Subsurface rocks,as complex porous media,exhibit multiscale pore structures and intricate physical properties.Digital rock physics technology has become increasingly influential in the study of subsurface rock propert...Subsurface rocks,as complex porous media,exhibit multiscale pore structures and intricate physical properties.Digital rock physics technology has become increasingly influential in the study of subsurface rock properties.Given the multiscale characteristics of rock pore structures,direct three-dimensional imaging at sub-micrometer and nanometer scales is typically infeasible.This study introduces a method for reconstructing porous media using multidimensional data,which combines one-dimensional pore structure parameters with two-dimensional images to reconstruct three-dimensional models.The pore network model(PNM)is stochastically reconstructed using one-dimensional parameters,and a generative adversarial network(GAN)is utilized to equip the PNM with pore morphologies derived from two-dimensional images.The digital rocks generated by this method possess excellent controllability.Using Berea sandstone and Grosmont carbonate samples,we performed digital rock reconstructions based on PNM extracted by the maximum ball algorithm and compared them with stochastically reconstructed PNM.Pore structure parameters,permeability,and formation factors were calculated.The results show that the generated samples exhibit good consistency with real samples in terms of pore morphology,pore structure,and physical properties.Furthermore,our method effectively supplements the micropores not captured in CT images,demonstrating its potential in multiscale carbonate samples.Thus,the proposed reconstruction method is promising for advancing porous media property research.展开更多
In recent years, the Cavally River has been subject to multiple activities, <span style="font-family:;" "="">including the construction of diversion channels and a bridge that makes it v...In recent years, the Cavally River has been subject to multiple activities, <span style="font-family:;" "="">including the construction of diversion channels and a bridge that makes it vulnerable to flooding. In order to assess the impact of these hydraulic structures on the <span>river hydrodynamic functioning, a 1D-2D model was realized. The</span> implementation of the 1D-2D model consisted </span><span style="font-family:;" "="">of </span><span style="font-family:;" "="">first </span><span style="font-family:;" "="">running</span><span style="font-family:;" "=""> </span><span style="font-family:;" "="">the 1D model, then the 2D model, and finally in coupling them. The 1D-2D model was designed with <span>the 1988 flood hydrograph, a Manning’s coefficient of 0.052 m<sup>1/3</sup>/s for the </span>minor bed and 0.06 m<sup>1/3</sup>/s for the major bed. The results of the hydraulic model show that the velocities are almost identical to those of the Cavally in natural operation. The values of the velocities are included between 0.4 m/s and 1.3 m/s at the level of the minor bed of the river and between 0.06 m/s and 0.71 m/s at the level of the floodplains. The average water level for flood propagation is 262.37 ± 0.44 m before construction of the structures and 262.23 ± <span>0.85 m after construction of the structures. The 0.41 m reduction in water</span> level due to the diversion canal and bridge is negligible compared to the total fluctuations of the Cavally River, which vary from 6 to 7 m over the year.</span>展开更多
Due to the high population density and economic property in urban environments,urban flooding can result in substantial economic losses.However,accurate urban flood modeling and assessing the associated damages are ch...Due to the high population density and economic property in urban environments,urban flooding can result in substantial economic losses.However,accurate urban flood modeling and assessing the associated damages are challenging due to complex urban layouts and rugged topography.Furthermore,the rapid development of urban underground spaces has introduced additional complexities.To address the demanding need for accurate flood modeling and damage assessment in cities,a fine-scale flood damage assessment method was proposed in this study,based on the 1D/2D coupled hydrodynamic model,which can not only assess the flood damage on the ground surface but also evaluate the flood loss in underground spaces.Taking the Gangxi drainage area in Wuhan City,China as a case,this study extensively discussed the flood inundation processes on the ground surface as well as in the buildings and underground spaces,under different rainfall scenarios with the return period ranging from 2 to 200 years.Based on the high spatial-temporal hydrodynamic simulations,the flood damage degrees were evaluated for the buildings and underground spaces with different industry types.The results indicated that the inundation of buildings and underground spaces in densely built cities cannot be neglected in urban flood modeling.Buildings with public service attributes can have a higher flood damage degree,as compared with other types of buildings and underground spaces.展开更多
