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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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  • 2
    Publication Date: 2014-10-09
    Description: The human immunodeficiency virus type 1 (HIV-1) envelope (Env) spike, comprising three gp120 and three gp41 subunits, is a conformational machine that facilitates HIV-1 entry by rearranging from a mature unliganded state, through receptor-bound intermediates, to a post-fusion state. As the sole viral antigen on the HIV-1 virion surface, Env is both the target of neutralizing antibodies and a focus of vaccine efforts. Here we report the structure at 3.5 A resolution for an HIV-1 Env trimer captured in a mature closed state by antibodies PGT122 and 35O22. This structure reveals the pre-fusion conformation of gp41, indicates rearrangements needed for fusion activation, and defines parameters of immune evasion and immune recognition. Pre-fusion gp41 encircles amino- and carboxy-terminal strands of gp120 with four helices that form a membrane-proximal collar, fastened by insertion of a fusion peptide-proximal methionine into a gp41-tryptophan clasp. Spike rearrangements required for entry involve opening the clasp and expelling the termini. N-linked glycosylation and sequence-variable regions cover the pre-fusion closed spike; we used chronic cohorts to map the prevalence and location of effective HIV-1-neutralizing responses, which were distinguished by their recognition of N-linked glycan and tolerance for epitope-sequence variation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4348022/" 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/PMC4348022/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pancera, Marie -- Zhou, Tongqing -- Druz, Aliaksandr -- Georgiev, Ivelin S -- Soto, Cinque -- Gorman, Jason -- Huang, Jinghe -- Acharya, Priyamvada -- Chuang, Gwo-Yu -- Ofek, Gilad -- Stewart-Jones, Guillaume B E -- Stuckey, Jonathan -- Bailer, Robert T -- Joyce, M Gordon -- Louder, Mark K -- Tumba, Nancy -- Yang, Yongping -- Zhang, Baoshan -- Cohen, Myron S -- Haynes, Barton F -- Mascola, John R -- Morris, Lynn -- Munro, James B -- Blanchard, Scott C -- Mothes, Walther -- Connors, Mark -- Kwong, Peter D -- AI0678501/AI/NIAID NIH HHS/ -- AI100645/AI/NIAID NIH HHS/ -- P01 GM056550/GM/NIGMS NIH HHS/ -- P01-GM56550/GM/NIGMS NIH HHS/ -- P30 AI050410/AI/NIAID NIH HHS/ -- R01 GM098859/GM/NIGMS NIH HHS/ -- R01-GM098859/GM/NIGMS NIH HHS/ -- R21 AI100696/AI/NIAID NIH HHS/ -- R21-AI100696/AI/NIAID NIH HHS/ -- UL1 TR000142/TR/NCATS NIH HHS/ -- UM1 AI100645/AI/NIAID NIH HHS/ -- ZIA AI005023-13/Intramural NIH HHS/ -- ZIA AI005024-13/Intramural NIH HHS/ -- England -- Nature. 2014 Oct 23;514(7523):455-61. doi: 10.1038/nature13808. Epub 2014 Oct 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ; HIV-Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Center for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS), Sandringham, Johannesburg 2131, South Africa. ; Departments of Medicine, Epidemiology, Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. ; Duke University Human Vaccine Institute, Departments of Medicine, Surgery, Pediatrics and Immunology, Duke University School of Medicine, and the Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham, North Carolina 27710, USA. ; 1] Center for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS), Sandringham, Johannesburg 2131, South Africa [2] University of the Witwatersrand, Braamfontein, Johannesburg 2000, South Africa [3] Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban 4041, South Africa. ; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut 06536, USA. ; Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, New York, New York 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25296255" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/chemistry/immunology ; Amino Acid Sequence ; Antibodies, Neutralizing/immunology ; Cohort Studies ; Crystallography, X-Ray ; Genetic Variation ; Glycosylation ; HIV Antibodies/immunology ; HIV Envelope Protein gp120/*chemistry/genetics/*immunology ; HIV Envelope Protein gp41/*chemistry/genetics/*immunology ; HIV Infections/immunology ; Humans ; Immune Evasion ; Membrane Fusion ; Models, Molecular ; Molecular Sequence Data ; Polysaccharides/chemistry/immunology ; Protein Multimerization ; Protein Structure, Quaternary ; Protein Subunits/chemistry/genetics/immunology ; Structural Homology, Protein ; Virus Internalization
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  • 3
    Publication Date: 2014-10-09
    Description: The neutralizing antibody response to influenza virus is dominated by antibodies that bind to the globular head of haemagglutinin, which undergoes a continuous antigenic drift, necessitating the re-formulation of influenza vaccines on an annual basis. Recently, several laboratories have described a new class of rare influenza-neutralizing antibodies that target a conserved site in the haemagglutinin stem. Most of these antibodies use the heavy-chain variable region VH1-69 gene, and structural data demonstrate that they bind to the haemagglutinin stem through conserved heavy-chain complementarity determining region (HCDR) residues. However, the VH1-69 antibodies are highly mutated and are produced by some but not all individuals, suggesting that several somatic mutations may be required for their development. To address this, here we characterize 197 anti-stem antibodies from a single donor, reconstruct the developmental pathways of several VH1-69 clones and identify two key elements that are required for the initial development of most VH1-69 antibodies: a polymorphic germline-encoded phenylalanine at position 54 and a conserved tyrosine at position 98 in HCDR3. Strikingly, in most cases a single proline to alanine mutation at position 52a in HCDR2 is sufficient to confer high affinity binding to the selecting H1 antigen, consistent with rapid affinity maturation. Surprisingly, additional favourable mutations continue to accumulate, increasing the breadth of reactivity and making both the initial mutations and phenylalanine at position 54 functionally redundant. These results define VH1-69 allele polymorphism, rearrangement of the VDJ gene segments and single somatic mutations as the three requirements for generating broadly neutralizing VH1-69 antibodies and reveal an unexpected redundancy in the affinity maturation process.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pappas, Leontios -- Foglierini, Mathilde -- Piccoli, Luca -- Kallewaard, Nicole L -- Turrini, Filippo -- Silacci, Chiara -- Fernandez-Rodriguez, Blanca -- Agatic, Gloria -- Giacchetto-Sasselli, Isabella -- Pellicciotta, Gabriele -- Sallusto, Federica -- Zhu, Qing -- Vicenzi, Elisa -- Corti, Davide -- Lanzavecchia, Antonio -- U19 AI-057266/AI/NIAID NIH HHS/ -- England -- Nature. 2014 Dec 18;516(7531):418-22. doi: 10.1038/nature13764. Epub 2014 Oct 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Insitute for Research in Biomedicine, Universita della Svizzera Italiana, Via Vincenzo Vela 6, 6500 Bellinzona, Switzerland. ; Department of Infectious Diseases and Vaccines MedImmune LLC, One MedImmune Way, Gaithersburg, Maryland 20878, USA. ; Viral Pathogens and Biosafety Unit, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy. ; Humabs BioMed SA, Via Mirasole 1, 6500 Bellinzona, Switzerland. ; Unit of Preventive Medicine, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy. ; 1] Insitute for Research in Biomedicine, Universita della Svizzera Italiana, Via Vincenzo Vela 6, 6500 Bellinzona, Switzerland [2] Humabs BioMed SA, Via Mirasole 1, 6500 Bellinzona, Switzerland [3]. ; 1] Insitute for Research in Biomedicine, Universita della Svizzera Italiana, Via Vincenzo Vela 6, 6500 Bellinzona, Switzerland [2] Insitute for Microbiology, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland [3].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25296253" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Amino Acid Sequence ; Antibodies, Neutralizing/*genetics ; Cells, Cultured ; Complementarity Determining Regions/chemistry/*genetics ; Female ; Hemagglutinin Glycoproteins, Influenza Virus/immunology ; Humans ; Immunoglobulin Heavy Chains/genetics ; Influenza, Human/*immunology/virology ; Male ; Middle Aged ; Models, Molecular ; Mutation/*genetics ; Orthomyxoviridae/*immunology/metabolism ; Polymorphism, Genetic ; Protein Binding/genetics ; Protein Structure, Tertiary ; Young Adult
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  • 4
    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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  • 5
    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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  • 6
    Publication Date: 2014-12-10
    Description: The widespread reorganization of cellular architecture in mitosis is achieved through extensive protein phosphorylation, driven by the coordinated activation of a mitotic kinase network and repression of counteracting phosphatases. Phosphatase activity must subsequently be restored to promote mitotic exit. Although Cdc14 phosphatase drives this reversal in budding yeast, protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) activities have each been independently linked to mitotic exit control in other eukaryotes. Here we describe a mitotic phosphatase relay in which PP1 reactivation is required for the reactivation of both PP2A-B55 and PP2A-B56 to coordinate mitotic progression and exit in fission yeast. The staged recruitment of PP1 (the Dis2 isoform) to the regulatory subunits of the PP2A-B55 and PP2A-B56 (B55 also known as Pab1; B56 also known as Par1) holoenzymes sequentially activates each phosphatase. The pathway is blocked in early mitosis because the Cdk1-cyclin B kinase (Cdk1 also known as Cdc2) inhibits PP1 activity, but declining cyclin B levels later in mitosis permit PP1 to auto-reactivate. PP1 first reactivates PP2A-B55; this enables PP2A-B55 in turn to promote the reactivation of PP2A-B56 by dephosphorylating a PP1-docking site in PP2A-B56, thereby promoting the recruitment of PP1. PP1 recruitment to human, mitotic PP2A-B56 holoenzymes and the sequences of these conserved PP1-docking motifs suggest that PP1 regulates PP2A-B55 and PP2A-B56 activities in a variety of signalling contexts throughout eukaryotes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338534/" 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/PMC4338534/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grallert, Agnes -- Boke, Elvan -- Hagting, Anja -- Hodgson, Ben -- Connolly, Yvonne -- Griffiths, John R -- Smith, Duncan L -- Pines, Jonathon -- Hagan, Iain M -- 092096/Wellcome Trust/United Kingdom -- A13678/Cancer Research UK/United Kingdom -- A16406/Cancer Research UK/United Kingdom -- C147/A16406/Cancer Research UK/United Kingdom -- C29/A13678/Cancer Research UK/United Kingdom -- England -- Nature. 2015 Jan 1;517(7532):94-8. doi: 10.1038/nature14019. Epub 2014 Dec 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Division Group, CRUK Manchester Institute, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK. ; The Gurdon Institute, Tennis Court Road, University of Cambridge, Cambridge, CB2 1QN, UK. ; Biological Mass Spectrometry, CRUK Manchester Institute, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25487150" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Binding Sites ; CDC2 Protein Kinase/metabolism ; Chromosome Segregation ; Conserved Sequence ; Cyclin B/metabolism ; Enzyme Activation ; HeLa Cells ; Holoenzymes/metabolism ; Humans ; Isoenzymes/metabolism ; *Mitosis ; Molecular Sequence Data ; Phosphorylation ; Protein Phosphatase 1/*metabolism ; Protein Phosphatase 2/chemistry/*metabolism ; Protein Subunits/chemistry/metabolism ; Schizosaccharomyces/*cytology/*enzymology ; Schizosaccharomyces pombe Proteins/chemistry/metabolism ; Signal Transduction
