G-protein coupled receptors and synaptic plasticity in sleep deprivation

Insufficient sleep has been correlated to many physiological and psychoneurological disorders.Over the years,our understanding of the state of sleep has transcended from an inactive period of rest to a more active state involving important cellular and molecular processes.In addition,during sleep,electrophysiological changes also occur in pathways in specific regions of the mammalian central nervous system(CNS).Activity mediated synaptic plasticity in the CNS can lead to long-term and sometimes permanent strengthening and/or weakening synaptic strength affecting neuronal network behaviour.Memory consolidation and learning that take place during sleep cycles,can be affected by changes in synaptic plasticity during sleep disturbances.G-protein coupled receptors(GPCRs),with their versatile structural and functional attributes,can regulate synaptic plasticity in CNS and hence,may be potentially affected in sleep deprived conditions.In this review,we aim to discuss important functional changes that can take place in the CNS during sleep and sleep deprivation and how changes in GPCRs can lead to potential problems with therapeutics with pharmacological interventions.

Insights into the structural biology of G-protein coupled receptors impacts drug design for central nervous system neurodegenerative processes

In the last few years, there have been important new insights into the structural biology of G-protein coupled receptors. It is now known that allosteric binding sites are involved in the affinity and selec- tivity of ligands for G-protein coupled receptors, and that signaling by these receptors involves both G-protein dependent and independent pathways. The present review outlines the physiological and pharmacological implications of this perspective for the design of new drugs to treat disorders of the central nervous system. Specifically, new possibilities are explored in relation to allosteric and or- thosteric binding sites on dopamine receptors for the treatment of Parkinson＇s disease, and on muscarinic receptors for Alzheimer＇s disease. Future research can seek to identify ligands that can bind to more than one site on the same receptor, or simultaneously bind to two receptors and form a dimer. For example, the design of bivalent drugs that can reach homo/hetero-dimers of D2 dopa- mine receptor holds promise as a relevant therapeutic strategy for Parkinson＇s disease. Regarding the treatment of Alzheimer＇s disease, the design of dualsteric ligands for mono-oligomeric mus- carinic receptors could increase therapeutic effectiveness by generating potent compounds that could activate more than one signaling pathway.

Isoleucine, an Essential Amino Acid, Induces the Expression of Human <i>β</i>Defensin 2 through the Activation of the G-Protein Coupled Receptor-ERK Pathway in the Intestinal Epithelia

Anti-microbial peptides are essential for the intestinal innate immunity that protects the intestinal epithelia from attacks by foreign pathogens. Human β-defensin (HBD) is one of the pivotal anti-microbial peptides that are expressed in the colonic epithelia. This study investigated the effect and the signaling mechanism of inducible β-defensin HBD2 by an essential amino acid, isoleucine (Ile) in colonic epithelial cells. Here we examined the expression level of HBD2 on induction of Ile in epithelial cells, and checked this pathway. HBD2 mRNA was induced by co-incubation with IL-1α and Ile in Caco2 cells, but not by Ile alone. An inhibitor of either ERK or Gi, a subunit of G-proteins, reduced the induction of HBD2 mRNA by Ile. The treatment with Ile also increased the intracellular calcium ion concentration, thus suggesting that the GPCR and ERK signaling pathway mediate the effects of Ile. These results indicate that an essential amino acid, Ile, enhances the expression of an inducible β-defensin, namely HBD2, by IL-1α through the activation of GPCRs and ERK signaling pathway. The administration of Ile may therefore represent a possible option to safely treat intestinal inflammation.

New insights into sodium transport regulation in the distal nephron:Role of G-protein coupled receptors

The renal handling of Na^+ balance is a major determinant of the blood pressure(BP) level. The inability of the kidney to excrete the daily load of Na+ represents the primary cause of chronic hypertension. Among the different segments that constitute the nephron, those present in the distal part(i.e., the cortical thick ascending limb, the distal convoluted tubule, the connecting and collecting tubules) play a central role in the fine-tuning of renal Na^+ excretion and are the target of many different regulatory processes that modulate Na^+ retention more or less efficiently. G-protein coupled receptors(GPCRs) are crucially involved in this regulation and could represent efficient pharmacological targets to control BP levels. In this review, we describe both classical and novel GPCR-dependent regulatory systems that have been shown to modulate renal Na^+ absorption in the distal nephron. In addition to the multiplicity of the GPCR that regulate Na^+ excretion, this review also highlights the complexity of these different pathways, and the connections between them.

