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中国遗传学会“发育、遗传和疾病”研讨会

作者： Xue-Song Liu~(1,4) Xi-Hua Li~1 Yi Wang~1 Run-Zhe Shu~(1,4) Long Wang~(1-3) Shun-Yuan Lu~(1-3) Hui Kong~3 Yue-E jin~1 Li-Jun Zhang~1 Jian Fei~3 Sai-Juan Chen~2 Zhu Chen~2 Ming-Min Gu~1 Zhen-Yu Lu~1 Zhu-Gang Wang~(1-3,*) 1 laboratory of Genetic Engineering,Institute of Health Sciences,shanghai Institutes for Biological Sciences,Chinese Academy of Sciences & shanghai jiao tong university school of medicine,shanghai 200025,pr china 2 state key laboratory of medical genomics,rui-jin hospital affiliated to shanghai jiao tong university school of medicine,shanghai 200025,pr china 3 shanghai Research Center for Model Organisms,shanghai 201203,pr china 4 Graduate school of Chinese Academy of Sciences,shanghai 200025,pr china.

Palladin was originally found up-regulated with NB4 cell differentiation induced by *** of palladin results in neural tube closure defects,liver herniation and embryonic *** we further report thatpailadinembryos exhibit a significant defect in erythropoiesis,characterized by dramatic reduction in definitive erythrocytes derived from fetal liver but not primitive erythrocytes from yolk *** reduction of erythrocytes is accompanied by increased apoptosis of erythroblasts and partial blockage of erythroid ***,colony forming assay shows no differences between wt and mutant fetal liver or yolk sac in the number and size of colonies *** addition,palladinfetal liver cells can reconstitute hematopoiesis in lethally-irradiated *** data strongly suggest that deficient erythropoiesis in palladin fetal liver is mainly due to compromised erythropoietic *** expected,erythroblastic island in palladin fetal liver was found *** liver cells fail to form erythroblastic island in ***,wt macrophages can form such units with either wt or mutant erythroblasts,while mutant macrophages lose their ability to bind wt or mutant *** data demonstrate that palladin is crucial for definitive erythropoiesis and erythroblastic island formation,and especially,required for normal function ofmacrophages in fetal liver.

关键词： Palladin Fetal liver Erythropoiesis Microenvironment Macrophage.

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*** as a model system for Parkinson disease

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Neuroscience Bulletin 2006年第2期22卷 124-128页

作者： Pu PU,Wei-Dong LE state key laboratory of medical genomics,ruijin hospital,shanghai jiao tong university school of medicine Institute of Health Sciences,shanghai Institutes for Biological Sciences,Chinese Academy of Sciences-shanghai jiao tong university school of medicine,shanghai 200031,china state key laboratory of medical genomics Ruijin HospitalShanghai Jiao Tong University School of Medicine Institute of Health Sciences Shanghai Institutes for Biological SciencesChinese Academy of Sciences-Shanghai Jiao Tong University School of MedicineShanghai 200031China

Parkinson disease(PD) is characterized by the selective loss of dopaminergic neurons in the substantia nigra. Although investigation in mammalian animal models of PD has enhanced our understanding of PD, the complexity of the mammalian nervous system and our inability to visualize DA neurons in vivo restricts the advances in elucidating the molecular mechanisms of PD. Conservation between C. elegans and mammals in genomic, biosynthetic and metabolic pathways as well as the advantages of observing DA neurons morphology in vivo and the ease of transgenic and genetic manipulation make C. elegans an excellent model organism for PD.