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  • 7
    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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  • 8
    Publication Date: 2014-04-12
    Description: Plant embryogenesis initiates with the establishment of an apical-basal axis; however, the molecular mechanisms accompanying this early event remain unclear. Here, we show that a small cysteine-rich peptide family is required for formation of the zygotic basal cell lineage and proembryo patterning in Arabidopsis. EMBRYO SURROUNDING FACTOR 1 (ESF1) peptides accumulate before fertilization in central cell gametes and thereafter in embryo-surrounding endosperm cells. Biochemical and structural analyses revealed cleavage of ESF1 propeptides to form biologically active mature peptides. Further, these peptides act in a non-cell-autonomous manner and synergistically with the receptor-like kinase SHORT SUSPENSOR to promote suspensor elongation through the YODA mitogen-activated protein kinase pathway. Our findings demonstrate that the second female gamete and its sexually derived endosperm regulate early embryonic patterning in flowering plants.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Costa, Liliana M -- Marshall, Eleanor -- Tesfaye, Mesfin -- Silverstein, Kevin A T -- Mori, Masashi -- Umetsu, Yoshitaka -- Otterbach, Sophie L -- Papareddy, Ranjith -- Dickinson, Hugh G -- Boutiller, Kim -- VandenBosch, Kathryn A -- Ohki, Shinya -- Gutierrez-Marcos, Jose F -- BB/F008082/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/L003023/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/L003023/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Apr 11;344(6180):168-72. doi: 10.1126/science.1243005.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Sciences, University of Oxford, South Parks Road, OX1 3RB, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24723605" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis/*embryology/genetics ; Arabidopsis Proteins/chemistry/genetics/*metabolism ; *Body Patterning ; Endosperm/embryology/genetics ; Flowers/*embryology/genetics ; Gene Duplication ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Plant ; Gene Knockout Techniques ; Interleukin-1 Receptor-Associated Kinases/metabolism ; MAP Kinase Kinase Kinases/metabolism ; Molecular Sequence Data ; Peptides/chemistry/genetics/metabolism ; Seeds/*embryology/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2014-09-23
    Description: Ribonucleotide reductase (RNR) supplies the balanced pools of deoxynucleotide triphosphates (dNTPs) necessary for DNA replication and maintenance of genomic integrity. RNR is subject to allosteric regulatory mechanisms in all eukaryotes, as well as to control by small protein inhibitors Sml1p and Spd1p in budding and fission yeast, respectively. Here, we show that the metazoan protein IRBIT forms a deoxyadenosine triphosphate (dATP)-dependent complex with RNR, which stabilizes dATP in the activity site of RNR and thus inhibits the enzyme. Formation of the RNR-IRBIT complex is regulated through phosphorylation of IRBIT, and ablation of IRBIT expression in HeLa cells causes imbalanced dNTP pools and altered cell cycle progression. We demonstrate a mechanism for RNR regulation in higher eukaryotes that acts by enhancing allosteric RNR inhibition by dATP.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arnaoutov, Alexei -- Dasso, Mary -- New York, N.Y. -- Science. 2014 Sep 19;345(6203):1512-5. doi: 10.1126/science.1251550.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Gene Regulation and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. arnaouta@mail.nih.gov. ; Laboratory of Gene Regulation and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25237103" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Amino Acid Sequence ; Catalytic Domain ; Deoxyadenine Nucleotides/*metabolism ; HeLa Cells ; Humans ; Immunoprecipitation ; Lectins, C-Type/genetics/*metabolism ; Membrane Proteins/genetics/*metabolism ; Molecular Sequence Data ; Phosphorylation ; Ribonucleotide Reductases/*antagonists & inhibitors/metabolism
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  • 10
    Publication Date: 2014-04-26
    Description: Using light to silence electrical activity in targeted cells is a major goal of optogenetics. Available optogenetic proteins that directly move ions to achieve silencing are inefficient, pumping only a single ion per photon across the cell membrane rather than allowing many ions per photon to flow through a channel pore. Building on high-resolution crystal-structure analysis, pore vestibule modeling, and structure-guided protein engineering, we designed and characterized a class of channelrhodopsins (originally cation-conducting) converted into chloride-conducting anion channels. These tools enable fast optical inhibition of action potentials and can be engineered to display step-function kinetics for stable inhibition, outlasting light pulses and for orders-of-magnitude-greater light sensitivity of inhibited cells. The resulting family of proteins defines an approach to more physiological, efficient, and sensitive optogenetic inhibition.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096039/" 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/PMC4096039/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Berndt, Andre -- Lee, Soo Yeun -- Ramakrishnan, Charu -- Deisseroth, Karl -- R01 DA020794/DA/NIDA NIH HHS/ -- R01 MH075957/MH/NIMH NIH HHS/ -- R01 MH086373/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Apr 25;344(6182):420-4. doi: 10.1126/science.1252367.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24763591" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Amino Acid Sequence ; Animals ; CA1 Region, Hippocampal/cytology ; CA3 Region, Hippocampal/cytology ; Chloride Channels/*chemistry/*metabolism ; Chlorides/*metabolism ; HEK293 Cells ; Humans ; Light ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Neurons/*physiology ; Optogenetics ; Patch-Clamp Techniques ; Protein Engineering ; Rats ; Rats, Sprague-Dawley ; Recombinant Fusion Proteins/chemistry/metabolism ; Rhodopsin/*chemistry/genetics/*metabolism
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  • 11
    Publication Date: 2014-03-08
    Description: The excitatory neurotransmitter glutamate induces modulatory actions via the metabotropic glutamate receptors (mGlus), which are class C G protein-coupled receptors (GPCRs). We determined the structure of the human mGlu1 receptor seven-transmembrane (7TM) domain bound to a negative allosteric modulator, FITM, at a resolution of 2.8 angstroms. The modulator binding site partially overlaps with the orthosteric binding sites of class A GPCRs but is more restricted than most other GPCRs. We observed a parallel 7TM dimer mediated by cholesterols, which suggests that signaling initiated by glutamate's interaction with the extracellular domain might be mediated via 7TM interactions within the full-length receptor dimer. A combination of crystallography, structure-activity relationships, mutagenesis, and full-length dimer modeling provides insights about the allosteric modulation and activation mechanism of class C GPCRs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991565/" 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/PMC3991565/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, Huixian -- Wang, Chong -- Gregory, Karen J -- Han, Gye Won -- Cho, Hyekyung P -- Xia, Yan -- Niswender, Colleen M -- Katritch, Vsevolod -- Meiler, Jens -- Cherezov, Vadim -- Conn, P Jeffrey -- Stevens, Raymond C -- P50 GM073197/GM/NIGMS NIH HHS/ -- R01 DK097376/DK/NIDDK NIH HHS/ -- R01 GM080403/GM/NIGMS NIH HHS/ -- R01 GM099842/GM/NIGMS NIH HHS/ -- R01 MH062646/MH/NIMH NIH HHS/ -- R01 MH090192/MH/NIMH NIH HHS/ -- R01 NS031373/NS/NINDS NIH HHS/ -- R21 NS078262/NS/NINDS NIH HHS/ -- R37 NS031373/NS/NINDS NIH HHS/ -- U54 GM094618/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):58-64. doi: 10.1126/science.1249489. Epub 2014 Mar 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24603153" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Allosteric Site ; Amino Acid Sequence ; Benzamides/*chemistry/*metabolism ; Binding Sites ; Cholesterol ; Crystallography, X-Ray ; Humans ; Hydrophobic and Hydrophilic Interactions ; Ligands ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Protein Conformation ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, Metabotropic Glutamate/*chemistry/*metabolism ; Structure-Activity Relationship ; Thiazoles/*chemistry/*metabolism
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  • 12
    Publication Date: 2014-10-25
    Description: In recent years, biologists have increasingly recognized that evolutionary change can occur rapidly when natural selection is strong; thus, real-time studies of evolution can be used to test classic evolutionary hypotheses directly. One such hypothesis is that negative interactions between closely related species can drive phenotypic divergence. Such divergence is thought to be ubiquitous, though well-documented cases are surprisingly rare. On small islands in Florida, we found that the lizard Anolis carolinensis moved to higher perches following invasion by Anolis sagrei and, in response, adaptively evolved larger toepads after only 20 generations. These results illustrate that interspecific interactions between closely related species can drive evolutionary change on observable time scales.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stuart, Y E -- Campbell, T S -- Hohenlohe, P A -- Reynolds, R G -- Revell, L J -- Losos, J B -- P30GM103324/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Oct 24;346(6208):463-6. doi: 10.1126/science.1257008.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Museum of Comparative Zoology and Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA. yestuart@utexas.edu. ; Department of Biology, University of Tampa, Tampa, FL, USA. ; Department of Biological Sciences and Institute for Bioinformatics and Evolutionary Studies, University of Idaho, Moscow, ID, USA. ; Museum of Comparative Zoology and Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA. Department of Biology, University of Massachusetts, Boston, MA, USA. ; Department of Biology, University of Massachusetts, Boston, MA, USA. ; Museum of Comparative Zoology and Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25342801" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Migration ; Animals ; *Evolution, Molecular ; Florida ; *Genetic Variation ; *Introduced Species ; Lizards/*genetics ; Phylogeny ; *Selection, Genetic ; Time Factors
