaling using common signal pair

    NASA Technical Reports Server (NTRS)

    Goodloe, R. R.; Toole, P. C.; Belt, J. L.; Leininger, D. B. (Inventor)

    1979-01-01

    An operator can rapidly and automatically produce coded electrical signals by manipulating mechanical thumb wheel switches so as to instruct a service center to connect any number of telephone lines to the console thus enabling the operator to listen and/or talk over several lines simultaneously. The system includes an on-site console having several mechanically operated thumb wheel switches to which the desired lines to be connected can be dialed in. Electrical coded signals are fed to a number of banks of line AND gates representing units, tens and hundreds, a group of channel gates, and a command gate. These signals are gated out in a controlled manner to an encoder which generates tones that are transmitted over a single line to a communication service center.

  13. Coupled adaptive complex networks

    NASA Astrophysics Data System (ADS)

    Shai, S.; Dobson, S.

    2013-04-01

    Adaptive networks, which combine topological evolution of the network with dynamics on the network, are ubiquitous across disciplines. Examples include technical distribution networks such as road networks and the internet, natural and biological networks, and social science networks. These networks often interact with or depend upon other networks, resulting in coupled adaptive networks. In this paper we study susceptible-infected-susceptible (SIS) epidemic dynamics on coupled adaptive networks, where susceptible nodes are able to avoid contact with infected nodes by rewiring their intranetwork connections. However, infected nodes can pass the disease through internetwork connections, which do not change with time: The dependencies between the coupled networks remain constant. We develop an analytical formalism for these systems and validate it using extensive numerical simulation. We find that stability is increased by increasing the number of internetwork links, in the sense that the range of parameters over which both endemic and healthy states coexist (both states are reachable depending on the initial conditions) becomes smaller. Finally, we find a new stable state that does not appear in the case of a single adaptive network but only in the case of weakly coupled networks, in which the infection is endemic in one network but neither becomes endemic nor dies out in the other. Instead, it persists only at the nodes that are coupled to nodes in the other network through internetwork links. We speculate on the implications of these findings.

  14. Quadrupole sensitive pulse for signal filtering

    NASA Astrophysics Data System (ADS)

    Evgeny, Nimerovsky; Jerschow, Alexej

    2016-04-01

    A longstanding problem in quadrupolar NMR of semi-solids is the selection of signals originating from ordered nuclei, i.e. those that experience a non-vanishing quadrupolar coupling. Established techniques, such as for example multiple-quantum filters are not adequate in situations when the radio frequency power is on the order of the quadrupolar coupling or the quadrupolar relaxation rates, such as may be the case on an MRI scanner, or in ex situ applications. In this manuscript we show a new method for the selective excitation of ordered spin-3/2 nuclei, which produces the desired results when the radio frequency power is approximately equal or smaller than quadrupolar frequency. Using a combination of simulations and experiments with 23Na in NaCl solution, Pf1-solutions, and bovine patellar cartilage samples we further show how the value of the quadrupolar frequency and global features of a quadrupolar coupling distribution can be extracted from these experiments.

  15. Energy efficiency of information transmission by electrically coupled neurons.

    PubMed

    Torrealdea, Francisco J; Sarasola, Cecilia; d'Anjou, Alicia; Moujahid, Abdelmalik; de Mendizábal, N Vélez

    2009-07-01

    The generation of spikes by neurons is energetically a costly process. This paper studies the consumption of energy and the information entropy in the signalling activity of a model neuron both when it is supposed isolated and when it is coupled to another neuron by an electrical synapse. The neuron has been modelled by a four-dimensional Hindmarsh-Rose type kinetic model for which an energy function has been deduced. For the isolated neuron values of energy consumption and information entropy at different signalling regimes have been computed. For two neurons coupled by a gap junction we have analyzed the roles of the membrane and synapse in the contribution of the energy that is required for their organized signalling. Computational results are provided for cases of identical and nonidentical neurons coupled by unidirectional and bidirectional gap junctions. One relevant result is that there are values of the coupling strength at which the organized signalling of two neurons induced by the gap junction takes place at relatively low values of energy consumption and the ratio of mutual information to energy consumption is relatively high. Therefore, communicating at these coupling values could be energetically the most efficient option. PMID:19397950

  16. Surface-plasmon-coupled emission microscopy with a polarization converter.

    PubMed

    Chen, Yikai; Zhang, Douguo; Han, Lu; Rui, Guanghao; Wang, Xiangxian; Wang, Pei; Ming, Hai

    2013-03-01

    Although surface-plasmon-coupled emission-based fluorescence microscopy proves high sensitivity for surface imaging, its donut shape point spread function (PSF) leads to low optical resolution and inefficient signal collection. In this Letter, we experimentally demonstrate the feasibility of solving this problem by the use of a liquid-crystal plate, which could convert the polarization state of surface-plasmon-coupled fluorescence from radial to linear. After being focused by the collection lens, an Airy disk-like PSF of small size can be realized. Experimental results reveal that both the lateral resolution and the signal-to-noise ratio can be enhanced simultaneously. PMID:23455282

  17. Transmission of a microwave cavity coupled to localized Shiba states

    NASA Astrophysics Data System (ADS)

    Chirla, Razvan; Manolescu, Andrei; Moca, Cǎtǎlin Paşcu

    2016-04-01

    We consider a strongly correlated quantum dot, tunnel coupled to two superconducting leads and capacitively coupled to a single mode microwave cavity. When the superconducting gap is the largest energy scale, multiple Shiba states are formed inside the gap. The competition of these states for the ground state signals a quantum phase transition. We demonstrate that photonic measurements can be used to probe such localized Shiba states. Moreover, the quantum phase transition can be pinpointed exactly from the sudden change in the transmission signal. Calculations were performed using the numerical renormalization-group approach.

  18. System for transmitting low frequency analog signals over AC power lines

    DOEpatents

    Baker, Steven P.; Durall, Robert L.; Haynes, Howard D.

    1989-09-05

    A system for transmitting low frequency analog signals over AC power lines using FM modulation. A low frequency analog signal to be transmitted is first applied to a voltage-to-frequency converter where it is converted to a signal whose frequency varies in proportion to the analog signal amplitude. This signal is then used to modulate the carrier frequency of an FM transmitter coupled to an AC power line. The modulation signal frequency range in selected to be within the response band of the FM transmitter. The FM modulated carrier signal is received by an FM receiver coupled to the AC power line, demodulated and the demodulated signal frequency is converted by a frequency-to-voltage converter back to the form of the original low frequency analog input signal.

  19. A system for tranmitting low frequency analog signals over ac power lines

    DOEpatents

    Baker, S.P.; Durall, R.L.; Haynes, H.D.

    1987-07-30

    A system for transmitting low frequency analog signals over ac power lines using FM modulation. A low frequency analog signal to be transmitted is first applied to a voltage-to-frequency converter where it is converted to a signal whose frequency varies in proportion to the analog signal amplitude. This signal is then used to modulate the carrier frequency of an FM transmitter coupled to an ac power line. The modulation signal frequency range is selected to be within the response band of the FM transmitter. The FM modulated carrier signal is received by an FM receiver coupled to the ac power line, demodulated and the demodulated signal frequency is converted by a frequency-to-voltage converter back to the form of the original low frequency analog input signal. 4 figs.

  20. System for transmitting low frequency analog signals over AC power lines

    DOEpatents

    Baker, Steven P.; Durall, Robert L.; Haynes, Howard D.

    1989-01-01

    A system for transmitting low frequency analog signals over AC power lines using FM modulation. A low frequency analog signal to be transmitted is first applied to a voltage-to-frequency converter where it is converted to a signal whose frequency varies in proportion to the analog signal amplitude. This signal is then used to modulate the carrier frequency of an FM transmitter coupled to an AC power line. The modulation signal frequency range in selected to be within the response band of the FM transmitter. The FM modulated carrier signal is received by an FM receiver coupled to the AC power line, demodulated and the demodulated signal frequency is converted by a frequency-to-voltage converter back to the form of the original low frequency analog input signal.

  1. Marriage Encounter Weekends: Couples Who Win and Couples Who Lose.

    ERIC Educational Resources Information Center

    Doherty, William J.; And Others

    1986-01-01

    Fifty couples who had the most positive or negative reactions in a group of Marriage Encounter couples were interviewed. Results indicated nine couples experienced significant negative changes related to Marriage Encounter, suggesting that distressed couples who attend Marriage Encounters are susceptible to further marital deterioration.…

  2. Requirements for security signalling

    SciTech Connect

    Pierson, L.G.; Tarman, T.D.

    1995-02-05

    There has been some interest lately in the need for ``authenticated signalling``, and the development of signalling specifications by the ATM Forum that support this need. The purpose of this contribution is to show that if authenticated signalling is required, then supporting signalling facilities for directory services (i.e. key management) are also required. Furthermore, this contribution identifies other security related mechanisms that may also benefit from ATM-level signalling accommodations. For each of these mechanisms outlined here, an overview of the signalling issues and a rough cut at the required fields for supporting Information Elements are provided. Finally, since each of these security mechanisms are specified by a number of different standards, issues pertaining to the selection of a particular security mechanism at connection setup time (i.e. specification of a required ``Security Quality of Service``) are also discussed.

  3. Saturation in coupled oscillators

    NASA Astrophysics Data System (ADS)

    Roman, Ahmed; Hanna, James

    2015-03-01

    We consider a weakly nonlinear system consisting of a resonantly forced oscillator coupled to an unforced oscillator. It has long been known that, for quadratic nonlinearities and a 2:1 resonance between the oscillators, a perturbative solution of the dynamics exhibits a phenomenon known as saturation. At low forcing, the forced oscillator responds, while the unforced oscillator is quiescent. Above a critical value of the forcing, the forced oscillator's steady-state amplitude reaches a plateau, while that of the unforced oscillator increases without bound. We show that, contrary to established folklore, saturation is not unique to quadratically nonlinear systems. We present conditions on the form of the nonlinear couplings and resonance that lead to saturation. Our results elucidate a mechanism for localization or diversion of energy in systems of coupled oscillators, and suggest new approaches for the control or suppression of vibrations in engineered systems.

