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  • Models, Biological  (251)
  • Nature Publishing Group (NPG)  (251)
  • American Institute of Physics (AIP)
  • 2010-2014  (251)
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  • 1
    Publication Date: 2014-02-07
    Description: Alveoli are gas-exchange sacs lined by squamous alveolar type (AT) 1 cells and cuboidal, surfactant-secreting AT2 cells. Classical studies suggested that AT1 arise from AT2 cells, but recent studies propose other sources. Here we use molecular markers, lineage tracing and clonal analysis to map alveolar progenitors throughout the mouse lifespan. We show that, during development, AT1 and AT2 cells arise directly from a bipotent progenitor, whereas after birth new AT1 cells derive from rare, self-renewing, long-lived, mature AT2 cells that produce slowly expanding clonal foci of alveolar renewal. This stem-cell function is broadly activated by AT1 injury, and AT2 self-renewal is selectively induced by EGFR (epidermal growth factor receptor) ligands in vitro and oncogenic Kras(G12D) in vivo, efficiently generating multifocal, clonal adenomas. Thus, there is a switch after birth, when AT2 cells function as stem cells that contribute to alveolar renewal, repair and cancer. We propose that local signals regulate AT2 stem-cell activity: a signal transduced by EGFR-KRAS controls self-renewal and is hijacked during oncogenesis, whereas another signal controls reprogramming to AT1 fate.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4013278/" 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/PMC4013278/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Desai, Tushar J -- Brownfield, Douglas G -- Krasnow, Mark A -- P30 CA124435/CA/NCI NIH HHS/ -- U01 HL099995/HL/NHLBI NIH HHS/ -- U01 HL099999/HL/NHLBI NIH HHS/ -- England -- Nature. 2014 Mar 13;507(7491):190-4. doi: 10.1038/nature12930. Epub 2014 Feb 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305-5307, USA [2] Department of Internal Medicine, Division of Pulmonary and Critical Care, Stanford University School of Medicine, Stanford, California 94305-5307, USA. ; Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305-5307, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24499815" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation ; Cell Division ; Cell Lineage ; Cell Transformation, Neoplastic/metabolism/pathology ; Cells, Cultured ; Cellular Reprogramming ; Clone Cells/cytology ; Female ; Lung/*cytology/embryology/*growth & development/pathology ; Lung Neoplasms/metabolism/*pathology ; Male ; Mice ; Models, Biological ; Multipotent Stem Cells/*cytology/metabolism/*pathology ; Proto-Oncogene Proteins p21(ras)/genetics/metabolism ; Pulmonary Alveoli/*cytology ; Receptor, Epidermal Growth Factor/metabolism ; *Regeneration ; Signal Transduction
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  • 2
    Publication Date: 2014-05-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gibney, Elizabeth -- England -- Nature. 2014 May 29;509(7502):544-5. doi: 10.1038/509544a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24870523" target="_blank"〉PubMed〈/a〉
    Keywords: Academies and Institutes/*organization & administration ; Biomedical Research/*manpower/methods/*organization & administration/trends ; Interdisciplinary Communication ; Interdisciplinary Studies/*trends ; London ; Models, Biological ; Physics/methods/*organization & administration ; *Research Personnel
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  • 3
    Publication Date: 2014-04-18
    Description: The equilibrium theory of island biogeography is the basis for estimating extinction rates and a pillar of conservation science. The default strategy for conserving biodiversity is the designation of nature reserves, treated as islands in an inhospitable sea of human activity. Despite the profound influence of islands on conservation theory and practice, their mainland analogues, forest fragments in human-dominated landscapes, consistently defy expected biodiversity patterns based on island biogeography theory. Countryside biogeography is an alternative framework, which recognizes that the fate of the world's wildlife will be decided largely by the hospitality of agricultural or countryside ecosystems. Here we directly test these biogeographic theories by comparing a Neotropical countryside ecosystem with a nearby island ecosystem, and show that each supports similar bat biodiversity in fundamentally different ways. The island ecosystem conforms to island biogeographic predictions of bat species loss, in which the water matrix is not habitat. In contrast, the countryside ecosystem has high species richness and evenness across forest reserves and smaller forest fragments. Relative to forest reserves and fragments, deforested countryside habitat supports a less species-rich, yet equally even, bat assemblage. Moreover, the bat assemblage associated with deforested habitat is compositionally novel because of predictable changes in abundances by many species using human-made habitat. Finally, we perform a global meta-analysis of bat biogeographic studies, spanning more than 700 species. It generalizes our findings, showing that separate biogeographic theories for countryside and island ecosystems are necessary. A theory of countryside biogeography is essential to conservation strategy in the agricultural ecosystems that comprise roughly half of the global land surface and are likely to increase even further.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mendenhall, Chase D -- Karp, Daniel S -- Meyer, Christoph F J -- Hadly, Elizabeth A -- Daily, Gretchen C -- England -- Nature. 2014 May 8;509(7499):213-7. doi: 10.1038/nature13139. Epub 2014 Apr 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Center for Conservation Biology, Stanford University, Stanford, California 94305, USA [2] Department of Biology, Stanford University, Stanford, California 94305, USA. ; 1] Center for Conservation Biology, Stanford University, Stanford, California 94305, USA [2] Department of Biology, Stanford University, Stanford, California 94305, USA [3] Department of Environmental Science, Policy & Management, University of California, Berkeley, California 94720, USA [4] The Nature Conservancy, Berkeley, California 94705, USA. ; 1] Institute of Experimental Ecology, University of Ulm, 89069 Ulm, Germany [2] Centre for Environmental Biology, University of Lisbon, 1749-016 Lisbon, Portugal. ; Department of Biology, Stanford University, Stanford, California 94305, USA. ; 1] Center for Conservation Biology, Stanford University, Stanford, California 94305, USA [2] Department of Biology, Stanford University, Stanford, California 94305, USA [3] Woods Institute for the Environment, Stanford University, Stanford, California 94305, USA [4] Global Economic Dynamics and the Biosphere, Royal Swedish Academy of Sciences, Stockholm, SE-104 05, Sweden [5] Stockholm Resilience Centre, University of Stockholm, Stockholm, SE-106 91, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24739971" target="_blank"〉PubMed〈/a〉
    Keywords: *Agriculture/methods ; Animals ; *Biodiversity ; Chiroptera/physiology ; *Conservation of Natural Resources ; Costa Rica ; Extinction, Biological ; *Geography ; Islands ; Lakes ; Models, Biological ; Population Dynamics ; Trees/*growth & development
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  • 4
    Publication Date: 2014-06-06
    Description: Advances in our understanding of the mechanisms that bring about the resolution of acute inflammation have uncovered a new genus of pro-resolving lipid mediators that include the lipoxin, resolvin, protectin and maresin families, collectively called specialized pro-resolving mediators. Synthetic versions of these mediators have potent bioactions when administered in vivo. In animal experiments, the mediators evoke anti-inflammatory and novel pro-resolving mechanisms, and enhance microbial clearance. Although they have been identified in inflammation resolution, specialized pro-resolving mediators are conserved structures that also function in host defence, pain, organ protection and tissue remodelling. This Review covers the mechanisms of specialized pro-resolving mediators and omega-3 essential fatty acid pathways that could help us to understand their physiological functions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263681/" 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/PMC4263681/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Serhan, Charles N -- P01 GM095467/GM/NIGMS NIH HHS/ -- P01GM095467/GM/NIGMS NIH HHS/ -- R01 GM038765/GM/NIGMS NIH HHS/ -- R01GM038765/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Jun 5;510(7503):92-101. doi: 10.1038/nature13479.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24899309" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chronic Disease ; Docosahexaenoic Acids/metabolism ; Fatty Acids, Omega-3/*metabolism ; Fatty Acids, Unsaturated/metabolism ; Humans ; Immunity ; Infection/metabolism ; Inflammation/drug therapy/*metabolism/pathology ; Inflammation Mediators/*metabolism/therapeutic use ; Models, Biological ; Pain/metabolism ; Regeneration ; Translational Medical Research ; Wound Healing
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  • 5
    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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  • 6
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    Nature Publishing Group (NPG)
    Publication Date: 2014-12-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Callaway, Ewen -- England -- Nature. 2014 Dec 11;516(7530):157. doi: 10.1038/516157a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25503215" target="_blank"〉PubMed〈/a〉
    Keywords: Academies and Institutes/*economics/*organization & administration ; Cell Biology/*economics/*organization & administration ; Epithelial Cells/cytology ; Goals ; Humans ; Induced Pluripotent Stem Cells/cytology ; Models, Biological ; Myocytes, Cardiac/cytology ; Organ Specificity
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  • 7
    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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  • 8
    Publication Date: 2014-09-26
    Description: For centuries, biogeographers have examined the factors that produce patterns of biodiversity across regions. The study of islands has proved particularly fruitful and has led to the theory that geographic area and isolation influence species colonization, extinction and speciation such that larger islands have more species and isolated islands have fewer species (that is, positive species-area and negative species-isolation relationships). However, experimental tests of this theory have been limited, owing to the difficulty in experimental manipulation of islands at the scales at which speciation and long-distance colonization are relevant. Here we have used the human-aided transport of exotic anole lizards among Caribbean islands as such a test at an appropriate scale. In accord with theory, as anole colonizations have increased, islands impoverished in native species have gained the most exotic species, the past influence of speciation on island biogeography has been obscured, and the species-area relationship has strengthened while the species-isolation relationship has weakened. Moreover, anole biogeography increasingly reflects anthropogenic rather than geographic processes. Unlike the island biogeography of the past that was determined by geographic area and isolation, in the Anthropocene--an epoch proposed for the present time interval--island biogeography is dominated by the economic isolation of human populations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Helmus, Matthew R -- Mahler, D Luke -- Losos, Jonathan B -- England -- Nature. 2014 Sep 25;513(7519):543-6. doi: 10.1038/nature13739.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Amsterdam Global Change Institute, Department of Animal Ecology, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands. ; Center for Population Biology, University of California, Davis, California 95616, USA. ; Department of Organismic and Evolutionary Biology and Museum of Comparative Zoology, Harvard University, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25254475" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biodiversity ; Commerce/history/statistics & numerical data ; Geography ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Human Activities/history/statistics & numerical data ; Introduced Species/history/*statistics & numerical data ; *Islands ; *Lizards/physiology ; Models, Biological ; Models, Economic ; Population Dynamics ; West Indies
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  • 9
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    Nature Publishing Group (NPG)
    Publication Date: 2014-06-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Spinney, Laura -- England -- Nature. 2014 Jun 5;510(7503):26-8. doi: 10.1038/510026a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24899289" target="_blank"〉PubMed〈/a〉
    Keywords: Age of Onset ; Alleles ; Alzheimer Disease/drug therapy/*genetics/metabolism/pathology ; Amyloid beta-Peptides/antagonists & inhibitors/metabolism ; Animals ; Apolipoprotein E2/genetics/metabolism ; Apolipoprotein E3/chemistry/genetics/metabolism ; Apolipoprotein E4/chemistry/*genetics/metabolism ; Case-Control Studies ; Chromosomes, Human, Pair 19/genetics ; Clinical Trials as Topic ; Genetic Predisposition to Disease/*genetics ; Humans ; Hypoglycemic Agents/pharmacology/therapeutic use ; Membrane Transport Proteins/genetics/metabolism ; Mice ; Mice, Transgenic ; Mitochondria/drug effects/pathology ; Models, Biological ; Thiazolidinediones/pharmacology/therapeutic use