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  • 13
    Publication Date: 2014-03-22
    Description: The development of cells specialized for water conduction or support is a striking innovation of plants that has enabled them to colonize land. The NAC transcription factors regulate the differentiation of these cells in vascular plants. However, the path by which plants with these cells have evolved from their nonvascular ancestors is unclear. We investigated genes of the moss Physcomitrella patens that encode NAC proteins. Loss-of-function mutants formed abnormal water-conducting and supporting cells, as well as malformed sporophyte cells, and overexpression induced ectopic differentiation of water-conducting-like cells. Our results show conservation of transcriptional regulation and cellular function between moss and Arabidopsis thaliana water-conducting cells. The conserved genetic basis suggests roles for NAC proteins in the adaptation of plants to land.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, Bo -- Ohtani, Misato -- Yamaguchi, Masatoshi -- Toyooka, Kiminori -- Wakazaki, Mayumi -- Sato, Mayuko -- Kubo, Minoru -- Nakano, Yoshimi -- Sano, Ryosuke -- Hiwatashi, Yuji -- Murata, Takashi -- Kurata, Tetsuya -- Yoneda, Arata -- Kato, Ko -- Hasebe, Mitsuyasu -- Demura, Taku -- New York, N.Y. -- Science. 2014 Mar 28;343(6178):1505-8. doi: 10.1126/science.1248417. Epub 2014 Mar 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24652936" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological/*genetics ; Amino Acid Sequence ; Arabidopsis/genetics/*physiology ; Bryopsida/genetics/*physiology ; *Gene Expression Regulation, Plant ; Genetic Loci ; Genome, Plant ; Molecular Sequence Data ; Plant Proteins/genetics/*physiology ; Plant Stems/growth & development ; Trans-Activators/genetics/*physiology ; Transcription, Genetic ; Water/*physiology
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  • 14
    Publication Date: 2014-08-26
    Description: Sensory systems define an animal's capacity for perception and can evolve to promote survival in new environmental niches. We have uncovered a noncanonical mechanism for sweet taste perception that evolved in hummingbirds since their divergence from insectivorous swifts, their closest relatives. We observed the widespread absence in birds of an essential subunit (T1R2) of the only known vertebrate sweet receptor, raising questions about how specialized nectar feeders such as hummingbirds sense sugars. Receptor expression studies revealed that the ancestral umami receptor (the T1R1-T1R3 heterodimer) was repurposed in hummingbirds to function as a carbohydrate receptor. Furthermore, the molecular recognition properties of T1R1-T1R3 guided taste behavior in captive and wild hummingbirds. We propose that changing taste receptor function enabled hummingbirds to perceive and use nectar, facilitating the massive radiation of hummingbird species.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302410/" 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/PMC4302410/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baldwin, Maude W -- Toda, Yasuka -- Nakagita, Tomoya -- O'Connell, Mary J -- Klasing, Kirk C -- Misaka, Takumi -- Edwards, Scott V -- Liberles, Stephen D -- R01 DC013289/DC/NIDCD NIH HHS/ -- R01DC013289/DC/NIDCD NIH HHS/ -- New York, N.Y. -- Science. 2014 Aug 22;345(6199):929-33. doi: 10.1126/science.1255097.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Organismic and Evolutionary Biology, Harvard University, and Museum of Comparative Zoology, Cambridge, MA 02138, USA. maudebaldwin@gmail.com stephen_liberles@hms.harvard.edu. ; Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan. ; Bioinformatics and Molecular Evolution Group, School of Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland. ; Department of Animal Science, University of California, Davis, Davis, CA 95616, USA. ; Department of Organismic and Evolutionary Biology, Harvard University, and Museum of Comparative Zoology, Cambridge, MA 02138, USA. ; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. maudebaldwin@gmail.com stephen_liberles@hms.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25146290" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; *Evolution, Molecular ; Mice ; Molecular Sequence Data ; Plant Nectar ; Protein Structure, Tertiary ; Receptors, G-Protein-Coupled/chemistry/classification/*genetics ; Taste/*physiology ; Taste Perception/genetics/*physiology
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  • 15
    Publication Date: 2014-04-26
    Description: The hierarchical packaging of eukaryotic chromatin plays a central role in transcriptional regulation and other DNA-related biological processes. Here, we report the 11-angstrom-resolution cryogenic electron microscopy (cryo-EM) structures of 30-nanometer chromatin fibers reconstituted in the presence of linker histone H1 and with different nucleosome repeat lengths. The structures show a histone H1-dependent left-handed twist of the repeating tetranucleosomal structural units, within which the four nucleosomes zigzag back and forth with a straight linker DNA. The asymmetric binding and the location of histone H1 in chromatin play a role in the formation of the 30-nanometer fiber. Our results provide mechanistic insights into how nucleosomes compact into higher-order chromatin fibers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Song, Feng -- Chen, Ping -- Sun, Dapeng -- Wang, Mingzhu -- Dong, Liping -- Liang, Dan -- Xu, Rui-Ming -- Zhu, Ping -- Li, Guohong -- New York, N.Y. -- Science. 2014 Apr 25;344(6182):376-80. doi: 10.1126/science.1251413.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24763583" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Chromatin/chemistry/metabolism/*ultrastructure ; Cryoelectron Microscopy ; DNA/chemistry/*ultrastructure ; Histones/*chemistry/metabolism ; Imaging, Three-Dimensional ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Nucleosomes/*ultrastructure ; Protein Conformation ; Recombinant Proteins/chemistry/metabolism ; Xenopus Proteins/chemistry ; Xenopus laevis
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  • 16
    Publication Date: 2014-10-18
    Description: Nitrogen (N) is a critical nutrient for plants but is often distributed unevenly in the soil. Plants therefore have evolved a systemic mechanism by which N starvation on one side of the root system leads to a compensatory and increased nitrate uptake on the other side. Here, we study the molecular systems that support perception of N and the long-distance signaling needed to alter root development. Rootlets starved of N secrete small peptides that are translocated to the shoot and received by two leucine-rich repeat receptor kinases (LRR-RKs). Arabidopsis plants deficient in this pathway show growth retardation accompanied with N-deficiency symptoms. Thus, signaling from the root to the shoot helps the plant adapt to fluctuations in local N availability.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tabata, Ryo -- Sumida, Kumiko -- Yoshii, Tomoaki -- Ohyama, Kentaro -- Shinohara, Hidefumi -- Matsubayashi, Yoshikatsu -- New York, N.Y. -- Science. 2014 Oct 17;346(6207):343-6. doi: 10.1126/science.1257800.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa, Nagoya 464-8602, Japan. ; Department of Applied Molecular Biosciences, Graduate School of Bio-Agricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan. ; Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa, Nagoya 464-8602, Japan. matsu@bio.nagoya-u.ac.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25324386" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis/genetics/*growth & development/metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Molecular Sequence Data ; Nitrogen/*metabolism ; Peptides/*metabolism ; Plant Roots/genetics/*growth & development/metabolism ; Plant Shoots/genetics/*growth & development/metabolism ; Receptors, Peptide/genetics/*metabolism ; Signal Transduction
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  • 17
    Publication Date: 2014-07-26
    Description: Proteins that cap the ends of the actin filament are essential regulators of cytoskeleton dynamics. Whereas several proteins cap the rapidly growing barbed end, tropomodulin (Tmod) is the only protein known to cap the slowly growing pointed end. The lack of structural information severely limits our understanding of Tmod's capping mechanism. We describe crystal structures of actin complexes with the unstructured amino-terminal and the leucine-rich repeat carboxy-terminal domains of Tmod. The structures and biochemical analysis of structure-inspired mutants showed that one Tmod molecule interacts with three actin subunits at the pointed end, while also contacting two tropomyosin molecules on each side of the filament. We found that Tmod achieves high-affinity binding through several discrete low-affinity interactions, which suggests a mechanism for controlled subunit exchange at the pointed end.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4367809/" 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/PMC4367809/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rao, Jampani Nageswara -- Madasu, Yadaiah -- Dominguez, Roberto -- GM-0080/GM/NIGMS NIH HHS/ -- R01 GM073791/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Jul 25;345(6195):463-7. doi: 10.1126/science.1256159.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. droberto@mail.med.upenn.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25061212" target="_blank"〉PubMed〈/a〉
    Keywords: Actin Cytoskeleton/*chemistry ; Actins/*chemistry ; Amino Acid Sequence ; Animals ; Crystallography, X-Ray ; Humans ; Molecular Sequence Data ; Mutation ; Protein Binding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Rabbits ; Tropomodulin/*chemistry/genetics
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  • 18
    Publication Date: 2014-01-18