In this study, 1D and 2D shallow-water models were coupled to simulate unsteady flow in channel networks and embayment. The 1D model solved the 1D shallow-water equations (St. Venant) using the Preissmann box method a...In this study, 1D and 2D shallow-water models were coupled to simulate unsteady flow in channel networks and embayment. The 1D model solved the 1D shallow-water equations (St. Venant) using the Preissmann box method and targeted long narrow reaches of the river networks, while the 2D model targeted broad channels and embayment and solved the 2D shallow-water equations using a semi-implicit scheme applied to an unstructured grid of triangular cells. The 1D and 2D models were solved simultaneously by building a matrix for the free surface elevation at every 1D junction and 2D cell center. Velocities were then computed explicitly based on the results at the previous time step and the updated water level. The originality of the scheme arose from a novel coupling method. The results showed that the coupled 1D/2D model produced identical results as the full 2D model in classical to benchmark problems with considerable savings in computational effort. Application of the model to the Pearl River Estuary in southern China showed that complex patterns of tidal wave propagation could be efficiently modeled.展开更多
The main stream of the Yangtze River, Dongting Lake, and the river network in the Jingjiang reach of the Yangtze River constitute a complex water system. This paper develops a one-dimensional （l-D） mathematical mode...The main stream of the Yangtze River, Dongting Lake, and the river network in the Jingjiang reach of the Yangtze River constitute a complex water system. This paper develops a one-dimensional （l-D） mathematical model for flood routing in the river network Of the Jingjiang River and Dongting Lake using the explicit finite volume method. Based on observed data during the flood periods in 1996 and 1998, the model was calibrated and validated, and the results show that the model is effective and has high accuracy. In addition, the one-dimensional mathematical model for the river network and the horizontal two-dimensional （2-D） mathematical model for the Jingjiang flood diversion area were coupled to simulate the flood process in the Jingjiang River, Dongting Lake, and the Jingjiang flood diversion area. The calculated results of the coupled model are consistent with the practical processes. Meanwhile, the results show that the flood diversion has significant effects on the decrease of the peak water level at the Shashi and Chenjiawan hydrological stations near the flood diversion gates, and the effect is more obvious in the downstream than in the upstream.展开更多
In many animal-related studies, a high-performance animal behavior recognition system can help researchers reduce or get rid of the limitation of human assessments and make the experiments easier to reproduce. Recentl...In many animal-related studies, a high-performance animal behavior recognition system can help researchers reduce or get rid of the limitation of human assessments and make the experiments easier to reproduce. Recently, although deep learning models are holding state-of-the-art performances in human action recognition tasks, these models are not well-studied in applying to animal behavior recognition tasks. One reason is the lack of extensive datasets which are required to train these deep models for good performances. In this research, we investigated two current state-of-the-art deep learning models in human action recognition tasks, the I3D model and the R(2 + 1)D model, in solving a mouse behavior recognition task. We compared their performances with other models from previous researches and the results showed that the deep learning models that pre-trained using human action datasets then fine-tuned using the mouse behavior dataset can outperform other models from previous researches. It also shows promises of applying these deep learning models to other animal behavior recognition tasks without any significant modification in the models’ architecture, all we need to do is collecting proper datasets for the tasks and fine-tuning the pre-trained models using the collected data.展开更多
