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  • Time Factors  (538)
  • Protein Binding  (278)
  • Nature Publishing Group (NPG)  (810)
  • American Institute of Physics
  • MDPI Publishing
  • 2010-2014  (810)
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  • 1
    Publication Date: 2014-12-17
    Description: Nitrous oxide (N2O) is an important greenhouse gas and ozone-depleting substance that has anthropogenic as well as natural marine and terrestrial sources. The tropospheric N2O concentrations have varied substantially in the past in concert with changing climate on glacial-interglacial and millennial timescales. It is not well understood, however, how N2O emissions from marine and terrestrial sources change in response to varying environmental conditions. The distinct isotopic compositions of marine and terrestrial N2O sources can help disentangle the relative changes in marine and terrestrial N2O emissions during past climate variations. Here we present N2O concentration and isotopic data for the last deglaciation, from 16,000 to 10,000 years before present, retrieved from air bubbles trapped in polar ice at Taylor Glacier, Antarctica. With the help of our data and a box model of the N2O cycle, we find a 30 per cent increase in total N2O emissions from the late glacial to the interglacial, with terrestrial and marine emissions contributing equally to the overall increase and generally evolving in parallel over the last deglaciation, even though there is no a priori connection between the drivers of the two sources. However, we find that terrestrial emissions dominated on centennial timescales, consistent with a state-of-the-art dynamic global vegetation and land surface process model that suggests that during the last deglaciation emission changes were strongly influenced by temperature and precipitation patterns over land surfaces. The results improve our understanding of the drivers of natural N2O emissions and are consistent with the idea that natural N2O emissions will probably increase in response to anthropogenic warming.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schilt, Adrian -- Brook, Edward J -- Bauska, Thomas K -- Baggenstos, Daniel -- Fischer, Hubertus -- Joos, Fortunat -- Petrenko, Vasilii V -- Schaefer, Hinrich -- Schmitt, Jochen -- Severinghaus, Jeffrey P -- Spahni, Renato -- Stocker, Thomas F -- England -- Nature. 2014 Dec 11;516(7530):234-7. doi: 10.1038/nature13971.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] College of Earth, Ocean, and Atmospheric Sciences, Oregon State University, Corvallis, Oregon 97331, USA [2] Climate and Environmental Physics, Physics Institute, and Oeschger Centre for Climate Change Research, University of Bern, 3012 Bern, Switzerland. ; College of Earth, Ocean, and Atmospheric Sciences, Oregon State University, Corvallis, Oregon 97331, USA. ; Scripps Institution of Oceanography, University of California, San Diego, California 92037, USA. ; Climate and Environmental Physics, Physics Institute, and Oeschger Centre for Climate Change Research, University of Bern, 3012 Bern, Switzerland. ; Department of Earth and Environmental Sciences, University of Rochester, Rochester, New York 14627, USA. ; National Institute of Water and Atmospheric Research, Wellington 6021, New Zealand.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25503236" target="_blank"〉PubMed〈/a〉
    Keywords: Antarctic Regions ; Aquatic Organisms/*metabolism ; Atmosphere/*chemistry ; Global Warming ; History, Ancient ; *Ice Cover ; Nitrogen Isotopes/analysis ; Nitrous Oxide/analysis/history/*metabolism ; Oxygen Isotopes/analysis ; Rain ; Temperature ; Time Factors
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2014-08-15
    Description: The balance between stem cell self-renewal and differentiation is controlled by intrinsic factors and niche signals. In the Drosophila melanogaster ovary, some intrinsic factors promote germline stem cell (GSC) self-renewal, whereas others stimulate differentiation. However, it remains poorly understood how the balance between self-renewal and differentiation is controlled. Here we use D. melanogaster ovarian GSCs to demonstrate that the differentiation factor Bam controls the functional switch of the COP9 complex from self-renewal to differentiation via protein competition. The COP9 complex is composed of eight Csn subunits, Csn1-8, and removes Nedd8 modifications from target proteins. Genetic results indicated that the COP9 complex is required intrinsically for GSC self-renewal, whereas other Csn proteins, with the exception of Csn4, were also required for GSC progeny differentiation. Bam-mediated Csn4 sequestration from the COP9 complex via protein competition inactivated the self-renewing function of COP9 and allowed other Csn proteins to promote GSC differentiation. Therefore, this study reveals a protein-competition-based mechanism for controlling the balance between stem cell self-renewal and differentiation. Because numerous self-renewal factors are ubiquitously expressed throughout the stem cell lineage in various systems, protein competition may function as an important mechanism for controlling the self-renewal-to-differentiation switch.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pan, Lei -- Wang, Su -- Lu, Tinglin -- Weng, Changjiang -- Song, Xiaoqing -- Park, Joseph K -- Sun, Jin -- Yang, Zhi-Hao -- Yu, Junjing -- Tang, Hong -- McKearin, Dennis M -- Chamovitz, Daniel A -- Ni, Jianquan -- Xie, Ting -- GM64428/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Oct 9;514(7521):233-6. doi: 10.1038/nature13562.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110, USA [2] Chinese Academy of Sciences Key Laboratory of Infection and Immunity, Institute of Biophysics, 15 Da Tun Road, Beijing 100101, China [3]. ; 1] Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110, USA [2] Department of Cell Biology and Anatomy, University of Kansas School of Medicine, 3901 Rainbow Boulevard, Kansas City, Kansas 66160, USA [3]. ; 1] Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China [2]. ; Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110, USA. ; 1] Department of Molecular Biology and Graduate School of Biomedical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9148, USA [2] Howard Hughes Medical Institute, Chevy Chase, Maryland 20815-6789, USA. ; Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China. ; 1] Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110, USA [2] Chinese Academy of Sciences Key Laboratory of Infection and Immunity, Institute of Biophysics, 15 Da Tun Road, Beijing 100101, China. ; Chinese Academy of Sciences Key Laboratory of Infection and Immunity, Institute of Biophysics, 15 Da Tun Road, Beijing 100101, China. ; Department of Plant Sciences, Tel Aviv University, Tel Aviv 69978, Israel. ; 1] Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110, USA [2] Department of Cell Biology and Anatomy, University of Kansas School of Medicine, 3901 Rainbow Boulevard, Kansas City, Kansas 66160, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25119050" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Binding, Competitive ; *Cell Differentiation ; Cell Proliferation ; DNA Helicases/metabolism ; Drosophila Proteins/metabolism ; Drosophila melanogaster/*cytology/*metabolism ; Female ; Intracellular Signaling Peptides and Proteins/metabolism ; Male ; Multiprotein Complexes/*chemistry/*metabolism ; Ovary/cytology ; Peptide Hydrolases/*chemistry/*metabolism ; Protein Binding ; Stem Cells/*cytology/*metabolism ; Ubiquitins/metabolism
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  • 3
    Publication Date: 2014-04-04
    Description: Autophagy, the process by which proteins and organelles are sequestered in double-membrane structures called autophagosomes and delivered to lysosomes for degradation, is critical in diseases such as cancer and neurodegeneration. Much of our understanding of this process has emerged from analysis of bulk cytoplasmic autophagy, but our understanding of how specific cargo, including organelles, proteins or intracellular pathogens, are targeted for selective autophagy is limited. Here we use quantitative proteomics to identify a cohort of novel and known autophagosome-enriched proteins in human cells, including cargo receptors. Like known cargo receptors, nuclear receptor coactivator 4 (NCOA4) was highly enriched in autophagosomes, and associated with ATG8 proteins that recruit cargo-receptor complexes into autophagosomes. Unbiased identification of NCOA4-associated proteins revealed ferritin heavy and light chains, components of an iron-filled cage structure that protects cells from reactive iron species but is degraded via autophagy to release iron through an unknown mechanism. We found that delivery of ferritin to lysosomes required NCOA4, and an inability of NCOA4-deficient cells to degrade ferritin led to decreased bioavailable intracellular iron. This work identifies NCOA4 as a selective cargo receptor for autophagic turnover of ferritin (ferritinophagy), which is critical for iron homeostasis, and provides a resource for further dissection of autophagosomal cargo-receptor connectivity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4180099/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4180099/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mancias, Joseph D -- Wang, Xiaoxu -- Gygi, Steven P -- Harper, J Wade -- Kimmelman, Alec C -- GM070565/GM/NIGMS NIH HHS/ -- GM095567/GM/NIGMS NIH HHS/ -- P50 CA127003/CA/NCI NIH HHS/ -- R01 CA157490/CA/NCI NIH HHS/ -- R01 GM070565/GM/NIGMS NIH HHS/ -- R01 GM095567/GM/NIGMS NIH HHS/ -- R01CA157490/CA/NCI NIH HHS/ -- England -- Nature. 2014 May 1;509(7498):105-9. doi: 10.1038/nature13148. Epub 2014 Mar 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Division of Genomic Stability and DNA Repair, Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA [3] Harvard Radiation Oncology Program, Boston, Massachusetts 02115, USA [4] Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. ; Division of Genomic Stability and DNA Repair, Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA. ; Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24695223" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/metabolism ; *Autophagy ; Biological Availability ; Ferritins/chemistry/*metabolism ; Homeostasis ; Humans ; Iron/metabolism ; Lysosomes/metabolism ; Microfilament Proteins/metabolism ; Nuclear Receptor Coactivators/deficiency/genetics/*metabolism ; Phagosomes/*metabolism ; Protein Binding ; Protein Transport ; *Proteomics ; Substrate Specificity
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  • 4
    Publication Date: 2014-06-05
    Description: Genome instability is central to ageing, cancer and other diseases. It is not only proteins involved in DNA replication or the DNA damage response (DDR) that are important for maintaining genome integrity: from yeast to higher eukaryotes, mutations in genes involved in pre-mRNA splicing and in the biogenesis and export of messenger ribonucleoprotein (mRNP) also induce DNA damage and genome instability. This instability is frequently mediated by R-loops formed by DNA-RNA hybrids and a displaced single-stranded DNA. Here we show that the human TREX-2 complex, which is involved in mRNP biogenesis and export, prevents genome instability as determined by the accumulation of gamma-H2AX (Ser-139 phosphorylated histone H2AX) and 53BP1 foci and single-cell electrophoresis in cells depleted of the TREX-2 subunits PCID2, GANP and DSS1. We show that the BRCA2 repair factor, which binds to DSS1, also associates with PCID2 in the cell. The use of an enhanced green fluorescent protein-tagged hybrid-binding domain of RNase H1 and the S9.6 antibody did not detect R-loops in TREX-2-depleted cells, but did detect the accumulation of R-loops in BRCA2-depleted cells. The results indicate that R-loops are frequently formed in cells and that BRCA2 is required for their processing. This link between BRCA2 and RNA-mediated genome instability indicates that R-loops may be a chief source of replication stress and cancer-associated instability.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bhatia, Vaibhav -- Barroso, Sonia I -- Garcia-Rubio, Maria L -- Tumini, Emanuela -- Herrera-Moyano, Emilia -- Aguilera, Andres -- England -- Nature. 2014 Jul 17;511(7509):362-5. doi: 10.1038/nature13374. Epub 2014 Jun 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centro Andaluz de Biologia Molecular y Medicina Regenerativa CABIMER, Universidad de Sevilla, Avenida Americo Vespucio s/n, 41092 Seville, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24896180" target="_blank"〉PubMed〈/a〉
    Keywords: Acetyltransferases/metabolism ; BRCA2 Protein/deficiency/genetics/*metabolism ; DNA Damage ; DNA Replication ; DNA, Single-Stranded/chemistry/*metabolism ; Exodeoxyribonucleases/chemistry/deficiency/*metabolism ; *Genomic Instability ; Histones/chemistry/metabolism ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism ; Nuclear Proteins/*metabolism ; Nucleic Acid Conformation ; Phosphoproteins/chemistry/deficiency/*metabolism ; Proteasome Endopeptidase Complex/metabolism ; Protein Binding ; RNA/chemistry/*metabolism ; *RNA Transport ; Ribonuclease H/chemistry ; Ribonucleoproteins/biosynthesis/metabolism
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  • 5
    Publication Date: 2014-04-18
    Description: Fertilization occurs when sperm and egg recognize each other and fuse to form a new, genetically distinct organism. The molecular basis of sperm-egg recognition is unknown, but is likely to require interactions between receptor proteins displayed on their surface. Izumo1 is an essential sperm cell-surface protein, but its receptor on the egg has not been described. Here we identify folate receptor 4 (Folr4) as the receptor for Izumo1 on the mouse egg, and propose to rename it Juno. We show that the Izumo1-Juno interaction is conserved within several mammalian species, including humans. Female mice lacking Juno are infertile and Juno-deficient eggs do not fuse with normal sperm. Rapid shedding of Juno from the oolemma after fertilization suggests a mechanism for the membrane block to polyspermy, ensuring eggs normally fuse with just a single sperm. Our discovery of an essential receptor pair at the nexus of conception provides opportunities for the rational development of new fertility treatments and contraceptives.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998876/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998876/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bianchi, Enrica -- Doe, Brendan -- Goulding, David -- Wright, Gavin J -- 098051/Wellcome Trust/United Kingdom -- England -- Nature. 2014 Apr 24;508(7497):483-7. doi: 10.1038/nature13203. Epub 2014 Apr 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK. ; Mouse Production Team, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK. ; Electron and Advanced Light Microscopy Suite, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24739963" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Conserved Sequence ; Evolution, Molecular ; Female ; Fertility/genetics ; Fertilization/genetics/*physiology ; Genes, Essential ; Glycosylphosphatidylinositols/metabolism ; Humans ; Immunoglobulins/*metabolism ; Infertility, Female/genetics ; Male ; Mammals ; Membrane Proteins/*metabolism ; Mice ; Oocytes/cytology/metabolism ; Ovum/cytology/*metabolism ; Parthenogenesis ; Receptors, Cell Surface/deficiency/genetics/*metabolism ; Sperm Injections, Intracytoplasmic ; Spermatozoa/*metabolism ; Time Factors
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  • 6
    Publication Date: 2014-12-04
    Description: T-helper type 17 (TH17) cells that produce the cytokines interleukin-17A (IL-17A) and IL-17F are implicated in the pathogenesis of several autoimmune diseases. The differentiation of TH17 cells is regulated by transcription factors such as RORgammat, but post-translational mechanisms preventing the rampant production of pro-inflammatory IL-17A have received less attention. Here we show that the deubiquitylating enzyme DUBA is a negative regulator of IL-17A production in T cells. Mice with DUBA-deficient T cells developed exacerbated inflammation in the small intestine after challenge with anti-CD3 antibodies. DUBA interacted with the ubiquitin ligase UBR5, which suppressed DUBA abundance in naive T cells. DUBA accumulated in activated T cells and stabilized UBR5, which then ubiquitylated RORgammat in response to TGF-beta signalling. Our data identify DUBA as a cell-intrinsic suppressor of IL-17 production.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rutz, Sascha -- Kayagaki, Nobuhiko -- Phung, Qui T -- Eidenschenk, Celine -- Noubade, Rajkumar -- Wang, Xiaoting -- Lesch, Justin -- Lu, Rongze -- Newton, Kim -- Huang, Oscar W -- Cochran, Andrea G -- Vasser, Mark -- Fauber, Benjamin P -- DeVoss, Jason -- Webster, Joshua -- Diehl, Lauri -- Modrusan, Zora -- Kirkpatrick, Donald S -- Lill, Jennie R -- Ouyang, Wenjun -- Dixit, Vishva M -- England -- Nature. 2015 Feb 19;518(7539):417-21. doi: 10.1038/nature13979. Epub 2014 Dec 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Genentech, 1 DNA Way, South San Francisco, California 94080, USA. ; Department of Physiological Chemistry, Genentech, 1 DNA Way, South San Francisco, California 94080, USA. ; Department of Protein Chemistry, Genentech, 1 DNA Way, South San Francisco, California 94080, USA. ; Department of Early Discovery Biochemistry, Genentech, 1 DNA Way, South San Francisco, California 94080, USA. ; Discovery Chemistry, Genentech, 1 DNA Way, South San Francisco, California 94080, USA. ; Department of Pathology, Genentech, 1 DNA Way, South San Francisco, California 94080, USA. ; Department of Molecular Biology, Genentech, 1 DNA Way, South San Francisco, California 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25470037" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Enzyme Stability ; Female ; Inflammation/genetics/pathology ; Interleukin-17/*biosynthesis ; Intestine, Small/metabolism/pathology ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Protein Binding ; *Protein Biosynthesis ; Signal Transduction ; Substrate Specificity ; Th17 Cells/*metabolism ; Transforming Growth Factor beta/metabolism ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitin-Specific Proteases/biosynthesis/deficiency/genetics/*metabolism ; Ubiquitination
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  • 7
    Publication Date: 2014-12-18
    Description: Endocytosis is required for internalization of micronutrients and turnover of membrane components. Endophilin has been assigned as a component of clathrin-mediated endocytosis. Here we show in mammalian cells that endophilin marks and controls a fast-acting tubulovesicular endocytic pathway that is independent of AP2 and clathrin, activated upon ligand binding to cargo receptors, inhibited by inhibitors of dynamin, Rac, phosphatidylinositol-3-OH kinase, PAK1 and actin polymerization, and activated upon Cdc42 inhibition. This pathway is prominent at the leading edges of cells where phosphatidylinositol-3,4-bisphosphate-produced by the dephosphorylation of phosphatidylinositol-3,4,5-triphosphate by SHIP1 and SHIP2-recruits lamellipodin, which in turn engages endophilin. This pathway mediates the ligand-triggered uptake of several G-protein-coupled receptors such as alpha2a- and beta1-adrenergic, dopaminergic D3 and D4 receptors and muscarinic acetylcholine receptor 4, the receptor tyrosine kinases EGFR, HGFR, VEGFR, PDGFR, NGFR and IGF1R, as well as interleukin-2 receptor. We call this new endocytic route fast endophilin-mediated endocytosis (FEME).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boucrot, Emmanuel -- Ferreira, Antonio P A -- Almeida-Souza, Leonardo -- Debard, Sylvain -- Vallis, Yvonne -- Howard, Gillian -- Bertot, Laetitia -- Sauvonnet, Nathalie -- McMahon, Harvey T -- U105178805/Medical Research Council/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- England -- Nature. 2015 Jan 22;517(7535):460-5. doi: 10.1038/nature14067. Epub 2014 Dec 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK [2] Institute of Structural and Molecular Biology, University College London &Birkbeck College, London WC1E 6BT, UK. ; Institute of Structural and Molecular Biology, University College London &Birkbeck College, London WC1E 6BT, UK. ; MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. ; 1] Institute of Structural and Molecular Biology, University College London &Birkbeck College, London WC1E 6BT, UK [2] Department of Biology, Ecole Normale Superieure de Cachan, 94235 Cachan, France. ; Institut Pasteur, Unite de Pathogenie Moleculaire Microbienne, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25517094" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/metabolism ; Acyltransferases/*metabolism ; Cell Line ; Clathrin ; Dynamins/metabolism ; *Endocytosis ; Humans ; Ligands ; Phosphatidylinositol Phosphates/metabolism ; Pseudopodia/metabolism ; Receptor Protein-Tyrosine Kinases/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Receptors, Interleukin-2/metabolism ; Signal Transduction ; Time Factors
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  • 8
    Publication Date: 2014-11-05
    Description: Plant stem cells in the shoot apical meristem (SAM) and root apical meristem are necessary for postembryonic development of aboveground tissues and roots, respectively, while secondary vascular stem cells sustain vascular development. WUSCHEL (WUS), a homeodomain transcription factor expressed in the rib meristem of the Arabidopsis SAM, is a key regulatory factor controlling SAM stem cell populations, and is thought to establish the shoot stem cell niche through a feedback circuit involving the CLAVATA3 (CLV3) peptide signalling pathway. WUSCHEL-RELATED HOMEOBOX 5 (WOX5), which is specifically expressed in the root quiescent centre, defines quiescent centre identity and functions interchangeably with WUS in the control of shoot and root stem cell niches. WOX4, expressed in Arabidopsis procambial cells, defines the vascular stem cell niche. WUS/WOX family proteins are evolutionarily and functionally conserved throughout the plant kingdom and emerge as key actors in the specification and maintenance of stem cells within all meristems. However, the nature of the genetic regime in stem cell niches that centre on WOX gene function has been elusive, and molecular links underlying conserved WUS/WOX function in stem cell niches remain unknown. Here we demonstrate that the Arabidopsis HAIRY MERISTEM (HAM) family of transcription regulators act as conserved interacting cofactors with WUS/WOX proteins. HAM and WUS share common targets in vivo and their physical interaction is important in driving downstream transcriptional programs and in promoting shoot stem cell proliferation. Differences in the overlapping expression patterns of WOX and HAM family members underlie the formation of diverse stem cell niche locations, and the HAM family is essential for all of these stem cell niches. These findings establish a new framework for the control of stem cell production during plant development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297503/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297503/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Yun -- Liu, Xing -- Engstrom, Eric M -- Nimchuk, Zachary L -- Pruneda-Paz, Jose L -- Tarr, Paul T -- Yan, An -- Kay, Steve A -- Meyerowitz, Elliot M -- GM056006/GM/NIGMS NIH HHS/ -- GM067837/GM/NIGMS NIH HHS/ -- GM094212/GM/NIGMS NIH HHS/ -- R01 GM056006/GM/NIGMS NIH HHS/ -- R01 GM067837/GM/NIGMS NIH HHS/ -- R01 GM104244/GM/NIGMS NIH HHS/ -- RC2 GM092412/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Jan 15;517(7534):377-80. doi: 10.1038/nature13853. Epub 2014 Oct 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA. ; Biology Department, College of William and Mary, Williamsburg, Virginia 23187-8795, USA. ; 1] Division of Biology, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA [2] Howard Hughes Medical Institute, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA. ; Section of Cell and Developmental Biology, Division of Biological Sciences, University of California San Diego, La Jolla, California 92093, USA. ; University of Southern California, Molecular and Computational Biology, Department of Biological Sciences, Dana and David Dornsife College of Letters, Arts and Sciences, Los Angeles, California 90089, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25363783" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/*cytology/genetics/*metabolism ; Arabidopsis Proteins/*metabolism ; Cell Proliferation ; *Gene Expression Regulation, Plant ; Histone Acetyltransferases/metabolism ; Homeodomain Proteins/metabolism ; Plant Shoots/cytology/genetics ; Protein Binding ; Stem Cell Niche ; Stem Cells/*cytology/*metabolism ; *Transcription, Genetic
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  • 9
    Publication Date: 2014-11-05
    Description: Establishing the hippocampal cellular ensemble that represents an animal's environment involves the emergence and disappearance of place fields in specific CA1 pyramidal neurons, and the acquisition of different spatial firing properties across the active population. While such firing flexibility and diversity have been linked to spatial memory, attention and task performance, the cellular and network origin of these place cell features is unknown. Basic integrate-and-fire models of place firing propose that such features result solely from varying inputs to place cells, but recent studies suggest instead that place cells themselves may play an active role through regenerative dendritic events. However, owing to the difficulty of performing functional recordings from place cell dendrites, no direct evidence of regenerative dendritic events exists, leaving any possible connection to place coding unknown. Using multi-plane two-photon calcium imaging of CA1 place cell somata, axons and dendrites in mice navigating a virtual environment, here we show that regenerative dendritic events do exist in place cells of behaving mice, and, surprisingly, their prevalence throughout the arbour is highly spatiotemporally variable. Furthermore, we show that the prevalence of such events predicts the spatial precision and persistence or disappearance of place fields. This suggests that the dynamics of spiking throughout the dendritic arbour may play a key role in forming the hippocampal representation of space.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289090/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289090/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sheffield, Mark E J -- Dombeck, Daniel A -- 1R01MH101297/MH/NIMH NIH HHS/ -- R01 MH101297/MH/NIMH NIH HHS/ -- England -- Nature. 2015 Jan 8;517(7533):200-4. doi: 10.1038/nature13871. Epub 2014 Oct 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Northwestern University, Evanston, Illinois 60208, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25363782" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Axons/metabolism ; Calcium/*metabolism ; *Calcium Signaling ; Dendrites/*metabolism ; Hippocampus/*cytology/*physiology ; Male ; Memory, Long-Term/physiology ; Mice ; Mice, Inbred C57BL ; Neuronal Plasticity/physiology ; Space Perception/*physiology ; Time Factors
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  • 10
    Publication Date: 2014-12-04
    Description: Muscle contraction is initiated by the release of calcium (Ca(2+)) from the sarcoplasmic reticulum into the cytoplasm of myocytes through ryanodine receptors (RyRs). RyRs are homotetrameric channels with a molecular mass of more than 2.2 megadaltons that are regulated by several factors, including ions, small molecules and proteins. Numerous mutations in RyRs have been associated with human diseases. The molecular mechanism underlying the complex regulation of RyRs is poorly understood. Using electron cryomicroscopy, here we determine the architecture of rabbit RyR1 at a resolution of 6.1 A. We show that the cytoplasmic moiety of RyR1 contains two large alpha-solenoid domains and several smaller domains, with folds suggestive of participation in protein-protein interactions. The transmembrane domain represents a chimaera of voltage-gated sodium and pH-activated ion channels. We identify the calcium-binding EF-hand domain and show that it functions as a conformational switch allosterically gating the channel.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Efremov, Rouslan G -- Leitner, Alexander -- Aebersold, Ruedi -- Raunser, Stefan -- England -- Nature. 2015 Jan 1;517(7532):39-43. doi: 10.1038/nature13916. Epub 2014 Dec 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany [2] Structural Biology Research Center, Vlaams Instituut voor Biotechnologie (VIB), 1050 Brussels, Belgium [3] Structural Biology Brussels, Vrije Universiteit Brussel (VUB), 1050 Brussels, Belgium. ; Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland. ; 1] Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland [2] Faculty of Science, University of Zurich, 8057 Zurich, Switzerland. ; Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25470059" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation/drug effects ; Animals ; Calcium/deficiency/metabolism/pharmacology ; Cryoelectron Microscopy ; Cytoplasm/metabolism ; Hydrogen-Ion Concentration ; Inositol 1,4,5-Trisphosphate Receptors/chemistry ; Ion Channel Gating/drug effects ; Models, Molecular ; Protein Binding ; Protein Structure, Tertiary/drug effects ; Rabbits ; Ryanodine Receptor Calcium Release Channel/chemistry/*metabolism/*ultrastructure ; Tacrolimus Binding Protein 1A/chemistry/metabolism/ultrastructure
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  • 11
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    Nature Publishing Group (NPG)
    Publication Date: 2014-07-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Power, Scott B -- England -- Nature. 2014 Jul 3;511(7507):38-9. doi: 10.1038/511038a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bureau of Meteorology, GPO Box 1289, Melbourne, Victoria 3001, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24990739" target="_blank"〉PubMed〈/a〉
    Keywords: Global Warming/*statistics & numerical data ; *Models, Statistical ; *Models, Theoretical ; Probability ; *Temperature ; Time Factors ; *Uncertainty
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  • 12
    Publication Date: 2014-08-15
    Description: The murine caspase-11 non-canonical inflammasome responds to various bacterial infections. Caspase-11 activation-induced pyroptosis, in response to cytoplasmic lipopolysaccharide (LPS), is critical for endotoxic shock in mice. The mechanism underlying cytosolic LPS sensing and the responsible pattern recognition receptor are unknown. Here we show that human monocytes, epithelial cells and keratinocytes undergo necrosis upon cytoplasmic delivery of LPS. LPS-induced cytotoxicity was mediated by human caspase-4 that could functionally complement murine caspase-11. Human caspase-4 and the mouse homologue caspase-11 (hereafter referred to as caspase-4/11) and also human caspase-5, directly bound to LPS and lipid A with high specificity and affinity. LPS associated with endogenous caspase-11 in pyroptotic cells. Insect-cell purified caspase-4/11 underwent oligomerization upon LPS binding, resulting in activation of the caspases. Underacylated lipid IVa and lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS) could bind to caspase-4/11 but failed to induce their oligomerization and activation. LPS binding was mediated by the CARD domain of the caspase. Binding-deficient CARD-domain point mutants did not respond to LPS with oligomerization or activation and failed to induce pyroptosis upon LPS electroporation or bacterial infections. The function of caspase-4/5/11 represents a new mode of pattern recognition in immunity and also an unprecedented means of caspase activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shi, Jianjin -- Zhao, Yue -- Wang, Yupeng -- Gao, Wenqing -- Ding, Jingjin -- Li, Peng -- Hu, Liyan -- Shao, Feng -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Oct 9;514(7521):187-92. doi: 10.1038/nature13683. Epub 2014 Aug 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, National Institute of Biological Sciences, Beijing 102206, China [2] National Institute of Biological Sciences, Beijing 102206, China [3]. ; 1] National Institute of Biological Sciences, Beijing 102206, China [2]. ; National Institute of Biological Sciences, Beijing 102206, China. ; 1] National Institute of Biological Sciences, Beijing 102206, China [2] National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. ; 1] Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, National Institute of Biological Sciences, Beijing 102206, China [2] National Institute of Biological Sciences, Beijing 102206, China [3] National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China [4] National Institute of Biological Sciences, Beijing, Collaborative Innovation Center for Cancer Medicine, Beijing 102206, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25119034" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caspases/chemistry/genetics/immunology/*metabolism ; Caspases, Initiator/chemistry/genetics/immunology/*metabolism ; Cell Death/drug effects ; Cells, Cultured ; Enzyme Activation/drug effects/genetics ; Epithelial Cells/cytology/metabolism ; Genetic Complementation Test ; Humans ; *Immunity, Innate ; Inflammation/enzymology ; Keratinocytes/cytology/metabolism ; Lipid A/metabolism ; Lipopolysaccharides/immunology/*metabolism/pharmacology ; Macrophages/cytology/drug effects/metabolism ; Mice ; Mutant Proteins/chemistry/metabolism ; Necrosis/chemically induced ; Protein Binding ; Protein Multimerization/drug effects/genetics ; Rhodobacter sphaeroides/chemistry/immunology ; Substrate Specificity ; Surface Plasmon Resonance