    Description: Transcription factors (TFs) are key players in evolution. Changes affecting their function can yield novel life forms but may also have deleterious effects. Consequently, gene duplication events that release one gene copy from selective pressure are thought to be the common mechanism by which TFs acquire new activities. Here, we show that LEAFY, a major regulator of flower development and cell division in land plants, underwent changes to its DNA binding specificity, even though plant genomes generally contain a single copy of the LEAFY gene. We examined how these changes occurred at the structural level and identify an intermediate LEAFY form in hornworts that appears to adopt all different specificities. This promiscuous intermediate could have smoothed the evolutionary transitions, thereby allowing LEAFY to evolve new binding specificities while remaining a single-copy gene.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sayou, Camille -- Monniaux, Marie -- Nanao, Max H -- Moyroud, Edwige -- Brockington, Samuel F -- Thevenon, Emmanuel -- Chahtane, Hicham -- Warthmann, Norman -- Melkonian, Michael -- Zhang, Yong -- Wong, Gane Ka-Shu -- Weigel, Detlef -- Parcy, Francois -- Dumas, Renaud -- New York, N.Y. -- Science. 2014 Feb 7;343(6171):645-8. doi: 10.1126/science.1248229. Epub 2014 Jan 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CNRS, Laboratoire de Physiologie Cellulaire et Vegetale (LPCV), UMR 5168, 38054 Grenoble, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24436181" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis Proteins/chemistry/classification/genetics ; DNA, Plant/*chemistry ; DNA-Binding Proteins/*chemistry/classification/*genetics ; Electrophoretic Mobility Shift Assay ; *Evolution, Molecular ; Gene Dosage ; Molecular Sequence Data ; Mutation ; Phylogeny ; Plant Proteins/*chemistry/classification/*genetics ; Protein Binding/genetics ; Protein Structure, Tertiary ; Species Specificity ; Transcription Factors/chemistry/classification/genetics
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  • 19
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-05-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Underwood, Emily -- New York, N.Y. -- Science. 2014 May 30;344(6187):954-5. doi: 10.1126/science.344.6187.954.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24876470" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Engineering/*instrumentation ; Biomedical Research/*instrumentation ; Brain/*physiology ; Humans ; Neurosciences/economics/*trends ; Physical Phenomena ; Physics
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  • 20
    Publication Date: 2014-07-12
    Description: Heterosexual transmission of HIV-1 typically results in one genetic variant establishing systemic infection. We compared, for 137 linked transmission pairs, the amino acid sequences encoded by non-envelope genes of viruses in both partners and demonstrate a selection bias for transmission of residues that are predicted to confer increased in vivo fitness on viruses in the newly infected, immunologically naive recipient. Although tempered by transmission risk factors, such as donor viral load, genital inflammation, and recipient gender, this selection bias provides an overall transmission advantage for viral quasispecies that are dominated by viruses with high in vivo fitness. Thus, preventative or therapeutic approaches that even marginally reduce viral fitness may lower the overall transmission rates and offer long-term benefits even upon successful transmission.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289910/" 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/PMC4289910/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carlson, Jonathan M -- Schaefer, Malinda -- Monaco, Daniela C -- Batorsky, Rebecca -- Claiborne, Daniel T -- Prince, Jessica -- Deymier, Martin J -- Ende, Zachary S -- Klatt, Nichole R -- DeZiel, Charles E -- Lin, Tien-Ho -- Peng, Jian -- Seese, Aaron M -- Shapiro, Roger -- Frater, John -- Ndung'u, Thumbi -- Tang, Jianming -- Goepfert, Paul -- Gilmour, Jill -- Price, Matt A -- Kilembe, William -- Heckerman, David -- Goulder, Philip J R -- Allen, Todd M -- Allen, Susan -- Hunter, Eric -- 2P51RR000165-51/RR/NCRR NIH HHS/ -- G108/626/Medical Research Council/United Kingdom -- OD P51OD11132/OD/NIH HHS/ -- P01-AI074415/AI/NIAID NIH HHS/ -- P30 AI050409/AI/NIAID NIH HHS/ -- P51 OD010425/OD/NIH HHS/ -- P51 OD011132/OD/NIH HHS/ -- P51RR165/RR/NCRR NIH HHS/ -- R01 AI064060/AI/NIAID NIH HHS/ -- R01 AI64060/AI/NIAID NIH HHS/ -- R37 AI051231/AI/NIAID NIH HHS/ -- R37 AI51231/AI/NIAID NIH HHS/ -- T32 AI007387/AI/NIAID NIH HHS/ -- T32-AI007387/AI/NIAID NIH HHS/ -- U01 AI 66454/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Jul 11;345(6193):1254031. doi: 10.1126/science.1254031. Epub 2014 Jul 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Microsoft Research, Redmond, WA 98052, USA. carlson@microsoft.com ehunte4@emory.edu. ; Emory Vaccine Center at Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA. ; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02114, USA. ; Microsoft Research, Redmond, WA 98052, USA. ; Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. ; Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX1 7BN, UK. National Institute of Health Research, Oxford Biomedical Research Centre, Oxford OX3 7LE, UK. Oxford Martin School, University of Oxford, Oxford OX1 3BD, UK. ; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02114, USA. HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4013, South Africa. KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4001, South Africa. Max Planck Institute for Infection Biology, D-10117 Berlin, Germany. ; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA. ; International AIDS Vaccine Initiative, London SW10 9NH, UK. Imperial College of Science Technology and Medicine, London SW10 9NH, UK. ; International AIDS Vaccine Initiative, San Francisco, CA 94105, USA. Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94105, USA. ; Rwanda-Zambia HIV Research Group: Zambia-Emory HIV Research Project, Lusaka, Zambia. ; Microsoft Research, Los Angeles, CA 98117, USA. ; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4013, South Africa. Department of Paediatrics, University of Oxford, Oxford OX1 3SY, UK. ; Rwanda-Zambia HIV Research Group: Zambia-Emory HIV Research Project, Lusaka, Zambia. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA. Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA. ; International AIDS Vaccine Initiative, San Francisco, CA 94105, USA. Microsoft Research, Los Angeles, CA 98117, USA. Department of Paediatrics, University of Oxford, Oxford OX1 3SY, UK. ; Emory Vaccine Center at Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA. Rwanda-Zambia HIV Research Group: Zambia-Emory HIV Research Project, Lusaka, Zambia. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA. carlson@microsoft.com ehunte4@emory.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25013080" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Consensus Sequence ; DNA Mutational Analysis ; Disease Transmission, Infectious/statistics & numerical data ; Female ; HIV Infections/*transmission ; HIV-1/*genetics ; *Heterosexuality ; High-Throughput Nucleotide Sequencing ; Human Immunodeficiency Virus Proteins/genetics ; Humans ; Male ; Models, Statistical ; Molecular Sequence Data ; Point Mutation ; Risk Factors ; *Selection, Genetic ; Viral Load
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 21
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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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  • 22
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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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  • 23
    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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  • 24
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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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  • 25
    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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  • 26
    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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  • 27
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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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  • 28
    Publication Date: 2014-03-05
    Description: Antibodies capable of neutralizing HIV-1 often target variable regions 1 and 2 (V1V2) of the HIV-1 envelope, but the mechanism of their elicitation has been unclear. Here we define the developmental pathway by which such antibodies are generated and acquire the requisite molecular characteristics for neutralization. Twelve somatically related neutralizing antibodies (CAP256-VRC26.01-12) were isolated from donor CAP256 (from the Centre for the AIDS Programme of Research in South Africa (CAPRISA)); each antibody contained the protruding tyrosine-sulphated, anionic antigen-binding loop (complementarity-determining region (CDR) H3) characteristic of this category of antibodies. Their unmutated ancestor emerged between weeks 30-38 post-infection with a 35-residue CDR H3, and neutralized the virus that superinfected this individual 15 weeks after initial infection. Improved neutralization breadth and potency occurred by week 59 with modest affinity maturation, and was preceded by extensive diversification of the virus population. HIV-1 V1V2-directed neutralizing antibodies can thus develop relatively rapidly through initial selection of B cells with a long CDR H3, and limited subsequent somatic hypermutation. These data provide important insights relevant to HIV-1 vaccine development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4395007/" 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/PMC4395007/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Doria-Rose, Nicole A -- Schramm, Chaim A -- Gorman, Jason -- Moore, Penny L -- Bhiman, Jinal N -- DeKosky, Brandon J -- Ernandes, Michael J -- Georgiev, Ivelin S -- Kim, Helen J -- Pancera, Marie -- Staupe, Ryan P -- Altae-Tran, Han R -- Bailer, Robert T -- Crooks, Ema T -- Cupo, Albert -- Druz, Aliaksandr -- Garrett, Nigel J -- Hoi, Kam H -- Kong, Rui -- Louder, Mark K -- Longo, Nancy S -- McKee, Krisha -- Nonyane, Molati -- O'Dell, Sijy -- Roark, Ryan S -- Rudicell, Rebecca S -- Schmidt, Stephen D -- Sheward, Daniel J -- Soto, Cinque -- Wibmer, Constantinos Kurt -- Yang, Yongping -- Zhang, Zhenhai -- NISC Comparative Sequencing Program -- Mullikin, James C -- Binley, James M -- Sanders, Rogier W -- Wilson, Ian A -- Moore, John P -- Ward, Andrew B -- Georgiou, George -- Williamson, Carolyn -- Abdool Karim, Salim S -- Morris, Lynn -- Kwong, Peter D -- Shapiro, Lawrence -- Mascola, John R -- P01 AI082362/AI/NIAID NIH HHS/ -- R01 AI100790/AI/NIAID NIH HHS/ -- UM1 AI100663/AI/NIAID NIH HHS/ -- Intramural NIH HHS/ -- Wellcome Trust/United Kingdom -- England -- Nature. 