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2012年海内外华人神经科学会议

作者： zhuo-hua zhang~* The state key laboratory of medical genetics Xiangya medical School Central South University Changsha Hunan China.

＜正＞Parkinson’s disease（PD） is the most common neurodegenerative movement *** pathological hallmarks of PD are loss of dopaminergic neurons in substantia nigra compacta（SNc） of midbrain and formation of intracellular aggregate Lowy bodies. Majority of PD patients are ***,about 10%PD cases are *** genetic studies of familial cases result in identification of causative mutations in multiple *** analysis of these PD linked genes has provided important insight into the disease pathogenic ***,the etiology of sporadic PD remains largely *** long-term research goal is to reveal the molecular mechanism of *** hypothesize that both genetic and environmental factors play important roles in PD pathogenesis and that the environmental factors regulate PD genesis and progression via at least partially epigenetic mechanism. Based on the hypothesis,our research focus includes to elucidate the pathophysiological function of PD linked genes and their pathogenic mutants and to identify the epigenetic changes associated with *** results suggest that PD-linked parkin,PINK1,and DJ-1 form a functional E3 ligase complex to promote ubiquitination and proteasomal degradation ofun/misfolded *** of the E3 ligase complex is regulated by nedd8 modification of both parkin and *** identify PD-associated epigenetic modification,we have performed genome-wide methylation sequencing of brain tissue DNAs from 5 PD patients and their matched *** reveal hypermethy lation of 234 genes in PD brain tissues over their *** 30%of these genes are related to *** vitro studies show that cells treated with sub-lethal dosage of PD neurotoxin MPP+ results in reduced expression of genes in neurogenesis pathway in addition to increased expression of immune related genes and cell death related genes. The study provides to our knowledge the first evidence of linking epigenetic

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Epigenetic regulation in Parkinson disease etiology

Epigenetic regulation in Parkinson disease etiology

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Cheng-Yuan TANG,Jie-Qiong TAN,Dan-Ling WANG,zhuo-hua zhang state key laboratory of medical genetics,Xiangya medical School,Central South University,Changsha,China

＜正＞It is well documented that both genetic and environmental factors play important roles in etiology of Parkinson disease（PD）.Genetic studies of familial cases identify mutations in more than 10 genes causing *** pathophysiological function of these genes remains largely ***,a number of pesticides and herbicides induce parkinsonism in both human and animal *** of them are shown to regulate PD associated genes. During the past decade,we have interested in roles of genes-environmental factors interaction in PD *** results suggest that PD-related environmental factors contribute to PD etiology likely via epigenetically regulation of PD associated *** this presentation,we will discuss in detail PD associated epigenetic modification.

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Asperochones A and B,two antimicrobial aromatic polyketides from the endophytic fungus Aspergillus ***-2

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Chinese Chemical Letters 2024年第9期35卷 206-209页

作者： Hong zhang Cui-Ping Li Li-Li Wang zhuo-Da Zhou Wen-Sen Li Ling-Yi Kong Ming-hua Yang Jiangsu key laboratory of Bioactive Natural Product Research and state key laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009China

Two novel fungal metabolites,asperochones A and B,were obtained from an Aspergillus *** structures were determined by 1D/2D nuclear magnetic resonance(NMR)spectroscopy,high resolution electrospray ionization mass spectroscopy(HRESIMS),and single-crystal X-ray diffraction *** A possesses an intriguing skeleton bearing 5/6/6/6/7/5/5/5 octacyclic ring system,and asperochone B also exhibits an unusual carbon skeleton with five stereochiral *** structures were proposed as heterotrimeric and heterodimeric products of aromatic *** addition,asperochone A exhibited a potential anti-tuberculosis effect since it showed a moderate potency against Mycobacterium smegmatis.

关键词： Aspergillus sp. Asperochones A and B Aromatic polyketides Heterotrimeric compound Anti-tuberculosis effect Antifibrotic activity

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Genetic mechanism of body size variation in groupers:Insights from phylotranscriptomics

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Zoological Research 2024年第2期45卷 314-328页

作者： Wei-Wei zhang zhuo-Ying Weng Xi Wang Yang Yang Duo Li Le Wang Xiao-Chun Liu Zi-Ning Meng state key laboratory of Biocontrol Institute of Aquatic Economic Animals and Guangdong Province Key Laboratory of Aquatic Economic AnimalsSchool of Life SciencesSun Yat-sen UniversityGuangzhouGuangdong 510275China Southern laboratory of Ocean Science and Engineering(Zhuhai) ZhuhaiGuangdong 519000China Area of Ecology and Biodiversity School of Biological SciencesUniversity of Hong KongHong Kong SAR 999077China Molecular Population genetics Group Temasek Life Sciences LaboratorySingapore City 117604Singapore