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  • 10
    Publication Date: 2014-01-28
    Description: To resolve the mechanisms that switch competition to cooperation is key to understanding biological organization. This is particularly relevant for intrasexual competition, which often leads to males harming females. Recent theory proposes that kin selection may modulate female harm by relaxing competition among male relatives. Here we experimentally manipulate the relatedness of groups of male Drosophila melanogaster competing over females to demonstrate that, as expected, within-group relatedness inhibits male competition and female harm. Females exposed to groups of three brothers unrelated to the female had higher lifetime reproductive success and slower reproductive ageing compared to females exposed to groups of three males unrelated to each other. Triplets of brothers also fought less with each other, courted females less intensively and lived longer than triplets of unrelated males. However, associations among brothers may be vulnerable to invasion by minorities of unrelated males: when two brothers were matched with an unrelated male, the unrelated male sired on average twice as many offspring as either brother. These results demonstrate that relatedness can profoundly affect fitness through its modulation of intrasexual competition, as flies plastically adjust sexual behaviour in a manner consistent with kin-selection theory.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carazo, Pau -- Tan, Cedric K W -- Allen, Felicity -- Wigby, Stuart -- Pizzari, Tommaso -- Wellcome Trust/United Kingdom -- England -- Nature. 2014 Jan 30;505(7485):672-5. doi: 10.1038/nature12949. Epub 2014 Jan 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Edward Grey Institute, Department of Zoology, University of Oxford, Oxford OX1 3PS, UK [2]. ; Edward Grey Institute, Department of Zoology, University of Oxford, Oxford OX1 3PS, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24463521" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Competitive Behavior/physiology ; *Cooperative Behavior ; Drosophila melanogaster/genetics/*physiology ; Female ; Heredity/physiology ; Longevity/genetics/physiology ; Male ; Models, Biological ; Reproduction/physiology ; Sexual Behavior, Animal/*physiology ; *Siblings
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  • 11
    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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  • 12
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    Nature Publishing Group (NPG)
    Publication Date: 2014-07-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hughes, Virginia -- England -- Nature. 2014 Jul 17;511(7509):282-4. doi: 10.1038/511282a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25030150" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Bariatric Surgery ; Bile Acids and Salts/metabolism ; Biomarkers/analysis ; Biomedical Research ; Diabetes Mellitus/metabolism/prevention & control ; Gammaproteobacteria/isolation & purification/metabolism ; Ghrelin/metabolism ; Glucose/metabolism ; Gram-Positive Bacteria/isolation & purification/metabolism ; Humans ; Hunger/physiology ; Mice ; Models, Animal ; Models, Biological ; Rats ; Receptors, Cytoplasmic and Nuclear/metabolism ; Stomach/*surgery ; *Weight Loss
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  • 13
    Publication Date: 2014-01-28
    Description: What mechanisms underlie the transitions responsible for the diverse shapes observed in the living world? Although bacteria exhibit a myriad of morphologies, the mechanisms responsible for the evolution of bacterial cell shape are not understood. We investigated morphological diversity in a group of bacteria that synthesize an appendage-like extension of the cell envelope called the stalk. The location and number of stalks varies among species, as exemplified by three distinct subcellular positions of stalks within a rod-shaped cell body: polar in the genus Caulobacter and subpolar or bilateral in the genus Asticcacaulis. Here we show that a developmental regulator of Caulobacter crescentus, SpmX, is co-opted in the genus Asticcacaulis to specify stalk synthesis either at the subpolar or bilateral positions. We also show that stepwise evolution of a specific region of SpmX led to the gain of a new function and localization of this protein, which drove the sequential transition in stalk positioning. Our results indicate that changes in protein function, co-option and modularity are key elements in the evolution of bacterial morphology. Therefore, similar evolutionary principles of morphological transitions apply to both single-celled prokaryotes and multicellular eukaryotes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4035126/" 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/PMC4035126/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jiang, Chao -- Brown, Pamela J B -- Ducret, Adrien -- Brun, Yves V -- AI072992/AI/NIAID NIH HHS/ -- GM051986/GM/NIGMS NIH HHS/ -- R01 GM051986/GM/NIGMS NIH HHS/ -- S10RR028697-01/RR/NCRR NIH HHS/ -- England -- Nature. 2014 Feb 27;506(7489):489-93. doi: 10.1038/nature12900. Epub 2014 Jan 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Indiana University, Bloomington, Indiana 47405, USA. ; 1] Department of Biology, Indiana University, Bloomington, Indiana 47405, USA [2] Division of Biological Sciences, University of Missouri, Columbia, Missouri 65211, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24463524" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteria/*cytology/*metabolism ; Bacterial Proteins/*metabolism ; *Biological Evolution ; Caulobacter crescentus/cytology/metabolism ; Caulobacteraceae/cytology/metabolism ; Cell Membrane/metabolism ; *Cell Polarity ; Evolution, Molecular ; Models, Biological ; Molecular Sequence Data ; Phylogeny ; Protein Transport
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  • 14
    Publication Date: 2014-09-05
    Description: Elucidating the role of molecular stochasticity in cellular growth is central to understanding phenotypic heterogeneity and the stability of cellular proliferation. The inherent stochasticity of metabolic reaction events should have negligible effect, because of averaging over the many reaction events contributing to growth. Indeed, metabolism and growth are often considered to be constant for fixed conditions. Stochastic fluctuations in the expression level of metabolic enzymes could produce variations in the reactions they catalyse. However, whether such molecular fluctuations can affect growth is unclear, given the various stabilizing regulatory mechanisms, the slow adjustment of key cellular components such as ribosomes, and the secretion and buffering of excess metabolites. Here we use time-lapse microscopy to measure fluctuations in the instantaneous growth rate of single cells of Escherichia coli, and quantify time-resolved cross-correlations with the expression of lac genes and enzymes in central metabolism. We show that expression fluctuations of catabolically active enzymes can propagate and cause growth fluctuations, with transmission depending on the limitation of the enzyme to growth. Conversely, growth fluctuations propagate back to perturb expression. Accordingly, enzymes were found to transmit noise to other unrelated genes via growth. Homeostasis is promoted by a noise-cancelling mechanism that exploits fluctuations in the dilution of proteins by cell-volume expansion. The results indicate that molecular noise is propagated not only by regulatory proteins but also by metabolic reactions. They also suggest that cellular metabolism is inherently stochastic, and a generic source of phenotypic heterogeneity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kiviet, Daniel J -- Nghe, Philippe -- Walker, Noreen -- Boulineau, Sarah -- Sunderlikova, Vanda -- Tans, Sander J -- England -- Nature. 2014 Oct 16;514(7522):376-9. doi: 10.1038/nature13582. Epub 2014 Sep 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] FOM institute AMOLF, Science Park 104, 1098 XG Amsterdam, the Netherlands [2] Department of Environmental Systems Science, ETH Zurich, Universitaetsstrasse 16, 8092 Zurich, Switzerland [3] Department of Environmental Microbiology, Eawag, Ueberlandstrasse 133, 8600 Duebendorf, Switzerland [4]. ; 1] FOM institute AMOLF, Science Park 104, 1098 XG Amsterdam, the Netherlands [2] Laboratoire de Biochimie, UMR 8231 CNRS/ESPCI, Ecole Superieure de Physique et de Chimie industrielles, 10 rue Vauquelin, 75005 Paris, France. [3]. ; FOM institute AMOLF, Science Park 104, 1098 XG Amsterdam, the Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25186725" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Enlargement ; Cell Proliferation ; Escherichia coli/enzymology/genetics/*growth & development/*metabolism ; Escherichia coli Proteins/genetics/metabolism ; Homeostasis ; Lac Operon/genetics ; Microscopy ; Models, Biological ; *Single-Cell Analysis ; Stochastic Processes ; Time-Lapse Imaging
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  • 15
    Publication Date: 2014-08-01
    Description: Mesenchymal stem cells occupy niches in stromal tissues where they provide sources of cells for specialized mesenchymal derivatives during growth and repair. The origins of mesenchymal stem cells have been the subject of considerable discussion, and current consensus holds that perivascular cells form mesenchymal stem cells in most tissues. The continuously growing mouse incisor tooth offers an excellent model to address the origin of mesenchymal stem cells. These stem cells dwell in a niche at the tooth apex where they produce a variety of differentiated derivatives. Cells constituting the tooth are mostly derived from two embryonic sources: neural crest ectomesenchyme and ectodermal epithelium. It has been thought for decades that the dental mesenchymal stem cells giving rise to pulp cells and odontoblasts derive from neural crest cells after their migration in the early head and formation of ectomesenchymal tissue. Here we show that a significant population of mesenchymal stem cells during development, self-renewal and repair of a tooth are derived from peripheral nerve-associated glia. Glial cells generate multipotent mesenchymal stem cells that produce pulp cells and odontoblasts. By combining a clonal colour-coding technique with tracing of peripheral glia, we provide new insights into the dynamics of tooth organogenesis and growth.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaukua, Nina -- Shahidi, Maryam Khatibi -- Konstantinidou, Chrysoula -- Dyachuk, Vyacheslav -- Kaucka, Marketa -- Furlan, Alessandro -- An, Zhengwen -- Wang, Longlong -- Hultman, Isabell -- Ahrlund-Richter, Lars -- Blom, Hans -- Brismar, Hjalmar -- Lopes, Natalia Assaife -- Pachnis, Vassilis -- Suter, Ueli -- Clevers, Hans -- Thesleff, Irma -- Sharpe, Paul -- Ernfors, Patrik -- Fried, Kaj -- Adameyko, Igor -- G0901599/Medical Research Council/United Kingdom -- MC_U117537087/Medical Research Council/United Kingdom -- England -- Nature. 2014 Sep 25;513(7519):551-4. doi: 10.1038/nature13536. Epub 2014 Jul 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Neuroscience, Karolinska Institutet, Stockholm 17177, Sweden [2]. ; 1] Department of Dental Medicine, Karolinska Institutet, Stockholm 17177, Sweden [2]. ; Division of Molecular Neurobiology, MRC National Institute for Medical Research, London NW7 1AA, UK. ; 1] Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm 17177, Sweden [2] A.V. Zhirmunsky Institute of Marine Biology of the Far Eastern Branch of the Russian Academy of Sciences, Vladivostok 690041, Russia. ; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm 17177, Sweden. ; Unit of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm 17177, Sweden. ; Department of Craniofacial Development and Stem Cell Biology, King's College London Dental Institute, Guy's Hospital, London SE1 3QD, UK. ; Department of Women's and Children's Health, Karolinska Institutet, Stockholm 17177, Sweden. ; Science for Life Laboratory, Royal Institute of Technology, Stockholm 17177, Sweden. ; Department of Biology, Institute of Molecular Health Sciences, ETH Zurich CH-8093, Switzerland. ; 1] Hubrecht Institute, Koninklijke Nederlandse Akademie van Wetenschappen (KNAW), PO Box 85164, 3508 AD Utrecht, the Netherlands [2] Department of Molecular Genetics, University Medical Center Utrecht, Utrecht 3508 GA, the Netherlands. ; Institute of Biotechnology, Developmental Biology Program, University of Helsinki, Helsinki FI-00014, Finland. ; Department of Neuroscience, Karolinska Institutet, Stockholm 17177, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25079316" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Differentiation ; *Cell Lineage ; Cell Tracking ; Clone Cells/cytology ; Dental Pulp/cytology ; Female ; Incisor/*cytology/embryology ; Male ; Mesenchymal Stromal Cells/*cytology ; Mice ; Models, Biological ; Neural Crest/cytology ; Neuroglia/*cytology ; Odontoblasts/cytology ; Regeneration ; Schwann Cells/cytology
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  • 16
    Publication Date: 2014-02-07