2014 May 1;509(7498):55-62. doi: 10.1038/nature13036. Epub 2014 Mar 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA [2]. ; 1] Department of Biochemistry, Columbia University, New York, New York 10032, USA [2]. ; 1] Center for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS), Johannesburg, 2131, South Africa [2] Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2050, South Africa [3] Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella, 4013, South Africa [4]. ; 1] Center for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS), Johannesburg, 2131, South Africa [2] Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2050, South Africa. ; Department of Chemical Engineering, University of Texas at Austin, Austin, Texas 78712, USA. ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ; 1] Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California 92037, USA [2] Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA [3] IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California 92037, USA. ; Torrey Pines Institute, San Diego, California 92037, USA. ; Weill Medical College of Cornell University, New York, New York 10065, USA. ; Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella, 4013, South Africa. ; Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas, USA. ; Center for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS), Johannesburg, 2131, South Africa. ; Institute of Infectious Diseases and Molecular Medicine, Division of Medical Virology, University of Cape Town and NHLS, Cape Town 7701, South Africa. ; Department of Biochemistry, Columbia University, New York, New York 10032, USA. ; 1] NISC Comparative Sequencing program, National Institutes of Health, Bethesda, Maryland 20892, USA [2] NIH Intramural Sequencing Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Department of Medical Microbiology, Academic Medical Center, Amsterdam 1105 AZ, Netherlands. ; 1] Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California 92037, USA [2] Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA [3] IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California 92037, USA [4] Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA. ; 1] Department of Chemical Engineering, University of Texas at Austin, Austin, Texas 78712, USA [2] Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas, USA [3] Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas 78712, USA. ; 1] Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella, 4013, South Africa [2] Institute of Infectious Diseases and Molecular Medicine, Division of Medical Virology, University of Cape Town and NHLS, Cape Town 7701, South Africa. ; 1] Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella, 4013, South Africa [2] Department of Epidemiology, Columbia University, New York, New York 10032, USA. ; 1] Center for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS), Johannesburg, 2131, South Africa [2] Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2050, South Africa [3] Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella, 4013, South Africa. ; 1] Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA [2] Department of Biochemistry, 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/24590074" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/chemistry/immunology ; Amino Acid Sequence ; Antibodies, Neutralizing/chemistry/genetics/*immunology/isolation & purification ; Antibody Affinity/genetics/immunology ; Antigens, CD4/immunology/metabolism ; B-Lymphocytes/cytology/immunology/metabolism ; Binding Sites/immunology ; Cell Lineage ; Complementarity Determining Regions/chemistry/genetics/immunology ; Epitope Mapping ; Epitopes, B-Lymphocyte/chemistry/immunology ; Evolution, Molecular ; HIV Antibodies/chemistry/genetics/*immunology/isolation & purification ; HIV Envelope Protein gp160/*chemistry/*immunology ; HIV Infections/immunology ; HIV-1/chemistry/immunology ; Humans ; Models, Molecular ; Molecular Sequence Data ; Neutralization Tests ; Protein Structure, Tertiary ; Somatic Hypermutation, Immunoglobulin/genetics
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  • 29
    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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  • 30
    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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  • 31
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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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  • 32
    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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  • 33
    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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  • 34
    Publication Date: 2014-02-28
    Description: Nitrate is a primary nutrient for plant growth, but its levels in soil can fluctuate by several orders of magnitude. Previous studies have identified Arabidopsis NRT1.1 as a dual-affinity nitrate transporter that can take up nitrate over a wide range of concentrations. The mode of action of NRT1.1 is controlled by phosphorylation of a key residue, Thr 101; however, how this post-translational modification switches the transporter between two affinity states remains unclear. Here we report the crystal structure of unphosphorylated NRT1.1, which reveals an unexpected homodimer in the inward-facing conformation. In this low-affinity state, the Thr 101 phosphorylation site is embedded in a pocket immediately adjacent to the dimer interface, linking the phosphorylation status of the transporter to its oligomeric state. Using a cell-based fluorescence resonance energy transfer assay, we show that functional NRT1.1 dimerizes in the cell membrane and that the phosphomimetic mutation of Thr 101 converts the protein into a monophasic high-affinity transporter by structurally decoupling the dimer. Together with analyses of the substrate transport tunnel, our results establish a phosphorylation-controlled dimerization switch that allows NRT1.1 to uptake nitrate with two distinct affinity modes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3968801/" 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/PMC3968801/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sun, Ji -- Bankston, John R -- Payandeh, Jian -- Hinds, Thomas R -- Zagotta, William N -- Zheng, Ning -- NS074545/NS/NINDS NIH HHS/ -- R01EY10329/EY/NEI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Mar 6;507(7490):73-7. doi: 10.1038/nature13074. Epub 2014 Feb 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Box 357280, University of Washington, Seattle, Washington 98195, USA. ; Department of Physiology and Biophysics, Box 357290, University of Washington, Seattle, Washington 98195, USA. ; 1] Department of Pharmacology, Box 357280, University of Washington, Seattle, Washington 98195, USA [2] Department of Structural Biology, Genentech Inc., South San Francisco, California 94080, USA. ; 1] Department of Pharmacology, Box 357280, University of Washington, Seattle, Washington 98195, USA [2] Howard Hughes Medical Institute, Box 357280, University of Washington, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24572362" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Anion Transport Proteins/*chemistry/genetics/metabolism ; Arabidopsis/*chemistry/genetics ; Binding Sites ; Biological Transport ; Cell Membrane/chemistry/metabolism ; Crystallography, X-Ray ; Fluorescence Resonance Energy Transfer ; Models, Biological ; Models, Molecular ; Molecular Sequence Data ; Mutation/genetics ; Nitrates/chemistry/metabolism ; Phosphorylation ; Phosphothreonine/chemistry/metabolism ; Plant Proteins/*chemistry/genetics/metabolism ; *Protein Multimerization ; Protein Structure, Quaternary ; Protons ; Structure-Activity Relationship
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  • 35
    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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  • 36
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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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  • 37
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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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  • 38
    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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  • 39
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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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  • 40
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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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  • 41
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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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  • 42
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    Nature Publishing Group (NPG)
    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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  • 43
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    Nature Publishing Group (NPG)
    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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  • 44
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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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  • 45
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    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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  • 46
    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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  • 47
    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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  • 48
    Publication Date: 2014-08-15