  4. Calcium signaling as a mediator of cell energy demand and a trigger to cell death.

    PubMed

    Bhosale, Gauri; Sharpe, Jenny A; Sundier, Stephanie Y; Duchen, Michael R

    2015-09-01

    Calcium signaling is pivotal to a host of physiological pathways. A rise in calcium concentration almost invariably signals an increased cellular energy demand. Consistent with this, calcium signals mediate a number of pathways that together serve to balance energy supply and demand. In pathological states, calcium signals can precipitate mitochondrial injury and cell death, especially when coupled to energy depletion and oxidative or nitrosative stress. This review explores the mechanisms that couple cell signaling pathways to metabolic regulation or to cell death. The significance of these pathways is exemplified by pathological case studies, such as those showing loss of mitochondrial calcium uptake 1 in patients and ischemia/reperfusion injury. PMID:26375864

  5. Calcium signaling as a mediator of cell energy demand and a trigger to cell death

    PubMed Central

    Bhosale, Gauri; Sharpe, Jenny A.; Sundier, Stephanie Y.

    2015-01-01

    Calcium signaling is pivotal to a host of physiological pathways. A rise in calcium concentration almost invariably signals an increased cellular energy demand. Consistent with this, calcium signals mediate a number of pathways that together serve to balance energy supply and demand. In pathological states, calcium signals can precipitate mitochondrial injury and cell death, especially when coupled to energy depletion and oxidative or nitrosative stress. This review explores the mechanisms that couple cell signaling pathways to metabolic regulation or to cell death. The significance of these pathways is exemplified by pathological case studies, such as those showing loss of mitochondrial calcium uptake 1 in patients and ischemia/reperfusion injury. PMID:26375864

  6. The coupling of pathways and processes through shared components

    PubMed Central

    2011-01-01

    Background The coupling of pathways and processes through shared components is being increasingly recognised as a common theme which occurs in many cell signalling contexts, in which it plays highly non-trivial roles. Results In this paper we develop a basic modelling and systems framework in a general setting for understanding the coupling of processes and pathways through shared components. Our modelling framework starts with the interaction of two components with a common third component and includes production and degradation of all these components. We analyze the signal processing in our model to elucidate different aspects of the coupling. We show how different kinds of responses, including "ultrasensitive" and adaptive responses, may occur in this setting. We then build on the basic model structure and examine the effects of additional control regulation, switch-like signal processing, and spatial signalling. In the process, we identify a way in which allosteric regulation may contribute to signalling specificity, and how competitive effects may allow an enzyme to robustly coordinate and time the activation of parallel pathways. Conclusions We have developed and analyzed a common systems platform for examining the effects of coupling of processes through shared components. This can be the basis for subsequent expansion and understanding the many biologically observed variations on this common theme. PMID:21714894

  7. Signal Processing, Analysis, & Display

    1986-06-01

    SIG is a general-purpose signal processing, analysis, and display program. Its main purpose is to perform manipulations on time- and frequency-domain signals. However, it has been designed to ultimately accommodate other representations for data such as multiplexed signals and complex matrices. Two user interfaces are provided in SIG - a menu mode for the unfamiliar user and a command mode for more experienced users. In both modes errors are detected as early as possible andmore » are indicated by friendly, meaningful messages. An on-line HELP package is also included. A variety of operations can be performed on time- and frequency-domain signals including operations on the samples of a signal, operations on the entire signal, and operations on two or more signals. Signal processing operations that can be performed are digital filtering (median, Bessel, Butterworth, and Chebychev), ensemble average, resample, auto and cross spectral density, transfer function and impulse response, trend removal, convolution, Fourier transform and inverse window functions (Hamming, Kaiser-Bessel), simulation (ramp, sine, pulsetrain, random), and read/write signals. User definable signal processing algorithms are also featured. SIG has many options including multiple commands per line, command files with arguments,commenting lines, defining commands, and automatic execution for each item in a repeat sequence. Graphical operations on signals and spectra include: x-y plots of time signals; real, imaginary, magnitude, and phase plots of spectra; scaling of spectra for continuous or discrete domain; cursor zoom; families of curves; and multiple viewports.« less

  8. Digital signal processing the Tevatron BPM signals

    SciTech Connect

    Cancelo, G.; James, E.; Wolbers, S.; /Fermilab

    2005-05-01

    The Beam Position Monitor (TeV BPM) readout system at Fermilab's Tevatron has been updated and is currently being commissioned. The new BPMs use new analog and digital hardware to achieve better beam position measurement resolution. The new system reads signals from both ends of the existing directional stripline pickups to provide simultaneous proton and antiproton measurements. The signals provided by the two ends of the BPM pickups are processed by analog band-pass filters and sampled by 14-bit ADCs at 74.3MHz. A crucial part of this work has been the design of digital filters that process the signal. This paper describes the digital processing and estimation techniques used to optimize the beam position measurement. The BPM electronics must operate in narrow-band and wide-band modes to enable measurements of closed-orbit and turn-by-turn positions. The filtering and timing conditions of the signals are tuned accordingly for the operational modes. The analysis and the optimized result for each mode are presented.

  9. Coupled moderator neutronics

    SciTech Connect

    Russell, G.J.; Pitcher, E.J.; Ferguson, P.D.

    1995-12-01

    Optimizing the neutronic performance of a coupled-moderator system for a Long-Pulse Spallation Source is a new and challenging area for the spallation target-system designer. For optimal performance of a neutron source, it is essential to have good communication with instrument scientists to obtain proper design criteria and continued interaction with mechanical, thermal-hydraulic, and materials engineers to attain a practical design. A good comprehension of the basics of coupled-moderator neutronics will aid in the proper design of a target system for a Long-Pulse Spallation Source.

  10. Precision signal power measurement

    NASA Technical Reports Server (NTRS)

    Winkelstein, R.

    1972-01-01

    Accurate estimation of signal power is an important Deep Space Network (DSN) consideration. Ultimately, spacecraft power and weight is saved if no reserve transmitter power is needed to compensate for inaccurate measurements. Spectral measurement of the received signal has proved to be an effective method of estimating signal power over a wide dynamic range. Furthermore, on-line spectral measurements provide an important diagnostic tool for examining spacecraft anomalies. Prototype equipment installed at a 64-m-diameter antenna site has been successfully used to make measurements of carrier power and sideband symmetry of telemetry signals received from the Mariner Mars 1971 spacecraft.

  11. Slit-Robo signaling.

    PubMed

    Blockus, Heike; Chédotal, Alain

    2016-09-01

    Slits are secreted proteins that bind to Roundabout (Robo) receptors. Slit-Robo signaling is best known for mediating axon repulsion in the developing nervous system. However, in recent years the functional repertoire of Slits and Robo has expanded tremendously and Slit-Robo signaling has been linked to roles in neurogenesis, angiogenesis and cancer progression among other processes. Likewise, our mechanistic understanding of Slit-Robo signaling has progressed enormously. Here, we summarize new insights into Slit-Robo evolutionary and system-dependent diversity, receptor-ligand interactions, signaling crosstalk and receptor activation. PMID:27578174

  12. Cytoskeleton in Mast Cell Signaling

    PubMed Central

    Dráber, Pavel; Sulimenko, Vadym; Dráberová, Eduarda

    2012-01-01

    Mast cell activation mediated by the high affinity receptor for IgE (FcεRI) is a key event in allergic response and inflammation. Other receptors on mast cells, as c-Kit for stem cell factor and G protein-coupled receptors (GPCRs) synergistically enhance the FcεRI-mediated release of inflammatory mediators. Activation of various signaling pathways in mast cells results in changes in cell morphology, adhesion to substrate, exocytosis, and migration. Reorganization of cytoskeleton is pivotal in all these processes. Cytoskeletal proteins also play an important role in initial stages of FcεRI and other surface receptors induced triggering. Highly dynamic microtubules formed by αβ-tubulin dimers as well as microfilaments build up from polymerized actin are affected in activated cells by kinases/phosphatases, Rho GTPases and changes in concentration of cytosolic Ca2+. Also important are nucleation proteins; the γ-tubulin complexes in case of microtubules or Arp 2/3 complex with its nucleation promoting factors and formins in case of microfilaments. The dynamic nature of microtubules and microfilaments in activated cells depends on many associated/regulatory proteins. Changes in rigidity of activated mast cells reflect changes in intermediate filaments build up from vimentin. This review offers a critical appraisal of current knowledge on the role of cytoskeleton in mast cells signaling. PMID:22654883

  13. Signal transduction of stress via ceramide.

    PubMed Central

    Mathias, S; Peña, L A; Kolesnick, R N

    1998-01-01

    The sphingomyelin (SM) pathway is a ubiquitous, evolutionarily conserved signalling system analogous to conventional systems such as the cAMP and phosphoinositide pathways. Ceramide, which serves as second messenger in this pathway, is generated from SM by the action of a neutral or acidic SMase, or by de novo synthesis co-ordinated through the enzyme ceramide synthase. A number of direct targets for ceramide action have now been identified, including ceramide-activated protein kinase, ceramide-activated protein phosphatase and protein kinase Czeta, which couple the SM pathway to well defined intracellular signalling cascades. The SM pathway induces differentiation, proliferation or growth arrest, depending on the cell type. Very often, however, the outcome of signalling through this pathway is apoptosis. Mammalian systems respond to diverse stresses with ceramide generation, and recent studies show that yeast manifest a form of this response. Thus ceramide signalling is an older stress response system than the caspase/apoptotic death pathway, and hence these two pathways must have become linked later in evolution. Signalling of the stress response through ceramide appears to play a role in the development of human diseases, including ischaemia/reperfusion injury, insulin resistance and diabetes, atherogenesis, septic shock and ovarian failure. Further, ceramide signalling mediates the therapeutic effects of chemotherapy and radiation in some cells. An understanding of the mechanisms by which ceramide regulates physiological and pathological events in specific cells may provide new targets for pharmacological intervention. PMID:9794783

  14. Multi-signal FIB/SEM tomography

    NASA Astrophysics Data System (ADS)

    Giannuzzi, Lucille A.

    2012-06-01

    Focused ion beam (FIB) milling coupled with scanning electron microscopy (SEM) on the same platform enables 3D microstructural analysis of structures using FIB for serial sectioning and SEM for imaging. Since FIB milling is a destructive technique, the acquisition of multiple signals from each slice is desirable. The feasibility of collecting both an inlens backscattered electron (BSE) signal and an inlens secondary electron (SE) simultaneously from a single scan of the electron beam from each FIB slice is demonstrated. The simultaneous acquisition of two different SE signals from two different detectors (inlens vs. Everhart-Thornley (ET) detector) is also possible. Obtaining multiple signals from each FIB slice with one scan increases the acquisition throughput. In addition, optimization of microstructural and morphological information from the target is achieved using multi-signals. Examples of multi-signal FIB/SEM tomography from a dental implant will be provided where both material contrast from the bone/ceramic coating/Ti substrate phases and porosity in the ceramic coating will be characterized.