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  • 13
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    Nature Publishing Group (NPG)
    Publication Date: 2014-07-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gould, Julie -- England -- Nature. 2014 Jul 24;511(7510):S52-3. doi: 10.1038/511S52a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25054851" target="_blank"〉PubMed〈/a〉
    Keywords: Australia ; *Budgets/statistics & numerical data ; Education/economics/manpower ; Evaluation Studies as Topic ; New Zealand ; Research Personnel/economics/standards ; Research Support as Topic/*economics/statistics & numerical data ; Science/*economics/education/standards ; Time Factors ; Universities/economics/manpower
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  • 14
    Publication Date: 2014-03-29
    Description: Human alterations to nutrient cycles and herbivore communities are affecting global biodiversity dramatically. Ecological theory predicts these changes should be strongly counteractive: nutrient addition drives plant species loss through intensified competition for light, whereas herbivores prevent competitive exclusion by increasing ground-level light, particularly in productive systems. Here we use experimental data spanning a globally relevant range of conditions to test the hypothesis that herbaceous plant species losses caused by eutrophication may be offset by increased light availability due to herbivory. This experiment, replicated in 40 grasslands on 6 continents, demonstrates that nutrients and herbivores can serve as counteracting forces to control local plant diversity through light limitation, independent of site productivity, soil nitrogen, herbivore type and climate. Nutrient addition consistently reduced local diversity through light limitation, and herbivory rescued diversity at sites where it alleviated light limitation. Thus, species loss from anthropogenic eutrophication can be ameliorated in grasslands where herbivory increases ground-level light.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Borer, Elizabeth T -- Seabloom, Eric W -- Gruner, Daniel S -- Harpole, W Stanley -- Hillebrand, Helmut -- Lind, Eric M -- Adler, Peter B -- Alberti, Juan -- Anderson, T Michael -- Bakker, Jonathan D -- Biederman, Lori -- Blumenthal, Dana -- Brown, Cynthia S -- Brudvig, Lars A -- Buckley, Yvonne M -- Cadotte, Marc -- Chu, Chengjin -- Cleland, Elsa E -- Crawley, Michael J -- Daleo, Pedro -- Damschen, Ellen I -- Davies, Kendi F -- DeCrappeo, Nicole M -- Du, Guozhen -- Firn, Jennifer -- Hautier, Yann -- Heckman, Robert W -- Hector, Andy -- HilleRisLambers, Janneke -- Iribarne, Oscar -- Klein, Julia A -- Knops, Johannes M H -- La Pierre, Kimberly J -- Leakey, Andrew D B -- Li, Wei -- MacDougall, Andrew S -- McCulley, Rebecca L -- Melbourne, Brett A -- Mitchell, Charles E -- Moore, Joslin L -- Mortensen, Brent -- O'Halloran, Lydia R -- Orrock, John L -- Pascual, Jesus -- Prober, Suzanne M -- Pyke, David A -- Risch, Anita C -- Schuetz, Martin -- Smith, Melinda D -- Stevens, Carly J -- Sullivan, Lauren L -- Williams, Ryan J -- Wragg, Peter D -- Wright, Justin P -- Yang, Louie H -- England -- Nature. 2014 Apr 24;508(7497):517-20. doi: 10.1038/nature13144. Epub 2014 Mar 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology, Evolution, and Behavior, University of Minnesota, St Paul, Minnesota 55108, USA. ; Department of Entomology, University of Maryland, College Park, Maryland 20742, USA. ; Department of Ecology, Evolution, and Organismal Biology, Iowa State University, Ames, Iowa 50011, USA. ; Institute for Chemistry and Biology of the Marine Environment, Carl-von- Ossietzky University, 26382 Wilhelmshaven, Oldenburg, Germany. ; Department of Wildland Resources and the Ecology Center, Utah State University, Logan, Utah 84322, USA. ; Instituto de Investigaciones Marinas y Costeras (IIMyC), Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Mar del Plata 7600 , Argentina. ; Department of Biology, Wake Forest University, Winston-Salem, North Carolina 27109, USA. ; School of Environmental and Forest Sciences, University of Washington, Seattle, Washington 98195, USA. ; Agricultural Research Service (ARS), United States Department of Agriculture, Fort Collins, Colorado 80526, USA. ; Deptartment of Forest, Rangeland and Watershed Stewardship, Colorado State University, Fort Collins, Colorado 80523, USA. ; Department of Plant Biology, Michigan State University, East Lansing, Michigan 48824, USA. ; 1] ARC Centre of Excellence for Environmental Decisions, School of Biological Sciences, The University of Queensland, Queensland 4072, Australia [2] School of Natural Sciences, Trinity College Dublin, Dublin 2, Ireland. ; Department of Ecology and Evolutionary Biology, University of Toronto Scarborough, Ontario M1C 1A4, Canada. ; State Key Laboratory of Grassland and Agro-Ecosystems, Research Station of Alpine Meadow and Wetland Ecosystems, School of Life Sciences, Lanzhou University, Lanzhou, 730000 Gansu, China. ; Division of Biological Sciences, University of California, San Diego, California 92093, USA. ; Department of Biology, Imperial College at Silwood Park, Ascot, Berkshire SL5 7PY, UK. ; Department of Zoology, University of Wisconsin, Madison, Wisconsin 53706, USA. ; Department of Ecology and Evolutionary Biology, University of Colorado, Boulder Colorado 80309, USA. ; US Geological Survey, Forest and Rangeland Ecosystem Science Center, Corvallis, Oregon 97331, USA. ; Queensland University of Technology, Biogeosciences, Brisbane, Queensland 4001, Australia. ; Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. ; Department of Plant Sciences, University of Oxford, Oxford OX1 3RB, UK. ; School of Biological Sciences, University of Nebraska, Lincoln, Nebraska 68588, USA. ; Berkeley Initiative for Global Change Biology, University of California, Berkeley 94704, USA. ; Department of Plant Biology, University of Illinois at Urbana-Champaign, llinois 61820, USA. ; Department of Integrative Biology, University of Guelph, Guelph, Ontario N1G 2W1, Canada. ; Department of Plant & Soil Sciences, University of Kentucky, Lexington, Kentucky 40546, USA. ; Australian Research Center for Urban Ecology, c/o School of Botany, University of Melbourne, Victoria 3010, Australia, and School of Biological Sciences, Monash University, Victoria 3800, Australia. ; Department of Zoology, Oregon State University, Corvallis, Oregon 97331, USA. ; CSIRO Ecosystem Sciences, Wembley, West Australia 6913, Australia. ; Swiss Federal Institute for Forest, Snow and Landscape Research, Birmensdorf 8903, Switzerland. ; Lancaster Environment Center, Lancaster University, Lancaster LA1 4YQ, UK. ; Department of Biology, Duke University, Durham, North Carolina 27708, USA. ; Department of Entomology, University of California, Davis, California 95616, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670649" target="_blank"〉PubMed〈/a〉
    Keywords: *Biodiversity ; Climate ; Eutrophication/drug effects/*radiation effects ; Geography ; Herbivory/*physiology ; Human Activities ; Internationality ; *Light ; Nitrogen/metabolism/pharmacology ; Plants/drug effects/*metabolism/*radiation effects ; *Poaceae/drug effects/physiology/radiation effects ; Time Factors
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  • 15
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    Nature Publishing Group (NPG)
    Publication Date: 2014-04-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gibney, Elizabeth -- England -- Nature. 2014 Apr 3;508(7494):19-20. doi: 10.1038/508019a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24695294" target="_blank"〉PubMed〈/a〉
    Keywords: Advisory Committees ; Europe ; Exobiology/instrumentation/*methods ; *Extraterrestrial Environment/chemistry ; *Mars ; Models, Theoretical ; Russia ; Space Flight/instrumentation/*methods ; Time Factors ; Water/analysis
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  • 16
    Publication Date: 2014-02-11
    Description: The reorganization of patterns of species diversity driven by anthropogenic climate change, and the consequences for humans, are not yet fully understood or appreciated. Nevertheless, changes in climate conditions are useful for predicting shifts in species distributions at global and local scales. Here we use the velocity of climate change to derive spatial trajectories for climatic niches from 1960 to 2009 (ref. 7) and from 2006 to 2100, and use the properties of these trajectories to infer changes in species distributions. Coastlines act as barriers and locally cooler areas act as attractors for trajectories, creating source and sink areas for local climatic conditions. Climate source areas indicate where locally novel conditions are not connected to areas where similar climates previously occurred, and are thereby inaccessible to climate migrants tracking isotherms: 16% of global surface area for 1960 to 2009, and 34% of ocean for the 'business as usual' climate scenario (representative concentration pathway (RCP) 8.5) representing continued use of fossil fuels without mitigation. Climate sink areas are where climate conditions locally disappear, potentially blocking the movement of climate migrants. Sink areas comprise 1.0% of ocean area and 3.6% of land and are prevalent on coasts and high ground. Using this approach to infer shifts in species distributions gives global and regional maps of the expected direction and rate of shifts of climate migrants, and suggests areas of potential loss of species richness.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burrows, Michael T -- Schoeman, David S -- Richardson, Anthony J -- Molinos, Jorge Garcia -- Hoffmann, Ary -- Buckley, Lauren B -- Moore, Pippa J -- Brown, Christopher J -- Bruno, John F -- Duarte, Carlos M -- Halpern, Benjamin S -- Hoegh-Guldberg, Ove -- Kappel, Carrie V -- Kiessling, Wolfgang -- O'Connor, Mary I -- Pandolfi, John M -- Parmesan, Camille -- Sydeman, William J -- Ferrier, Simon -- Williams, Kristen J -- Poloczanska, Elvira S -- England -- Nature. 2014 Mar 27;507(7493):492-5. doi: 10.1038/nature12976. Epub 2014 Feb 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology, Scottish Association for Marine Science, Scottish Marine Institute, Oban, Argyll, PA37 1QA, Scotland, UK. ; School of Science and Engineering, University of the Sunshine Coast, Maroochydore, Queensland QLD 4558, Australia. ; 1] Climate Adaptation Flagship, CSIRO Marine and Atmospheric Research, Ecosciences Precinct, GPO Box 2583, Brisbane, Queensland 4001, Australia [2] Centre for Applications in Natural Resource Mathematics (CARM), School of Mathematics and Physics, The University of Queensland, St Lucia, Queensland 4072, Australia. ; Department of Genetics, University of Melbourne, 30 Flemington Road, Parkville, Victoria 3010, Australia. ; Department of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3280, USA. ; 1] Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DA, UK [2] Centre for Marine Ecosystems Research, Edith Cowan University, Perth 6027, Australia. ; The Global Change Institute, The University of Queensland, Brisbane, Queensland 4072, Australia. ; 1] The UWA Oceans Institute, University of Western Australia, 35 Stirling Highway, Crawley 6009, Australia [2] Department of Global Change Research, IMEDEA (UIB-CSIC), Instituto Mediterraneo de Estudios Avanzados, Esporles 07190, Spain [3] Department of Marine Biology, Faculty of Marine Sciences, King Abdulaziz University, PO Box 80207, Jeddah 21589, Saudi Arabia. ; 1] Bren School of Environmental Science and Management, University of California, Santa Barbara, California 93106, USA [2] Imperial College London, Silwood Park Campus, Buckhurst Road, Ascot SL5 7PY, UK. ; Bren School of Environmental Science and Management, University of California, Santa Barbara, California 93106, USA. ; 1] GeoZentrum Nordbayern, Palaoumwelt, Universitat Erlangen-Nurnberg, Loewenichstrasse 28, 91054 Erlangen, Germany [2] Museum fur Naturkunde, Invalidenstr asse 43, 10115 Berlin, Germany. ; Department of Zoology and Biodiversity Research Centre, University of British Columbia, Vancouver V6T 1Z4, Canada. ; School of Biological Sciences, Australian Research Council Centre of Excellence for Coral Reef Studies, The University of Queensland, Brisbane, Queensland 4072, Australia. ; 1] Integrative Biology, University of Texas, Austin, Texas 78712, USA [2] Marine Institute, Drake Circus, University of Plymouth, Devon PL4 8AA, UK. ; Farallon Institute for Advanced Ecosystem Research, 101 H Street, Suite Q, Petaluma, California 94952, USA. ; Climate Adaptation Flagship, CSIRO Ecosystem Sciences, GPO Box 1700, Canberra, Australian Capital Territory 2601, Australia. ; Climate Adaptation Flagship, CSIRO Marine and Atmospheric Research, Ecosciences Precinct, GPO Box 2583, Brisbane, Queensland 4001, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24509712" target="_blank"〉PubMed〈/a〉
    Keywords: *Animal Migration ; Animals ; Australia ; Biodiversity ; *Climate ; *Climate Change ; *Ecosystem ; *Geographic Mapping ; *Geography ; Models, Theoretical ; Population Dynamics ; Seawater ; Temperature ; Time Factors ; Uncertainty
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  • 17
    Publication Date: 2014-09-26
    Description: Billions of organisms, from bacteria to humans, migrate each year and research on their migration biology is expanding rapidly through ever more sophisticated remote sensing technologies. However, little is known about how migratory performance develops through life for any organism. To date, age variation has been almost systematically simplified into a dichotomous comparison between recently born juveniles at their first migration versus adults of unknown age. These comparisons have regularly highlighted better migratory performance by adults compared with juveniles, but it is unknown whether such variation is gradual or abrupt and whether it is driven by improvements within the individual, by selective mortality of poor performers, or both. Here we exploit the opportunity offered by long-term monitoring of individuals through Global Positioning System (GPS) satellite tracking to combine within-individual and cross-sectional data on 364 migration episodes from 92 individuals of a raptorial bird, aged 1-27 years old. We show that the development of migratory behaviour follows a consistent trajectory, more gradual and prolonged than previously appreciated, and that this is promoted by both individual improvements and selective mortality, mainly operating in early life and during the pre-breeding migration. Individuals of different age used different travelling tactics and varied in their ability to exploit tailwinds or to cope with wind drift. All individuals seemed aligned along a race with their contemporary peers, whose outcome was largely determined by the ability to depart early, affecting their subsequent recruitment, reproduction and survival. Understanding how climate change and human action can affect the migration of younger animals may be the key to managing and forecasting the declines of many threatened migrants.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sergio, Fabrizio -- Tanferna, Alessandro -- De Stephanis, Renaud -- Jimenez, Lidia Lopez -- Blas, Julio -- Tavecchia, Giacomo -- Preatoni, Damiano -- Hiraldo, Fernando -- England -- Nature. 2014 Nov 20;515(7527):410-3. doi: 10.1038/nature13696. Epub 2014 Sep 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Conservation Biology, Estacion Biologica de Donana-CSIC, Avenida Americo Vespucio, 41092 Seville, Spain. ; Population Ecology Group, Institute for Mediterranean Studies (IMEDEA), CSIC-UIB, 07190 Esporles, Spain. ; Department of Theoretical and Applied Sciences, Insubria University, 21100 Varese, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25252973" target="_blank"〉PubMed〈/a〉
    Keywords: Africa ; Age Factors ; Aging/*physiology ; Animal Migration/*physiology ; Animals ; Conservation of Natural Resources ; Geographic Information Systems ; Global Warming ; Human Activities ; Raptors/*physiology ; Reproduction/physiology ; Spain ; Survival Rate ; Time Factors ; Wind
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  • 18
    Publication Date: 2014-11-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Settembre, Carmine -- Ballabio, Andrea -- England -- Nature. 2014 Dec 4;516(7529):40-1. doi: 10.1038/nature13939. Epub 2014 Nov 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Telethon Institute of Genetics and Medicine, Naples 80078, Italy; in the Department of Translational Medicine, Federico II University, Naples; and in the Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25383529" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autophagy/*genetics ; Cyclic AMP Response Element-Binding Protein/metabolism ; Fatty Acids/metabolism ; *Gene Expression Regulation ; Liver/cytology/*metabolism ; PPAR alpha/metabolism ; Promoter Regions, Genetic ; Protein Binding ; Receptors, Cytoplasmic and Nuclear/metabolism
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  • 19
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    Nature Publishing Group (NPG)
    Publication Date: 2014-09-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gilbert, Natasha -- England -- Nature. 2014 Sep 18;513(7518):292. doi: 10.1038/513292a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25230627" target="_blank"〉PubMed〈/a〉
    Keywords: Acclimatization/*genetics/*physiology ; Agriculture/*methods ; *Breeding ; Crops, Agricultural/*genetics/*physiology ; Disasters ; Droughts ; Food, Genetically Modified ; Plants, Genetically Modified/genetics/physiology ; Rain ; Time Factors ; Zea mays/genetics/physiology
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  • 20
    Publication Date: 2014-11-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Whitty, Christopher J M -- Farrar, Jeremy -- Ferguson, Neil -- Edmunds, W John -- Piot, Peter -- Leach, Melissa -- Davies, Sally C -- England -- Nature. 2014 Nov 13;515(7526):192-4. doi: 10.1038/515192a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25391946" target="_blank"〉PubMed〈/a〉
    Keywords: Bed Occupancy/statistics & numerical data ; Compassionate Use Trials/trends ; Contact Tracing/*methods ; Ebola Vaccines/supply & distribution ; Facility Design and Construction ; Great Britain ; Hemorrhagic Fever, Ebola/diagnosis/epidemiology/*prevention & ; control/*transmission ; Humans ; Models, Biological ; Patient Isolation/*methods ; Quarantine/*methods ; Self Report ; Sierra Leone/epidemiology ; Time Factors
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 21
    Publication Date: 2014-07-22
    Description: The viral reservoir represents a critical challenge for human immunodeficiency virus type 1 (HIV-1) eradication strategies. However, it remains unclear when and where the viral reservoir is seeded during acute infection and the extent to which it is susceptible to early antiretroviral therapy (ART). Here we show that the viral reservoir is seeded rapidly after mucosal simian immunodeficiency virus (SIV) infection of rhesus monkeys and before systemic viraemia. We initiated suppressive ART in groups of monkeys on days 3, 7, 10 and 14 after intrarectal SIVMAC251 infection. Treatment with ART on day 3 blocked the emergence of viral RNA and proviral DNA in peripheral blood and also substantially reduced levels of proviral DNA in lymph nodes and gastrointestinal mucosa as compared with treatment at later time points. In addition, treatment on day 3 abrogated the induction of SIV-specific humoral and cellular immune responses. Nevertheless, after discontinuation of ART following 24 weeks of fully suppressive therapy, virus rebounded in all animals, although the monkeys that were treated on day 3 exhibited a delayed viral rebound as compared with those treated on days 7, 10 and 14. The time to viral rebound correlated with total viraemia during acute infection and with proviral DNA at the time of ART discontinuation. These data demonstrate that the viral reservoir is seeded rapidly after intrarectal SIV infection of rhesus monkeys, during the 'eclipse' phase, and before detectable viraemia. This strikingly early seeding of the refractory viral reservoir raises important new challenges for HIV-1 eradication strategies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4126858/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4126858/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Whitney, James B -- Hill, Alison L -- Sanisetty, Srisowmya -- Penaloza-MacMaster, Pablo -- Liu, Jinyan -- Shetty, Mayuri -- Parenteau, Lily -- Cabral, Crystal -- Shields, Jennifer -- Blackmore, Stephen -- Smith, Jeffrey Y -- Brinkman, Amanda L -- Peter, Lauren E -- Mathew, Sheeba I -- Smith, Kaitlin M -- Borducchi, Erica N -- Rosenbloom, Daniel I S -- Lewis, Mark G -- Hattersley, Jillian -- Li, Bei -- Hesselgesser, Joseph -- Geleziunas, Romas -- Robb, Merlin L -- Kim, Jerome H -- Michael, Nelson L -- Barouch, Dan H -- AI060354/AI/NIAID NIH HHS/ -- AI078526/AI/NIAID NIH HHS/ -- AI084794/AI/NIAID NIH HHS/ -- AI095985/AI/NIAID NIH HHS/ -- AI096040/AI/NIAID NIH HHS/ -- AI100645/AI/NIAID NIH HHS/ -- R01 AI084794/AI/NIAID NIH HHS/ -- R56 AI091514/AI/NIAID NIH HHS/ -- T32 AI007245/AI/NIAID NIH HHS/ -- U19 AI078526/AI/NIAID NIH HHS/ -- U19 AI095985/AI/NIAID NIH HHS/ -- U19 AI096040/AI/NIAID NIH HHS/ -- UM1 AI100645/AI/NIAID NIH HHS/ -- UM1 AI100663/AI/NIAID NIH HHS/ -- England -- Nature. 2014 Aug 7;512(7512):74-7. doi: 10.1038/nature13594. Epub 2014 Jul 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA [2] Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts 02139, USA. ; Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts 02138 USA. ; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. ; Bioqual, Rockville, Maryland 20852, USA. ; Gilead Sciences, Foster City, California 94404, USA. ; US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25042999" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Retroviral Agents/administration & dosage/pharmacology/therapeutic use ; Carrier State/drug therapy/virology ; DNA, Viral/analysis/biosynthesis/blood ; Disease Models, Animal ; Female ; Kinetics ; Macaca mulatta/immunology/*virology ; Male ; Proviruses/genetics ; RNA, Viral/blood ; Rectum/virology ; Simian Acquired Immunodeficiency Syndrome/drug therapy/immunology/*virology ; Simian Immunodeficiency Virus/drug effects/*growth & ; development/immunology/physiology ; Time Factors ; Treatment Failure ; *Viral Load/drug effects ; Viremia/drug therapy/*virology ; Virus Replication/drug effects
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 22
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2014-02-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sharpe, Katherine -- England -- Nature. 2014 Feb 13;506(7487):146-8. doi: 10.1038/506146a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24522583" target="_blank"〉PubMed〈/a〉
    Keywords: *Achievement ; Antisocial Personality Disorder/prevention & control ; Attention/drug effects ; Attention Deficit Disorder with Hyperactivity/*drug ; therapy/physiopathology/psychology ; Biomedical Enhancement ; Child ; Child, Preschool ; Educational Measurement ; Humans ; Longitudinal Studies ; Memory, Short-Term/drug effects ; Methylphenidate/adverse effects/pharmacology/therapeutic use ; Randomized Controlled Trials as Topic ; Time Factors
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 23
    Publication Date: 2014-07-22
    Description: Hundreds of tail-anchored proteins, including soluble N-ethylmaleimide-sensitive factor attachment receptors (SNAREs) involved in vesicle fusion, are inserted post-translationally into the endoplasmic reticulum membrane by a dedicated protein-targeting pathway. Before insertion, the carboxy-terminal transmembrane domains of tail-anchored proteins are shielded in the cytosol by the conserved targeting factor Get3 (in yeast; TRC40 in mammals). The Get3 endoplasmic-reticulum receptor comprises the cytosolic domains of the Get1/2 (WRB/CAML) transmembrane complex, which interact individually with the targeting factor to drive a conformational change that enables substrate release and, as a consequence, insertion. Because tail-anchored protein insertion is not associated with significant translocation of hydrophilic protein sequences across the membrane, it remains possible that Get1/2 cytosolic domains are sufficient to place Get3 in proximity with the endoplasmic-reticulum lipid bilayer and permit spontaneous insertion to occur. Here we use cell reporters and biochemical reconstitution to define mutations in the Get1/2 transmembrane domain that disrupt tail-anchored protein insertion without interfering with Get1/2 cytosolic domain function. These mutations reveal a novel Get1/2 insertase function, in the absence of which substrates stay bound to Get3 despite their proximity to the lipid bilayer; as a consequence, the notion of spontaneous transmembrane domain insertion is a non sequitur. Instead, the Get1/2 transmembrane domain helps to release substrates from Get3 by capturing their transmembrane domains, and these transmembrane interactions define a bona fide pre-integrated intermediate along a facilitated route for tail-anchor entry into the lipid bilayer. Our work sheds light on the fundamental point of convergence between co-translational and post-translational endoplasmic-reticulum membrane protein targeting and insertion: a mechanism for reducing the ability of a targeting factor to shield its substrates enables substrate handover to a transmembrane-domain-docking site embedded in the endoplasmic-reticulum membrane.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342754/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342754/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Fei -- Chan, Charlene -- Weir, Nicholas R -- Denic, Vladimir -- R01 GM099943/GM/NIGMS NIH HHS/ -- R01GM0999943-01/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Aug 28;512(7515):441-4. doi: 10.1038/nature13471. Epub 2014 Jul 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Harvard University, Northwest Labs, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043001" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Vesicular Transport/chemistry/genetics/*metabolism ; Adenosine Triphosphatases/metabolism ; Binding Sites ; Endoplasmic Reticulum/chemistry/enzymology/*metabolism ; Guanine Nucleotide Exchange Factors/metabolism ; Intracellular Membranes/chemistry/enzymology/*metabolism ; Lipid Bilayers/chemistry/metabolism ; Membrane Proteins/chemistry/genetics/*metabolism ; Multiprotein Complexes/chemistry/*metabolism ; Mutant Proteins/chemistry/genetics/metabolism ; Mutation ; Protein Binding ; Protein Structure, Tertiary/genetics ; Protein Transport/genetics ; Saccharomyces cerevisiae/*cytology/*enzymology/genetics/metabolism ; Saccharomyces cerevisiae Proteins/chemistry/genetics/*metabolism
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 24
    Publication Date: 2014-02-07
    Description: Although it is generally agreed that the Arctic flora is among the youngest and least diverse on Earth, the processes that shaped it are poorly understood. Here we present 50 thousand years (kyr) of Arctic vegetation history, derived from the first large-scale ancient DNA metabarcoding study of circumpolar plant diversity. For this interval we also explore nematode diversity as a proxy for modelling vegetation cover and soil quality, and diets of herbivorous megafaunal mammals, many of which became extinct around 10 kyr bp (before present). For much of the period investigated, Arctic vegetation consisted of dry steppe-tundra dominated by forbs (non-graminoid herbaceous vascular plants). During the Last Glacial Maximum (25-15 kyr bp), diversity declined markedly, although forbs remained dominant. Much changed after 10 kyr bp, with the appearance of moist tundra dominated by woody plants and graminoids. Our analyses indicate that both graminoids and forbs would have featured in megafaunal diets. As such, our findings question the predominance of a Late Quaternary graminoid-dominated Arctic mammoth steppe.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Willerslev, Eske -- Davison, John -- Moora, Mari -- Zobel, Martin -- Coissac, Eric -- Edwards, Mary E -- Lorenzen, Eline D -- Vestergard, Mette -- Gussarova, Galina -- Haile, James -- Craine, Joseph -- Gielly, Ludovic -- Boessenkool, Sanne -- Epp, Laura S -- Pearman, Peter B -- Cheddadi, Rachid -- Murray, David -- Brathen, Kari Anne -- Yoccoz, Nigel -- Binney, Heather -- Cruaud, Corinne -- Wincker, Patrick -- Goslar, Tomasz -- Alsos, Inger Greve -- Bellemain, Eva -- Brysting, Anne Krag -- Elven, Reidar -- Sonstebo, Jorn Henrik -- Murton, Julian -- Sher, Andrei -- Rasmussen, Morten -- Ronn, Regin -- Mourier, Tobias -- Cooper, Alan -- Austin, Jeremy -- Moller, Per -- Froese, Duane -- Zazula, Grant -- Pompanon, Francois -- Rioux, Delphine -- Niderkorn, Vincent -- Tikhonov, Alexei -- Savvinov, Grigoriy -- Roberts, Richard G -- MacPhee, Ross D E -- Gilbert, M Thomas P -- Kjaer, Kurt H -- Orlando, Ludovic -- Brochmann, Christian -- Taberlet, Pierre -- England -- Nature. 2014 Feb 6;506(7486):47-51. doi: 10.1038/nature12921.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Centre for GeoGenetics, Natural History Museum, University of Copenhagen, Oster Voldgade 5-7, DK-1350 Copenhagen K, Denmark [2]. ; 1] Department of Botany, Institute of Ecology and Earth Sciences, University of Tartu, 40 Lai Street, 51005 Tartu, Estonia [2]. ; 1] Laboratoire d'Ecologie Alpine (LECA) CNRS UMR 5553, University Joseph Fourier, BP 53, 38041 Grenoble Cedex 9, France [2]. ; 1] Geography and Environment, University of Southampton, Southampton SO17 1BJ, UK [2]. ; 1] Centre for GeoGenetics, Natural History Museum, University of Copenhagen, Oster Voldgade 5-7, DK-1350 Copenhagen K, Denmark [2] Department of Integrative Biology, University of California Berkeley, 1005 Valley Life Sciences Building, Berkeley, 94720 California, USA [3]. ; 1] National Centre for Biosystematics, Natural History Museum, University of Oslo, PO Box 1172, Blindern, NO-0318 Oslo, Norway [2] Department of Botany, Saint Petersburg State University, Universitetskaya nab. 7/9, 199034 Saint Petersburg, Russia [3]. ; 1] Centre for GeoGenetics, Natural History Museum, University of Copenhagen, Oster Voldgade 5-7, DK-1350 Copenhagen K, Denmark [2] Ancient DNA Laboratory, Veterinary and Life Sciences School, Murdoch University, 90 South Street, Perth, 6150 Western Australia, Australia [3]. ; Division of Biology, Kansas State University, Manhattan, 66506-4901 Kansas, USA. ; Laboratoire d'Ecologie Alpine (LECA) CNRS UMR 5553, University Joseph Fourier, BP 53, 38041 Grenoble Cedex 9, France. ; 1] National Centre for Biosystematics, Natural History Museum, University of Oslo, PO Box 1172, Blindern, NO-0318 Oslo, Norway [2] Centre for Ecological and Evolutionary Synthesis, Department of Biosciences, University of Oslo, PO Box 1066, Blindern, NO-0318 Oslo, Norway (S.B.); Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research, Research Unit Potsdam, Telegrafenberg A 43, 14473 Potsdam, Germany (L.S.E.); SpyGen, Savoie Technolac, 17 allee du lac Saint Andre, BP 274, 73375 Le Bourget-du-Lac Cedex, France (E.B.). ; Landscape Dynamics Unit, Swiss Federal Research Institute WSL, Zurcherstrasse 111, CH-8903 Birmensdorf, Switzerland. ; Institut des Sciences de l'Evolution de Montpellier, UMR 5554 Universite Montpellier 2, Bat.22, CC061, Place Eugene Bataillon, 34095 Montpellier Cedex 5, France. ; University of Alaska Museum of the North, Fairbanks, 99775-6960 Alaska, USA. ; Department of Arctic and Marine Biology, UiT, The Arctic University of Norway, NO-9037 Tromso, Norway. ; Geography and Environment, University of Southampton, Southampton SO17 1BJ, UK. ; Genoscope, Institut de Genomique du Commissariat a l'Energie Atomique (CEA), 91000 Evry, France. ; 1] Adam Mickiewicz University, Faculty of Physics, Umultowska 85, 61-614 Poznan, Poland [2] Poznan Radiocarbon Laboratory, Poznan Science and Technology Park, Rubiez 46, 61-612 Poznan, Poland. ; Tromso University Museum, NO-9037 Tromso, Norway. ; Centre for Ecological and Evolutionary Synthesis, Department of Biosciences, University of Oslo, P.O. Box 1066, Blindern, NO-0316 Oslo, Norway. ; National Centre for Biosystematics, Natural History Museum, University of Oslo, PO Box 1172, Blindern, NO-0318 Oslo, Norway. ; Permafrost Laboratory, Department of Geography, University of Sussex, Brighton BN1 9QJ, UK. ; 1] Institute of Ecology and Evolution, Russian Academy of Sciences, 33 Leninsky Prospect, 119071 Moscow, Russia [2]. ; Centre for GeoGenetics, Natural History Museum, University of Copenhagen, Oster Voldgade 5-7, DK-1350 Copenhagen K, Denmark. ; Department of Biology, Terrestrial Ecology, Universitetsparken 15, DK- 2100 Copenhagen O, Denmark. ; Australian Centre for Ancient DNA, School of Earth & Environmental Sciences, University of Adelaide, Adelaide, 5005 South Australia, Australia. ; Department of Geology/Quaternary Sciences, Lund University Solvegatan 12, SE-223 62 Lund, Sweden. ; Department of Earth and Atmospheric Sciences, University of Alberta, T6G 2E3 Edmonton, Alberta, Canada. ; Government of Yukon, Department of Tourism and Culture, Yukon Palaeontology Program, PO Box 2703 L2A, Y1A 2C6 Whitehorse, Yukon Territory, Canada. ; INRA, UMR1213 Herbivores, F-63122 Saint-Genes-Champanelle, France. ; Zoological Institute of Russian Academy of Sciences, Universitetskaya nab. 1, 199034 Saint-Petersburg, Russia. ; Institute of Applied Ecology of the North of North-Eastern Federal University, Belinskogo Street 58, 677000 Yakutsk, Republic of Sakha (Yakutia), Russia. ; Centre for Archaeological Science, School of Earth and Environmental Sciences, University of Wollongong, Wollongong, 2522 New South Wales, Australia. ; Division of Vertebrate Zoology/Mammalogy, American Museum of Natural History, New York, 10024 New York, USA. ; 1] National Centre for Biosystematics, Natural History Museum, University of Oslo, PO Box 1172, Blindern, NO-0318 Oslo, Norway [2].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24499916" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arctic Regions ; *Biodiversity ; Bison/physiology ; Cold Climate ; *Diet ; Freezing ; *Herbivory ; High-Throughput Nucleotide Sequencing ; Horses/physiology ; Mammoths/physiology ; *Nematoda/classification/genetics/isolation & purification ; *Plants/classification/genetics ; Poaceae/genetics/growth & development ; Soil ; Time Factors ; Yukon Territory
