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  • Cell Research
    H Eileen Tan 3 4 Dongye Wang 1 Donghai Wu 1 H Eric Xu 3 5 and Karsten Melcher 3 1 Key Laboratory of Regenerative Biology Guangzhou Institute of Biomedicine and Health Chinese Academy of Sciences Guangzhou Guangdong 510530 China 2 School of Life Science University of Science and Technology of China Hefei Anhui 230027 China 3 Laboratory of Structural Sciences Van Andel Research Institute 333 Bostwick Ave NE Grand Rapids MI 49503 USA 4 Department of Obstetrics Gynecology National University Hospital Yong Loo Lin School of Medicine National University of Singapore 119074 Singapore 5 VARI SIMM Center CAS Key Laboratory of Receptor Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 China Correspondence Karsten Melcher E mail karsten melcher vai org AMP activated protein kinase AMPK is a central cellular energy sensor and regulator of energy homeostasis and a promising drug target for the treatment of diabetes obesity and cancer Here we present low resolution crystal structures of the human α1β2γ1 holo AMPK complex bound to its allosteric modulators AMP and the glycogen mimic cyclodextrin both in the phosphorylated 4 05 Å and non phosphorylated 4 60 Å state In addition we have solved a 2

    Original URL path: http://www.cell-research.com/arts.asp?id=2040 (2016-02-14)
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  • Cell Research
    State Key Laboratory of Cell Biology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences 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 College of Life Science China West Normal University Nanchong Sichuan 637002 China 4 Biodynamic Optical Imaging Center Ministry of Education Key Laboratory of Cell Proliferation and Differentiation College of Life Sciences Peking University Beijing 100871 China 5 State Key Laboratory of Molecular Biology Shanghai Key Laboratory of Molecular Andrology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China 6 School of Life Science and Technology Shanghai Tech University Shanghai 200031 China 7 Animal Core Facility Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China 8 National Population and Family Planning Committee Key Laboratory of Contraceptive Drugs and Devices Shanghai Institute of Planned Parenthood Research Shanghai 200032 China Correspondence Jinsong Li E mail jsli sibcb ac cn Fuchou Tang E mail tangfuchou pku edu cn Ligang Wu E mail lgwu sibcb ac cn Spermatogonial stem cells SSCs can produce numerous male gametes after transplantation into recipient testes presenting a valuable approach for gene therapy and continuous production of gene modified animals However successful genetic manipulation of SSCs has been limited partially due to complexity and low efficiency of currently available genetic editing techniques Here we show that efficient genetic modifications can be introduced into SSCs using the CRISPR Cas9 system We used the CRISPR Cas9 system to mutate an EGFP transgene or the endogenous Crygc gene in SCCs The mutated SSCs underwent spermatogenesis after transplantation into the seminiferous tubules of infertile mouse testes

    Original URL path: http://www.cell-research.com/arts.asp?id=2041 (2016-02-14)
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  • Cell Research
    Chromatin and Human Disease Chinese Academy of Sciences Guangzhou Guangdong 510530 China 2 Key Laboratory of Regenerative Biology South China Institute for Stem Cell Biology and Regenerative Medicine Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou Guangdong 510530 China 3 University of Chinese Academy of Sciences Beijing 100049 China 4 Laboratory of RNA Chemical Biology State Key Laboratory of Respiratory Diseases Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou Guangdong 510530 China 5 School of Life Sciences Shandong University Jinan Shandong 250100 China 6 Department of Radiation Medicine School of Public Health and Tropic Medicine Southern Medical University Guangzhou Guangdong 510515 China 7 Drug Discovery Pipeline Group Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou Guangdong 510530 China 8 Laboratory of Metabolism and Cell Fate Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou Guangdong 510530 China 9 Hong Kong Guangdong Joint Laboratory of Stem Cells and Regenerative Medicine the University of Hong Kong and Guangzhou Institutes of Biomedicine and Health Guangzhou Guangdong 510530 China 10 School of Immunity and Infection College of Medical and Dental Sciences University of Birmingham Birmingham B15 2TT UK 11 Cardiology Division Department of medicine Queen Mary Hospital The University of Hong Kong Hong Kong SAR China 12 Shenzhen Institutes of Research and Innovation The University of Hong Kong Hong Kong SAR China 13 Li Ka Shing Institute of Health Sciences Department of Orthopaedics and Traumatology The Chinese University of Hong Kong Hong Kong SAR China Correspondence Xichen Bao Tel 86 20 3229 0481 Fax 86 20 3206 8110 E mail bao xichen gibh ac cn Miguel A Esteban Tel 86 20 3202 2920 Fax 86 20 3206 8110 E mail miguel gibh ac cn Recent studies have boosted our understanding of long noncoding

