Neural stem cells （NSCs） are present not only during the embryonic development but also in the adult brain of all mammalian species, including humans. Stem cell niche architecture in vivo enables adult NSCs to conti...Neural stem cells （NSCs） are present not only during the embryonic development but also in the adult brain of all mammalian species, including humans. Stem cell niche architecture in vivo enables adult NSCs to continuously generate functional neurons in specific brain regions throughout life. The adult neurogenesis process is subject to dynamic regulation by various physiological, pathological and pharmacological stimuli. Multipotent adult NSCs also appear to be intrinsically plastic, amenable to genetic programing during normal differentiation, and to epigenetic reprograming during de-differentiation into pluripotency. Increasing evidence suggests that adult NSCs significantly contribute to specialized neural functions under physiological and pathological conditions. Fully understanding the biology of adult NSCs will provide crucial insights into both the etiology and potential therapeutic interventions of major brain disorders. Here, we review recent progress on adult NSCs of the mammalian central nervous system, including topics on their identity, niche, function, plasticity, and emerging roles in cancer and regenerative medicine.展开更多
The data of field surveys during 2009 to 2018 was analyzed to understand the seasonality and inter-annual variability of the floating Ulva and Sargassum in the Subei Shoal,the southwestern Yellow Sea of China on decad...The data of field surveys during 2009 to 2018 was analyzed to understand the seasonality and inter-annual variability of the floating Ulva and Sargassum in the Subei Shoal,the southwestern Yellow Sea of China on decadal scale.The floating Ulva biomass was consistently originated from the central region of the Subei Shoal in middle to late April,increased rapidly,drifted and extended into the offshore water in May and June.The average floating Ulva biomass in the shoal generally increased over the years with evident inter-annual fluctuations.In contrast,pelagic Sargassum was accumulated in the Subei Shoal and formed the spring bloom only in 2013,2017 and 2018,and the biomass was higher than the co-occurring Ulva during the survey in these three years.Compared to the raft-origin floating Ulva,genesis and development of the pelagic Sargassum was distinct.Based on the current research,the Sargassum biomass was exotic and often initiated in the offshore water in March,and intruded into the shoal in April and May.The analysis on the environmental parameters was inconclusive since multiple anthropogenic and non-indigenous factors could influence the green tides in this region.Further research covering both the East China Sea and the Yellow Sea is needed to trace the origin of the floating Sargassum and to understand the interactions between these two co-occurring seaweeds.展开更多
To solve the mapping problem for the mobile robots in the unknown environment, a dynamic growing self-organizing map with growing-threshold tuning automatically algorithm (DGSOMGT) based on Self-organizing Map is prop...To solve the mapping problem for the mobile robots in the unknown environment, a dynamic growing self-organizing map with growing-threshold tuning automatically algorithm (DGSOMGT) based on Self-organizing Map is proposed. It introduces a value of spread factor to describe the changing process of the growing threshold dynamically. The method realizes the network structure growing by training through mobile robot movement constantly in the unknown environment. The proposed algorithm is based on self-organizing map and can adjust the growing-threshold value by the number of network neurons increasing. It avoids tuning the parameters repeatedly by human. The experimental results show that the proposed method detects the complex environment quickly, effectively and correctly. The robot can realize environment mapping automatically. Compared with the other methods the proposed mapping strategy has better topological properties and time property.展开更多