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  • 25
    Publication Date: 2014-11-20
    Description: Influenza virus polymerase uses a capped primer, derived by 'cap-snatching' from host pre-messenger RNA, to transcribe its RNA genome into mRNA and a stuttering mechanism to generate the poly(A) tail. By contrast, genome replication is unprimed and generates exact full-length copies of the template. Here we use crystal structures of bat influenza A and human influenza B polymerases (FluA and FluB), bound to the viral RNA promoter, to give mechanistic insight into these distinct processes. In the FluA structure, a loop analogous to the priming loop of flavivirus polymerases suggests that influenza could initiate unprimed template replication by a similar mechanism. Comparing the FluA and FluB structures suggests that cap-snatching involves in situ rotation of the PB2 cap-binding domain to direct the capped primer first towards the endonuclease and then into the polymerase active site. The polymerase probably undergoes considerable conformational changes to convert the observed pre-initiation state into the active initiation and elongation states.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reich, Stefan -- Guilligay, Delphine -- Pflug, Alexander -- Malet, Helene -- Berger, Imre -- Crepin, Thibaut -- Hart, Darren -- Lunardi, Thomas -- Nanao, Max -- Ruigrok, Rob W H -- Cusack, Stephen -- England -- Nature. 2014 Dec 18;516(7531):361-6. doi: 10.1038/nature14009. Epub 2014 Nov 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] European Molecular Biology Laboratory, Grenoble Outstation, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France [2] University Grenoble Alpes-Centre National de la Recherche Scientifique-EMBL Unit of Virus Host-Cell Interactions, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France. ; University Grenoble Alpes-Centre National de la Recherche Scientifique-EMBL Unit of Virus Host-Cell Interactions, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25409151" target="_blank"〉PubMed〈/a〉
    Keywords: Catalytic Domain ; Crystallization ; DNA-Directed RNA Polymerases/chemistry/*metabolism ; Gene Expression Regulation, Viral ; Influenza A virus/chemistry/*enzymology ; Influenza B virus/chemistry/*enzymology ; *Models, Molecular ; Promoter Regions, Genetic ; Protein Binding ; Protein Structure, Tertiary ; *RNA Caps/chemistry/metabolism ; RNA, Viral/*biosynthesis/*chemistry ; Virus Replication
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  • 26
    Publication Date: 2014-05-09
    Description: During immune responses, B lymphocytes clonally expand and undergo secondary diversification of their immunoglobulin genes in germinal centres (GCs). High-affinity B cells are expanded through iterative interzonal cycles of division and hypermutation in the GC dark zone followed by migration to the GC light zone, where they are selected on the basis of affinity to return to the dark zone. Here we combine a transgenic strategy to measure cell division and a photoactivatable fluorescent reporter to examine whether the extent of clonal expansion and hypermutation are regulated during interzonal GC cycles. We find that both cell division and hypermutation are directly proportional to the amount of antigen captured and presented by GC B cells to follicular helper T cells in the light zone. Our data explain how GC B cells with the highest affinity for antigen are selectively expanded and diversified.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4271732/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4271732/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gitlin, Alexander D -- Shulman, Ziv -- Nussenzweig, Michel C -- 1UM1 AI100663-01/AI/NIAID NIH HHS/ -- AI037526-19/AI/NIAID NIH HHS/ -- AI072529-06/AI/NIAID NIH HHS/ -- R01 AI037526/AI/NIAID NIH HHS/ -- R01 AI072529/AI/NIAID NIH HHS/ -- T32GM07739/GM/NIGMS NIH HHS/ -- UM1 AI100663/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 May 29;509(7502):637-40. doi: 10.1038/nature13300. Epub 2014 May 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA. ; 1] Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA [2] Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24805232" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibody Affinity/immunology ; Antigen Presentation/immunology ; Antigens/immunology ; B-Lymphocytes/*cytology/immunology/*metabolism ; Cell Movement ; Cell Proliferation ; *Clonal Selection, Antigen-Mediated/immunology ; Clone Cells/cytology/immunology/metabolism ; Genes, Reporter/genetics ; Germinal Center/*cytology/*immunology ; Male ; Mice ; S Phase ; Somatic Hypermutation, Immunoglobulin/*genetics ; T-Lymphocytes, Helper-Inducer/cytology/immunology ; Time Factors
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  • 27
    Publication Date: 2014-07-11
    Description: N-methyl-d-aspartate (NMDA) receptors are Hebbian-like coincidence detectors, requiring binding of glycine and glutamate in combination with the relief of voltage-dependent magnesium block to open an ion conductive pore across the membrane bilayer. Despite the importance of the NMDA receptor in the development and function of the brain, a molecular structure of an intact receptor has remained elusive. Here we present X-ray crystal structures of the Xenopus laevis GluN1-GluN2B NMDA receptor with the allosteric inhibitor, Ro25-6981, partial agonists and the ion channel blocker, MK-801. Receptor subunits are arranged in a 1-2-1-2 fashion, demonstrating extensive interactions between the amino-terminal and ligand-binding domains. The transmembrane domains harbour a closed-blocked ion channel, a pyramidal central vestibule lined by residues implicated in binding ion channel blockers and magnesium, and a approximately twofold symmetric arrangement of ion channel pore loops. These structures provide new insights into the architecture, allosteric coupling and ion channel function of NMDA receptors.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263351/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263351/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Chia-Hsueh -- Lu, Wei -- Michel, Jennifer Carlisle -- Goehring, April -- Du, Juan -- Song, Xianqiang -- Gouaux, Eric -- R37 NS038631/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jul 10;511(7508):191-7. doi: 10.1038/nature13548. Epub 2014 Jun 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Vollum Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA [2]. ; 1] Vollum Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA [2] Howard Hughes Medical Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA. ; Vollum Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25008524" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dizocilpine Maleate/chemistry ; Ion Channels/chemistry ; Ligands ; *Models, Molecular ; Phenols ; Piperidines/chemistry ; Protein Binding ; Protein Structure, Tertiary ; Protein Subunits/chemistry ; Receptors, N-Methyl-D-Aspartate/*chemistry ; Xenopus laevis/*physiology
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  • 28
    Publication Date: 2014-09-12
    Description: To prime reverse transcription, retroviruses require annealing of a transfer RNA molecule to the U5 primer binding site (U5-PBS) region of the viral genome. The residues essential for primer annealing are initially locked in intramolecular interactions; hence, annealing requires the chaperone activity of the retroviral nucleocapsid (NC) protein to facilitate structural rearrangements. Here we show that, unlike classical chaperones, the Moloney murine leukaemia virus NC uses a unique mechanism for remodelling: it specifically targets multiple structured regions in both the U5-PBS and tRNA(Pro) primer that otherwise sequester residues necessary for annealing. This high-specificity and high-affinity binding by NC consequently liberates these sequestered residues--which are exactly complementary--for intermolecular interactions. Furthermore, NC utilizes a step-wise, entropy-driven mechanism to trigger both residue-specific destabilization and residue-specific release. Our structures of NC bound to U5-PBS and tRNA(Pro) reveal the structure-based mechanism for retroviral primer annealing and provide insights as to how ATP-independent chaperones can target specific RNAs amidst the cellular milieu of non-target RNAs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Sarah B -- Yildiz, F Zehra -- Lo, Jennifer A -- Wang, Bo -- D'Souza, Victoria M -- England -- Nature. 2014 Nov 27;515(7528):591-5. doi: 10.1038/nature13709. Epub 2014 Sep 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA [2] Department of Biology, Georgetown University, Washington DC 20057, USA. [3]. ; 1] Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA [2]. ; Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25209668" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Genome, Viral/genetics ; Humans ; *Models, Molecular ; *Moloney murine leukemia virus/chemistry/genetics ; Nuclear Magnetic Resonance, Biomolecular ; *Nucleocapsid Proteins/chemistry/metabolism ; Protein Binding ; Protein Structure, Tertiary ; *RNA, Transfer/chemistry/metabolism ; RNA, Viral/*chemistry/*metabolism ; Reverse Transcription/genetics/*physiology
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  • 29
    Publication Date: 2014-08-22
    Description: Cys-loop receptors are neurotransmitter-gated ion channels that are essential mediators of fast chemical neurotransmission and are associated with a large number of neurological diseases and disorders, as well as parasitic infections. Members of this ion channel superfamily mediate excitatory or inhibitory neurotransmission depending on their ligand and ion selectivity. Structural information for Cys-loop receptors comes from several sources including electron microscopic studies of the nicotinic acetylcholine receptor, high-resolution X-ray structures of extracellular domains and X-ray structures of bacterial orthologues. In 2011 our group published structures of the Caenorhabditis elegans glutamate-gated chloride channel (GluCl) in complex with the allosteric partial agonist ivermectin, which provided insights into the structure of a possibly open state of a eukaryotic Cys-loop receptor, the basis for anion selectivity and channel block, and the mechanism by which ivermectin and related molecules stabilize the open state and potentiate neurotransmitter binding. However, there remain unanswered questions about the mechanism of channel opening and closing, the location and nature of the shut ion channel gate, the transitions between the closed/resting, open/activated and closed/desensitized states, and the mechanism by which conformational changes are coupled between the extracellular, orthosteric agonist binding domain and the transmembrane, ion channel domain. Here we present two conformationally distinct structures of C. elegans GluCl in the absence of ivermectin. Structural comparisons reveal a quaternary activation mechanism arising from rigid-body movements between the extracellular and transmembrane domains and a mechanism for modulation of the receptor by phospholipids.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255919/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255919/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Althoff, Thorsten -- Hibbs, Ryan E -- Banerjee, Surajit -- Gouaux, Eric -- F32 NS061404/NS/NINDS NIH HHS/ -- F32NS061404/NS/NINDS NIH HHS/ -- P41 GM103403/GM/NIGMS NIH HHS/ -- R01 GM100400/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Aug 21;512(7514):333-7. doi: 10.1038/nature13669.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Vollum Institute, Oregon Health &Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA [2] Department of Physiology, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, California 90095-1751, USA (T.A.); Department of Neuroscience, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas 75390-9111, USA (R.E.H.). [3]. ; NE-CAT/Cornell University, 9700 South Cass Avenue, Building 436 E001, Argonne, Illinois 60439, USA. ; 1] Vollum Institute, Oregon Health &Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA [2] Howard Hughes Medical Institute, Oregon Health &Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25143115" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation/drug effects ; Animals ; Apoproteins/*chemistry/metabolism ; Binding Sites ; Binding, Competitive/drug effects ; Caenorhabditis elegans/*chemistry ; Cell Membrane/metabolism ; Chloride Channels/*chemistry/*metabolism ; Crystallography, X-Ray ; Cysteine Loop Ligand-Gated Ion Channel Receptors/*chemistry/*metabolism ; Drug Partial Agonism ; Glutamic Acid/metabolism ; Ion Channel Gating ; Ivermectin/chemistry/metabolism/pharmacology ; Ligands ; Models, Molecular ; Movement/drug effects ; Phosphatidylcholines/chemistry/metabolism/pharmacology ; Protein Binding ; Protein Multimerization/drug effects ; Protein Structure, Tertiary/drug effects ; Structure-Activity Relationship
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  • 30
    Publication Date: 2014-10-03
    Description: Bone-marrow transplantation is an effective cell therapy but requires myeloablation, which increases infection risk and mortality. Recent lineage-tracing studies documenting that resident macrophage populations self-maintain independently of haematological progenitors prompted us to consider organ-targeted, cell-specific therapy. Here, using granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor-beta-deficient (Csf2rb(-/-)) mice that develop a myeloid cell disorder identical to hereditary pulmonary alveolar proteinosis (hPAP) in children with CSF2RA or CSF2RB mutations, we show that pulmonary macrophage transplantation (PMT) of either wild-type or Csf2rb-gene-corrected macrophages without myeloablation was safe and well-tolerated and that one administration corrected the lung disease, secondary systemic manifestations and normalized disease-related biomarkers, and prevented disease-specific mortality. PMT-derived alveolar macrophages persisted for at least one year as did therapeutic effects. Our findings identify mechanisms regulating alveolar macrophage population size in health and disease, indicate that GM-CSF is required for phenotypic determination of alveolar macrophages, and support translation of PMT as the first specific therapy for children with hPAP.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4236859/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4236859/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Suzuki, Takuji -- Arumugam, Paritha -- Sakagami, Takuro -- Lachmann, Nico -- Chalk, Claudia -- Sallese, Anthony -- Abe, Shuichi -- Trapnell, Cole -- Carey, Brenna -- Moritz, Thomas -- Malik, Punam -- Lutzko, Carolyn -- Wood, Robert E -- Trapnell, Bruce C -- 8UL1TR000077-05/TR/NCATS NIH HHS/ -- AR-47363/AR/NIAMS NIH HHS/ -- DK78392/DK/NIDDK NIH HHS/ -- DK90971/DK/NIDDK NIH HHS/ -- P30 AR047363/AR/NIAMS NIH HHS/ -- R01 HL069549/HL/NHLBI NIH HHS/ -- R01 HL085453/HL/NHLBI NIH HHS/ -- R01 HL118342/HL/NHLBI NIH HHS/ -- R01HL085453/HL/NHLBI NIH HHS/ -- R01HL118342/HL/NHLBI NIH HHS/ -- R21 HL106134/HL/NHLBI NIH HHS/ -- U54 HL127672/HL/NHLBI NIH HHS/ -- England -- Nature. 2014 Oct 23;514(7523):450-4. doi: 10.1038/nature13807. Epub 2014 Oct 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA. ; Division of Experimental Hematology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA. ; RG Reprograming and Gene Therapy, Institute of Experimental Hematology, Hannover Medical School, Carl Neuberg-Str. 1, 30625 Hannover, Germany. ; 1] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA [2] Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02138, USA. ; Division of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA. ; 1] Division of Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA [2] Division of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA [3] Division of Pulmonary, Critical Care, and Sleep Medicine, University of Cincinnati Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25274301" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Separation ; *Cell Transplantation ; Cytokine Receptor Common beta Subunit/deficiency/*genetics ; Female ; *Genetic Therapy ; Lung/*cytology/metabolism/pathology ; Macrophages, Alveolar/*metabolism/*transplantation ; Male ; Mice ; Oligonucleotide Array Sequence Analysis ; Phenotype ; Pulmonary Alveolar Proteinosis/genetics/pathology/*therapy ; Time Factors
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  • 31
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    Nature Publishing Group (NPG)
    Publication Date: 2014-08-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Callaway, Ewen -- England -- Nature. 2014 Aug 21;512(7514):242. doi: 10.1038/512242a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25143094" target="_blank"〉PubMed〈/a〉
    Keywords: Acculturation/history ; Animals ; Bone and Bones/*chemistry ; Europe ; *Fossils ; History, Ancient ; Humans ; Hybridization, Genetic ; *Neanderthals/genetics ; Radiometric Dating ; Time Factors ; Uncertainty
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  • 32
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    Nature Publishing Group (NPG)
    Publication Date: 2014-12-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Witze, Alexandra -- England -- Nature. 2014 Dec 11;516(7530):151-2. doi: 10.1038/516151a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25503211" target="_blank"〉PubMed〈/a〉
    Keywords: *Communication ; Disaster Planning/economics/*methods ; Disasters/economics/*prevention & control ; Emergency Shelter ; Humans ; Indian Ocean ; Indonesia ; Maps as Topic ; Pilot Projects ; Time Factors ; *Tsunamis/economics
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  • 33
    Publication Date: 2014-05-03
    Description: The response of the tropical climate in the Indian Ocean realm to abrupt climate change events in the North Atlantic Ocean is contentious. Repositioning of the intertropical convergence zone is thought to have been responsible for changes in tropical hydroclimate during North Atlantic cold spells, but the dearth of high-resolution records outside the monsoon realm in the Indian Ocean precludes a full understanding of this remote relationship and its underlying mechanisms. Here we show that slowdowns of the Atlantic meridional overturning circulation during Heinrich stadials and the Younger Dryas stadial affected the tropical Indian Ocean hydroclimate through changes to the Hadley circulation including a southward shift in the rising branch (the intertropical convergence zone) and an overall weakening over the southern Indian Ocean. Our results are based on new, high-resolution sea surface temperature and seawater oxygen isotope records of well-dated sedimentary archives from the tropical eastern Indian Ocean for the past 45,000 years, combined with climate model simulations of Atlantic circulation slowdown under Marine Isotope Stages 2 and 3 boundary conditions. Similar conditions in the east and west of the basin rule out a zonal dipole structure as the dominant forcing of the tropical Indian Ocean hydroclimate of millennial-scale events. Results from our simulations and proxy data suggest dry conditions in the northern Indian Ocean realm and wet and warm conditions in the southern realm during North Atlantic cold spells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mohtadi, Mahyar -- Prange, Matthias -- Oppo, Delia W -- De Pol-Holz, Ricardo -- Merkel, Ute -- Zhang, Xiao -- Steinke, Stephan -- Luckge, Andreas -- England -- Nature. 2014 May 1;509(7498):76-80. doi: 10.1038/nature13196.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MARUM-Center for Marine Environmental Sciences, University of Bremen, 28359 Bremen, Germany. ; Geology and Geophysics, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts 02543, USA. ; Department of Oceanography, University of Concepcion, Concepcion, Chile. ; Federal Institute for Geosciences and Natural Resources, 30655 Hannover, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24784218" target="_blank"〉PubMed〈/a〉
    Keywords: Africa, Eastern ; Air ; Atlantic Ocean ; Borneo ; Geologic Sediments/chemistry ; Greenland ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; Humidity ; Hydrology ; Ice Cover ; Indian Ocean ; Indonesia ; Lakes ; *Models, Theoretical ; Oxygen Isotopes ; Rain ; Salinity ; Seasons ; Seawater/analysis/chemistry ; Temperature ; Time Factors ; *Tropical Climate ; Water Movements
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  • 34
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    Nature Publishing Group (NPG)
    Publication Date: 2014-10-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ravn, Karen -- England -- Nature. 2014 Oct 23;514(7523):523-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25346972" target="_blank"〉PubMed〈/a〉
    Keywords: *Career Mobility ; Commerce/*education ; Curriculum ; *Education, Graduate ; Research Personnel/*education ; Time Factors ; United States
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  • 35
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    Nature Publishing Group (NPG)
    Publication Date: 2014-10-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heymann, David L -- England -- Nature. 2014 Oct 16;514(7522):299-300. doi: 10.1038/514299a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25318509" target="_blank"〉PubMed〈/a〉
    Keywords: Africa, Western/epidemiology ; Cities/epidemiology ; *Clinical Trials as Topic/ethics ; Congo/epidemiology ; *Contact Tracing ; Cross Infection/epidemiology ; Disease Outbreaks/prevention & control/statistics & numerical data ; Fever/diagnosis ; Funeral Rites ; *Hemorrhagic Fever, Ebola/diagnosis/epidemiology/prevention & ; control/therapy/transmission ; History, 20th Century ; History, 21st Century ; Humans ; Plasmapheresis/utilization ; Protective Clothing ; *Quarantine ; Rural Population/statistics & numerical data ; Survivors ; Time Factors ; Urban Population/statistics & numerical data ; World Health Organization
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  • 36
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    Nature Publishing Group (NPG)
    Publication Date: 2014-10-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reardon, Sara -- England -- Nature. 2014 Oct 2;514(7520):13-4. doi: 10.1038/514013a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25279893" target="_blank"〉PubMed〈/a〉
    Keywords: Exome/genetics ; Genetic Diseases, Inborn/*diagnosis/*genetics ; *Genetic Testing/trends ; Genomics/trends ; Humans ; Infant ; Infant, Newborn ; Infant, Newborn, Diseases/*diagnosis/*genetics ; Intensive Care Units, Neonatal ; Male ; National Institutes of Health (U.S.) ; *Neonatal Screening/trends ; Time Factors ; United States ; United States Food and Drug Administration
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  • 37
    Publication Date: 2014-08-15
    Description: The role of long noncoding RNA (lncRNA) in adult hearts is unknown; also unclear is how lncRNA modulates nucleosome remodelling. An estimated 70% of mouse genes undergo antisense transcription, including myosin heavy chain 7 (Myh7), which encodes molecular motor proteins for heart contraction. Here we identify a cluster of lncRNA transcripts from Myh7 loci and demonstrate a new lncRNA-chromatin mechanism for heart failure. In mice, these transcripts, which we named myosin heavy-chain-associated RNA transcripts (Myheart, or Mhrt), are cardiac-specific and abundant in adult hearts. Pathological stress activates the Brg1-Hdac-Parp chromatin repressor complex to inhibit Mhrt transcription in the heart. Such stress-induced Mhrt repression is essential for cardiomyopathy to develop: restoring Mhrt to the pre-stress level protects the heart from hypertrophy and failure. Mhrt antagonizes the function of Brg1, a chromatin-remodelling factor that is activated by stress to trigger aberrant gene expression and cardiac myopathy. Mhrt prevents Brg1 from recognizing its genomic DNA targets, thus inhibiting chromatin targeting and gene regulation by Brg1. It does so by binding to the helicase domain of Brg1, a domain that is crucial for tethering Brg1 to chromatinized DNA targets. Brg1 helicase has dual nucleic-acid-binding specificities: it is capable of binding lncRNA (Mhrt) and chromatinized--but not naked--DNA. This dual-binding feature of helicase enables a competitive inhibition mechanism by which Mhrt sequesters Brg1 from its genomic DNA targets to prevent chromatin remodelling. A Mhrt-Brg1 feedback circuit is thus crucial for heart function. Human MHRT also originates from MYH7 loci and is repressed in various types of myopathic hearts, suggesting a conserved lncRNA mechanism in human cardiomyopathy. Our studies identify a cardioprotective lncRNA, define a new targeting mechanism for ATP-dependent chromatin-remodelling factors, and establish a new paradigm for lncRNA-chromatin interaction.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4184960/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4184960/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Han, Pei -- Li, Wei -- Lin, Chiou-Hong -- Yang, Jin -- Shang, Ching -- Nurnberg, Sylvia T -- Jin, Kevin Kai -- Xu, Weihong -- Lin, Chieh-Yu -- Lin, Chien-Jung -- Xiong, Yiqin -- Chien, Huan-Chieh -- Zhou, Bin -- Ashley, Euan -- Bernstein, Daniel -- Chen, Peng-Sheng -- Chen, Huei-Sheng Vincent -- Quertermous, Thomas -- Chang, Ching-Pin -- HL105194/HL/NHLBI NIH HHS/ -- HL109512/HL/NHLBI NIH HHS/ -- HL111770/HL/NHLBI NIH HHS/ -- HL116997/HL/NHLBI NIH HHS/ -- HL118087/HL/NHLBI NIH HHS/ -- HL121197/HL/NHLBI NIH HHS/ -- HL71140/HL/NHLBI NIH HHS/ -- HL78931/HL/NHLBI NIH HHS/ -- R01 HL111770/HL/NHLBI NIH HHS/ -- R01 HL116997/HL/NHLBI NIH HHS/ -- R01 HL121197/HL/NHLBI NIH HHS/ -- England -- Nature. 2014 Oct 2;514(7520):102-6. doi: 10.1038/nature13596. Epub 2014 Aug 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA [2] Division of Cardiovascular Medicine, Cardiovascular Institute, Stanford University School of Medicine, Stanford, California 94305, USA. ; 1] Division of Cardiovascular Medicine, Cardiovascular Institute, Stanford University School of Medicine, Stanford, California 94305, USA [2]. ; Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. ; Division of Cardiovascular Medicine, Cardiovascular Institute, Stanford University School of Medicine, Stanford, California 94305, USA. ; Stanford Genome Technology Center, Stanford University School of Medicine, Stanford, California 94305, USA. ; Department of Genetics, Pediatrics, and Medicine (Cardiology), Albert Einstein College of Medicine of Yeshiva University, 1301 Morris Park Avenue, Price Center 420, Bronx, New York 10461, USA. ; Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305, USA. ; Del E. Webb Neuroscience, Aging &Stem Cell Research Center, Sanford/Burnham Medical Research Institute, La Jolla, California 92037, USA. ; 1] Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA [2] Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA [3] Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25119045" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cardiac Myosins/genetics ; Cardiomegaly/*genetics/*pathology/prevention & control ; Cardiomyopathies/genetics/pathology/prevention & control ; Chromatin/genetics/metabolism ; Chromatin Assembly and Disassembly ; DNA Helicases/antagonists & inhibitors/chemistry/genetics/metabolism ; Feedback, Physiological ; Heart Failure/genetics/pathology/prevention & control ; Histone Deacetylases/metabolism ; Humans ; Mice ; Myocardium/metabolism/pathology ; Myosin Heavy Chains/*genetics ; Nuclear Proteins/antagonists & inhibitors/chemistry/genetics/metabolism ; Organ Specificity ; Poly(ADP-ribose) Polymerases/metabolism ; Protein Binding ; Protein Structure, Tertiary ; RNA, Long Noncoding/antagonists & inhibitors/*genetics/metabolism ; Transcription Factors/antagonists & inhibitors/chemistry/genetics/metabolism
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    Publication Date: 2014-07-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Witze, Alexandra -- England -- Nature. 2014 Jul 24;511(7510):396. doi: 10.1038/511396a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25056044" target="_blank"〉PubMed〈/a〉
    Keywords: Exobiology ; *Extraterrestrial Environment/chemistry ; *Mars ; Space Flight ; Time Factors
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  • 39