    Description: Neurotransmitter-gated ion channels of the Cys-loop receptor family mediate fast neurotransmission throughout the nervous system. The molecular processes of neurotransmitter binding, subsequent opening of the ion channel and ion permeation remain poorly understood. Here we present the X-ray structure of a mammalian Cys-loop receptor, the mouse serotonin 5-HT3 receptor, at 3.5 A resolution. The structure of the proteolysed receptor, made up of two fragments and comprising part of the intracellular domain, was determined in complex with stabilizing nanobodies. The extracellular domain reveals the detailed anatomy of the neurotransmitter binding site capped by a nanobody. The membrane domain delimits an aqueous pore with a 4.6 A constriction. In the intracellular domain, a bundle of five intracellular helices creates a closed vestibule where lateral portals are obstructed by loops. This 5-HT3 receptor structure, revealing part of the intracellular domain, expands the structural basis for understanding the operating mechanism of mammalian Cys-loop receptors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hassaine, Gherici -- Deluz, Cedric -- Grasso, Luigino -- Wyss, Romain -- Tol, Menno B -- Hovius, Ruud -- Graff, Alexandra -- Stahlberg, Henning -- Tomizaki, Takashi -- Desmyter, Aline -- Moreau, Christophe -- Li, Xiao-Dan -- Poitevin, Frederic -- Vogel, Horst -- Nury, Hugues -- England -- Nature. 2014 Aug 21;512(7514):276-81. doi: 10.1038/nature13552. Epub 2014 Aug 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne, Switzerland [2] [3] Theranyx, 163 Avenue de Luminy, 13288 Marseille, France. ; 1] Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne, Switzerland [2]. ; Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne, Switzerland. ; Center for Cellular Imaging and NanoAnalytics, Biozentrum, University of Basel, CH-4058 Basel, Switzerland. ; Swiss Light Source, Paul Scherrer Institute, CH-5234 Villigen, Switzerland. ; Architecture et Fonction des Macromolecules Biologiques, CNRS UMR 7257 and Universite Aix-Marseille, F-13288 Marseille, France. ; 1] Universite Grenoble Alpes, IBS, F-38000 Grenoble, France [2] CNRS, IBS, F-38000 Grenoble, France [3] CEA, DSV, IBS, F-38000 Grenoble, France. ; Laboratory of Biomolecular Research, Paul Scherrer Institute, CH-5232 Villigen, Switzerland. ; Unite de Dynamique Structurale des Macromolecules, Institut Pasteur, CNRS UMR3528, F-75015 Paris, France. ; 1] Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne, Switzerland [2] Universite Grenoble Alpes, IBS, F-38000 Grenoble, France [3] CNRS, IBS, F-38000 Grenoble, France [4] CEA, DSV, IBS, F-38000 Grenoble, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25119048" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Crystallography, X-Ray ; Mice ; Models, Molecular ; Molecular Sequence Data ; Neurotransmitter Agents/metabolism ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; Protein Subunits/chemistry/metabolism ; Receptors, Serotonin, 5-HT3/*chemistry/metabolism
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  • 49
    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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  • 50
    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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  • 51
    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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  • 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: 2014-11-11
    Description: The TMEM16 family of proteins, also known as anoctamins, features a remarkable functional diversity. This family contains the long sought-after Ca(2+)-activated chloride channels as well as lipid scramblases and cation channels. Here we present the crystal structure of a TMEM16 family member from the fungus Nectria haematococca that operates as a Ca(2+)-activated lipid scramblase. Each subunit of the homodimeric protein contains ten transmembrane helices and a hydrophilic membrane-traversing cavity that is exposed to the lipid bilayer as a potential site of catalysis. This cavity harbours a conserved Ca(2+)-binding site located within the hydrophobic core of the membrane. Mutations of residues involved in Ca(2+) coordination affect both lipid scrambling in N. haematococca TMEM16 and ion conduction in the Cl(-) channel TMEM16A. The structure reveals the general architecture of the family and its mode of Ca(2+) activation. It also provides insight into potential scrambling mechanisms and serves as a framework to unravel the conduction of ions in certain TMEM16 proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brunner, Janine D -- Lim, Novandy K -- Schenck, Stephan -- Duerst, Alessia -- Dutzler, Raimund -- England -- Nature. 2014 Dec 11;516(7530):207-12. doi: 10.1038/nature13984. Epub 2014 Nov 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25383531" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites/genetics ; Calcium/chemistry/*metabolism/pharmacology ; Chloride Channels/*chemistry/genetics/*metabolism ; Crystallography, X-Ray ; Electric Conductivity ; Humans ; Hydrophobic and Hydrophilic Interactions ; Ion Transport/drug effects ; Lipid Bilayers/chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Nectria/*chemistry/enzymology/genetics ; Neoplasm Proteins/chemistry ; Phospholipid Transfer Proteins/*chemistry/genetics/*metabolism ; Protein Multimerization ; Protein Structure, Secondary ; Protein Subunits/chemistry/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
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    Nature Publishing Group (NPG)
    Publication Date: 2014-04-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boone, David -- England -- Nature. 2014 Apr 10;508(7495):186. doi: 10.1038/508186e.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Indiana University School of Medicine - South Bend, Indiana, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24717504" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Catalytic Domain ; Humans ; Skin Neoplasms/genetics ; Tumor Suppressor Proteins/*chemistry/genetics
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  • 64
    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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  • 65
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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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  • 66
    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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  • 67
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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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  • 68
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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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  • 69
    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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  • 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: 2014-08-30
    Description: Without an approved vaccine or treatments, Ebola outbreak management has been limited to palliative care and barrier methods to prevent transmission. These approaches, however, have yet to end the 2014 outbreak of Ebola after its prolonged presence in West Africa. Here we show that a combination of monoclonal antibodies (ZMapp), optimized from two previous antibody cocktails, is able to rescue 100% of rhesus macaques when treatment is initiated up to 5 days post-challenge. High fever, viraemia and abnormalities in blood count and blood chemistry were evident in many animals before ZMapp intervention. Advanced disease, as indicated by elevated liver enzymes, mucosal haemorrhages and generalized petechia could be reversed, leading to full recovery. ELISA and neutralizing antibody assays indicate that ZMapp is cross-reactive with the Guinean variant of Ebola. ZMapp exceeds the efficacy of any other therapeutics described so far, and results warrant further development of this cocktail for clinical use.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214273/" 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/PMC4214273/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Qiu, Xiangguo -- Wong, Gary -- Audet, Jonathan -- Bello, Alexander -- Fernando, Lisa -- Alimonti, Judie B -- Fausther-Bovendo, Hugues -- Wei, Haiyan -- Aviles, Jenna -- Hiatt, Ernie -- Johnson, Ashley -- Morton, Josh -- Swope, Kelsi -- Bohorov, Ognian -- Bohorova, Natasha -- Goodman, Charles -- Kim, Do -- Pauly, Michael H -- Velasco, Jesus -- Pettitt, James -- Olinger, Gene G -- Whaley, Kevin -- Xu, Bianli -- Strong, James E -- Zeitlin, Larry -- Kobinger, Gary P -- U19 AI109762/AI/NIAID NIH HHS/ -- U19AI109762/AI/NIAID NIH HHS/ -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2014 Oct 2;514(7520):47-53. doi: 10.1038/nature13777. Epub 2014 Aug 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada. ; 1] National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada [2] Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada. ; 1] National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada [2] Institute of Infectious Disease, Henan Centre for Disease Control and Prevention, Zhengzhou, 450012 Henan, China. ; Kentucky BioProcessing, Owensboro, Kentucky 42301, USA. ; Mapp Biopharmaceutical Inc., San Diego, California 92121, USA. ; 1] United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland 21702, USA [2] Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland 21702, USA. ; Institute of Infectious Disease, Henan Centre for Disease Control and Prevention, Zhengzhou, 450012 Henan, China. ; 1] National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada [2] Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada [3] Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba R3A 1S1, Canada. ; 1] National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada [2] Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada [3] Department of Immunology, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada [4] Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25171469" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antibodies, Monoclonal/immunology/*therapeutic use ; Antibodies, Neutralizing/immunology/therapeutic use ; Antibodies, Viral/immunology/*therapeutic use ; Cross Reactions/immunology ; Ebolavirus/immunology ; Enzyme-Linked Immunosorbent Assay ; Female ; Guinea ; Guinea Pigs ; Hemorrhagic Fever, Ebola/blood/*drug therapy/immunology/virology ; *Immunization, Passive ; Macaca mulatta/immunology/virology ; Male ; Molecular Sequence Data ; Sequence Alignment ; Viral Envelope Proteins/chemistry/immunology ; Viremia/drug therapy/immunology/virology
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  • 72
    Publication Date: 2014-11-05
