Primary central nervous system lymphoma(PCNSL)is an uncommon non-Hodgkin’s lymphoma with poor prognosis.This study aimed to depict the genetic landscape of Chinese PCNSLs.Whole-genome sequencing was performed on 68 n...Primary central nervous system lymphoma(PCNSL)is an uncommon non-Hodgkin’s lymphoma with poor prognosis.This study aimed to depict the genetic landscape of Chinese PCNSLs.Whole-genome sequencing was performed on 68 newly diagnosed Chinese PCNSL samples,whose genomic characteristics and clinicopathologic features were also analyzed.Structural variations were identified in all patients with a mean of 349,which did not significantly influence prognosis.Copy loss occurred in all samples,while gains were detected in 77.9%of the samples.The high level of copy number variations was significantly associated with poor progression-free survival(PFS)and overall survival(OS).A total of 263 genes mutated in coding regions were identified,including 6 newly discovered genes(ROBO2,KMT2C,CXCR4,MYOM2,BCLAF1,and NRXN3)detected in≥10%of the cases.CD79B mutation was significantly associated with lower PFS,TMSB4X mutation and high expression of TMSB4X protein was associated with lower OS.A prognostic risk scoring system was also established for PCNSL,which included Karnofsky performance status and six mutated genes(BRD4,EBF1,BTG1,CCND3,STAG2,and TMSB4X).Collectively,this study comprehensively reveals the genomic landscape of newly diagnosed Chinese PCNSLs,thereby enriching the present understanding of the genetic mechanisms of PCNSL.展开更多
microRNA(miRNA)是一类由内源基因编码的长度约22个核苷酸的单链非编码RNA分子,其通过剪切信使RNA或非编码RNA、沉默或激活转录、primary mi RNA(pri-miRNA)加工及mRNA翻译,调控几乎所有细胞增殖分化、个体生长发育及内环境稳态.大量研...microRNA(miRNA)是一类由内源基因编码的长度约22个核苷酸的单链非编码RNA分子,其通过剪切信使RNA或非编码RNA、沉默或激活转录、primary mi RNA(pri-miRNA)加工及mRNA翻译,调控几乎所有细胞增殖分化、个体生长发育及内环境稳态.大量研究已对miRNA的生物发生和调控机制进行了清晰阐述.然而,关于miRNA的转换机制,尤其是miRNA在特定条件下的快速变化,仍尚未解决.近年来研究发现,靶基因能以序列依赖性方式调控miRNA的生成和降解,表明miRNA和靶基因之间的调控不是单向的,而是相互调控.本文详细概述靶基因调控miRNA的最新进展,归纳二者相互作用的条件和机制,提出miRNA转换的研究方向,以期为深入研究机体内miRNA与靶基因的相互作用及开发miRNA靶向治疗药物提供理论基础.展开更多
Mitochondria are the central hub for many metabolic processes,including the citric acid cycle,oxidative phosphorylation,and fatty acid oxidation.Recent studies have identified a new mitochondrial protein family,Fam210...Mitochondria are the central hub for many metabolic processes,including the citric acid cycle,oxidative phosphorylation,and fatty acid oxidation.Recent studies have identified a new mitochondrial protein family,Fam210,that regulates bone metabolism and red cell development in vertebrates.The model organism Caenorhabditis elegans has a Fam210 gene,y56a3a.22,but it lacks both bones and red blood cells.In this study,we report that Y56A3A.22 plays a crucial role in regulating mitochondrial protein homeostasis and reproduction.The nematode y56a3a.22 is expressed in various tissues,including the intestine,muscle,hypodermis,and germline,and its encoded protein is predominantly localized in mitochondria.y56a3a.22 deletion mutants are sterile owing to impaired oogenesis.Loss of Y56A3A.22 induced mitochondrial unfolded protein response(UPRmt),which is mediated through the ATFS-1-dependent pathway,in tissues such as the intestine,germline,hypodermis,and vulval muscle.We further show that infertility and UPRmt induces by Y56A3A.22 deficiency are not attributed to systemic iron deficiency.Together,our study reveals an important role of Y56A3A.22 in regulating mitochondrial protein homeostasis and oogenesis and provides a new genetic tool for exploring the mechanisms regulating mitochondrial metabolism and reproduction as well as the fundamental role of the Fam210 family.展开更多
