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  • Cell Research
    2 and Wanli Liu 1 3 1 MOE Key Laboratory of Protein Science School of Life Sciences Tsinghua University Beijing 100084 China 2 Laboratory of Immunogenetics National Institute of Allergy and Infectious Diseases NIH Rockville MD 20852 USA 3 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases Tsinghua University Beijing 100084 China Correspondence Susan K Pierce Tel 301 496 9589 Fax 301 402 0259 E mail spierce nih gov Wanli Liu Tel 86 10 6277 2730 E mail liuwanli biomed tsinghua edu cn Acquired immunological memory is a striking phenomenon A lethal epidemic sweeps through a naïve population many die but those who survive are never attacked twice never at least fatally as the historian Thucydides observed in 430 BCE Antibody memory is critical for protection against many human infectious diseases and is the basis for nearly all current human vaccines Antibody memory is encoded in part in isotype switched immunoglobulin Ig G expressing memory B cells that are generated in the primary response to antigen and give rise to rapid high affinity and high titered antibody responses upon challenge with the same antigen How IgG B cell receptors BCRs and antigen induced IgG BCR signaling contribute to

    Original URL path: http://www.cell-research.com/arts.asp?id=1935 (2016-02-14)
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  • Cell Research
    Wang 2 Wuzhou Yang 2 and Gang Pei 1 3 1 State Key Laboratory of Cell Biology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences 320 Yueyang Road Shanghai 200031 China 2 Institute of Neurobiology Institutes of Brain Science and State Key Laboratory of Medical Neurobiology Fudan University Shanghai 200032 China 3 School of Life Science and Technology Tongji University Shanghai 200092 China Correspondence Gang Pei E mail gpei sibs ac cn Jian Zhao E mail jzhao sibs ac cn Neural progenitor cells NPCs can be induced from somatic cells by defined factors Here we report that NPCs can be generated from mouse embryonic fibroblasts by a chemical cocktail namely VCR V VPA an inhibitor of HDACs C CHIR99021 an inhibitor of GSK 3 kinases and R Repsox an inhibitor of TGF β pathways under a physiological hypoxic condition These chemical induced NPCs ciNPCs resemble mouse brain derived NPCs regarding their proliferative and self renewing abilities gene expression profiles and multipotency for different neuroectodermal lineages in vitro and in vivo Further experiments reveal that alternative cocktails with inhibitors of histone deacetylation glycogen synthase kinase and TGF β pathways show similar efficacies for ciNPC

    Original URL path: http://www.cell-research.com/arts.asp?id=1936 (2016-02-14)
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  • Cell Research
    Xin Wang 1 2 Hairi Li 4 Min Min Hua 1 2 Shuang Zhao 1 2 Si Da Hu 1 2 Li Gang Wu 1 2 Hui Juan Shi 5 Yong Li 6 Xiang Dong Fu 4 Liang Hu Qu 3 En Duo Wang 1 and Mo Fang Liu 1 2 1 Center for RNA Research State Key Laboratory of Molecular Biology University of Chinese Academy of Sciences Shanghai 200031 China 2 Shanghai Key Laboratory of Molecular Andrology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China 3 Key Laboratory of Gene Engineering of the Ministry of Education State Key Laboratory of Biocontrol Sun Yat sen University Guangzhou 510275 China 4 Department of Cellular and Molecular Medicine University of California San Diego La Jolla CA 92093 0651 USA 5 National Population and Family Planning Committee Key Laboratory of Contraceptive Drugs Devices Shanghai Institute of Planned Parenthood Research Shanghai 200032 China 6 Department of Biochemistry and Molecular Biology and Center for Genetics and Molecular Medicine School of Medicine University of Louisville Louisville KY 40202 US Correspondence Mo Fang Liu Tel 86 21 54921146 Fax 86 21 54921011 E mail mfliu sibcb ac cn Spermatogenesis in mammals is characterized by two waves of piRNA expression one corresponds to classic piRNAs responsible for silencing retrotransponsons and the second wave is predominantly derived from nontransposon intergenic regions in pachytene spermatocytes but the function of these pachytene piRNAs is largely unknown Here we report the involvement of pachytene piRNAs in instructing massive mRNA elimination in mouse elongating spermatids ES We demonstrate that a piRNA induced silencing complex pi RISC containing murine PIWI MIWI and deadenylase CAF1 is selectively assembled in ES which is responsible for inducing mRNA deadenylation and decay via a mechanism that resembles the

