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
Introduction:Astrocytes play important roles in the central nervous system(CNS)to support and regulate CNS function.They are abundant type of glia that form a meshwork of interconnected cells almost completely tiling ...Introduction:Astrocytes play important roles in the central nervous system(CNS)to support and regulate CNS function.They are abundant type of glia that form a meshwork of interconnected cells almost completely tiling the CNS.Each astrocyte extends densely ramified processes that establish close contacts and interaction with other astrocytes,neurons and blood vessels,placing these cells in an ideal position to control extracellular milieu and to exert global effects on CNS physiology.展开更多
Studying the membrane physiology of filamentous fungi is key to understanding their interactions with the environment and crucial for developing new therapeutic strategies for disease-causing pathogens.However,their p...Studying the membrane physiology of filamentous fungi is key to understanding their interactions with the environment and crucial for developing new therapeutic strategies for disease-causing pathogens.However,their plasma membrane has been inaccessible for a micron-sized patch-clamp pipette for pA current recordings due to the rigid chitinous cell wall.Here,we report the first femtosecond IR laser nanosurgery of the cell wall of the filamentous fungi,which enabled patch-clamp measurements on protoplasts released from hyphae.A reproducible and highly precise(diffraction-limited,submicron resolution)method for obtaining viable released protoplasts was developed.Protoplast release from the nanosurgery-generated incisions in the cell wall was achieved from different regions of the hyphae.The plasma membrane of the obtained protoplasts formed tight and high-resistance(GΩ)contacts with the recording pipette.The entire nanosurgical procedure followed by the patch-clamp technique could be completed in less than 1 hour.Compared to previous studies using heterologously expressed channels,this technique provides the opportunity to identify new ionic currents and to study the properties of the ion channels in the protoplasts of filamentous fungi in their native environment.展开更多
Schreiber’s bent-winged bat Miniopterus schreibersii and the greater horseshoe bat Rhinolophus ferrumequinum are widespread and common cavernicolous species across southern Europe that host numerous specialized ectop...Schreiber’s bent-winged bat Miniopterus schreibersii and the greater horseshoe bat Rhinolophus ferrumequinum are widespread and common cavernicolous species across southern Europe that host numerous specialized ectoparasite species.The objective of this study was to characterize the species assemblage,genetic diversity,and host specificity of bat flies(Nycteribiidae,Diptera)and wing mites(Spinturnicidae,Acari)found on these bat hosts in Serbia and Bosnia and Herzegovina.Notably,while bat flies lay puparia on the cave walls and can thus be transmitted indirectly,wing mites require direct body contact for transmission.Morphological identification and sequencing of a 710-bp fragment of cytochrome oxidase I gene of 207 bat flies yielded 4 species,3 on M.schreibersii and 1 on R.ferrumequinum.Sequencing of a 460-bp small subunit ribosomal RNA fragment,in all 190 collected wing mites revealed 2 species,1 per host.In no case was a parasite associated with 1 host found on the other host.Species and genetic diversity of flies were higher in M.schreibersii,likely reflecting their host’s larger colony sizes and migratory potential.Mite species of both hosts showed similarly low diversity,likely due to their faster life history and lower winter survival.Our findings highlight a remarkably high host-specificity and segregation of ectoparasite species despite direct contact among their hosts in the roost,suggesting a defined host preference in the investigated ectoparasite species.Furthermore,the differences in ectoparasite genetic diversity exemplify the interplay between host and parasite life histories in shaping parasite population genetic structure.展开更多
Piliostigma thonningii (Fabaceae) is a versatile medicinal plant used as a traditional remedy,especially in African countries.In the present study,ethyl acetate,methanolic and water extracts of different parts of (fru...Piliostigma thonningii (Fabaceae) is a versatile medicinal plant used as a traditional remedy,especially in African countries.In the present study,ethyl acetate,methanolic and water extracts of different parts of (fruits,leaves,stem barks) P.thonningii were evaluated for their bioactive contents,enzyme inhibitory,antioxidant and antimicrobial activities.Antioxidant potentials were also displayed in various methods like phosphomolybdenum assay (0.79–5.94 mmol TE/g),radical scavenging assays (DPPH:20.39–471.28 mg TE/g;ABTS:42.43–654.14 mg TE/g);reducing assays (CUPRAC:102.98–1207.42 mg TE/g;FRAP:45.30–656.25 mg TE/g) and metal chelating activity (2.55–22.32 mg EDTAE/g).In particular,the methanolic and water extracts showed better antioxidant potential.Except for a few,the extracts were also found to act as inhibitors of enzymes such as acetylcholinesterase (2.35–5.35 mg GALAE/g),butyrylcholinesterase (0.83–13.80 mg GALAE/g),tyrosinase (4.03–143.86 mg KAE/g),amylase (0.21–1.39 mmol ACAE/g) and glucosidase (3.52–7.13 mmol ACAE/g).Additionally,all the tested extracts possessed significant antibacterial (minimum inhibitory concentration (MIC) and minimum bactericidal concentration:0.11–0.61 mg/ml) and antifungal (MIC and minimum fungicidal concentration:0.04–0.61 mg/ml) effects.Indeed,the data garnered from the present study provides a bright scope for the advanced investigation on this particular plant possessing pharmacologically active traits.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.