Taxonomic sufficiency(TS)refers to identifying taxa to a taxonomic level sufficient to detect community changes in stressed environments and may provide a cost-effective approach in routine monitoring programs.However...Taxonomic sufficiency(TS)refers to identifying taxa to a taxonomic level sufficient to detect community changes in stressed environments and may provide a cost-effective approach in routine monitoring programs.However,there is still limited information regarding the seasonal impact of applying TS and its implications for the ecological quality evaluation in the estuarine ecosystem.This study investigated the relationship between the multivariate-AZTI’s Marine Biotic Index(M-AMBI)and environmental variables in three seasons(i.e.,spring,summer,and autumn)in the Liaohe River Estuary.We tested the reliability of TS for simplifying the M-AMBI methodology.The results showed that family and genus level data could reproduce the spatial-temporal patterns of community structure at the species level.The M-AMBI values showed a consistent spatial distribution pattern in all sampling seasons,with a decreasing trend with the increasing distance from the estuary mouth.Both genus and family level data performed nearly as well as species level in detecting the seasonal variations of pollutants(i.e.,nutrients and total organic content).The family level M-AMBI was feasible to discern stress in the Liaohe River Estuary because of the high aggregation ratios at different taxonomic levels in all sampling seasons.These findings suggest that applying taxonomic sufficiency based on the M-AMBI provides an efficient approach for evaluating ecological quality in the Liaohe River Estuary.展开更多
The dielectrophoretic gate and sorter system has been widely applied for preconcentrating and sorting of bioparticles for biodetection. In such systems, the dielectrophoretic force is generated by applying an AC elect...The dielectrophoretic gate and sorter system has been widely applied for preconcentrating and sorting of bioparticles for biodetection. In such systems, the dielectrophoretic force is generated by applying an AC electric field on the three dimensional electrode systems (containing a pair of electrodes on the top and bottom of the channel). Particles are held and sorted by balancing the DEP force with the hydrodynamic drag force. The holding capability is very important for such systems because it determines the preconcentration and sorting efficiency. In this paper, we investigate the holding capability of a simple dielectrophoretic gate system. Initially, a three dimensional numerical scheme was introduced to estimate the holding capability and was further validated by comparing with experimental results. Second, we systematically investigated the effects of the phase difference between the top and bottom electrodes;the height and width of the channel, and the relative position and size of top and bottom electrodes. The results demonstrated that the maximum holding capability is reached when the phase difference between the top and bottom electrodes is around 180o. The results also show that the holding capability varied with the size and relative position of electrodes on the top and bottom, and the maximum holding capability is obtained when the top and bottom electrodes had the same size and the centers of both electrodes overlapped.展开更多
The adult subventricular zone of the lateral ventricles and the subgranular zone in the hippocampal dentate gyrus(DG)are the two brain regions where neurogenesis occurs throughout life in the adult mammalian brain(Min...The adult subventricular zone of the lateral ventricles and the subgranular zone in the hippocampal dentate gyrus(DG)are the two brain regions where neurogenesis occurs throughout life in the adult mammalian brain(Ming and Song,2011).Adult quiescent hippocampal neural stem cells(NSCs)are bona fide stem cells and,when activated,give rise to newborn granule neurons in the adult brain,which play vital roles in learning,memory,mood,and affective cognition(Bonaguidi et al.,2011;Ming and Song,2011).展开更多
Neurogenesis persists in two locations of the adult mammalian brain, the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus in the hippocampus. In the adult subgranular zone, r...Neurogenesis persists in two locations of the adult mammalian brain, the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus in the hippocampus. In the adult subgranular zone, radial glial- like cells （RGLs） are multipotent stem cells that can give rise to both astrocytes and neurons. In the process of generating neurons, RGLs divide asymmetrically to give rise to one RGL and one intermediate progenitor cell （IPC）. IPCs are considered to be a population of transit amplifying cells that proliferate and eventually give rise to mature granule neurons. The properties of individual IPCs at the clonai level are not well understood. Furthermore, it is not clear whether IPCs can generate astrocytes or revert back to RGLs, besides generating neurons. Here we developed a genetic marking strategy for clonal analysis and lineage-tracing of individual Tbr2-expressing IPCs in the adult hippocampus in vivo using Tbr2-CreERT2 mice. Using this technique we identified Tbr2-CreERT2 labeled IPCs as unipotent neuronal precursors that do not generate astrocytes or RGLs under homeostasis. Additionally, we showed that these labeled IPCs rapidly generate immature neurons in a synchronous manner and do not undergo a significant amount of amplification under homeostasis, in animals subjected to an enriched environment/running, or in animals with different age. In summary, our study suggests that Tbr2-expressing IPCs in the adult mouse hippocampus are unipotent precursors and rapidly give rise to immature neurons without major amplification.展开更多
