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  • Cell Research
    Jiang 1 2 4 1 State Key Laboratory of Protein and Plant Gene Research School of Life Sciences Peking University Beijing 100871 China 2 Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education School of Life Sciences Peking University Beijing 100871 China 3 Biodynamic Optical Imaging Center BIOPIC School of Life Sciences Peking University Beijing 100871 China 4 Peking Tsinghua Center for Life Sciences Beijing China 5 State Key Laboratory for Infectious Disease Prevention and Control National Institute for Communicable Disease Control and Prevention Chinese Centre for Disease Control and Prevention Beijing 102206 China 6 Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases Hangzhou 310003 China Correspondence Xiaodong Su Zhengfan Jiang E mail xdsu pku edu cn jiangzf pku edu cn Cyclic dinucleotides act as intracellular second messengers modulating a variety of cellular activities including innate immune activation Although phosphodiesterases PDEs hydrolyzing c di GMP and c di AMP have been identified no PDEs for cGAMPs have been reported Here we identified the first three cGAMP specific PDEs in V cholerae herein designated as V cGAP1 2 3 V cGAPs are HD GYP domain containing proteins and specifically break 3 3 cGAMP but not other forms of cGAMP 3 3 cGAMP is first linearized by all three V cGAPs to produce 5 pApG which is further hydrolyzed into 5 ApG by V cGAP1 In this two step reaction V cGAP1 functions as both a PDE and a 5 nucleotidase In vivo experiments demonstrated that V cGAPs play non redundant roles in cGAMP degradation The high specificity of V cGAPs on 3 3 cGAMP suggests the existence of specific PDEs for other cGAMPs including 2 3 cGAMP in mammalian cells The absolute requirement of the GYP motif for 3 3 cGAMP degradation suggests that HD domain

    Original URL path: http://www.cell-research.com/arts.asp?id=2098 (2016-02-14)
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  • Cell Research
    Sen Fang Sui 1 1 State Key Laboratory of Biomembrane and Membrane Biotechnology Center for Structural Biology School of Life Sciences Tsinghua University Beijing 100084 China 2 Ministry of Education Key Laboratory of Protein Science Center for Structural Biology Tsinghua Peking Joint Center for Life Sciences School of Life Sciences Tsinghua University Beijing 100084 China Correspondence Sen Fang Sui Hong Wei Wang E mail suisf mail tsinghua edu cn hongweiwang tsinghua edu cn N ethylmaleimide sensitive factor NSF and α soluble NSF attachment proteins α SNAPs work together within a 20S particle to disassemble and recycle the SNAP receptor SNARE complex after intracellular membrane fusion To understand the disassembly mechanism of the SNARE complex by NSF and α SNAP we performed single particle cryo electron microscopy analysis of 20S particles and determined the structure of the α SNAP SNARE assembly portion at a resolution of 7 35 Å The structure illustrates that four α SNAPs wrap around the single left handed SNARE helical bundle as a right handed cylindrical assembly within a 20S particle A conserved hydrophobic patch connecting helices 9 and 10 of each α SNAP forms a chock protruding into the groove of the SNARE four helix bundle