关键词： caenorhabditis elegans( C. elegans) Parkinson disease dopaminergic neuron

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From dissection of disease pathogenesis to elucidation of mechanisms of targeted therapies:leukemia research in the genomic era

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Acta Pharmacologica Sinica 2007年第9期28卷 1434-1449页

作者： Guang-blao ZHOU~(1,2),Guo LI~1,Sai-juan CHEN~1,Zhu CHEN~(1,3)~1 state key laboratory of medical genomics and shanghai Institute of Hematology,rui jin hospital affiliated to shanghai jiao tonguniversity school of medicine,shanghai 200025, china ~2 Guangzhou Institute of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou 510663,china state key laboratory of medical genomics and shanghai Institute of Hematology Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China Guangzhou Institute of Biomedicine and Health Chinese Academy of Sciences Guangzhou China

Leukemia is a group of heterozygous diseases of hematopoietic stem/progenitorcells that involves dynamic change in the *** of genetic abnor-malities critical to leukemia initiation provides insights into the elusiveleukemogenesis,identifies distinct subsets of leukemia and predicts prognosisindividually,and can also provide rational therapeutic targets for *** past three decades have seen tremendous advances in theanalysis of genotype-phenotype connection of leukemia,and in the identifica-tion of molecular biomarkers for leukemia ***,differentiationtherapy,targeted therapy and chemotherapy have turned several subtypes ofleukemia from highly fatal to highly *** use of all-trans retinoic acid andarsenic trioxide,which trigger degradation of PML-RARα,the causative fusionprotein generated by t (15;17) translocation in acute promyelocytic leukemia (APL),has led to a dramatic improvement of APL clinical outcome,lmatinib mesylate/Gleevec/STI571,which inhibits the tyrosine kinase activity of BCR-ABLoncoprotein,has now become the new gold standard for the treatmtent of chronicmyeloid *** use of chemotherapeutic agents together with a strin-gent application of prognostic factors for risk-directed therapy in clinical trialshas resulted in a steady improvement in the treatment outcome of acute lympho-blastic ***,the pace of progress extrapolates to a prediction ofleukemia control in the twenty-first century.

关键词： leukemia genomics cancer therapy

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Back to the future of oridonin: again,compound from medicinal herb shows potent antileukemia efficacies in vitro and in vivo

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Cell Research 2007年第4期17卷 274-276页

作者： Guang-Biao Zhou~(1,2) Sai-Juan Chen~1 Zhen-Yi Wang~1 Zhu Chen~1 ~1state key laboratory of medical genomics and shanghai Institute of Hematology,ruijin hospital affiliated to shanghai jiao tong university school of medicine,197 ruijin Road II,shanghai 200025,china ~2Guangzhou Institute of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou Science Park,Guangzhou 510663,china state key laboratory of medical genomics and shanghai Institute of Hematology Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China Guangzhou Institute of Biomedicine and Health Chinese Academy of Sciences Guangzhou Science Park Guangzhou China

Traditional Chinese medicine(TCM)has been widelyand successfully used in treating illnesses ranging frominflammation to cancer,and compounds from medicinalherbs and minerals are playing more and more importantroles in taming various kinds of diseases[1],exemplifiedby artemisinin and arsenic trioxide(ATO).Artemisinin(or Qinghaosu in Chinese)is isolated from a plant calledsweet wormwood(Artemisia annua;or Qinghao in Chi-nese)which has been used as an antipyretic remedy formore than 1500 years in *** has impressiveparasiticidal properties in vitro and in vivo,and is now oneof the most important class of antimalarial agents[2,3].ATO is a common,naturally occurring substance whichhad been used in china for a long time as a therapeuticagent for some severe diseases with the ancient philosophyof'treating an evil with a toxic'[4].In 1990s,ATO wasshown to be able to cause partial differentiation at low doseand apoptosis at high concentration of acute promyelocyticleukemia(APL)cells[5],and induce complete remissionin 90% of patients with relapsed or refractory APL[6-8].

关键词： AML Back to the future of oridonin again,compound from medicinal herb shows potent antileukemia efficacies in vitro and in vivo

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Germinal cell aplasia in Kif18a mutant male mice due to impaired chromosome congression and dysregulated CENP-E and BubR1

Germinal cell aplasia in Kif18a mutant male mice due to impa...

