BACKGROUND： Previous studies have demonstrated that mutant amyloid precursor protein （APP） or presenilin-1 （PS1） genes increase susceptibility to ischemic brain damage induced by middle cerebral artery occlusion....BACKGROUND： Previous studies have demonstrated that mutant amyloid precursor protein （APP） or presenilin-1 （PS1） genes increase susceptibility to ischemic brain damage induced by middle cerebral artery occlusion. Possible mechanisms include over-production of beta-amyloid peptide （Aβ）. OBJECTIVE： Because Aβ is over-produced in the APP/PS1 double-transgenic mouse, the present study focused on mechanisms of increased ischemic damage due to mutant APP and PS1 genes by measuring oxidative stress, mitochondrial function, and calcium homeostasis. DESIGN, TIME AND SETTING： The non-randomized, controlled, in vivo and in vitro experiments were performed at the Medical Research Center, Second Clinical College, Jinan University between May and October 2008. MATERIALS： Male APP transgenic mice carrying the mutant 695swe gene and female PS1 transgenic mice carrying the mutant Leu235Pro gene were donated from the University of Hong Kong. SHSY5Y human neureblastoma cells were purchased from ATCC （Manassas, VA, USA）, and Aβ1-42 was obtained from Sigma-Aldrich （St. Louis, MO, USA）. METHODS： APP transgenic mice were mated with PS1 transgenic mice to produce APP/PS1 double-transgenic mice and wildtype littermates mice. The photothrombotic stroke model was induced in six APP/PS1 double-transgenic and 6 wildtype littermates mice. SHSY5Y human neuroblastoma cells were cultured in vitro, and were divided into 4 groups： Aβ group, cells were exposed to 5 pmol/L Aβ for 24 hours; oxygen-glucose deprivation （OGD） group, cells were exposed to OGD for 1 hour after treatment with sterile, ultra-pure water for 24 hours; OGD＋Aβ group, cells were exposed to OGD and Aβfor 1 hour after treatment with 5 pmol/L Aβ for 24 hours; sham control group： cells were exposed to sterile, ultra-pure water for 25 hours. OGD was achieved by exposing the cells to glucose-free DMEM and placing the cells in an anaerobic chamber flushed with 5% CO2 and 95% N2 （v/v） at 37 ℃ for 1 hour. MAIN OUTCOME MEASURES： TTC staining was used to measure infarct volume 7 days after photothrombotic stroke. Cell viability was evaluated using the MTT kit. Opening of the mitochondrial permeability transition pore, intracellular concentration of superoxide anion, and calcium after OGD were detected with fluorescence intensity of calcein-AM, hydroethidine, and fluo-3/AM. RESULTS： At 7 days after stroke, total infarct volume and cortical infarct volume were significantly greater in the APP/PS1 transgenic mice compared with the wildtype littermates mice （P 〈 0.01）. Aβ, OGD, and Aβ ＋ OGD significantly decreased cell viability and increased fluorescence intensity of hydroethidine and fluo-3/AM （P 〈 0.01）. Compared with the Aβ or OGD group, Aβ ＋ OGD significantly decreased cell viability （P 〈 0.01） and significantly increased fluorescence intensity of calcein-AM, hydroethidine, and fluo-3/AM （P 〈 0.01 or P 〈 0.05）. CONCLUSION： The APP/PS1 double-transgenic mice were more vulnerable to ischemia. The possible mechanisms included enhanced opening of the mitochondrial permeability transition pore, overproduction of superoxide anion due to pore opening, and disturbed calcium homeostasis induced by excess superoxide anion.展开更多
The determinants of local differences in species and functions matter for reservoir management but have seldom been investigated.To this aim,we explored fish taxonomic,and functional beta diversity between local assem...The determinants of local differences in species and functions matter for reservoir management but have seldom been investigated.To this aim,we explored fish taxonomic,and functional beta diversity between local assem-blages in a large Chinese reservoir.Taxonomicβdiversity was primarily driven by species richness differences(54%–72%),while functionalβdiversity was almost equally driven by turnover and nestedness components.Environmental characteristics of the sites were significant predictors of all facets of fishβdiversity.Additionally,site contributions to taxonomic(LCBD)and functional(XLCBD)βdiversity were significantly associated with human activity variables,suggesting that there is a pressing need to mitigate human-induced disturbances for the conservation of biodiversity.Species contributions to taxonomic(SCBD)and functional(XSCBD)βdiversity exhibited positive correlations primarily with species occupancy and abundance,suggesting the potential uniqueness of certain common species.Priority conservation areas in the upstream area and rare but key species such as Tachysurus and Siniperca were identified based on site and species contributions.We thus propose to focus on habitat restoration actions to upstream areas by restricting sand mining,as the current mining activities in the river channel can directly alter riverbed morphology and damage the spawning grounds of fish.We also emphasize the necessity for increased conservation efforts through the development of sustainable recreational fishing policies and stock recovery programs for sensitive species such as Pelteobagrus vachelli and Acheilognathus macropterus.These species have lower SCBD or XLCBD values than others and possess unique feeding habits or high economic value,making them primary targets for recreational fishing.This research highlights the impor-tance of integrating taxonomic and functionalβdiversity to effectively evaluate biodiversity changes and develop more comprehensive and sustainable conservation strategies for fish diversity conservation.展开更多