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    Publication Date: 2014-09-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reardon, Sara -- England -- Nature. 2014 Sep 25;513(7519):471. doi: 10.1038/513471a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25254455" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Diseases/drug therapy/microbiology/*prevention & control ; Animals ; Animals, Domestic/growth & development/microbiology ; *Anti-Bacterial Agents/administration & dosage/pharmacology/therapeutic use ; Bacterial Infections/*drug therapy/prevention & control/transmission/veterinary ; Clinical Trials as Topic ; *Drug Discovery ; *Drug Resistance, Microbial/drug effects ; Government Regulation ; Humans ; Time Factors ; United States ; United States Food and Drug Administration/legislation & jurisprudence ; Zoonoses/microbiology/prevention & control
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  • 40
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    Nature Publishing Group (NPG)
    Publication Date: 2014-04-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Anthes, Emily -- England -- Nature. 2014 Apr 17;508(7496):S54-6. doi: 10.1038/508S54a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24740127" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Anti-Obesity Agents/pharmacology/therapeutic use ; Body Mass Index ; Child ; Chronic Disease/therapy ; Diet ; Exercise/physiology ; Humans ; Life Style ; Obesity/diet therapy/drug therapy/prevention & control/*therapy ; Randomized Controlled Trials as Topic ; Time Factors ; *Weight Gain/drug effects ; Weight Loss ; Weight Reduction Programs
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 41
    Publication Date: 2014-03-29
    Description: The light-harvesting core antenna (LH1) and the reaction centre (RC) of purple photosynthetic bacteria form a supramolecular complex (LH1-RC) to use sunlight energy in a highly efficient manner. Here we report the first near-atomic structure, to our knowledge, of a LH1-RC complex, namely that of a Ca(2+)-bound complex from Thermochromatium tepidum, which reveals detailed information on the arrangement and interactions of the protein subunits and the cofactors. The RC is surrounded by 16 heterodimers of the LH1 alphabeta-subunit that form a completely closed structure. The Ca(2+) ions are located at the periplasmic side of LH1. Thirty-two bacteriochlorophyll and 16 spirilloxanthin molecules in the LH1 ring form an elliptical assembly. The geometries of the pigment assembly involved in the absorption characteristics of the bacteriochlorophyll in LH1 and excitation energy transfer among the pigments are reported. In addition, possible ubiquinone channels in the closed LH1 complex are proposed based on the atomic structure.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Niwa, Satomi -- Yu, Long-Jiang -- Takeda, Kazuki -- Hirano, Yu -- Kawakami, Tomoaki -- Wang-Otomo, Zheng-Yu -- Miki, Kunio -- England -- Nature. 2014 Apr 10;508(7495):228-32. doi: 10.1038/nature13197. Epub 2014 Mar 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan [2]. ; 1] Faculty of Science, Ibaraki University, Mito, Ibaraki 310-8512, Japan [2]. ; Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan. ; Faculty of Science, Ibaraki University, Mito, Ibaraki 310-8512, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670637" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteriochlorophylls/chemistry/metabolism ; Calcium/metabolism ; Chromatiaceae/*chemistry ; Coenzymes/chemistry/metabolism ; Crystallography, X-Ray ; Light-Harvesting Protein Complexes/*chemistry/metabolism ; Models, Molecular ; Protein Binding ; Protein Structure, Quaternary ; Protein Subunits/chemistry/metabolism ; Ubiquinone/metabolism ; Xanthophylls/chemistry/metabolism
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  • 42
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    Nature Publishing Group (NPG)
    Publication Date: 2014-06-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Witze, Alexandra -- England -- Nature. 2014 Jun 12;510(7504):196-7. doi: 10.1038/510196a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24919901" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Environmental Monitoring/instrumentation/methods ; Humans ; Hypogravity ; Laboratories/*utilization ; Mice ; *Research/trends ; Russia ; *Spacecraft ; Time Factors ; United States ; United States National Aeronautics and Space Administration
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  • 43
    Publication Date: 2014-08-29
    Description: Discovering the structure and dynamics of transcriptional regulatory events in the genome with cellular and temporal resolution is crucial to understanding the regulatory underpinnings of development and disease. We determined the genomic distribution of binding sites for 92 transcription factors and regulatory proteins across multiple stages of Caenorhabditis elegans development by performing 241 ChIP-seq (chromatin immunoprecipitation followed by sequencing) experiments. Integration of regulatory binding and cellular-resolution expression data produced a spatiotemporally resolved metazoan transcription factor binding map. Using this map, we explore developmental regulatory circuits that encode combinatorial logic at the levels of co-binding and co-expression of transcription factors, characterizing the genomic coverage and clustering of regulatory binding, the binding preferences of, and biological processes regulated by, transcription factors, the global transcription factor co-associations and genomic subdomains that suggest shared patterns of regulation, and identifying key transcription factors and transcription factor co-associations for fate specification of individual lineages and cell types.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530805/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530805/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Araya, Carlos L -- Kawli, Trupti -- Kundaje, Anshul -- Jiang, Lixia -- Wu, Beijing -- Vafeados, Dionne -- Terrell, Robert -- Weissdepp, Peter -- Gevirtzman, Louis -- Mace, Daniel -- Niu, Wei -- Boyle, Alan P -- Xie, Dan -- Ma, Lijia -- Murray, John I -- Reinke, Valerie -- Waterston, Robert H -- Snyder, Michael -- R01 GM072675/GM/NIGMS NIH HHS/ -- U01 HG004267/HG/NHGRI NIH HHS/ -- England -- Nature. 2014 Aug 28;512(7515):400-5. doi: 10.1038/nature13497.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA. ; Department of Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. ; Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA. ; Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520, USA. ; Institute for Genomics and Systems Biology, University of Chicago, Chicago, Illinois 60637, USA. ; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25164749" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Caenorhabditis elegans/cytology/embryology/*genetics/*growth & development ; Caenorhabditis elegans Proteins/metabolism ; Cell Lineage ; Chromatin Immunoprecipitation ; Gene Expression Regulation, Developmental/*genetics ; Genome, Helminth/*genetics ; Genomics ; Larva/cytology/genetics/growth & development/metabolism ; Protein Binding ; *Spatio-Temporal Analysis ; Transcription Factors/*metabolism
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  • 44
    Publication Date: 2014-06-12
    Description: Spontaneous changes in the reading frame of translation are rare (frequency of 10(-3) to 10(-4) per codon), but can be induced by specific features in the messenger RNA (mRNA). In the presence of mRNA secondary structures, a heptanucleotide 'slippery sequence' usually defined by the motif X XXY YYZ, and (in some prokaryotic cases) mRNA sequences that base pair with the 3' end of the 16S ribosomal rRNA (internal Shine-Dalgarno sequences), there is an increased probability that a specific programmed change of frame occurs, wherein the ribosome shifts one nucleotide backwards into an overlapping reading frame (-1 frame) and continues by translating a new sequence of amino acids. Despite extensive biochemical and genetic studies, there is no clear mechanistic description for frameshifting. Here we apply single-molecule fluorescence to track the compositional and conformational dynamics of individual ribosomes at each codon during translation of a frameshift-inducing mRNA from the dnaX gene in Escherichia coli. Ribosomes that frameshift into the -1 frame are characterized by a tenfold longer pause in elongation compared to non-frameshifted ribosomes, which translate through unperturbed. During the pause, interactions of the ribosome with the mRNA stimulatory elements uncouple EF-G catalysed translocation from normal ribosomal subunit reverse-rotation, leaving the ribosome in a non-canonical intersubunit rotated state with an exposed codon in the aminoacyl-tRNA site (A site). tRNA(Lys) sampling and accommodation to the empty A site and EF-G action either leads to the slippage of the tRNAs into the -1 frame or maintains the ribosome into the 0 frame. Our results provide a general mechanistic and conformational framework for -1 frameshifting, highlighting multiple kinetic branchpoints during elongation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4472451/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4472451/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Jin -- Petrov, Alexey -- Johansson, Magnus -- Tsai, Albert -- O'Leary, Sean E -- Puglisi, Joseph D -- GM099687/GM/NIGMS NIH HHS/ -- GM51266/GM/NIGMS NIH HHS/ -- R01 GM051266/GM/NIGMS NIH HHS/ -- R01 GM099687/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Aug 21;512(7514):328-32. doi: 10.1038/nature13428. Epub 2014 Jun 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Applied Physics, Stanford University, Stanford, California 94305-4090, USA [2] Department of Structural Biology, Stanford University School of Medicine, Stanford, California 94305-5126, USA. ; Department of Structural Biology, Stanford University School of Medicine, Stanford, California 94305-5126, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24919156" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/genetics ; Codon/genetics ; DNA Polymerase III/genetics ; Escherichia coli ; *Frameshifting, Ribosomal ; Kinetics ; *Peptide Chain Elongation, Translational ; Peptide Elongation Factor G/metabolism ; RNA, Messenger/genetics ; RNA, Transfer, Amino Acyl/metabolism ; Reading Frames/genetics ; Ribosome Subunits/chemistry/metabolism ; Ribosomes/chemistry/*metabolism ; Rotation ; Time Factors
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  • 45
    Publication Date: 2014-04-18
    Description: Ice volume (and hence sea level) and deep-sea temperature are key measures of global climate change. Sea level has been documented using several independent methods over the past 0.5 million years (Myr). Older periods, however, lack such independent validation; all existing records are related to deep-sea oxygen isotope (delta(18)O) data that are influenced by processes unrelated to sea level. For deep-sea temperature, only one continuous high-resolution (Mg/Ca-based) record exists, with related sea-level estimates, spanning the past 1.5 Myr. Here we present a novel sea-level reconstruction, with associated estimates of deep-sea temperature, which independently validates the previous 0-1.5 Myr reconstruction and extends it back to 5.3 Myr ago. We find that deep-sea temperature and sea level generally decreased through time, but distinctly out of synchrony, which is remarkable given the importance of ice-albedo feedbacks on the radiative forcing of climate. In particular, we observe a large temporal offset during the onset of Plio-Pleistocene ice ages, between a marked cooling step at 2.73 Myr ago and the first major glaciation at 2.15 Myr ago. Last, we tentatively infer that ice sheets may have grown largest during glacials with more modest reductions in deep-sea temperature.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rohling, E J -- Foster, G L -- Grant, K M -- Marino, G -- Roberts, A P -- Tamisiea, M E -- Williams, F -- England -- Nature. 2014 Apr 24;508(7497):477-82. doi: 10.1038/nature13230. Epub 2014 Apr 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Research School of Earth Sciences, The Australian National University, Canberra 0200, Australia [2] Ocean and Earth Science, University of Southampton, National Oceanography Centre, Southampton SO14 3ZH, UK. ; Ocean and Earth Science, University of Southampton, National Oceanography Centre, Southampton SO14 3ZH, UK. ; Research School of Earth Sciences, The Australian National University, Canberra 0200, Australia. ; National Oceanography Centre, Joseph Proudman Building, Liverpool L3 5DA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24739960" target="_blank"〉PubMed〈/a〉
    Keywords: Foraminifera ; History, Ancient ; Ice Cover ; Mediterranean Sea ; Oxygen Isotopes ; Reproducibility of Results ; Seawater/*analysis ; *Temperature ; Time Factors
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  • 46
    Publication Date: 2014-01-17
    Description: Forests are major components of the global carbon cycle, providing substantial feedback to atmospheric greenhouse gas concentrations. Our ability to understand and predict changes in the forest carbon cycle--particularly net primary productivity and carbon storage--increasingly relies on models that represent biological processes across several scales of biological organization, from tree leaves to forest stands. Yet, despite advances in our understanding of productivity at the scales of leaves and stands, no consensus exists about the nature of productivity at the scale of the individual tree, in part because we lack a broad empirical assessment of whether rates of absolute tree mass growth (and thus carbon accumulation) decrease, remain constant, or increase as trees increase in size and age. Here we present a global analysis of 403 tropical and temperate tree species, showing that for most species mass growth rate increases continuously with tree size. Thus, large, old trees do not act simply as senescent carbon reservoirs but actively fix large amounts of carbon compared to smaller trees; at the extreme, a single big tree can add the same amount of carbon to the forest within a year as is contained in an entire mid-sized tree. The apparent paradoxes of individual tree growth increasing with tree size despite declining leaf-level and stand-level productivity can be explained, respectively, by increases in a tree's total leaf area that outpace declines in productivity per unit of leaf area and, among other factors, age-related reductions in population density. Our results resolve conflicting assumptions about the nature of tree growth, inform efforts to undertand and model forest carbon dynamics, and have additional implications for theories of resource allocation and plant senescence.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stephenson, N L -- Das, A J -- Condit, R -- Russo, S E -- Baker, P J -- Beckman, N G -- Coomes, D A -- Lines, E R -- Morris, W K -- Ruger, N -- Alvarez, E -- Blundo, C -- Bunyavejchewin, S -- Chuyong, G -- Davies, S J -- Duque, A -- Ewango, C N -- Flores, O -- Franklin, J F -- Grau, H R -- Hao, Z -- Harmon, M E -- Hubbell, S P -- Kenfack, D -- Lin, Y -- Makana, J-R -- Malizia, A -- Malizia, L R -- Pabst, R J -- Pongpattananurak, N -- Su, S-H -- Sun, I-F -- Tan, S -- Thomas, D -- van Mantgem, P J -- Wang, X -- Wiser, S K -- Zavala, M A -- England -- Nature. 2014 Mar 6;507(7490):90-3. doi: 10.1038/nature12914. Epub 2014 Jan 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉US Geological Survey, Western Ecological Research Center, Three Rivers, California 93271, USA. ; Smithsonian Tropical Research Institute, Apartado 0843-03092, Balboa, Republic of Panama. ; School of Biological Sciences, University of Nebraska, Lincoln, Nebraska 68588, USA. ; Department of Forest and Ecosystem Science, University of Melbourne, Victoria 3121, Australia. ; 1] School of Biological Sciences, University of Nebraska, Lincoln, Nebraska 68588, USA [2] Mathematical Biosciences Institute, Ohio State University, Columbus, Ohio 43210, USA (N.G.B.); German Centre for Integrative Biodiversity Research (iDiv), Halle-Jena-Leipzig, 04103 Leipzig, Germany (N.R.). ; Department of Plant Sciences, University of Cambridge, Cambridge CB2 3EA, UK. ; Department of Geography, University College London, London WC1E 6BT, UK. ; School of Botany, University of Melbourne, Victoria 3010, Australia. ; 1] Smithsonian Tropical Research Institute, Apartado 0843-03092, Balboa, Republic of Panama [2] Spezielle Botanik und Funktionelle Biodiversitat, Universitat Leipzig, 04103 Leipzig, Germany [3] Mathematical Biosciences Institute, Ohio State University, Columbus, Ohio 43210, USA (N.G.B.); German Centre for Integrative Biodiversity Research (iDiv), Halle-Jena-Leipzig, 04103 Leipzig, Germany (N.R.). ; Jardin Botanico de Medellin, Calle 73, No. 51D-14, Medellin, Colombia. ; Instituto de Ecologia Regional, Universidad Nacional de Tucuman, 4107 Yerba Buena, Tucuman, Argentina. ; Research Office, Department of National Parks, Wildlife and Plant Conservation, Bangkok 10900, Thailand. ; Department of Botany and Plant Physiology, Buea, Southwest Province, Cameroon. ; Smithsonian Institution Global Earth Observatory-Center for Tropical Forest Science, Smithsonian Institution, PO Box 37012, Washington, DC 20013, USA. ; Universidad Nacional de Colombia, Departamento de Ciencias Forestales, Medellin, Colombia. ; Wildlife Conservation Society, Kinshasa/Gombe, Democratic Republic of the Congo. ; Unite Mixte de Recherche-Peuplements Vegetaux et Bioagresseurs en Milieu Tropical, Universite de la Reunion/CIRAD, 97410 Saint Pierre, France. ; School of Environmental and Forest Sciences, University of Washington, Seattle, Washington 98195, USA. ; State Key Laboratory of Forest and Soil Ecology, Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang 110164, China. ; Department of Forest Ecosystems and Society, Oregon State University, Corvallis, Oregon 97331, USA. ; 1] Smithsonian Tropical Research Institute, Apartado 0843-03092, Balboa, Republic of Panama [2] Department of Ecology and Evolutionary Biology, University of California, Los Angeles, California 90095, USA. ; Department of Life Science, Tunghai University, Taichung City 40704, Taiwan. ; Facultad de Ciencias Agrarias, Universidad Nacional de Jujuy, 4600 San Salvador de Jujuy, Argentina. ; Faculty of Forestry, Kasetsart University, ChatuChak Bangkok 10900, Thailand. ; Taiwan Forestry Research Institute, Taipei 10066, Taiwan. ; Department of Natural Resources and Environmental Studies, National Dong Hwa University, Hualien 97401, Taiwan. ; Sarawak Forestry Department, Kuching, Sarawak 93660, Malaysia. ; Department of Botany and Plant Pathology, Oregon State University, Corvallis, Oregon 97331, USA. ; US Geological Survey, Western Ecological Research Center, Arcata, California 95521, USA. ; Landcare Research, PO Box 40, Lincoln 7640, New Zealand. ; Forest Ecology and Restoration Group, Department of Life Sciences, University of Alcala, Alcala de Henares, 28805 Madrid, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24429523" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/metabolism ; Biomass ; *Body Size ; Carbon/*metabolism ; *Carbon Cycle ; Climate ; Geography ; Models, Biological ; Plant Leaves/growth & development/metabolism ; Sample Size ; Species Specificity ; Time Factors ; Trees/*anatomy & histology/classification/growth & development/*metabolism ; Tropical Climate
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  • 47
    Publication Date: 2014-07-22
    Description: In the 1950s, the drug thalidomide, administered as a sedative to pregnant women, led to the birth of thousands of children with multiple defects. Despite the teratogenicity of thalidomide and its derivatives lenalidomide and pomalidomide, these immunomodulatory drugs (IMiDs) recently emerged as effective treatments for multiple myeloma and 5q-deletion-associated dysplasia. IMiDs target the E3 ubiquitin ligase CUL4-RBX1-DDB1-CRBN (known as CRL4(CRBN)) and promote the ubiquitination of the IKAROS family transcription factors IKZF1 and IKZF3 by CRL4(CRBN). Here we present crystal structures of the DDB1-CRBN complex bound to thalidomide, lenalidomide and pomalidomide. The structure establishes that CRBN is a substrate receptor within CRL4(CRBN) and enantioselectively binds IMiDs. Using an unbiased screen, we identified the homeobox transcription factor MEIS2 as an endogenous substrate of CRL4(CRBN). Our studies suggest that IMiDs block endogenous substrates (MEIS2) from binding to CRL4(CRBN) while the ligase complex is recruiting IKZF1 or IKZF3 for degradation. This dual activity implies that small molecules can modulate an E3 ubiquitin ligase and thereby upregulate or downregulate the ubiquitination of proteins.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4423819/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4423819/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fischer, Eric S -- Bohm, Kerstin -- Lydeard, John R -- Yang, Haidi -- Stadler, Michael B -- Cavadini, Simone -- Nagel, Jane -- Serluca, Fabrizio -- Acker, Vincent -- Lingaraju, Gondichatnahalli M -- Tichkule, Ritesh B -- Schebesta, Michael -- Forrester, William C -- Schirle, Markus -- Hassiepen, Ulrich -- Ottl, Johannes -- Hild, Marc -- Beckwith, Rohan E J -- Harper, J Wade -- Jenkins, Jeremy L -- Thoma, Nicolas H -- AG011085/AG/NIA NIH HHS/ -- R01 AG011085/AG/NIA NIH HHS/ -- England -- Nature. 2014 Aug 7;512(7512):49-53. doi: 10.1038/nature13527. Epub 2014 Jul 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland [2] University of Basel, Petersplatz 10, CH-4003 Basel, Switzerland. ; Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA. ; Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA. ; 1] Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland [2] University of Basel, Petersplatz 10, CH-4003 Basel, Switzerland [3] Swiss Institute of Bioinformatics, Maulbeerstrasse 66, CH-4058 Basel, Switzerland. ; Novartis Pharma AG, Institutes for Biomedical Research, Novartis Campus, CH-4056 Basel, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043012" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography, X-Ray ; DNA-Binding Proteins/agonists/antagonists & inhibitors/chemistry/metabolism ; Homeodomain Proteins/metabolism ; Humans ; Models, Molecular ; Multiprotein Complexes/agonists/antagonists & inhibitors/chemistry/metabolism ; Peptide Hydrolases/*chemistry/metabolism ; Protein Binding ; Structure-Activity Relationship ; Substrate Specificity ; Thalidomide/analogs & derivatives/*chemistry/metabolism ; Transcription Factors/metabolism ; Ubiquitin-Protein Ligases/antagonists & inhibitors/*chemistry/metabolism
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  • 48
    Publication Date: 2014-07-18
    Description: Malignancy is associated with altered expression of glycans and glycoproteins that contribute to the cellular glycocalyx. We constructed a glycoprotein expression signature, which revealed that metastatic tumours upregulate expression of bulky glycoproteins. A computational model predicted that these glycoproteins would influence transmembrane receptor spatial organization and function. We tested this prediction by investigating whether bulky glycoproteins in the glycocalyx promote a tumour phenotype in human cells by increasing integrin adhesion and signalling. Our data revealed that a bulky glycocalyx facilitates integrin clustering by funnelling active integrins into adhesions and altering integrin state by applying tension to matrix-bound integrins, independent of actomyosin contractility. Expression of large tumour-associated glycoproteins in non-transformed mammary cells promoted focal adhesion assembly and facilitated integrin-dependent growth factor signalling to support cell growth and survival. Clinical studies revealed that large glycoproteins are abundantly expressed on circulating tumour cells from patients with advanced disease. Thus, a bulky glycocalyx is a feature of tumour cells that could foster metastasis by mechanically enhancing cell-surface receptor function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4487551/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4487551/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Paszek, Matthew J -- DuFort, Christopher C -- Rossier, Olivier -- Bainer, Russell -- Mouw, Janna K -- Godula, Kamil -- Hudak, Jason E -- Lakins, Jonathon N -- Wijekoon, Amanda C -- Cassereau, Luke -- Rubashkin, Matthew G -- Magbanua, Mark J -- Thorn, Kurt S -- Davidson, Michael W -- Rugo, Hope S -- Park, John W -- Hammer, Daniel A -- Giannone, Gregory -- Bertozzi, Carolyn R -- Weaver, Valerie M -- 1U01 ES019458-01/ES/NIEHS NIH HHS/ -- 2R01GM059907-13/GM/NIGMS NIH HHS/ -- AI082292-03A1/AI/NIAID NIH HHS/ -- CA138818-01A1/CA/NCI NIH HHS/ -- GM59907/GM/NIGMS NIH HHS/ -- K99 EB013446-02/EB/NIBIB NIH HHS/ -- R00 EB013446/EB/NIBIB NIH HHS/ -- R01 CA138818/CA/NCI NIH HHS/ -- R01 GM059907/GM/NIGMS NIH HHS/ -- T32 GM066698/GM/NIGMS NIH HHS/ -- U01 CA151925/CA/NCI NIH HHS/ -- U54 CA143836/CA/NCI NIH HHS/ -- U54 CA163155/CA/NCI NIH HHS/ -- U54CA143836-01/CA/NCI NIH HHS/ -- U54CA163155-01/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jul 17;511(7509):319-25. doi: 10.1038/nature13535. Epub 2014 Jun 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Surgery and Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, California 94143, USA [2] Bay Area Physical Sciences-Oncology Program, University of California, Berkeley, California 94720, USA [3] School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York 14853, USA [4] Laboratory for Atomic and Solid State Physics and Kavli Institute at Cornell for Nanoscale Science, Cornell University, Ithaca, New York 14853, USA. ; 1] Department of Surgery and Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, California 94143, USA [2] Bay Area Physical Sciences-Oncology Program, University of California, Berkeley, California 94720, USA. ; 1] Interdisciplinary Institute for Neuroscience, University of Bordeaux, UMR 5297, F-33000 Bordeaux, France [2] CNRS, Interdisciplinary Institute for Neuroscience, University of Bordeaux, UMR 5297, F-33000 Bordeaux, France. ; Department of Surgery and Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, California 94143, USA. ; 1] Department of Chemistry, University of California, Berkeley, California 94720, USA [2] The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA [3] Department of Chemistry and Biochemistry, University of California, San Diego, California 92093, USA. ; Department of Chemistry, University of California, Berkeley, California 94720, USA. ; 1] Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California 94143, USA [2] Division of Hematology/Oncology, University of California, San Francisco, California 94143, USA. ; Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158, USA. ; National High Magnetic Field Laboratory and Department of Biological Science, The Florida State University, Tallahassee, Florida 32310, USA. ; Departments of Chemical and Biomolecular Engineering and Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; 1] Department of Chemistry, University of California, Berkeley, California 94720, USA [2] Department of Molecular Biology, University of California, Berkeley, California 94720, USA [3] Howard Hughes Medical Institute, University of California, Berkeley, California 94720, USA. ; 1] Department of Surgery and Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, California 94143, USA [2] Bay Area Physical Sciences-Oncology Program, University of California, Berkeley, California 94720, USA [3] Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California 94143, USA [4] Departments of Anatomy and Bioengineering and Therapeutic Sciences and Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, California 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25030168" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breast/cytology/metabolism/pathology ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; Fibroblasts ; Glycocalyx/chemistry/*metabolism ; Glycoproteins/*metabolism ; Humans ; Immobilized Proteins/chemistry/metabolism ; Integrins/chemistry/*metabolism ; Mice ; Molecular Targeted Therapy ; Mucin-1/metabolism ; Neoplasm Metastasis/pathology ; Neoplasms/*metabolism/*pathology ; Neoplastic Cells, Circulating ; Protein Binding ; Receptors, Cell Surface
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  • 49
    Publication Date: 2014-07-18
    Description: Generating engraftable human haematopoietic cells from autologous tissues is a potential route to new therapies for blood diseases. However, directed differentiation of pluripotent stem cells yields haematopoietic cells that engraft poorly. Here, we have devised a method to phenocopy the vascular-niche microenvironment of haemogenic cells, thereby enabling reprogramming of human endothelial cells into engraftable haematopoietic cells without transition through a pluripotent intermediate. Highly purified non-haemogenic human umbilical vein endothelial cells or adult dermal microvascular endothelial cells were transduced with the transcription factors FOSB, GFI1, RUNX1 and SPI1 (hereafter referred to as FGRS), and then propagated on serum-free instructive vascular niche monolayers to induce outgrowth of haematopoietic colonies containing cells with functional and immunophenotypic features of multipotent progenitor cells (MPPs). These endothelial cells that have been reprogrammed into human MPPs (rEC-hMPPs) acquire colony-forming-cell potential and durably engraft into immune-deficient mice after primary and secondary transplantation, producing long-term rEC-hMPP-derived myeloid (granulocytic/monocytic, erythroid, megakaryocytic) and lymphoid (natural killer and B cell) progenies. Conditional expression of FGRS transgenes, combined with vascular induction, activates endogenous FGRS genes, endowing rEC-hMPPs with a transcriptional and functional profile similar to that of self-renewing MPPs. Our approach underscores the role of inductive cues from the vascular niche in coordinating and sustaining haematopoietic specification and may prove useful for engineering autologous haematopoietic grafts to treat inherited and acquired blood disorders.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159670/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159670/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sandler, Vladislav M -- Lis, Raphael -- Liu, Ying -- Kedem, Alon -- James, Daylon -- Elemento, Olivier -- Butler, Jason M -- Scandura, Joseph M -- Rafii, Shahin -- CA159175/CA/NCI NIH HHS/ -- CA163167/CA/NCI NIH HHS/ -- HL055748/HL/NHLBI NIH HHS/ -- HL119872/HL/NHLBI NIH HHS/ -- R01 DK095039/DK/NIDDK NIH HHS/ -- R01 HL097797/HL/NHLBI NIH HHS/ -- R01 HL115128/HL/NHLBI NIH HHS/ -- R01 HL119872/HL/NHLBI NIH HHS/ -- R01DK095039/DK/NIDDK NIH HHS/ -- R01HL097797/HL/NHLBI NIH HHS/ -- R01HL119872/HL/NHLBI NIH HHS/ -- U01 HL099997/HL/NHLBI NIH HHS/ -- U01-HL099997/HL/NHLBI NIH HHS/ -- U54 CA163167/CA/NCI NIH HHS/ -- U54CA163167/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jul 17;511(7509):312-8. doi: 10.1038/nature13547. Epub 2014 Jul 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ansary Stem Cell Institute, Department of Genetic Medicine, and Howard Hughes Medical Institute, Weill Cornell Medical College, New York, New York 10065, USA. ; 1] Ansary Stem Cell Institute, Department of Genetic Medicine, and Howard Hughes Medical Institute, Weill Cornell Medical College, New York, New York 10065, USA [2] Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, New York, New York 10065, USA. ; HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medical College, New York, New York 10065, USA. ; Department of Medicine, Hematology-Oncology, Weill Cornell Medical College and the New York Presbyterian Hospital, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25030167" target="_blank"〉PubMed〈/a〉
    Keywords: Adult Stem Cells/cytology/metabolism/transplantation ; Animals ; Aorta ; Cell Lineage ; *Cellular Microenvironment ; *Cellular Reprogramming ; Endothelial Cells/*cytology/metabolism ; Female ; Gene Expression Regulation ; Gonads ; Hematopoiesis ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/*cytology/metabolism ; Humans ; Lymphocytes/cytology ; Mesonephros ; Mice ; Multipotent Stem Cells/*cytology/metabolism/transplantation ; Myeloid Cells/cytology ; Pluripotent Stem Cells ; Time Factors ; Transcription Factors/genetics/metabolism ; Transgenes/genetics
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  • 50
    Publication Date: 2014-01-28