Characterized by special morphologic,geographic,hydrologic,and societal behaviors,the water resources management of the Mediterranean catchment often shows a higher level of complexity including security issues of wat...Characterized by special morphologic,geographic,hydrologic,and societal behaviors,the water resources management of the Mediterranean catchment often shows a higher level of complexity including security issues of water supply,inundation risks,and environment management under the perspective of climate change.To have a comprehensive understanding of the Mediterranean water-cycle system,a deterministic distributed hydrologic modeling approach has been developed and presented in this study based on an application in the Var catchment(2800 km^(2))located at the French Mediterranean region.A 1D and 2D coupled model of MIKE SHE and MIKE 11 has been set up under a series of hypotheses to represent the whole hydrologic and hydrodynamic processes including rainfall-runoff,snow-melting,channel flow,overland flow,and the water exchange between land surface and unsaturated/saturated zones.The developed model was first calibrated with 4 years daily records from 2008 to 2011,then to be validated and further run within hourly time interval to produce detailed representation of the catchment water-cycle from 2012 to 2014.The deterministic distributed modeling approach presented in this study is able to represent its complicated water-cycle and used for supporting the decision‐making process of the water resources management of the catchment.展开更多
The purpose of this study is to set up a dynamically linked 1D and 2D hydrodynamic and sediment transport models for dam break flow.The 1D-2D coupling model solves the generalized shallow water equations,the non-equil...The purpose of this study is to set up a dynamically linked 1D and 2D hydrodynamic and sediment transport models for dam break flow.The 1D-2D coupling model solves the generalized shallow water equations,the non-equilibrium sediment transport and bed change equations in a coupled fashion using an explicit finite volume method.It considers interactions among transient flow,strong sediment transport and rapid bed change by including bed change and variable flow density in the flow continuity and momentum equations.An unstructured Quadtree rectangular grid with local refinement is used in the 2D model.The intercell flux is computed by the HLL approximate Riemann solver with shock captured capability for computing the dry-to-wet interface for all models.The effects of pressure and gravity are included in source term in this coupling model which can simplify the computation and eliminate numerical imbalance between source and flux terms.The developed model has been tested against experimental and real-life case of dam-break flow over fix bed and movable bed.The results are compared with analytical solution and measured data with good agreement.The simulation results demonstrate that the coupling model is capable of calculating the flow,erosion and deposition for dam break flows in complicated natural domains.展开更多
A coupled one-dimensional （1-D） and two-dimensional （2-D） channel network mathematical model is proposed for flow calculations at nodes in a channel network system in this article. For the 1-D model, the finite di...A coupled one-dimensional （1-D） and two-dimensional （2-D） channel network mathematical model is proposed for flow calculations at nodes in a channel network system in this article. For the 1-D model, the finite difference method is used to discretize the Saint-Venant equations in all channels of a looped network. The Alternating Direction Implicit （ADI） method is adopted for the 2-D model at the nodes. In the coupled model, the 1-D model provides a good approximation with small computational effort, while the 2-D model is applied for complex topography to achieve a high accuracy. An Artificial Neural Network （ANN.） method is used for the data exchange and the connectivity between the 1-D and 2-D models. The coupled model is applied to the Jingjiang-Dongting Lake region, to simulate the tremendous looped channel network system, and the results are compared with field data. The good agreement shows that the coupled hydraulic model is more effective than the conventional 1-D model.展开更多
