检索结果-南通市图书馆

Targeted methylation sequencing reveals dysregulated Wnt signaling in Parkinson disease

Journal of Genetics and Genomics 2016年第10期43卷 587-592页

作者： Lusi zhang Jie Deng Qian Pan Yan Zhan Jian-Bing Fan Kun zhang zhuohua zhang Institute of Precision Medicine The Xiangya Hospital State Key Laboratory of Medical Genetics Xiangya Medical School Central South University Department of Bioengineering University of California at San Diego Anchor Dx Corporation International Bio-island

Parkinson disease（PD） is a progressive neurodegenerative movement disorder. Both environmental and genetic factors play important roles in PD etiology. A number of environmental toxins cause parkinsonism in human and animal models. Genetic studies of rare early onset familial PD cases resulted in identification of disease-linked mutations in multiple genes. Nevertheless, the potential interaction between environment and genetics in PD pathogenesis remains largely unknown. We hypothesized that environmental factors induce abnormal epigenetic regulation that is involved in the pathogenesis of both familial and sporadic PD. We determined the global methylation status of 80,000e110,000 Cp G sites in each of the five sporadic PD patient brains and five age and postmodern interval matched control brains utilizing bisulfite padlock sequencing. Multiple genes involved in neurogenesis, particularly the ones in the Wnt signaling pathway, were hypermethylated in PD brains compared to their matched control brains. Consistent with the DNA methylation changes, marked reduction of protein expression was observed for four Wnt and neurogenesis related genes（FOXC1, NEURG2, SPRY1, and CTNNB1） in midbrain dopaminergic（DA） neurons of PD. The treatment of low concentration of 1-methyl-4-phenylpyridinium（MPPt） for cells resulted in downregulation of Wnt related genes. The study revealed an important link between the epigenetic disregulation of Wnt signaling and the pathogenesis and progression of PD.

关键词： Epigenetic regulation Neurodegenerative diseases Environmental toxins Neurogenesis

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Trafficking abnormality and ER stress underlie functional deficiency of hearing impairmentassociated connexin-31 mutants

引用

Protein & Cell 2010年第10期1卷 935-943页

作者： Kun Xia Hong Ma Hui Xiong Qian Pan Liangqun Huang Danling Wang zhuohua zhang State Key Laboratory of Medical Genetics Central South UniversityChangsha 410083China Burnham Institute for Medical Research La JollaCA 92037USA

Hearing impairment(HI)affects 1/1000 children and over 2%of the aged *** have previously reported that mutations in the gene encoding gap junction protein connexin-31(Cx31)are associated with *** pathological mechanism of the disease mutations remains ***,we show that expression of Cx31 in the mouse inner ear is developmentally regulated with a high level in adult inner hair cells and spiral ganglion neurons that are critical for the hearing *** transfected cells,wild type Cx31 protein(Cx31wt)forms functional gap junction at *** contrast,two HIassociated Cx31 mutants,Cx31R180X and Cx31E183K resided primarily in the ER and Golgi-like intracellular punctate structures,respectively,and failed to mediate lucifer yellow *** of Cx31 mutants but not Cx31wt leads to upregulation of and increased association with the ER chaperone BiP indicating ER stress ***,the HI-associated Cx31 mutants are impaired in trafficking,promote ER stress,and hence lose the ability to assemble functional gap *** study reveals a potential pathological mechanism of HI-associated Cx31 mutations.

关键词： gap junction bip inner ear protein folding

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Protein O-GlcNAcylation homeostasis regulates facultative heterochromatin to fine-tune sog-Dpp signaling during Drosophila early embryogenesis