Identification of a key G-protein coupled receptor in mediating appressorium formation and fungal virulence against insects

Fungal G-protein coupled receptors(GPCRs)play essential roles in sensing environmental cues including host signals.The study of GPCR in mediating fungus-insect interactions is still limited.Here we report the evolution of GPCR genes encoded in the entomopathogenic Metarhizium species and found the expansion of Pth11-like GPCRs in the generalist species with a wide host range.By deletion of ten candidate genes MrGpr1–MrGpr10 selected from the six obtained subfamilies in the generalist M.robertsii,we found that each of them played a varied level of roles in mediating appressorium formation.In particular,deletion of MrGpr8 resulted in the failure of appressorium formation on different substrates and the loss of virulence during topical infection of insects but not during injection assays when compared with the wild-type(WT)strain.Further analysis revealed that disruption of MrGpr8 substantially impaired the nucleus translocation of the mitogen-activated protein kinase(MAPK)Mero-Fus3 but not the MAPK Mero-Slt2 during appressorium formation.We also found that the defect ofΔMrGpr8 could not be rescued with the addition of cyclic AMP for appressorium formation.Relative to the WT,differential expression of the selected genes have also been detected inΔMrGpr8.The results of this study may benefit the understanding of fungus-interactions mediated by GPCRs.

The complexity of G-protein coupled receptor-ligand interactions

The G-protein coupled receptors(GPCRs)play fundamental roles in the human biololgy and drug discovery.GPCRs function as signalling molecules that transduce extracellular signals into cells.The signalling transduction is generally triggered by interacting with ligands,including photons,ions,small organic compounds,peptides,proteins and lipids.In this review,we focus on interactions with diffusible ligands such as hormones and neurotransmitters.We discuss three aspects of the complexity of the GPCR-ligand interactions:functional selectivity of ligands,receptor subtype selectivity of ligands and orphan GPCRs.

A semi-analytical model for coupled flow in stress-sensitive multi-scale shale reservoirs with fractal characteristics

A large number of nanopores and complex fracture structures in shale reservoirs results in multi-scale flow of oil. With the development of shale oil reservoirs, the permeability of multi-scale media undergoes changes due to stress sensitivity, which plays a crucial role in controlling pressure propagation and oil flow. This paper proposes a multi-scale coupled flow mathematical model of matrix nanopores, induced fractures, and hydraulic fractures. In this model, the micro-scale effects of shale oil flow in fractal nanopores, fractal induced fracture network, and stress sensitivity of multi-scale media are considered. We solved the model iteratively using Pedrosa transform, semi-analytic Segmented Bessel function, Laplace transform. The results of this model exhibit good agreement with the numerical solution and field production data, confirming the high accuracy of the model. As well, the influence of stress sensitivity on permeability, pressure and production is analyzed. It is shown that the permeability and production decrease significantly when induced fractures are weakly supported. Closed induced fractures can inhibit interporosity flow in the stimulated reservoir volume (SRV). It has been shown in sensitivity analysis that hydraulic fractures are beneficial to early production, and induced fractures in SRV are beneficial to middle production. The model can characterize multi-scale flow characteristics of shale oil, providing theoretical guidance for rapid productivity evaluation.

Uncertainty quantification of mechanism motion based on coupled mechanism—motor dynamic model for ammunition delivery system

In this paper,a dynamic modeling method of motor driven electromechanical system is presented,and the uncertainty quantification of mechanism motion is investigated based on this method.The main contribution is to propose a novel mechanism-motor coupling dynamic modeling method,in which the relationship between mechanism motion and motor rotation is established according to the geometric coordination of the system.The advantages of this include establishing intuitive coupling between the mechanism and motor,facilitating the discussion for the influence of both mechanical and electrical parameters on the mechanism,and enabling dynamic simulation with controller to take the randomness of the electric load into account.Dynamic simulation considering feedback control of ammunition delivery system is carried out,and the feasibility of the model is verified experimentally.Based on probability density evolution theory,we comprehensively discuss the effects of system parameters on mechanism motion from the perspective of uncertainty quantization.Our work can not only provide guidance for engineering design of ammunition delivery mechanism,but also provide theoretical support for modeling and uncertainty quantification research of mechatronics system.