Dendrite growth and branching occur mainly during the developmental stage,and their spatial and temporal wiring is highly linked to the proper functioning of neuronal networks(Jan and Jan,2003).Although it is well kno...Dendrite growth and branching occur mainly during the developmental stage,and their spatial and temporal wiring is highly linked to the proper functioning of neuronal networks(Jan and Jan,2003).Although it is well known that neuronal dendrites are easily damaged during traumatic brain injury,stroke,and seizure,very little is known about how neurons respond to dendrite injury and initiate regeneration(Liu and Jan,2020).Thus,understanding the cellular and molecular mechanisms of dendrite regeneration and maintenance after injury holds the key to develop novel treatments for human brain damage.展开更多
The comparison between nonprofit and for-profit organizations has been a lingering question for scholars and practitioners.This research explores employee wage differentials across sectors using a national sample of c...The comparison between nonprofit and for-profit organizations has been a lingering question for scholars and practitioners.This research explores employee wage differentials across sectors using a national sample of child care workforce.After controlling for a range of individual,occupational,organizational,and community factors,this research reports a significant wage premium for nonprofit child care teachers.In addition,this study finds evidence for both the labor donation and property rights hypotheses,but the property rights theory demonstrates comparatively stronger explanatory power.Although individuals with stronger intrinsic motivation are more willing to donate labor for charitable outputs,inefficient management in nonprofits actually sets wage levels over the market level.Overall,the study highlights nonprofits*comparative advantage in employee motivation but disadvantage in efficient management.The findings have implications for public and nonprofit management.展开更多
基金supported by funds from the Translational Research Grant of National Clinical Research Center for Hematologic Disease (No.2020ZKZC01)the National Natural Science Foundation of China (Nos.81830006,82170219,and 81800188)the Lymphoma Research Fund of China Anti-Cancer Association.
文摘Primary central nervous system lymphoma(PCNSL)is an uncommon non-Hodgkin’s lymphoma with poor prognosis.This study aimed to depict the genetic landscape of Chinese PCNSLs.Whole-genome sequencing was performed on 68 newly diagnosed Chinese PCNSL samples,whose genomic characteristics and clinicopathologic features were also analyzed.Structural variations were identified in all patients with a mean of 349,which did not significantly influence prognosis.Copy loss occurred in all samples,while gains were detected in 77.9%of the samples.The high level of copy number variations was significantly associated with poor progression-free survival(PFS)and overall survival(OS).A total of 263 genes mutated in coding regions were identified,including 6 newly discovered genes(ROBO2,KMT2C,CXCR4,MYOM2,BCLAF1,and NRXN3)detected in≥10%of the cases.CD79B mutation was significantly associated with lower PFS,TMSB4X mutation and high expression of TMSB4X protein was associated with lower OS.A prognostic risk scoring system was also established for PCNSL,which included Karnofsky performance status and six mutated genes(BRD4,EBF1,BTG1,CCND3,STAG2,and TMSB4X).Collectively,this study comprehensively reveals the genomic landscape of newly diagnosed Chinese PCNSLs,thereby enriching the present understanding of the genetic mechanisms of PCNSL.