    Description: The seasonality of sunlight and rainfall regulates net primary production in tropical forests. Previous studies have suggested that light is more limiting than water for tropical forest productivity, consistent with greening of Amazon forests during the dry season in satellite data. We evaluated four potential mechanisms for the seasonal green-up phenomenon, including increases in leaf area or leaf reflectance, using a sophisticated radiative transfer model and independent satellite observations from lidar and optical sensors. Here we show that the apparent green up of Amazon forests in optical remote sensing data resulted from seasonal changes in near-infrared reflectance, an artefact of variations in sun-sensor geometry. Correcting this bidirectional reflectance effect eliminated seasonal changes in surface reflectance, consistent with independent lidar observations and model simulations with unchanging canopy properties. The stability of Amazon forest structure and reflectance over seasonal timescales challenges the paradigm of light-limited net primary production in Amazon forests and enhanced forest growth during drought conditions. Correcting optical remote sensing data for artefacts of sun-sensor geometry is essential to isolate the response of global vegetation to seasonal and interannual climate variability.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morton, Douglas C -- Nagol, Jyoteshwar -- Carabajal, Claudia C -- Rosette, Jacqueline -- Palace, Michael -- Cook, Bruce D -- Vermote, Eric F -- Harding, David J -- North, Peter R J -- England -- Nature. 2014 Feb 13;506(7487):221-4. doi: 10.1038/nature13006. Epub 2014 Feb 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉NASA Goddard Space Flight Center, Greenbelt, Maryland 20771, USA. ; 1] University of Maryland, College Park, Department of Geographical Sciences, College Park, Maryland 20742, USA [2] Global Land Cover Facility, College Park, Maryland 20740, USA. ; 1] NASA Goddard Space Flight Center, Greenbelt, Maryland 20771, USA [2] Sigma Space Corporation, Lantham, Maryland 20706, USA. ; 1] NASA Goddard Space Flight Center, Greenbelt, Maryland 20771, USA [2] University of Maryland, College Park, Department of Geographical Sciences, College Park, Maryland 20742, USA [3] Swansea University, Department of Geography, Singleton Park, Swansea SA2 8PP, UK. ; Earth System Research Center, University of New Hampshire, Durham, New Hampshire 03824, USA. ; Swansea University, Department of Geography, Singleton Park, Swansea SA2 8PP, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24499816" target="_blank"〉PubMed〈/a〉
    Keywords: Artifacts ; Brazil ; Color ; *Droughts ; Ecosystem ; Fresh Water/analysis ; Models, Biological ; Photosynthesis ; Pigmentation/*physiology ; Plant Leaves/anatomy & histology/growth & development/*physiology ; Rain ; Satellite Imagery ; *Seasons ; *Sunlight ; Trees/anatomy & histology/growth & development/*physiology ; *Tropical Climate
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  • 17
    Publication Date: 2014-06-05
    Description: Therapeutic food interventions have reduced mortality in children with severe acute malnutrition (SAM), but incomplete restoration of healthy growth remains a major problem. The relationships between the type of nutritional intervention, the gut microbiota, and therapeutic responses are unclear. In the current study, bacterial species whose proportional representation define a healthy gut microbiota as it assembles during the first two postnatal years were identified by applying a machine-learning-based approach to 16S ribosomal RNA data sets generated from monthly faecal samples obtained from birth onwards in a cohort of children living in an urban slum of Dhaka, Bangladesh, who exhibited consistently healthy growth. These age-discriminatory bacterial species were incorporated into a model that computes a 'relative microbiota maturity index' and 'microbiota-for-age Z-score' that compare postnatal assembly (defined here as maturation) of a child's faecal microbiota relative to healthy children of similar chronologic age. The model was applied to twins and triplets (to test for associations of these indices with genetic and environmental factors, including diarrhoea), children with SAM enrolled in a randomized trial of two food interventions, and children with moderate acute malnutrition. Our results indicate that SAM is associated with significant relative microbiota immaturity that is only partially ameliorated following two widely used nutritional interventions. Immaturity is also evident in less severe forms of malnutrition and correlates with anthropometric measurements. Microbiota maturity indices provide a microbial measure of human postnatal development, a way of classifying malnourished states, and a parameter for judging therapeutic efficacy. More prolonged interventions with existing or new therapeutic foods and/or addition of gut microbes may be needed to achieve enduring repair of gut microbiota immaturity in childhood malnutrition and improve clinical outcomes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189846/" 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/PMC4189846/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Subramanian, Sathish -- Huq, Sayeeda -- Yatsunenko, Tanya -- Haque, Rashidul -- Mahfuz, Mustafa -- Alam, Mohammed A -- Benezra, Amber -- DeStefano, Joseph -- Meier, Martin F -- Muegge, Brian D -- Barratt, Michael J -- VanArendonk, Laura G -- Zhang, Qunyuan -- Province, Michael A -- Petri, William A Jr -- Ahmed, Tahmeed -- Gordon, Jeffrey I -- AI043596/AI/NIAID NIH HHS/ -- R01 AI043596/AI/NIAID NIH HHS/ -- T32 GM007067/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Jun 19;510(7505):417-21. doi: 10.1038/nature13421. Epub 2014 Jun 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Genome Sciences and Systems Biology, Washington University in St. Louis, St. Louis, Missouri 63108, USA. ; Centre for Nutrition and Food Security, International Centre for Diarrhoeal Disease Research, Dhaka 1212, Bangladesh. ; 1] Center for Genome Sciences and Systems Biology, Washington University in St. Louis, St. Louis, Missouri 63108, USA [2] Department of Anthropology, New School for Social Research, New York, New York 10003, USA. ; Division of Statistical Genomics, Washington University in St. Louis, St. Louis, Missouri 63108, USA. ; Departments of Medicine, Microbiology and Pathology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24896187" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteria/classification/genetics ; *Bacterial Physiological Phenomena ; Bangladesh ; *Biodiversity ; Feces/microbiology ; Female ; Gastrointestinal Tract/microbiology ; Humans ; Infant ; Infant Nutrition Disorders/diet therapy/*microbiology ; Male ; *Microbiota ; Models, Biological ; Nutritional Status ; RNA, Ribosomal, 16S/genetics
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  • 18
    Publication Date: 2014-09-12
    Description: Since the recognition that allopatric speciation can be induced by large-scale reconfigurations of the landscape that isolate formerly continuous populations, such as the separation of continents by plate tectonics, the uplift of mountains or the formation of large rivers, landscape change has been viewed as a primary driver of biological diversification. This process is referred to in biogeography as vicariance. In the most species-rich region of the world, the Neotropics, the sundering of populations associated with the Andean uplift is ascribed this principal role in speciation. An alternative model posits that rather than being directly linked to landscape change, allopatric speciation is initiated to a greater extent by dispersal events, with the principal drivers of speciation being organism-specific abilities to persist and disperse in the landscape. Landscape change is not a necessity for speciation in this model. Here we show that spatial and temporal patterns of genetic differentiation in Neotropical birds are highly discordant across lineages and are not reconcilable with a model linking speciation solely to landscape change. Instead, the strongest predictors of speciation are the amount of time a lineage has persisted in the landscape and the ability of birds to move through the landscape matrix. These results, augmented by the observation that most species-level diversity originated after episodes of major Andean uplift in the Neogene period, suggest that dispersal and differentiation on a matrix previously shaped by large-scale landscape events was a major driver of avian speciation in lowland Neotropical rainforests.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smith, Brian Tilston -- McCormack, John E -- Cuervo, Andres M -- Hickerson, Michael J -- Aleixo, Alexandre -- Cadena, Carlos Daniel -- Perez-Eman, Jorge -- Burney, Curtis W -- Xie, Xiaoou -- Harvey, Michael G -- Faircloth, Brant C -- Glenn, Travis C -- Derryberry, Elizabeth P -- Prejean, Jesse -- Fields, Samantha -- Brumfield, Robb T -- England -- Nature. 2014 Nov 20;515(7527):406-9. doi: 10.1038/nature13687. Epub 2014 Sep 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Museum of Natural Science, Louisiana State University, Baton Rouge, Louisiana 70803, USA [2] Department of Ornithology, American Museum of Natural History, New York, New York 10024, USA [3]. ; 1] Museum of Natural Science, Louisiana State University, Baton Rouge, Louisiana 70803, USA [2] Moore Laboratory of Zoology, Occidental College, 1600 Campus Road, Los Angeles, California 90041, USA (J.E.M.); Department of Ecology and Evolutionary Biology, Tulane University, New Orleans, Louisiana 70118, USA (A.M.C. &E.P.D.); Department of Biology, 2355 Faculty Drive, Suite 2P483, United States Air Force Academy, Colorado 80840, USA (C.W.B.); Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana 70803, USA (B.C.F.). ; 1] Museum of Natural Science, Louisiana State University, Baton Rouge, Louisiana 70803, USA [2] Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana 70803, USA [3] Moore Laboratory of Zoology, Occidental College, 1600 Campus Road, Los Angeles, California 90041, USA (J.E.M.); Department of Ecology and Evolutionary Biology, Tulane University, New Orleans, Louisiana 70118, USA (A.M.C. &E.P.D.); Department of Biology, 2355 Faculty Drive, Suite 2P483, United States Air Force Academy, Colorado 80840, USA (C.W.B.); Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana 70803, USA (B.C.F.). ; 1] Biology Department, City College of New York, New York, New York 10031, USA [2] Division of Invertebrate Zoology, American Museum of Natural History, New York, New York 10024, USA. ; Coordenacao de Zoologia, Museu Paraense Emilio Goeldi, Caixa Postal 399, CEP 66040-170, Belem, Brazil. ; Laboratorio de Biologia Evolutiva de Vertebrados, Departamento de Ciencias Biologicas, Universidad de los Andes, Bogota, Colombia. ; 1] Instituto de Zoologia y Ecologia Tropical, Universidad Central de Venezuela, Av. Los Ilustres, Los Chaguaramos, Apartado Postal 47058, Caracas 1041-A, Venezuela [2] Coleccion Ornitologica Phelps, Apartado 2009, Caracas 1010-A, Venezuela. ; Biology Department, City College of New York, New York, New York 10031, USA. ; 1] Museum of Natural Science, Louisiana State University, Baton Rouge, Louisiana 70803, USA [2] Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana 70803, USA. ; 1] Department of Ecology and Evolutionary Biology, University of California, Los Angeles, California 90095, USA [2] Moore Laboratory of Zoology, Occidental College, 1600 Campus Road, Los Angeles, California 90041, USA (J.E.M.); Department of Ecology and Evolutionary Biology, Tulane University, New Orleans, Louisiana 70118, USA (A.M.C. &E.P.D.); Department of Biology, 2355 Faculty Drive, Suite 2P483, United States Air Force Academy, Colorado 80840, USA (C.W.B.); Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana 70803, USA (B.C.F.). ; Department of Environmental Health Science, University of Georgia, Athens, Georgia 30602, USA. ; 1] Museum of Natural Science, Louisiana State University, Baton Rouge, Louisiana 70803, USA [2] Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana 70803, USA [3].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25209666" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biodiversity ; Birds/*classification/*genetics ; *Genetic Speciation ; Models, Biological ; Molecular Sequence Data ; Panama ; *Phylogeny ; *Rainforest ; Rivers ; South America ; *Tropical Climate
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  • 19
    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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  • 20
    Publication Date: 2014-05-16
    Description: MicroRNA and protein sequestration by non-coding RNAs (ncRNAs) has recently generated much interest. In the bacterial Csr/Rsm system, which is considered to be the most general global post-transcriptional regulatory system responsible for bacterial virulence, ncRNAs such as CsrB or RsmZ activate translation initiation by sequestering homodimeric CsrA-type proteins from the ribosome-binding site of a subset of messenger RNAs. However, the mechanism of ncRNA-mediated protein sequestration is not understood at the molecular level. Here we show for Pseudomonas fluorescens that RsmE protein dimers assemble sequentially, specifically and cooperatively onto the ncRNA RsmZ within a narrow affinity range. This assembly yields two different native ribonucleoprotein structures. Using a powerful combination of nuclear magnetic resonance and electron paramagnetic resonance spectroscopy we elucidate these 70-kilodalton solution structures, thereby revealing the molecular mechanism of the sequestration process and how RsmE binding protects the ncRNA from RNase E degradation. Overall, our findings suggest that RsmZ is well-tuned to sequester, store and release RsmE and therefore can be viewed as an ideal protein 'sponge'.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Duss, Olivier -- Michel, Erich -- Yulikov, Maxim -- Schubert, Mario -- Jeschke, Gunnar -- Allain, Frederic H-T -- England -- Nature. 2014 May 29;509(7502):588-92. doi: 10.1038/nature13271. Epub 2014 May 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Biology and Biophysics, ETH Zurich, CH-8093 Zurich, Switzerland. ; Laboratory of Physical Chemistry, ETH Zurich, CH-8093 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24828038" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Electron Spin Resonance Spectroscopy ; Escherichia coli/chemistry/genetics/metabolism ; Escherichia coli Proteins/chemistry/*metabolism ; Methyltransferases/chemistry/*metabolism ; Models, Biological ; Models, Molecular ; Molecular Weight ; Nuclear Magnetic Resonance, Biomolecular ; Nucleic Acid Conformation ; *Protein Binding ; Protein Multimerization ; RNA, Untranslated/chemistry/genetics/*metabolism ; Ribonucleases/metabolism ; Ribonucleoproteins/chemistry/genetics/metabolism
