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  • Cell Research
    an important role in silencing gene expression including the repression of transposable elements TEs Given that the activation of TEs during preimplantation development correlates with loss of DNA methylation it is believed that paternal DNA demethylation may have an important role in TE activation Here we examined this hypothesis and found that Tet3 mediated 5mC oxidation does not have a significant contribution to TE activation We show that the expression of LINE 1 long interspersed nucleotide element 1 and ERVL endogenous retroviruses class III are activated from both paternal and maternal genomes in zygotes Inhibition of 5mC oxidation by siRNA mediated depletion of Tet3 affected neither TE activation nor global transcription in zygotes Thus our study provides the first evidence demonstrating that activation of both TEs and global transcription in zygotes are independent of Tet3 mediated 5mC oxidation Tonoplast calcium sensors CBL2 and CBL3 control plant growth and ion homeostasis through regulating V ATPase activity in Arabidopsis Ren Jie Tang 1 2 Hua Liu 1 Yang Yang 1 Lei Yang 1 3 Xiao Shu Gao 1 Veder J Garcia 2 Sheng Luan 2 3 and Hong Xia Zhang 1 Cell Research 2012 22 1650 1665 doi 10 1038 cr 2012 161 published online 27 November 2012 Full Text PDF Plant responses to developmental and environmental cues are often mediated by calcium Ca 2 signals that are transmitted by diverse calcium sensors The calcineurin B like CBL protein family represents calcium sensors that decode calcium signals through specific interactions with a group of CBL interacting protein kinases We report functional analysis of Arabidopsis CBL2 and CBL3 two closely related CBL members that are localized to the vacuolar membrane through the N terminal tonoplast targeting sequence While cbl2 or cbl3 single mutant did not show any phenotypic difference from the wild type the cbl2 cbl3 double mutant was stunted with leaf tip necrosis underdeveloped roots shorter siliques and fewer seeds These defects were reminiscent of those in the vha a2 vha a3 double mutant deficient in vacuolar H ATPase V ATPase Indeed the V ATPase activity was reduced in the cbl2 cbl3 double mutant connecting tonoplast CBL type calcium sensors to the regulation of V ATPase Furthermore cbl2 cbl3 double mutant was compromised in ionic tolerance and micronutrient accumulation consistent with the defect in V ATPase activity that has been shown to function in ion compartmentalization Our results suggest that calcium sensors CBL2 and CBL3 serve as molecular links between calcium signaling and V ATPase a central regulator of intracellular ion homeostasis The novel quantitative trait locus GL3 1 controls rice grain size and yield by regulating Cyclin T1 3 Peng Qi 1 You Shun Lin 2 Xian Jun Song 1 Jin Bo Shen 2 Wei Huang 1 Jun Xiang Shan 1 Mei Zhen Zhu 1 Liwen Jiang 2 Ji Ping Gao 1 and Hong Xuan Lin Cell Research 2012 22 1666 1680 doi 10 1038 cr 2012 151 published 13 November 2012 Full Text PDF Increased crop yields are required to