引用

Journal of Genetics and Genomics 2023年第12期50卷 948-959页

作者： Yaowen zhang Haibin Yu Dandan Wang Xiaoyun Lei Yang Meng Na zhang Fang Chen Lu Lv Qian Pan Hongtao Qin zhuohua zhang Daan M.F.van Aalten Kai Yuan Center for Medical Genetics School of Life Sciences&Hunan Key Laboratory of Molecular Precision MedicineDepartment of OncologyXiangya HospitalCentral South UniversityChangshaHunan 410008China State Key Laboratory of Chemo/Biosensing and Chemometrics College of BiologyHunan UniversityChangshaHunan 410082China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan 410008China Division of Cell and Developmental Biology School of Life SciencesUniversity of DundeeDundee DD15EHUK Department of Molecular Biology and Genetics University of AarhusAarhus 8000Denmark The Biobank of Xiangya Hospital Central South UniversityChangshaHunan 410008China

Protein O-GlcNAcylation is a monosaccharide post-translational modification maintained by two evolutionarily conserved enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Mutations in human OGT have recently been associated with neurodevelopmental disorders, although the mechanisms linking O-GlcNAc homeostasis to neurodevelopment are not understood. Here, we investigate the effects of perturbing protein O-GlcNAcylation using transgenic Drosophila lines that overexpress a highly active OGA. We reveal that temporal reduction of protein O-GlcNAcylation in early embryos leads to reduced brain size and olfactory learning in adult Drosophila. Downregulation of O-GlcNAcylation induced by the exogenous OGA activity promotes nuclear foci formation of Polycomb-group protein Polyhomeotic and the accumulation of excess K27 trimethylation of histone H3 (H3K27me3) at the mid-blastula transition. These changes interfere with the zygotic expression of several neurodevelopmental genes, particularly short gastrulation (sog), a component of an evolutionarily conserved sog-Decapentaplegic (Dpp) signaling system required for neuroectoderm specification. Our findings highlight the importance of early embryonic O-GlcNAcylation homeostasis for the fidelity of facultative heterochromatin redeployment and initial cell fate commitment of neuronal lineages, suggesting a possible mechanism underpinning OGT-associated intellectual disability.

关键词： Protein O-GlcNAcylation Drosophila Early embryogenesis Polycomb repressive complex Facultative heterochromatin Neurodevelopment sog

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Transcriptional pausing induced by ionizing radiation enables the acquisition of radioresistance in nasopharyngeal carcinoma

引用

Journal of Molecular Cell Biology 2023年第7期15卷 15-30页

作者： Honglu Liu Huanyi Fu Chunhong Yu Na zhang Canhua Huang Lu Lv Chunhong Hu Fang Chen Zhiqiang Xiao zhuohua zhang Huasong Lu Kai Yuan Hunan Key Laboratory of Molecular Precision Medicine Department of OncologyXiangya HospitalCentral South UniversityChangsha 410008China Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology Life Sciences InstituteZhejiang UniversityHangzhou 310058China Hunan Key Laboratory of Medical Genetics School of Life SciencesCentral South UniversityChangsha 410008China Department of Oncology The Second Xiangya HospitalCentral South UniversityChangsha 410011China Research Center of Carcinogenesis and Targeted Therapy Xiangya HospitalCentral South UniversityChangsha 410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha 410008China The Biobank of Xiangya Hospital Central South UniversityChangsha 410008China

Lesions on the DNA template can impact transcription via distinct regulatory *** radiation(IR)as the mainstay modality for many malignancies elicits most of the cytotoxicity by inducing a variety of DNA damages in the *** the IR treatment alters the transcription cycle and whether it contributes to the development of radioresistance remain poorly ***,we report an increase in the paused RNA polymerase II(RNAPII),as indicated by the phosphorylation at serine 5 residue of its C-terminal domain,in recurrent nasopharyngeal carcinoma(NPC)patient samples after IR treatment and cultured NPC cells developing IR *** the pool of paused RNAPII by either inhibiting TFIIH-associated CDK7 or stimulating the positive transcription elongation factor b,a CDK9-CycT1 heterodimer,attenuates IR resistance of NPC ***,the poly(ADP-ribosyl)ation of CycT1,which disrupts its phase separation,is elevated in the IR-resistant *** of the major poly(ADP-ribosyl)ation sites of CycT1 decreases RNAPII pausing and restores IR ***-wide chromatin immunoprecipitation followed by sequencing analyses reveal that several genes involved in radiation response and cell cycle control are subject to the regulation imposed by the paused ***,we identify the NIMA-related kinase NEK7 under such regulation as a new radioresistancefactor,whose downregulation results in the increased chromosome instability,enabling the development of IR ***,our results highlight a novel link between the alteration in the transcription cycle and the acquisition of IR resistance,opening up new opportunities to increase the efficacy of radiotherapy and thwart radioresistance in NpC.