Mounting evidence points to critical roles for DNA modifications, including 5-methylcytosine （5mC） and its oxidized forms, in the development, plasticity and disorders of the mammalian nervous system. The novel DNA ...Mounting evidence points to critical roles for DNA modifications, including 5-methylcytosine （5mC） and its oxidized forms, in the development, plasticity and disorders of the mammalian nervous system. The novel DNA base 5- hydroxymethylcytosine （5hmC） is known to be capable of initiating passive or active DNA demethylation, but whether and how extensively 5hmC functions in shaping the post-mitotic neuronal DNA methylome is unclear. Here we report the genome-wide distribution of 5hmC in dentate granule neurons from adult mouse hippocampus in vivo. 5hmC in the neuronal genome is highly enriched in gene bodies, especially in exons, and correlates with gene expression. Direct genome-wide comparison of 5hmC distribution between embryonic stem cells and neurons reveals extensive differences, reflecting the functional disparity between these two cell types. Importantly, integrative analysis of 5hmC, overall DNA methylation and gene expression profiles of dentate granule neurons in vivo reveals the genome-wide antagonism between these two states of cytosine modifications, supporting a role for 5hmC in shaping the neuronal DNA methylome by promoting active DNA demethylation.展开更多
Epigenetic regulation via chromatin modulation plays pivotal roles in regulating neural stem cells(NSCs)both during embryonic development and in adult neurogenesis(Yao et al.,2016).One classic epigenetic mechanism is ...Epigenetic regulation via chromatin modulation plays pivotal roles in regulating neural stem cells(NSCs)both during embryonic development and in adult neurogenesis(Yao et al.,2016).One classic epigenetic mechanism is covalent post-translational modifications to histone proteins,including methylation,phosphorylation,acetylation,ubiquitination,and sumoylation.In particular,methylation of histone H3 at K4 and K27 positions act antagonistically to maintain active and repressed gene expression states,respectively.Although it is established that gene expression regulated by H3K27 methylation is one of the major determinants of the capacity of NSCs for either self-renewal or lineage differentiation,little is known about the role of H3KA methylation in NSC regulation(Albert and Huttner,2018).展开更多
The Zika virus(ZIKV)and dengue virus(DENV)flaviviruses exhibit similar replicative processes but have distinct clinical outcomes.A systematic understanding of virus–host protein–protein interaction networks can reve...The Zika virus(ZIKV)and dengue virus(DENV)flaviviruses exhibit similar replicative processes but have distinct clinical outcomes.A systematic understanding of virus–host protein–protein interaction networks can reveal cellular pathways critical to viral replication and disease pathogenesis.Here we employed three independent systems biology approaches toward this goal.First,protein array analysis of direct interactions between individual ZIKV/DENV viral proteins and20,240 human proteins revealed multiple conserved cellular pathways and protein complexes,including proteasome complexes.Second,an RNAi screen of 10,415 druggable genes identified the host proteins required for ZIKV infection and uncovered that proteasome proteins were crucial in this process.Third,high-throughput screening of 6016 bioactive compounds for ZIKV inhibition yielded 134 effective compounds,including six proteasome inhibitors that suppress both ZIKV and DENV replication.Integrative analyses of these orthogonal datasets pinpoint proteasomes as critical host machinery for ZIKV/DENV replication.Our study provides multi-omics datasets for further studies of flavivirus–host interactions,disease pathogenesis,and new drug targets.展开更多