γ-Aminobutyric acid（GABA）,plays a key role in all stages of life,also is considered the main inhibitory neurotransmitter.GABA activates two kind of membrane receptors known as GABAA and GABAB,the first one is respo...γ-Aminobutyric acid（GABA）,plays a key role in all stages of life,also is considered the main inhibitory neurotransmitter.GABA activates two kind of membrane receptors known as GABAA and GABAB,the first one is responsible to render tonic inhibition by pentameric receptors containing α4-6,β3,δ,or ρ1-3 subunits,they are located at perisynaptic and/or in extrasynaptic regions.The biophysical properties of GABAA tonic inhibition have been related with cellular protection against excitotoxic injury and cell death in presence of excessive excitation.On this basis,GABAA tonic inhibition has been proposed as a potential target for therapeutic intervention of Huntington＇s disease.Huntington＇s disease is a neurodegenerative disorder caused by a genetic mutation of the huntingtin protein.For experimental studies of Huntington＇s disease mouse models have been developed,such as R6/1,R6/2,Hdh Q92,Hdh Q150,as well as YAC128.In all of them,some key experimental reports are focused on neostriatum.The neostriatum is considered as the most important connection between cerebral cortex and basal ganglia structures,its cytology display two pathways called direct and indirect constituted by medium sized spiny neurons expressing dopamine D1 and D2 receptors respectively,they display strong expression of many types of GABAA receptors,including tonic subunits.The studies about of GABAA tonic subunits and Huntington＇s disease into the neostriatum are rising in recent years,suggesting interesting changes in their expression and localization which can be used as a strategy to delay the cellular damage caused by the imbalance between excitation and inhibition,a hallmark of Huntington＇s disease.展开更多
Familial acne inversa (AI) is an autoinflammatory disorder that affects hair follicles and is caused by loss-of-function mutations in y-secretase component genes.We and other researchers showed that nicastrin (NCSTN) ...Familial acne inversa (AI) is an autoinflammatory disorder that affects hair follicles and is caused by loss-of-function mutations in y-secretase component genes.We and other researchers showed that nicastrin (NCSTN) is the most frequently mutated gene in familial AI.In this study,we generated a keratin 5-Cre-driven epidermis-specific Ncstn conditional knockout mutant in mice.We determined that this mutant recapitulated the major phenotypes of AI,including hyperkeratosis of hair follicles and inflammation.In Ncstnflox/flox;K5-Cre mice,the IL-36a expression level markedly increased starting from postnatal day 0 (P0),and this increase occurred much earlier than those of TNF-α,IL-23A,IL-1 3,and TLR4.RNA-Seq analysis indicated that Sprr2d,a member of the small proline-rich protein 2 family,in the skin tissues of the Ncstnflox/flox,;K5-Cre mice was also upregulated on P0.Quantitative reverse-transcription polymerase chain reaction showed that other Sprr2 genes had a similar expression pattern.Our findings suggested that IL-36a might be a key inflammatory cytokine in the pathophysiology of AI and implicate malfunction of the skin barrier in the pathogenesis of AI.展开更多
基金supported by the Shandong Provincial Natural Science Foundation(ZR2024MD116)National Natural Science Foundation of China(Grant Nos.42174143,42004098)Technology Innovation Leading Program of Shaanxi(No.2024 ZC-YYDP-27).
文摘Subsurface rocks,as complex porous media,exhibit multiscale pore structures and intricate physical properties.Digital rock physics technology has become increasingly influential in the study of subsurface rock properties.Given the multiscale characteristics of rock pore structures,direct three-dimensional imaging at sub-micrometer and nanometer scales is typically infeasible.This study introduces a method for reconstructing porous media using multidimensional data,which combines one-dimensional pore structure parameters with two-dimensional images to reconstruct three-dimensional models.The pore network model(PNM)is stochastically reconstructed using one-dimensional parameters,and a generative adversarial network(GAN)is utilized to equip the PNM with pore morphologies derived from two-dimensional images.The digital rocks generated by this method possess excellent controllability.Using Berea sandstone and Grosmont carbonate samples,we performed digital rock reconstructions based on PNM extracted by the maximum ball algorithm and compared them with stochastically reconstructed PNM.Pore structure parameters,permeability,and formation factors were calculated.The results show that the generated samples exhibit good consistency with real samples in terms of pore morphology,pore structure,and physical properties.Furthermore,our method effectively supplements the micropores not captured in CT images,demonstrating its potential in multiscale carbonate samples.Thus,the proposed reconstruction method is promising for advancing porous media property research.