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第十一届中国细胞生物学学术大会暨2009西安细胞生物学国际会议

作者： Zhu-Gang Wang Department of medical Genetics,Faculty of Basic medicine,shanghai jiao tong university school of medicine (SJTUSM),shanghai 200025,china state key laboratory of medical genomics,rui-jin hospital affiliated to SJTUSM,shanghai 200025,china shanghai Research Centre for Model Organisms,shanghai 201210,china

Orderly chromosome congression at the metaphase plate,paramount to vertebrate mitosis and meiosis,is controlled by a number of molecular regulators including ***-8 motor Kif18a functions to control mitotic chromosome alignment at the midzone by negative control of kinetochore *** we report that ablation of Kif18a function results in complete sterility in male but not in female *** examination reveals that Kif18a

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The relationship between interleukin-6 circulating levels and coronary heart disease;a meta-analysis implementing mendelian randomization approach

The relationship between interleukin-6 circulating levels an...

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InternationalHeartForum

作者： Wenquan Niu 1 state key laboratory of medical genomics ruijin hospital shanghai jiao tong university school of medicine ruijin Second Road 197 shanghai 200025 china 2 shanghai Institute of Hypertension ruijin Second Road 197 shanghai 200025 china

＜正＞Objective We aimed to investigate whether there was causal relevance between circulating interleukin 6（IL-6） levels and CHD by implementing meta-analysis-based mendelian randomization approach with IL-6 gene G-174C as an instrument. Methods and Results Data were available from 19 studies involving 9417 CHD patients and 15982 ***-effects model was *** comparison of IL6 gene allele - 174C with -174G had only 4%increased risk for CHD(95%confidence

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Nurrl is essential for the differentiation of DA neurons during zebrafish embryogenesis

Nurrl is essential for the differentiation of DA neurons dur...

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中国神经科学学会第四次会员代表大会暨第七届全国学术会议

作者： Guang-rui LUO,Yi CHEN,Xu-Ping LI,Ting-Xi LIU~*,Wei-Dong LE~* Institute of Health Sciences,shanghai Institutes for Biological Sciences,Chinese Academy of Sciences and shanghai jiao tong university school of medicine,200025,shanghai,china state key laboratory for medical genomics, ruijin hospital,jiao tong university school of medicine,200025,shanghai,china Institute of Neurology,ruijin hospital,jiao tong university school of medicine,200025,shanghai.china odel Organism Division E-Institutes of shanghai Universities,shanghai,china

＜正＞Nurrl has been recently found to be critical for the development and maintenance of mesencephalic dopamine （DA） *** uncover the molecular mechanisms by which Nurr 1 contributes to the development of DA neurons,we have applied zebrafish to study the topographic distribution of nurrl transcripts during the early embryogenesis because of its ectogenesis and transparent,as well as its correlation with neuron progenitor marker（ngn1） and DA neuron markers （tyrosine hydroxylase,TH and DA transporter,DAT）.Our studies show that although nurrl transcripts did not co-localize with TH and DAT transcripts in the basal forebrain,it partially co-expressed with ngn1 in the region before 36 hpf. Knockdown of Nurr1 resulted in significant decrease of TH+ and DAT+ DA neurons,accompanied by reduction of DA transmitter and locomotive *** number of DA neurons and reduced DA transmitter in Nurr1-deficient embryos were significantly rescued by the injection of mouse Nurrl ***,the number of nurrl + cells in Nurr1-deficient embryos was increased by 1.6 *** results suggest that Nurrl plays a crucial role in the differentiation and maturation rather than the survival of DA progenitors during zebrafish early embryogenesis.

关键词： nurr1 DA progenitors and zebrafish

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Palladin Regulates Cell and Extracellular Matrix Interaction through Maintaining Normal Actin Cytoskeleton Architecture and Stabilizing Beta1-integrin.

Palladin Regulates Cell and Extracellular Matrix Interaction...

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中国遗传学会七届二次青年研讨会

作者： Xue-Song Liu,Hui-Jun Luo,Hua Yang,Long Wang,Hui Kong,Yue-E jin,Fang Wang,Ming-Min Gu,Zhu Chen,Zhen-Yu Lu,Zhu-Gang Wang laboratory of Genetic Engineering,Department of medical Genetics,Institute of Health Sciences Jointly Founded by shanghai jiao tong university medical school & shanghai Institutes for Biological Sciences of Chinese Academy of Sciences,shanghai 200025,pr china state key laboratory of medical genomics,rui-jin hospital affiliated to shanghai jiao tong university medical Schooi,shanghai 200025,pr china shanghai Research Center for Model Organisms,shanghai 201203,pr china Graduate school of Chinese Academy of Sciences,shanghai 200025,pr china