Cellular reprogramming allows for the de novo generation of human neurons and glial cells from patients with neurological and psychiatric disorders. Crucially, this technology preserves the genome of the donor individ...Cellular reprogramming allows for the de novo generation of human neurons and glial cells from patients with neurological and psychiatric disorders. Crucially, this technology preserves the genome of the donor individual and thus provides a unique opportunity for systematic investigation of genetic influences on neuronal pathophysiology. Although direct reprogramming of adult somatic cells to neurons is now possible, the majority of recent studies have used induced pluripotent stem cells （iPSCs） derived from patient fibroblasts to generate neural progenitors that can be differentiated to specific neural cell types. Investigations of monogenic diseases have established proof-of-principle for many aspects of cellular disease modeling, including targeted differentiation of neuronal populations and rescue of phenotypes in patient iPSC lines. Refinement of protocols to allow for efficient generation of iPSC lines from large patient cohorts may reveal common functional pathology and genetic interactions in diseases with a polygenic basis. We review several recent studies that illustrate the utility of iPSC-based cellular models of neurodevelopmental and neurodegenerative disorders to identify novel phenotypes and therapeutic approaches.展开更多
文摘Neural stem cells （NSCs） are present not only during the embryonic development but also in the adult brain of all mammalian species, including humans. Stem cell niche architecture in vivo enables adult NSCs to continuously generate functional neurons in specific brain regions throughout life. The adult neurogenesis process is subject to dynamic regulation by various physiological, pathological and pharmacological stimuli. Multipotent adult NSCs also appear to be intrinsically plastic, amenable to genetic programing during normal differentiation, and to epigenetic reprograming during de-differentiation into pluripotency. Increasing evidence suggests that adult NSCs significantly contribute to specialized neural functions under physiological and pathological conditions. Fully understanding the biology of adult NSCs will provide crucial insights into both the etiology and potential therapeutic interventions of major brain disorders. Here, we review recent progress on adult NSCs of the mammalian central nervous system, including topics on their identity, niche, function, plasticity, and emerging roles in cancer and regenerative medicine.
基金Foundation item:The National Key Research and Development Program of China under contract No.2016YFC1402100the Marine S&T Fund of Shandong Province for Pilot National Laboratory for Marine Science and Technology(Qingdao)under contract No.2018SDKJ0505-4+1 种基金the National Natural Science Foundation of China under contract No.41876137the NSFC-Shandong Joint Funded Project under contract No.U1606404.
文摘The data of field surveys during 2009 to 2018 was analyzed to understand the seasonality and inter-annual variability of the floating Ulva and Sargassum in the Subei Shoal,the southwestern Yellow Sea of China on decadal scale.The floating Ulva biomass was consistently originated from the central region of the Subei Shoal in middle to late April,increased rapidly,drifted and extended into the offshore water in May and June.The average floating Ulva biomass in the shoal generally increased over the years with evident inter-annual fluctuations.In contrast,pelagic Sargassum was accumulated in the Subei Shoal and formed the spring bloom only in 2013,2017 and 2018,and the biomass was higher than the co-occurring Ulva during the survey in these three years.Compared to the raft-origin floating Ulva,genesis and development of the pelagic Sargassum was distinct.Based on the current research,the Sargassum biomass was exotic and often initiated in the offshore water in March,and intruded into the shoal in April and May.The analysis on the environmental parameters was inconclusive since multiple anthropogenic and non-indigenous factors could influence the green tides in this region.Further research covering both the East China Sea and the Yellow Sea is needed to trace the origin of the floating Sargassum and to understand the interactions between these two co-occurring seaweeds.
文摘To solve the mapping problem for the mobile robots in the unknown environment, a dynamic growing self-organizing map with growing-threshold tuning automatically algorithm (DGSOMGT) based on Self-organizing Map is proposed. It introduces a value of spread factor to describe the changing process of the growing threshold dynamically. The method realizes the network structure growing by training through mobile robot movement constantly in the unknown environment. The proposed algorithm is based on self-organizing map and can adjust the growing-threshold value by the number of network neurons increasing. It avoids tuning the parameters repeatedly by human. The experimental results show that the proposed method detects the complex environment quickly, effectively and correctly. The robot can realize environment mapping automatically. Compared with the other methods the proposed mapping strategy has better topological properties and time property.
基金The National Marine Public Welfare Research Project of China under contract No.201305030the Open Fund from Observation and Research Station of Bohai Strait Eco-Corridor under contract No.BH202201.
