Alcohol, a widely abused drug, has deleterious effects on the immature nervous system. This study investigates the effect of chronic in vitro ethanol exposure on the metabolism of immature rat cerebellar granular cell...Alcohol, a widely abused drug, has deleterious effects on the immature nervous system. This study investigates the effect of chronic in vitro ethanol exposure on the metabolism of immature rat cerebellar granular cells(CGCs) and on their response to oxygen-glucose deprivation(OGD). Primary CGC cultures were exposed to ethanol(100 mM in culture medium) or to control ethanol-free medium starting day one in vitro(DIV1). At DIV8, the expression of ATP synthase gene ATP5 g3 was quantified using real-time PCR, then cultures were exposed to 3 hours of OGD or normoxic conditions. Subsequently, cellular metabolism was assessed by a resazurin assay and by ATP level measurement. ATP5 g3 expression was reduced by 12-fold(P = 0.03) and resazurin metabolism and ATP level were decreased to 74.4 ± 4.6% and 55.5 ± 6.9%, respectively after chronic ethanol treatment compared to control values(P < 0.01). Additionally, after OGD exposure of ethanol-treated cultures, resazurin metabolism and ATP level were decreased to 12.7 ± 1.0% and 9.0 ± 2.0% from control values(P < 0.01). These results suggest that chronic ethanol exposure reduces the cellular ATP level, possibly through a gene expression down-regulation mechanism, and increases the vulnerability to oxygen-glucose deprivation. Thus, interventions which improve metabolic function and sustain ATP-levels could attenuate ethanol-induced neuronal dysfunction and should be addressed in future studies.展开更多
Social epigenomics is a new field of research that studies how the social environment shapes the epigenome and how in turn the epigenome modulates behavior.We focus on describing known gene-environment interactions(GE...Social epigenomics is a new field of research that studies how the social environment shapes the epigenome and how in turn the epigenome modulates behavior.We focus on describing known gene-environment interactions(GEIs)and epigenetic mechanisms in different mammalian social systems.To illustrate how epigenetic mechanisms integrate GEIs,we highlight examples where epigenetic mechanisms are associated with social behaviors and with their maintenance through neuroendocrine,locomotor,and metabolic responses.We discuss future research trajectories and open questions for the emerging field of social epigenomics in nonmodel and naturally occurring social systems.Finally,we outline the technological advances that aid the study of epigenetic mechanisms in the establishment of GEIs and vice versa.展开更多
Orphan genes that lack detectable homologues in other lineages could contribute to a variety of biological functions. However,their origination and function mechanisms remain largely unknown. Herein, through a compreh...Orphan genes that lack detectable homologues in other lineages could contribute to a variety of biological functions. However,their origination and function mechanisms remain largely unknown. Herein, through a comprehensive and systematic computational pipeline, we identified 893 orphan genes in the lineage of C. elegans, of which only a low fraction(0.9%) were derived from transposon elements. Six new protein-coding genes that de novo originated from non-coding DNA sequences in the genome of C. elegans were also identified. The authenticity and functionality of these orphan genes and de novo genes are supported by three lines of evidences, consisting of transcriptional data, and in silico proteomic data, and the fixation status data in wild populations. Orphan genes and de novo genes exhibited simple gene structures, such as, short in protein length, of fewer exons,and are frequently X-linked. RNA-seq data analysis showed these orphan genes are enriched with expression in embryo development and gonad, and their potential function in early development was further supported by gene ontology enrichment analysis results. Meanwhile, de novo genes were found to be with significant expression in gonad, and functional enrichment analysis of the co-expression genes of these de novo genes suggested they may be functionally involved in signaling transduction pathway and metabolism process. Our results presented the first systematic evidence on the evolution of orphan genes and de novo origin of genes in nematodes and their impacts on the functional and phenotypic evolution, and thus could shed new light on our appreciation of the importance of these new genes.展开更多
基金supported by a grant of the Romanian National Authority for Scientific Research,project PN-II-PT-PCCA-2011-3,No 80/2012
文摘Alcohol, a widely abused drug, has deleterious effects on the immature nervous system. This study investigates the effect of chronic in vitro ethanol exposure on the metabolism of immature rat cerebellar granular cells(CGCs) and on their response to oxygen-glucose deprivation(OGD). Primary CGC cultures were exposed to ethanol(100 mM in culture medium) or to control ethanol-free medium starting day one in vitro(DIV1). At DIV8, the expression of ATP synthase gene ATP5 g3 was quantified using real-time PCR, then cultures were exposed to 3 hours of OGD or normoxic conditions. Subsequently, cellular metabolism was assessed by a resazurin assay and by ATP level measurement. ATP5 g3 expression was reduced by 12-fold(P = 0.03) and resazurin metabolism and ATP level were decreased to 74.4 ± 4.6% and 55.5 ± 6.9%, respectively after chronic ethanol treatment compared to control values(P < 0.01). Additionally, after OGD exposure of ethanol-treated cultures, resazurin metabolism and ATP level were decreased to 12.7 ± 1.0% and 9.0 ± 2.0% from control values(P < 0.01). These results suggest that chronic ethanol exposure reduces the cellular ATP level, possibly through a gene expression down-regulation mechanism, and increases the vulnerability to oxygen-glucose deprivation. Thus, interventions which improve metabolic function and sustain ATP-levels could attenuate ethanol-induced neuronal dysfunction and should be addressed in future studies.
文摘Social epigenomics is a new field of research that studies how the social environment shapes the epigenome and how in turn the epigenome modulates behavior.We focus on describing known gene-environment interactions(GEIs)and epigenetic mechanisms in different mammalian social systems.To illustrate how epigenetic mechanisms integrate GEIs,we highlight examples where epigenetic mechanisms are associated with social behaviors and with their maintenance through neuroendocrine,locomotor,and metabolic responses.We discuss future research trajectories and open questions for the emerging field of social epigenomics in nonmodel and naturally occurring social systems.Finally,we outline the technological advances that aid the study of epigenetic mechanisms in the establishment of GEIs and vice versa.
基金supported by EEgrid cluster of the University of Chicagosupported by National Natural Science Foundation of China(31600670 to W.Zhang,31670851 to B.Shen)
文摘Orphan genes that lack detectable homologues in other lineages could contribute to a variety of biological functions. However,their origination and function mechanisms remain largely unknown. Herein, through a comprehensive and systematic computational pipeline, we identified 893 orphan genes in the lineage of C. elegans, of which only a low fraction(0.9%) were derived from transposon elements. Six new protein-coding genes that de novo originated from non-coding DNA sequences in the genome of C. elegans were also identified. The authenticity and functionality of these orphan genes and de novo genes are supported by three lines of evidences, consisting of transcriptional data, and in silico proteomic data, and the fixation status data in wild populations. Orphan genes and de novo genes exhibited simple gene structures, such as, short in protein length, of fewer exons,and are frequently X-linked. RNA-seq data analysis showed these orphan genes are enriched with expression in embryo development and gonad, and their potential function in early development was further supported by gene ontology enrichment analysis results. Meanwhile, de novo genes were found to be with significant expression in gonad, and functional enrichment analysis of the co-expression genes of these de novo genes suggested they may be functionally involved in signaling transduction pathway and metabolism process. Our results presented the first systematic evidence on the evolution of orphan genes and de novo origin of genes in nematodes and their impacts on the functional and phenotypic evolution, and thus could shed new light on our appreciation of the importance of these new genes.