Coupled multiphysical model for investigation of influence factors in the application of microbially induced calcite precipitation

The study presents a comprehensive coupled thermo-bio-chemo-hydraulic(T-BCH)modeling framework for stabilizing soils using microbially induced calcite precipitation(MICP).The numerical model considers relevant multiphysics involved in MICP,such as bacterial ureolytic activities,biochemical reactions,multiphase and multicomponent transport,and alteration of the porosity and permeability.The model incorporates multiphysical coupling effects through well-established constitutive relations that connect parameters and variables from different physical fields.It was implemented in the open-source finite element code OpenGeoSys(OGS),and a semi-staggered solution strategy was designed to solve the couplings,allowing for flexible model settings.Therefore,the developed model can be easily adapted to simulate MICP applications in different scenarios.The numerical model was employed to analyze the effect of various factors,including temperature,injection strategies,and application scales.Besides,a TBCH modeling study was conducted on the laboratory-scale domain to analyze the effects of temperature on urease activity and precipitated calcium carbonate.To understand the scale dependency of MICP treatment,a large-scale heterogeneous domain was subjected to variable biochemical injection strategies.The simulations conducted at the field-scale guided the selection of an injection strategy to achieve the desired type and amount of precipitation.Additionally,the study emphasized the potential of numerical models as reliable tools for optimizing future developments in field-scale MICP treatment.The present study demonstrates the potential of this numerical framework for designing and optimizing the MICP applications in laboratory-,prototype-,and field-scale scenarios.

Nonlinearly induced entanglement in dissipatively coupled optomechanical system

Nonlinearly induced steady-state photon–phonon entanglement of a dissipative coupled system is studied in the bistable regime. Quantum dynamical characteristics are analysed by solving the mean-field and fluctuation equations of the system. It is shown that dissipative coupling can induce bistable behaviour for the effective dissipation of the system.Under suitable parameters, one of the steady states significantly reduces the dissipative effect of the system. Consequently,a larger steady-state entanglement can be achieved compared to linear dynamics. Furthermore, the experimental feasibility of the parameters is analysed. Our results provide a new perspective for the implementation of steady-state optomechanical entanglement.

Seismic performance evaluation of hybrid coupled shear wall system with shear and flexural fuse-type steel coupling beams

Replaceable flexural and shear fuse-type coupling beams are used in hybrid coupled shear wall(HCSW)systems,enabling concrete buildings to be promptly recovered after severe earthquakes.This study aimed to analytically evaluate the seismic behavior of flexural and shear fuse beams situated in short-,medium-and high-rise RC buildings that have HCSWs.Three building groups hypothetically located in a high seismic hazard zone were studied.A series of 2D nonlinear time history analyses was accomplished in OpenSees,using the ground motion records scaled at the design basis earthquake level.It was found that the effectiveness of fuses in HCSWs depends on various factors such as size and scale of the building,allowable rotation value,inter-story drift ratio,residual drift quantity,energy dissipation value of the fuses,etc.The results show that shear fuses better meet the requirements of rotations and drifts.In contrast,flexural fuses dissipate more energy,but their sectional stiffness should increase to meet other requirements.It was concluded that adoption of proper fuses depends on the overall scale of the building and on how associated factors are considered.

Effects of asymmetric coupling and boundary on the dynamic behaviors of a random nearest neighbor coupled system

This study investigates the dynamical behaviors of nearest neighbor asymmetric coupled systems in a confined space.First, the study derivative analytical stability and synchronization conditions for the asymmetrically coupled system in an unconfined space, which are then validated through numerical simulations. Simulation results show that asymmetric coupling has a significant impact on synchronization conditions. Moreover, it is observed that irrespective of whether the system is confined, an increase in coupling asymmetry leads to a hastened synchronization pace. Additionally, the study examines the effects of boundaries on the system's collective behaviors via numerical experiments. The presence of boundaries ensures the system's stability and synchronization, and reducing these boundaries can expedite the synchronization process and amplify its effects. Finally, the study reveals that the system's output amplitude exhibits stochastic resonance as the confined boundary size increases.