Cell and extracellular matrix (ECM) interaction plays an important role in development and normal cellular function. Cell adhesion and cell spreading on ECM are two basic cellular behaviours related to cell-ECM interaction. Here we show that palladin, a novel actin cytoskeleton-associated protein, is actively involved in the regulation of cell-ECM interaction. It was found that palladin-deficient mouse embryonic fibrobiasts (MEFS) display decreased cell adhesion and compromised cell spreading on various ECMs. Disorganized actin cytoskeleton architecture characterized by faint stress fibers, less lamellipodia and focal adhesions can account for the weakened cell-ECM interaction in palladia MEFs. Furthermore, decreased polymerized filament actin and increased globular actin can be observed in palladin MEFs, strongly suggesting that palladin is essential for the formation or stabilization of polymerized filament actin. Elevated phospho-cofilin level and proper responses in cofilin phosphorylation to either Rho signal agonist or antagonist in palladin MEFs indicate that disrupted stress fibers in pallacdin MEFs is not associated with cofilin phosphoryiation. More interestingly, the protein level of ECM receptor β1-integrin is dramatically decreased in MEFs lacking palladin. Down-regulation of β1-integrin protein can be restored by proteasome inhibitor MG-132 treatment. All these data implicate that palladin is essential for cell-ECM interaction through maintaining normal actin cytoskeleton architecture and stabilizing β1-integrin protein.

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Acute promyelocytic leukemia:from highly fatal to highly curable

Acute promyelocytic leukemia:from highly fatal to highly cur...

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2008全国消化肿瘤新技术治疗研讨会

作者： Zhen-Yi Wang~1 Zhu Chen~(1,2) 1 shanghai Institute of Hematology and state key laboratory of medical genomics,rui jin hospital affiliated to the shanghai jiao tong university (SJTU) school of medicine,shanghai 2 shanghai Canter for Systems Biomedicine at SJTU,shanghai,china

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid ***,it is identified as the M3 subtype of acute myeloid leukemia by the French-American- British classification and cytogenetically is characterized by a balanced reciprocal translocation between chromosomes 15 and 17,which results in the fusion between promyelocytic leukemia (PML)gene and retinoic acid receptor(RAR).It seems that the disease is the most malignant form of acute leukemia with a severe bleeding tendency and a fatal course of only weeks. Chemotherapy (CT;daunorubicin,idarubicin and cytosine arabinoside)was the front-line treatment of APL with a complete remission (CR) rate of 75% to 80% in newly diagnosed patients. Despite all these progresses,the median duration of remission ranged from 11 to 25 months and only 35% to 45% of the patients could be cured by *** the introduction of all-trans retinoic acid (ATRA) in the beatment and optimization of the ATRA-based regimens,the CR rate was raised up to 90% to 95% and 5-yeer disease free survival(DFS) to 74%.The use of arsenic trioxide(ATO) since early 1990s further improved the clinical outcome of refractory or relapsed as well as newly diagnosed *** this article,we review the history of introduction of ATRA and ATO into clinical use and the mechanistic studies in understanding this model of cancer targeted therapy.

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The influence of the genetic and non-genetic factors on bone mineral density and osteoporotic fracture

The influence of the genetic and non-genetic factors on bone...

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中华医学会第十次全国内分泌学学术会议

作者： Yan-hua Deng,Jan-min Liu,Lin Zhao,Min- jia Zhang~(,state key laboratory of medical genomics,Molecular medicine Center,rui-jin hospital,shanghai jiao-tong university school of medicine

Objectlve:Osteoporosis is a complex polygenic disease that is characterized by reduced bone mass and microarchitectural deterioration of bone tissue,thereby leading to a loss of strength and increased risk of *** underlying causes of osteoporosis and osteoporotic fractures are multiple,including several environmental factors and genetic *** research aimed to investigate the effects of genetic and nongenetic factors on bone mineral density(BMD)and osteoporotic fractures.

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