  15. Lysophosphatidic Acid signaling in the nervous system.

    PubMed

    Yung, Yun C; Stoddard, Nicole C; Mirendil, Hope; Chun, Jerold

    2015-02-18

    The brain is composed of many lipids with varied forms that serve not only as structural components but also as essential signaling molecules. Lysophosphatidic acid (LPA) is an important bioactive lipid species that is part of the lysophospholipid (LP) family. LPA is primarily derived from membrane phospholipids and signals through six cognate G protein-coupled receptors (GPCRs), LPA1-6. These receptors are expressed on most cell types within central and peripheral nervous tissues and have been functionally linked to many neural processes and pathways. This Review covers a current understanding of LPA signaling in the nervous system, with particular focus on the relevance of LPA to both physiological and diseased states. PMID:25695267

  16. Glutathione and redox signaling in substance abuse

    PubMed Central

    Uys, Joachim D.; Mulholland, Patrick J.; Townsend, Danyelle M.

    2015-01-01

    Throughout the last couple decades, the cause and consequences of substance abuse has expanded to identify the underlying neurobiological signaling mechanisms associated with addictive behavior. Chronic use of drugs, such as cocaine, methamphetamine and alcohol leads to the formation of oxidative or nitrosative stress (ROS/RNS) and changes in glutathione and redox homeostasis. Of importance, redox-sensitive post-translational modifications on cysteine residues, such as S-glutathionylation and S-nitrosylation could impact on the structure and function of addiction related signaling proteins. In this commentary, we evaluate the role of glutathione and redox signaling in cocaine-, methamphetamine- and alcohol addiction and conclude by discussing the possibility of targeting redox pathways for the therapeutic intervention of these substance abuse disorders. PMID:25027386

  17. Glutathione and redox signaling in substance abuse.

    PubMed

    Uys, Joachim D; Mulholland, Patrick J; Townsend, Danyelle M

    2014-07-01

    Throughout the last couple decades, the cause and consequences of substance abuse has expanded to identify the underlying neurobiological signaling mechanisms associated with addictive behavior. Chronic use of drugs, such as cocaine, methamphetamine and alcohol leads to the formation of oxidative or nitrosative stress (ROS/RNS) and changes in glutathione and redox homeostasis. Of importance, redox-sensitive post-translational modifications on cysteine residues, such as S-glutathionylation and S-nitrosylation could impact on the structure and function of addiction related signaling proteins. In this commentary, we evaluate the role of glutathione and redox signaling in cocaine-, methamphetamine- and alcohol addiction and conclude by discussing the possibility of targeting redox pathways for the therapeutic intervention of these substance abuse disorders. PMID:25027386

  18. Bile acid signaling and biliary functions

    PubMed Central

    Jones, Hannah; Alpini, Gianfranco; Francis, Heather

    2015-01-01

    This review focuses on various components of bile acid signaling in relation to cholangiocytes. Their roles as targets for potential therapies for cholangiopathies are also explored. While many factors are involved in these complex signaling pathways, this review emphasizes the roles of transmembrane G protein coupled receptor (TGR5), farnesoid X receptor (FXR), ursodeoxycholic acid (UDCA) and the bicarbonate umbrella. Following a general background on cholangiocytes and bile acids, we will expand the review and include sections that are most recently known (within 5–7 years) regarding the field of bile acid signaling and cholangiocyte function. These findings all demonstrate that bile acids influence biliary functions which can, in turn, regulate the cholangiocyte response during pathological events. PMID:26579437

  19. Coupling Gammasphere and ORRUBA

    SciTech Connect

    Ratkiewicz, A.; Cizewski, J. A.; Manning, B.; Pain, S. D.; Bardayan, D. W.; Blackmon, J. C.; Matos, M.; Chipps, K. A.; Hardy, S.; Shand, C.; Jones, K. L.; Kozub, R. L.; Lister, C. J.; Peters, W. A.; Seweryniak, D.

    2013-04-19

    The coincident detection of particles and gamma rays allows the study of the structure of exotic nuclei via inverse kinematics reactions using radioactive ion beams and thick targets. We report on the status of the project to couple the highresolution charged-particle detector ORRUBA to Gammasphere, a high-efficiency, high-resolution gamma ray detector.

  20. The Coupling Controversy

    PubMed Central

    Fox, Peter T.

    2014-01-01

    Functional magnetic resonance imaging (fMRI) relies on the well-known phenomenon of coupling between neuronal activity and brain blood flow. For nearly a century, the presumption was that hemodynamics were coupled to neuronal activity via energy demand and oxidative metabolism. Early 15O positron-emission tomographic (PET) studies challenged this theory, demonstrating a physiological “uncoupling” between brain blood flow and oxygen metabolism. These PET observations played a pivotal role in guiding the development of fMRI, by demonstrating which physiological parameters were most closely coupled to neuronal activity and by presaging the BOLD-contrast effect. Subsequent PET studies were crucial for constraining theories concerning the physiological mechanisms underlying hemodynamic/neuronal coupling and, thereby, guiding the development of models for quantification of oxygen metabolic rate %Δ from fMRI. A first-person account of the PET “coupling” studies and their influence on the development of fMRI is provided. PMID:22306802

  1. Coupled Oscillators with Chemotaxis

    NASA Astrophysics Data System (ADS)

    Sawai, Satoshi; Aizawa, Yoji

    1998-08-01

    A simple coupled oscillator system with chemotaxis is introducedto study morphogenesis of cellular slime molds. The modelsuccessfuly explains the migration of pseudoplasmodium which hasbeen experimentally predicted to be lead by cells with higherintrinsic frequencies. Results obtained predict that its velocityattains its maximum value in the interface region between totallocking and partial locking and also suggest possible rolesplayed by partial synchrony during multicellular development.

  2. The Pregnant Couple.

    ERIC Educational Resources Information Center

    Soule, A. Bradley, III

    This paper reports some of the preliminary findings of an investigation of the ways in which married couples experience pregnancy. Demographic, historical, personal, and marital information was gathered through individual interviews with each prospective parent. The 57 variables measured were combined to make six clusters: (1) experience of…

  3. Too Many Couples

    ERIC Educational Resources Information Center

    Kay, Joseph

    2007-01-01

    In this article, the author offers his ad hoc reflections on the question of just how many academic couples a department could comfortably accommodate from the point of view of good governance, in the hope of getting an honest dialogue started and seeing some reasonable guidelines eventually created by one organization or another as a result. He…

  4. A biomimetic coupled circuit based microphone array for sound source localization.

    PubMed

    Xu, Huping; Xu, Xiangyuan; Jia, Han; Guan, Luyang; Bao, Ming

    2015-09-01

    An equivalent analog circuit is designed to mimic the coupled ears of the fly Ormia ochracea for sound source localization. This coupled circuit receives two signals with tiny phase difference from a space closed two-microphone array, and produces two signals with obvious intensity difference. The response sensitivity can be adjusted through the coupled circuit parameters. The directional characteristics of the coupled circuit have been demonstrated in the experiment. The miniature microphone array can localize the sound source with low computational burden by using the intensity difference. This system has significant advantages in various applications where the array size is limited. PMID:26428825

  5. Orexin/hypocretin receptor signalling cascades

    PubMed Central

    Kukkonen, JP; Leonard, CS

    2014-01-01

    Orexin (hypocretin) peptides and their two known G-protein-coupled receptors play essential roles in sleep–wake control and powerfully influence other systems regulating appetite/metabolism, stress and reward. Consequently, drugs that influence signalling by these receptors may provide novel therapeutic opportunities for treating sleep disorders, obesity and addiction. It is therefore critical to understand how these receptors operate, the nature of the signalling cascades they engage and their physiological targets. In this review, we evaluate what is currently known about orexin receptor signalling cascades, while a sister review (Leonard & Kukkonen, this issue) focuses on tissue-specific responses. The evidence suggests that orexin receptor signalling is multifaceted and is substantially more diverse than originally thought. Indeed, orexin receptors are able to couple to members of at least three G-protein families and possibly other proteins, through which they regulate non-selective cation channels, phospholipases, adenylyl cyclase, and protein and lipid kinases. In the central nervous system, orexin receptors produce neuroexcitation by postsynaptic depolarization via activation of non-selective cation channels, inhibition of K+ channels and activation of Na+/Ca2+ exchange, but they also can stimulate the release of neurotransmitters by presynaptic actions and modulate synaptic plasticity. Ca2+ signalling is also prominently influenced by these receptors, both via the classical phospholipase C−Ca2+ release pathway and via Ca2+ influx, mediated by several pathways. Upon longer-lasting stimulation, plastic effects are observed in some cell types, while others, especially cancer cells, are stimulated to die. Thus, orexin receptor signals appear highly tunable, depending on the milieu in which they are operating. Linked ArticlesThis article is part of a themed section on Orexin Receptors. To view the other articles in this section visit http://dx.doi.org/10

  6. Signaling by Gasotransmitters

    PubMed Central

    Mustafa, Asif K.; Gadalla, Moataz M.; Snyder, Solomon H.

    2009-01-01

    Nitric oxide is well established as a major signaling molecule. Evidence is accumulating that carbon monoxide and hydrogen sulfide also are physiologic mediators in the cardiovascular, immune, and nervous systems. This Review focuses on mechanisms whereby they signal by binding to metal centers in metalloproteins, such as in guanylyl cyclase, or modifying sulfhydryl groups in protein targets. PMID:19401594

  7. Broadband directional coupling in aluminum nitride nanophotonic circuits.

    PubMed

    Stegmaier, Matthias; Pernice, Wolfram H P

    2013-03-25

    Aluminum nitride (AlN)-on-insulator has emerged as a promising platform for the realization of linear and non-linear integrated photonic circuits. In order to efficiently route optical signals on-chip, precise control over the interaction and polarization of evanescently coupled waveguide modes is required. Here we employ nanophotonic AlN waveguides to realize directional couplers with a broad coupling bandwidth and low insertion loss. We achieve uniform splitting of incoming modes, confirmed by high extinction-ratio exceeding 33dB in integrated Mach-Zehnder Interferometers. Optimized three-waveguide couplers furthermore allow for extending the coupling bandwidth over traditional side-coupled devices by almost an order of magnitude, with variable splitting ratio. Our work illustrates the potential of AlN circuits for coupled waveguide optics, DWDM applications and integrated polarization diversity schemes. PMID:23546114

  8. Seismic signal of avalanches

    NASA Astrophysics Data System (ADS)

    Pesaresi, Damiano; Ravanat, Xavier; Thibert, Emmanuel

    2010-05-01

    The characterization of avalanches with seismic signals is an important task. For risk mitigation, estimating remotely avalanche activity by means of seismic signals is a good alternative to direct observations that are often limited by visual conditions and observer's availability. In seismology, the main challenge is to discriminate avalanche signals within the natural earth seismic activity and background noise. Some anthropogenic low frequency (infra-sound) sources like helicopters also generate seismic signals. In order to characterize an avalanche seismic signal, a 3-axis broad band seismometer (Guralp 3T) has been set-up on a real scale avalanche test site in Lautaret (France). The sensor is located in proximity of 2 avalanche paths where avalanches can be artificially released. Preliminary results of seismic records are presented, correlated with avalanche physical parameters (volume released, velocity, energy).