关键词： RNA polymerase II transcriptional pausing radioresistance CDK7 NEK7 nasopharyngeal carcinoma

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Autophagy impairment induces cell-non-autonomous mitochondrial degeneration

Autophagy impairment induces cell-non-autonomous mitochondri...

引用

中国神经科学学会第十届全国学术会议

作者： Chengyuan Tang zhuohua zhang State key Laboratory of Medical Genetics Central south University

Autophagy is implicated in pathogenesis of multiple diseases,including Parkinson disease（PD）.However,mechamsm of autophagy defects to cause human diseases remains largely *** this study,we demonstrate that genetic inhibition of autophagy genes,dAtg5,dAtg7,and dAtg12,in dopaminergic（DA） neurons of Drosophila brain results in abnormal wing position,reduced life span,defective climbing,and loss of DA ***,these flies develop mitochondrial abnormalities not only in neurons in brains but also in distal peripheral tissues,including muscles and adipose *** of either PD-related parkin or PINK1 in DA neurons alone suppresses the abnormal phenotypes and prevents mitochondrial degeneration in peripheral *** results suggest that parkin and PINK1 regulated autophagy plays an essential role in maintaining DA neuronal functions in central nervous system（CNS）,therefore,to regulate mitochondrial homeostasis of peripheral non-neuronal tissues via a mechanism independent of cell-autonomous *** study reveals a novel mechamsm of neural control and opens a new avenue to investigate pathogenesis of neurodegenerative diseases,particularly,PD.

关键词：

来源： cnki会议评论

在线全文

cnki会议

学校读者我要写书评

暂无评论

PCDH17 restricts dendritic spine morphogenesis by regulating ROCK2-dependent control of the actin cytoskeleton,modulating emotional behavior

引用

Zoological Research 2024年第3期45卷 535-550页

作者： Laidong Yu Fangfang Zeng Mengshu Fan Kexuan zhang Jingjing Duan Yalu Tan Panlin Liao Jin Wen Chenyu Wang Meilin Wang Jialong Yuan Xinxin Pang Yan Huang Yangzhou zhang Jia-Da Li zhuohua zhang Zhonghua Hu Hunan Key Laboratory of Molecular Precision Medicine Department of Critical Care MedicineXiangya HospitalCentral South UniversityChangshaHunan 410008China Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics School of Life SciencesCentral South UniversityChangshaHunan 410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan 410008China Hunan Provincial Clinical Research Center for Critical Care Medicine Xiangya HospitalCentral South UniversityChangshaHunan 410008China Hunan Key Laboratory of Animal Models for Human Diseases School of Life SciencesCentral South UniversityChangshaHunan 410008China MOE Key Lab of Rare Pediatric Diseases School of Life SciencesCentral South UniversityChangshaHunan 410008China Department of Neurosciences University of South China Medical SchoolHengyangHunan 421001China

Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain *** abnormalities,such as defects in the density and morphology of postsynaptic dendritic spines,underlie the pathology of various neuropsychiatric *** 17(PCDH17)is associated with major mood disorders,including bipolar disorder and ***,the molecular mechanisms by which PCDH17 regulates spine number,morphology,and behavior remain *** this study,we found that PCDH17 functions at postsynaptic sites,restricting the number and size of dendritic spines in excitatory *** overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety-and depression-like behaviors in ***,PCDH17 interacts with actin-relevant proteins and regulates actin filament(F-actin)***,PCDH17 binds to ROCK2,increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3(Ser3).Inhibition of ROCK2 activity with belumosudil(KD025)ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression,suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine ***,these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior,providing pathological insights into the neurobiological basis of mood disorders.