基金Supported by: Shenzhen Science Technology Project from Shenzhen Bureau of Science Technology and Information, No. 200702029Medicial Science Technology Research Fund of Guangdong Province, No. A2008601 & A2007570
文摘BACKGROUND： Previous studies have demonstrated that mutant amyloid precursor protein （APP） or presenilin-1 （PS1） genes increase susceptibility to ischemic brain damage induced by middle cerebral artery occlusion. Possible mechanisms include over-production of beta-amyloid peptide （Aβ）. OBJECTIVE： Because Aβ is over-produced in the APP/PS1 double-transgenic mouse, the present study focused on mechanisms of increased ischemic damage due to mutant APP and PS1 genes by measuring oxidative stress, mitochondrial function, and calcium homeostasis. DESIGN, TIME AND SETTING： The non-randomized, controlled, in vivo and in vitro experiments were performed at the Medical Research Center, Second Clinical College, Jinan University between May and October 2008. MATERIALS： Male APP transgenic mice carrying the mutant 695swe gene and female PS1 transgenic mice carrying the mutant Leu235Pro gene were donated from the University of Hong Kong. SHSY5Y human neureblastoma cells were purchased from ATCC （Manassas, VA, USA）, and Aβ1-42 was obtained from Sigma-Aldrich （St. Louis, MO, USA）. METHODS： APP transgenic mice were mated with PS1 transgenic mice to produce APP/PS1 double-transgenic mice and wildtype littermates mice. The photothrombotic stroke model was induced in six APP/PS1 double-transgenic and 6 wildtype littermates mice. SHSY5Y human neuroblastoma cells were cultured in vitro, and were divided into 4 groups： Aβ group, cells were exposed to 5 pmol/L Aβ for 24 hours; oxygen-glucose deprivation （OGD） group, cells were exposed to OGD for 1 hour after treatment with sterile, ultra-pure water for 24 hours; OGD＋Aβ group, cells were exposed to OGD and Aβfor 1 hour after treatment with 5 pmol/L Aβ for 24 hours; sham control group： cells were exposed to sterile, ultra-pure water for 25 hours. OGD was achieved by exposing the cells to glucose-free DMEM and placing the cells in an anaerobic chamber flushed with 5% CO2 and 95% N2 （v/v） at 37 ℃ for 1 hour. MAIN OUTCOME MEASURES： TTC staining was used to measure infarct volume 7 days after photothrombotic stroke. Cell viability was evaluated using the MTT kit. Opening of the mitochondrial permeability transition pore, intracellular concentration of superoxide anion, and calcium after OGD were detected with fluorescence intensity of calcein-AM, hydroethidine, and fluo-3/AM. RESULTS： At 7 days after stroke, total infarct volume and cortical infarct volume were significantly greater in the APP/PS1 transgenic mice compared with the wildtype littermates mice （P 〈 0.01）. Aβ, OGD, and Aβ ＋ OGD significantly decreased cell viability and increased fluorescence intensity of hydroethidine and fluo-3/AM （P 〈 0.01）. Compared with the Aβ or OGD group, Aβ ＋ OGD significantly decreased cell viability （P 〈 0.01） and significantly increased fluorescence intensity of calcein-AM, hydroethidine, and fluo-3/AM （P 〈 0.01 or P 〈 0.05）. CONCLUSION： The APP/PS1 double-transgenic mice were more vulnerable to ischemia. The possible mechanisms included enhanced opening of the mitochondrial permeability transition pore, overproduction of superoxide anion due to pore opening, and disturbed calcium homeostasis induced by excess superoxide anion.
基金supported by the China Agriculture Research System of MOF and MARA(CARS-46)the Central Public-interest Scientific Institution Basal Research Fund,CAFS(grant 2023TD61,YFI20240102 and YFI202418)the Key Research and Development Program of Jiangxi Province,China(grant 20223BBF61010).
文摘The determinants of local differences in species and functions matter for reservoir management but have seldom been investigated.To this aim,we explored fish taxonomic,and functional beta diversity between local assem-blages in a large Chinese reservoir.Taxonomicβdiversity was primarily driven by species richness differences(54%–72%),while functionalβdiversity was almost equally driven by turnover and nestedness components.Environmental characteristics of the sites were significant predictors of all facets of fishβdiversity.Additionally,site contributions to taxonomic(LCBD)and functional(XLCBD)βdiversity were significantly associated with human activity variables,suggesting that there is a pressing need to mitigate human-induced disturbances for the conservation of biodiversity.Species contributions to taxonomic(SCBD)and functional(XSCBD)βdiversity exhibited positive correlations primarily with species occupancy and abundance,suggesting the potential uniqueness of certain common species.Priority conservation areas in the upstream area and rare but key species such as Tachysurus and Siniperca were identified based on site and species contributions.We thus propose to focus on habitat restoration actions to upstream areas by restricting sand mining,as the current mining activities in the river channel can directly alter riverbed morphology and damage the spawning grounds of fish.We also emphasize the necessity for increased conservation efforts through the development of sustainable recreational fishing policies and stock recovery programs for sensitive species such as Pelteobagrus vachelli and Acheilognathus macropterus.These species have lower SCBD or XLCBD values than others and possess unique feeding habits or high economic value,making them primary targets for recreational fishing.This research highlights the impor-tance of integrating taxonomic and functionalβdiversity to effectively evaluate biodiversity changes and develop more comprehensive and sustainable conservation strategies for fish diversity conservation.