  9. Bioelectric Signal Measuring System

    NASA Astrophysics Data System (ADS)

    Guadarrama-Santana, A.; Pólo-Parada, L.; García-Valenzuela, A.

    2015-01-01

    We describe a low noise measuring system based on interdigitated electrodes for sensing bioelectrical signals. The system registers differential voltage measurements in order of microvolts. The base noise during measurements was in nanovolts and thus, the sensing signals presented a very good signal to noise ratio. An excitation voltage of 1Vrms with 10 KHz frequency was applied to an interdigitated capacitive sensor without a material under test and to a mirror device simultaneously. The output signals of both devices was then subtracted in order to obtain an initial reference value near cero volts and reduce parasitic capacitances due to the electronics, wiring and system hardware as well. The response of the measuring system was characterized by monitoring temporal bioelectrical signals in real time of biological materials such as embryo chicken heart cells and bovine suprarenal gland cells.

  10. Exosomes in developmental signalling.

    PubMed

    McGough, Ian John; Vincent, Jean-Paul

    2016-07-15

    In order to achieve coordinated growth and patterning during development, cells must communicate with one another, sending and receiving signals that regulate their activities. Such developmental signals can be soluble, bound to the extracellular matrix, or tethered to the surface of adjacent cells. Cells can also signal by releasing exosomes - extracellular vesicles containing bioactive molecules such as RNA, DNA and enzymes. Recent work has suggested that exosomes can also carry signalling proteins, including ligands of the Notch receptor and secreted proteins of the Hedgehog and WNT families. Here, we describe the various types of exosomes and their biogenesis. We then survey the experimental strategies used so far to interfere with exosome formation and critically assess the role of exosomes in developmental signalling. PMID:27436038

  11. Biological signals as handicaps.

    PubMed

    Grafen, A

    1990-06-21

    An ESS model of Zahavi's handicap principle is constructed. This allows a formal exposition of how the handicap principle works, and shows that its essential elements are strategic. The handicap model is about signalling, and it is proved under fairly general conditions that if the handicap principle's conditions are met, then an evolutionarily stable signalling equilibrium exists in a biological signalling system, and that any signalling equilibrium satisfies the conditions of the handicap principle. Zahavi's major claims for the handicap principle are thus vindicated. The place of cheating is discussed in view of the honesty that follows from the handicap principle. Parallel signalling models in economics are discussed. Interpretations of the handicap principle are compared. The models are not fully explicit about how females use information about male quality, and, less seriously, have no genetics. A companion paper remedies both defects in a model of the handicap principle at work in sexual selection. PMID:2402153

  12. Mitochondrial emitted electromagnetic signals mediate retrograde signaling.

    PubMed

    Bagkos, Georgios; Koufopoulos, Kostas; Piperi, Christina

    2015-12-01

    Recent evidence shows that mitochondria regulate nuclear transcriptional activity both in normal and cell stress conditions, known as retrograde signaling. Under normal mitochondrial function, retrograde signaling is associated with mitochondrial biogenesis, normal cell phenotype and metabolic profile. In contrast, mitochondrial dysfunction leads to abnormal (oncogenic) cell phenotype and altered bio-energetic profile (nucleus reprogramming). Despite intense research efforts, a concrete mechanism through which mitochondria determine the group of genes expressed by the nucleus is still missing. The present paper proposes a novel hypothesis regarding retrograde signaling. More specifically, it reveals the mitochondrial membrane potential (MMP) and the accompanied strong electromagnetic field (EF) as key regulatory factors of nuclear activity. Mitochondrial emitted EFs extend in long distance and affect the function of nuclear membrane receptors. Depending on their frequencies, EFs can directly activate or deactivate different groups of nuclear receptors and so determine nuclear gene expression. One of the key features of the above hypothesis is that nuclear membrane receptors, besides their own endogenous or chemical ligands (hormones, lipids, etc.), can also be activated by electromagnetic signals. Moreover, normal MMP values (about -140 mV) are associated with the production of high ATP quantities and small levels of reactive oxygen species (ROS) while the hyperpolarization observed in all cancer cell types leads to a dramatic fall in ATP production and an analogous increase in ROS. The diminished ATP and increased ROS production negatively affect the function of all cellular systems including nucleus. Restoration of mitochondrial function, which is characterized by the fluctuation of MMP and EF values within a certain (normal) range, is proposed as a necessary condition for normal nuclear function and cancer therapy. PMID:26474928

  13. New signatures of flavor violating Higgs couplings

    NASA Astrophysics Data System (ADS)

    Buschmann, Malte; Kopp, Joachim; Liu, Jia; Wang, Xiao-Ping

    2016-06-01

    We explore several novel LHC signatures arising from quark or lepton flavor violating couplings in the Higgs sector, and we constrain such couplings using LHC data. Since the largest signals are possible in channels involving top quarks or tau leptons, we consider in particular the following flavor violating processes: (1) pp → thh (top plus di-Higgs final state) arising from a dimension six coupling of up-type quarks to three insertions of the Higgs field. We develop a search strategy for this final state and demonstrate that detection is possible at the high luminosity LHC if flavor violating top-up-Higgs couplings are not too far below the current limit. (2) pp → tH 0, where H 0 is the heavy neutral CP-even Higgs boson in a two Higgs doublet model (2HDM). We consider the decay channels H 0 → tu, WW, ZZ, hh and use existing LHC data to constrain the first three of them. For the fourth, we adapt our search for the thh final state, and we demonstrate that in large regions of the parameter space, it is superior to other searches, including searches for flavor violating top quark decays ( t → hq). (3) H 0 → τ μ, again in the context of a 2HDM. This channel is particularly well motivated by the recent CMS excess in h → τ μ, and we use the data from this search to constrain the properties of H 0.

  14. Optimizing plasmonic nanoantennas via coordinated multiple coupling

    PubMed Central

    Lin, Linhan; Zheng, Yuebing

    2015-01-01

    Plasmonic nanoantennas, which can efficiently convert light from free space into sub-wavelength scale with the local field enhancement, are fundamental building blocks for nanophotonic systems. Predominant design methods, which exploit a single type of near- or far-field coupling in pairs or arrays of plasmonic nanostructures, have limited the tunability of spectral response and the local field enhancement. To overcome this limit, we are developing a general strategy towards exploiting the coordinated effects of multiple coupling. Using Au bowtie nanoantenna arrays with metal-insulator-metal configuration as examples, we numerically demonstrate that coordinated design and implementation of various optical coupling effects leads to both the increased tunability in the spectral response and the significantly enhanced electromagnetic field. Furthermore, we design and analyze a refractive index sensor with an ultra-high figure-of-merit (254), a high signal-to-noise ratio and a wide working range of refractive indices, and a narrow-band near-infrared plasmonic absorber with 100% absorption efficiency, high quality factor of up to 114 and a wide range of tunable wavelength from 800 nm to 1,500 nm. The plasmonic nanoantennas that exploit coordinated multiple coupling will benefit a broad range of applications, including label-free bio-chemical detection, reflective filter, optical trapping, hot-electron generation, and heat-assisted magnetic recording. PMID:26423015

  15. Optimizing plasmonic nanoantennas via coordinated multiple coupling

    NASA Astrophysics Data System (ADS)

    Lin, Linhan; Zheng, Yuebing

    2015-10-01

    Plasmonic nanoantennas, which can efficiently convert light from free space into sub-wavelength scale with the local field enhancement, are fundamental building blocks for nanophotonic systems. Predominant design methods, which exploit a single type of near- or far-field coupling in pairs or arrays of plasmonic nanostructures, have limited the tunability of spectral response and the local field enhancement. To overcome this limit, we are developing a general strategy towards exploiting the coordinated effects of multiple coupling. Using Au bowtie nanoantenna arrays with metal-insulator-metal configuration as examples, we numerically demonstrate that coordinated design and implementation of various optical coupling effects leads to both the increased tunability in the spectral response and the significantly enhanced electromagnetic field. Furthermore, we design and analyze a refractive index sensor with an ultra-high figure-of-merit (254), a high signal-to-noise ratio and a wide working range of refractive indices, and a narrow-band near-infrared plasmonic absorber with 100% absorption efficiency, high quality factor of up to 114 and a wide range of tunable wavelength from 800 nm to 1,500 nm. The plasmonic nanoantennas that exploit coordinated multiple coupling will benefit a broad range of applications, including label-free bio-chemical detection, reflective filter, optical trapping, hot-electron generation, and heat-assisted magnetic recording.

  16. Optimizing plasmonic nanoantennas via coordinated multiple coupling.

    PubMed

    Lin, Linhan; Zheng, Yuebing

    2015-01-01

    Plasmonic nanoantennas, which can efficiently convert light from free space into sub-wavelength scale with the local field enhancement, are fundamental building blocks for nanophotonic systems. Predominant design methods, which exploit a single type of near- or far-field coupling in pairs or arrays of plasmonic nanostructures, have limited the tunability of spectral response and the local field enhancement. To overcome this limit, we are developing a general strategy towards exploiting the coordinated effects of multiple coupling. Using Au bowtie nanoantenna arrays with metal-insulator-metal configuration as examples, we numerically demonstrate that coordinated design and implementation of various optical coupling effects leads to both the increased tunability in the spectral response and the significantly enhanced electromagnetic field. Furthermore, we design and analyze a refractive index sensor with an ultra-high figure-of-merit (254), a high signal-to-noise ratio and a wide working range of refractive indices, and a narrow-band near-infrared plasmonic absorber with 100% absorption efficiency, high quality factor of up to 114 and a wide range of tunable wavelength from 800 nm to 1,500 nm. The plasmonic nanoantennas that exploit coordinated multiple coupling will benefit a broad range of applications, including label-free bio-chemical detection, reflective filter, optical trapping, hot-electron generation, and heat-assisted magnetic recording. PMID:26423015

  17. Parametric amplification by coupled flux qubits

    SciTech Connect

    Rehák, M.; Neilinger, P.; Grajcar, M.; Oelsner, G.; Hübner, U.; Meyer, H.-G.; Il'ichev, E.