    Original URL path: http://www.cell-research.com/artsmore.asp?id=8 (2016-02-14)
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  • Cell Research
    4 Warren Strober 7 Chang Chen 3 Guangxun Meng 2 and Bing Sun 1 2 Cell Research 2013 23 201 212 doi 10 1038 cr 2013 6 published online 15 January 2013 Full Text PDF Inflammasomes are multi protein complexes that trigger the activation of caspase 1 and the maturation of interleukin 1β IL 1β yet the regulation of these complexes remains poorly characterized Here we show that nitric oxide NO inhibited the NLRP3 mediated ASC pyroptosome formation caspase 1 activation and IL 1β secretion in myeloid cells from both mice and humans Meanwhile endogenous NO derived from iNOS inducible form of NO synthase also negatively regulated NLRP3 inflammasome activation Depletion of iNOS resulted in increased accumulation of dysfunctional mitochondria in response to LPS and ATP which was responsible for the increased IL 1β production and caspase 1 activation iNOS deficiency or pharmacological inhibition of NO production enhanced NLRP3 dependent cytokine production in vivo thus increasing mortality from LPS induced sepsis in mice which was prevented by NLRP3 deficiency Our results thus identify NO as a critical negative regulator of the NLRP3 inflammasome via the stabilization of mitochondria This study has important implications for the design of new strategies to control NLRP3 related diseases Intermolecular recognition revealed by the complex structure of human CLOCK BMAL1 basic helix loop helix domains with E box DNA Zixi Wang 1 Yaling Wu 2 Lanfen Li 1 and Xiao Dong Su 1 Cell Research 2013 23 213 224 doi 10 1038 cr 2012 170 published online 11 December 2012 Full Text PDF CLOCK circadian locomotor output cycles kaput and BMAL1 brain and muscle ARNT like 1 are both transcription factors of the circadian core loop in mammals Recently published mouse CLOCK BMAL1 bHLH basic helix loop helix PAS period ARNT single minded complex structure sheds light on the mechanism for heterodimer formation but the structural details of the protein DNA recognition mechanisms remain elusive Here we have elucidated the crystal structure of human CLOCK BMAL1 bHLH domains bound to a canonical E box DNA We demonstrate that CLOCK and BMAL1 bHLH domains can be mutually selected and that hydrogen bonding networks mediate their E box recognition We identified a hydrophobic contact between BMAL1 Ile80 and a flanking thymine nucleotide suggesting that CLOCK BMAL1 actually reads 7 bp DNA and not the previously believed 6 bp DNA To find potential non canonical E boxes that could be recognized by CLOCK BMAL1 we constructed systematic single nucleotide mutations on the E box and measured their relevant affinities We defined two non canonical E box patterns with high affinities AACGTGA and CATGTGA in which the flanking A7 T7 base pair is indispensable for recognition These results will help us to identify functional CLOCK BMAL1 binding sites in vivo and to search for clock controlled genes Furthermore we assessed the inhibitory role of potential phosphorylation sites in bHLH regions We found that the phospho mimicking mutation on BMAL1 Ser78 could efficiently block DNA binding as well as abolish normal circadian oscillation in cells We propose that BMAL1 Ser78 should be a key residue mediating input signal regulated transcriptional inhibition for external cues to entrain the circadian clock by kinase cascade Structure function analysis reveals a novel mechanism for regulation of histone demethylase LSD2 AOF1 KDM1b Qi Zhang 1 Shankang Qi 2 Mingchu Xu 2 Lin Yu 1 Ye Tao 3 Zengqin Deng 1 Wei Wu 1 Jiwen Li 2 Zhongzhou Chen 1 and Jiemin Wong 2 Cell Research 2013 23 225 241 doi 10 1038 cr 2012 177 published online 25 December 2012 Full Text PDF LSD2 AOF1 KDM1b catalyzes demethylation of mono and di methylated H3K4 and plays an important role in transcriptional regulation and genomic imprinting Here we report the high resolution crystal structures of apo LSD2 and LSD2 in complex with a peptide that mimics H3K4me2 Three structural domains of LSD2 namely the novel N terminal zinc finger the centrally located SWIRM domain and the C terminal oxidase domain closely pack together to form a boot shaped structure The active site cavity in the oxidase domain is large enough to accommodate several residues of the histone H3 tail and cannot discriminate between the different states of H3K4 methylation The N terminal zinc finger domain composed of a novel C4H2C2 type zinc finger and a specific CW type zinc finger is required for demethylase activity and surprisingly the binding of cofactor flavin adenine dinucleotide FAD In fact a relay of extensive interactions through the zinc finger SWIRM oxidase domains is required for LSD2 demethylase activity and the binding of FAD These results reveal a novel mechanism for the zinc finger and SWIRM domains in controlling LSD2 demethylase activity and provide a framework for elucidating the regulation and function of LSD2 A functional variant in the cystathionine β synthase gene promoter significantly reduces congenital heart disease susceptibility in a Han Chinese population Jian Yuan Zhao 1 7 Xue Yan Yang 1 Kai Hu Shi 2 Shu Na Sun 3 Jia Hou 3 Zhi Zhou Ye 1 Jue Wang 1 Wen Yuan Duan 4 Bin Qiao 4 Yi Jiang Chen 5 Hong Bing Shen 6 Guo Ying Huang 3 Li Jin 1 8 and Hong Yan Wang 1 3 8 Cell Research 2013 23 242 253 doi 10 1038 cr 2012 135 published online 18 September 2012 Full Text PDF Homocysteine is an independent risk factor for various cardiovascular diseases There are two ways to remove homocysteine from embryonic cardiac cells remethylation to form methionine or transsulfuration to form cysteine Cystathionine β synthase CBS catalyzes the first step of homocysteine transsulfuration as a rate limiting enzyme In this study we identified a functional variant 4673C G rs2850144 in the CBS gene promoter region that significantly reduces the susceptibility to congenital heart disease CHD in a Han Chinese population consisting of 2 340 CHD patients and 2 270 controls Individuals carrying the heterozygous CG and homozygous GG genotypes had a 15 odds ratio OR 0 85 95 confidence interval