关键词： Synapse development Dendritic spine Mood disorder Actin cytoskeleton Animal behavior

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Association of variants in the KIF1A gene with amyotrophic lateral sclerosis

引用

Translational Neurodegeneration 2022年第1期11卷 235-247页

作者： Panlin Liao Yanchun Yuan Zhen Liu Xiaorong Hou Wanzhen Li Jin Wen Kexuan zhang Bin Jiao Lu Shen Hong Jiang Jifeng Guo Beisha Tang zhuohua zhang Zhonghua Hu Junling Wang Hunan Key Laboratory of Molecular Precision Medicine Department of Critical Care MedicineXiangya HospitalCentral South UniversityChangsha 410008China Department of Neurology Xiangya HospitalCentral South UniversityChangsha 410008China National Clinical Research Center for Geriatric Diseases Xiangya HospitalCentral South UniversityChangsha 410008China Key Laboratory of Hunan Province in Neurodegenerative Disorders Central South UniversityChangsha 410008China Center for Medical Genetics School of Life SciencesCentral South UniversityChangsha 410008China Engineering Research Center of Hunan Province in Cognitive Impairment Disorders Central South UniversityChangsha 410008China Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases Changsha 410008China Hunan Provincial Clinical Research Center for Critical Care Medicine Xiangya HospitalCentral South UniversityChangsha 410008China Hunan Key Laboratory of Animal Models for Human Diseases School of Life SciencesCentral South UniversityChangsha 410008China.

Background:Amyotrophic lateral sclerosis(ALS)is a devastating progressive neurodegenerative disease that affects neurons in the central nervous system and the spinal *** in many other neurodegenerative disorders,the genetic risk factors and pathogenesis of ALS involve dysregulation of cytoskeleton and neuronal ***,sen-sory and motor neuron diseases such as hereditary sensory and autonomic neuropathy type 2(HSAN2)and spastic paraplegia 30(SPG30)share several causative genes with ALS,as well as having common clinical ***1A encodes a kinesin 3 motor that transports presynaptic vesicle precursors(SVPs)and dense core vesicles and has been reported as a causative gene for HSAN2 and ***:Here,we analyzed whole-exome sequencing data from 941 patients with ALS to investigate the genetic association of KIF1A with ***:We identified rare damage variants(RDVs)in the KIF1A gene associated with ALS and delineated the clini-cal characteristics of ALS patients with KIF1A ***,these patients tended to exhibit sensory ***,the majority of these variants are located at the C-terminal cargo-binding region of the KIF1A *** examination revealed that the ALS-associated KIF1A variants located in the C-terminal region preferentially enhanced the binding of SVPs containing RAB3A,VAMP2,and *** of several disease-related KIF1A mutants in cultured mouse cortical neurons led to enhanced colocalization of RAB3A or VAMP2 with the KIF1A ***:Our study highlighted the importance of KIF1A motor-mediated transport in the pathogenesis of ALS,indicating KIF1A as an important player in the oligogenic scenario of ALS.

关键词： Amyotrophic lateral sclerosis KIF1A Axonal transport Presynaptic vesicle precursors

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Loss of Lrrk2 might cause liver hemangiomas in mice

Loss of Lrrk2 might cause liver hemangiomas in mice

引用

第十四次全国医学遗传学学术会议

作者： Ben Wu zhuohua zhang Long Ma The State Key Laboratory of Medical Genetics Central South University

Parkinson’s disease(PD)is a severe nervous system disorder exemplified by progressive loss of dopaminergic neurons in the substantial nuclei of the *** date over 18 genes have been identified to be associated with PD,among which LRRK2mutations are found in most familial cases of *** the function of LRRK2 remains to be *** we found that mice homozygous for a LRRK2 null mutation developed localized overgrowth of liver blood vessels similar to hemangiomas at 20-24 months *** penetrance of the blood vessel overgrowth is around 70%(9/13).We did not find similar liver phenotypes in LRRK2 null mice younger than 18 months old,suggesting that this phenotype is strongly *** also found that LRRK2protein is apparently expressed in the kidney,spleen and relatively weakly in *** LRRK2 could not be detected in the mouse *** propose that LRRK2 might inhibit angiogenesis in mouse liver and are in process of determining the molecular mechanism underlying this phenotype.