    Original URL path: http://www.cell-research.com/arts.asp?id=2099 (2016-02-14)
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  • Cell Research
    Zhou 5 Jing Gao 5 Bo Zhang 1 2 3 Wenyan Xu 1 2 3 Jiang Liu 1 2 3 Dingkong Liang 1 2 3 Liang Liu 1 2 3 Chen Liu 1 2 3 Jiang Long 1 2 3 Haijun Zhou 6 Paul J Chiao 6 Jin Xu 1 2 3 Quanxing Ni 1 2 3 Daming Gao 4 and Xianjun Yu 1 2 3 1 Department of Pancreatic and Hepatobiliary Surgery Fudan University Shanghai Cancer Center Shanghai 200032 China 2 Department of Oncology Shanghai Medical College Fudan University Shanghai 200032 China 3 Pancreatic Cancer Institute Fudan University Shanghai 200032 China 4 Key Laboratory of System Biology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China 5 Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 China 6 Department of Molecular and Cellular Oncology the University of Texas MD Anderson Cancer Center Houston TX 77030 USA Correspondence Xianjun Yu E mail yuxianjun fudan edu cn yuxianjun fudanpci org F box and WD repeat domain containing 7 FBW7 is the substrate recognition component of the Skp1 Cul1 F box SCF ubiquitin ligase complex and functions as a major tumor suppressor by targeting various oncoproteins for degradation Genomic deletion or mutation of FBW7 has frequently been identified in many human cancers but not in pancreatic ductal adenocarcinoma Thus it is important to know how the tumor suppressive function of FBW7 is impaired in pancreatic cancer In this study we first observed that low FBW7 expression correlated significantly with ERK activation in pancreatic cancer clinical samples primarily due to KRAS mutations in pancreatic cancer We further showed that ERK directly interacted with FBW7 and phosphorylated FBW7 at Thr205 which sequentially promoted FBW7 ubiquitination and proteasomal degradation Furthermore the phospho deficient T205A

    Original URL path: http://www.cell-research.com/arts.asp?id=2100 (2016-02-14)
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  • Cell Research
    of Sciences Max Planck Partner Institute for Computational Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences 320 Yue Yang Road Shanghai 200031 China 2 University of Chinese Academy of Sciences Beijing 100049 China 3 Beijing Centers for Diseases Control and Prevention CDC Centers for Preventive Medical Research Beijing 100013 China 4 Collaborative Innovation Center for Genetics and Developmental Biology Fudan University Shanghai 200433 China Correspondence Jing Dong J Han Tel 86 21 54920458 E mail jdhan picb ac cn Aging is associated with many complex diseases Reliable prediction of the aging process is important for assessing the risks of aging associated diseases However despite intense research so far there is no reliable aging marker Here we addressed this problem by examining whether human 3D facial imaging features could be used as reliable aging markers We collected 300 3D human facial images and blood profiles well distributed across ages of 17 to 77 years By analyzing the morphological profiles we generated the first comprehensive map of the aging human facial phenome We identified quantitative facial features such as eye slopes highly associated with age We constructed a robust age predictor and found that on average people of the same

    Original URL path: http://www.cell-research.com/arts.asp?id=2101 (2016-02-14)
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  • Cell Research
    Cai 1 Jun Ji 1 Jian Fang Li 1 Lotfi Chouchane 3 Ying Yan Yu 1 Fang Zhen Sun 2 Zhi Heng Xu 2 Bing Ya Liu 1 and Zheng Gang Zhu 1 1 Department of Surgery Shanghai Key Laboratory of Gastric Neoplasms Shanghai Institute of Digestive Surgery Ruijin Hospital School of Medicine Shanghai Jiao Tong University 197 Ruijin Er Rd Shanghai 200025 China 2 State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental Biology Chinese Academy of Sciences 1 West Beichen Rd Beijing 100101 China 3 Laboratory of Genetic Medicine and Immnology Weill Cornell Medical College in Qatar Education City P O Box 24144 Doha Qatar Correspondence Zheng Gang Zhu Bing Ya Liu Zhi Heng Xu Tel 86 21 6433 3414 E mail zhenggang zhu yahoo com byliu sjtu edu cn zhxu genetics ac cn Tumor initiation and growth depend on its microenvironment in which cancer associated fibroblasts CAFs in tumor stroma play an important role Prostaglandin E2 PGE2 and interleukin IL 6 signal pathways are involved in the crosstalk between tumor and stromal cells However how PGE2 mediated signaling modulates this crosstalk remains unclear Here we show that microRNA miR 149 links PGE2 and IL 6 signaling in mediating the crosstalk between tumor cells and CAFs in gastric cancer GC miR 149 inhibited fibroblast activation by targeting IL 6 and miR 149 expression was substantially suppressed in the CAFs of GC miR 149 negatively regulated CAFs and their effect on GC development both in vitro and in vivo CAFs enhanced epithelial to mesenchymal transition EMT and the stem like properties of GC cells in a miR 149 IL 6 dependent manner In addition to IL 6 PGE2 receptor 2 PTGER2 EP2 was revealed as another potential target of miR 149 in fibroblasts Furthermore H pylori