    Original URL path: http://www.cell-research.com/arts.asp?id=1937 (2016-02-14)
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  • Cell Research
    Sung 2 Yingrui Li 1 and Jun Wang 1 9 10 11 1 BGI Shenzhen Shenzhen Guangdong 518083 China 2 Institute of Digestive Disease and the Department of Medicine and Therapeutics State Key Laboratory of Digestive Disease Li Ka Shing Institute of Health Sciences The Chinese University of Hong Kong Hong Kong 3 Laboratory of Molecular Oncology Key Laboratory of Carcinogenesis and Translational Research Ministry of Education Peking University School of Oncology Beijing Cancer Hospital Institute Beijing 100142 China 4 School of Biological Science and Medical Engineering Southeast University Nanjing China 5 State Key Laboratory of Bioelectronics Southeast University Nanjing Jiangsu 210096 China 6 Department of Peadiatrics Adolescent medicine The University of Hong Kong Hong Kong 7 Department of Computational Medicine and Bioinformatics Medical School University of Michigan Ann Arbor USA 8 Department of Surgery Peking University School of Oncology Beijing Cancer Hospital Institute Beijing 100142 China 9 Department of Biology University of Copenhagen Ole Maaløes Vej 5 2200 Copenhagen Denmark 10 Princess Al Jawhara Center of Excellence in the Research of Hereditary Disorders King Abdulaziz University Jeddah 21589 Saudi Arabia 11 Macau University of Science and Technology Avenida Wai long Taipa Macau 999078 China Correspondence Jun Wang Tel 86 10 80481662 Fax 86 10 80498676 E mail wangj genomics org cn Yingrui Li Tel 86 10 80481662 Fax 86 10 80498676 E mail liyr genomics cn Joseph JY Sung Tel 852 37636103 Fax 852 21445330 E mail jjysung cuhk edu hk Single cell sequencing is a powerful tool for delineating clonal relationship and identifying key driver genes for personalized cancer management Here we performed single cell sequencing analysis of a case of colon cancer Population genetics analyses identified two independent clones in tumor cell population The major tumor clone harbored APC and TP53 mutations as early oncogenic events whereas

    Original URL path: http://www.cell-research.com/arts.asp?id=1938 (2016-02-14)
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  • Cell Research
    Jiang 3 Karsten Melcher 1 and H Eric Xu 1 2 1 Laboratory of Structural Sciences Van Andel Research Institute Grand Rapids MI 49503 USA 2 VARI SIMM Center Center for Structure and Function of Drug Targets Key Laboratory of Receptor Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 China 3 Center for Drug Discovery and Design State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 China Correspondence H Eric Xu Tel 1 616 234 5772 E mail eric xu vai org Yuanzheng He E mail ajian he vai org Wei Yi E mail yiwei simm simm ac cn The evolution of glucocorticoid drugs was driven by the demand of lowering the unwanted side effects while keeping the beneficial anti inflammatory effects Potency is an important aspect of this evolution as many undesirable side effects are associated with use of high dose glucocorticoids The side effects can be minimized by highly potent glucocorticoids that achieve the same treatment effects at lower doses This demand propelled the continuous development of synthetic glucocorticoids with increased potencies but the structural basis of their potencies is poorly understood To determine the mechanisms underlying potency we solved the X ray structures of the glucocorticoid receptor GR ligand binding domain LBD bound to its endogenous ligand cortisol which has relatively low potency and a highly potent synthetic glucocorticoid mometasone furoate MF The cortisol bound GR LBD revealed that the flexibility of the C1 C2 single bond in the steroid A ring is primarily responsible for the low affinity of cortisol to GR In contrast we demonstrate that the very high potency of MF is achieved by its C 17α furoate group completely filling the ligand binding pocket thus providing additional anchor contacts for high