Customized modulation on plasma uniformity by non-uniform magnetic field in capacitively coupled plasma

A two-dimensional fluid model based on COMSOL Multiphysics is developed to investigate the modulation of static magnetic field on plasma homogeneity in a capacitively coupled plasma(CCP)chamber. To generate a static magnetic field, direct current is applied to a circular coil located at the top of the chamber. By adjusting the magnetic field's configuration, which is done by altering the coil current and position, both the plasma uniformity and density can be significantly modulated. In the absence of the magnetic field, the plasma density exhibits an inhomogeneous distribution characterized by higher values at the plasma edge and lower values at the center. The introduction of a magnetic field generated by coils results in a significant increase in electron density near the coils. Furthermore, an increase in the sets of coils improves the uniformity of the plasma. By flexibly adjusting the positions of the coils and the applied current,a substantial enhancement in overall uniformity can be achieved. These findings demonstrate the feasibility of using this method for achieving uniform plasma densities in industrial applications.

A Coupled Thermomechanical Crack Propagation Behavior of Brittle Materials by Peridynamic Differential Operator

This study proposes a comprehensive,coupled thermomechanical model that replaces local spatial derivatives in classical differential thermomechanical equations with nonlocal integral forms derived from the peridynamic differential operator(PDDO),eliminating the need for calibration procedures.The model employs a multi-rate explicit time integration scheme to handle varying time scales in multi-physics systems.Through simulations conducted on granite and ceramic materials,this model demonstrates its effectiveness.It successfully simulates thermal damage behavior in granite arising from incompatible mineral expansion and accurately calculates thermal crack propagation in ceramic slabs during quenching.To account for material heterogeneity,the model utilizes the Shuffle algorithm andWeibull distribution,yielding results that align with numerical simulations and experimental observations.This coupled thermomechanical model shows great promise for analyzing intricate thermomechanical phenomena in brittle materials.

Beauty-charm meson family with coupled channel effects and their strong decays

We systematically examined the mass spectra and their two-body hadronic decays of the beauty-charm meson family considering coupled channel effects.Our results can effectively explain the observed Bemeson spectrum,and the prediction of the mass spectrum for unobserved beauty-charm mesons can be tested in future experiments.Compared with previous studies,we systematically examine the beauty-charm meson family within the coupled channel components.The 1S state in beauty-charm meson family has few percent of coupled channel component,while the 2S,1P,and 1D states have more than ten percent of coupled channel component.The two-body hadronic decay widths of the 2^(3)P_(2) state is as narrow as 3 MeV.The two-body hadronic decay widths of 3^(1)S_(0),3^(3)S_(1),2^(3)D_(1),2D,2D',and 2^(3)D_(3) are approximately 109,67,60,57,201,and 76 MeV,respectively.Furthermore,the mixing effects between B_(c)(n^(3)L_(L))and B_(c)(n^(1)L_(L))states are discussed.

Coexisting fast–slow dendritic traveling waves in a 3D-array electric field coupled neuronal network

Coexistence of fast and slow traveling waves without synaptic transmission has been found in hhhippocampal tissues,which is closely related to both normal brain activity and abnormal neural activity such as epileptic discharge. However, the propagation mechanism behind this coexistence phenomenon remains unclear. In this paper, a three-dimensional electric field coupled hippocampal neural network is established to investigate generation of coexisting spontaneous fast and slow traveling waves. This model captures two types of dendritic traveling waves propagating in both transverse and longitude directions: the N-methyl-D-aspartate(NMDA)-dependent wave with a speed of about 0.1 m/s and the Ca-dependent wave with a speed of about 0.009 m/s. These traveling waves are synaptic-independent and could be conducted only by the electric fields generated by neighboring neurons, which are basically consistent with the in vitro data measured experiments. It is also found that the slow Ca wave could trigger generation of fast NMDA waves in the propagation path of slow waves whereas fast NMDA waves cannot affect the propagation of slow Ca waves. These results suggest that dendritic Ca waves could acted as the source of the coexistence fast and slow waves. Furthermore, we also confirm the impact of cellular spacing heterogeneity on the onset of coexisting fast and slow waves. The local region with decreasing distances among neighbor neurons is more liable to promote the onset of spontaneous slow waves which, as sources, excite propagation of fast waves. These modeling studies provide possible biophysical mechanisms underlying the neural dynamics of spontaneous traveling waves in brain tissues.