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  • 21
    Publication Date: 2014-03-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Callaway, Ewen -- England -- Nature. 2014 Mar 27;507(7493):414-6. doi: 10.1038/507414a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670743" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/history ; Animals ; Animals, Domestic/genetics ; Dogs ; *Evolution, Molecular ; Extinction, Biological ; Fossils ; Genomics/*methods/trends ; History, Ancient ; Hominidae/classification/genetics ; Horses/genetics ; Humans ; Models, Biological ; Neanderthals/*classification/*genetics ; Paleontology/methods/trends ; *Phylogeny ; Selection, Genetic ; Sequence Analysis, DNA/methods ; Wolves/genetics
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  • 22
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    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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  • 23
    Publication Date: 2014-10-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Victor, David G -- Kennel, Charles F -- England -- Nature. 2014 Oct 2;514(7520):30-1. doi: 10.1038/514030a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of International Relations and Pacific Studies, University of California, San Diego, La Jolla, California, USA. ; Scripps Institution of Oceanography, University of California, San Diego, La Jolla, California, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25279903" target="_blank"〉PubMed〈/a〉
    Keywords: Atmosphere/chemistry ; Carbon Dioxide/analysis ; Environmental Policy/*legislation & jurisprudence/trends ; Global Warming/*prevention & control/*statistics & numerical data ; *Goals ; Human Activities ; International Cooperation ; Models, Biological ; *Policy Making ; Risk Assessment ; Seawater/analysis ; *Temperature
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  • 24
    Publication Date: 2014-08-01
    Description: Cancers arise through a process of somatic evolution that can result in substantial sub-clonal heterogeneity within tumours. The mechanisms responsible for the coexistence of distinct sub-clones and the biological consequences of this coexistence remain poorly understood. Here we used a mouse xenograft model to investigate the impact of sub-clonal heterogeneity on tumour phenotypes and the competitive expansion of individual clones. We found that tumour growth can be driven by a minor cell subpopulation, which enhances the proliferation of all cells within a tumour by overcoming environmental constraints and yet can be outcompeted by faster proliferating competitors, resulting in tumour collapse. We developed a mathematical modelling framework to identify the rules underlying the generation of intra-tumour clonal heterogeneity. We found that non-cell-autonomous driving of tumour growth, together with clonal interference, stabilizes sub-clonal heterogeneity, thereby enabling inter-clonal interactions that can lead to new phenotypic traits.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4184961/" 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/PMC4184961/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marusyk, Andriy -- Tabassum, Doris P -- Altrock, Philipp M -- Almendro, Vanessa -- Michor, Franziska -- Polyak, Kornelia -- U54 CA143798/CA/NCI NIH HHS/ -- U54CA143798/CA/NCI NIH HHS/ -- England -- Nature. 2014 Oct 2;514(7520):54-8. doi: 10.1038/nature13556. Epub 2014 Jul 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA [3] Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] BBS Program, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA [3] Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts 02138, USA. ; 1] Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA. ; 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA [3] Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA [4] BBS Program, Harvard Medical School, Boston, Massachusetts 02115, USA [5] Harvard Stem Cell Institute and the Broad Institute, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25079331" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line, Tumor ; Cell Proliferation ; Clone Cells/*metabolism/*pathology ; Epigenesis, Genetic/genetics ; Female ; Interleukin-11/metabolism ; Mice ; Models, Biological ; Neoplasm Metastasis ; Neoplasms/*genetics/metabolism/*pathology ; Phenotype ; Tumor Microenvironment
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  • 25
    Publication Date: 2014-01-17
    Description: Many species travel in highly organized groups. The most quoted function of these configurations is to reduce energy expenditure and enhance locomotor performance of individuals in the assemblage. The distinctive V formation of bird flocks has long intrigued researchers and continues to attract both scientific and popular attention. The well-held belief is that such aggregations give an energetic benefit for those birds that are flying behind and to one side of another bird through using the regions of upwash generated by the wings of the preceding bird, although a definitive account of the aerodynamic implications of these formations has remained elusive. Here we show that individuals of northern bald ibises (Geronticus eremita) flying in a V flock position themselves in aerodynamically optimum positions, in that they agree with theoretical aerodynamic predictions. Furthermore, we demonstrate that birds show wingtip path coherence when flying in V positions, flapping spatially in phase and thus enabling upwash capture to be maximized throughout the entire flap cycle. In contrast, when birds fly immediately behind another bird--in a streamwise position--there is no wingtip path coherence; the wing-beats are in spatial anti-phase. This could potentially reduce the adverse effects of downwash for the following bird. These aerodynamic accomplishments were previously not thought possible for birds because of the complex flight dynamics and sensory feedback that would be required to perform such a feat. We conclude that the intricate mechanisms involved in V formation flight indicate awareness of the spatial wake structures of nearby flock-mates, and remarkable ability either to sense or predict it. We suggest that birds in V formation have phasing strategies to cope with the dynamic wakes produced by flapping wings.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Portugal, Steven J -- Hubel, Tatjana Y -- Fritz, Johannes -- Heese, Stefanie -- Trobe, Daniela -- Voelkl, Bernhard -- Hailes, Stephen -- Wilson, Alan M -- Usherwood, James R -- 095061/Wellcome Trust/United Kingdom -- 095061/Z/10/Z/Wellcome Trust/United Kingdom -- BB/J018007/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- England -- Nature. 2014 Jan 16;505(7483):399-402. doi: 10.1038/nature12939.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structure & Motion Laboratory, the Royal Veterinary College, University of London, Hatfield, Hertfordshire AL9 7TA, UK. ; Waldrappteam, Schulgasse 28, 6162 Mutters, Austria. ; 1] Waldrappteam, Schulgasse 28, 6162 Mutters, Austria [2] Institute for Theoretical Biology, Humboldt University at Berlin, Invalidenstrasse 43, 10115 Berlin, Germany [3] Edward Grey Institute, Department of Zoology, University of Oxford, Oxford OX1 3PS, UK. ; 1] Structure & Motion Laboratory, the Royal Veterinary College, University of London, Hatfield, Hertfordshire AL9 7TA, UK [2] Department of Computer Science, University College London, Gower Street, London WC1E 6BT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24429637" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomechanical Phenomena ; Birds/*physiology ; Flight, Animal/*physiology ; *Group Processes ; Models, Biological ; Movement/*physiology ; Wings, Animal/*physiology
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  • 26
    Publication Date: 2014-09-16
    Description: Curli are functional amyloid fibres that constitute the major protein component of the extracellular matrix in pellicle biofilms formed by Bacteroidetes and Proteobacteria (predominantly of the alpha and gamma classes). They provide a fitness advantage in pathogenic strains and induce a strong pro-inflammatory response during bacteraemia. Curli formation requires a dedicated protein secretion machinery comprising the outer membrane lipoprotein CsgG and two soluble accessory proteins, CsgE and CsgF. Here we report the X-ray structure of Escherichia coli CsgG in a non-lipidated, soluble form as well as in its native membrane-extracted conformation. CsgG forms an oligomeric transport complex composed of nine anticodon-binding-domain-like units that give rise to a 36-stranded beta-barrel that traverses the bilayer and is connected to a cage-like vestibule in the periplasm. The transmembrane and periplasmic domains are separated by a 0.9-nm channel constriction composed of three stacked concentric phenylalanine, asparagine and tyrosine rings that may guide the extended polypeptide substrate through the secretion pore. The specificity factor CsgE forms a nonameric adaptor that binds and closes off the periplasmic face of the secretion channel, creating a 24,000 A(3) pre-constriction chamber. Our structural, functional and electrophysiological analyses imply that CsgG is an ungated, non-selective protein secretion channel that is expected to employ a diffusion-based, entropy-driven transport mechanism.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4268158/" 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/PMC4268158/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goyal, Parveen -- Krasteva, Petya V -- Van Gerven, Nani -- Gubellini, Francesca -- Van den Broeck, Imke -- Troupiotis-Tsailaki, Anastassia -- Jonckheere, Wim -- Pehau-Arnaudet, Gerard -- Pinkner, Jerome S -- Chapman, Matthew R -- Hultgren, Scott J -- Howorka, Stefan -- Fronzes, Remi -- Remaut, Han -- R01 A1073847/PHS HHS/ -- R01 AI048689/AI/NIAID NIH HHS/ -- R01 AI073847/AI/NIAID NIH HHS/ -- R01 AI099099/AI/NIAID NIH HHS/ -- R56 AI073847/AI/NIAID NIH HHS/ -- England -- Nature. 2014 Dec 11;516(7530):250-3. doi: 10.1038/nature13768. Epub 2014 Sep 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Structural and Molecular Microbiology, Structural Biology Research Center, VIB, Pleinlaan 2, 1050 Brussels, Belgium [2] Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium. ; 1] Unite G5 Biologie structurale de la secretion bacterienne, Institut Pasteur, 25-28 rue du Docteur Roux, 75015 Paris, France [2] UMR 3528, CNRS, Institut Pasteur, 25-28 rue du Docteur Roux, 75015 Paris, France. ; Structure et Fonction des Membranes Biologiques (SFMB), Universite Libre de Bruxelles, 1050 Brussels, Belgium. ; UMR 3528, CNRS, Institut Pasteur, 25-28 rue du Docteur Roux, 75015 Paris, France. ; Department of Molecular Microbiology and Microbial Pathogenesis, Washington University in Saint Louis School of Medicine, St Louis, Missouri 63110-1010, USA. ; Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109-1048, USA. ; Department of Chemistry, Institute for Structural and Molecular Biology, University College London, London WC1H 0AJ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25219853" target="_blank"〉PubMed〈/a〉
    Keywords: Amyloid/*secretion ; Biofilms ; Cell Membrane ; Crystallography, X-Ray ; Diffusion ; Entropy ; Escherichia coli/*chemistry ; Escherichia coli Proteins/*chemistry/*metabolism ; Lipoproteins/*chemistry/*metabolism ; Membrane Transport Proteins/metabolism ; Models, Biological ; Models, Molecular ; Periplasm/metabolism ; Protein Conformation ; Protein Transport
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  • 27
    Publication Date: 2014-05-23
    Description: The glucose transporter GLUT1 catalyses facilitative diffusion of glucose into erythrocytes and is responsible for glucose supply to the brain and other organs. Dysfunctional mutations may lead to GLUT1 deficiency syndrome, whereas overexpression of GLUT1 is a prognostic indicator for cancer. Despite decades of investigation, the structure of GLUT1 remains unknown. Here we report the crystal structure of human GLUT1 at 3.2 A resolution. The full-length protein, which has a canonical major facilitator superfamily fold, is captured in an inward-open conformation. This structure allows accurate mapping and potential mechanistic interpretation of disease-associated mutations in GLUT1. Structure-based analysis of these mutations provides an insight into the alternating access mechanism of GLUT1 and other members of the sugar porter subfamily. Structural comparison of the uniporter GLUT1 with its bacterial homologue XylE, a proton-coupled xylose symporter, allows examination of the transport mechanisms of both passive facilitators and active transporters.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Deng, Dong -- Xu, Chao -- Sun, Pengcheng -- Wu, Jianping -- Yan, Chuangye -- Hu, Mingxu -- Yan, Nieng -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jun 5;510(7503):121-5. doi: 10.1038/nature13306. Epub 2014 May 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] State Key Laboratory of Bio-membrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China [2] Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China [3] Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China [4]. ; 1] State Key Laboratory of Bio-membrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China [2] Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China [3]. ; 1] State Key Laboratory of Bio-membrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China [2] Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China. ; 1] State Key Laboratory of Bio-membrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China [2] Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China [3] Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24847886" target="_blank"〉PubMed〈/a〉