文摘microRNA(miRNA)是一类由内源基因编码的长度约22个核苷酸的单链非编码RNA分子,其通过剪切信使RNA或非编码RNA、沉默或激活转录、primary mi RNA(pri-miRNA)加工及mRNA翻译,调控几乎所有细胞增殖分化、个体生长发育及内环境稳态.大量研究已对miRNA的生物发生和调控机制进行了清晰阐述.然而,关于miRNA的转换机制,尤其是miRNA在特定条件下的快速变化,仍尚未解决.近年来研究发现,靶基因能以序列依赖性方式调控miRNA的生成和降解,表明miRNA和靶基因之间的调控不是单向的,而是相互调控.本文详细概述靶基因调控miRNA的最新进展,归纳二者相互作用的条件和机制,提出miRNA转换的研究方向,以期为深入研究机体内miRNA与靶基因的相互作用及开发miRNA靶向治疗药物提供理论基础.
基金the Caenorhabditis Genetics Center(CGC,funded by NIH Office of Research Infrastructure Programs P40 OD010440)the National Bioresource Project+3 种基金supported by funding from the Zhejiang Natural Science Foundation(LR17C110001)the National Natural Science Foundation of China(31871200 and 31371435)the National Key Basic Research Program of China(2015CB150300)to C.Cthe National Natural Science Foundation of China(31671522,31972891 and 91754111)to S.X
文摘Mitochondria are the central hub for many metabolic processes,including the citric acid cycle,oxidative phosphorylation,and fatty acid oxidation.Recent studies have identified a new mitochondrial protein family,Fam210,that regulates bone metabolism and red cell development in vertebrates.The model organism Caenorhabditis elegans has a Fam210 gene,y56a3a.22,but it lacks both bones and red blood cells.In this study,we report that Y56A3A.22 plays a crucial role in regulating mitochondrial protein homeostasis and reproduction.The nematode y56a3a.22 is expressed in various tissues,including the intestine,muscle,hypodermis,and germline,and its encoded protein is predominantly localized in mitochondria.y56a3a.22 deletion mutants are sterile owing to impaired oogenesis.Loss of Y56A3A.22 induced mitochondrial unfolded protein response(UPRmt),which is mediated through the ATFS-1-dependent pathway,in tissues such as the intestine,germline,hypodermis,and vulval muscle.We further show that infertility and UPRmt induces by Y56A3A.22 deficiency are not attributed to systemic iron deficiency.Together,our study reveals an important role of Y56A3A.22 in regulating mitochondrial protein homeostasis and oogenesis and provides a new genetic tool for exploring the mechanisms regulating mitochondrial metabolism and reproduction as well as the fundamental role of the Fam210 family.
基金funded by NIH Office of Research Infrastructure Programs(P40 OD010440)the MITANI Lab through the National Bio-Resource Project of the MEXT,Japansupported by the National Natural Science Foundation of China grants(91754111,31972891,and 31671522)to S.X.and(31800861,31970919)to W.Z。
文摘Dendrite growth and branching occur mainly during the developmental stage,and their spatial and temporal wiring is highly linked to the proper functioning of neuronal networks(Jan and Jan,2003).Although it is well known that neuronal dendrites are easily damaged during traumatic brain injury,stroke,and seizure,very little is known about how neurons respond to dendrite injury and initiate regeneration(Liu and Jan,2020).Thus,understanding the cellular and molecular mechanisms of dendrite regeneration and maintenance after injury holds the key to develop novel treatments for human brain damage.
文摘The comparison between nonprofit and for-profit organizations has been a lingering question for scholars and practitioners.This research explores employee wage differentials across sectors using a national sample of child care workforce.After controlling for a range of individual,occupational,organizational,and community factors,this research reports a significant wage premium for nonprofit child care teachers.In addition,this study finds evidence for both the labor donation and property rights hypotheses,but the property rights theory demonstrates comparatively stronger explanatory power.Although individuals with stronger intrinsic motivation are more willing to donate labor for charitable outputs,inefficient management in nonprofits actually sets wage levels over the market level.Overall,the study highlights nonprofits*comparative advantage in employee motivation but disadvantage in efficient management.The findings have implications for public and nonprofit management.