基金supported by the Ministry of Education,Science and Technological Development of Republic of Serbia (Contract No. 451-03-68/2020-14/200007 (to LN), 451-03-68/2020-14/200053)(to JBP)a Fellowship Start up for Science from the Centre for Leadership Development (to LN)
文摘Introduction:Astrocytes play important roles in the central nervous system(CNS)to support and regulate CNS function.They are abundant type of glia that form a meshwork of interconnected cells almost completely tiling the CNS.Each astrocyte extends densely ramified processes that establish close contacts and interaction with other astrocytes,neurons and blood vessels,placing these cells in an ideal position to control extracellular milieu and to exert global effects on CNS physiology.
基金supported by the Ministry of Science,Technological Development and Innovations,Republic of Serbia[contract numbers:451-03-47/2023-01/200178 and 451-03-47/2023-01/200007]the Project Advanced Biophysical Methods for Soil Targeted Fungi-Based Biocontrol Agents-BioPhysFUN[Grant number 4545]from the Program DEVELOPMENT-Green program of cooperation between science and industry,Science Fund of the Republic of Serbia+1 种基金the Project HEMMAGINERO[Grant number 6066079]from the Program PROMIS,Science Fund of the Republic of Serbiaand the Institute of Physics Belgrade through grants from the Ministry of Science,Technological Development and Innovations of the Republic of Serbia.
文摘Studying the membrane physiology of filamentous fungi is key to understanding their interactions with the environment and crucial for developing new therapeutic strategies for disease-causing pathogens.However,their plasma membrane has been inaccessible for a micron-sized patch-clamp pipette for pA current recordings due to the rigid chitinous cell wall.Here,we report the first femtosecond IR laser nanosurgery of the cell wall of the filamentous fungi,which enabled patch-clamp measurements on protoplasts released from hyphae.A reproducible and highly precise(diffraction-limited,submicron resolution)method for obtaining viable released protoplasts was developed.Protoplast release from the nanosurgery-generated incisions in the cell wall was achieved from different regions of the hyphae.The plasma membrane of the obtained protoplasts formed tight and high-resistance(GΩ)contacts with the recording pipette.The entire nanosurgical procedure followed by the patch-clamp technique could be completed in less than 1 hour.Compared to previous studies using heterologously expressed channels,this technique provides the opportunity to identify new ionic currents and to study the properties of the ion channels in the protoplasts of filamentous fungi in their native environment.
基金Ministry of Education,Science and Technological Development of Republic of Serbia,contract no.451-03-9/2021-14/200007.B.P.was supported by a Deutscher Akademischer Austauschdienst(DAAD)grant which covered living expenses while doing a part of experimental work in Greifswald,Germany。
文摘Schreiber’s bent-winged bat Miniopterus schreibersii and the greater horseshoe bat Rhinolophus ferrumequinum are widespread and common cavernicolous species across southern Europe that host numerous specialized ectoparasite species.The objective of this study was to characterize the species assemblage,genetic diversity,and host specificity of bat flies(Nycteribiidae,Diptera)and wing mites(Spinturnicidae,Acari)found on these bat hosts in Serbia and Bosnia and Herzegovina.Notably,while bat flies lay puparia on the cave walls and can thus be transmitted indirectly,wing mites require direct body contact for transmission.Morphological identification and sequencing of a 710-bp fragment of cytochrome oxidase I gene of 207 bat flies yielded 4 species,3 on M.schreibersii and 1 on R.ferrumequinum.Sequencing of a 460-bp small subunit ribosomal RNA fragment,in all 190 collected wing mites revealed 2 species,1 per host.In no case was a parasite associated with 1 host found on the other host.Species and genetic diversity of flies were higher in M.schreibersii,likely reflecting their host’s larger colony sizes and migratory potential.Mite species of both hosts showed similarly low diversity,likely due to their faster life history and lower winter survival.Our findings highlight a remarkably high host-specificity and segregation of ectoparasite species despite direct contact among their hosts in the roost,suggesting a defined host preference in the investigated ectoparasite species.Furthermore,the differences in ectoparasite genetic diversity exemplify the interplay between host and parasite life histories in shaping parasite population genetic structure.
文摘Piliostigma thonningii (Fabaceae) is a versatile medicinal plant used as a traditional remedy,especially in African countries.In the present study,ethyl acetate,methanolic and water extracts of different parts of (fruits,leaves,stem barks) P.thonningii were evaluated for their bioactive contents,enzyme inhibitory,antioxidant and antimicrobial activities.Antioxidant potentials were also displayed in various methods like phosphomolybdenum assay (0.79–5.94 mmol TE/g),radical scavenging assays (DPPH:20.39–471.28 mg TE/g;ABTS:42.43–654.14 mg TE/g);reducing assays (CUPRAC:102.98–1207.42 mg TE/g;FRAP:45.30–656.25 mg TE/g) and metal chelating activity (2.55–22.32 mg EDTAE/g).In particular,the methanolic and water extracts showed better antioxidant potential.Except for a few,the extracts were also found to act as inhibitors of enzymes such as acetylcholinesterase (2.35–5.35 mg GALAE/g),butyrylcholinesterase (0.83–13.80 mg GALAE/g),tyrosinase (4.03–143.86 mg KAE/g),amylase (0.21–1.39 mmol ACAE/g) and glucosidase (3.52–7.13 mmol ACAE/g).Additionally,all the tested extracts possessed significant antibacterial (minimum inhibitory concentration (MIC) and minimum bactericidal concentration:0.11–0.61 mg/ml) and antifungal (MIC and minimum fungicidal concentration:0.04–0.61 mg/ml) effects.Indeed,the data garnered from the present study provides a bright scope for the advanced investigation on this particular plant possessing pharmacologically active traits.