    2014-04-21

    We report parametric amplification of a microwave signal in a Kerr medium formed from superconducting qubits. Two mutually coupled flux qubits, embedded in the current antinode of a superconducting coplanar waveguide resonator, are used as a nonlinear element. Shared Josephson junctions provide the qubit-resonator coupling, resulting in a device with a tunable Kerr constant (up to 3 × 10{sup −3}) and a measured gain of about 20 dB. This arrangement represents a unit cell which can be straightforwardly extended to a quasi one-dimensional quantum metamaterial with large tunable Kerr nonlinearity, providing a basis for implementation of wide-band travelling wave parametric amplifiers.

  18. Testing of Josephson Spectrometer with Waveguide Coupling

    NASA Astrophysics Data System (ADS)

    Lyatti, M.; Gundareva, I.; Pavlovskii, V.; Poppe, U.; Divin, Y.

    2014-05-01

    One of the challenges in public security is the quick and reliable identification of threat liquids in bottles, when vapour analysis is not possible. Recently, we demonstrated that it is possible to rapidly identify liquids by EM measurements of their dielectric functions in the sub-THz range with a high-Tc Josephson spectrometer. Following this approach, we have developed a Josephson spectrometer with a new radiation coupling system, based on dielectric waveguides. In this paper, we present the results of spectroscopic measurements on liquid samples of various purities including 30% H2O2/H2O, performed using our Josephson spectrometer with waveguide coupling. Also, the signal and noise characteristics of a classical Josephson detector used in our liquid identifier were numerically simulated and the power dynamic range was estimated for a wide spread of junction parameters.

  19. Coupled External Cavity Photonic Crystal Enhanced Fluorescence

    PubMed Central

    Pokhriyal, Anusha; Lu, Meng; Ge, Chun; Cunningham, Brian T.

    2016-01-01

    We report a fundamentally new approach to enhance fluorescence in which surface adsorbed fluorophore-tagged biomolecules are excited on a photonic crystal surface that functions as a narrow bandwidth and tunable mirror of an external cavity laser. This scheme leads to ~10× increase in the electromagnetic enhancement factor compared to ordinary photonic crystal enhanced fluorescence. In our experiments, the cavity automatically tunes its lasing wavelength to the resonance wavelength of the photonic crystal, ensuring optimal on-resonance coupling even in the presence of variable device parameters and variations in the density of surface-adsorbed capture molecules. We achieve ~105× improvement in the limit of detection of a fluorophore-tagged protein compared to its detection on an unpatterned glass substrate. The enhanced fluorescence signal and easy optical alignment make cavity-coupled photonic crystals a viable approach for further reducing detection limits of optically-excited light emitters that are used in biological assays. PMID:23129575

  20. Microwave signal processing with photorefractive dynamic holography

    NASA Astrophysics Data System (ADS)

    Fotheringham, Edeline B.

    Have you ever found yourself listening to the music playing from the closest stereo rather than to the bromidic (uninspiring) person speaking to you? Your ears receive information from two sources but your brain listens to only one. What if your cell phone could distinguish among signals sharing the same bandwidth too? There would be no "full" channels to stop you from placing or receiving a call. This thesis presents a nonlinear optical circuit capable of distinguishing uncorrelated signals that have overlapping temporal bandwidths. This so called autotuning filter is the size of a U.S. quarter dollar and requires less than 3 mW of optical power to operate. It is basically an oscillator in which the losses are compensated with dynamic holographic gain. The combination of two photorefractive crystals in the resonator governs the filter's winner-take-all dynamics through signal-competition for gain. This physical circuit extracts what is mathematically referred to as the largest principal component of its spatio-temporal input space. The circuit's practicality is demonstrated by its incorporation in an RF-photonic system. An unknown mixture of unknown microwave signals, received by an antenna array, constitutes the input to the system. The output electronically returns one of the original microwave signals. The front-end of the system down converts the 10 GHz microwave signals and amplifies them before the signals phase modulate optical beams. The optical carrier is suppressed from these beams so that it may not be considered as a signal itself to the autotuning filter. The suppression is achieved with two-beam coupling in a single photorefractive crystal. The filter extracts the more intense of the signals present on the carrier-suppressed input beams. The detection of the extracted signal restores the microwave signal to an electronic form. The system, without the receiving antenna array, is packaged in a 13 x 18 x 6″ briefcase. Its power consumption equals that

  1. Signal Transduction in Histidine Kinases: Insights from New Structures

    PubMed Central

    Bhate, Manasi P.; Molnar, Kathleen S.; Goulian, Mark; DeGrado, William F.

    2015-01-01

    Histidine kinases (HKs) are major players in bacterial signaling. There has been an explosion of new HK crystal structures in the last five years. We globally analyze the structures of HKs to yield insights into the mechanisms by which signals are transmitted to and across protein structures in this family. We interpret known enzymological data in the context of new structural data to show how asymmetry across the dimer interface is a key feature of signal transduction in HKs, and discuss how different HK domains undergo asymmetric-to-symmetric transitions during signal transduction and catalysis. A thermodynamic framework for signaling that encompasses these various properties is presented and the consequences of weak thermodynamic coupling are discussed. The synthesis of observations from enzymology, structural biology, protein engineering and thermodynamics paves the way for a deeper molecular understanding of histidine kinase signal transduction. PMID:25982528

  2. Anomalous gauge boson couplings

    SciTech Connect

    Barklow, T.; Rizzo, T.; Baur, U.

    1997-01-13

    The measurement of anomalous gauge boson self couplings is reviewed for a variety of present and planned accelerators. Sensitivities are compared for these accelerators using models based on the effective Lagrangian approach. The sensitivities described here are for measurement of {open_quotes}generic{close_quotes} parameters {kappa}{sub V}, {lambda}{sub V}, etc., defined in the text. Pre-LHC measurements will not probe these coupling parameters to precision better than O(10{sup -1}). The LHC should be sensitive to better than O(10{sup -2}), while a future NLC should achieve sensitivity of O(10{sup -3}) to O(10{sup -4}) for center of mass energies ranging from 0.5 to 1.5 TeV.

  3. Do earthquakes generate EM signals?

    NASA Astrophysics Data System (ADS)

    Walter, Christina; Onacha, Stephen; Malin, Peter; Shalev, Eylon; Lucas, Alan

    2010-05-01

    In recent years there has been significant interest in the seismoelectric effect which is the conversion of acoustic energy into electromagnetic energy. At the onset of the earthquake and at layer interfaces, it is postulated that the seismoelectric signal propagates at the speed of light and thus travels much faster than the acoustic wave. The focus has mainly been to use this method as a tool of predicting earthquakes. Our main objective is to study the possibility of using the seismoelectric effect to determine the origin time of an earthquake, establish an accurate velocity model and accurately locate microearthquakes. Another aspect of this research is to evaluate the possibility of detecting porous zones where seismic activity is postulated to generate fluid movement through porous medium. The displacement of pore fluid relative to the porous medium solid grains generates electromagnetic signals. The Institute of Earth Science and Engineering (IESE) has installed electromagnetic coils in 3 different areas to investigate the seismoelectric effect. Two of the research areas (Krafla in Iceland and Wairakei in New Zealand) are in active geothermal fields where high microearthquake activity has been recorded. The other area of research is at the site of the San Andreas Fault Observatory at Depth (SAFOD) at Parkfield area on the active San Andreas Fault which is associated with repeating earthquakes. In the Wairakei and Parkfield cases a single borehole electromagnetic coil close to borehole seismometers has been used whereas in the Krafla study area, 3 borehole electromagnetic coils coupled to borehole seismometers have been used. The technical difficulties of working in the borehole environment mean that some of these deployments had a short life span. Nevertheless in all cases data was gathered and is being analysed. At the SAFOD site, the electromagnetic coil recorded seismoelectric signals very close to a magnitude 2 earthquake. In the Wairakei and Krafla

  4. Electromagnetically coupled microstrip dipoles

    NASA Astrophysics Data System (ADS)

    Oltman, H. G.; Huebner, D. A.

    1981-01-01

    A new class of printed circuit radiator consisting of a microstrip dipole electromagnetically coupled to a microstrip feed line is described. Several configurations which differ in bandwidth, efficiency, and construction simplicity are presented. A geometry which has been found to be optimum for many applications is noted. Radiation characteristics of both isolated elements and arrays of elements are examined. Experimental and theoretical results are presented.

  5. Thermal coupling measurement method

    NASA Technical Reports Server (NTRS)

    Rosenthal, L. A.; Menichelli, V. J.

    1974-01-01

    Heat flow from an embedded heated wire responds to a change in the ambient environment. The wire is part of a self-balancing bridge system, and heat flow is measured directly in watts. Steady-state and transient thermal coupling can be measured directly and is an indication of the thermal resistance and diffusivity for the system under study. The method is applied to an aerospace electroexplosive component.

  6. Magnetic coupling device

    DOEpatents

    Nance, Thomas A.

    2009-08-18

    A quick connect/disconnect coupling apparatus is provided in which a base member is engaged by a locking housing through a series of interengagement pins. The pins maintain the shaft in a locked position. Upon exposure to an appropriately positioned magnetic field, pins are removed a sufficient distance such that the shaft may be withdrawn from the locking housing. The ability to lock and unlock the connector assembly requires no additional tools or parts apart from a magnetic key.