    Original URL path: http://www.cell-research.com/arts.asp?id=1939 (2016-02-14)
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  • Cell Research
    3 5 and Xia Lin 2 1 Life Sciences Institute Zhejiang University Hangzhou Zhejiang 310058 China 2 Michael E DeBakey Department of Surgery Baylor College of Medicine Houston TX 77030 USA 3 Department of Molecular Cellular Biology Baylor College of Medicine Houston TX 77030 USA 4 Institute of Biosciences and Technology Texas A M University Health Science Center Houston TX 77030 USA 5 Department of Molecular Physiology and Biophysics Baylor College of Medicine Houston TX 77030 USA Correspondence Xin Hua Feng Xia Lin E mail xfeng bcm edu xialin bcm edu Bone morphogenetic proteins BMPs belong to the TGF β superfamily of structurally related signaling proteins that regulate a wide array of cellular functions The key step in BMP signal transduction is the BMP receptor mediated phosphorylation of transcription factors Smad1 5 and 8 collectively Smad1 5 8 which leads to the subsequent activation of BMP induced gene transcription in the nucleus In this study we describe the identification and characterization of PPM1H as a novel cytoplasm localized Smad1 5 8 specific phosphatase PPM1H directly interacts with Smad1 5 8 through its Smad binding domain and dephosphorylates phospho Smad1 5 8 P Smad1 5 8 in the cytoplasm Ectopic expression

    Original URL path: http://www.cell-research.com/arts.asp?id=1940 (2016-02-14)
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  • Cell Research
    Chen 1 Tao Li 6 Ping Xie 1 Lin Yuan 1 Lei Song 1 Lanzhi Ma 7 Lujing Ding 7 Fuchu He 1 and Lingqiang Zhang 1 2 1 State Key Laboratory of Proteomics Beijing Proteome Research Center Beijing Institute of Radiation Medicine Collaborative Innovation Center for Cancer Medicine Beijing China 2 Institute of Cancer Stem Cell Dalian Medical University Dalian Liaoning Province China 3 Department of Biomedical Engineering Chinese PLA 307 Hospital Beijing China 4 Department of Experimental Hematology Beijing Institute of Radiation Medicine Beijing China 5 Department of Experimental Pathology Beijing Institute of Radiation Medicine Beijing China 6 Institute of Basic Medical Sciences China National Center of Biomedical Analysis Beijing China 7 Laboratory Animal Center of the Academy of Military Medical Sciences Beijing China Correspondence Lingqiang Zhang E mail zhanglq nic bmi ac cn Fuchu He E mail hefc nic bmi ac cn Macrophages play pivotal roles in development homeostasis tissue repair and immunity Macrophage proliferation is promoted by macrophage colony stimulating factor M CSF induced Akt signaling yet how this process is terminated remains unclear Here we identify casein kinase 2 interacting protein 1 CKIP 1 as a novel inhibitor of macrophage proliferation In resting macrophages CKIP 1 was phosphorylated at Serine 342 by constitutively active GSK3β the downstream target of Akt This phosphorylation triggers the polyubiquitination and proteasomal degradation of CKIP 1 Upon M CSF stimulation Akt is activated by CSF 1R PI3K and then inactivates GSK3β leading to the stabilization of CKIP 1 and β catenin proteins β catenin promotes the expression of proliferation genes including cyclin D and c Myc CKIP 1 interacts with TRAF6 a ubiquitin ligase required for K63 linked ubiquitination and plasma membrane recruitment of Akt and terminates TRAF6 mediated Akt activation By this means CKIP 1 inhibits macrophage proliferation specifically

    Original URL path: http://www.cell-research.com/arts.asp?id=1941 (2016-02-14)
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  • Cell Research
    Life Sciences School of Life Sciences Tsinghua University Beijing 100084 China 2 Department of Pharmacology and Pharmaceutical Sciences School of Medicine Tsinghua University Beijing 100084 China 3 State Key Laboratory of Medical Molecular Biology Institute of Basic Medical Sciences Chinese Academy of Medical Sciences Peking Union Medical College Tsinghua University Beijing 100005 China 4 State Key Laboratory of Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 China 5 Howard Hughes Medical Institute Department of Pharmacology University of Texas Southwestern Medical Center Dallas TX 75390 USA Correspondence Maojun Yang Tel 86 10 6278 9400 Fax 86 10 6279 2736 E mail maojunyang tsinghua edu cn Wei Li Tel 86 10 6480 7529 Fax 86 10 6480 7529 E mail leways ioz ac cn Linfang Wang Tel 86 10 6224 0803 Fax 86 10 6224 0529 E mail wang linfang imicams ac cn TRIM proteins play important roles in a wide range of biological processes including cell proliferation differentiation development apoptosis oncogenesis and innate immunity1 2 The N terminal regions of all TRIM proteins contain a RING finger domain followed by one or two B box domains and a coiled coil domain CCD The RING finger domain comprises conserved

    Original URL path: http://www.cell-research.com/arts.asp?id=1942 (2016-02-14)
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