    Keywords: Carbohydrate Metabolism, Inborn Errors/genetics ; Crystallography, X-Ray ; Escherichia coli Proteins ; Glucose Transporter Type 1/*chemistry/deficiency/genetics/metabolism ; Humans ; Ligands ; Models, Biological ; Models, Molecular ; Monosaccharide Transport Proteins/deficiency/genetics ; Mutation/genetics ; Protein Structure, Tertiary ; Structure-Activity Relationship ; Symporters
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  • 28
    Publication Date: 2014-02-18
    Description: The rapid turnover of the mammalian intestinal epithelium is supported by stem cells located around the base of the crypt. In addition to the Lgr5 marker, intestinal stem cells have been associated with other markers that are expressed heterogeneously within the crypt base region. Previous quantitative clonal fate analyses have led to the proposal that homeostasis occurs as the consequence of neutral competition between dividing stem cells. However, the short-term behaviour of individual Lgr5(+) cells positioned at different locations within the crypt base compartment has not been resolved. Here we establish the short-term dynamics of intestinal stem cells using the novel approach of continuous intravital imaging of Lgr5- Confetti mice. We find that Lgr5(+) cells in the upper part of the niche (termed 'border cells') can be passively displaced into the transit-amplifying domain, after the division of proximate cells, implying that the determination of stem-cell fate can be uncoupled from division. Through quantitative analysis of individual clonal lineages, we show that stem cells at the crypt base, termed 'central cells', experience a survival advantage over border stem cells. However, through the transfer of stem cells between the border and central regions, all Lgr5(+) cells are endowed with long-term self-renewal potential. These findings establish a novel paradigm for stem-cell maintenance in which a dynamically heterogeneous cell population is able to function long term as a single stem-cell pool.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964820/" 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/PMC3964820/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ritsma, Laila -- Ellenbroek, Saskia I J -- Zomer, Anoek -- Snippert, Hugo J -- de Sauvage, Frederic J -- Simons, Benjamin D -- Clevers, Hans -- van Rheenen, Jacco -- 092096/Wellcome Trust/United Kingdom -- 098357/Wellcome Trust/United Kingdom -- 098357/Z/12/Z/Wellcome Trust/United Kingdom -- England -- Nature. 2014 Mar 20;507(7492):362-5. doi: 10.1038/nature12972. Epub 2014 Feb 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Cancer Genomics Netherlands, Hubrecht Institute-KNAW and University Medical Centre Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands [2]. ; Cancer Genomics Netherlands, Hubrecht Institute-KNAW and University Medical Centre Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands. ; University Medical Centre Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands. ; Department of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA. ; 1] Cavendish Laboratory, Department of Physics, J. J. Thomson Avenue, University of Cambridge, Cambridge CB3 0HE, UK [2] The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK [3] The Wellcome Trust/Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24531760" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Division ; Cell Lineage ; Cell Survival ; Clone Cells/cytology ; Female ; *Homeostasis ; Intestinal Mucosa/*cytology ; Male ; Mice ; Models, Biological ; Molecular Imaging ; Receptors, G-Protein-Coupled/genetics/metabolism ; *Single-Cell Analysis ; Stem Cells/*cytology
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  • 29
    Publication Date: 2014-09-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Muller, Franz-Josef -- Loring, Jeanne F -- England -- Nature. 2014 Sep 25;513(7519):498-9. doi: 10.1038/513498a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Zentrum fur Integrative Psychiatrie Kiel, Universitatsklinikum Schleswig-Holstein, 24105 Kiel, Germany. ; Department of Chemical Physiology, Center for Regenerative Medicine, The Scripps Research Institute, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25254472" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Cell Differentiation/*genetics ; *Cell Engineering/methods ; Cellular Reprogramming/genetics ; Epigenesis, Genetic ; Gene Expression Profiling/methods ; Gene Regulatory Networks/*genetics ; Humans ; Induced Pluripotent Stem Cells/cytology/metabolism ; Models, Biological ; Regenerative Medicine ; Social Networking ; *Software ; Stem Cells/*cytology/*metabolism
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  • 30
    Publication Date: 2014-01-28
    Description: Tropical forests are important reservoirs of biodiversity, but the processes that maintain this diversity remain poorly understood. The Janzen-Connell hypothesis suggests that specialized natural enemies such as insect herbivores and fungal pathogens maintain high diversity by elevating mortality when plant species occur at high density (negative density dependence; NDD). NDD has been detected widely in tropical forests, but the prediction that NDD caused by insects and pathogens has a community-wide role in maintaining tropical plant diversity remains untested. We show experimentally that changes in plant diversity and species composition are caused by fungal pathogens and insect herbivores. Effective plant species richness increased across the seed-to-seedling transition, corresponding to large changes in species composition. Treating seeds and young seedlings with fungicides significantly reduced the diversity of the seedling assemblage, consistent with the Janzen-Connell hypothesis. Although suppressing insect herbivores using insecticides did not alter species diversity, it greatly increased seedling recruitment and caused a marked shift in seedling species composition. Overall, seedling recruitment was significantly reduced at high conspecific seed densities and this NDD was greatest for the species that were most abundant as seeds. Suppressing fungi reduced the negative effects of density on recruitment, confirming that the diversity-enhancing effect of fungi is mediated by NDD. Our study provides an overall test of the Janzen-Connell hypothesis and demonstrates the crucial role that insects and pathogens have both in structuring tropical plant communities and in maintaining their remarkable diversity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bagchi, Robert -- Gallery, Rachel E -- Gripenberg, Sofia -- Gurr, Sarah J -- Narayan, Lakshmi -- Addis, Claire E -- Freckleton, Robert P -- Lewis, Owen T -- England -- Nature. 2014 Feb 6;506(7486):85-8. doi: 10.1038/nature12911. Epub 2014 Jan 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK [2] Ecosystem Management Group, Institute of Terrestrial Ecosystems, ETH Zurich, Universitatstrasse 16, 8092 Zurich, Switzerland. ; 1] Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK [2] School of Natural Resources and the Environment, University of Arizona, Tucson, Arizona 85721, USA. ; 1] Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK [2] Section of Biodiversity and Environmental Research, Department of Biology, University of Turku, 20014 Turku, Finland. ; 1] Department of BioSciences, Geoffrey Pope Building, University of Exeter, Exeter EX4 4QD, UK [2] Department of Plant Sciences, University of Oxford, South Parks Road, Oxford OX1 3RB, UK. ; Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK. ; Department of Animal and Plant Science, University of Sheffield, Western Bank, Sheffield S10 2TN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24463522" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Belize ; *Biodiversity ; Fungi/drug effects/*physiology ; Fungicides, Industrial/pharmacology ; *Herbivory ; Insecticides/pharmacology ; Insects/drug effects/*physiology ; Methacrylates/pharmacology ; Models, Biological ; Pyrimidines/pharmacology ; Seedlings/drug effects/microbiology/parasitology/physiology ; Seeds/drug effects/physiology ; Trees/drug effects/*microbiology/parasitology/*physiology ; Tropical Climate
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  • 31
    Publication Date: 2014-05-09
    Description: If and how the heart regenerates after an injury event is highly debated. c-kit-expressing cardiac progenitor cells have been reported as the primary source for generation of new myocardium after injury. Here we generated two genetic approaches in mice to examine whether endogenous c-kit(+) cells contribute differentiated cardiomyocytes to the heart during development, with ageing or after injury in adulthood. A complementary DNA encoding either Cre recombinase or a tamoxifen-inducible MerCreMer chimaeric protein was targeted to the Kit locus in mice and then bred with reporter lines to permanently mark cell lineage. Endogenous c-kit(+) cells did produce new cardiomyocytes within the heart, although at a percentage of approximately 0.03 or less, and if a preponderance towards cellular fusion is considered, the percentage falls to below approximately 0.008. By contrast, c-kit(+) cells amply generated cardiac endothelial cells. Thus, endogenous c-kit(+) cells can generate cardiomyocytes within the heart, although probably at a functionally insignificant level.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4127035/" 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/PMC4127035/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉van Berlo, Jop H -- Kanisicak, Onur -- Maillet, Marjorie -- Vagnozzi, Ronald J -- Karch, Jason -- Lin, Suh-Chin J -- Middleton, Ryan C -- Marban, Eduardo -- Molkentin, Jeffery D -- P01 HL108806/HL/NHLBI NIH HHS/ -- P50 HL052318/HL/NHLBI NIH HHS/ -- P50 HL077101/HL/NHLBI NIH HHS/ -- R00 HL112852/HL/NHLBI NIH HHS/ -- R01 HL105924/HL/NHLBI NIH HHS/ -- R37 HL060562/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 May 15;509(7500):337-41. doi: 10.1038/nature13309. Epub 2014 May 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA [2] Department of Medicine, division of Cardiology, Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota 55455, USA [3]. ; 1] Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA [2]. ; Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. ; Cedars-Sinai Heart Institute, 8700 Beverly Boulevard, Los Angeles, California 90048, USA. ; 1] Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA [2] Howard Hughes Medical Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24805242" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/physiology ; Animals ; Cell Differentiation ; Cell Fusion ; *Cell Lineage ; Endothelial Cells/cytology/metabolism ; Female ; Heart/growth & development ; Heart Injuries/*pathology ; Integrases/genetics/metabolism ; Male ; Mice ; Models, Biological ; Myoblasts, Cardiac/*cytology/*metabolism ; Myocardium/*cytology ; Myocytes, Cardiac/*cytology/metabolism ; Proto-Oncogene Proteins c-kit/*metabolism ; Regeneration/physiology ; Tamoxifen/pharmacology
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  • 32
    Publication Date: 2014-05-23
    Description: Cellular senescence has historically been viewed as an irreversible cell-cycle arrest mechanism that acts to protect against cancer, but recent discoveries have extended its known role to complex biological processes such as development, tissue repair, ageing and age-related disorders. New insights indicate that, unlike a static endpoint, senescence represents a series of progressive and phenotypically diverse cellular states acquired after the initial growth arrest. A deeper understanding of the molecular mechanisms underlying the multi-step progression of senescence and the development and function of acute versus chronic senescent cells may lead to new therapeutic strategies for age-related pathologies and extend healthy lifespan.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214092/" 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/PMC4214092/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉van Deursen, Jan M -- AG41122-01P2/AG/NIA NIH HHS/ -- R01 CA096985/CA/NCI NIH HHS/ -- R01 CA166347/CA/NCI NIH HHS/ -- R01CA166347/CA/NCI NIH HHS/ -- R01CA96985/CA/NCI NIH HHS/ -- England -- Nature. 2014 May 22;509(7501):439-46. doi: 10.1038/nature13193.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatric and Adolescent Medicine and Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24848057" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/*pathology ; Animals ; Cell Aging/*physiology ; Disease ; Humans ; Longevity ; Mitosis ; Models, Biological
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  • 33
    Publication Date: 2014-04-11