  7. Hedgehog signaling and steroidogenesis.

    PubMed

    Finco, Isabella; LaPensee, Christopher R; Krill, Kenneth T; Hammer, Gary D

    2015-01-01

    Since its discovery nearly 30 years ago, the Hedgehog (Hh) signaling pathway has been shown to be pivotal in many developmental and pathophysiological processes in several steroidogenic tissues, including the testis, ovary, adrenal cortex, and placenta. New evidence links the evolutionarily conserved Hh pathway to the steroidogenic organs, demonstrating how Hh signaling can influence their development and homeostasis and can act in concert with steroids to mediate physiological functions. In this review, we highlight the role of the components of the Hh signaling pathway in steroidogenesis of endocrine tissues. PMID:25668018

  8. Plant Cyclic Nucleotide Signalling

    PubMed Central

    Martinez-Atienza, Juliana; Van Ingelgem, Carl; Roef, Luc

    2007-01-01

    The presence of the cyclic nucleotides 3′,5′-cyclic adenyl monophosphate (cAMP) and 3′,5′-cyclic guanyl monophosphate (cGMP) in plants is now generally accepted. In addition, cAMP and cGMP have been implicated in the regulation of important plant processes such as stomatal functioning, monovalent and divalent cation fluxes, chloroplast development, gibberellic acid signalling, pathogen response and gene transcription. However, very little is known regarding the components of cyclic nucleotide signalling in plants. In this addendum, the evidence for specific mechanisms of plant cyclic nucleotide signalling is evaluated and discussed. PMID:19704553

  9. Signal processing for microcalorimeters

    NASA Astrophysics Data System (ADS)

    Szymkowiak, A. E.; Kelley, R. L.; Moseley, S. H.; Stahle, C. K.

    1993-11-01

    Most of the power in the signals from microcalorimeters occurs at relatively low frequencies. At these frequencies, typical amplifiers will have significant amounts of 1/f noise. Our laboratory systems can also suffer from pickup at several harmonics of the AC power line, and from microphonic pickup at frequencies that vary with the configuration of the apparatus. We have developed some optimal signal processing techniques in order to construct the best possible estimates of our pulse heights in the presence of these non-ideal effects. In addition to a discussion of our laboratory systems, we present our plans for providing this kind of signal processing in flight experiments.

  10. Signal-3L: A 3-layer approach for predicting signal peptides.

    PubMed

    Shen, Hong-Bin; Chou, Kuo-Chen

    2007-11-16

    Functioning as an "address tag" that directs nascent proteins to their proper cellular and extracellular locations, signal peptides have become a crucial tool in finding new drugs or reprogramming cells for gene therapy. To effectively and timely use such a tool, however, the first important thing is to develop an automated method for rapidly and accurately identifying the signal peptide for a given nascent protein. With the avalanche of new protein sequences generated in the post-genomic era, the challenge has become even more urgent and critical. In this paper, we have developed a novel method for predicting signal peptide sequences and their cleavage sites in human, plant, animal, eukaryotic, Gram-positive, and Gram-negative protein sequences, respectively. The new predictor is called Signal-3L that consists of three prediction engines working, respectively, for the following three progressively deepening layers: (1) identifying a query protein as secretory or non-secretory by an ensemble classifier formed by fusing many individual OET-KNN (optimized evidence-theoretic K nearest neighbor) classifiers operated in various dimensions of PseAA (pseudo amino acid) composition spaces; (2) selecting a set of candidates for the possible signal peptide cleavage sites of a query secretory protein by a subsite-coupled discrimination algorithm; (3) determining the final cleavage site by fusing the global sequence alignment outcome for each of the aforementioned candidates through a voting system. Signal-3L is featured by high success prediction rates with short computational time, and hence is particularly useful for the analysis of large-scale datasets. Signal-3L is freely available as a web-server at http://chou.med.harvard.edu/bioinf/Signal-3L/ or http://202.120.37.186/bioinf/Signal-3L, where, to further support the demand of the related areas, the signal peptides identified by Signal-3L for all the protein entries in Swiss-Prot databank that do not have signal peptide

  11. [Comorbidity in infertile couples].

    PubMed

    Sartorius, Gideon A; Bürgin, Laila; Kaufmann, Fabrice; De Geyter, Christian

    2009-12-01

    Pregnancy is the result of a series of highly complex processes, which can be deranged by multiple disturbances on many different levels. Physicians are increasingly dealing with couples suffering from infertility. This rise in case numbers is mainly due to the fact that couples are more and more delaying childbearing until a later phase of their reproductive life, when their social and professional careers are established. The increasing mean age at the first birth has a negative impact on fertility by deteriorating quality and reducing the quantity of oocytes. With increasing age systemic diseases are becoming more coincidental, which in turn tend to exert negative effects on fecundity and fertility both in males and females. This review highlights some associations between infertility and various common systemic diseases. Both general practitioners and gynecologists should counsel young women about the finity of the reproductive phase of their life. Young couples are to be informed, that a "healthy lifestyle" without smoking, sexual transmitted diseases and without metabolic diseases as diabetes and obesity can have a positive effect not only on their general health but also on their fertility and the outcome of future pregnancies. PMID:19950056

  12. Quick torque coupling

    DOEpatents

    Luft, Peter A.

    2009-05-12

    A coupling for mechanically connecting modular tubular struts of a positioning apparatus or space frame, comprising a pair of toothed rings (10, 12) attached to separate strut members (16), the teeth (18, 20) of the primary rings (10, 12) mechanically interlocking in both an axial and circumferential manner, and a third part comprising a sliding, toothed collar (14) the teeth (22) of which interlock the teeth (18, 20) of the primary rings (10, 12), preventing them from disengaging, and completely locking the assembly together. A secondary mechanism provides a nesting force for the collar, and/or retains it. The coupling is self-contained and requires no external tools for installation, and can be assembled with gloved hands in demanding environments. No gauging or measured torque is required for assembly. The assembly can easily be visually inspected to determine a "go" or "no-go" status. The coupling is compact and relatively light-weight. Because of it's triply interlocking teeth, the connection is rigid. The connection does not primarily rely on clamps, springs or friction based fasteners, and is therefore reliable in fail-safe applications.

  13. Conference on Charge-Coupled Device Technology and Applications

    NASA Technical Reports Server (NTRS)

    1976-01-01

    Papers were presented from the conference on charge coupled device technology and applications. The following topics were investigated: data processing; infrared; devices and testing; electron-in, x-ray, radiation; and applications. The emphasis was on the advances of mutual relevance and potential significance both to industry and NASA's current and future requirements in all fields of imaging, signal processing and memory.

  14. Passive silicon photonic devices for microwave photonic signal processing

    NASA Astrophysics Data System (ADS)

    Wu, Jiayang; Peng, Jizong; Liu, Boyu; Pan, Ting; Zhou, Huanying; Mao, Junming; Yang, Yuxing; Qiu, Ciyuan; Su, Yikai

    2016-08-01

    We present our recent progress on microwave signal processing (MSP) using on-chip passive silicon photonic devices, including tunable microwave notch filtering/millimeter-wave (MMW) signal generation based on self-coupled micro-resonators (SCMRs), and tunable radio-frequency (RF) phase shifting implemented by a micro-disk resonator (MDR). These schemes can provide improved flexibility and performances of MSP. The experimental results are in good agreement with theoretical predictions, which validate the effectiveness of the proposed schemes.

  15. SNS LINAC Wire Scanner System : Signal Levels and Accuracy.

    SciTech Connect

    Plum, M. A.; Christensen, W.; Myer, R. E.; Rose, C. R.

    2002-01-01

    The linac wire scanner system for the Spallation Neutron Source (SNS) at Oak Ridge, TN, USA, calls for 5 units in the medium energy beam transport (MEBT), 5 in the drift tube linac (DTL), and 10 in the coupled cavity linac (CCL). In this paper we present expected signal levels and an analysis of the error in the beam size measurement as functions of wire position and electrical signal errors.

  16. Dynamic coupling of plasmonic resonators

    PubMed Central

    Lee, Suyeon; Park, Q-Han

    2016-01-01

    We clarify the nature of dynamic coupling in plasmonic resonators and determine the dynamic coupling coefficient using a simple analytic model. We show that plasmonic resonators, such as subwavelength holes in a metal film which can be treated as bound charge oscillators, couple to each other through the retarded interaction of oscillating screened charges. Our dynamic coupling model offers, for the first time, a quantitative analytic description of the fundamental symmetric and anti-symmetric modes of coupled resonators which agrees with experimental results. Our model also reveals that plasmonic electromagnetically induced transparency arises in any coupled resonators of slightly unequal lengths, as confirmed by a rigorous numerical calculation and experiments. PMID:26911786

  17. The QCD running coupling

    NASA Astrophysics Data System (ADS)

    Deur, Alexandre; Brodsky, Stanley J.; de Téramond, Guy F.

    2016-09-01

    We review the present theoretical and empirical knowledge for αs, the fundamental coupling underlying the interactions of quarks and gluons in Quantum Chromodynamics (QCD). The dependence of αs(Q2) on momentum transfer Q encodes the underlying dynamics of hadron physics-from color confinement in the infrared domain to asymptotic freedom at short distances. We review constraints on αs(Q2) at high Q2, as predicted by perturbative QCD, and its analytic behavior at small Q2, based on models of nonperturbative dynamics. In the introductory part of this review, we explain the phenomenological meaning of the coupling, the reason for its running, and the challenges facing a complete understanding of its analytic behavior in the infrared domain. In the second, more technical, part of the review, we discuss the behavior of αs(Q2) in the high momentum transfer domain of QCD. We review how αs is defined, including its renormalization scheme dependence, the definition of its renormalization scale, the utility of effective charges, as well as "Commensurate Scale Relations" which connect the various definitions of the QCD coupling without renormalization-scale ambiguity. We also report recent significant measurements and advanced theoretical analyses which have led to precise QCD predictions at high energy. As an example of an important optimization procedure, we discuss the "Principle of Maximum Conformality", which enhances QCD's predictive power by removing the dependence of the predictions for physical observables on the choice of theoretical conventions such as the renormalization scheme. In the last part of the review, we discuss the challenge of understanding the analytic behavior αs(Q2) in the low momentum transfer domain. We survey various theoretical models for the nonperturbative strongly coupled regime, such as the light-front holographic approach to QCD. This new framework predicts the form of the quark-confinement potential underlying hadron spectroscopy and

  18. Bile acids are nutrient signaling hormones.

    PubMed

    Zhou, Huiping; Hylemon, Phillip B

    2014-08-01

    Bile salts play crucial roles in allowing the gastrointestinal system to digest, transport and metabolize nutrients. They function as nutrient signaling hormones by activating specific nuclear receptors (FXR, PXR, Vitamin D) and G-protein coupled receptors [TGR5, sphingosine-1 phosphate receptor 2 (S1PR2), muscarinic receptors]. Bile acids and insulin appear to collaborate in regulating the metabolism of nutrients in the liver. They both activate the AKT and ERK1/2 signaling pathways. Bile acid induction of the FXR-α target gene, small heterodimer partner (SHP), is highly dependent on the activation PKCζ, a branch of the insulin signaling pathway. SHP is an important regulator of glucose and lipid metabolism in the liver. One might hypothesize that chronic low grade inflammation which is associated with insulin resistance, may inhibit bile acid signaling and disrupt lipid metabolism. The disruption of these signaling pathways may increase the risk of fatty liver and non-alcoholic fatty liver disease (NAFLD). Finally, conjugated bile acids appear to promote cholangiocarcinoma growth via the activation of S1PR2. PMID:24819989

  19. Signal processing in SETI

    NASA Technical Reports Server (NTRS)

    Cullers, D. K.; Linscott, I. R.; Oliver, B. M.