文摘In recent years, the Cavally River has been subject to multiple activities, <span style="font-family:;" "="">including the construction of diversion channels and a bridge that makes it vulnerable to flooding. In order to assess the impact of these hydraulic structures on the <span>river hydrodynamic functioning, a 1D-2D model was realized. The</span> implementation of the 1D-2D model consisted </span><span style="font-family:;" "="">of </span><span style="font-family:;" "="">first </span><span style="font-family:;" "="">running</span><span style="font-family:;" "=""> </span><span style="font-family:;" "="">the 1D model, then the 2D model, and finally in coupling them. The 1D-2D model was designed with <span>the 1988 flood hydrograph, a Manning’s coefficient of 0.052 m<sup>1/3</sup>/s for the </span>minor bed and 0.06 m<sup>1/3</sup>/s for the major bed. The results of the hydraulic model show that the velocities are almost identical to those of the Cavally in natural operation. The values of the velocities are included between 0.4 m/s and 1.3 m/s at the level of the minor bed of the river and between 0.06 m/s and 0.71 m/s at the level of the floodplains. The average water level for flood propagation is 262.37 ± 0.44 m before construction of the structures and 262.23 ± <span>0.85 m after construction of the structures. The 0.41 m reduction in water</span> level due to the diversion canal and bridge is negligible compared to the total fluctuations of the Cavally River, which vary from 6 to 7 m over the year.</span>
基金National Natural Science Foundation of China,Grant/Award Numbers:41890820,51725902,52209098Special Fund for Science and Technology Innovation Strategy of Guangdong Province,Grant/Award Number:gdsky2023-02+1 种基金Newton Advanced Fellowships from the NSFC and the UK Royal Society,Grant/Award Numbers:52061130219,NAF\R1\201156Science and Technology Innovation Program from Water Resources of Guangdong Province,Grant/Award Numbers:2022-01,2023-05。
文摘Due to the high population density and economic property in urban environments,urban flooding can result in substantial economic losses.However,accurate urban flood modeling and assessing the associated damages are challenging due to complex urban layouts and rugged topography.Furthermore,the rapid development of urban underground spaces has introduced additional complexities.To address the demanding need for accurate flood modeling and damage assessment in cities,a fine-scale flood damage assessment method was proposed in this study,based on the 1D/2D coupled hydrodynamic model,which can not only assess the flood damage on the ground surface but also evaluate the flood loss in underground spaces.Taking the Gangxi drainage area in Wuhan City,China as a case,this study extensively discussed the flood inundation processes on the ground surface as well as in the buildings and underground spaces,under different rainfall scenarios with the return period ranging from 2 to 200 years.Based on the high spatial-temporal hydrodynamic simulations,the flood damage degrees were evaluated for the buildings and underground spaces with different industry types.The results indicated that the inundation of buildings and underground spaces in densely built cities cannot be neglected in urban flood modeling.Buildings with public service attributes can have a higher flood damage degree,as compared with other types of buildings and underground spaces.
基金financially supporrted by the National Key Research and Development Program of China(Grant No.2017YFC1404200)the National Natural Science Foundation of China(Grant Nos.51779150 and 51979040)
文摘In this study, 1D and 2D shallow-water models were coupled to simulate unsteady flow in channel networks and embayment. The 1D model solved the 1D shallow-water equations (St. Venant) using the Preissmann box method and targeted long narrow reaches of the river networks, while the 2D model targeted broad channels and embayment and solved the 2D shallow-water equations using a semi-implicit scheme applied to an unstructured grid of triangular cells. The 1D and 2D models were solved simultaneously by building a matrix for the free surface elevation at every 1D junction and 2D cell center. Velocities were then computed explicitly based on the results at the previous time step and the updated water level. The originality of the scheme arose from a novel coupling method. The results showed that the coupled 1D/2D model produced identical results as the full 2D model in classical to benchmark problems with considerable savings in computational effort. Application of the model to the Pearl River Estuary in southern China showed that complex patterns of tidal wave propagation could be efficiently modeled.
基金supported by the National Key Technologies Research and Development Program (Grant No. 2006BAB05B02)
文摘The main stream of the Yangtze River, Dongting Lake, and the river network in the Jingjiang reach of the Yangtze River constitute a complex water system. This paper develops a one-dimensional （l-D） mathematical model for flood routing in the river network Of the Jingjiang River and Dongting Lake using the explicit finite volume method. Based on observed data during the flood periods in 1996 and 1998, the model was calibrated and validated, and the results show that the model is effective and has high accuracy. In addition, the one-dimensional mathematical model for the river network and the horizontal two-dimensional （2-D） mathematical model for the Jingjiang flood diversion area were coupled to simulate the flood process in the Jingjiang River, Dongting Lake, and the Jingjiang flood diversion area. The calculated results of the coupled model are consistent with the practical processes. Meanwhile, the results show that the flood diversion has significant effects on the decrease of the peak water level at the Shashi and Chenjiawan hydrological stations near the flood diversion gates, and the effect is more obvious in the downstream than in the upstream.