    Original URL path: http://www.cell-research.com/artsmore.asp?id=146 (2016-02-14)
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  • Cell Research

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    Original URL path: /artsmore1.asp?id=6 (2016-02-14)


  • Cell Research
    10 526 Thomson Reuters 2013 Free Sample Issue Submission Advanced Online Publication Current Issue Top 10 VOLUME 23 ISSUE 1 1 2013 1 2 The 2013 special issue on stem cell biology Dangsheng Li Deputy Editor in Chief Cell Research Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Correspondence Dangsheng Li E mail dsli sibs ac cn Cell Research 2013 23 1 2 doi 10 1038 cr 2013 4

    Original URL path: http://www.cell-research.com/arts.asp?id=47 (2016-02-14)
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  • Cell Research
    Torrey Pines Road La Jolla CA 92037 USA 2 National Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China 3 Center for Regenerative Medicine in Barcelona Dr Aiguader 88 08003 Barcelona Spain Correspondence Guang Hui Liu Juan Carlos Izpisua Belmonte E mail ghliu ibp ac cn belmonte salk edu izpisua cmrb eu Efficient generation of functional human vascular endothelial cells and smooth muscle cells from pluripotent

    Original URL path: http://www.cell-research.com/arts.asp?id=48 (2016-02-14)
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  • Cell Research
    92037 USA 2 Department of Human Genetics University of Michigan Medical School Ann Arbor MI 48109 USA Correspondence Anjana Rao E mail arao liai org In zygotes a global loss of DNA methylation occurs selectively in the paternal pronucleus before the first cell division concomitantly with the appearance of modified forms of 5 methylcytosine The adjacent maternal pronucleus and certain paternally imprinted loci are protected from this process Nakamura et

    Original URL path: http://www.cell-research.com/arts.asp?id=49 (2016-02-14)
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  • Cell Research
    joins the debate Ling Li and Ravi Bhatia Division of Hematopoietic Stem cell and Leukemia Research City of Hope National Medical Center Duarte CA 91010 USA Correspondence Ravi Bhatia Tel 1 626 359 8111 ext 62705 E mail rbhatia coh org Sirtuins are NAD dependent deacetylases that are conserved from yeast to mammals A new report sheds light on the function of SIRT7 the least understood member of the Sirtuin

    Original URL path: http://www.cell-research.com/arts.asp?id=50 (2016-02-14)
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  • Cell Research
    the Massachusetts Institute of Technology 7 Cambridge Center Cambridge MA 02142 USA 2 Department of Medical Oncology Dana Farber Cancer Institute Harvard Medical School 450 Brookline Avenue Boston MA 02215 USA 3 Department of Medicine Brigham and Women s Hospital Harvard Medical School 75 Francis Street Boston MA 02115 USA Correspondence Levi A Garraway E mail levi garraway dfci harvard edu Two recent papers identify KRAS activation as a mechanism

    Original URL path: http://www.cell-research.com/arts.asp?id=51 (2016-02-14)
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