文摘Taxonomic sufficiency(TS)refers to identifying taxa to a taxonomic level sufficient to detect community changes in stressed environments and may provide a cost-effective approach in routine monitoring programs.However,there is still limited information regarding the seasonal impact of applying TS and its implications for the ecological quality evaluation in the estuarine ecosystem.This study investigated the relationship between the multivariate-AZTI’s Marine Biotic Index(M-AMBI)and environmental variables in three seasons(i.e.,spring,summer,and autumn)in the Liaohe River Estuary.We tested the reliability of TS for simplifying the M-AMBI methodology.The results showed that family and genus level data could reproduce the spatial-temporal patterns of community structure at the species level.The M-AMBI values showed a consistent spatial distribution pattern in all sampling seasons,with a decreasing trend with the increasing distance from the estuary mouth.Both genus and family level data performed nearly as well as species level in detecting the seasonal variations of pollutants(i.e.,nutrients and total organic content).The family level M-AMBI was feasible to discern stress in the Liaohe River Estuary because of the high aggregation ratios at different taxonomic levels in all sampling seasons.These findings suggest that applying taxonomic sufficiency based on the M-AMBI provides an efficient approach for evaluating ecological quality in the Liaohe River Estuary.
文摘The dielectrophoretic gate and sorter system has been widely applied for preconcentrating and sorting of bioparticles for biodetection. In such systems, the dielectrophoretic force is generated by applying an AC electric field on the three dimensional electrode systems (containing a pair of electrodes on the top and bottom of the channel). Particles are held and sorted by balancing the DEP force with the hydrodynamic drag force. The holding capability is very important for such systems because it determines the preconcentration and sorting efficiency. In this paper, we investigate the holding capability of a simple dielectrophoretic gate system. Initially, a three dimensional numerical scheme was introduced to estimate the holding capability and was further validated by comparing with experimental results. Second, we systematically investigated the effects of the phase difference between the top and bottom electrodes;the height and width of the channel, and the relative position and size of top and bottom electrodes. The results demonstrated that the maximum holding capability is reached when the phase difference between the top and bottom electrodes is around 180o. The results also show that the holding capability varied with the size and relative position of electrodes on the top and bottom, and the maximum holding capability is obtained when the top and bottom electrodes had the same size and the centers of both electrodes overlapped.
基金supported by National Institutes of Health(R35NS137480,R35NS116843,and RF1AG079557)by Dr.Miriam and Sheldon G.Adelson Medical Research Foundation.
文摘The adult subventricular zone of the lateral ventricles and the subgranular zone in the hippocampal dentate gyrus(DG)are the two brain regions where neurogenesis occurs throughout life in the adult mammalian brain(Ming and Song,2011).Adult quiescent hippocampal neural stem cells(NSCs)are bona fide stem cells and,when activated,give rise to newborn granule neurons in the adult brain,which play vital roles in learning,memory,mood,and affective cognition(Bonaguidi et al.,2011;Ming and Song,2011).
文摘Neurogenesis persists in two locations of the adult mammalian brain, the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus in the hippocampus. In the adult subgranular zone, radial glial- like cells （RGLs） are multipotent stem cells that can give rise to both astrocytes and neurons. In the process of generating neurons, RGLs divide asymmetrically to give rise to one RGL and one intermediate progenitor cell （IPC）. IPCs are considered to be a population of transit amplifying cells that proliferate and eventually give rise to mature granule neurons. The properties of individual IPCs at the clonai level are not well understood. Furthermore, it is not clear whether IPCs can generate astrocytes or revert back to RGLs, besides generating neurons. Here we developed a genetic marking strategy for clonal analysis and lineage-tracing of individual Tbr2-expressing IPCs in the adult hippocampus in vivo using Tbr2-CreERT2 mice. Using this technique we identified Tbr2-CreERT2 labeled IPCs as unipotent neuronal precursors that do not generate astrocytes or RGLs under homeostasis. Additionally, we showed that these labeled IPCs rapidly generate immature neurons in a synchronous manner and do not undergo a significant amount of amplification under homeostasis, in animals subjected to an enriched environment/running, or in animals with different age. In summary, our study suggests that Tbr2-expressing IPCs in the adult mouse hippocampus are unipotent precursors and rapidly give rise to immature neurons without major amplification.