    Description: Touch submodalities, such as flutter and pressure, are mediated by somatosensory afferents whose terminal specializations extract tactile features and encode them as action potential trains with unique activity patterns. Whether non-neuronal cells tune touch receptors through active or passive mechanisms is debated. Terminal specializations are thought to function as passive mechanical filters analogous to the cochlea's basilar membrane, which deconstructs complex sounds into tones that are transduced by mechanosensory hair cells. The model that cutaneous specializations are merely passive has been recently challenged because epidermal cells express sensory ion channels and neurotransmitters; however, direct evidence that epidermal cells excite tactile afferents is lacking. Epidermal Merkel cells display features of sensory receptor cells and make 'synapse-like' contacts with slowly adapting type I (SAI) afferents. These complexes, which encode spatial features such as edges and texture, localize to skin regions with high tactile acuity, including whisker follicles, fingertips and touch domes. Here we show that Merkel cells actively participate in touch reception in mice. Merkel cells display fast, touch-evoked mechanotransduction currents. Optogenetic approaches in intact skin show that Merkel cells are both necessary and sufficient for sustained action-potential firing in tactile afferents. Recordings from touch-dome afferents lacking Merkel cells demonstrate that Merkel cells confer high-frequency responses to dynamic stimuli and enable sustained firing. These data are the first, to our knowledge, to directly demonstrate a functional, excitatory connection between epidermal cells and sensory neurons. Together, these findings indicate that Merkel cells actively tune mechanosensory responses to facilitate high spatio-temporal acuity. Moreover, our results indicate a division of labour in the Merkel cell-neurite complex: Merkel cells signal static stimuli, such as pressure, whereas sensory afferents transduce dynamic stimuli, such as moving gratings. Thus, the Merkel cell-neurite complex is an unique sensory structure composed of two different receptor cell types specialized for distinct elements of discriminative touch.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4097312/" 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/PMC4097312/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maksimovic, Srdjan -- Nakatani, Masashi -- Baba, Yoshichika -- Nelson, Aislyn M -- Marshall, Kara L -- Wellnitz, Scott A -- Firozi, Pervez -- Woo, Seung-Hyun -- Ranade, Sanjeev -- Patapoutian, Ardem -- Lumpkin, Ellen A -- 5T32HL087745-05/HL/NHLBI NIH HHS/ -- F32 NS080544/NS/NINDS NIH HHS/ -- F32NS080544/NS/NINDS NIH HHS/ -- P30 AR044535/AR/NIAMS NIH HHS/ -- P30 CA125123/CA/NCI NIH HHS/ -- P30AR044535/AR/NIAMS NIH HHS/ -- P30CA013696/CA/NCI NIH HHS/ -- P30CA125123/CA/NCI NIH HHS/ -- R01 AR051219/AR/NIAMS NIH HHS/ -- R01 DE022358/DE/NIDCR NIH HHS/ -- R01AR051219/AR/NIAMS NIH HHS/ -- R01DE022358/DE/NIDCR NIH HHS/ -- R21 AR062307/AR/NIAMS NIH HHS/ -- R21AR062307/AR/NIAMS NIH HHS/ -- T32 HL087745/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 May 29;509(7502):617-21. doi: 10.1038/nature13250. Epub 2014 Apr 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Dermatology, Columbia University, New York, New York 10032, USA [2]. ; 1] Department of Dermatology, Columbia University, New York, New York 10032, USA [2] Graduate School of System Design and Management, Keio University, Yokohama 223-8526, Japan [3]. ; 1] Department of Dermatology, Columbia University, New York, New York 10032, USA [2] Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77006, USA. ; Department of Dermatology, Columbia University, New York, New York 10032, USA. ; Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77006, USA. ; Howard Hughes Medical Institute, Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla California 92037, USA. ; 1] Department of Dermatology, Columbia University, New York, New York 10032, USA [2] Department of Physiology & Cellular Biophysics, Columbia University, New York, New York 10032, USA [3] Program in Neurobiology & Behavior, 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/24717432" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; *Afferent Pathways ; Animals ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Electric Conductivity ; Epidermis/*cytology/*innervation ; Female ; Ion Channels/metabolism ; Male ; *Mechanotransduction, Cellular ; Merkel Cells/*metabolism ; Mice ; Models, Biological ; Neurites/metabolism ; Neurons, Afferent/metabolism ; Optogenetics ; Pressure ; Touch/*physiology
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  • 34
    Publication Date: 2014-12-10
    Description: The concept of germ layers has been one of the foremost organizing principles in developmental biology, classification, systematics and evolution for 150 years (refs 1 - 3). Of the three germ layers, the mesoderm is found in bilaterian animals but is absent in species in the phyla Cnidaria and Ctenophora, which has been taken as evidence that the mesoderm was the final germ layer to evolve. The origin of the ectoderm and endoderm germ layers, however, remains unclear, with models supporting the antecedence of each as well as a simultaneous origin. Here we determine the temporal and spatial components of gene expression spanning embryonic development for all Caenorhabditis elegans genes and use it to determine the evolutionary ages of the germ layers. The gene expression program of the mesoderm is induced after those of the ectoderm and endoderm, thus making it the last germ layer both to evolve and to develop. Strikingly, the C. elegans endoderm and ectoderm expression programs do not co-induce; rather the endoderm activates earlier, and this is also observed in the expression of endoderm orthologues during the embryology of the frog Xenopus tropicalis, the sea anemone Nematostella vectensis and the sponge Amphimedon queenslandica. Querying the phylogenetic ages of specifically expressed genes reveals that the endoderm comprises older genes. Taken together, we propose that the endoderm program dates back to the origin of multicellularity, whereas the ectoderm originated as a secondary germ layer freed from ancestral feeding functions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359913/" 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/PMC4359913/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hashimshony, Tamar -- Feder, Martin -- Levin, Michal -- Hall, Brian K -- Yanai, Itai -- 310927/European Research Council/International -- England -- Nature. 2015 Mar 12;519(7542):219-22. doi: 10.1038/nature13996. Epub 2014 Dec 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Technion - Israel Institute of Technology, Haifa 32000, Israel. ; Department of Biology, Dalhousie University, Halifax, Nova Scotia B3H 4JI, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25487147" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/cytology/*embryology/*genetics ; Cell Lineage ; Eating ; Ectoderm/cytology/embryology/metabolism ; Endoderm/cytology/embryology/*metabolism ; *Evolution, Molecular ; Gene Expression Profiling ; Gene Expression Regulation, Developmental/*genetics ; Mesoderm/cytology/embryology/metabolism ; Models, Biological ; Porifera/cytology/embryology/genetics ; Sea Anemones/cytology/embryology/genetics ; *Spatio-Temporal Analysis ; Time Factors ; Transcriptome/*genetics ; Xenopus/embryology/genetics
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  • 35
    Publication Date: 2014-12-30
    Description: Hox genes regulate regionalization of the axial skeleton in vertebrates, and changes in their expression have been proposed to be a fundamental mechanism driving the evolution of new body forms. The origin of the snake-like body form, with its deregionalized pre-cloacal axial skeleton, has been explained as either homogenization of Hox gene expression domains, or retention of standard vertebrate Hox domains with alteration of downstream expression that suppresses development of distinct regions. Both models assume a highly regionalized ancestor, but the extent of deregionalization of the primaxial domain (vertebrae, dorsal ribs) of the skeleton in snake-like body forms has never been analysed. Here we combine geometric morphometrics and maximum-likelihood analysis to show that the pre-cloacal primaxial domain of elongate, limb-reduced lizards and snakes is not deregionalized compared with limbed taxa, and that the phylogenetic structure of primaxial morphology in reptiles does not support a loss of regionalization in the evolution of snakes. We demonstrate that morphometric regional boundaries correspond to mapped gene expression domains in snakes, suggesting that their primaxial domain is patterned by a normally functional Hox code. Comparison of primaxial osteology in fossil and modern amniotes with Hox gene distributions within Amniota indicates that a functional, sequentially expressed Hox code patterned a subtle morphological gradient along the anterior-posterior axis in stem members of amniote clades and extant lizards, including snakes. The highly regionalized skeletons of extant archosaurs and mammals result from independent evolution in the Hox code and do not represent ancestral conditions for clades with snake-like body forms. The developmental origin of snakes is best explained by decoupling of the primaxial and abaxial domains and by increases in somite number, not by changes in the function of primaxial Hox genes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Head, Jason J -- Polly, P David -- England -- Nature. 2015 Apr 2;520(7545):86-9. doi: 10.1038/nature14042. Epub 2015 Jan 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Earth and Atmospheric Sciences and Nebraska State Museum of Natural History, University of Nebraska-Lincoln, Lincoln, Nebraska 68588-0340, USA. ; Departments of Geological Sciences, Biology and Anthropology, Indiana University, Bloomington, Indiana 47405-1405, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25539083" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cloaca ; Developmental Biology ; Extremities/anatomy & histology ; *Fossils ; Genes, Homeobox/*genetics ; Lizards/anatomy & histology ; Models, Biological ; *Phylogeny ; Sacrum ; Snakes/*anatomy & histology/*genetics ; Spine/*anatomy & histology
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  • 36
    Publication Date: 2014-12-10
    Description: A defining feature of vertebrates (craniates) is a pronounced head that is supported and protected by a robust cellular endoskeleton. In the first vertebrates, this skeleton probably consisted of collagenous cellular cartilage, which forms the embryonic skeleton of all vertebrates and the adult skeleton of modern jawless and cartilaginous fish. In the head, most cellular cartilage is derived from a migratory cell population called the neural crest, which arises from the edges of the central nervous system. Because collagenous cellular cartilage and neural crest cells have not been described in invertebrates, the appearance of cellular cartilage derived from neural crest cells is considered a turning point in vertebrate evolution. Here we show that a tissue with many of the defining features of vertebrate cellular cartilage transiently forms in the larvae of the invertebrate chordate Branchiostoma floridae (Florida amphioxus). We also present evidence that during evolution, a key regulator of vertebrate cartilage development, SoxE, gained new cis-regulatory sequences that subsequently directed its novel expression in neural crest cells. Together, these results suggest that the origin of the vertebrate head skeleton did not depend on the evolution of a new skeletal tissue, as is commonly thought, but on the spread of this tissue throughout the head. We further propose that the evolution of cis-regulatory elements near an ancient regulator of cartilage differentiation was a major factor in the evolution of the vertebrate head skeleton.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jandzik, David -- Garnett, Aaron T -- Square, Tyler A -- Cattell, Maria V -- Yu, Jr-Kai -- Medeiros, Daniel M -- England -- Nature. 2015 Feb 26;518(7540):534-7. doi: 10.1038/nature14000. Epub 2014 Dec 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Ecology and Evolutionary Biology, University of Colorado, Boulder, Colorado 80309, USA [2] Department of Zoology, Comenius University, Bratislava 84215, Slovakia. ; Department of Ecology and Evolutionary Biology, University of Colorado, Boulder, Colorado 80309, USA. ; Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 11529, Taiwan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25487155" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; *Cartilage/cytology/metabolism ; Fibroblast Growth Factors/metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Developmental/genetics ; Genes, Reporter/genetics ; *Head ; Lancelets/*anatomy & histology/cytology/*growth & development ; Larva/anatomy & histology/cytology ; Models, Biological ; Mouth/anatomy & histology ; Neural Crest/cytology ; SOXE Transcription Factors/genetics/metabolism ; Signal Transduction ; *Skull/cytology/metabolism ; Vertebrates/*anatomy & histology ; Zebrafish/embryology/genetics
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  • 37
    Publication Date: 2014-10-21