文摘In many animal-related studies, a high-performance animal behavior recognition system can help researchers reduce or get rid of the limitation of human assessments and make the experiments easier to reproduce. Recently, although deep learning models are holding state-of-the-art performances in human action recognition tasks, these models are not well-studied in applying to animal behavior recognition tasks. One reason is the lack of extensive datasets which are required to train these deep models for good performances. In this research, we investigated two current state-of-the-art deep learning models in human action recognition tasks, the I3D model and the R(2 + 1)D model, in solving a mouse behavior recognition task. We compared their performances with other models from previous researches and the results showed that the deep learning models that pre-trained using human action datasets then fine-tuned using the mouse behavior dataset can outperform other models from previous researches. It also shows promises of applying these deep learning models to other animal behavior recognition tasks without any significant modification in the models’ architecture, all we need to do is collecting proper datasets for the tasks and fine-tuning the pre-trained models using the collected data.
基金supported by the National Key R&D Program of China(No.2023YFC3006702)the Natural Science Foundation of Beijing Municipality(IS23117).
文摘Characterized by special morphologic,geographic,hydrologic,and societal behaviors,the water resources management of the Mediterranean catchment often shows a higher level of complexity including security issues of water supply,inundation risks,and environment management under the perspective of climate change.To have a comprehensive understanding of the Mediterranean water-cycle system,a deterministic distributed hydrologic modeling approach has been developed and presented in this study based on an application in the Var catchment(2800 km^(2))located at the French Mediterranean region.A 1D and 2D coupled model of MIKE SHE and MIKE 11 has been set up under a series of hypotheses to represent the whole hydrologic and hydrodynamic processes including rainfall-runoff,snow-melting,channel flow,overland flow,and the water exchange between land surface and unsaturated/saturated zones.The developed model was first calibrated with 4 years daily records from 2008 to 2011,then to be validated and further run within hourly time interval to produce detailed representation of the catchment water-cycle from 2012 to 2014.The deterministic distributed modeling approach presented in this study is able to represent its complicated water-cycle and used for supporting the decision‐making process of the water resources management of the catchment.
基金supported by the National Basic Research Program of China(Grant No.2013CB430403)the Public Science and Technology Research Funds Projects of Ocean(Grant No.201205023)+3 种基金the Program for Liaoning Excellent Talents in University(Grant No.LJQ2013077)the Science and Technology Foundation of Dalian City(Grant No.2013J21DW009)the Special Funds for Postdoctoral Innovative Projects of Liaoning Province(Grant No.2011921018)the Special Funds for Talent Projects of Dalian Ocean University(Grant No.SYYJ2011004)
文摘The purpose of this study is to set up a dynamically linked 1D and 2D hydrodynamic and sediment transport models for dam break flow.The 1D-2D coupling model solves the generalized shallow water equations,the non-equilibrium sediment transport and bed change equations in a coupled fashion using an explicit finite volume method.It considers interactions among transient flow,strong sediment transport and rapid bed change by including bed change and variable flow density in the flow continuity and momentum equations.An unstructured Quadtree rectangular grid with local refinement is used in the 2D model.The intercell flux is computed by the HLL approximate Riemann solver with shock captured capability for computing the dry-to-wet interface for all models.The effects of pressure and gravity are included in source term in this coupling model which can simplify the computation and eliminate numerical imbalance between source and flux terms.The developed model has been tested against experimental and real-life case of dam-break flow over fix bed and movable bed.The results are compared with analytical solution and measured data with good agreement.The simulation results demonstrate that the coupling model is capable of calculating the flow,erosion and deposition for dam break flows in complicated natural domains.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.10872110,10902061)
文摘A coupled one-dimensional （1-D） and two-dimensional （2-D） channel network mathematical model is proposed for flow calculations at nodes in a channel network system in this article. For the 1-D model, the finite difference method is used to discretize the Saint-Venant equations in all channels of a looped network. The Alternating Direction Implicit （ADI） method is adopted for the 2-D model at the nodes. In the coupled model, the 1-D model provides a good approximation with small computational effort, while the 2-D model is applied for complex topography to achieve a high accuracy. An Artificial Neural Network （ANN.） method is used for the data exchange and the connectivity between the 1-D and 2-D models. The coupled model is applied to the Jingjiang-Dongting Lake region, to simulate the tremendous looped channel network system, and the results are compared with field data. The good agreement shows that the coupled hydraulic model is more effective than the conventional 1-D model.