    1985-01-01

    It is believed that the Galaxy might contain ten billion potential life sites. In view of the physical inaccessibility of extraterrestrial life on account of the vast distances involved, a logical first step in a search for extraterrestrial intelligence (SETI) appears to be an attempt to detect signals already being radiated. The characteristics of the signals to be expected are discussed together with the search strategy of a NASA program. It is pointed out that all presently planned searches will use existing radio-astronomy antennas. If no extraterrestrial intelligence signals are discovered, society will have to decide whether SETI justifies a dedicated facility of much greater collecting area. Attention is given to a multichannel spectrum analyzer, CW signal detection, pulse detection, the pattern detector, and details of SETI system operation.

  20. GNSS Ocean Reflected Signals

    NASA Astrophysics Data System (ADS)

    Hoeg, P.

    2012-12-01

    Ocean reflected signals from the GNSS satellites (received at low-Earth orbiting satellites, airplanes and fixed mountain locations) describe the ocean surface mean height, waves, roughness, spectral reflectivity and emissivity. The estimated accuracy of the average surface height is of the order of 10 cm for smooth conditions. Thus global observations could be an important new contribution to long-term variations of the ocean mean height as well as the monitoring of ocean mesoscale eddies, which result in sea-height changes much larger than the accuracy of the GNSS technique for reflected signals. The ocean reflected signals can be divided into two set of measurements, 1) high elevation measurements (equal to low incidence angles) and 2) low elevation grazing angle measurements. For the first type the ocean reflection cross-section has a limited extent. The reflected signal is coherent with smaller errors due to ocean waves, sampling rate and the internal processing method of the receiver. For low elevations, the signal reveals the incoherent scatter process at the reflection zone. To quantify the potential of the GNSS signals for determining spectral reflectivity at low elevations, we present ocean reflection GPS measurements from the Haleakala Summit on Maui, Hawaii, revealing the spectral characteristics of both the direct satellite signal and the ocean reflected signal for low elevation angles. The characteristics of the reflected signal depend on the scattering properties of the sea surface and the footprint of the reflection zone. While the footprint size and shape in turn depends on the signal incidence angle, the ocean mean tilt, and the relative velocities of transmitter and receiver to the reflection point. Thus the scattering properties of the sea surface are related to the sea surface roughness. We present the spectral properties of the signals as received by a high precision GPS instrument, simultaneously in both phase-locked mode and open-loop raw

  1. Signals and Receptors.

    PubMed

    Heldin, Carl-Henrik; Lu, Benson; Evans, Ron; Gutkind, J Silvio

    2016-04-01

    Communication between cells in a multicellular organism occurs by the production of ligands (proteins, peptides, fatty acids, steroids, gases, and other low-molecular-weight compounds) that are either secreted by cells or presented on their surface, and act on receptors on, or in, other target cells. Such signals control cell growth, migration, survival, and differentiation. Signaling receptors can be single-span plasma membrane receptors associated with tyrosine or serine/threonine kinase activities, proteins with seven transmembrane domains, or intracellular receptors. Ligand-activated receptors convey signals into the cell by activating signaling pathways that ultimately affect cytosolic machineries or nuclear transcriptional programs or by directly translocating to the nucleus to regulate transcription. PMID:27037414

  2. Audio signal processor

    NASA Technical Reports Server (NTRS)

    Hymer, R. L.

    1970-01-01

    System provides automatic volume control for an audio amplifier or a voice communication system without introducing noise surges during pauses in the input, and without losing the initial signal when the input resumes.

  3. Signals from the Cosmos.

    ERIC Educational Resources Information Center

    Lichtman, Jeffrey M.

    1991-01-01

    Introduces the basics of radio astronomy and describes how to assemble several simple systems for receiving radio signals from the cosmos. Includes schematics, parts lists, working drawings, and contact information for radio astronomy suppliers. (11 references) (Author/JJK)

  4. IRAK signalling in cancer.

    PubMed

    Rhyasen, G W; Starczynowski, D T

    2015-01-20

    Innate immune signalling has an essential role in inflammation, and the dysregulation of signalling components of this pathway is increasingly being recognised as an important mediator in cancer initiation and progression. In some malignancies, dysregulation of inflammatory toll-like receptor (TLR) and interleukin-1 receptor (IL1R) signalling is typified by increased NF-κB activity, and it occurs through somatic mutations, chromosomal deletions, and/or transcriptional deregulation. Interleukin-1 receptor-associated kinase (IRAK) family members are mediators of TLR/IL1R superfamily signalling, and mounting evidence implicates these kinases as viable cancer targets. Although there have been previous efforts aimed at the development of IRAK kinase inhibitors, this is currently an area of renewed interest for cancer drug development. PMID:25290089

  5. Quantifying Ubiquitin Signaling

    PubMed Central

    Ordureau, Alban; Münch, Christian; Harper, J. Wade

    2015-01-01

    Ubiquitin (UB)-driven signaling systems permeate biology, and are often integrated with other types of post-translational modifications (PTMs), most notably phosphorylation. Flux through such pathways is typically dictated by the fractional stoichiometry of distinct regulatory modifications and protein assemblies as well as the spatial organization of pathway components. Yet, we rarely understand the dynamics and stoichiometry of rate-limiting intermediates along a reaction trajectory. Here, we review how quantitative proteomic tools and enrichment strategies are being used to quantify UB-dependent signaling systems, and to integrate UB signaling with regulatory phosphorylation events. A key regulatory feature of ubiquitylation is that the identity of UB chain linkage types can control downstream processes. We also describe how proteomic and enzymological tools can be used to identify and quantify UB chain synthesis and linkage preferences. The emergence of sophisticated quantitative proteomic approaches will set a new standard for elucidating biochemical mechanisms of UB-driven signaling systems. PMID:26000850

  6. Advanced signal processing

    NASA Astrophysics Data System (ADS)

    Creasey, D. J.

    1985-12-01

    A collection of papers on advanced signal processing in radar, sonar, and communications is presented. The topics addressed include: transmitter aerials, high-power amplifier design for active sonar, radar transmitters, receiver array technology for sonar, new underwater acoustic detectors, diversity techniques in communications receivers, GaAs IC amplifiers for radar and communication receivers, integrated optical techniques for acoustooptic receivers, logarithmic receivers, CCD processors for sonar, acoustooptic correlators, designing in silicon, very high performance integrated circuits, and digital filters. Also discussed are: display types, scan converters in sonar, display ergonomics, simulators, high throughput sonar processors, optical fiber systems for signal processing, satellite communications, VLSI array processor for image and signal processing, ADA, future of cryogenic devices for signal processing applications, advanced image understanding, and VLSI architectures for real-time image processing.

  7. Modularity in signaling systems

    NASA Astrophysics Data System (ADS)

    Del Vecchio, Domitilla

    2012-08-01

    Modularity is a property by which the behavior of a system does not change upon interconnection. It is crucial for understanding the behavior of a complex system from the behavior of the composing subsystems. Whether modularity holds in biology is an intriguing and largely debated question. In this paper, we discuss this question taking a control system theory view and focusing on signaling systems. In particular, we argue that, despite signaling systems being constituted of structural modules, such as covalent modification cycles, modularity does not hold in general. As in any engineering system, impedance-like effects, called retroactivity, appear at interconnections and alter the behavior of connected modules. We further argue that while signaling systems have evolved sophisticated ways to counter-act retroactivity and enforce modularity, retroactivity may also be exploited to finely control the information processing of signaling pathways. Testable predictions and experimental evidence are discussed with their implications.

  8. Error-prone signalling.

    PubMed

    Johnstone, R A; Grafen, A

    1992-06-22

    The handicap principle of Zahavi is potentially of great importance to the study of biological communication. Existing models of the handicap principle, however, make the unrealistic assumption that communication is error free. It seems possible, therefore, that Zahavi's arguments do not apply to real signalling systems, in which some degree of error is inevitable. Here, we present a general evolutionarily stable strategy (ESS) model of the handicap principle which incorporates perceptual error. We show that, for a wide range of error functions, error-prone signalling systems must be honest at equilibrium. Perceptual error is thus unlikely to threaten the validity of the handicap principle. Our model represents a step towards greater realism, and also opens up new possibilities for biological signalling theory. Concurrent displays, direct perception of quality, and the evolution of 'amplifiers' and 'attenuators' are all probable features of real signalling systems, yet handicap models based on the assumption of error-free communication cannot accommodate these possibilities. PMID:1354361

  9. Coupling light in photonic crystal waveguides: A review

    NASA Astrophysics Data System (ADS)

    Dutta, Hemant Sankar; Goyal, Amit Kumar; Srivastava, Varun; Pal, Suchandan

    2016-07-01

    Submicron scale structures with high index contrast are key to compact structures for realizing photonic integrated structures. Ultra-compact optical devices in silicon-on-insulator (SOI) substrates serve compatibility with semiconductor fabrication technology leading to reduction of cost and mass production. Photonic crystal structures possess immense potential for realizing various compact optical devices. However, coupling light to photonic crystal waveguide structures is crucial in order to achieve strong transmission and wider bandwidth of signal. Widening of bandwidth will increase potential for various applications and high transmission will make easy signal detection at the output. In this paper, the techniques reported so far for coupling light in photonic crystal waveguides have been reviewed and analyzed so that a comprehensive guide for an efficient coupling to photonic crystal waveguides can be made possible.