Animal body size variation is of particular interest in evolutionary biology,but the genetic basis remains largely *** studies have shown the presence of two parallel evolutionary genetic clusters within the fish genus Epinephelus with evident divergence in body size,providing an excellent opportunity to investigate the genetic basis of body size variation in ***,we performed phylotranscriptomic analysis and reconstructed the phylogeny of 13 epinephelids originating from the South China *** genetic clades with an estimated divergence time of approximately 15.4 million years ago were correlated with large and small body size,respectively.A total of 180 rapidly evolving genes and two positively selected genes were identified between the two *** enrichment analyses of these candidate genes revealed distinct enrichment categories between the two *** pathways and genes may play important roles in body size variation in groupers through complex regulatory *** on our results,we speculate that the ancestors of the two divergent groups of groupers may have adapted to different environments through habitat selection,leading to genetic variations in metabolic patterns,organ development,and lifespan,resulting in body size divergence between the two locally adapted *** findings provide important insights into the genetic mechanisms underlying body size variation in groupers and species differentiation.

关键词： Phylotranscriptomics Grouper Body size Rapidly evolving genes(REGs) Positively selected genes(PSGs)

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Enhancement of naked FIX minigene expression by chloroquine in mice

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Acta Pharmacologica Sinica 2004年第5期25卷 28-33页

作者： Hong-yan CHEN, huan-zhang ZHU, Bin LU, Xuan XU, Ji-hua YAO, Qi SHEN, Jing-lun XUE1state key laboratory of Genetic Engineering, Institute of genetics,School of Life Sciences, Fudan University, Shanghai 200433, China state key laboratory of Genetic Engineering Institute of Genetics School of Life Sciences Fudan University Shanghai 200433 China

AIM: To study the effect of chloroquine on the expression of human clotting factor IX (hFIX) in mice. METHODS:Hydrodynamics-based naked DNA plasmid administration was performed by tail vein injection of 10 g of pCMV-hFIX and chloroquine (0, 100, 200, and 500 mol/L) in 2.2 mL of Ringer solution within 6-7 s, the level andstability of hFIX expression, liver damage and toxicity were then examined. RESULTS: The maximum expression ofhFIX level was 4.41.8 mg/L at 8 h after injection, 9.71.6 mg/L at 24 h only existed in 200 mol/L chloroquine-treated animals, which is 3-4 fold higher than that of control (P0.05). CONCLUSION: Chloroquine can enhance and sustain exogenous geneexpression in vivo without side effect under our experimental conditions.

关键词： chloroquine factor IX naked plasmids

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Conditional and unconditional mapping of quantitative trait loci underlying plant height and tiller number in rice (Oryza sativa L.) grown at two nitrogen levels

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Progress in Natural Science:Materials International 2008年第12期18卷 1539-1547页

作者： hua Jiang~(a,b) Liang Jiang~b Longbiao Guo~b Zhenyu Gao~b Dali Zeng~b Lihuang Zhu~c Guohua Liang~a Qian Qian~b a state key laboratory of Rice Biology/key laboratory of Plant Functional Genomies,Ministry of Education of China,Yangzhou University,Yangzhou 225009,China b state key laboratory of Rice Biology,China National Rice Research Institute,Hangzhou 310006,China c Institute of genetics,Chinese Academy of Sciences,Beijing 100101,China state key laboratory of Rice Biology/key laboratory of Plant Functional Genomics Ministry of Education of China Yangzhou University Yangzhou 225009 China state key laboratory of Rice Biology China National Rice Research Institute Hangzhou 310006 China Institute of genetics Chinese Academy of Sciences Beijing 100101 China

In this study,we used 127 double haploid (DH) lines to analyze agricultural traits of *** DH lines,derived from a ZYQ8 (indica)/JX17 (japonica) cross by anther culture,contained 160 RFLP and 83 SSR *** and conditional quantitative trait loci (QTL) mapping was conducted to analyze plant height (PH) and tillers per plant (TP) at five growth stages that were grown at two nitrogen *** PH and 13 TP unconditional QTL were identified in the different growth stages,including 19 QTL from high-nitrogen (HN) and 14 QTL from low-nitrogen (LN) *** conditional QTL for 14 genomic regions under LN/HN con- ditions showed that there was a significant effect on PH and TP across the different *** one conditional QTL,ph2-3,was unable to be detected in unconditional *** QTL were detected in the first four rice growth stages than in the final ***- more,a line from the DH mapping population,DH78,was identified in extreme phenotypes of PH and TP that exhibited dwarfism and less-tiller (dft) *** gene dft1 was mapped to chromosome 2 using a backcrossed population of DH78/JX17 through a map- based cloning *** location of dft1 coincided with the mapping region of the small-LOD peak,QTL ph2 and tp2,which were identified in plants grown in low-nitrogen *** backcrossing and fine-mapping successfully delimited the dft1 locus to a 91 kb region.