    Original URL path: http://www.cell-research.com/arts.asp?id=2042 (2016-02-14)
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  • Cell Research
    Dai 1 2 Honggang Wu 1 2 Wen Dui 1 2 Wu Min Deng 3 and Renjie Jiao 1 4 1 State Key Laboratory of Brain and Cognitive Science Institute of Biophysics the Chinese Academy of Sciences Datun Road 15 Beijing 100101 China 2 University of Chinese Academy of Sciences Beijing 100080 China 3 Department of Biological Science Florida State University Tallahassee Florida 32304 4295 USA 4 Guangzhou Hoffmann Institute of Immunology School of Basic Sciences Guangzhou Medical University Dongfengxi Road 195 Guangzhou Guangdong 510182 China Correspondence Renjie Jiao Tel 86 10 6486 7568 E mail rjiao sun5 ibp ac cn Wu Min Deng Tel 1 850 6451501 E mail wumin bio fsu edu Deregulation of the evolutionarily conserved Hippo pathway has been implicated in abnormal development of animals and in several types of cancer One mechanism of Hippo pathway regulation is achieved by controlling the stability of its regulatory components However the executive E3 ligases that are involved in this process and how the process is regulated remain poorly defined In this study we identify through a genetic candidate screen the SCFSlmb E3 ligase as a novel negative regulator of the Hippo pathway in Drosophila imaginal tissues via mediation

    Original URL path: http://www.cell-research.com/arts.asp?id=2043 (2016-02-14)
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  • Cell Research
    kinase PEPR1 Jiao Tang 1 Zhifu Han 1 Yadong Sun 1 Heqiao Zhang 1 Xinqi Gong 1 and Jijie Chai 1 1 Tsinghua Peking Center for Life Sciences School of Life Sciences Tsinghua University Beijing 100084 China Correspondence Jijie Chai E mail chaijj tsinghua edu cn The endogenous peptides AtPep1 8 in Arabidopsis mature from the conserved C terminal portions of their precursor proteins PROPEP1 8 respectively The two homologous leucine rich repeat receptor kinases LRR RKs PEPR1 and PEPR2 act as receptors of AtPeps AtPep binding leads to stable association of PEPR1 2 with the shared receptor LRR RK BAK1 eliciting immune responses similar to those induced by pathogens Here we report a crystal structure of the extracellular LRR domain of PEPR1 PEPR1LRR in complex with AtPep1 The structure reveals that AtPep1 adopts a fully extended conformation and binds to the inner surface of the superhelical PEPR1LRR Biochemical assays showed that AtPep1 is capable of inducing PEPR1LRR BAK1LRR heterodimerization The conserved C terminal portion of AtPep1 dominates AtPep1 binding to PEPR1LRR with the last amino acid of AtPep1 Asn23 forming extensive interactions with PEPR1LRR Deletion of the last residue of AtPep1 significantly compromised AtPep1 interaction with PEPR1LRR Together our