    Description: H2A.Z is an essential histone variant implicated in the regulation of key nuclear events. However, the metazoan chaperones responsible for H2A.Z deposition and its removal from chromatin remain unknown. Here we report the identification and characterization of the human protein ANP32E as a specific H2A.Z chaperone. We show that ANP32E is a member of the presumed H2A.Z histone-exchange complex p400/TIP60. ANP32E interacts with a short region of the docking domain of H2A.Z through a new motif termed H2A.Z interacting domain (ZID). The 1.48 A resolution crystal structure of the complex formed between the ANP32E-ZID and the H2A.Z/H2B dimer and biochemical data support an underlying molecular mechanism for H2A.Z/H2B eviction from the nucleosome and its stabilization by ANP32E through a specific extension of the H2A.Z carboxy-terminal alpha-helix. Finally, analysis of H2A.Z localization in ANP32E(-/-) cells by chromatin immunoprecipitation followed by sequencing shows genome-wide enrichment, redistribution and accumulation of H2A.Z at specific chromatin control regions, in particular at enhancers and insulators.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Obri, Arnaud -- Ouararhni, Khalid -- Papin, Christophe -- Diebold, Marie-Laure -- Padmanabhan, Kiran -- Marek, Martin -- Stoll, Isabelle -- Roy, Ludovic -- Reilly, Patrick T -- Mak, Tak W -- Dimitrov, Stefan -- Romier, Christophe -- Hamiche, Ali -- England -- Nature. 2014 Jan 30;505(7485):648-53. doi: 10.1038/nature12922. Epub 2014 Jan 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Departement de Genomique Fonctionnelle et Cancer, Institut de Genetique et Biologie Moleculaire et Cellulaire (IGBMC), Universite de Strasbourg, CNRS, INSERM, 1 rue Laurent Fries, B.P. 10142, 67404 Illkirch Cedex, France [2]. ; Departement de Biologie Structurale Integrative, Institut de Genetique et Biologie Moleculaire et Cellulaire (IGBMC), Universite de Strasbourg, CNRS, INSERM, 1 rue Laurent Fries, B.P. 10142, 67404 Illkirch Cedex, France. ; Equipe labelisee Ligue contre le Cancer, INSERM/Universite Joseph Fourier , Institut Albert Bonniot, U823, Site Sante-BP 170, 38042 Grenoble Cedex 9, France. ; Departement de Genomique Fonctionnelle et Cancer, Institut de Genetique et Biologie Moleculaire et Cellulaire (IGBMC), Universite de Strasbourg, CNRS, INSERM, 1 rue Laurent Fries, B.P. 10142, 67404 Illkirch Cedex, France. ; Laboratory of Inflammation Biology, Division of Cellular and Molecular Research, National Cancer Centre, Singapore, Singapore. ; 1] Laboratory of Inflammation Biology, Division of Cellular and Molecular Research, National Cancer Centre, Singapore, Singapore [2] The Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, Ontario, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24463511" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cell Line ; Cell Nucleus/chemistry/metabolism ; Chromatin/*chemistry/genetics/*metabolism ; Chromatin Immunoprecipitation ; Crystallography, X-Ray ; DNA/genetics/metabolism ; Genome, Human/genetics ; Histones/chemistry/isolation & purification/*metabolism ; Humans ; Models, Molecular ; Molecular Chaperones/chemistry/*metabolism ; Molecular Sequence Data ; Nuclear Proteins/chemistry/*metabolism ; Nucleosomes/chemistry/metabolism ; Phosphoproteins/chemistry/*metabolism ; Protein Binding ; Protein Conformation ; Substrate Specificity
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  • 51
    Publication Date: 2014-06-10
    Description: RNA is arguably the most functionally diverse biological macromolecule. In some cases a single discrete RNA sequence performs multiple roles, and this can be conferred by a complex three-dimensional structure. Such multifunctionality can also be driven or enhanced by the ability of a given RNA to assume different conformational (and therefore functional) states. Despite its biological importance, a detailed structural understanding of the paradigm of RNA structure-driven multifunctionality is lacking. To address this gap it is useful to study examples from single-stranded positive-sense RNA viruses, a prototype being the tRNA-like structure (TLS) found at the 3' end of the turnip yellow mosaic virus (TYMV). This TLS not only acts like a tRNA to drive aminoacylation of the viral genomic (g)RNA, but also interacts with other structures in the 3' untranslated region of the gRNA, contains the promoter for negative-strand synthesis, and influences several infection-critical processes. TLS RNA can provide a glimpse into the structural basis of RNA multifunctionality and plasticity, but for decades its high-resolution structure has remained elusive. Here we present the crystal structure of the complete TYMV TLS to 2.0 A resolution. Globally, the RNA adopts a shape that mimics tRNA, but it uses a very different set of intramolecular interactions to achieve this shape. These interactions also allow the TLS to readily switch conformations. In addition, the TLS structure is 'two faced': one face closely mimics tRNA and drives aminoacylation, the other face diverges from tRNA and enables additional functionality. The TLS is thus structured to perform several functions and interact with diverse binding partners, and we demonstrate its ability to specifically bind to ribosomes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4136544/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4136544/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Colussi, Timothy M -- Costantino, David A -- Hammond, John A -- Ruehle, Grant M -- Nix, Jay C -- Kieft, Jeffrey S -- GM081346/GM/NIGMS NIH HHS/ -- GM097333/GM/NIGMS NIH HHS/ -- P30 CA046934/CA/NCI NIH HHS/ -- P30CA046934/CA/NCI NIH HHS/ -- R01 GM081346/GM/NIGMS NIH HHS/ -- R01 GM097333/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jul 17;511(7509):366-9. doi: 10.1038/nature13378. Epub 2014 Jun 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA [2] Howard Hughes Medical Institute, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA [3] Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, USA (T.M.C.); Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, California 92037, USA (J.A.H.). ; 1] Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA [2] Howard Hughes Medical Institute, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA. ; 1] Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA [2] Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, USA (T.M.C.); Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, California 92037, USA (J.A.H.). ; Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA. ; Molecular Biology Consortium, Advanced Light Source, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24909993" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions ; Amino Acyl-tRNA Synthetases/metabolism ; Aminoacylation ; Base Sequence ; Crystallography, X-Ray ; Models, Molecular ; *Molecular Mimicry ; Molecular Sequence Data ; *Nucleic Acid Conformation ; Protein Binding ; RNA Folding ; RNA, Guide/genetics/metabolism ; RNA, Transfer/*chemistry/genetics/metabolism ; RNA, Viral/*chemistry/genetics/*metabolism ; Ribosomes/chemistry/metabolism ; Tymovirus/*genetics
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  • 52
    Publication Date: 2014-11-28
    Description: Evidence is mounting that the immense diversity of microorganisms and animals that live belowground contributes significantly to shaping aboveground biodiversity and the functioning of terrestrial ecosystems. Our understanding of how this belowground biodiversity is distributed, and how it regulates the structure and functioning of terrestrial ecosystems, is rapidly growing. Evidence also points to soil biodiversity as having a key role in determining the ecological and evolutionary responses of terrestrial ecosystems to current and future environmental change. Here we review recent progress and propose avenues for further research in this field.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bardgett, Richard D -- van der Putten, Wim H -- England -- Nature. 2014 Nov 27;515(7528):505-11. doi: 10.1038/nature13855.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Faculty of Life Sciences, Michael Smith Building, The University of Manchester, Manchester M13 9PT, United Kingdom. ; 1] Department of Terrestrial Ecology, Netherlands Institute of Ecology (NIOO-KNAW), PO Box 50, 6700 AB Wageningen, The Netherlands [2] Laboratory of Nematology, Wageningen University, PO Box 8123, 6700 ES Wageningen, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25428498" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biodiversity ; *Ecosystem ; Food Chain ; Introduced Species ; Population Dynamics ; Soil Microbiology ; Time Factors
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  • 53
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    Nature Publishing Group (NPG)
    Publication Date: 2014-04-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Trivedi, Bijal P -- England -- Nature. 2014 Apr 17;508(7496):S64-5. doi: 10.1038/508S64a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24740131" target="_blank"〉PubMed〈/a〉
    Keywords: Agouti-Related Protein/metabolism ; Animals ; Anorexia/drug therapy/metabolism ; Appetite/*physiology ; Arcuate Nucleus of Hypothalamus/physiology ; Calcitonin Gene-Related Peptide/metabolism ; Feeding Behavior/*physiology/psychology ; Humans ; Hunger/physiology ; Mice ; Neurons/metabolism ; Neuropeptide Y/metabolism ; Obesity/drug therapy/metabolism ; Paraventricular Hypothalamic Nucleus/physiology ; Prader-Willi Syndrome/metabolism/pathology ; Pro-Opiomelanocortin/metabolism ; Time Factors ; gamma-Aminobutyric Acid/metabolism
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  • 54
    Publication Date: 2014-01-07
    Description: There are no clinically relevant treatments available that improve function in the growing population of very preterm infants (less than 32 weeks' gestation) with neonatal brain injury. Diffuse white matter injury (DWMI) is a common finding in these children and results in chronic neurodevelopmental impairments. As shown recently, failure in oligodendrocyte progenitor cell maturation contributes to DWMI. We demonstrated previously that the epidermal growth factor receptor (EGFR) has an important role in oligodendrocyte development. Here we examine whether enhanced EGFR signalling stimulates the endogenous response of EGFR-expressing progenitor cells during a critical period after brain injury, and promotes cellular and behavioural recovery in the developing brain. Using an established mouse model of very preterm brain injury, we demonstrate that selective overexpression of human EGFR in oligodendrocyte lineage cells or the administration of intranasal heparin-binding EGF immediately after injury decreases oligodendroglia death, enhances generation of new oligodendrocytes from progenitor cells and promotes functional recovery. Furthermore, these interventions diminish ultrastructural abnormalities and alleviate behavioural deficits on white-matter-specific paradigms. Inhibition of EGFR signalling with a molecularly targeted agent used for cancer therapy demonstrates that EGFR activation is an important contributor to oligodendrocyte regeneration and functional recovery after DWMI. Thus, our study provides direct evidence that targeting EGFR in oligodendrocyte progenitor cells at a specific time after injury is clinically feasible and potentially applicable to the treatment of premature children with white matter injury.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106485/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106485/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scafidi, Joseph -- Hammond, Timothy R -- Scafidi, Susanna -- Ritter, Jonathan -- Jablonska, Beata -- Roncal, Maria -- Szigeti-Buck, Klara -- Coman, Daniel -- Huang, Yuegao -- McCarter, Robert J Jr -- Hyder, Fahmeed -- Horvath, Tamas L -- Gallo, Vittorio -- DP1 OD006850/OD/NIH HHS/ -- K08 NS069815/NS/NINDS NIH HHS/ -- K08 NS073793/NS/NINDS NIH HHS/ -- K08NS069815/NS/NINDS NIH HHS/ -- K08NS073793/NS/NINDS NIH HHS/ -- K12NS052159/NS/NINDS NIH HHS/ -- P01 NS062686/NS/NINDS NIH HHS/ -- P30 HD040677/HD/NICHD NIH HHS/ -- P30 NS05219/NS/NINDS NIH HHS/ -- P30 NS052519/NS/NINDS NIH HHS/ -- P30HD040677/HD/NICHD NIH HHS/ -- R01 NS045702/NS/NINDS NIH HHS/ -- R01MH067528/MH/NIMH NIH HHS/ -- R01NS045702/NS/NINDS NIH HHS/ -- R01NS056427/NS/NINDS NIH HHS/ -- England -- Nature. 2014 Feb 13;506(7487):230-4. doi: 10.1038/nature12880. Epub 2013 Dec 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Center for Neuroscience Research, Children's National Medical Center, Washington DC 20010, USA [2] Department of Neurology, Children's National Medical Center, Washington DC 20010, USA. ; 1] Center for Neuroscience Research, Children's National Medical Center, Washington DC 20010, USA [2] Institute for Biomedical Sciences, The George Washington University, Washington DC 20052, USA. ; Department of Anesthesiology & Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. ; Center for Neuroscience Research, Children's National Medical Center, Washington DC 20010, USA. ; Department of Neurobiology, Yale University, New Haven, Connecticut 06520, USA. ; MRRC, Department of Diagnostic Radiology, Yale University, New Haven, Connecticut 06520, USA. ; Center for Translational Science, Children's National Medical Center, Washington DC 20010, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24390343" target="_blank"〉PubMed〈/a〉
    Keywords: Administration, Intranasal ; Animals ; Animals, Newborn ; Anoxia/genetics/metabolism/pathology/physiopathology ; Brain Injuries/*congenital/*drug therapy/pathology/prevention & control ; Cell Differentiation/drug effects ; Cell Division/drug effects ; Cell Lineage/drug effects ; Cell Survival/drug effects ; Demyelinating Diseases/congenital/metabolism/pathology/prevention & control ; Disease Models, Animal ; Epidermal Growth Factor/administration & dosage/*pharmacology/*therapeutic use ; Humans ; Infant, Premature, Diseases/drug therapy/metabolism/pathology ; Male ; Mice ; Molecular Targeted Therapy ; Oligodendroglia/cytology/*drug effects/metabolism/pathology ; Receptor, Epidermal Growth Factor/genetics/metabolism ; Regeneration/drug effects ; Signal Transduction/drug effects ; Stem Cells/cytology/drug effects/metabolism ; Time Factors
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  • 55
    Publication Date: 2014-04-25
    Description: Tropical forests are global epicentres of biodiversity and important modulators of climate change, and are mainly constrained by rainfall patterns. The severe short-term droughts that occurred recently in Amazonia have drawn attention to the vulnerability of tropical forests to climatic disturbances. The central African rainforests, the second-largest on Earth, have experienced a long-term drying trend whose impacts on vegetation dynamics remain mostly unknown because in situ observations are very limited. The Congolese forest, with its drier conditions and higher percentage of semi-evergreen trees, may be more tolerant to short-term rainfall reduction than are wetter tropical forests, but for a long-term drought there may be critical thresholds of water availability below which higher-biomass, closed-canopy forests transition to more open, lower-biomass forests. Here we present observational evidence for a widespread decline in forest greenness over the past decade based on analyses of satellite data (optical, thermal, microwave and gravity) from several independent sensors over the Congo basin. This decline in vegetation greenness, particularly in the northern Congolese forest, is generally consistent with decreases in rainfall, terrestrial water storage, water content in aboveground woody and leaf biomass, and the canopy backscatter anomaly caused by changes in structure and moisture in upper forest layers. It is also consistent with increases in photosynthetically active radiation and land surface temperature. These multiple lines of evidence indicate that this large-scale vegetation browning, or loss of photosynthetic capacity, may be partially attributable to the long-term drying trend. Our results suggest that a continued gradual decline of photosynthetic capacity and moisture content driven by the persistent drying trend could alter the composition and structure of the Congolese forest to favour the spread of drought-tolerant species.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Liming -- Tian, Yuhong -- Myneni, Ranga B -- Ciais, Philippe -- Saatchi, Sassan -- Liu, Yi Y -- Piao, Shilong -- Chen, Haishan -- Vermote, Eric F -- Song, Conghe -- Hwang, Taehee -- England -- Nature. 2014 May 1;509(7498):86-90. doi: 10.1038/nature13265. Epub 2014 Apr 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Atmospheric and Environmental Sciences, University at Albany, State University of New York (SUNY), Albany, New York 12222, USA. ; I. M. Systems Group (IMSG), National Oceanic and Atmospheric Administration/National Environmental Satellite, Data, and Information Service/The Center for Satellite Applications and Research (NOAA/NESDIS/STAR), 5830 University Research Court, College Park, Maryland 20740, USA. ; Department of Earth and Environment, Boston University, Boston, Massachusetts 02215, USA. ; Laboratoire des Sciences du Climat et de l'Environnement (LSCE), CEA-CNRS-UVSQ, 91191 Gif sur Yvette Cedex, France. ; Jet Propulsion Laboratory, Pasadena, California 91109, USA. ; ARC Centre of Excellence for Climate Systems Science & Climate Change Research Centre, University of New South Wales, Sydney, New South Wales 2052, Australia. ; Department of Ecology, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China. ; Key Laboratory of Meteorological Disaster, Ministry of Education, Nanjing University of Information Science and Technology, Nanjing 210044, China. ; NASA Goddard Space Flight Center, Code 619, Greenbelt, Maryland 20771, USA. ; 1] Department of Geography, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 29599, USA [2] School of Forestry and Landscape Architecture, Anhui Agricultural University, Hefei, Anhui 230036, China. ; Institute for the Environment, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 29599, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24759324" target="_blank"〉PubMed〈/a〉
    Keywords: Acclimatization ; Biodiversity ; Biomass ; Chlorophyll/analysis/metabolism ; Climate Change/*statistics & numerical data ; Congo ; Droughts/statistics & numerical data ; Photosynthesis ; Plant Leaves/*growth & development/metabolism ; *Rain ; Satellite Imagery ; Seasons ; Temperature ; Time Factors ; Trees/*growth & development/metabolism ; *Tropical Climate ; Water/analysis/metabolism ; Wood/growth & development/metabolism
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  • 56
    Publication Date: 2014-12-04
    Description: Photosynthesis converts light energy into biologically useful chemical energy vital to life on Earth. The initial reaction of photosynthesis takes place in photosystem II (PSII), a 700-kilodalton homodimeric membrane protein complex that catalyses photo-oxidation of water into dioxygen through an S-state cycle of the oxygen evolving complex (OEC). The structure of PSII has been solved by X-ray diffraction (XRD) at 1.9 angstrom resolution, which revealed that the OEC is a Mn4CaO5-cluster coordinated by a well defined protein environment. However, extended X-ray absorption fine structure (EXAFS) studies showed that the manganese cations in the OEC are easily reduced by X-ray irradiation, and slight differences were found in the Mn-Mn distances determined by XRD, EXAFS and theoretical studies. Here we report a 'radiation-damage-free' structure of PSII from Thermosynechococcus vulcanus in the S1 state at a resolution of 1.95 angstroms using femtosecond X-ray pulses of the SPring-8 angstrom compact free-electron laser (SACLA) and hundreds of large, highly isomorphous PSII crystals. Compared with the structure from XRD, the OEC in the X-ray free electron laser structure has Mn-Mn distances that are shorter by 0.1-0.2 angstroms. The valences of each manganese atom were tentatively assigned as Mn1D(III), Mn2C(IV), Mn3B(IV) and Mn4A(III), based on the average Mn-ligand distances and analysis of the Jahn-Teller axis on Mn(III). One of the oxo-bridged oxygens, O5, has significantly longer distances to Mn than do the other oxo-oxygen atoms, suggesting that O5 is a hydroxide ion instead of a normal oxygen dianion and therefore may serve as one of the substrate oxygen atoms. These findings provide a structural basis for the mechanism of oxygen evolution, and we expect that this structure will provide a blueprint for the design of artificial catalysts for water oxidation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Suga, Michihiro -- Akita, Fusamichi -- Hirata, Kunio -- Ueno, Go -- Murakami, Hironori -- Nakajima, Yoshiki -- Shimizu, Tetsuya -- Yamashita, Keitaro -- Yamamoto, Masaki -- Ago, Hideo -- Shen, Jian-Ren -- England -- Nature. 2015 Jan 1;517(7532):99-103. doi: 10.1038/nature13991. Epub 2014 Nov 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Photosynthesis Research Center, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima Naka, Okayama 700-8530, Japan. ; 1] RIKEN SPring-8 Center, 1-1-1 Kouto Sayo, Hyogo 679-5148, Japan [2] Japan Science and Technology Agency (JST), Core Research for Evolutional Science and Technology (CREST), Kawaguchi, Saitama 332-0012, Japan. ; RIKEN SPring-8 Center, 1-1-1 Kouto Sayo, Hyogo 679-5148, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25470056" target="_blank"〉PubMed〈/a〉
    Keywords: Catalytic Domain ; Crystallization ; Cyanobacteria/*enzymology ; Electrons ; Lasers ; Manganese/chemistry ; Models, Molecular ; Oxygen/chemistry/metabolism ; Photosystem II Protein Complex/*chemistry/*radiation effects ; Synchrotrons ; Time Factors ; Water/chemistry/metabolism ; *X-Rays
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  • 57
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    Nature Publishing Group (NPG)
    Publication Date: 2014-08-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Padma, T V -- England -- Nature. 2014 Aug 28;512(7515):359. doi: 10.1038/512359a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25164731" target="_blank"〉PubMed〈/a〉
    Keywords: *Altitude ; Animals ; *Biodiversity ; Fruit/anatomy & histology/physiology ; *Global Warming ; India ; Pinus/growth & development ; Plants/*classification ; *Temperature ; Time Factors
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  • 58
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    Nature Publishing Group (NPG)
    Publication Date: 2014-10-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2014 Oct 30;514(7524):535-6. doi: 10.1038/514535b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25355322" target="_blank"〉PubMed〈/a〉
    Keywords: Africa/epidemiology ; Animals ; Biomedical Research/*trends ; Chiroptera/virology ; Developed Countries ; Disease Outbreaks/prevention & control/statistics & numerical data/veterinary ; Disease Reservoirs/veterinary/virology ; *Ebola Vaccines/supply & distribution ; Filoviridae/isolation & purification/pathogenicity/physiology ; Hemorrhagic Fever, Ebola/epidemiology/prevention & control/*therapy/*virology ; Humans ; Laboratories/supply & distribution ; Swine/virology ; Time Factors
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  • 59
    Publication Date: 2014-11-20
    Description: Oxidative stress promotes genomic instability and human diseases. A common oxidized nucleoside is 8-oxo-7,8-dihydro-2'-deoxyguanosine, which is found both in DNA (8-oxo-G) and as a free nucleotide (8-oxo-dGTP). Nucleotide pools are especially vulnerable to oxidative damage. Therefore cells encode an enzyme (MutT/MTH1) that removes free oxidized nucleotides. This cleansing function is required for cancer cell survival and to modulate Escherichia coli antibiotic sensitivity in a DNA polymerase (pol)-dependent manner. How polymerases discriminate between damaged and non-damaged nucleotides is not well understood. This analysis is essential given the role of oxidized nucleotides in mutagenesis, cancer therapeutics, and bacterial antibiotics. Even with cellular sanitizing activities, nucleotide pools contain enough 8-oxo-dGTP to promote mutagenesis. This arises from the dual coding potential where 8-oxo-dGTP(anti) base pairs with cytosine and 8-oxo-dGTP(syn) uses its Hoogsteen edge to base pair with adenine. Here we use time-lapse crystallography to follow 8-oxo-dGTP insertion opposite adenine or cytosine with human pol beta, to reveal that insertion is accommodated in either the syn- or anti-conformation, respectively. For 8-oxo-dGTP(anti) insertion, a novel divalent metal relieves repulsive interactions between the adducted guanine base and the triphosphate of the oxidized nucleotide. With either templating base, hydrogen-bonding interactions between the bases are lost as the enzyme reopens after catalysis, leading to a cytotoxic nicked DNA repair intermediate. Combining structural snapshots with kinetic and computational analysis reveals how 8-oxo-dGTP uses charge modulation during insertion that can lead to a blocked DNA repair intermediate.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312183/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312183/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Freudenthal, Bret D -- Beard, William A -- Perera, Lalith -- Shock, David D -- Kim, Taejin -- Schlick, Tamar -- Wilson, Samuel H -- 1U19CA105010/CA/NCI NIH HHS/ -- U19 CA177547/CA/NCI NIH HHS/ -- Z01-ES050158/ES/NIEHS NIH HHS/ -- Z01-ES050161/ES/NIEHS NIH HHS/ -- ZIA ES050158-18/Intramural NIH HHS/ -- ZIA ES050159-18/Intramural NIH HHS/ -- ZIC-ES043010/ES/NIEHS NIH HHS/ -- England -- Nature. 2015 Jan 29;517(7536):635-9. doi: 10.1038/nature13886. Epub 2014 Nov 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, PO Box 12233, Research Triangle Park, North Carolina 27709-2233, USA. ; 1] Department of Chemistry, New York University, and NYU-ECNU Center for Computational Chemistry at NYU Shanghai, 10th Floor Silver Center, 100 Washington Square East, New York, New York 10003, USA [2] Courant Institute of Mathematical Sciences, New York University, 251 Mercer Street, New York, New York 10012, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25409153" target="_blank"〉PubMed〈/a〉
    Keywords: Adenine/chemistry/metabolism ; Base Pairing ; Catalytic Domain ; Crystallography, X-Ray ; Cytosine/chemistry/metabolism ; Cytotoxins/chemistry/*metabolism/toxicity ; DNA/biosynthesis/chemistry ; *DNA Damage ; DNA Polymerase beta/*chemistry/*metabolism ; DNA Repair ; DNA Replication ; Deoxyguanine Nucleotides/chemistry/*metabolism/*toxicity ; Guanine/analogs & derivatives/chemistry/metabolism ; Humans ; Hydrogen Bonding ; Kinetics ; Models, Molecular ; Molecular Conformation ; *Mutagenesis ; Neoplasms/enzymology/genetics ; Oxidation-Reduction ; Oxidative Stress ; Static Electricity ; Substrate Specificity ; Time Factors
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  • 60
    Publication Date: 2014-07-22
    Description: Aberrant regulation of RNA stability has an important role in many disease states. Deregulated post-transcriptional modulation, such as that governed by microRNAs targeting linear sequence elements in messenger RNAs, has been implicated in the progression of many cancer types. A defining feature of RNA is its ability to fold into structures. However, the roles of structural mRNA elements in cancer progression remain unexplored. Here we performed an unbiased search for post-transcriptional modulators of mRNA stability in breast cancer by conducting whole-genome transcript stability measurements in poorly and highly metastatic isogenic human breast cancer lines. Using a computational framework that searches RNA sequence and structure space, we discovered a family of GC-rich structural cis-regulatory RNA elements, termed sRSEs for structural RNA stability elements, which are significantly overrepresented in transcripts displaying reduced stability in highly metastatic cells. By integrating computational and biochemical approaches, we identified TARBP2, a double-stranded RNA-binding protein implicated in microRNA processing, as the trans factor that binds the sRSE family and similar structural elements--collectively termed TARBP2-binding structural elements (TBSEs)--in transcripts. TARBP2 is overexpressed in metastatic cells and metastatic human breast tumours and destabilizes transcripts containing TBSEs. Endogenous TARBP2 promotes metastatic cell invasion and colonization by destabilizing amyloid precursor protein (APP) and ZNF395 transcripts, two genes previously associated with Alzheimer's and Huntington's disease, respectively. We reveal these genes to be novel metastasis suppressor genes in breast cancer. The cleavage product of APP, extracellular amyloid-alpha peptide, directly suppresses invasion while ZNF395 transcriptionally represses a pro-metastatic gene expression program. The expression levels of TARBP2, APP and ZNF395 in human breast carcinomas support their experimentally uncovered roles in metastasis. Our findings establish a non-canonical and direct role for TARBP2 in mammalian gene expression regulation and reveal that regulated RNA destabilization through protein-mediated binding of mRNA structural elements can govern cancer progression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4440807/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4440807/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goodarzi, Hani -- Zhang, Steven -- Buss, Colin G -- Fish, Lisa -- Tavazoie, Saeed -- Tavazoie, Sohail F -- R01 HG003219/HG/NHGRI NIH HHS/ -- England -- Nature. 2014 Sep 11;513(7517):256-60. doi: 10.1038/nature13466. Epub 2014 Jul 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Systems Cancer Biology, Rockefeller University, 1230 York Avenue, New York, New York 10065, USA. ; Department of Biochemistry and Molecular Biophysics, and Department of Systems Biology, Columbia University, New York, New York 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043050" target="_blank"〉PubMed〈/a〉
    Keywords: Amyloid beta-Protein Precursor/metabolism ; Breast Neoplasms/pathology ; Cell Line, Tumor ; DNA-Binding Proteins/metabolism ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; HEK293 Cells ; Humans ; Neoplasm Metastasis ; Protein Binding ; *RNA Stability ; RNA, Messenger/*metabolism ; RNA-Binding Proteins/genetics/*metabolism ; Transcription Factors/metabolism
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  • 61
    Publication Date: 2014-03-05
    Description: Filoviruses are emerging pathogens and causative agents of viral haemorrhagic fever. Case fatality rates of filovirus disease outbreaks are among the highest reported for any human pathogen, exceeding 90% (ref. 1). Licensed therapeutic or vaccine products are not available to treat filovirus diseases. Candidate therapeutics previously shown to be efficacious in non-human primate disease models are based on virus-specific designs and have limited broad-spectrum antiviral potential. Here we show that BCX4430, a novel synthetic adenosine analogue, inhibits infection of distinct filoviruses in human cells. Biochemical, reporter-based and primer-extension assays indicate that BCX4430 inhibits viral RNA polymerase function, acting as a non-obligate RNA chain terminator. Post-exposure intramuscular administration of BCX4430 protects against Ebola virus and Marburg virus disease in rodent models. Most importantly, BCX4430 completely protects cynomolgus macaques from Marburg virus infection when administered as late as 48 hours after infection. In addition, BCX4430 exhibits broad-spectrum antiviral activity against numerous viruses, including bunyaviruses, arenaviruses, paramyxoviruses, coronaviruses and flaviviruses. This is the first report, to our knowledge, of non-human primate protection from filovirus disease by a synthetic drug-like small molecule. We provide additional pharmacological characterizations supporting the potential development of BCX4430 as a countermeasure against human filovirus diseases and other viral diseases representing major public health threats.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Warren, Travis K -- Wells, Jay -- Panchal, Rekha G -- Stuthman, Kelly S -- Garza, Nicole L -- Van Tongeren, Sean A -- Dong, Lian -- Retterer, Cary J -- Eaton, Brett P -- Pegoraro, Gianluca -- Honnold, Shelley -- Bantia, Shanta -- Kotian, Pravin -- Chen, Xilin -- Taubenheim, Brian R -- Welch, Lisa S -- Minning, Dena M -- Babu, Yarlagadda S -- Sheridan, William P -- Bavari, Sina -- HHSN272201100016I/PHS HHS/ -- HHSN272201100019I/PHS HHS/ -- HHSN27220110005I/PHS HHS/ -- England -- Nature. 2014 Apr 17;508(7496):402-5. doi: 10.1038/nature13027. Epub 2014 Mar 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Molecular and Translational Sciences, Therapeutic Discovery Center, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Maryland 21702, USA. ; BioCryst Pharmaceuticals Inc., Durham, North Carolina 27703, USA. ; 1] BioCryst Pharmaceuticals Inc., Durham, North Carolina 27703, USA [2] Wilco Consulting, LLC, Durham, North Carolina 27712, USA. ; MedExpert Consulting, Inc., Indialantic, Florida 32903, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24590073" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine/*analogs & derivatives ; Administration, Oral ; Animals ; Antiviral Agents/administration & dosage/chemistry/pharmacokinetics/*pharmacology ; DNA-Directed RNA Polymerases/antagonists & inhibitors/metabolism ; Disease Models, Animal ; Ebolavirus/drug effects ; Filoviridae/*drug effects/enzymology ; Filoviridae Infections/*prevention & control/*virology ; Hemorrhagic Fever, Ebola/prevention & control/virology ; Humans ; Injections, Intramuscular ; Macaca fascicularis/virology ; Marburg Virus Disease/prevention & control/virology ; Marburgvirus/drug effects ; Purine Nucleosides/administration & ; dosage/chemistry/pharmacokinetics/*pharmacology ; RNA/biosynthesis ; Time Factors