基金the programs for the postdoctoral fellowships-Chilean CONICYT-FONDECYT#3140218,Mexican CONACYT#164978 and DID-UACh S-2015-81Sistema Nacional de Investigadores#58512 to Abraham Rosas-Arellano+2 种基金supported by USACH PhD fellowshipsupported with a PhD fellowship from CONACYT(#299627)FONDECYT grants 1151206 and 1110571 to Maite A.Castro
文摘γ-Aminobutyric acid（GABA）,plays a key role in all stages of life,also is considered the main inhibitory neurotransmitter.GABA activates two kind of membrane receptors known as GABAA and GABAB,the first one is responsible to render tonic inhibition by pentameric receptors containing α4-6,β3,δ,or ρ1-3 subunits,they are located at perisynaptic and/or in extrasynaptic regions.The biophysical properties of GABAA tonic inhibition have been related with cellular protection against excitotoxic injury and cell death in presence of excessive excitation.On this basis,GABAA tonic inhibition has been proposed as a potential target for therapeutic intervention of Huntington＇s disease.Huntington＇s disease is a neurodegenerative disorder caused by a genetic mutation of the huntingtin protein.For experimental studies of Huntington＇s disease mouse models have been developed,such as R6/1,R6/2,Hdh Q92,Hdh Q150,as well as YAC128.In all of them,some key experimental reports are focused on neostriatum.The neostriatum is considered as the most important connection between cerebral cortex and basal ganglia structures,its cytology display two pathways called direct and indirect constituted by medium sized spiny neurons expressing dopamine D1 and D2 receptors respectively,they display strong expression of many types of GABAA receptors,including tonic subunits.The studies about of GABAA tonic subunits and Huntington＇s disease into the neostriatum are rising in recent years,suggesting interesting changes in their expression and localization which can be used as a strategy to delay the cellular damage caused by the imbalance between excitation and inhibition,a hallmark of Huntington＇s disease.
基金This work was financially supported by the National Key Research and Development Program of China(No.2016Y FC0905100)the CAMS Innovation Fund for Medical Sciences(No.2016-I2M-1-002)+3 种基金the National Natural Science Foundation of China(NSFCNos.81788101 and 81230015)the Beijing Municipal Science and Technology Commission(No.Z151100003915078)for Xue Zhangby the National NSFC(No.31271345)for Yaping Liu.
文摘Familial acne inversa (AI) is an autoinflammatory disorder that affects hair follicles and is caused by loss-of-function mutations in y-secretase component genes.We and other researchers showed that nicastrin (NCSTN) is the most frequently mutated gene in familial AI.In this study,we generated a keratin 5-Cre-driven epidermis-specific Ncstn conditional knockout mutant in mice.We determined that this mutant recapitulated the major phenotypes of AI,including hyperkeratosis of hair follicles and inflammation.In Ncstnflox/flox;K5-Cre mice,the IL-36a expression level markedly increased starting from postnatal day 0 (P0),and this increase occurred much earlier than those of TNF-α,IL-23A,IL-1 3,and TLR4.RNA-Seq analysis indicated that Sprr2d,a member of the small proline-rich protein 2 family,in the skin tissues of the Ncstnflox/flox,;K5-Cre mice was also upregulated on P0.Quantitative reverse-transcription polymerase chain reaction showed that other Sprr2 genes had a similar expression pattern.Our findings suggested that IL-36a might be a key inflammatory cytokine in the pathophysiology of AI and implicate malfunction of the skin barrier in the pathogenesis of AI.