    Original URL path: http://www.cell-research.com/arts.asp?id=2044 (2016-02-14)
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  • Cell Research
    Hongya Gu 1 2 Li Jia Qu 1 2 3 and Genji Qin 1 1 State Key Laboratory of Protein and Plant Gene Research College of Life Sciences Peking University Beijing 100871 China 2 The National Plant Gene Research Center Beijing Beijing 100101 China 3 Peking Tsinghua Center for Life Sciences Peking University Beijing 100871 China Correspondence Genji Qin E mail qingenji pku edu cn Ovules are essential for plant reproduction and develop into seeds after fertilization SPOROCYTELESS NOZZLE SPL NZZ has been known for more than 15 years as an essential factor for ovule development in Arabidopsis but the biochemical nature of SPL function has remained unsolved Here we demonstrate that SPL functions as an adaptor like transcriptional repressor We show that SPL recruits TOPLESS TOPLESS RELATED TPL TPR co repressors to inhibit the CINCINNATA CIN like TEOSINTE BRANCHED1 CYCLOIDEA PCF TCP transcription factors We reveal that SPL uses its EAR motif at the C terminal end to recruit TPL TPRs and its N terminal part to bind and inhibit the TCPs We demonstrate that either disruption of TPL TPRs or overexpression of TCPs partially phenocopies the defects of megasporogenesis in spl Moreover disruption of TCPs causes phenotypes that

    Original URL path: http://www.cell-research.com/arts.asp?id=2045 (2016-02-14)
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  • Cell Research
    2015 135 138 EGF promotes mammalian cell growth by suppressing cellular senescence FREE Peter B Alexander 1 Lifeng Yuan 1 Pengyuan Yang 1 Tao Sun1 Rui Chen 1 Handan Xiang 1 Jiekai Chen 2 Haoyu Wu 2 Daniel R Radiloff 3 and Xiao Fan Wang 1 1 Department of Pharmacology and Cancer Biology Duke University Medical Center Durham NC 27710 USA2Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou Guangdong 510530 China3Department of Pediatrics University of British Columbia Vancouver V6T 1Z4 Canada Correspondence Xiao Fan Wang E mail xiao fan wang duke edu Cellular senescence is a state of irreversible proliferative arrest that is believed to be an important determinant of both cancer development and organismal aging1 Although numerous molecules have been found to promote senescence little is known about the nature of anti senescent factors under physiological conditions To identify factors that may control the cellular senescent process we cultured human mammary epithelial HME or human bronchial epithelial HBE cells in either complete growth medium or medium formulated to lack individual hormones growth factors and other supplements commonly used in primary cell culture Whereas most culture conditions had no noticeable effect on cell growth one week incubation

    Original URL path: http://www.cell-research.com/arts.asp?id=2046 (2016-02-14)
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  • Cell Research
    Hongshan Guo 1 3 Binxiao Feng 1 Yuhong Pang 1 3 Aaron M Streets 1 2 Fuchou Tang 1 3 and Yanyi Huang 1 2 1 Biodynamic Optical Imaging Center BIOPIC Peking University Beijing 100871 China 2 College of Engineering Peking University Beijing 100871 China 3 School of Life Sciences Peking University Beijing 100871 China Correspondence Yanyi Huang E mail yanyi pku edu cn Fuchou Tang E mail tangfuchou pku edu cn Epigenetic regulation is crucial to the establishment and maintenance of the identity of a cell Recent studies suggest that transcription is implemented amongst a mixture of various histone modifications1 It has also been recognized that to interrogate function of genetic information comprehensively systematic profiling of the epigenome in multiple cell stages and types is required2 Chromatin immunoprecipitation ChIP has become one of the most critical assays to investigate the complex DNA protein interactions3 Combined with profiling technologies such as microarrays ChIP on chip or high throughput sequencing ChIP Seq this assay becomes a great tool to study the epigenetic regulatory networks in cells4 5 6 However the ChIP process produces limited amount of DNA due to the low yield of antibody pull down DNA damage during fragmentation and

    Original URL path: http://www.cell-research.com/arts.asp?id=2048 (2016-02-14)
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