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  • 62
    Publication Date: 2014-03-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉DiNezio, Pedro -- England -- Nature. 2014 Mar 27;507(7493):437-9. doi: 10.1038/507437a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Oceanography, School of Ocean and Earth Science and Technology, University of Hawaii, Honolulu, Hawaii 96822, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670757" target="_blank"〉PubMed〈/a〉
    Keywords: Computer Simulation ; *El Nino-Southern Oscillation ; *Forecasting ; Nonlinear Dynamics ; Pacific Ocean ; Temperature ; Time Factors ; Tropical Climate ; *Uncertainty
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  • 63
    Publication Date: 2014-04-18
    Description: A primary goal of the Human Microbiome Project (HMP) was to provide a reference collection of 16S ribosomal RNA gene sequences collected from sites across the human body that would allow microbiologists to better associate changes in the microbiome with changes in health. The HMP Consortium has reported the structure and function of the human microbiome in 300 healthy adults at 18 body sites from a single time point. Using additional data collected over the course of 12-18 months, we used Dirichlet multinomial mixture models to partition the data into community types for each body site and made three important observations. First, there were strong associations between whether individuals had been breastfed as an infant, their gender, and their level of education with their community types at several body sites. Second, although the specific taxonomic compositions of the oral and gut microbiomes were different, the community types observed at these sites were predictive of each other. Finally, over the course of the sampling period, the community types from sites within the oral cavity were the least stable, whereas those in the vagina and gut were the most stable. Our results demonstrate that even with the considerable intra- and interpersonal variation in the human microbiome, this variation can be partitioned into community types that are predictive of each other and are probably the result of life-history characteristics. Understanding the diversity of community types and the mechanisms that result in an individual having a particular type or changing types, will allow us to use their community types to assess disease risk and to personalize therapies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139711/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139711/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ding, Tao -- Schloss, Patrick D -- P30 DK034933/DK/NIDDK NIH HHS/ -- P30DK034933/DK/NIDDK NIH HHS/ -- R01 GM099514/GM/NIGMS NIH HHS/ -- R01 HG005975/HG/NHGRI NIH HHS/ -- R01GM099514/GM/NIGMS NIH HHS/ -- R01HG005975/HG/NHGRI NIH HHS/ -- England -- Nature. 2014 May 15;509(7500):357-60. doi: 10.1038/nature13178. Epub 2014 Apr 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, 1500 W. Medical Center, University of Michigan, Ann Arbor, Michigan 48109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24739969" target="_blank"〉PubMed〈/a〉
    Keywords: Breast Feeding ; Disease Susceptibility ; Educational Status ; Feces/microbiology ; Female ; Gastrointestinal Tract/microbiology ; Health ; *Human Body ; Humans ; Life Style ; Male ; Metagenome/genetics ; *Microbiota/genetics ; Mouth/microbiology ; *Organ Specificity ; Precision Medicine ; RNA, Ribosomal, 16S/genetics ; Sex Characteristics ; Time Factors ; Vagina/microbiology
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  • 64
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    Nature Publishing Group (NPG)
    Publication Date: 2014-04-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2014 Apr 17;508(7496):287.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24745067" target="_blank"〉PubMed〈/a〉
    Keywords: *Democracy ; Embryonic Stem Cells ; *European Union ; Humans ; *Public Opinion ; Stem Cell Research/economics/*legislation & jurisprudence ; Time Factors
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  • 65
    Publication Date: 2014-05-09
    Description: Efficient duplication of the genome requires the concerted action of helicase and DNA polymerases at replication forks to avoid stalling of the replication machinery and consequent genomic instability. In eukaryotes, the physical coupling between helicase and DNA polymerases remains poorly understood. Here we define the molecular mechanism by which the yeast Ctf4 protein links the Cdc45-MCM-GINS (CMG) DNA helicase to DNA polymerase alpha (Pol alpha) within the replisome. We use X-ray crystallography and electron microscopy to show that Ctf4 self-associates in a constitutive disk-shaped trimer. Trimerization depends on a beta-propeller domain in the carboxy-terminal half of the protein, which is fused to a helical extension that protrudes from one face of the trimeric disk. Critically, Pol alpha and the CMG helicase share a common mechanism of interaction with Ctf4. We show that the amino-terminal tails of the catalytic subunit of Pol alpha and the Sld5 subunit of GINS contain a conserved Ctf4-binding motif that docks onto the exposed helical extension of a Ctf4 protomer within the trimer. Accordingly, we demonstrate that one Ctf4 trimer can support binding of up to three partner proteins, including the simultaneous association with both Pol alpha and GINS. Our findings indicate that Ctf4 can couple two molecules of Pol alpha to one CMG helicase within the replisome, providing a new model for lagging-strand synthesis in eukaryotes that resembles the emerging model for the simpler replisome of Escherichia coli. The ability of Ctf4 to act as a platform for multivalent interactions illustrates a mechanism for the concurrent recruitment of factors that act together at the fork.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059944/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059944/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Simon, Aline C -- Zhou, Jin C -- Perera, Rajika L -- van Deursen, Frederick -- Evrin, Cecile -- Ivanova, Marina E -- Kilkenny, Mairi L -- Renault, Ludovic -- Kjaer, Svend -- Matak-Vinkovic, Dijana -- Labib, Karim -- Costa, Alessandro -- Pellegrini, Luca -- 084279/Wellcome Trust/United Kingdom -- Wellcome Trust/United Kingdom -- Medical Research Council/United Kingdom -- England -- Nature. 2014 Jun 12;510(7504):293-7. doi: 10.1038/nature13234. Epub 2014 May 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK [2]. ; 1] Clare Hall Laboratories, Cancer Research UK London Research Institute, London EN6 3LD, UK [2]. ; 1] Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK [2] Imperial College, South Kensington, London SW7 2AZ, UK (R.L.P.); Cancer Research UK London Research Institute, London WC2A 3LY, UK (M.E.I.). ; Cancer Research UK Manchester Institute, University of Manchester, Manchester M20 4BX, UK. ; MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK. ; Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK. ; Clare Hall Laboratories, Cancer Research UK London Research Institute, London EN6 3LD, UK. ; Protein purification, Cancer Research UK London Research Institute, London WC2A 3LY, UK. ; Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24805245" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Catalytic Domain ; Conserved Sequence ; Crystallography, X-Ray ; DNA Helicases/chemistry/*metabolism/ultrastructure ; DNA Polymerase I/chemistry/*metabolism/ultrastructure ; *DNA Replication ; DNA-Binding Proteins/*chemistry/*metabolism/ultrastructure ; DNA-Directed DNA Polymerase/*chemistry/*metabolism ; Microscopy, Electron ; Minichromosome Maintenance Proteins/chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Multienzyme Complexes/*chemistry/*metabolism ; Nuclear Proteins/chemistry/metabolism ; Protein Binding ; *Protein Multimerization ; Protein Structure, Quaternary ; Protein Subunits/chemistry/metabolism ; Saccharomyces cerevisiae/*chemistry/ultrastructure ; Saccharomyces cerevisiae Proteins/*chemistry/*metabolism/ultrastructure
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  • 66
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    Nature Publishing Group (NPG)
    Publication Date: 2014-12-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2014 Dec 11;516(7530):154-5. doi: 10.1038/516154a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25503213" target="_blank"〉PubMed〈/a〉
    Keywords: Africa, Western/epidemiology ; *Early Diagnosis ; Ebolavirus/genetics/*isolation & purification ; Hemorrhagic Fever, Ebola/*diagnosis/epidemiology/*prevention & ; control/transmission ; Humans ; Quarantine ; Reverse Transcriptase Polymerase Chain Reaction ; Time Factors ; World Health Organization
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  • 67
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    Nature Publishing Group (NPG)
    Publication Date: 2014-05-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gravitz, Lauren -- England -- Nature. 2014 May 29;509(7502):S52-4. doi: 10.1038/509S52a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24870820" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; Benzamides/pharmacology/therapeutic use ; Biological Evolution ; Biopsy/methods ; DNA Mutational Analysis ; DNA, Neoplasm/blood/genetics ; Disease Progression ; Drug Delivery Systems ; Drug Resistance, Neoplasm ; Genes, Tumor Suppressor ; Genetics, Medical/trends ; Genomics/trends ; Humans ; Imatinib Mesylate ; Immunotherapy/*methods/trends ; Indoles/pharmacology/therapeutic use ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis/drug therapy/genetics ; Middle Aged ; Nanoparticles/administration & dosage ; Neoplasms/diagnosis/*genetics/immunology/*therapy ; *Pharmacogenetics/trends ; Piperazines/pharmacology/therapeutic use ; Precision Medicine/*methods/*trends ; Proto-Oncogene Proteins B-raf/genetics ; Pyrimidines/pharmacology/therapeutic use ; RNA Interference ; RNA, Small Interfering/genetics/therapeutic use ; Sulfonamides/pharmacology/therapeutic use ; Time Factors ; Transcriptome
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  • 68
    Publication Date: 2014-03-05
    Description: Recognition of modified histones by 'reader' proteins plays a critical role in the regulation of chromatin. H3K36 trimethylation (H3K36me3) is deposited onto the nucleosomes in the transcribed regions after RNA polymerase II elongation. In yeast, this mark in turn recruits epigenetic regulators to reset the chromatin to a relatively repressive state, thus suppressing cryptic transcription. However, much less is known about the role of H3K36me3 in transcription regulation in mammals. This is further complicated by the transcription-coupled incorporation of the histone variant H3.3 in gene bodies. Here we show that the candidate tumour suppressor ZMYND11 specifically recognizes H3K36me3 on H3.3 (H3.3K36me3) and regulates RNA polymerase II elongation. Structural studies show that in addition to the trimethyl-lysine binding by an aromatic cage within the PWWP domain, the H3.3-dependent recognition is mediated by the encapsulation of the H3.3-specific 'Ser 31' residue in a composite pocket formed by the tandem bromo-PWWP domains of ZMYND11. Chromatin immunoprecipitation followed by sequencing shows a genome-wide co-localization of ZMYND11 with H3K36me3 and H3.3 in gene bodies, and its occupancy requires the pre-deposition of H3.3K36me3. Although ZMYND11 is associated with highly expressed genes, it functions as an unconventional transcription co-repressor by modulating RNA polymerase II at the elongation stage. ZMYND11 is critical for the repression of a transcriptional program that is essential for tumour cell growth; low expression levels of ZMYND11 in breast cancer patients correlate with worse prognosis. Consistently, overexpression of ZMYND11 suppresses cancer cell growth in vitro and tumour formation in mice. Together, this study identifies ZMYND11 as an H3.3-specific reader of H3K36me3 that links the histone-variant-mediated transcription elongation control to tumour suppression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142212/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142212/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wen, Hong -- Li, Yuanyuan -- Xi, Yuanxin -- Jiang, Shiming -- Stratton, Sabrina -- Peng, Danni -- Tanaka, Kaori -- Ren, Yongfeng -- Xia, Zheng -- Wu, Jun -- Li, Bing -- Barton, Michelle C -- Li, Wei -- Li, Haitao -- Shi, Xiaobing -- CA016672/CA/NCI NIH HHS/ -- P30 CA016672/CA/NCI NIH HHS/ -- R01 GM090077/GM/NIGMS NIH HHS/ -- R01 HG007538/HG/NHGRI NIH HHS/ -- R01GM090077/GM/NIGMS NIH HHS/ -- R01HG007538/HG/NHGRI NIH HHS/ -- England -- Nature. 2014 Apr 10;508(7495):263-8. doi: 10.1038/nature13045. Epub 2014 Mar 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [2] Center for Cancer Epigenetics, Center for Genetics and Genomics, and Center for Stem Cell and Developmental Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [3]. ; 1] MOE Key Laboratory of Protein Sciences, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China [2] Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China [3]. ; 1] Dan L. Duncan Cancer Center, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA [2]. ; Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. ; 1] MOE Key Laboratory of Protein Sciences, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China [2] Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China. ; Dan L. Duncan Cancer Center, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA. ; Department of Molecular Biology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. ; 1] Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [2] Center for Cancer Epigenetics, Center for Genetics and Genomics, and Center for Stem Cell and Developmental Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [3] Genes and Development Graduate Program, The University of Texas Graduate School of Biomedical Sciences, Houston, Teaxs 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24590075" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Breast Neoplasms/*genetics/metabolism/*pathology ; Carrier Proteins/chemistry/*metabolism ; Chromatin/genetics/metabolism ; Co-Repressor Proteins/chemistry/metabolism ; Crystallography, X-Ray ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Histones/chemistry/*metabolism ; Humans ; Lysine/*metabolism ; Methylation ; Mice ; Mice, Nude ; Models, Molecular ; Molecular Sequence Data ; Oncogenes/genetics ; Prognosis ; Protein Binding ; Protein Conformation ; Protein Structure, Tertiary ; RNA Polymerase II/*metabolism ; Substrate Specificity ; *Transcription Elongation, Genetic
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  • 69
    Publication Date: 2014-08-19
    Description: Dysregulated neurodevelopment with altered structural and functional connectivity is believed to underlie many neuropsychiatric disorders, and 'a disease of synapses' is the major hypothesis for the biological basis of schizophrenia. Although this hypothesis has gained indirect support from human post-mortem brain analyses and genetic studies, little is known about the pathophysiology of synapses in patient neurons and how susceptibility genes for mental disorders could lead to synaptic deficits in humans. Genetics of most psychiatric disorders are extremely complex due to multiple susceptibility variants with low penetrance and variable phenotypes. Rare, multiply affected, large families in which a single genetic locus is probably responsible for conferring susceptibility have proven invaluable for the study of complex disorders. Here we generated induced pluripotent stem (iPS) cells from four members of a family in which a frameshift mutation of disrupted in schizophrenia 1 (DISC1) co-segregated with major psychiatric disorders and we further produced different isogenic iPS cell lines via gene editing. We showed that mutant DISC1 causes synaptic vesicle release deficits in iPS-cell-derived forebrain neurons. Mutant DISC1 depletes wild-type DISC1 protein and, furthermore, dysregulates expression of many genes related to synapses and psychiatric disorders in human forebrain neurons. Our study reveals that a psychiatric disorder relevant mutation causes synapse deficits and transcriptional dysregulation in human neurons and our findings provide new insight into the molecular and synaptic etiopathology of psychiatric disorders.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4501856/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4501856/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wen, Zhexing -- Nguyen, Ha Nam -- Guo, Ziyuan -- Lalli, Matthew A -- Wang, Xinyuan -- Su, Yijing -- Kim, Nam-Shik -- Yoon, Ki-Jun -- Shin, Jaehoon -- Zhang, Ce -- Makri, Georgia -- Nauen, David -- Yu, Huimei -- Guzman, Elmer -- Chiang, Cheng-Hsuan -- Yoritomo, Nadine -- Kaibuchi, Kozo -- Zou, Jizhong -- Christian, Kimberly M -- Cheng, Linzhao -- Ross, Christopher A -- Margolis, Russell L -- Chen, Gong -- Kosik, Kenneth S -- Song, Hongjun -- Ming, Guo-li -- AG045656/AG/NIA NIH HHS/ -- F31 MH102978/MH/NIMH NIH HHS/ -- MH087874/MH/NIMH NIH HHS/ -- MH102978/MH/NIMH NIH HHS/ -- NS047344/NS/NINDS NIH HHS/ -- NS048271/NS/NINDS NIH HHS/ -- R01 AG024984/AG/NIA NIH HHS/ -- R01 AG045656/AG/NIA NIH HHS/ -- R01 MH083911/MH/NIMH NIH HHS/ -- R01 MH105128/MH/NIMH NIH HHS/ -- R01 NS047344/NS/NINDS NIH HHS/ -- R01 NS048271/NS/NINDS NIH HHS/ -- R21 ES021957/ES/NIEHS NIH HHS/ -- R21 MH092740/MH/NIMH NIH HHS/ -- T32 GM008752/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Nov 20;515(7527):414-8. doi: 10.1038/nature13716. Epub 2014 Aug 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [3]. ; 1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [3]. ; 1] Department of Biology, Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802, USA [2]. ; Neuroscience Research Institute, Department of Molecular Cellular and Developmental Biology, Biomolecular Science and Engineering Program, University of California, Santa Barbara, California 93106, USA. ; 1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. ; 1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ; 1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ; 1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ; 1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [3] The Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ; Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Showa, Nagoya 466-8550, Japan. ; 1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ; 1] Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] The Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [3] Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ; Department of Biology, Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802, USA. ; 1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [3] Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [4] The Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25132547" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation ; Fibroblasts ; Glutamine/metabolism ; Humans ; Induced Pluripotent Stem Cells/metabolism/*pathology ; Male ; Mental Disorders/genetics/metabolism/*pathology ; Mice ; Mutant Proteins/genetics/metabolism ; Mutation/genetics ; Nerve Tissue Proteins/genetics/metabolism ; Neurons/cytology/metabolism/pathology ; Pedigree ; Presynaptic Terminals/metabolism/pathology ; Prosencephalon/metabolism/pathology ; Protein Binding ; Synapses/metabolism/*pathology ; Transcriptome
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  • 70
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    Nature Publishing Group (NPG)
    Publication Date: 2014-11-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Werner, Michael J -- England -- Nature. 2014 Nov 20;515(7527):S126. doi: 10.1038/515S126a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Holland and Knight in Washington DC and a policy adviser for the Public Access to Sunscreens Coalition.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25407712" target="_blank"〉PubMed〈/a〉
    Keywords: Drug Approval/*legislation & jurisprudence/*methods ; European Union ; Humans ; Phenols/supply & distribution ; *Sunscreening Agents/supply & distribution ; Time Factors ; Triazines/supply & distribution ; Ultraviolet Rays/*adverse effects ; United States ; United States Food and Drug Administration/*legislation & jurisprudence
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  • 71
    Publication Date: 2014-07-06
    Description: Lipopolysaccharide (LPS) is essential for most Gram-negative bacteria and has crucial roles in protection of the bacteria from harsh environments and toxic compounds, including antibiotics. Seven LPS transport proteins (that is, LptA-LptG) form a trans-envelope protein complex responsible for the transport of LPS from the inner membrane to the outer membrane, the mechanism for which is poorly understood. Here we report the first crystal structure of the unique integral membrane LPS translocon LptD-LptE complex. LptD forms a novel 26-stranded beta-barrel, which is to our knowledge the largest beta-barrel reported so far. LptE adopts a roll-like structure located inside the barrel of LptD to form an unprecedented two-protein 'barrel and plug' architecture. The structure, molecular dynamics simulations and functional assays suggest that the hydrophilic O-antigen and the core oligosaccharide of the LPS may pass through the barrel and the lipid A of the LPS may be inserted into the outer leaflet of the outer membrane through a lateral opening between strands beta1 and beta26 of LptD. These findings not only help us to understand important aspects of bacterial outer membrane biogenesis, but also have significant potential for the development of novel drugs against multi-drug resistant pathogenic bacteria.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dong, Haohao -- Xiang, Quanju -- Gu, Yinghong -- Wang, Zhongshan -- Paterson, Neil G -- Stansfeld, Phillip J -- He, Chuan -- Zhang, Yizheng -- Wang, Wenjian -- Dong, Changjiang -- 083501/Z/07/Z/Wellcome Trust/United Kingdom -- England -- Nature. 2014 Jul 3;511(7507):52-6. doi: 10.1038/nature13464. Epub 2014 Jun 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK [2] Biomedical Sciences Research Complex, School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, UK. ; 1] Biomedical Sciences Research Complex, School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, UK [2] Department of Microbiology, College of Resource and Environment Science, Sichuan Agriculture University, Yaan 625000, China. ; Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK. ; 1] Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK [2] Biomedical Sciences Research Complex, School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, UK [3] College of Life Sciences, Sichuan University, Chengdu 610065, China. ; Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE, UK. ; Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. ; 1] Biomedical Sciences Research Complex, School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, UK [2] School of Electronics and Information, Wuhan Technical College of Communications, No.6 Huangjiahu West Road, Hongshan District, Wuhan, Hubei 430065, China. ; College of Life Sciences, Sichuan University, Chengdu 610065, China. ; Laboratory of Department of Surgery, the First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, Guangdong 510080, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24990744" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Outer Membrane Proteins/*chemistry/*metabolism ; Cell Membrane/chemistry/metabolism ; Cell Wall/chemistry/metabolism ; Crystallography, X-Ray ; Lipopolysaccharides/chemistry/*metabolism ; Models, Molecular ; Multiprotein Complexes/*chemistry/*metabolism ; Protein Binding ; Protein Structure, Secondary ; Salmonella typhimurium/*chemistry/cytology ; Structure-Activity Relationship
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  • 72
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    Nature Publishing Group (NPG)
    Publication Date: 2014-05-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kessler, Rebecca -- England -- Nature. 2014 May 29;509(7502):S62-3. doi: 10.1038/509S62a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24870824" target="_blank"〉PubMed〈/a〉
    Keywords: Air Pollution/adverse effects/analysis ; Carcinogens/analysis/*toxicity ; Child ; China ; Disease Susceptibility ; Endocrine Disruptors/adverse effects ; Environmental Exposure/*adverse effects/*prevention & control ; Environmental Pollution/*adverse effects/prevention & control/statistics & ; numerical data ; Epigenesis, Genetic/drug effects ; Female ; Humans ; Life Style ; Neoplasms/*chemically induced/genetics/*prevention & control ; Occupational Exposure/adverse effects/statistics & numerical data ; Particulate Matter/adverse effects ; Pregnancy ; Risk Reduction Behavior ; Tetrachloroethylene/adverse effects ; Time Factors ; United States ; United States Environmental Protection Agency ; World Health Organization
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  • 73
    Publication Date: 2014-01-07
    Description: Wnts are evolutionarily conserved secreted signalling proteins that, in various developmental contexts, spread from their site of synthesis to form a gradient and activate target-gene expression at a distance. However, the requirement for Wnts to spread has never been directly tested. Here we used genome engineering to replace the endogenous wingless gene, which encodes the main Drosophila Wnt, with one that expresses a membrane-tethered form of the protein. Surprisingly, the resulting flies were viable and produced normally patterned appendages of nearly the right size, albeit with a delay. We show that, in the prospective wing, prolonged wingless transcription followed by memory of earlier signalling allows persistent expression of relevant target genes. We suggest therefore that the spread of Wingless is dispensable for patterning and growth even though it probably contributes to increasing cell proliferation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alexandre, Cyrille -- Baena-Lopez, Alberto -- Vincent, Jean-Paul -- 082694/Z/07/Z/Wellcome Trust/United Kingdom -- U117584268/Medical Research Council/United Kingdom -- England -- Nature. 2014 Jan 9;505(7482):180-5. doi: 10.1038/nature12879. Epub 2013 Dec 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK [2]. ; MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24390349" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; *Body Patterning/genetics ; Cell Membrane/*metabolism ; Cell Proliferation ; Chemokine CX3CL1/metabolism ; Diffusion ; Drosophila Proteins/deficiency/genetics/*metabolism ; Drosophila melanogaster/cytology/genetics/*growth & development/*metabolism ; Gene Expression Regulation, Developmental ; Mutation ; Organ Specificity ; Promoter Regions, Genetic/genetics ; Signal Transduction ; Time Factors ; Transcription, Genetic ; Wings, Animal/cytology/growth & development/metabolism ; Wnt1 Protein/deficiency/genetics/*metabolism
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  • 74
    Publication Date: 2014-02-14
    Description: It has been theorized for decades that mitochondria act as the biological clock of ageing, but the evidence is incomplete. Here we show a strong coupling between mitochondrial function and ageing by in vivo visualization of the mitochondrial flash (mitoflash), a frequency-coded optical readout reflecting free-radical production and energy metabolism at the single-mitochondrion level. Mitoflash activity in Caenorhabditis elegans pharyngeal muscles peaked on adult day 3 during active reproduction and on day 9 when animals started to die off. A plethora of genetic mutations and environmental factors inversely modified the lifespan and the day-3 mitoflash frequency. Even within an isogenic population, the day-3 mitoflash frequency was negatively correlated with the lifespan of individual animals. Furthermore, enhanced activity of the glyoxylate cycle contributed to the decreased day-3 mitoflash frequency and the longevity of daf-2 mutant animals. These results demonstrate that the day-3 mitoflash frequency is a powerful predictor of C. elegans lifespan across genetic, environmental and stochastic factors. They also support the notion that the rate of ageing, although adjustable in later life, has been set to a considerable degree before reproduction ceases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shen, En-Zhi -- Song, Chun-Qing -- Lin, Yuan -- Zhang, Wen-Hong -- Su, Pei-Fang -- Liu, Wen-Yuan -- Zhang, Pan -- Xu, Jiejia -- Lin, Na -- Zhan, Cheng -- Wang, Xianhua -- Shyr, Yu -- Cheng, Heping -- Dong, Meng-Qiu -- England -- Nature. 2014 Apr 3;508(7494):128-32. doi: 10.1038/nature13012. Epub 2014 Feb 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] College of Biological Sciences, China Agricultural University, Beijing 100094, China [2] National Institute of Biological Sciences, Beijing, Beijing 102206, China [3]. ; 1] State Key Laboratory of Biomembrane and Membrane Biotechnology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China [2]. ; National Institute of Biological Sciences, Beijing, Beijing 102206, China. ; Department of Statistics, National Cheng Kung University, Tainan 70101, Taiwan. ; State Key Laboratory of Biomembrane and Membrane Biotechnology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. ; Vanderbilt Centre for Quantitative Sciences, Vanderbilt University, Nashville, Tennessee 37232, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24522532" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/metabolism ; Animals ; Animals, Genetically Modified ; Caenorhabditis elegans/cytology/genetics/*metabolism/physiology ; Caenorhabditis elegans Proteins/genetics ; Death ; Energy Metabolism ; Environment ; Glyoxylates/metabolism ; Hermaphroditic Organisms ; *Longevity/genetics/physiology ; Male ; Mitochondria/*metabolism ; Models, Biological ; Muscles/cytology ; Mutation ; Oxidative Stress ; Receptor, Insulin/genetics ; Reproduction ; Stochastic Processes ; Superoxides/analysis/*metabolism ; Time Factors
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  • 75
    Publication Date: 2014-01-10
