Epilepsy is a neurological disorder caused by the pathological hyper-synchronization of neuronal discharges.The fundamental research of epilepsy mechanisms and the targets of drug design options for its treatment have...Epilepsy is a neurological disorder caused by the pathological hyper-synchronization of neuronal discharges.The fundamental research of epilepsy mechanisms and the targets of drug design options for its treatment have focused on neurons.However,approximately 30%of patients suffering from epilepsy show resistance to standard anti-epileptic chemotherapeutic agents while the symptoms of the remaining 70%of patients can be alleviated but not completely removed by the current medications.Thus,new strategies for the treatment of epilepsy are in urgent demand.Over the past decades,with the increase in knowledge on the role of glia in the genesis and development of epilepsy,glial cells are receiving renewed attention.In a normal brain,glial cells maintain neuronal health and in partnership with neurons regulate virtually every aspect of brain function.In epilepsy,however,the supportive roles of glial cells are compromised,and their interaction with neurons is altered,which disrupts brain function.In this review,we will focus on the role of glia-related processes in epileptogenesis and their contribution to abnormal neuronal activity,with the major focus on the dysfunction of astroglial potassium channels,water channels,gap junctions,glutamate transporters,purinergic signaling,synaptogenesis,on the roles of microglial inflammatory cytokines,microglia-astrocyte interactions in epilepsy,and on the oligodendroglial potassium channels and myelin abnormalities in the epileptic brain.These recent findings suggest that glia should be considered as the promising next-generation targets for designing anti-epileptic drugs that may improve epilepsy and drug-resistant epilepsy.展开更多
Facility management departments’responsibilities include monitoring and maintenance of building infrastructure,such as water,gas or electricity.Very often these tasks are completed using paper maps,which make integra...Facility management departments’responsibilities include monitoring and maintenance of building infrastructure,such as water,gas or electricity.Very often these tasks are completed using paper maps,which make integrated analysis of networks challenging.Ability to consider interior network structure and provide semantic and connectivity information supporting the required analysis operations are thus crucial.This paper presents an approach relying on Building Information Model(BIM)as a data source for obtaining information about interior utilities.The semantic and connectivity information of BIM is mapped onto a new model called Network for Interior Building Utilities(NIBU).NIBU is based on the semantic categorisation of utilities,and the spatial functions that have to be performed.Three scenarios(‘maintenance operation’,‘emergency response’and‘inspection operation’)are developed to test the proposed approach.The model and its functions are implemented in spatial DBMS.The model is populated directly from a BIM server applying an Industrial Foundation Class(IFC)parser developed in-house.Five analysis functions are implemented to support spatial operations:trace upstream,trace downstream,find ancestors,find source and find disconnected.The investigation proves that BIM provides both the required semantics and attributes,and connectivity information that can facilitate analysis of interior utility networks.NIBU provides a simple yet flexible way to manage interior network information,which can be integrated into Digital Earth.展开更多
Metabotropic glutamate receptors are expressed at excitatory synapses and control synaptic transmission in mammalian brain. These receptors are involved in numerous patho-physiological functions. However, little is kn...Metabotropic glutamate receptors are expressed at excitatory synapses and control synaptic transmission in mammalian brain. These receptors are involved in numerous patho-physiological functions. However, little is known about the molecular determinants responsible for their intracellular transport and membrane targeting. Here we investigated the nature of the molecular motor and adaptor protein responsible for trafficking and membrane localization of the group I metabotropic glutamate mGlu1 postsynaptic receptor in cultured hippocampal neurons. In proteomic studies, we identified the synaptosome-associated protein 23 （SNAP23） and the molecular motor Kif5 kinesin as proteins interacting with mGlu1 receptor. We showed that SNAP23, but not Kif5, directly interacts with mGlu1 receptor carboxyl terminus. Using a recombination approach to impair or enhance the interaction between SNAP23 and KifS, we found that the SNAP23-Kif5 complex controls the trafficking of mGlu1 receptor along microtubules. Additional fluorescence recovery after cleavage experiments allowed us to identify a role of the complex in the receptor cell surface targeting. In conclusion, our study indicates that along dendritic processes Kif5-SNAP23 complex contributes to proper mGlu1 receptor trafficking and cell surface expression.展开更多