    Description: The genetic architecture of autism spectrum disorder involves the interplay of common and rare variants and their impact on hundreds of genes. Using exome sequencing, here we show that analysis of rare coding variation in 3,871 autism cases and 9,937 ancestry-matched or parental controls implicates 22 autosomal genes at a false discovery rate (FDR) 〈 0.05, plus a set of 107 autosomal genes strongly enriched for those likely to affect risk (FDR 〈 0.30). These 107 genes, which show unusual evolutionary constraint against mutations, incur de novo loss-of-function mutations in over 5% of autistic subjects. Many of the genes implicated encode proteins for synaptic formation, transcriptional regulation and chromatin-remodelling pathways. These include voltage-gated ion channels regulating the propagation of action potentials, pacemaking and excitability-transcription coupling, as well as histone-modifying enzymes and chromatin remodellers-most prominently those that mediate post-translational lysine methylation/demethylation modifications of histones.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4402723/" 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/PMC4402723/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉De Rubeis, Silvia -- He, Xin -- Goldberg, Arthur P -- Poultney, Christopher S -- Samocha, Kaitlin -- Cicek, A Erucment -- Kou, Yan -- Liu, Li -- Fromer, Menachem -- Walker, Susan -- Singh, Tarinder -- Klei, Lambertus -- Kosmicki, Jack -- Shih-Chen, Fu -- Aleksic, Branko -- Biscaldi, Monica -- Bolton, Patrick F -- Brownfeld, Jessica M -- Cai, Jinlu -- Campbell, Nicholas G -- Carracedo, Angel -- Chahrour, Maria H -- Chiocchetti, Andreas G -- Coon, Hilary -- Crawford, Emily L -- Curran, Sarah R -- Dawson, Geraldine -- Duketis, Eftichia -- Fernandez, Bridget A -- Gallagher, Louise -- Geller, Evan -- Guter, Stephen J -- Hill, R Sean -- Ionita-Laza, Juliana -- Jimenz Gonzalez, Patricia -- Kilpinen, Helena -- Klauck, Sabine M -- Kolevzon, Alexander -- Lee, Irene -- Lei, Irene -- Lei, Jing -- Lehtimaki, Terho -- Lin, Chiao-Feng -- Ma'ayan, Avi -- Marshall, Christian R -- McInnes, Alison L -- Neale, Benjamin -- Owen, Michael J -- Ozaki, Noriio -- Parellada, Mara -- Parr, Jeremy R -- Purcell, Shaun -- Puura, Kaija -- Rajagopalan, Deepthi -- Rehnstrom, Karola -- Reichenberg, Abraham -- Sabo, Aniko -- Sachse, Michael -- Sanders, Stephan J -- Schafer, Chad -- Schulte-Ruther, Martin -- Skuse, David -- Stevens, Christine -- Szatmari, Peter -- Tammimies, Kristiina -- Valladares, Otto -- Voran, Annette -- Li-San, Wang -- Weiss, Lauren A -- Willsey, A Jeremy -- Yu, Timothy W -- Yuen, Ryan K C -- DDD Study -- Homozygosity Mapping Collaborative for Autism -- UK10K Consortium -- Cook, Edwin H -- Freitag, Christine M -- Gill, Michael -- Hultman, Christina M -- Lehner, Thomas -- Palotie, Aaarno -- Schellenberg, Gerard D -- Sklar, Pamela -- State, Matthew W -- Sutcliffe, James S -- Walsh, Christiopher A -- Scherer, Stephen W -- Zwick, Michael E -- Barett, Jeffrey C -- Cutler, David J -- Roeder, Kathryn -- Devlin, Bernie -- Daly, Mark J -- Buxbaum, Joseph D -- 5UL1 RR024975/RR/NCRR NIH HHS/ -- MH077139/MH/NIMH NIH HHS/ -- MH089482/MH/NIMH NIH HHS/ -- MH095034/MH/NIMH NIH HHS/ -- P30 HD15052/HD/NICHD NIH HHS/ -- P50 HD055751/HD/NICHD NIH HHS/ -- R01 MH061009/MH/NIMH NIH HHS/ -- R01 MH083565/MH/NIMH NIH HHS/ -- R01 MH089482/MH/NIMH NIH HHS/ -- R01 MH094400/MH/NIMH NIH HHS/ -- R01 MH095797/MH/NIMH NIH HHS/ -- R01 MH097849/MH/NIMH NIH HHS/ -- R01 MH100229/MH/NIMH NIH HHS/ -- R01 NS073601/NS/NINDS NIH HHS/ -- R01MH083565/MH/NIMH NIH HHS/ -- R01MH089208/MH/NIMH NIH HHS/ -- R37 MH057881/MH/NIMH NIH HHS/ -- RC2MH089952/MH/NIMH NIH HHS/ -- T32 HG002295/HG/NHGRI NIH HHS/ -- U01 MH100209/MH/NIMH NIH HHS/ -- U01 MH100229/MH/NIMH NIH HHS/ -- U01 MH100233/MH/NIMH NIH HHS/ -- U01 MH100239/MH/NIMH NIH HHS/ -- U01MH100209/MH/NIMH NIH HHS/ -- U01MH100229/MH/NIMH NIH HHS/ -- U01MH100233/MH/NIMH NIH HHS/ -- U01MH100239/MH/NIMH NIH HHS/ -- U54 HG003067/HG/NHGRI NIH HHS/ -- UL1TR000445/TR/NCATS NIH HHS/ -- WT091310/Wellcome Trust/United Kingdom -- WT098051/Wellcome Trust/United Kingdom -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Nov 13;515(7526):209-15. doi: 10.1038/nature13772. Epub 2014 Oct 29.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25363760" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Child Development Disorders, Pervasive/*genetics/pathology ; Chromatin/*genetics/metabolism ; Chromatin Assembly and Disassembly ; Exome/genetics ; Female ; Genetic Predisposition to Disease/*genetics ; Germ-Line Mutation/genetics ; Humans ; Male ; Molecular Sequence Data ; Mutation/*genetics ; Mutation, Missense/genetics ; Nerve Net/metabolism ; Odds Ratio ; Synapses/*metabolism ; Transcription, Genetic/*genetics
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  • 73
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    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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  • 74
    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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  • 75
    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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  • 76
    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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  • 77
    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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  • 78
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    Unknown
    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: 2014-09-05
    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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  • 80
    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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  • 81
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    Unknown
    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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  • 82
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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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  • 83
    Publication Date: 2014-05-13
    Description: 2-Oxoglutarate (2OG)-dependent oxygenases have important roles in the regulation of gene expression via demethylation of N-methylated chromatin components and in the hydroxylation of transcription factors and splicing factor proteins. Recently, 2OG-dependent oxygenases that catalyse hydroxylation of transfer RNA and ribosomal proteins have been shown to be important in translation relating to cellular growth, TH17-cell differentiation and translational accuracy. The finding that ribosomal oxygenases (ROXs) occur in organisms ranging from prokaryotes to humans raises questions as to their structural and evolutionary relationships. In Escherichia coli, YcfD catalyses arginine hydroxylation in the ribosomal protein L16; in humans, MYC-induced nuclear antigen (MINA53; also known as MINA) and nucleolar protein 66 (NO66) catalyse histidine hydroxylation in the ribosomal proteins RPL27A and RPL8, respectively. The functional assignments of ROXs open therapeutic possibilities via either ROX inhibition or targeting of differentially modified ribosomes. Despite differences in the residue and protein selectivities of prokaryotic and eukaryotic ROXs, comparison of the crystal structures of E. coli YcfD and Rhodothermus marinus YcfD with those of human MINA53 and NO66 reveals highly conserved folds and novel dimerization modes defining a new structural subfamily of 2OG-dependent oxygenases. ROX structures with and without their substrates support their functional assignments as hydroxylases but not demethylases, and reveal how the subfamily has evolved to catalyse the hydroxylation of different residue side chains of ribosomal proteins. Comparison of ROX crystal structures with those of other JmjC-domain-containing hydroxylases, including the hypoxia-inducible factor asparaginyl hydroxylase FIH and histone N(epsilon)-methyl lysine demethylases, identifies branch points in 2OG-dependent oxygenase evolution and distinguishes between JmjC-containing hydroxylases and demethylases catalysing modifications of translational and transcriptional machinery. The structures reveal that new protein hydroxylation activities can evolve by changing the coordination position from which the iron-bound substrate-oxidizing species reacts. This coordination flexibility has probably contributed to the evolution of the wide range of reactions catalysed by oxygenases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066111/" 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/PMC4066111/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chowdhury, Rasheduzzaman -- Sekirnik, Rok -- Brissett, Nigel C -- Krojer, Tobias -- Ho, Chia-Hua -- Ng, Stanley S -- Clifton, Ian J -- Ge, Wei -- Kershaw, Nadia J -- Fox, Gavin C -- Muniz, Joao R C -- Vollmar, Melanie -- Phillips, Claire -- Pilka, Ewa S -- Kavanagh, Kathryn L -- von Delft, Frank -- Oppermann, Udo -- McDonough, Michael A -- Doherty, Aidan J -- Schofield, Christopher J -- 092809/Wellcome Trust/United Kingdom -- 6947/Cancer Research UK/United Kingdom -- BB/C518230/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/L009846/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- Arthritis Research UK/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- Cancer Research UK/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2014 Jun 19;510(7505):422-6. doi: 10.1038/nature13263. Epub 2014 May 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Department of Chemistry and Oxford Centre for Integrative Systems Biology, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK. ; 1] The Department of Chemistry and Oxford Centre for Integrative Systems Biology, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK [2]. ; 1] Genome Damage and Stability Centre, University of Sussex, Brighton BN1 9RQ, UK [2]. ; Structural Genomics Consortium, University of Oxford, Headington, Oxford OX3 7DQ, UK. ; Synchrotron SOLEIL, Saint Aubin, 91192 Gif-sur-Yvette Cedex, France. ; 1] Structural Genomics Consortium, University of Oxford, Headington, Oxford OX3 7DQ, UK [2] NIHR Oxford Biomedical Research Unit, Botnar Research Centre, Oxford OX3 7LD, UK. ; Genome Damage and Stability Centre, University of Sussex, Brighton BN1 9RQ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24814345" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Catalytic Domain ; Conserved Sequence ; Eukaryota/classification/*enzymology ; Humans ; *Models, Molecular ; Oxygenases/*chemistry/metabolism ; Phylogeny ; Prokaryotic Cells/classification/*enzymology ; Protein Folding ; Protein Structure, Tertiary ; Ribosomes/*enzymology ; Sequence Alignment
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  • 84
    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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  • 85
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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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  • 86
    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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  • 87
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    Nature Publishing Group (NPG)
    Publication Date: 2014-01-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, David -- England -- Nature. 2014 Jan 9;505(7482):153-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24409511" target="_blank"〉PubMed〈/a〉
    Keywords: Cooperative Behavior ; History, 20th Century ; History, 21st Century ; Interdisciplinary Communication ; Physics ; Research/economics/*history/*organization & administration/trends ; Research Support as Topic/economics/history/trends ; United States ; World War II