关键词： Oryza sativa Quantitative trait loci Double haploid (DH) population Developmental behavior Nitrogen Map-based cloning

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Identification of QTLs for grain size and characterization of the beneficial alleles of grain size genes in large grain rice variety BL129

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Journal of Integrative Agriculture 2016年第1期15卷 1-9页

作者： GAO Xua ZHU Xu-dong FANG Na DUAN Peng-gen WU Ying-bao LUO Yue-hua LI Yun-hai Hainan key laboratory for Sustainable Utilization of Tropical Bioresources/Agricultural College Hainan UniversityHaikou 570228P.R.China state key laboratory of Rice Biology China National Rice Research InstituteChinese Academy of Agricultural SciencesHangzhou 310006P.R.China state key laboratory of Plant Cell and Chromosome Engineering Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101P.R.China

Grain size is one of the most important agronomic components of grain yield. Grain length, width and thickness are controlled by multiple quantitative trait loci （QTLs）. To understand genetic basis of large grain shape and explore the beneficial alleles for grain size improvement, we perform QTL analysis using an F2 population derived from a cross between the japonica variety Beilu 129 （BL129, wide and thick grain） and the elite indica variety huazhan （HZ, narrow and long grain）. A total number of eight major QTLs are detected on three different chromosomes. QTLs for grain width （qGW）, grain thickness （qGT）, brown grain width （qBGW）, and brown grain thickness （qBGT） explained 77.67, 36.24, 89.63, and 39.41% of total phenotypic variation, respectively. The large grain rice variety BL129 possesses the beneficial alleles of GW2 and qSW5/ GW5, which have been known to control grain width and weight, indicating that the accumulation of the beneficial alleles causes large grain shape in BL129. Further results reveal that the rare gw2 allele from BL129 increases grain width, thickness and weight of the elite indica variety huazhan, which is used as a parental line in hybrid rice breeding. Thus, our findings will help breeders to carry out molecular design breeding on rice grain size and shape.

关键词： rice quantitative trait grain size GW2 GW5

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Ancient mitochondrial genome depicts sheep maternal dispersal and migration in Eastern Asia

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Journal of genetics and Genomics 2024年第1期51卷 87-95页

作者： Liu Yang Xing zhang Yaning Hu Piao Zhu hua Li Zhenyu Peng Hai Xiang Xinying Zhou Xingbo Zhao National Engineering laboratory for Animal Breeding Key Laboratory of AnimalGeneticsBreeding and ReproductionMinistry of Agriculture and Rural AffairsCollege of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193China Guangdong Provincial key laboratory of Animal Molecular Design and Precise Breeding School of Life Science and EngineeringFoshan UniversityFoshanGuangdong 528225China state key laboratory of Agricultural Genomics BGI-ShenzhenShenzhenGuangdong 518083China key laboratory of Vertebrate Evolution and Human Origins Institute of Vertebrate Paleontology and PaleoanthropologyChinese Academy of SciencesBeijing 100044China

Sheep have been one of the most important groups of animals since ancient ***,the knowledge of their migration routes and genetic relationships is still poorly *** investigate sheep maternal migration histories alongside Eurasian communications routes,in this study,we obtain mitochondrial genomes(mitogenomes)from 17 sheep remains in 6 Chinese sites and 1 Uzbekistan site dated 4429–3100 years before present(BP).By obtaining the mitogenomes from the sheep(4429–3556 BP)found in the Tongtian Cave site in Xinjiang,Altai region of northwest China,our results support the emergence of haplogroup C sheep in Xinjiang as early as 4429–3556 *** combined phylogenetic analyses with extant ancient and modern sheep mitogenomes suggest that the Uzbekistan-Altai region may have been a migration hub for early sheep in eastern *** least two migration events have taken place for sheep crossing Eurasia to China,one passing by Uzbekistan and Northwest China to the middle and lower reaches of the Yellow River at approximately 4000 BP and another following the Altai region to middle Inner Mongolia from 4429 BP to 2500 ***,this study provides further evidence for early sheep utilization and migration patterns in Eastern Asia.