    Description: The human immunodeficiency virus (HIV)-1 protein Vif has a central role in the neutralization of host innate defences by hijacking cellular proteasomal degradation pathways to subvert the antiviral activity of host restriction factors; however, the underlying mechanism by which Vif achieves this remains unclear. Here we report a crystal structure of the Vif-CBF-beta-CUL5-ELOB-ELOC complex. The structure reveals that Vif, by means of two domains, organizes formation of the pentameric complex by interacting with CBF-beta, CUL5 and ELOC. The larger domain (alpha/beta domain) of Vif binds to the same side of CBF-beta as RUNX1, indicating that Vif and RUNX1 are exclusive for CBF-beta binding. Interactions of the smaller domain (alpha-domain) of Vif with ELOC and CUL5 are cooperative and mimic those of SOCS2 with the latter two proteins. A unique zinc-finger motif of Vif, which is located between the two Vif domains, makes no contacts with the other proteins but stabilizes the conformation of the alpha-domain, which may be important for Vif-CUL5 interaction. Together, our data reveal the structural basis for Vif hijacking of the CBF-beta and CUL5 E3 ligase complex, laying a foundation for rational design of novel anti-HIV drugs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guo, Yingying -- Dong, Liyong -- Qiu, Xiaolin -- Wang, Yishu -- Zhang, Bailing -- Liu, Hongnan -- Yu, You -- Zang, Yi -- Yang, Maojun -- Huang, Zhiwei -- England -- Nature. 2014 Jan 9;505(7482):229-33. doi: 10.1038/nature12884.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, China [2]. ; School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, China. ; MOE Key Laboratory of Protein Sciences, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24402281" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Core Binding Factor Alpha 2 Subunit/metabolism ; Core Binding Factor beta Subunit/*chemistry/*metabolism ; Crystallography, X-Ray ; Cullin Proteins/*chemistry/*metabolism ; Humans ; Models, Molecular ; Molecular Sequence Data ; Multiprotein Complexes/chemistry/metabolism ; Protein Binding ; Protein Stability ; Protein Structure, Tertiary ; Suppressor of Cytokine Signaling Proteins ; Transcription Factors/chemistry/metabolism ; vif Gene Products, Human Immunodeficiency Virus/*chemistry/*metabolism
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  • 76
    Publication Date: 2014-10-23
    Description: Morphogenesis is the process whereby cell collectives are shaped into differentiated tissues and organs. The self-organizing nature of morphogenesis has been recently demonstrated by studies showing that stem cells in three-dimensional culture can generate complex organoids, such as mini-guts, optic-cups and even mini-brains. To achieve this, cell collectives must regulate the activity of secreted signalling molecules that control cell differentiation, presumably through the self-assembly of microenvironments or niches. However, mechanisms that allow changes in tissue architecture to feedback directly on the activity of extracellular signals have not been described. Here we investigate how the process of tissue assembly controls signalling activity during organogenesis in vivo, using the migrating zebrafish lateral line primordium. We show that fibroblast growth factor (FGF) activity within the tissue controls the frequency at which it deposits rosette-like mechanosensory organs. Live imaging reveals that FGF becomes specifically concentrated in microluminal structures that assemble at the centre of these organs and spatially constrain its signalling activity. Genetic inhibition of microlumen assembly and laser micropuncture experiments demonstrate that microlumina increase signalling responses in participating cells, thus allowing FGF to coordinate the migratory behaviour of cell groups at the tissue rear. As the formation of a central lumen is a self-organizing property of many cell types, such as epithelia and embryonic stem cells, luminal signalling provides a potentially general mechanism to locally restrict, coordinate and enhance cell communication within tissues.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Durdu, Sevi -- Iskar, Murat -- Revenu, Celine -- Schieber, Nicole -- Kunze, Andreas -- Bork, Peer -- Schwab, Yannick -- Gilmour, Darren -- England -- Nature. 2014 Nov 6;515(7525):120-4. doi: 10.1038/nature13852. Epub 2014 Oct 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Molecular Biology Laboratory Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25337877" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Communication ; Cell Differentiation ; Cell Movement ; Dose-Response Relationship, Drug ; Extracellular Space/metabolism ; Fibroblast Growth Factors/metabolism/secretion ; *Organogenesis ; *Signal Transduction ; Time Factors ; Zebrafish/*embryology/metabolism
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  • 77
    Publication Date: 2014-07-22
    Description: Ubiquitination is a crucial cellular signalling process, and is controlled on multiple levels. Cullin-RING E3 ubiquitin ligases (CRLs) are regulated by the eight-subunit COP9 signalosome (CSN). CSN inactivates CRLs by removing their covalently attached activator, NEDD8. NEDD8 cleavage by CSN is catalysed by CSN5, a Zn(2+)-dependent isopeptidase that is inactive in isolation. Here we present the crystal structure of the entire approximately 350-kDa human CSN holoenzyme at 3.8 A resolution, detailing the molecular architecture of the complex. CSN has two organizational centres: a horseshoe-shaped ring created by its six proteasome lid-CSN-initiation factor 3 (PCI) domain proteins, and a large bundle formed by the carboxy-terminal alpha-helices of every subunit. CSN5 and its dimerization partner, CSN6, are intricately embedded at the core of the helical bundle. In the substrate-free holoenzyme, CSN5 is autoinhibited, which precludes access to the active site. We find that neddylated CRL binding to CSN is sensed by CSN4, and communicated to CSN5 with the assistance of CSN6, resulting in activation of the deneddylase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lingaraju, Gondichatnahalli M -- Bunker, Richard D -- Cavadini, Simone -- Hess, Daniel -- Hassiepen, Ulrich -- Renatus, Martin -- Fischer, Eric S -- Thoma, Nicolas H -- England -- Nature. 2014 Aug 14;512(7513):161-5. doi: 10.1038/nature13566. Epub 2014 Jul 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland [2] University of Basel, Petersplatz 10, 4003 Basel, Switzerland [3]. ; 1] Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland [2] University of Basel, Petersplatz 10, 4003 Basel, Switzerland. ; Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland. ; Novartis Pharma AG, Institutes for Biomedical Research, Novartis Campus, 4056 Basel, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043011" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Catalytic Domain ; Crystallography, X-Ray ; Enzyme Activation ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism ; *Models, Molecular ; Multiprotein Complexes/*chemistry ; Peptide Hydrolases/*chemistry/metabolism ; Protein Binding ; Protein Structure, Tertiary ; Transcription Factors/metabolism
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  • 78
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    Nature Publishing Group (NPG)
    Publication Date: 2014-06-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yong, Ed -- England -- Nature. 2014 Jun 26;510(7506):S5. doi: 10.1038/510S5a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24964025" target="_blank"〉PubMed〈/a〉
    Keywords: Humans ; *Mobile Health Units/economics ; Paralysis/etiology/prevention & control ; Stroke/complications/*physiopathology/*therapy ; Time Factors ; Tissue Plasminogen Activator/therapeutic use
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  • 79
    Publication Date: 2014-05-16
    Description: Metabolism and ageing are intimately linked. Compared with ad libitum feeding, dietary restriction consistently extends lifespan and delays age-related diseases in evolutionarily diverse organisms. Similar conditions of nutrient limitation and genetic or pharmacological perturbations of nutrient or energy metabolism also have longevity benefits. Recently, several metabolites have been identified that modulate ageing; however, the molecular mechanisms underlying this are largely undefined. Here we show that alpha-ketoglutarate (alpha-KG), a tricarboxylic acid cycle intermediate, extends the lifespan of adult Caenorhabditis elegans. ATP synthase subunit beta is identified as a novel binding protein of alpha-KG using a small-molecule target identification strategy termed drug affinity responsive target stability (DARTS). The ATP synthase, also known as complex V of the mitochondrial electron transport chain, is the main cellular energy-generating machinery and is highly conserved throughout evolution. Although complete loss of mitochondrial function is detrimental, partial suppression of the electron transport chain has been shown to extend C. elegans lifespan. We show that alpha-KG inhibits ATP synthase and, similar to ATP synthase knockdown, inhibition by alpha-KG leads to reduced ATP content, decreased oxygen consumption, and increased autophagy in both C. elegans and mammalian cells. We provide evidence that the lifespan increase by alpha-KG requires ATP synthase subunit beta and is dependent on target of rapamycin (TOR) downstream. Endogenous alpha-KG levels are increased on starvation and alpha-KG does not extend the lifespan of dietary-restricted animals, indicating that alpha-KG is a key metabolite that mediates longevity by dietary restriction. Our analyses uncover new molecular links between a common metabolite, a universal cellular energy generator and dietary restriction in the regulation of organismal lifespan, thus suggesting new strategies for the prevention and treatment of ageing and age-related diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263271/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263271/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chin, Randall M -- Fu, Xudong -- Pai, Melody Y -- Vergnes, Laurent -- Hwang, Heejun -- Deng, Gang -- Diep, Simon -- Lomenick, Brett -- Meli, Vijaykumar S -- Monsalve, Gabriela C -- Hu, Eileen -- Whelan, Stephen A -- Wang, Jennifer X -- Jung, Gwanghyun -- Solis, Gregory M -- Fazlollahi, Farbod -- Kaweeteerawat, Chitrada -- Quach, Austin -- Nili, Mahta -- Krall, Abby S -- Godwin, Hilary A -- Chang, Helena R -- Faull, Kym F -- Guo, Feng -- Jiang, Meisheng -- Trauger, Sunia A -- Saghatelian, Alan -- Braas, Daniel -- Christofk, Heather R -- Clarke, Catherine F -- Teitell, Michael A -- Petrascheck, Michael -- Reue, Karen -- Jung, Michael E -- Frand, Alison R -- Huang, Jing -- DP2 OD008398/OD/NIH HHS/ -- P01 HL028481/HL/NHLBI NIH HHS/ -- P40 OD010440/OD/NIH HHS/ -- T32 CA009120/CA/NCI NIH HHS/ -- T32 GM007104/GM/NIGMS NIH HHS/ -- T32 GM007185/GM/NIGMS NIH HHS/ -- T32 GM008496/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Jun 19;510(7505):397-401. doi: 10.1038/nature13264. Epub 2014 May 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biology Institute, University of California Los Angeles, Los Angeles, California 90095, USA. ; Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California 90095, USA. ; 1] Molecular Biology Institute, University of California Los Angeles, Los Angeles, California 90095, USA [2]. ; 1] Department of Human Genetics, University of California Los Angeles, Los Angeles, California 90095, USA [2]. ; 1] Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California 90095, USA [2]. ; Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, California 90095, USA. ; Department of Biological Chemistry, University of California Los Angeles, Los Angeles, California 90095, USA. ; Department of Surgery, University of California Los Angeles, Los Angeles, California 90095, USA. ; Small Molecule Mass Spectrometry Facility, FAS Division of Science, Harvard University, Cambridge, Massachusetts 02138, USA. ; Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037, USA. ; Pasarow Mass Spectrometry Laboratory, Department of Psychiatry and Biobehavioral Sciences and Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, California 90095, USA. ; Department of Environmental Health Sciences, University of California Los Angeles, Los Angeles, California 90095, USA. ; Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California 90095, USA. ; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA. ; 1] Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California 90095, USA [2] UCLA Metabolomics Center, University of California Los Angeles, Los Angeles, California 90095, USA. ; 1] Molecular Biology Institute, University of California Los Angeles, Los Angeles, California 90095, USA [2] Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, California 90095, USA. ; 1] Molecular Biology Institute, University of California Los Angeles, Los Angeles, California 90095, USA [2] Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California 90095, USA. ; 1] Molecular Biology Institute, University of California Los Angeles, Los Angeles, California 90095, USA [2] Department of Human Genetics, University of California Los Angeles, Los Angeles, California 90095, USA. ; 1] Molecular Biology Institute, University of California Los Angeles, Los Angeles, California 90095, USA [2] Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24828042" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/*drug effects ; Cell Line ; Enzyme Activation/drug effects ; Enzyme Inhibitors/pharmacology ; Gene Knockdown Techniques ; HEK293 Cells ; Humans ; Jurkat Cells ; Ketoglutaric Acids/*pharmacology ; Longevity/drug effects/genetics/*physiology ; Mice ; Mitochondrial Proton-Translocating ATPases/genetics/*metabolism ; Protein Binding ; TOR Serine-Threonine Kinases/*metabolism
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  • 80
    Publication Date: 2014-06-12
    Description: Cytosolic inflammasome complexes mediated by a pattern recognition receptor (PRR) defend against pathogen infection by activating caspase 1. Pyrin, a candidate PRR, can bind to the inflammasome adaptor ASC to form a caspase 1-activating complex. Mutations in the Pyrin-encoding gene, MEFV, cause a human autoinflammatory disease known as familial Mediterranean fever. Despite important roles in immunity and disease, the physiological function of Pyrin remains unknown. Here we show that Pyrin mediates caspase 1 inflammasome activation in response to Rho-glucosylation activity of cytotoxin TcdB, a major virulence factor of Clostridium difficile, which causes most cases of nosocomial diarrhoea. The glucosyltransferase-inactive TcdB mutant loses the inflammasome-stimulating activity. Other Rho-inactivating toxins, including FIC-domain adenylyltransferases (Vibrio parahaemolyticus VopS and Histophilus somni IbpA) and Clostridium botulinum ADP-ribosylating C3 toxin, can also biochemically activate the Pyrin inflammasome in their enzymatic activity-dependent manner. These toxins all target the Rho subfamily and modify a switch-I residue. We further demonstrate that Burkholderia cenocepacia inactivates RHOA by deamidating Asn 41, also in the switch-I region, and thereby triggers Pyrin inflammasome activation, both of which require the bacterial type VI secretion system (T6SS). Loss of the Pyrin inflammasome causes elevated intra-macrophage growth of B. cenocepacia and diminished lung inflammation in mice. Thus, Pyrin functions to sense pathogen modification and inactivation of Rho GTPases, representing a new paradigm in mammalian innate immunity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, Hao -- Yang, Jieling -- Gao, Wenqing -- Li, Lin -- Li, Peng -- Zhang, Li -- Gong, Yi-Nan -- Peng, Xiaolan -- Xi, Jianzhong Jeff -- Chen, She -- Wang, Fengchao -- Shao, Feng -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Sep 11;513(7517):237-41. doi: 10.1038/nature13449. Epub 2014 Jun 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] National Institute of Biological Sciences, Beijing 102206, China [2]. ; 1] National Institute of Biological Sciences, Beijing 102206, China [2] National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China [3]. ; National Institute of Biological Sciences, Beijing 102206, China. ; Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China. ; 1] National Institute of Biological Sciences, Beijing 102206, China [2] National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China [3] National Institute of Biological Sciences, Beijing, Collaborative Innovation Center for Cancer Medicine, Beijing 102206, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24919149" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Proteins/genetics/metabolism ; Bacterial Toxins/genetics/metabolism ; Burkholderia cenocepacia/metabolism ; Caspase 1/metabolism ; Cell Line ; Clostridium difficile/metabolism ; Cytoskeletal Proteins/genetics/*metabolism ; Humans ; Immunity, Innate/genetics/*immunology ; Inflammasomes/*metabolism ; Mice ; Mice, Inbred Strains ; Mutation ; Protein Binding ; Receptors, Pattern Recognition/metabolism ; U937 Cells ; rho GTP-Binding Proteins/*metabolism
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  • 81
    Publication Date: 2014-09-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Witze, Alexandra -- England -- Nature. 2014 Sep 4;513(7516):18. doi: 10.1038/513018a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25186881" target="_blank"〉PubMed〈/a〉
    Keywords: California ; *Disaster Planning/economics ; Disasters/prevention & control/*statistics & numerical data ; Earthquakes/mortality/*statistics & numerical data ; Forecasting/*methods ; Humans ; Oregon ; Time Factors ; Washington
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  • 82
    Publication Date: 2014-08-22
    Description: The timing of Neanderthal disappearance and the extent to which they overlapped with the earliest incoming anatomically modern humans (AMHs) in Eurasia are key questions in palaeoanthropology. Determining the spatiotemporal relationship between the two populations is crucial if we are to understand the processes, timing and reasons leading to the disappearance of Neanderthals and the likelihood of cultural and genetic exchange. Serious technical challenges, however, have hindered reliable dating of the period, as the radiocarbon method reaches its limit at approximately 50,000 years ago. Here we apply improved accelerator mass spectrometry (14)C techniques to construct robust chronologies from 40 key Mousterian and Neanderthal archaeological sites, ranging from Russia to Spain. Bayesian age modelling was used to generate probability distribution functions to determine the latest appearance date. We show that the Mousterian ended by 41,030-39,260 calibrated years bp (at 95.4% probability) across Europe. We also demonstrate that succeeding 'transitional' archaeological industries, one of which has been linked with Neanderthals (Chatelperronian), end at a similar time. Our data indicate that the disappearance of Neanderthals occurred at different times in different regions. Comparing the data with results obtained from the earliest dated AMH sites in Europe, associated with the Uluzzian technocomplex, allows us to quantify the temporal overlap between the two human groups. The results reveal a significant overlap of 2,600-5,400 years (at 95.4% probability). This has important implications for models seeking to explain the cultural, technological and biological elements involved in the replacement of Neanderthals by AMHs. A mosaic of populations in Europe during the Middle to Upper Palaeolithic transition suggests that there was ample time for the transmission of cultural and symbolic behaviours, as well as possible genetic exchanges, between the two groups.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Higham, Tom -- Douka, Katerina -- Wood, Rachel -- Ramsey, Christopher Bronk -- Brock, Fiona -- Basell, Laura -- Camps, Marta -- Arrizabalaga, Alvaro -- Baena, Javier -- Barroso-Ruiz, Cecillio -- Bergman, Christopher -- Boitard, Coralie -- Boscato, Paolo -- Caparros, Miguel -- Conard, Nicholas J -- Draily, Christelle -- Froment, Alain -- Galvan, Bertila -- Gambassini, Paolo -- Garcia-Moreno, Alejandro -- Grimaldi, Stefano -- Haesaerts, Paul -- Holt, Brigitte -- Iriarte-Chiapusso, Maria-Jose -- Jelinek, Arthur -- Jorda Pardo, Jesus F -- Maillo-Fernandez, Jose-Manuel -- Marom, Anat -- Maroto, Julia -- Menendez, Mario -- Metz, Laure -- Morin, Eugene -- Moroni, Adriana -- Negrino, Fabio -- Panagopoulou, Eleni -- Peresani, Marco -- Pirson, Stephane -- de la Rasilla, Marco -- Riel-Salvatore, Julien -- Ronchitelli, Annamaria -- Santamaria, David -- Semal, Patrick -- Slimak, Ludovic -- Soler, Joaquim -- Soler, Narcis -- Villaluenga, Aritza -- Pinhasi, Ron -- Jacobi, Roger -- England -- Nature. 2014 Aug 21;512(7514):306-9. doi: 10.1038/nature13621.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Oxford Radiocarbon Accelerator Unit, Research Laboratory for Archaeology &the History of Art, University of Oxford, Oxford OX1 3QY, UK. ; 1] Oxford Radiocarbon Accelerator Unit, Research Laboratory for Archaeology &the History of Art, University of Oxford, Oxford OX1 3QY, UK [2] Research School for Earth Sciences, Australian National University, Canberra 0200, Australia. ; School of Geography, Archaeology and Palaeoecology (GAP), Queen's University Belfast, Belfast BT7 1NN, UK. ; School of Languages, Literatures and Cultures, College Park, 4102 Jimenez Hall, University of Maryland, Maryland 20742-4821, USA. ; Research Team on Prehistory (IT-622-13), IKERBASQUE, University of the Basque Country (UPV-EHU), Tomas y Valiente Street, 01006 Vitoria-Gasteiz, Spain. ; Departimento Prehistoria y Arqueologia, Universidad Autonoma de Madrid, Campus Cantoblanco, 28049 Madrid, Spain. ; Fundacion Instituto de Investigacion de Prehistoria y Evolucion Humana, Plaza del Coso 1, 14900 Lucena, Cordoba, Spain. ; URS, 525 Vine Street, Suite 1800, Cincinnati, Ohio 45202, USA. ; 8 rue des Sapins, 67100 Strasbourg, France. ; Dipartimento di Scienze Fisiche, della Terra e dell'Ambiente, U.R. Preistoria e Antropologia, Universita degli Studi di Siena, Via Laterina 8, 53100 Siena, Italy. ; Departement de Prehistoire, Museum National d'Histoire Naturelle, 75013 Paris, France. ; 1] Abt. Altere Urgeschichte und Quartarokologie, Universitat Tubingen, Schloss Hohentubingen, 72070 Tubingen, Germany [2] Tubingen Senckenberg Center for Human Evolution and Paleoecology, Schloss Hohentubingen, 72070 Tubingen, Germany. ; Service public de Wallonie, DGO4, Service de l'Archeologie, rue des Martyrs, 22, B-6700 Arlon, Belgium. ; Laboratoire d'Eco-antropologie et Ethnobiologie, Musee de l'Homme, 17 place du Trocadero, 75116 Paris, France. ; Departamento de Prehistoria, Arqueologia, Antropologia e Historia Antigua, Universidad de La Laguna, Campus de Guajara, 38071 Tenerife, Spain. ; 1] Monrepos Archaeological Research Centre and Museum for Human Behavioural Evolution, Schloss Monrepos, D-56567 Neuwied, Germany [2] The Cantabria International Institute for Prehistoric Research (IIIPC), University of Cantabria, Avda. Los Castros, s/n. 39005 Santander, Spain. ; Laboratorio di Preistoria 'B. Bagolini', Dipartimento di Lettere e Filosofia, Universita degli Studi di Trento, via Tommaso Gar, 14 I-38122 Trento, Italy. ; Institut Royal des Sciences Naturelles de Belgique, rue Vautier 29, B-1000 Brussels, Belgium. ; Department of Anthropology, University of Massachusetts, 103 Machmer Hall, Amherst, Massachusetts 01003, USA. ; School of Anthropology, Emil W. Haury Building, University of Arizona, Tucson, Arizona 85721-0030, USA. ; Departamento de Prehistoria y Arqueologia, UNED. Paseo Senda del Rey 7, 20840, Madrid, Spain. ; 1] Oxford Radiocarbon Accelerator Unit, Research Laboratory for Archaeology &the History of Art, University of Oxford, Oxford OX1 3QY, UK [2] The Kimmel Center for Archaeological Science, Weizmann Institute of Science, Rehovot 76100, Israel. ; rea de Prehistoria, Universitat de Girona, pl. Ferrater Mora 1, 17071 Girona, Spain. ; CNRS, UMR 5608, TRACES, Toulouse Jean Jaures University, Maison de la Recherche, 5 Allees Antonio Machado, 31058 Toulouse, Cedex 9, France. ; Department of Anthropology, Trent University, Life and Health Sciences Building Block C, 2140 East Bank Drive, Peterborough, Ontario K9J 7B8, Canada. ; Dipartimento di Antichita, Filosofia e Storia, Universita di Genova, Via Balbi 2, Genova I-16126, Italy. ; Ephoreia of Paleoanthropology of Southern Greece, Ardittou 34B, Athens 11636, Greece. ; Universita di Ferrara, Dipartimento di Studi Umanistici, Sezione di Scienze Preistoriche e Antropologiche, Corso Ercole I d'Este 32, I-44100 Ferrara, Italy. ; Service public de Wallonie, DGO4, Direction de l'Archeologie, rue des Brigades d'Irlande, 1, B-5100 Jambes, Belgium. ; Departamento de Historia, Universidad de Oviedo, c/Teniente Alfonso Martinez, s/n, 33011 Oviedo, Spain. ; Departement d'Anthropologie, Universite de Montreal, C. P. 6128, Succursale Centre-ville, Montreal, Quebec H3T 1N8, Canada. ; Service of Scientific Heritage, Royal Belgian Institute of Natural Sciences, 1000 Brussels, Belgium. ; Monrepos Archaeological Research Centre and Museum for Human Behavioural Evolution, Schloss Monrepos, D-56567 Neuwied, Germany. ; UCD Earth Institute and School of Archaeology, University College Dublin, Belfield, Dublin 4, Ireland. ; 1] Department of Prehistory and Europe, Franks House, The British Museum, London N1 5QJ, UK [2] The Natural History Museum, Cromwell Road, London SW7 5BD, UK [3].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25143113" target="_blank"〉PubMed〈/a〉
    Keywords: Acculturation/*history ; Animals ; Bayes Theorem ; *Extinction, Biological ; *Geography ; History, Ancient ; Humans ; Mass Spectrometry ; *Neanderthals/genetics/physiology ; Radiometric Dating ; *Spatio-Temporal Analysis ; Time Factors ; Tool Use Behavior ; Uncertainty
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  • 83
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    Nature Publishing Group (NPG)
    Publication Date: 2014-04-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fortunato, Santo -- England -- Nature. 2014 Apr 10;508(7495):186. doi: 10.1038/508186a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Aalto University, Finland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24717507" target="_blank"〉PubMed〈/a〉
    Keywords: Age Factors ; Life Expectancy ; *Nobel Prize ; *Research Personnel ; Time Factors
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  • 84
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2014-04-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Anthes, Emily -- England -- Nature. 2014 Apr 3;508(7494):S16-7. doi: 10.1038/508S16a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24695330" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Aged ; Aging, Premature/*complications/etiology/pathology/*physiopathology ; Antipsychotic Agents/adverse effects ; Brain/pathology/physiopathology ; Cardiovascular Diseases/complications ; Confounding Factors (Epidemiology) ; Diabetes Mellitus, Type 2/complications ; Glucose Intolerance/complications ; Health Surveys ; Humans ; Longevity/drug effects ; Middle Aged ; Models, Biological ; Schizophrenia/*complications/drug therapy/pathology/*physiopathology ; Telomere/metabolism ; Time Factors
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  • 85
    Publication Date: 2014-09-26
    Description: In eukaryotic cells, post-translational histone modifications have an important role in gene regulation. Starting with early work on histone acetylation, a variety of residue-specific modifications have now been linked to RNA polymerase II (RNAP2) activity, but it remains unclear if these markers are active regulators of transcription or just passive byproducts. This is because studies have traditionally relied on fixed cell populations, meaning temporal resolution is limited to minutes at best, and correlated factors may not actually be present in the same cell at the same time. Complementary approaches are therefore needed to probe the dynamic interplay of histone modifications and RNAP2 with higher temporal resolution in single living cells. Here we address this problem by developing a system to track residue-specific histone modifications and RNAP2 phosphorylation in living cells by fluorescence microscopy. This increases temporal resolution to the tens-of-seconds range. Our single-cell analysis reveals histone H3 lysine-27 acetylation at a gene locus can alter downstream transcription kinetics by as much as 50%, affecting two temporally separate events. First acetylation enhances the search kinetics of transcriptional activators, and later the acetylation accelerates the transition of RNAP2 from initiation to elongation. Signatures of the latter can be found genome-wide using chromatin immunoprecipitation followed by sequencing. We argue that this regulation leads to a robust and potentially tunable transcriptional response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stasevich, Timothy J -- Hayashi-Takanaka, Yoko -- Sato, Yuko -- Maehara, Kazumitsu -- Ohkawa, Yasuyuki -- Sakata-Sogawa, Kumiko -- Tokunaga, Makio -- Nagase, Takahiro -- Nozaki, Naohito -- McNally, James G -- Kimura, Hiroshi -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Dec 11;516(7530):272-5. doi: 10.1038/nature13714. Epub 2014 Sep 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Graduate School of Frontier Biosciences, Osaka University, Osaka, 565-0871, Japan [2] Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523-1870, USA [3] Transcription Imaging Consortium, Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia 20147, USA. ; 1] Graduate School of Frontier Biosciences, Osaka University, Osaka, 565-0871, Japan [2] Japan Science and Technology Agency (JST), Core Research for Evolutional Science and Technology (CREST), Kawaguchi, Saitama, 332-0012, Japan [3] Department of Biological Sciences, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, 226-8501, Japan. ; 1] Graduate School of Frontier Biosciences, Osaka University, Osaka, 565-0871, Japan [2] Department of Biological Sciences, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, 226-8501, Japan. ; Department of Advanced Medical Initiatives, Faculty of Medicine, Kyushu University, Fukuoka, 812-8582, Japan. ; 1] Japan Science and Technology Agency (JST), Core Research for Evolutional Science and Technology (CREST), Kawaguchi, Saitama, 332-0012, Japan [2] Department of Advanced Medical Initiatives, Faculty of Medicine, Kyushu University, Fukuoka, 812-8582, Japan. ; 1] Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, 226-8501, Japan [2] RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, 230-0045, Japan. ; Department of Biotechnology Research, Kazusa DNA Research Institute, Chiba, 292-0818, Japan. ; Mab Institute Inc., Sapporo, 001-0021, Japan. ; 1] Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA [2] Institute for Soft Matter and Functional Materials, Helmholtz Zentrum Berlin, Berlin, 14109, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25252976" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Animals ; Cell Line, Tumor ; Cell Survival ; Chromatin Immunoprecipitation ; Enzyme Activation ; Genome/genetics ; Histones/*chemistry/*metabolism ; Kinetics ; Lysine/metabolism ; Mice ; Microscopy, Fluorescence ; Phosphorylation ; RNA Polymerase II/*metabolism ; *Single-Cell Analysis ; Time Factors ; Transcription Elongation, Genetic ; Transcription Initiation, Genetic ; *Transcription, Genetic
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  • 86
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    Nature Publishing Group (NPG)
    Publication Date: 2014-05-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reardon, Sara -- England -- Nature. 2014 May 1;509(7498):22-4. doi: 10.1038/509022a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24784198" target="_blank"〉PubMed〈/a〉
    Keywords: Centers for Disease Control and Prevention (U.S.) ; DNA, Viral/analysis/isolation & purification ; *Disease Eradication/statistics & numerical data ; Evolution, Molecular ; Female ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; Humans ; Male ; Mummies/*virology ; Smallpox/epidemiology/*history/transmission/*virology ; Smallpox Vaccine/history ; Time Factors ; United States ; Variola virus/genetics/*isolation & purification
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  • 87
    Publication Date: 2014-09-19