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  • 88
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    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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  • 89
    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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  • 90
    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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  • 91
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    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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  • 92
    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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  • 93
    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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  • 94
    Publication Date: 2014-07-22
    Description: Programmed -1 ribosomal frameshift (-1 PRF) signals redirect translating ribosomes to slip back one base on messenger RNAs. Although well characterized in viruses, how these elements may regulate cellular gene expression is not understood. Here we describe a -1 PRF signal in the human mRNA encoding CCR5, the HIV-1 co-receptor. CCR5 mRNA-mediated -1 PRF is directed by an mRNA pseudoknot, and is stimulated by at least two microRNAs. Mapping the mRNA-miRNA interaction suggests that formation of a triplex RNA structure stimulates -1 PRF. A -1 PRF event on the CCR5 mRNA directs translating ribosomes to a premature termination codon, destabilizing it through the nonsense-mediated mRNA decay pathway. At least one additional mRNA decay pathway is also involved. Functional -1 PRF signals that seem to be regulated by miRNAs are also demonstrated in mRNAs encoding six other cytokine receptors, suggesting a novel mode through which immune responses may be fine-tuned in mammalian cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4369343/" 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/PMC4369343/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Belew, Ashton Trey -- Meskauskas, Arturas -- Musalgaonkar, Sharmishtha -- Advani, Vivek M -- Sulima, Sergey O -- Kasprzak, Wojciech K -- Shapiro, Bruce A -- Dinman, Jonathan D -- 5 R01GM058859/GM/NIGMS NIH HHS/ -- HHSN261200800001/PHS HHS/ -- R01 GM058859/GM/NIGMS NIH HHS/ -- R01 HL119439/HL/NHLBI NIH HHS/ -- R21 GM068123/GM/NIGMS NIH HHS/ -- R21GM068123/GM/NIGMS NIH HHS/ -- T32 AI051967/AI/NIAID NIH HHS/ -- T32AI051967/AI/NIAID NIH HHS/ -- T32GM080201/GM/NIGMS NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2014 Aug 21;512(7514):265-9. doi: 10.1038/nature13429. Epub 2014 Jul 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland 20742, USA [2]. ; 1] Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland 20742, USA [2] Department of Biotechnology and Microbiology, Vilnius University, Vilnius, LT 03101, Lithuania [3]. ; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland 20742, USA. ; 1] Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland 20742, USA [2] VIB Center for the Biology of Disease, KU Leuven, Campus Gasthuisberg, Herestraat 49, bus 602, 3000 Leuven, Belgium. ; Basic Science Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA. ; Basic Research Laboratory, National Cancer Institute, Frederick, Maryland 21702, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043019" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding Sites ; Cell Survival ; Codon, Nonsense/genetics ; Frameshifting, Ribosomal/*genetics ; HeLa Cells ; Humans ; MicroRNAs/*genetics ; Models, Molecular ; Molecular Sequence Data ; *Nonsense Mediated mRNA Decay ; Nucleic Acid Conformation ; RNA, Messenger/chemistry/*genetics/*metabolism ; Receptors, CCR5/*genetics ; Receptors, Interleukin/genetics ; Regulatory Sequences, Ribonucleic Acid ; Ribosomes/metabolism
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  • 95
    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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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 96
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    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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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 97
    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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  • 98
    Publication Date: 2014-10-16
    Description: The most important energy development of the past decade has been the wide deployment of hydraulic fracturing technologies that enable the production of previously uneconomic shale gas resources in North America. If these advanced gas production technologies were to be deployed globally, the energy market could see a large influx of economically competitive unconventional gas resources. The climate implications of such abundant natural gas have been hotly debated. Some researchers have observed that abundant natural gas substituting for coal could reduce carbon dioxide (CO2) emissions. Others have reported that the non-CO2 greenhouse gas emissions associated with shale gas production make its lifecycle emissions higher than those of coal. Assessment of the full impact of abundant gas on climate change requires an integrated approach to the global energy-economy-climate systems, but the literature has been limited in either its geographic scope or its coverage of greenhouse gases. Here we show that market-driven increases in global supplies of unconventional natural gas do not discernibly reduce the trajectory of greenhouse gas emissions or climate forcing. Our results, based on simulations from five state-of-the-art integrated assessment models of energy-economy-climate systems independently forced by an abundant gas scenario, project large additional natural gas consumption of up to +170 per cent by 2050. The impact on CO2 emissions, however, is found to be much smaller (from -2 per cent to +11 per cent), and a majority of the models reported a small increase in climate forcing (from -0.3 per cent to +7 per cent) associated with the increased use of abundant gas. Our results show that although market penetration of globally abundant gas may substantially change the future energy system, it is not necessarily an effective substitute for climate change mitigation policy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McJeon, Haewon -- Edmonds, Jae -- Bauer, Nico -- Clarke, Leon -- Fisher, Brian -- Flannery, Brian P -- Hilaire, Jerome -- Krey, Volker -- Marangoni, Giacomo -- Mi, Raymond -- Riahi, Keywan -- Rogner, Holger -- Tavoni, Massimo -- England -- Nature. 2014 Oct 23;514(7523):482-5. doi: 10.1038/nature13837. Epub 2014 Oct 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Pacific Northwest National Laboratory, JGCRI, 5825 University Research Court, Suite 3500, College Park, Maryland 20740, USA. ; Potsdam Institute for Climate Impact Research, PO Box 60 12 03, D-14412 Potsdam, Germany. ; BAEconomics, PO Box 5447, Kingston, Australian Capital Territory 2604, Australia. ; Resources for the Future, 1616 P Street Northwest, Washington, DC 20036, USA. ; International Institute for Applied Systems Analysis, Schlossplatz 1, A-2361 Laxenburg, Austria. ; Centro Euromediterraneo sui Cambiamenti Climatici and Politecnico di Milano, Via Lambruschini 4b, 20156 Milan, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25317557" target="_blank"〉PubMed〈/a〉
    Keywords: Carbon Dioxide/analysis ; Climate Change/*statistics & numerical data ; *Environmental Policy ; Greenhouse Effect/prevention & control/statistics & numerical data ; Models, Theoretical ; Natural Gas/economics/supply & distribution/*utilization ; Time Factors
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 99
    Publication Date: 2014-03-29
    Description: Many aspects of cellular physiology remain unstudied in somatic stem cells, for example, there are almost no data on protein synthesis in any somatic stem cell. Here we set out to compare protein synthesis in haematopoietic stem cells (HSCs) and restricted haematopoietic progenitors. We found that the amount of protein synthesized per hour in HSCs in vivo was lower than in most other haematopoietic cells, even if we controlled for differences in cell cycle status or forced HSCs to undergo self-renewing divisions. Reduced ribosome function in Rpl24(Bst/+) mice further reduced protein synthesis in HSCs and impaired HSC function. Pten deletion increased protein synthesis in HSCs but also reduced HSC function. Rpl24(Bst/+) cell-autonomously rescued the effects of Pten deletion in HSCs; blocking the increase in protein synthesis, restoring HSC function, and delaying leukaemogenesis. Pten deficiency thus depletes HSCs and promotes leukaemia partly by increasing protein synthesis. Either increased or decreased protein synthesis impairs HSC function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4015626/" 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/PMC4015626/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Signer, Robert A J -- Magee, Jeffrey A -- Salic, Adrian -- Morrison, Sean J -- K12-HD068369/HD/NICHD NIH HHS/ -- MFE-106993/Canadian Institutes of Health Research/Canada -- R01 DK100848/DK/NIDDK NIH HHS/ -- R37 AG024945/AG/NIA NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 May 1;509(7498):49-54. doi: 10.1038/nature13035. Epub 2014 Mar 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Children's Research Institute, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, 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/24670665" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Proliferation ; Cell Transformation, Neoplastic/genetics/metabolism/pathology ; Female ; Flow Cytometry ; Genetic Complementation Test ; Hematopoietic Stem Cells/cytology/drug effects/*metabolism/pathology ; Homeostasis/drug effects/genetics ; Kinetics ; Leukemia/genetics/metabolism/pathology ; Male ; Mice ; Mutation/genetics ; PTEN Phosphohydrolase/deficiency/genetics ; Proteasome Endopeptidase Complex/drug effects/metabolism ; *Protein Biosynthesis/drug effects/genetics ; Puromycin/analogs & derivatives/metabolism ; Ribosomal Proteins/genetics/metabolism ; Ribosomes/genetics/metabolism ; Time Factors
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 100
    Publication Date: 2014-09-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kelly, J Daniel -- England -- Nature. 2014 Sep 11;513(7517):145. doi: 10.1038/513145a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25209763" target="_blank"〉PubMed〈/a〉
    Keywords: Africa, Western ; Diagnostic Equipment/standards ; Health Facilities/standards/supply & distribution ; Hemorrhagic Fever, Ebola/*diagnosis/therapy ; Humans ; Mobile Health Units ; 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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