This paper describes a framework for modeling interdependencies between different network systems and building structures.It provides an approach for the integrated analysis of interior building utilities by describin...This paper describes a framework for modeling interdependencies between different network systems and building structures.It provides an approach for the integrated analysis of interior building utilities by describing a framework to model and simulate infrastructure interdependencies and their complex behaviors.It is a graph-based spatial model that can support use cases such as providing the location and specifications of interior utilities to a technician who wants to perform a maintenance operation.This location could be needed for maintenance or replacement,or to investigate the result of damage to the building structure on another utility network,or to estimate the effect of different maintenance operations in different locations along utilities service systems.The model accounts for two important aspects:first,the relationship between interior utilities and building elements or spaces and second,the building hierarchy structure to which the utilities network is related.A proper hierarchy of the building is developed which supports the generation of human-oriented descriptions of interior utilities,where a method for partitions of large building element and spaces as well as a method to reference a network element to another building are developed.The connection of the different utilities network systems and buildings are generated using joints,which are based on a containment relation.An example is presented which shows the effectiveness of this approach for supporting maintenance operations,as well as the independences between the maintenance operation location and the other network systems.The paper presents the data model and explains the links with current 3D building model standards.展开更多
According to the International Union for Conservation of Nature Red List,41%of the world’s amphibian species are threatened with extinction,making them more threatened than any other vertebrate group nowadays.Given t...According to the International Union for Conservation of Nature Red List,41%of the world’s amphibian species are threatened with extinction,making them more threatened than any other vertebrate group nowadays.Given the global amphibian crisis,comprehensive understanding of demographics and population trends of declining and threatened species is essential for effective management and conservation strategies.Counting egg spawns is widely used to assess population abundance in pond breeding anurans.However,it is unknown how such counts translate into robust population size estimations.We monitored the breeding activity of the Natterjack toad(Epidalea calamita),combining egg string counts and individual photo-identification with Capture-Mark-Recapture population size and operational sex ratio estimation.Male Natterjack toads were identified by the pattern of natural markings with repeated ID of the same individual confirmed for 10%of the samples using genetic fingerprinting.We identified 647 unique individuals within a closed study population at Caherdaniel,Co Kerry.Population estimates derived from egg string counts estimated a breeding population of 368 females(95%CI 353–384)and Capture-Mark-Recapture estimated a breeding population of 1698 males(95%CI 1000–2397).The female:male sex ratio was conservatively estimated at 1:5(95%CI 1:3–1:6)where 62%±6%of females were assumed to spawn.These substantially departed from any priori assumption of 1:1 which could have underestimated the breeding population by up to 72%.Where amphibian absolute population size estimation is necessary,methods should include empirical survey data on operational sex ratios and not rely on assumptions or those derived from the literature which may be highly population and/or context-dependent.展开更多
基金supported by the Ministry of Education,Science and Technological Development of Republic of Serbia,Nos.451-03-68/2022-14/200007 and 451-03-68/2022-14/200053(to LN and JBP),Grants from European Commission(H2020 MSCA-ITN EU-GliaPhD No.72205)(to PN)Agence Nationale de la Recherche,Nos.ANR-19-CE16-0018-03 and ANR-20CE16-0003-02(to PN)+1 种基金Grants from Science and Technology Department of Zhejiang Province,China,No.2021RC051(to WS)Scientific Research Foundation for Returned Scholars of Hangzhou City,China,No.2019(to WS).
文摘Epilepsy is a neurological disorder caused by the pathological hyper-synchronization of neuronal discharges.The fundamental research of epilepsy mechanisms and the targets of drug design options for its treatment have focused on neurons.However,approximately 30%of patients suffering from epilepsy show resistance to standard anti-epileptic chemotherapeutic agents while the symptoms of the remaining 70%of patients can be alleviated but not completely removed by the current medications.Thus,new strategies for the treatment of epilepsy are in urgent demand.Over the past decades,with the increase in knowledge on the role of glia in the genesis and development of epilepsy,glial cells are receiving renewed attention.In a normal brain,glial cells maintain neuronal health and in partnership with neurons regulate virtually every aspect of brain function.In epilepsy,however,the supportive roles of glial cells are compromised,and their interaction with neurons is altered,which disrupts brain function.In this review,we will focus on the role of glia-related processes in epileptogenesis and their contribution to abnormal neuronal activity,with the major focus on the dysfunction of astroglial potassium channels,water channels,gap junctions,glutamate transporters,purinergic signaling,synaptogenesis,on the roles of microglial inflammatory cytokines,microglia-astrocyte interactions in epilepsy,and on the oligodendroglial potassium channels and myelin abnormalities in the epileptic brain.These recent findings suggest that glia should be considered as the promising next-generation targets for designing anti-epileptic drugs that may improve epilepsy and drug-resistant epilepsy.