文摘Mounting evidence points to critical roles for DNA modifications, including 5-methylcytosine （5mC） and its oxidized forms, in the development, plasticity and disorders of the mammalian nervous system. The novel DNA base 5- hydroxymethylcytosine （5hmC） is known to be capable of initiating passive or active DNA demethylation, but whether and how extensively 5hmC functions in shaping the post-mitotic neuronal DNA methylome is unclear. Here we report the genome-wide distribution of 5hmC in dentate granule neurons from adult mouse hippocampus in vivo. 5hmC in the neuronal genome is highly enriched in gene bodies, especially in exons, and correlates with gene expression. Direct genome-wide comparison of 5hmC distribution between embryonic stem cells and neurons reveals extensive differences, reflecting the functional disparity between these two cell types. Importantly, integrative analysis of 5hmC, overall DNA methylation and gene expression profiles of dentate granule neurons in vivo reveals the genome-wide antagonism between these two states of cytosine modifications, supporting a role for 5hmC in shaping the neuronal DNA methylome by promoting active DNA demethylation.
文摘Epigenetic regulation via chromatin modulation plays pivotal roles in regulating neural stem cells(NSCs)both during embryonic development and in adult neurogenesis(Yao et al.,2016).One classic epigenetic mechanism is covalent post-translational modifications to histone proteins,including methylation,phosphorylation,acetylation,ubiquitination,and sumoylation.In particular,methylation of histone H3 at K4 and K27 positions act antagonistically to maintain active and repressed gene expression states,respectively.Although it is established that gene expression regulated by H3K27 methylation is one of the major determinants of the capacity of NSCs for either self-renewal or lineage differentiation,little is known about the role of H3KA methylation in NSC regulation(Albert and Huttner,2018).
基金supported by the National Institutes of Health(NIH),USA(Grant Nos.U19AI131130,R01GM111514,R21AI131706,R35NS097370,and R37NS047344)the Intramural Research Program of the NCATS/NIH,USA
文摘The Zika virus(ZIKV)and dengue virus(DENV)flaviviruses exhibit similar replicative processes but have distinct clinical outcomes.A systematic understanding of virus–host protein–protein interaction networks can reveal cellular pathways critical to viral replication and disease pathogenesis.Here we employed three independent systems biology approaches toward this goal.First,protein array analysis of direct interactions between individual ZIKV/DENV viral proteins and20,240 human proteins revealed multiple conserved cellular pathways and protein complexes,including proteasome complexes.Second,an RNAi screen of 10,415 druggable genes identified the host proteins required for ZIKV infection and uncovered that proteasome proteins were crucial in this process.Third,high-throughput screening of 6016 bioactive compounds for ZIKV inhibition yielded 134 effective compounds,including six proteasome inhibitors that suppress both ZIKV and DENV replication.Integrative analyses of these orthogonal datasets pinpoint proteasomes as critical host machinery for ZIKV/DENV replication.Our study provides multi-omics datasets for further studies of flavivirus–host interactions,disease pathogenesis,and new drug targets.
文摘Cellular reprogramming allows for the de novo generation of human neurons and glial cells from patients with neurological and psychiatric disorders. Crucially, this technology preserves the genome of the donor individual and thus provides a unique opportunity for systematic investigation of genetic influences on neuronal pathophysiology. Although direct reprogramming of adult somatic cells to neurons is now possible, the majority of recent studies have used induced pluripotent stem cells （iPSCs） derived from patient fibroblasts to generate neural progenitors that can be differentiated to specific neural cell types. Investigations of monogenic diseases have established proof-of-principle for many aspects of cellular disease modeling, including targeted differentiation of neuronal populations and rescue of phenotypes in patient iPSC lines. Refinement of protocols to allow for efficient generation of iPSC lines from large patient cohorts may reveal common functional pathology and genetic interactions in diseases with a polygenic basis. We review several recent studies that illustrate the utility of iPSC-based cellular models of neurodevelopmental and neurodegenerative disorders to identify novel phenotypes and therapeutic approaches.