  10. Optimizing information flow in small genetic networks. IV. Spatial coupling

    NASA Astrophysics Data System (ADS)

    Sokolowski, Thomas R.; Tkačik, Gašper

    2015-06-01

    We typically think of cells as responding to external signals independently by regulating their gene expression levels, yet they often locally exchange information and coordinate. Can such spatial coupling be of benefit for conveying signals subject to gene regulatory noise? Here we extend our information-theoretic framework for gene regulation to spatially extended systems. As an example, we consider a lattice of nuclei responding to a concentration field of a transcriptional regulator (the input) by expressing a single diffusible target gene. When input concentrations are low, diffusive coupling markedly improves information transmission; optimal gene activation functions also systematically change. A qualitatively different regulatory strategy emerges where individual cells respond to the input in a nearly steplike fashion that is subsequently averaged out by strong diffusion. While motivated by early patterning events in the Drosophila embryo, our framework is generically applicable to spatially coupled stochastic gene expression models.

  11. Optimizing information flow in small genetic networks. IV. Spatial coupling.

    PubMed

    Sokolowski, Thomas R; Tkačik, Gašper

    2015-06-01

    We typically think of cells as responding to external signals independently by regulating their gene expression levels, yet they often locally exchange information and coordinate. Can such spatial coupling be of benefit for conveying signals subject to gene regulatory noise? Here we extend our information-theoretic framework for gene regulation to spatially extended systems. As an example, we consider a lattice of nuclei responding to a concentration field of a transcriptional regulator (the input) by expressing a single diffusible target gene. When input concentrations are low, diffusive coupling markedly improves information transmission; optimal gene activation functions also systematically change. A qualitatively different regulatory strategy emerges where individual cells respond to the input in a nearly steplike fashion that is subsequently averaged out by strong diffusion. While motivated by early patterning events in the Drosophila embryo, our framework is generically applicable to spatially coupled stochastic gene expression models. PMID:26172739

  12. Sparse Bayesian learning for DOA estimation with mutual coupling.

    PubMed

    Dai, Jisheng; Hu, Nan; Xu, Weichao; Chang, Chunqi

    2015-01-01

    Sparse Bayesian learning (SBL) has given renewed interest to the problem of direction-of-arrival (DOA) estimation. It is generally assumed that the measurement matrix in SBL is precisely known. Unfortunately, this assumption may be invalid in practice due to the imperfect manifold caused by unknown or misspecified mutual coupling. This paper describes a modified SBL method for joint estimation of DOAs and mutual coupling coefficients with uniform linear arrays (ULAs). Unlike the existing method that only uses stationary priors, our new approach utilizes a hierarchical form of the Student t prior to enforce the sparsity of the unknown signal more heavily. We also provide a distinct Bayesian inference for the expectation-maximization (EM) algorithm, which can update the mutual coupling coefficients more efficiently. Another difference is that our method uses an additional singular value decomposition (SVD) to reduce the computational complexity of the signal reconstruction process and the sensitivity to the measurement noise. PMID:26501284

  13. Sparse Bayesian Learning for DOA Estimation with Mutual Coupling

    PubMed Central

    Dai, Jisheng; Hu, Nan; Xu, Weichao; Chang, Chunqi

    2015-01-01

    Sparse Bayesian learning (SBL) has given renewed interest to the problem of direction-of-arrival (DOA) estimation. It is generally assumed that the measurement matrix in SBL is precisely known. Unfortunately, this assumption may be invalid in practice due to the imperfect manifold caused by unknown or misspecified mutual coupling. This paper describes a modified SBL method for joint estimation of DOAs and mutual coupling coefficients with uniform linear arrays (ULAs). Unlike the existing method that only uses stationary priors, our new approach utilizes a hierarchical form of the Student t prior to enforce the sparsity of the unknown signal more heavily. We also provide a distinct Bayesian inference for the expectation-maximization (EM) algorithm, which can update the mutual coupling coefficients more efficiently. Another difference is that our method uses an additional singular value decomposition (SVD) to reduce the computational complexity of the signal reconstruction process and the sensitivity to the measurement noise. PMID:26501284

  14. Signal-light nomogram

    NASA Technical Reports Server (NTRS)

    Gordon, J. I.; Edgerton, C. F.; Duntley, S. Q.

    1975-01-01

    A nomogram is presented for predicting the sighting range for white, steady-burning signal lights. The theoretical and experimental bases are explained and instructions are provided for its use for a variety of practical problems concerning the visibility of signal lights. The nomogram is appropriate for slant path as well as horizontal sightings, and the gain of range achieved by utilizing binoculars can be predicted by use of it.

  15. Wnt Signaling in Bone

    PubMed Central

    Kubota, Takuo; Michigami, Toshimi; Ozono, Keiichi

    2010-01-01

    Wnt signaling is involved not only in embryonic development but also in maintenance of homeostasis in postnatal tissues. Multiple lines of evidence have increased understanding of the roles of Wnt signaling in bone since mutations in the LRP5 gene were identified in human bone diseases. Canonical Wnt signaling promotes mesenchymal progenitor cells to differentiate into osteoblasts. The canonical Wnt/β-catenin pathway possibly through Lrp6, a co-receptor for Wnts as well as Lrp5, in osteoblasts regulates bone resorption by increasing the OPG/RANKL ratio. However, endogenous inhibitors of Wnt signaling including sclerostin block bone formation. Regulation of sclerostin appears to be one of the mechanisms of PTH anabolic actions on bone. Since sclerostin is almost exclusively expressed in osteocytes, inhibition of sclerostin is the most promising design. Surprisingly, Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum, but not by directly promoting bone formation. Pharmacological intervention may be considered in many components of the canonical Wnt signaling pathway, although adverse effects and tumorigenicity to other tissues are important. More studies will be needed to fully understand how the Wnt signaling pathway actually influences bone metabolism and to assure the safety of new interventions. PMID:23926379

  16. Sucrose signaling in plants

    PubMed Central

    Tognetti, Jorge A.; Pontis, Horacio G.; Martínez-Noël, Giselle M.A.

    2013-01-01

    The role of sucrose as a signaling molecule in plants was originally proposed several decades ago. However, recognition of sucrose as a true signal has been largely debated and only recently this role has been fully accepted. The best-studied cases of sucrose signaling involve metabolic processes, such as the induction of fructan or anthocyanin synthesis, but a large volume of scattered information suggests that sucrose signals may control a vast array of developmental processes along the whole life cycle of the plant. Also, wide gaps exist in our current understanding of the intracellular steps that mediate sucrose action. Sucrose concentration in plant tissues tends to be directly related to light intensity, and inversely related to temperature, and accordingly, exogenous sucrose supply often mimics the effect of high light and cold. However, many exceptions to this rule seem to occur due to interactions with other signaling pathways. In conclusion, the sucrose role as a signal molecule in plants is starting to be unveiled and much research is still needed to have a complete map of its significance in plant function. PMID:23333971

  17. Semaphorin signaling in bone.

    PubMed

    Verlinden, Lieve; Vanderschueren, Dirk; Verstuyf, Annemieke

    2016-09-01

    Semaphorin molecules regulate cell adhesion and motility in a wide variety of cell types and are therefore involved in numerous processes including axon guidance, angiogenesis, cardiogenesis, tumor growth, and immune response. Increasing evidence points to a role of transmembrane, membrane-associated and soluble semaphorins during bone development as well as in the control of normal bone homeostasis. Within bone, semaphorins are implicated in the communication between different cell types by relaying signals in an autocrine or paracrine way. Semaphorins are not only involved in bone resorption but also in bone formation. Therefore, targeting semaphorin-induced signaling in bone may constitute an interesting new therapeutic strategy in osteoporosis. However, all the pioneering research on semaphorins is performed in mice and it remains to be established to what extent semaphorin signaling pathways are conserved between mice and men. In addition, knowledge of semaphorin signaling in bone mostly arises from loss/gain of function studies of one single semaphorin and/or receptor. However, different semaphorin molecules are co-expressed in bone and their signaling pathways are likely to interact in a complex and coherent way that needs proper understanding before targeting semaphorin signaling can be therapeutically exploited. PMID:26365296

  18. Pulse code modulated signal synchronizer

    NASA Technical Reports Server (NTRS)

    Kobayashi, H. S. (Inventor)

    1974-01-01

    A bit synchronizer for a split phase PCM transmission is reported that includes three loop circuits which receive incoming phase coded PCM signals. In the first loop, called a Q-loop, a generated, phase coded, PCM signal is multiplied with the incoming signals, and the frequency and phase of the generated signal are nulled to that of the incoming subcarrier signal. In the second loop, called a B-loop, a circuit multiplies a generated signal with incoming signals to null the phase of the generated signal in a bit phase locked relationship to the incoming signal. In a third loop, called the I-loop, a phase coded PCM signal is multiplied with the incoming signals for decoding the bit information from the PCM signal. A counter means is used for timing of the generated signals and timing of sample intervals for each bit period.

  19. Twin-capacitive shaft angle encoder with analog output signal

    NASA Technical Reports Server (NTRS)

    Hruby, R. J.; Wilson, R. L. (Inventor)

    1977-01-01

    A precision capacitive shaft encoder providing a dc signal corresponding to the angular position of a shaft is described. Two variable capacitances are coupled in tandem by a rotatable shaft. Each capacitor has a capacitance that varies linearly with a change in the angular position of the shaft. The sum of the two capacitances is always constant for any angular position of the shaft. Each capacitance is alternately coupled to a reference dc voltage and a discharge circuit. The capacitances are electrically coupled in series and the charge periodically acquired at the junction of the capacitance is a function of the position of the shaft. An error-compensating voltage is imposed on the junction when the capacitances are coupled to the reference voltages. The junction is coupled to sample-and-hold apparatus provided with a error-correcting circuit.

  20. Stability and time-domain analysis of the dispersive tristability in microresonators under modal coupling

    SciTech Connect

    Dumeige, Yannick; Feron, Patrice

    2011-10-15

    Coupled nonlinear resonators have potential applications for the integration of multistable photonic devices. The dynamic properties of two coupled-mode nonlinear microcavities made of Kerr material are studied by linear stability analysis. Using a suitable combination of the modal coupling rate and the frequency detuning, it is possible to obtain configurations where a hysteresis loop is included inside other bistable cycles. We show that a single resonator with two modes both linearly and nonlinearly coupled via the cross-Kerr effect can have a multistable behavior. This could be implemented in semiconductor nonlinear whispering-gallery-mode microresonators under modal coupling for all optical signal processing or ternary optical logic applications.