文摘Facility management departments’responsibilities include monitoring and maintenance of building infrastructure,such as water,gas or electricity.Very often these tasks are completed using paper maps,which make integrated analysis of networks challenging.Ability to consider interior network structure and provide semantic and connectivity information supporting the required analysis operations are thus crucial.This paper presents an approach relying on Building Information Model(BIM)as a data source for obtaining information about interior utilities.The semantic and connectivity information of BIM is mapped onto a new model called Network for Interior Building Utilities(NIBU).NIBU is based on the semantic categorisation of utilities,and the spatial functions that have to be performed.Three scenarios(‘maintenance operation’,‘emergency response’and‘inspection operation’)are developed to test the proposed approach.The model and its functions are implemented in spatial DBMS.The model is populated directly from a BIM server applying an Industrial Foundation Class(IFC)parser developed in-house.Five analysis functions are implemented to support spatial operations:trace upstream,trace downstream,find ancestors,find source and find disconnected.The investigation proves that BIM provides both the required semantics and attributes,and connectivity information that can facilitate analysis of interior utility networks.NIBU provides a simple yet flexible way to manage interior network information,which can be integrated into Digital Earth.
文摘Metabotropic glutamate receptors are expressed at excitatory synapses and control synaptic transmission in mammalian brain. These receptors are involved in numerous patho-physiological functions. However, little is known about the molecular determinants responsible for their intracellular transport and membrane targeting. Here we investigated the nature of the molecular motor and adaptor protein responsible for trafficking and membrane localization of the group I metabotropic glutamate mGlu1 postsynaptic receptor in cultured hippocampal neurons. In proteomic studies, we identified the synaptosome-associated protein 23 （SNAP23） and the molecular motor Kif5 kinesin as proteins interacting with mGlu1 receptor. We showed that SNAP23, but not Kif5, directly interacts with mGlu1 receptor carboxyl terminus. Using a recombination approach to impair or enhance the interaction between SNAP23 and KifS, we found that the SNAP23-Kif5 complex controls the trafficking of mGlu1 receptor along microtubules. Additional fluorescence recovery after cleavage experiments allowed us to identify a role of the complex in the receptor cell surface targeting. In conclusion, our study indicates that along dendritic processes Kif5-SNAP23 complex contributes to proper mGlu1 receptor trafficking and cell surface expression.
基金the German Academic Exchange Service (DAAD) under the Program:Research Grants for Doctoral Candidates and Young Academics and Scientists
文摘This paper describes a framework for modeling interdependencies between different network systems and building structures.It provides an approach for the integrated analysis of interior building utilities by describing a framework to model and simulate infrastructure interdependencies and their complex behaviors.It is a graph-based spatial model that can support use cases such as providing the location and specifications of interior utilities to a technician who wants to perform a maintenance operation.This location could be needed for maintenance or replacement,or to investigate the result of damage to the building structure on another utility network,or to estimate the effect of different maintenance operations in different locations along utilities service systems.The model accounts for two important aspects:first,the relationship between interior utilities and building elements or spaces and second,the building hierarchy structure to which the utilities network is related.A proper hierarchy of the building is developed which supports the generation of human-oriented descriptions of interior utilities,where a method for partitions of large building element and spaces as well as a method to reference a network element to another building are developed.The connection of the different utilities network systems and buildings are generated using joints,which are based on a containment relation.An example is presented which shows the effectiveness of this approach for supporting maintenance operations,as well as the independences between the maintenance operation location and the other network systems.The paper presents the data model and explains the links with current 3D building model standards.
基金This study was part of a larger monitoring and surveillance project commissioned and funded by the National Parks and Wildlife Service(NPWS)Department of Culture,Heritage and the Gaeltacht(CHG)Republic of Ireland.Natterjack toads were collected under Government license(No.C098/2016).
文摘According to the International Union for Conservation of Nature Red List,41%of the world’s amphibian species are threatened with extinction,making them more threatened than any other vertebrate group nowadays.Given the global amphibian crisis,comprehensive understanding of demographics and population trends of declining and threatened species is essential for effective management and conservation strategies.Counting egg spawns is widely used to assess population abundance in pond breeding anurans.However,it is unknown how such counts translate into robust population size estimations.We monitored the breeding activity of the Natterjack toad(Epidalea calamita),combining egg string counts and individual photo-identification with Capture-Mark-Recapture population size and operational sex ratio estimation.Male Natterjack toads were identified by the pattern of natural markings with repeated ID of the same individual confirmed for 10%of the samples using genetic fingerprinting.We identified 647 unique individuals within a closed study population at Caherdaniel,Co Kerry.Population estimates derived from egg string counts estimated a breeding population of 368 females(95%CI 353–384)and Capture-Mark-Recapture estimated a breeding population of 1698 males(95%CI 1000–2397).The female:male sex ratio was conservatively estimated at 1:5(95%CI 1:3–1:6)where 62%±6%of females were assumed to spawn.These substantially departed from any priori assumption of 1:1 which could have underestimated the breeding population by up to 72%.Where amphibian absolute population size estimation is necessary,methods should include empirical survey data on operational sex ratios and not rely on assumptions or those derived from the literature which may be highly population and/or context-dependent.