    Description: To repair double-strand DNA breaks by homologous recombination, the 5'-terminated DNA strand must first be resected, which generates 3' single-stranded DNA overhangs. Genetic evidence suggests that this process is initiated by the Mre11-Rad50-Xrs2 (MRX) complex. However, its involvement was puzzling, as the complex possesses exonuclease activity with the opposite (3' to 5') polarity from that required for homologous recombination. Consequently, a bidirectional model has been proposed whereby dsDNA is first incised endonucleolytically and MRX then proceeds back to the dsDNA end using its 3' to 5' exonuclease. The endonuclease creates entry sites for Sgs1-Dna2 and/or Exo1, which then carry out long-range resection in the 5' to 3' direction. However, the identity of the endonuclease remained unclear. Using purified Saccharomyces cerevisiae proteins, we show that Sae2 promotes dsDNA-specific endonuclease activity by the Mre11 subunit within the MRX complex. The endonuclease preferentially cleaves the 5'-terminated dsDNA strand, which explains the polarity paradox. The dsDNA end clipping is strongly stimulated by protein blocks at the DNA end, and requires the ATPase activity of Rad50 and physical interactions between MRX and Sae2. Our results suggest that MRX initiates dsDNA break processing by dsDNA endonuclease rather than exonuclease activity, and that Sae2 is the key regulator of this process. These findings demonstrate a probable mechanism for the initiation of dsDNA break processing in both vegetative and meiotic cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cannavo, Elda -- Cejka, Petr -- England -- Nature. 2014 Oct 2;514(7520):122-5. doi: 10.1038/nature13771. Epub 2014 Sep 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Cancer Research, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25231868" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/metabolism ; *DNA Breaks, Double-Stranded ; DNA, Fungal/metabolism ; DNA-Binding Proteins/*metabolism ; Endodeoxyribonucleases/*metabolism ; Endonucleases/*metabolism ; Exodeoxyribonucleases/*metabolism ; *Homologous Recombination ; Meiosis ; Multiprotein Complexes/chemistry/metabolism ; Protein Binding ; Protein Subunits/metabolism ; Saccharomyces cerevisiae/*enzymology/genetics ; Saccharomyces cerevisiae Proteins/*metabolism
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  • 88
    Publication Date: 2014-01-24
    Description: In recent decades, Antarctica has experienced pronounced climate changes. The Antarctic Peninsula exhibited the strongest warming of any region on the planet, causing rapid changes in land ice. Additionally, in contrast to the sea-ice decline over the Arctic, Antarctic sea ice has not declined, but has instead undergone a perplexing redistribution. Antarctic climate is influenced by, among other factors, changes in radiative forcing and remote Pacific climate variability, but none explains the observed Antarctic Peninsula warming or the sea-ice redistribution in austral winter. However, in the north and tropical Atlantic Ocean, the Atlantic Multidecadal Oscillation (a leading mode of sea surface temperature variability) has been overlooked in this context. Here we show that sea surface warming related to the Atlantic Multidecadal Oscillation reduces the surface pressure in the Amundsen Sea and contributes to the observed dipole-like sea-ice redistribution between the Ross and Amundsen-Bellingshausen-Weddell seas and to the Antarctic Peninsula warming. Support for these findings comes from analysis of observational and reanalysis data, and independently from both comprehensive and idealized atmospheric model simulations. We suggest that the north and tropical Atlantic is important for projections of future climate change in Antarctica, and has the potential to affect the global thermohaline circulation and sea-level change.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Xichen -- Holland, David M -- Gerber, Edwin P -- Yoo, Changhyun -- England -- Nature. 2014 Jan 23;505(7484):538-42. doi: 10.1038/nature12945.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Courant Institute of Mathematical Sciences, New York University, 251 Mercer Street, New York, New York 10012, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24451542" target="_blank"〉PubMed〈/a〉
    Keywords: Antarctic Regions ; Atlantic Ocean ; Computer Simulation ; Global Warming ; *Ice Cover ; Models, Theoretical ; Pacific Ocean ; Pressure ; Seasons ; Seawater/*chemistry ; Temperature ; Time Factors ; *Tropical Climate
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  • 89
    Publication Date: 2014-11-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wolchok, Jedd D -- Chan, Timothy A -- P30 CA008748/CA/NCI NIH HHS/ -- England -- Nature. 2014 Nov 27;515(7528):496-8. doi: 10.1038/515496a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine and the Ludwig Center, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA. ; Department of Radiation Oncology and the Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25428495" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal/*therapeutic use ; Antineoplastic Agents/*therapeutic use ; Gene Expression Regulation, Neoplastic ; Humans ; *Immunotherapy ; Neoplasms/*therapy ; Programmed Cell Death 1 Receptor/genetics/metabolism ; Protein Binding
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  • 90
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2014-10-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Birkhead, Tim -- England -- Nature. 2014 Oct 23;514(7523):405. doi: 10.1038/514405a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Sheffield, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25341754" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Charadriiformes/*physiology ; Climate Change ; Conservation of Natural Resources/economics/trends ; Ecology/*economics/*trends ; Population Dynamics ; Research Support as Topic/*trends ; Time Factors
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  • 91
    Publication Date: 2014-01-10
    Description: The emergence of jawed vertebrates (gnathostomes) from jawless vertebrates was accompanied by major morphological and physiological innovations, such as hinged jaws, paired fins and immunoglobulin-based adaptive immunity. Gnathostomes subsequently diverged into two groups, the cartilaginous fishes and the bony vertebrates. Here we report the whole-genome analysis of a cartilaginous fish, the elephant shark (Callorhinchus milii). We find that the C. milii genome is the slowest evolving of all known vertebrates, including the 'living fossil' coelacanth, and features extensive synteny conservation with tetrapod genomes, making it a good model for comparative analyses of gnathostome genomes. Our functional studies suggest that the lack of genes encoding secreted calcium-binding phosphoproteins in cartilaginous fishes explains the absence of bone in their endoskeleton. Furthermore, the adaptive immune system of cartilaginous fishes is unusual: it lacks the canonical CD4 co-receptor and most transcription factors, cytokines and cytokine receptors related to the CD4 lineage, despite the presence of polymorphic major histocompatibility complex class II molecules. It thus presents a new model for understanding the origin of adaptive immunity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964593/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964593/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Venkatesh, Byrappa -- Lee, Alison P -- Ravi, Vydianathan -- Maurya, Ashish K -- Lian, Michelle M -- Swann, Jeremy B -- Ohta, Yuko -- Flajnik, Martin F -- Sutoh, Yoichi -- Kasahara, Masanori -- Hoon, Shawn -- Gangu, Vamshidhar -- Roy, Scott W -- Irimia, Manuel -- Korzh, Vladimir -- Kondrychyn, Igor -- Lim, Zhi Wei -- Tay, Boon-Hui -- Tohari, Sumanty -- Kong, Kiat Whye -- Ho, Shufen -- Lorente-Galdos, Belen -- Quilez, Javier -- Marques-Bonet, Tomas -- Raney, Brian J -- Ingham, Philip W -- Tay, Alice -- Hillier, LaDeana W -- Minx, Patrick -- Boehm, Thomas -- Wilson, Richard K -- Brenner, Sydney -- Warren, Wesley C -- AI27877/AI/NIAID NIH HHS/ -- R01 AI027877/AI/NIAID NIH HHS/ -- R01 OD010549/OD/NIH HHS/ -- RR006603/RR/NCRR NIH HHS/ -- U41 HG002371/HG/NHGRI NIH HHS/ -- U54 HG003079/HG/NHGRI NIH HHS/ -- England -- Nature. 2014 Jan 9;505(7482):174-9. doi: 10.1038/nature12826.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Comparative Genomics Laboratory, Institute of Molecular and Cell Biology, A*STAR, Biopolis, Singapore 138673 [2] Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228. ; Comparative Genomics Laboratory, Institute of Molecular and Cell Biology, A*STAR, Biopolis, Singapore 138673. ; Developmental and Biomedical Genetics Laboratory, Institute of Molecular and Cell Biology, A*STAR, Biopolis, Singapore 138673. ; Department of Developmental Immunology, Max-Planck-Institute of Immunobiology and Epigenetics, Stuebeweg 51, 79108 Freiburg, Germany. ; Department of Microbiology and Immunology, University of Maryland, Baltimore, Maryland 21201, USA. ; Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan. ; Molecular Engineering Laboratory, Biomedical Sciences Institutes, A*STAR, Biopolis, Singapore 138673. ; Department of Biology, San Francisco State University, San Francisco, California 94132, USA. ; Banting and Best Department of Medical Research and Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada. ; Fish Developmental Biology Laboratory, Institute of Molecular and Cell Biology, A*STAR, Biopolis, Singapore 138673. ; 1] Institut de Biologia Evolutiva (UPF-CSIC), PRBB, 08003 Barcelona, Spain [2] Institucio Catalana de Recerca i Estudis Avancats (ICREA), 08010 Barcelona, Catalonia, Spain. ; Center for Biomolecular Science and Engineering, School of Engineering, University of California Santa Cruz, Santa Cruz, California 95064, USA. ; The Genome Institute at Washington University, St Louis, Missouri 63108, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24402279" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/metabolism ; Cell Lineage/immunology ; *Evolution, Molecular ; Fish Proteins/classification/genetics ; Gene Deletion ; Genome/*genetics ; Genomics ; Immunity, Cellular/genetics ; Molecular Sequence Annotation ; Molecular Sequence Data ; Osteogenesis/genetics ; Phosphoproteins/genetics/metabolism ; Phylogeny ; Protein Structure, Tertiary/genetics ; Sharks/*genetics/immunology ; T-Lymphocytes/cytology/immunology ; Time Factors ; Vertebrates/classification/genetics ; Zebrafish/genetics/growth & development
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  • 92
    Publication Date: 2014-03-05
    Description: Ubiquitin (Ub) has important roles in a wide range of intracellular signalling pathways. In the conventional view, ubiquitin alters the signalling activity of the target protein through covalent modification, but accumulating evidence points to the emerging role of non-covalent interaction between ubiquitin and the target. In the innate immune signalling pathway of a viral RNA sensor, RIG-I, both covalent and non-covalent interactions with K63-linked ubiquitin chains (K63-Ubn) were shown to occur in its signalling domain, a tandem caspase activation and recruitment domain (hereafter referred to as 2CARD). Non-covalent binding of K63-Ubn to 2CARD induces its tetramer formation, a requirement for downstream signal activation. Here we report the crystal structure of the tetramer of human RIG-I 2CARD bound by three chains of K63-Ub2. 2CARD assembles into a helical tetramer resembling a 'lock-washer', in which the tetrameric surface serves as a signalling platform for recruitment and activation of the downstream signalling molecule, MAVS. Ubiquitin chains are bound along the outer rim of the helical trajectory, bridging adjacent subunits of 2CARD and stabilizing the 2CARD tetramer. The combination of structural and functional analyses reveals that binding avidity dictates the K63-linkage and chain-length specificity of 2CARD, and that covalent ubiquitin conjugation of 2CARD further stabilizes the Ub-2CARD interaction and thus the 2CARD tetramer. Our work provides unique insights into the novel types of ubiquitin-mediated signal-activation mechanism, and previously unexpected synergism between the covalent and non-covalent ubiquitin interaction modes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Peisley, Alys -- Wu, Bin -- Xu, Hui -- Chen, Zhijian J -- Hur, Sun -- R01-GM63692/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 May 1;509(7498):110-4. doi: 10.1038/nature13140. Epub 2014 Mar 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115 USA [2] Program in Cellular and Molecular Medicine, Children's Hospital Boston, Boston, Massachusetts 02115, USA. ; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. ; 1] Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA [2] Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24590070" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/chemistry/metabolism ; Caspases/metabolism ; Crystallography, X-Ray ; DEAD-box RNA Helicases/*chemistry/*metabolism ; Humans ; Models, Molecular ; Protein Binding ; Protein Multimerization ; Protein Stability ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; Protein Subunits/chemistry/metabolism ; RNA, Viral/analysis/metabolism ; Signal Transduction ; Structure-Activity Relationship ; Substrate Specificity ; Ubiquitin/*chemistry/*metabolism
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  • 93
    Publication Date: 2014-07-22
    Description: The great therapeutic achievements of antibiotics have been dramatically undercut by the evolution of bacterial strategies that overcome antibiotic stress. These strategies fall into two classes. 'Resistance' makes it possible for a microorganism to grow in the constant presence of the antibiotic, provided that the concentration of the antibiotic is not too high. 'Tolerance' allows a microorganism to survive antibiotic treatment, even at high antibiotic concentrations, as long as the duration of the treatment is limited. Although both resistance and tolerance are important reasons for the failure of antibiotic treatments, the evolution of resistance is much better understood than that of tolerance. Here we followed the evolution of bacterial populations under intermittent exposure to the high concentrations of antibiotics used in the clinic and characterized the evolved strains in terms of both resistance and tolerance. We found that all strains adapted by specific genetic mutations, which became fixed in the evolved populations. By monitoring the phenotypic changes at the population and single-cell levels, we found that the first adaptive change to antibiotic stress was the development of tolerance through a major adjustment in the single-cell lag-time distribution, without a change in resistance. Strikingly, we found that the lag time of bacteria before regrowth was optimized to match the duration of the antibiotic-exposure interval. Whole genome sequencing of the evolved strains and restoration of the wild-type alleles allowed us to identify target genes involved in this antibiotic-driven phenotype: 'tolerance by lag' (tbl). Better understanding of lag-time evolution as a key determinant of the survival of bacterial populations under high antibiotic concentrations could lead to new approaches to impeding the evolution of antibiotic resistance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fridman, Ofer -- Goldberg, Amir -- Ronin, Irine -- Shoresh, Noam -- Balaban, Nathalie Q -- England -- Nature. 2014 Sep 18;513(7518):418-21. doi: 10.1038/nature13469. Epub 2014 Jun 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Racah Institute of Physics, The Sudarsky Center for Computational Biology and the Center for NanoScience, Edmond J. Safra Campus, The Hebrew University, Jerusalem 91904, Israel. ; Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043002" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Ampicillin/*pharmacology ; Anti-Bacterial Agents/*pharmacology ; Drug Resistance, Bacterial/drug effects ; *Drug Tolerance ; Escherichia coli/cytology/*drug effects/growth & development ; Phenotype ; Time Factors
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  • 94
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2014-03-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cyranoski, David -- England -- Nature. 2014 Mar 6;507(7490):16-7. doi: 10.1038/507016a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24598617" target="_blank"〉PubMed〈/a〉
    Keywords: *Fukushima Nuclear Accident ; Japan ; Nuclear Energy/economics/*statistics & numerical data ; Radioactive Hazard Release/*prevention & control ; Renewable Energy/economics/*statistics & numerical data ; Time Factors
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  • 95
    Publication Date: 2014-12-24
    Description: Intrinsically disordered proteins play important roles in cell signalling, transcription, translation and cell cycle regulation. Although they lack stable tertiary structure, many intrinsically disordered proteins undergo disorder-to-order transitions upon binding to partners. Similarly, several folded proteins use regulated order-to-disorder transitions to mediate biological function. In principle, the function of intrinsically disordered proteins may be controlled by post-translational modifications that lead to structural changes such as folding, although this has not been observed. Here we show that multisite phosphorylation induces folding of the intrinsically disordered 4E-BP2, the major neural isoform of the family of three mammalian proteins that bind eIF4E and suppress cap-dependent translation initiation. In its non-phosphorylated state, 4E-BP2 interacts tightly with eIF4E using both a canonical YXXXXLPhi motif (starting at Y54) that undergoes a disorder-to-helix transition upon binding and a dynamic secondary binding site. We demonstrate that phosphorylation at T37 and T46 induces folding of residues P18-R62 of 4E-BP2 into a four-stranded beta-domain that sequesters the helical YXXXXLPhi motif into a partly buried beta-strand, blocking its accessibility to eIF4E. The folded state of pT37pT46 4E-BP2 is weakly stable, decreasing affinity by 100-fold and leading to an order-to-disorder transition upon binding to eIF4E, whereas fully phosphorylated 4E-BP2 is more stable, decreasing affinity by a factor of approximately 4,000. These results highlight stabilization of a phosphorylation-induced fold as the essential mechanism for phospho-regulation of the 4E-BP:eIF4E interaction and exemplify a new mode of biological regulation mediated by intrinsically disordered proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bah, Alaji -- Vernon, Robert M -- Siddiqui, Zeba -- Krzeminski, Mickael -- Muhandiram, Ranjith -- Zhao, Charlie -- Sonenberg, Nahum -- Kay, Lewis E -- Forman-Kay, Julie D -- MOP-114985/Canadian Institutes of Health Research/Canada -- MOP-119579/Canadian Institutes of Health Research/Canada -- England -- Nature. 2015 Mar 5;519(7541):106-9. doi: 10.1038/nature13999. Epub 2014 Dec 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Molecular Structure and Function Program, Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada [2] Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; Molecular Structure and Function Program, Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada. ; 1] Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada [2] Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec H3G 1Y6, Canada. ; 1] Molecular Structure and Function Program, Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada [2] Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada [3] Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada [4] Department of Chemistry, University of Toronto, Toronto, Ontario M5S 3H6, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25533957" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Eukaryotic Initiation Factor-4E/*chemistry/*metabolism ; Eukaryotic Initiation Factors/*chemistry/*metabolism ; Humans ; Intrinsically Disordered Proteins/*chemistry/*metabolism ; Models, Molecular ; Nuclear Magnetic Resonance, Biomolecular ; Phosphorylation ; Protein Binding ; *Protein Folding ; Protein Structure, Secondary ; Signal Transduction
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  • 96
    Publication Date: 2014-02-28
    Description: The seasonal human influenza A/H3N2 virus undergoes rapid evolution, which produces significant year-to-year sequence turnover in the population of circulating strains. Adaptive mutations respond to human immune challenge and occur primarily in antigenic epitopes, the antibody-binding domains of the viral surface protein haemagglutinin. Here we develop a fitness model for haemagglutinin that predicts the evolution of the viral population from one year to the next. Two factors are shown to determine the fitness of a strain: adaptive epitope changes and deleterious mutations outside the epitopes. We infer both fitness components for the strains circulating in a given year, using population-genetic data of all previous strains. From fitness and frequency of each strain, we predict the frequency of its descendent strains in the following year. This fitness model maps the adaptive history of influenza A and suggests a principled method for vaccine selection. Our results call for a more comprehensive epidemiology of influenza and other fast-evolving pathogens that integrates antigenic phenotypes with other viral functions coupled by genetic linkage.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Luksza, Marta -- Lassig, Michael -- England -- Nature. 2014 Mar 6;507(7490):57-61. doi: 10.1038/nature13087. Epub 2014 Feb 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Institute for Theoretical Physics, University of Cologne, Zulpicher Strasse 77, 50937 Koln, Germany [2] Biological Sciences, Columbia University, 607D Fairchild Center, New York, New York 10027, USA. ; Institute for Theoretical Physics, University of Cologne, Zulpicher Strasse 77, 50937 Koln, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24572367" target="_blank"〉PubMed〈/a〉
    Keywords: Computer Simulation ; Epitopes/genetics/immunology ; *Evolution, Molecular ; Genes, Viral/genetics ; Genetic Fitness/genetics/immunology/physiology ; Genetics, Population ; Hemagglutinin Glycoproteins, Influenza Virus/chemistry/*genetics/*immunology ; Humans ; Influenza A Virus, H3N2 Subtype/chemistry/classification/*genetics/immunology ; Influenza Vaccines/chemistry/genetics/*immunology ; Influenza, Human/epidemiology/immunology/*virology ; Models, Immunological ; Mutation/genetics ; Time Factors
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 97
    Publication Date: 2014-10-16
    Description: In experimental plant communities, relationships between biodiversity and ecosystem functioning have been found to strengthen over time, a fact often attributed to increased resource complementarity between species in mixtures and negative plant-soil feedbacks in monocultures. Here we show that selection for niche differentiation between species can drive this increasing biodiversity effect. Growing 12 grassland species in test monocultures and mixtures, we found character displacement between species and increased biodiversity effects when plants had been selected over 8 years in species mixtures rather than in monocultures. When grown in mixtures, relative differences in height and specific leaf area between plant species selected in mixtures (mixture types) were greater than between species selected in monocultures (monoculture types). Furthermore, net biodiversity and complementarity effects were greater in mixtures of mixture types than in mixtures of monoculture types. Our study demonstrates a novel mechanism for the increase in biodiversity effects: selection for increased niche differentiation through character displacement. Selection in diverse mixtures may therefore increase species coexistence and ecosystem functioning in natural communities and may also allow increased mixture yields in agriculture or forestry. However, loss of biodiversity and prolonged selection of crops in monoculture may compromise this potential for selection in the longer term.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zuppinger-Dingley, Debra -- Schmid, Bernhard -- Petermann, Jana S -- Yadav, Varuna -- De Deyn, Gerlinde B -- Flynn, Dan F B -- England -- Nature. 2014 Nov 6;515(7525):108-11. doi: 10.1038/nature13869. Epub 2014 Oct 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Evolutionary Biology and Environmental Studies &Zurich-Basel Plant Science Center, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. ; 1] Institute of Biology, Freie Universitat Berlin, Konigin-Luise-Str. 1-3, 14195 Berlin, Germany [2] Berlin-Brandenburg Institute of Advanced Biodiversity Research (BBIB), 14195 Berlin, Germany. ; Environmental Sciences, University of Wageningen, Droevendaalsesteeg 4, 6708PB Wageningen, the Netherlands. ; 1] Institute of Evolutionary Biology and Environmental Studies &Zurich-Basel Plant Science Center, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland [2] Arnold Arboretum, Harvard University, Boston, Massachusetts 02131, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25317555" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptation, Biological ; Asteraceae/physiology ; *Biodiversity ; Biological Evolution ; Biomass ; Fabaceae/physiology ; *Plant Physiological Phenomena ; Poaceae/physiology ; Selection, Genetic ; Time Factors
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  • 98
    Publication Date: 2014-04-04
    Description: An interhemispheric hydrologic seesaw--in which latitudinal migrations of the Intertropical Convergence Zone (ITCZ) produce simultaneous wetting (increased precipitation) in one hemisphere and drying in the other--has been discovered in some tropical and subtropical regions. For instance, Chinese and Brazilian subtropical speleothem (cave formations such as stalactites and stalagmites) records show opposite trends in time series of oxygen isotopes (a proxy for precipitation variability) at millennial to orbital timescales, suggesting that hydrologic cycles were antiphased in the northerly versus southerly subtropics. This tropical to subtropical hydrologic phenomenon is likely to be an initial and important climatic response to orbital forcing. The impacts of such an interhemispheric hydrologic seesaw on higher-latitude regions and the global climate system, however, are unknown. Here we show that the antiphasing seen in the tropical records is also present in both hemispheres of the mid-latitude western Pacific Ocean. Our results are based on a new 550,000-year record of the growth frequency of speleothems from the Korean peninsula, which we compare to Southern Hemisphere equivalents. The Korean data are discontinuous and derived from 24 separate speleothems, but still allow the identification of periods of peak speleothem growth and, thus, precipitation. The clear hemispheric antiphasing indicates that the sphere of influence of the interhemispheric hydrologic seesaw over the past 550,000 years extended at least to the mid-latitudes, such as northeast Asia, and that orbital-timescale ITCZ shifts can have serious effects on temperate climate systems. Furthermore, our result implies that insolation-driven ITCZ dynamics may provoke water vapour and vegetation feedbacks in northern mid-latitude regions and could have regulated global climate conditions throughout the late Quaternary ice age cycles.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jo, Kyoung-nam -- Woo, Kyung Sik -- Yi, Sangheon -- Yang, Dong Yoon -- Lim, Hyoun Soo -- Wang, Yongjin -- Cheng, Hai -- Edwards, R Lawrence -- England -- Nature. 2014 Apr 17;508(7496):378-82. doi: 10.1038/nature13076. Epub 2014 Mar 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Korea Institute of Geoscience and Mineral Resources, Daejeon 305-350, South Korea. ; Department of Geology, Kangwon National University, Gangwondo 200-701, South Korea. ; Department of Geological Sciences, Pusan National University, Busan 609-735, South Korea. ; College of Geography Science, Nanjing Normal University, Nanjing 210097, China. ; 1] Institute of Global Environmental Change, Xi'an Jiaotong University, Xi'an 710049, China [2] Department of Geology and Geophysics, University of Minnesota, Minneapolis, Minnesota 55455, USA. ; Department of Geology and Geophysics, University of Minnesota, Minneapolis, Minnesota 55455, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24695222" target="_blank"〉PubMed〈/a〉
    Keywords: *Climate ; History, Ancient ; *Hydrology ; Ice Cover ; Korea ; Pacific Ocean ; Rain ; Time Factors ; Tropical Climate
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  • 99
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2014-06-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2014 Jun 5;510(7503):7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24910865" target="_blank"〉PubMed〈/a〉
    Keywords: Biotechnology/economics ; Diffusion of Innovation ; Drug Industry/economics ; *Federal Government ; Inventions/*economics/*legislation & jurisprudence ; Patents as Topic/*ethics/*legislation & jurisprudence ; Proteomics/economics ; Research/economics ; Time Factors ; United States ; Universities/economics
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  • 100
    Publication Date: 2014-04-11
    Description: One promise of synthetic biology is the creation of genetic circuitry that enables the execution of logical programming in living cells. Such 'wet programming' is positioned to transform a wide and diverse swathe of biotechnology ranging from therapeutics and diagnostics to water treatment strategies. Although progress in the development of a library of genetic modules continues apace, a major challenge for their integration into larger circuits is the generation of sufficiently fast and precise communication between modules. An attractive approach is to integrate engineered circuits with host processes that facilitate robust cellular signalling. In this context, recent studies have demonstrated that bacterial protein degradation can trigger a precise response to stress by overloading a limited supply of intracellular proteases. Here we use protease competition to engineer rapid and tunable coupling of genetic circuits across multiple spatial and temporal scales. We characterize coupling delay times that are more than an order of magnitude faster than standard transcription-factor-based coupling methods (less than 1 min compared with approximately 20-40 min) and demonstrate tunability through manipulation of the linker between the protein and its degradation tag. We use this mechanism as a platform to couple genetic clocks at the intracellular and colony level, then synchronize the multi-colony dynamics to reduce variability in both clocks. We show how the coupled clock network can be used to encode independent environmental inputs into a single time series output, thus enabling frequency multiplexing (information transmitted on a common channel by distinct frequencies) in a genetic circuit context. Our results establish a general framework for the rapid and tunable coupling of genetic circuits through the use of native 'queueing' processes such as competitive protein degradation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142690/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142690/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Prindle, Arthur -- Selimkhanov, Jangir -- Li, Howard -- Razinkov, Ivan -- Tsimring, Lev S -- Hasty, Jeff -- P50 GM085764/GM/NIGMS NIH HHS/ -- R01 GM069811/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Apr 17;508(7496):387-91. doi: 10.1038/nature13238. Epub 2014 Apr 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Bioengineering, University of California, San Diego, La Jolla, California 92093, USA [2]. ; Department of Bioengineering, University of California, San Diego, La Jolla, California 92093, USA. ; BioCircuits Institute, University of California, San Diego, La Jolla, California 92093, USA. ; 1] Department of Bioengineering, University of California, San Diego, La Jolla, California 92093, USA [2] BioCircuits Institute, University of California, San Diego, La Jolla, California 92093, USA [3] Molecular Biology Section, Division of Biological Science, University of California, San Diego, La Jolla, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24717442" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/genetics/metabolism ; Biological Clocks/genetics ; *Gene Regulatory Networks ; Peptide Hydrolases/metabolism ; *Protein Biosynthesis ; *Proteolysis ; Signal Transduction ; Synthetic Biology ; Time Factors ; Transcription Factors/metabolism ; Transcription, Genetic
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