Multi-soliton solutions of coupled Lakshmanan-Porsezian-Daniel equations with variable coefficients under nonzero boundary conditions

This paper aims to investigate the multi-soliton solutions of the coupled Lakshmanan–Porsezian–Daniel equations with variable coefficients under nonzero boundary conditions.These equations are utilized to model the phenomenon of nonlinear waves propagating simultaneously in non-uniform optical fibers.By analyzing the Lax pair and the Riemann–Hilbert problem,we aim to provide a comprehensive understanding of the dynamics and interactions of solitons of this system.Furthermore,we study the impacts of group velocity dispersion or the fourth-order dispersion on soliton behaviors.Through appropriate parameter selections,we observe various nonlinear phenomena,including the disappearance of solitons after interaction and their transformation into breather-like solitons,as well as the propagation of breathers with variable periodicity and interactions between solitons with variable periodicities.

A mechanically coupled MEMS filter with high-Q width extensional mode resonators

This work presents a novel radio frequency(RF)narrowband Si micro-electro-mechanical systems(MEMS)filter based on capacitively transduced slotted width extensional mode(WEM)resonators.The flexibility of the plate leads to multiple modes near the target frequency.The high Q-factor resonators of around 100000 enable narrow bandwidth filters with small size and simplified design.The 1-wavelength and 2-wavelength WEMs were first developed as a pair of coupled modes to form a passband.To reduce bandwidth,two plates are coupled with aλ-length coupling beam.The 79.69 MHz coupled plate filter(CPF)achieved a narrow bandwidth of 8.8 kHz,corresponding to a tiny 0.011%.The CPF exhibits an impressive 34.84 dB stopband rejection and 7.82 dB insertion loss with near-zero passband ripple.In summary,the RF MEMS filter presented in this work shows promising potential for application in RF transceiver front-ends.

Coupled effects of climate change and human activities on vegetation dynamics in the Southwestern Alpine Canyon Region of China

The driving effects of climate change and human activities on vegetation change have always been a focal point of research.However,the coupling mechanisms of these driving factors across different temporal and spatial scales remain controversial.The Southwestern Alpine Canyon Region of China(SACR),as an ecologically fragile area,is highly sensitive to the impacts of climate change and human activities.This study constructed a vegetation cover dataset for the SACR based on the Enhanced Vegetation Index(EVI)from 2000 to 2020.Spatial autocorrelation,Theil-Sen trend,and Mann-Kendall tests were used to analyze the spatiotemporal characteristics of vegetation cover changes.The main drivers of spatial heterogeneity in vegetation cover were identified using the optimal parameter geographic detector,and an improved residual analysis model was employed to quantify the relative contributions of climate change and human activities to interannual vegetation cover changes.The main findings are as follows:Spatially,vegetation cover exceeds 60%in most areas,especially in the southern part of the study area.However,the border area between Linzhi and Changdu exhibits lower vegetation cover.Climate factors are the primary drivers of spatial heterogeneity in vegetation cover,with temperature having the most significant influence,as indicated by its q-value,which far exceeds that of other factors.Additionally,the interaction q-value between the two factors significantly increases,showing a relationship of bivariate enhancement and nonlinear enhancement.In terms of temporal changes,vegetation cover shows an overall improving trend from 2000 to 2020,with significant increases observed in 68.93%of the study area.Among these,human activities are the main factors driving vegetation cover change,with a relative contribution rate of 41.31%,while climate change and residual factors contribute 35.66%and 23.53%,respectively.By thoroughly exploring the coupled mechanisms of vegetation change,this study provides important references for the sustainable management and conservation of the vegetation ecosystem in the SACR.

Abnormal transition of the electron energy distribution with excitation of the second harmonic in low-pressure radio-frequency capacitively coupled plasmas

The self-excited second harmonic in radio-frequency capacitively coupled plasma was significantly enhanced by adjusting the external variable capacitor.At a lower pressure of 3 Pa,the excitation of the second harmonic caused an abnormal transition of the electron energy probability function,resulting in abrupt changes in the electron density and temperature.Such changes in the electron energy probability function as well as the electron density and temperature were not observed at the higher pressure of 16 Pa under similar harmonic changes.The phenomena are related to the influence of the second harmonic on stochastic heating,which is determined by both amplitude and the relative phase of the harmonics.The results suggest that the self-excited high-order harmonics must be considered in practical applications of lowpressure radio-frequency capacitively coupled plasmas.