    Description: Reproduction in jawed vertebrates (gnathostomes) involves either external or internal fertilization. It is commonly argued that internal fertilization can evolve from external, but not the reverse. Male copulatory claspers are present in certain placoderms, fossil jawed vertebrates retrieved as a paraphyletic segment of the gnathostome stem group in recent studies. This suggests that internal fertilization could be primitive for gnathostomes, but such a conclusion depends on demonstrating that copulation was not just a specialized feature of certain placoderm subgroups. The reproductive biology of antiarchs, consistently identified as the least crownward placoderms and thus of great interest in this context, has until now remained unknown. Here we show that certain antiarchs possessed dermal claspers in the males, while females bore paired dermal plates inferred to have facilitated copulation. These structures are not associated with pelvic fins. The clasper morphology resembles that of ptyctodonts, a more crownward placoderm group, suggesting that all placoderm claspers are homologous and that internal fertilization characterized all placoderms. This implies that external fertilization and spawning, which characterize most extant aquatic gnathostomes, must be derived from internal fertilization, even though this transformation has been thought implausible. Alternatively, the substantial morphological evidence for placoderm paraphyly must be rejected.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Long, John A -- Mark-Kurik, Elga -- Johanson, Zerina -- Lee, Michael S Y -- Young, Gavin C -- Min, Zhu -- Ahlberg, Per E -- Newman, Michael -- Jones, Roger -- den Blaauwen, Jan -- Choo, Brian -- Trinajstic, Kate -- England -- Nature. 2015 Jan 8;517(7533):196-9. doi: 10.1038/nature13825. Epub 2014 Oct 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] School of Biological Sciences, Flinders University, 2100, Adelaide, South Australia 5001, Australia [2] Natural History Museum of Los Angeles County, 900 Exposition Boulevard, Los Angeles, California 9007, USA [3] Museum Victoria, PO Box 666, Melbourne, Victoria 3001, Australia. ; Institute of Geology at Tallinn University of Technology, Ehitajate tee 5, 19086 Tallinn, Estonia. ; Department of Earth Sciences, Natural History Museum, London SW7 5BD, UK. ; 1] South Australian Museum, North Terrace, Adelaide, South Australia 5000, Australia [2] School of Earth and Environmental Sciences, The University of Adelaide, South Australia 5005, Australia. ; Research School of Earth Sciences, The Australian National University, Canberra, Australian Capital Territory 0200, Australia. ; Key Laboratory of Evolutionary Systematics of Vertebrates, Institute of Vertebrate Paleontology and Paleoanthropology, Chinese Academy of Sciences, PO Box 643, Beijing 100044, China. ; Department of Organismal Biology, Evolutionary Biology Centre, Uppsala University, Norbyvagen 18A, 752 36 Uppsala, Sweden. ; Vine Lodge, Vine Road, Johnston, Haverfordwest, Pembrokeshire SA62 3NZ, UK. ; 6 Burghley Road, Wimbledon, London SW19 5BH, UK. ; University of Amsterdam, Science Park 904, 1098XH, Amsterdam, The Netherlands. ; School of Biological Sciences, Flinders University, 2100, Adelaide, South Australia 5001, Australia. ; 1] Western Australian Organic and Isotope Geochemistry Centre, Department of Chemistry, Curtin University, Perth, Western Australia 6102, Australia [2] Earth and Planetary Sciences, Western Australian Museum, Perth, Western Australia 6000, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25327249" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Copulation/*physiology ; Female ; Fertilization/*physiology ; Fishes/*anatomy & histology/*physiology ; Fossils ; *Jaw ; Male ; Models, Biological ; Phylogeny ; Sex Characteristics ; Vertebrates/anatomy & histology/*physiology
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  • 38
    Publication Date: 2013-06-07
    Description: G-protein-gated inward rectifier K(+) (GIRK) channels allow neurotransmitters, through G-protein-coupled receptor stimulation, to control cellular electrical excitability. In cardiac and neuronal cells this control regulates heart rate and neural circuit activity, respectively. Here we present the 3.5 A resolution crystal structure of the mammalian GIRK2 channel in complex with betagamma G-protein subunits, the central signalling complex that links G-protein-coupled receptor stimulation to K(+) channel activity. Short-range atomic and long-range electrostatic interactions stabilize four betagamma G-protein subunits at the interfaces between four K(+) channel subunits, inducing a pre-open state of the channel. The pre-open state exhibits a conformation that is intermediate between the closed conformation and the open conformation of the constitutively active mutant. The resultant structural picture is compatible with 'membrane delimited' activation of GIRK channels by G proteins and the characteristic burst kinetics of channel gating. The structures also permit a conceptual understanding of how the signalling lipid phosphatidylinositol-4,5-bisphosphate (PIP2) and intracellular Na(+) ions participate in multi-ligand regulation of GIRK channels.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4654628/" 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/PMC4654628/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Whorton, Matthew R -- MacKinnon, Roderick -- 1S10RR022321-01/RR/NCRR NIH HHS/ -- 1S10RR027037-01/RR/NCRR NIH HHS/ -- S10 RR027037/RR/NCRR NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Jun 13;498(7453):190-7. doi: 10.1038/nature12241. Epub 2013 Jun 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Neurobiology and Biophysics, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23739333" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Crystallography, X-Ray ; G Protein-Coupled Inwardly-Rectifying Potassium ; Channels/*chemistry/genetics/metabolism ; Heterotrimeric GTP-Binding Proteins/*chemistry/genetics/metabolism ; Humans ; Ion Channel Gating ; Models, Biological ; Models, Molecular ; Phosphatidylinositol 4,5-Diphosphate/metabolism ; Protein Conformation ; Protein Interaction Domains and Motifs ; Protein Subunits/chemistry/metabolism ; Sodium/metabolism ; Static Electricity
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  • 39
    Publication Date: 2013-10-15
    Description: The mechanisms by which genetic variation affects transcription regulation and phenotypes at the nucleotide level are incompletely understood. Here we use natural genetic variation as an in vivo mutagenesis screen to assess the genome-wide effects of sequence variation on lineage-determining and signal-specific transcription factor binding, epigenomics and transcriptional outcomes in primary macrophages from different mouse strains. We find substantial genetic evidence to support the concept that lineage-determining transcription factors define epigenetic and transcriptomic states by selecting enhancer-like regions in the genome in a collaborative fashion and facilitating binding of signal-dependent factors. This hierarchical model of transcription factor function suggests that limited sets of genomic data for lineage-determining transcription factors and informative histone modifications can be used for the prioritization of disease-associated regulatory variants.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994126/" 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/PMC3994126/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heinz, S -- Romanoski, C E -- Benner, C -- Allison, K A -- Kaikkonen, M U -- Orozco, L D -- Glass, C K -- 5T32DK007494/DK/NIDDK NIH HHS/ -- CA17390/CA/NCI NIH HHS/ -- DK063491/DK/NIDDK NIH HHS/ -- DK091183/DK/NIDDK NIH HHS/ -- P01 DK074868/DK/NIDDK NIH HHS/ -- P30 CA023100/CA/NCI NIH HHS/ -- P30 DK063491/DK/NIDDK NIH HHS/ -- R01 CA173903/CA/NCI NIH HHS/ -- R01 DK091183/DK/NIDDK NIH HHS/ -- T32 AR059033/AR/NIAMS NIH HHS/ -- England -- Nature. 2013 Nov 28;503(7477):487-92. doi: 10.1038/nature12615. Epub 2013 Oct 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, Mail Code 0651, La Jolla, California 92093, USA [2].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24121437" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs/genetics ; Animals ; Base Sequence ; Cell Lineage/genetics ; DNA-Binding Proteins/metabolism ; Enhancer Elements, Genetic/*genetics ; Gene Expression Regulation/*genetics ; Genetic Variation/*genetics ; Histones/chemistry/metabolism ; Macrophages/metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Models, Biological ; Mutation/genetics ; NF-kappa B/metabolism ; Protein Binding ; Reproducibility of Results ; Selection, Genetic/*genetics ; Transcription Factor RelA/metabolism ; Transcription Factors/*metabolism
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  • 40
    Publication Date: 2013-07-23
    Description: Loss of sexual reproduction is considered an evolutionary dead end for metazoans, but bdelloid rotifers challenge this view as they appear to have persisted asexually for millions of years. Neither male sex organs nor meiosis have ever been observed in these microscopic animals: oocytes are formed through mitotic divisions, with no reduction of chromosome number and no indication of chromosome pairing. However, current evidence does not exclude that they may engage in sex on rare, cryptic occasions. Here we report the genome of a bdelloid rotifer, Adineta vaga (Davis, 1873), and show that its structure is incompatible with conventional meiosis. At gene scale, the genome of A. vaga is tetraploid and comprises both anciently duplicated segments and less divergent allelic regions. However, in contrast to sexual species, the allelic regions are rearranged and sometimes even found on the same chromosome. Such structure does not allow meiotic pairing; instead, we find abundant evidence of gene conversion, which may limit the accumulation of deleterious mutations in the absence of meiosis. Gene families involved in resistance to oxidation, carbohydrate metabolism and defence against transposons are significantly expanded, which may explain why transposable elements cover only 3% of the assembled sequence. Furthermore, 8% of the genes are likely to be of non-metazoan origin and were probably acquired horizontally. This apparent convergence between bdelloids and prokaryotes sheds new light on the evolutionary significance of sex.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Flot, Jean-Francois -- Hespeels, Boris -- Li, Xiang -- Noel, Benjamin -- Arkhipova, Irina -- Danchin, Etienne G J -- Hejnol, Andreas -- Henrissat, Bernard -- Koszul, Romain -- Aury, Jean-Marc -- Barbe, Valerie -- Barthelemy, Roxane-Marie -- Bast, Jens -- Bazykin, Georgii A -- Chabrol, Olivier -- Couloux, Arnaud -- Da Rocha, Martine -- Da Silva, Corinne -- Gladyshev, Eugene -- Gouret, Philippe -- Hallatschek, Oskar -- Hecox-Lea, Bette -- Labadie, Karine -- Lejeune, Benjamin -- Piskurek, Oliver -- Poulain, Julie -- Rodriguez, Fernando -- Ryan, Joseph F -- Vakhrusheva, Olga A -- Wajnberg, Eric -- Wirth, Benedicte -- Yushenova, Irina -- Kellis, Manolis -- Kondrashov, Alexey S -- Mark Welch, David B -- Pontarotti, Pierre -- Weissenbach, Jean -- Wincker, Patrick -- Jaillon, Olivier -- Van Doninck, Karine -- England -- Nature. 2013 Aug 22;500(7463):453-7. doi: 10.1038/nature12326. Epub 2013 Jul 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Namur, Department of Biology, URBE, Laboratory of Evolutionary Genetics and Ecology, 5000 Namur, Belgium. jean-francois.flot@ds.mpg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23873043" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Gene Conversion/*genetics ; Gene Transfer, Horizontal/genetics ; Genome/*genetics ; Genomics ; Meiosis/genetics ; Models, Biological ; Reproduction, Asexual/*genetics ; Rotifera/*genetics ; Tetraploidy
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  • 41
    Publication Date: 2013-11-08
    Description: In nuclear pre-messenger RNA splicing, introns are excised by the spliceosome, a dynamic machine composed of both proteins and small nuclear RNAs (snRNAs). Over thirty years ago, after the discovery of self-splicing group II intron RNAs, the snRNAs were proposed to catalyse splicing. However, no definitive evidence for a role of either RNA or protein in catalysis by the spliceosome has been reported so far. By using metal rescue strategies in spliceosomes from budding yeast, here we show that the U6 snRNA catalyses both of the two splicing reactions by positioning divalent metals that stabilize the leaving groups during each reaction. Notably, all of the U6 catalytic metal ligands we identified correspond to the ligands observed to position catalytic, divalent metals in crystal structures of a group II intron RNA. These findings indicate that group II introns and the spliceosome share common catalytic mechanisms and probably common evolutionary origins. Our results demonstrate that RNA mediates catalysis within the spliceosome.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666680/" 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/PMC4666680/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fica, Sebastian M -- Tuttle, Nicole -- Novak, Thaddeus -- Li, Nan-Sheng -- Lu, Jun -- Koodathingal, Prakash -- Dai, Qing -- Staley, Jonathan P -- Piccirilli, Joseph A -- 5T32GM008720/GM/NIGMS NIH HHS/ -- R01 GM088656/GM/NIGMS NIH HHS/ -- R01GM088656/GM/NIGMS NIH HHS/ -- England -- Nature. 2013 Nov 14;503(7475):229-34. doi: 10.1038/nature12734. Epub 2013 Nov 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Graduate Program in Cell and Molecular Biology, The University of Chicago, Chicago, Illinois 60637, USA [2] Department of Molecular Genetics and Cell Biology, Cummings Life Sciences Center, 920 East 58th Street, The University of Chicago, Chicago, Illinois 60637, USA [3].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24196718" target="_blank"〉PubMed〈/a〉
    Keywords: Catalysis ; Cell Nucleus/metabolism ; Introns/genetics ; Metals/metabolism ; Models, Biological ; RNA Precursors/*metabolism ; *RNA Splicing ; RNA, Fungal/metabolism ; RNA, Small Nuclear/*metabolism ; Saccharomyces cerevisiae/*genetics/*metabolism ; Spliceosomes/metabolism
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  • 42
    Publication Date: 2013-04-26