关键词： Lrrk2 liver hemangiomas angiogenesis

来源： cnki会议评论

在线全文

cnki会议

学校读者我要写书评

暂无评论

PINK1-mediated Drp1^(S616) phosphorylation modulates synaptic development and plasticity via promoting mitochondrial fission

引用

Signal Transduction and Targeted Therapy 2022年第5期7卷 1719-1734页

作者： Qingtao Gao Runyi Tian Hailong Han Jesse Slone Caifang Wang Xiao Ke Tongmei zhang Xiangyu Li Yuhong He Panlin Liao Fang Wang Ye Chen Shiqing Fu Kexuan zhang Fangfang Zeng Yingxuan Yang Zhuo Li Jieqiong Tan Jiada Li Youming Lu Taosheng Huang Zhonghua Hu zhuohua zhang Institute of Molecular Precision Medicine Xiangya HospitalKey Laboratory of Molecular Precision Medicine of Hunan Province and Center for Medical GeneticsHunan Key Laboratory of Medical GeneticsCentral South UniversityChangshaHunan 410008China Department of Pediatrics Jacobs School of Medicine and Biomedical SciencesUniversity at BuffaloBuffaloNew York 14203USA Department of Physiology School of Basic Medicine and Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China The Institute for Brain Research Collaborative Innovation Center for Brain ScienceHuazhong University of Science and TechnologyWuhanHubei 430030China Hunan Key Laboratory of Animal Models for Human Diseases School of Life SciencesCentral South UniversityChangshaHunan 410008China Department of Neurosciences University of South China Medical SchoolHengyangHunan 421001China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Critical Care Medicine Hunan Provincial Clinical Research Center for Critical Care MedicineXiangya HospitalCentral South UniversityChangshaHunan 410008China

Dynamic change of mitochondrial morphology and distribution along neuronal branches are essential for neural circuitry formation and synaptic ***,the underlying mechanism remains *** show here that Pink1 knockout(KO)mice display defective dendritic spine maturation,reduced axonal synaptic vesicles,abnormal synaptic connection,and attenuated long-term synaptic potentiation(LTP).Drp1 activation via ^(S616) phosphorylation rescues deficits of spine maturation in Pink1 KO neurons.

关键词： plasticity activation synaptic

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

WTO框架下粤港澳合作模式的探讨

引用

特区经济 2002年第1期 21-23页

作者：张灼华

一、中国加入WTO对于粤港澳合作所带来的机遇与挑战1.对产业合作的影响在传统的'前厂后店'的产业合作模式之下,粤港澳三地形成了亚太地区一个重要的劳动密集型产品生产基地,港商投资的工厂在珠江三角洲区域比比皆是.从技术含量比较低的... 详细信息

一、中国加入WTO对于粤港澳合作所带来的机遇与挑战1.对产业合作的影响在传统的'前厂后店'的产业合作模式之下,粤港澳三地形成了亚太地区一个重要的劳动密集型产品生产基地,港商投资的工厂在珠江三角洲区域比比皆是.从技术含量比较低的手工产品到技术含量相对较高的电子周边产品和电讯产品,都占据了一定的国际市场份额.中国入世后,关税大幅度下降,对于中国一些传统强势产品歧视性的配额限制的取消,都将有利于广东省借机扩大出口,获得更多的国际市场份额.根据规定,美国等发达国家将在2005年之前取消对中国纺织品歧视性的配额限制.纺织、服装和鞋帽都是广东的传统出口产品,此外,家电、文教、食品和部分机电产品等也具有一定优势.关税的减少将使三资企业的产品在市场上更具有价格上的竞争优势.

关键词： WTO 广东香港澳门经贸合作合作模式

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：