    Original URL path: http://www.cell-research.com/arts.asp?id=2102 (2016-02-14)
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  • Cell Research
    Wang 1 Jun Zhang 2 Mun Hon Ng 1 2 Choy Leong Hew 3 5 Shaowei Li 1 2 Ningshao Xia 1 2 and J Sivaraman 3 1 State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics School of Life Sciences Xiamen University Xiamen Fujian 361005 China 2 National Institute of Diagnostics and Vaccine Development in Infectious Disease School of Public Health Xiamen University Xiamen Fujian 361005 China 3 Department of Biological Sciences National University of Singapore Singapore 117543 Singapore 4 Current address Institute of Molecular and Cell Biology Singapore 138673 Singapore 5 Current address Mechanobiology Institute National University of Singapore Singapore 117411 Singapore Correspondence J Sivaraman Shaowei Li Ningshao Xia E mail dbsjayar nus edu sg shaowei xmu edu cn nsxia xmu edu cn Hepatitis E virus HEV a non enveloped positive sense single stranded RNA virus is a major cause of enteric hepatitis Classified into the family Hepeviridae HEV comprises four genotypes genotypes 1 4 which belong to a single serotype We describe a monoclonal antibody mAb 8G12 which equally recognizes all four genotypes of HEV with 2 53 3 45 nM binding affinity The mAb 8G12 has a protective neutralizing capacity which can significantly block virus infection in host cells Animal studies with genotypes 1 3 and 4 confirmed the cross genotype neutralizing capacity of 8G12 and its effective prevention of hepatitis E disease The complex crystal structures of 8G12 with the HEV E2s domain the most protruded region of the virus capsid of the abundant genotypes 1 and 4 were determined at 4 0 and 2 3 Å resolution respectively These structures revealed that 8G12 recognizes both genotypes through the epitopes in the E2s dimerization region Structure based mutagenesis and cell model assays with virus like particles identified several conserved residues Glu549 Lys554 and Gly591 that

    Original URL path: http://www.cell-research.com/arts.asp?id=2103 (2016-02-14)
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  • Cell Research
    1 Jianru Zuo 1 Yonghong Wang 1 and Jiayang Li 1 1 State Key Laboratory of Plant Genomics and National Center for Plant Gene Research Beijing Institute of Genetics and Developmental Biology Chinese Academy of Sciences Beijing 100101 China 2 Current address Department of Pathology and Cell Biology University of South Florida Tampa FL 33612 USA Correspondence Jiayang Li Tel 86 10 6480 6577 E mail jyli genetics ac cn Programmed cell death PCD is of fundamental importance to development and defense in animals and plants In plants a well recognized form of PCD is hypersensitive response HR triggered by pathogens which involves the generation of reactive oxygen species ROS and other signaling molecules While the mitochondrion is a master regulator of PCD in animals the chloroplast is known to regulate PCD in plants Arabidopsis Mosaic Death 1 MOD1 an enoyl acyl carrier protein ACP reductase essential for fatty acid biosynthesis in chloroplasts negatively regulates PCD in Arabidopsis Here we report that PCD in mod1 results from accumulated ROS and can be suppressed by mutations in mitochondrial complex I components and that the suppression is confirmed by pharmaceutical inhibition of the complex I generated ROS We further show that intact

    Original URL path: http://www.cell-research.com/arts.asp?id=2104 (2016-02-14)
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  • Cell Research
    2 Yong gang Ren 1 Shan ye Gu 1 4 Yuan hang Xiang 3 Cheng Huang 4 and Jiu lin Du 1 2 3 1 Institute of Neuroscience State Key Laboratory of Neuroscience Center for Excellence in Brain Science Shanghai Institutes for Biological Sciences Chinese Academy of Sciences 320 Yue Yang Road Shanghai 200031 China 2 Graduate School University of Chinese Academy of Sciences 320 Yue Yang Road Shanghai 200031

    Original URL path: http://www.cell-research.com/arts.asp?id=2105 (2016-02-14)
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