关键词： Sheep Ancient DNA Eastern Asia Mitochondrial genome Migration Altai

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Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

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Military medical Research 2024年第1期11卷 19-33页

作者： Liang-Kun Guo Yi Su Yu-Ya-Nan zhang Hao Yu Zhe Lu Wen-Qiang Li Yong-Feng Yang Xiao Xiao Hao Yan Tian-Lan Lu Jun Li Yun-Dan Liao Zhe-Wei Kang Li-Fang Wang Yue Li Ming Li Bing Liu Hai-Liang huang Lu-Xian Lv Yin Yao Yun-Long Tan Gerome Breen Ian Everall Hong-Xing Wang zhuo huang Dai zhang Wei-hua Yue Institute of Mental Health Peking University Sixth HospitalBeijing 100191China National Clinical Research Center for Mental Disorders Peking University Sixth HospitalBeijing 100191China NHC key laboratory of Mental Health and Research Unit of Diagnosis and Treatment of Mood Cognitive Disorder(2018RU006) Chinese Academy of Medical SciencesBeijing 100191China Peking University Huilongguan Clinical medical School Beijing Huilongguan HospitalBeijing 100096China Department of Psychiatry Jining Medical UniversityJining 272067ShandongChina Henan key Lab of Biological Psychiatry the Second Affiliated Hospital of Xinxiang Medical UniversityXinxiang 435001HenanChina key laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Institute of Psychiatry Psychology and NeuroscienceKing’s College LondonLondon WC2R 2LSUK state key laboratory of Cognitive Neuroscience and Learning Beijing Normal UniversityBeijing 100875China Analytic and Translational genetics Unit Massachusetts General HospitalBostonMA 02114USA Stanley Center for Psychiatric Research the Broad Institute of MIT and HarvardCambridgeMA 02141USA Department of Medicine Harvard Medical SchoolBostonMA 02115USA Department of Biostatistics and Computational Biology School of Life SciencesFudan UniversityShanghai 200438China Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijing 100053China state key laboratory of Natural and Biomimetic Drugs Key Laboratory for Neuroscience for Ministry of EducationSchool of Pharmaceutical SciencesPeking University Health Science CenterBeijing 100191China PKU-IDG/McGovern Institute for Brain Research Peking UniversityBeijing 100871China Chinese Institute for Brain Research Beijing 102206China

Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective *** studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been ***,further research is imperative to enhance precision medicine in SCZ ***:Participants with SCZ were recruited from two randomized *** discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)*** external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole ***,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic *** genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,*** study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin *** learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve ***:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment *** developed and externally validated predictio

关键词： Schizophrenia Antipsychotic drug Treatment response Prediction model genetics Epigenetics

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HvMPK4 phosphorylates HvWRKY1 to enhance its suppression of barley immunity to powdery mildew fungus

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Journal of genetics and Genomics 2024年第3期51卷 313-325页

作者： Pengya Xue Ling zhang Renchun Fan Yanan Li Xinyun Han Ting Qi Lifang Zhao Deshui Yu Qian-hua Shen state key laboratory of Plant Cell and Chromosome Engineering Institute of Genetics and Developmental BiologyInnovation Academy for Seed DesignChinese Academy of SciencesBeijing 100101China CAS Center for Excellence in Biotic Interactions College of Advanced Agricultural SciencesUniversity of Chinese Academy of SciencesBeijing 100049China Department of Nutritional Sciences&Toxicology University of CaliforniaBerkeleyCA 94720USA Lushan Botanical Garden Chinese Academy of ScienceJiujiangJiangxi 332900China

Mitogen-activated protein kinase(MAPK)cascades play important roles in disease resistance in model plant ***,the functions of MAPK signaling pathways in crop disease resistance are largely *** we report the function of HvMKK1-HvMPK4-HvWRKY1 module in barley immune ***4 is identified to play a negative role in barley immune response against Bgh,as virus-induced gene silencing of HvMPK4 results in enhanced disease resistance whilst stably overexpressing HvMPK4 leads to super-susceptibility to Bgh ***,the barley MAPK kinase HvMKK1 is found to specifically interact with HvMPK4,and the activated HvMKK1^(DD) variant specifically phosphorylates HvMPK4 in ***,the transcription factor HvWRKY1 is identified to be a downstream target of HvMPK4 and phosphorylated by HvMPK4 in vitro in the presence of HvMKK1^(DD).Phosphorylation assay coupled with mutagenesis analyses identifies S122,T284,and S347 in HvWRKY1 as the major residues phosphorylated by ***1 is phosphorylated in barley at the early stages of Bgh infection,which enhances its suppression on barley immunity likely due to enhanced DNA-binding and transcriptional repression *** data suggest that the HvMKK1-HvMPK4 kinase pair acts upstream of HvWRKY1 to negatively regulate barley immunity against powdery mildew.

关键词： Barley MPK4 WRKY1 Phosphorylation Disease resistance Powdery mildew

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