    Description: Cell-surface-receptor binding by influenza viruses is a key determinant of their transmissibility, both from avian and animal species to humans as well as from human to human. Highly pathogenic avian H5N1 viruses that are a threat to public health have been observed to acquire affinity for human receptors, and transmissible-mutant-selection experiments have identified a virus that is transmissible in ferrets, the generally accepted experimental model for influenza in humans. Here, our quantitative biophysical measurements of the receptor-binding properties of haemagglutinin (HA) from the transmissible mutant indicate a small increase in affinity for human receptor and a marked decrease in affinity for avian receptor. From analysis of virus and HA binding data we have derived an algorithm that predicts virus avidity from the affinity of individual HA-receptor interactions. It reveals that the transmissible-mutant virus has a 200-fold preference for binding human over avian receptors. The crystal structure of the transmissible-mutant HA in complex with receptor analogues shows that it has acquired the ability to bind human receptor in the same folded-back conformation as seen for HA from the 1918, 1957 (ref. 4), 1968 (ref. 5) and 2009 (ref. 6) pandemic viruses. This binding mode is substantially different from that by which non-transmissible wild-type H5 virus HA binds human receptor. The structure of the complex also explains how the change in preference from avian to human receptors arises from the Gln226Leu substitution, which facilitates binding to human receptor but restricts binding to avian receptor. Both features probably contribute to the acquisition of transmissibility by this mutant virus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xiong, Xiaoli -- Coombs, Peter J -- Martin, Stephen R -- Liu, Junfeng -- Xiao, Haixia -- McCauley, John W -- Locher, Kathrin -- Walker, Philip A -- Collins, Patrick J -- Kawaoka, Yoshihiro -- Skehel, John J -- Gamblin, Steven J -- BB/E010806/Biotechnology and Biological Sciences Research Council/United Kingdom -- MC_U117512723/Medical Research Council/United Kingdom -- MC_U117584222/Medical Research Council/United Kingdom -- U117512723/Medical Research Council/United Kingdom -- U117570592/Medical Research Council/United Kingdom -- U117584222/Medical Research Council/United Kingdom -- England -- Nature. 2013 May 16;497(7449):392-6. doi: 10.1038/nature12144. Epub 2013 Apr 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉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/23615615" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Birds/metabolism/virology ; Chick Embryo ; Crystallography, X-Ray ; Ferrets/*virology ; Hemagglutinin Glycoproteins, Influenza Virus/*chemistry/genetics/*metabolism ; *Host Specificity ; Humans ; Influenza A Virus, H5N1 Subtype/chemistry/*genetics/*metabolism/pathogenicity ; Models, Biological ; Models, Molecular ; Mutation ; Orthomyxoviridae Infections/*transmission/*virology ; Protein Conformation ; Receptors, Virus/*metabolism ; Species Specificity
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  • 43
    Publication Date: 2013-06-01
    Description: Cytosolic DNA arising from intracellular bacterial or viral infections is a powerful pathogen-associated molecular pattern (PAMP) that leads to innate immune host defence by the production of type I interferon and inflammatory cytokines. Recognition of cytosolic DNA by the recently discovered cyclic-GMP-AMP (cGAMP) synthase (cGAS) induces the production of cGAMP to activate the stimulator of interferon genes (STING). Here we report the crystal structure of cGAS alone and in complex with DNA, ATP and GTP along with functional studies. Our results explain the broad DNA sensing specificity of cGAS, show how cGAS catalyses dinucleotide formation and indicate activation by a DNA-induced structural switch. cGAS possesses a remarkable structural similarity to the antiviral cytosolic double-stranded RNA sensor 2'-5'oligoadenylate synthase (OAS1), but contains a unique zinc thumb that recognizes B-form double-stranded DNA. Our results mechanistically unify dsRNA and dsDNA innate immune sensing by OAS1 and cGAS nucleotidyl transferases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3768140/" 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/PMC3768140/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Civril, Filiz -- Deimling, Tobias -- de Oliveira Mann, Carina C -- Ablasser, Andrea -- Moldt, Manuela -- Witte, Gregor -- Hornung, Veit -- Hopfner, Karl-Peter -- 243046/European Research Council/International -- U19 AI083025/AI/NIAID NIH HHS/ -- U19AI083025/AI/NIAID NIH HHS/ -- England -- Nature. 2013 Jun 20;498(7454):332-7. doi: 10.1038/nature12305. Epub 2013 May 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Gene Center, Ludwig-Maximilians-University, 81377 Munich, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23722159" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/chemistry/metabolism ; Animals ; Base Sequence ; Catalytic Domain ; Crystallography, X-Ray ; *Cytosol ; DNA/chemistry/*metabolism/pharmacology ; Guanosine Triphosphate/chemistry/metabolism ; HEK293 Cells ; Humans ; Membrane Proteins/genetics/metabolism ; Mice ; Models, Biological ; Models, Molecular ; Mutation ; Nucleotidyltransferases/*chemistry/genetics/metabolism ; Protein Conformation/drug effects ; Structure-Activity Relationship ; Substrate Specificity ; Swine ; Uridine Triphosphate/chemistry/metabolism ; Zinc/chemistry/metabolism
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  • 44
    Publication Date: 2013-05-31
    Description: Human language, as well as birdsong, relies on the ability to arrange vocal elements in new sequences. However, little is known about the ontogenetic origin of this capacity. Here we track the development of vocal combinatorial capacity in three species of vocal learners, combining an experimental approach in zebra finches (Taeniopygia guttata) with an analysis of natural development of vocal transitions in Bengalese finches (Lonchura striata domestica) and pre-lingual human infants. We find a common, stepwise pattern of acquiring vocal transitions across species. In our first study, juvenile zebra finches were trained to perform one song and then the training target was altered, prompting the birds to swap syllable order, or insert a new syllable into a string. All birds solved these permutation tasks in a series of steps, gradually approximating the target sequence by acquiring new pairwise syllable transitions, sometimes too slowly to accomplish the task fully. Similarly, in the more complex songs of Bengalese finches, branching points and bidirectional transitions in song syntax were acquired in a stepwise fashion, starting from a more restrictive set of vocal transitions. The babbling of pre-lingual human infants showed a similar pattern: instead of a single developmental shift from reduplicated to variegated babbling (that is, from repetitive to diverse sequences), we observed multiple shifts, where each new syllable type slowly acquired a diversity of pairwise transitions, asynchronously over development. Collectively, these results point to a common generative process that is conserved across species, suggesting that the long-noted gap between perceptual versus motor combinatorial capabilities in human infants may arise partly from the challenges in constructing new pairwise vocal transitions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3676428/" 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/PMC3676428/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lipkind, Dina -- Marcus, Gary F -- Bemis, Douglas K -- Sasahara, Kazutoshi -- Jacoby, Nori -- Takahasi, Miki -- Suzuki, Kenta -- Feher, Olga -- Ravbar, Primoz -- Okanoya, Kazuo -- Tchernichovski, Ofer -- R01 DC004722/DC/NIDCD NIH HHS/ -- England -- Nature. 2013 Jun 6;498(7452):104-8. doi: 10.1038/nature12173. Epub 2013 May 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychology, Hunter College, City University of New York, New York, NY 10065, USA. dina.lipkind@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23719373" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Evolution ; *Child Language ; Finches/*physiology ; Humans ; Infant ; Male ; Models, Biological ; Phonetics ; Speech/physiology ; Time Factors ; Vocalization, Animal/*physiology
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  • 45
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    Nature Publishing Group (NPG)
    Publication Date: 2013-11-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2013 Nov 7;503(7474):6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24218658" target="_blank"〉PubMed〈/a〉
    Keywords: Electric Stimulation ; Humans ; Hydrodynamics ; *Mass Behavior ; *Microspheres ; Models, Biological ; Plastics ; Static Electricity
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  • 46
    Publication Date: 2013-07-05
    Description: We have taken the first steps towards a complete reconstruction of the Mycobacterium tuberculosis regulatory network based on ChIP-Seq and combined this reconstruction with system-wide profiling of messenger RNAs, proteins, metabolites and lipids during hypoxia and re-aeration. Adaptations to hypoxia are thought to have a prominent role in M. tuberculosis pathogenesis. Using ChIP-Seq combined with expression data from the induction of the same factors, we have reconstructed a draft regulatory network based on 50 transcription factors. This network model revealed a direct interconnection between the hypoxic response, lipid catabolism, lipid anabolism and the production of cell wall lipids. As a validation of this model, in response to oxygen availability we observe substantial alterations in lipid content and changes in gene expression and metabolites in corresponding metabolic pathways. The regulatory network reveals transcription factors underlying these changes, allows us to computationally predict expression changes, and indicates that Rv0081 is a regulatory hub.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4087036/" 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/PMC4087036/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Galagan, James E -- Minch, Kyle -- Peterson, Matthew -- Lyubetskaya, Anna -- Azizi, Elham -- Sweet, Linsday -- Gomes, Antonio -- Rustad, Tige -- Dolganov, Gregory -- Glotova, Irina -- Abeel, Thomas -- Mahwinney, Chris -- Kennedy, Adam D -- Allard, Rene -- Brabant, William -- Krueger, Andrew -- Jaini, Suma -- Honda, Brent -- Yu, Wen-Han -- Hickey, Mark J -- Zucker, Jeremy -- Garay, Christopher -- Weiner, Brian -- Sisk, Peter -- Stolte, Christian -- Winkler, Jessica K -- Van de Peer, Yves -- Iazzetti, Paul -- Camacho, Diogo -- Dreyfuss, Jonathan -- Liu, Yang -- Dorhoi, Anca -- Mollenkopf, Hans-Joachim -- Drogaris, Paul -- Lamontagne, Julie -- Zhou, Yiyong -- Piquenot, Julie -- Park, Sang Tae -- Raman, Sahadevan -- Kaufmann, Stefan H E -- Mohney, Robert P -- Chelsky, Daniel -- Moody, D Branch -- Sherman, David R -- Schoolnik, Gary K -- HHSN272200800059C/AI/NIAID NIH HHS/ -- HHSN272200800059C/PHS HHS/ -- R01 AI 071155/AI/NIAID NIH HHS/ -- R01 AI071155/AI/NIAID NIH HHS/ -- U19 AI 076217/AI/NIAID NIH HHS/ -- U19 AI076217/AI/NIAID NIH HHS/ -- England -- Nature. 2013 Jul 11;499(7457):178-83. doi: 10.1038/nature12337. Epub 2013 Jul 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA. jgalag@bu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23823726" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological ; Anoxia/*genetics/metabolism ; Bacterial Proteins/genetics/metabolism ; Binding Sites ; Chromatin Immunoprecipitation ; Gene Expression Profiling ; *Gene Regulatory Networks/genetics ; Genomics ; Lipid Metabolism/genetics ; Metabolic Networks and Pathways/*genetics ; Models, Biological ; Mycobacterium tuberculosis/drug effects/*genetics/*metabolism/physiology ; Oxygen/pharmacology ; Proteolysis ; RNA, Messenger/genetics/metabolism ; Reproducibility of Results ; Sequence Analysis, DNA ; Transcription Factors/genetics/metabolism ; Tuberculosis/metabolism/microbiology
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  • 47
    Publication Date: 2013-12-18
    Description: Strigolactones (SLs) are a group of newly identified plant hormones that control plant shoot branching. SL signalling requires the hormone-dependent interaction of DWARF 14 (D14), a probable candidate SL receptor, with DWARF 3 (D3), an F-box component of the Skp-Cullin-F-box (SCF) E3 ubiquitin ligase complex. Here we report the characterization of a dominant SL-insensitive rice (Oryza sativa) mutant dwarf 53 (d53) and the cloning of D53, which encodes a substrate of the SCF(D3) ubiquitination complex and functions as a repressor of SL signalling. Treatments with GR24, a synthetic SL analogue, cause D53 degradation via the proteasome in a manner that requires D14 and the SCF(D3) ubiquitin ligase, whereas the dominant form of D53 is resistant to SL-mediated degradation. Moreover, D53 can interact with transcriptional co-repressors known as TOPLESS-RELATED PROTEINS. Our results suggest a model of SL signalling that involves SL-dependent degradation of the D53 repressor mediated by the D14-D3 complex.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jiang, Liang -- Liu, Xue -- Xiong, Guosheng -- Liu, Huihui -- Chen, Fulu -- Wang, Lei -- Meng, Xiangbing -- Liu, Guifu -- Yu, Hong -- Yuan, Yundong -- Yi, Wei -- Zhao, Lihua -- Ma, Honglei -- He, Yuanzheng -- Wu, Zhongshan -- Melcher, Karsten -- Qian, Qian -- Xu, H Eric -- Wang, Yonghong -- Li, Jiayang -- England -- Nature. 2013 Dec 19;504(7480):401-5. doi: 10.1038/nature12870. Epub 2013 Dec 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] State Key Laboratory of Plant Genomics and National Center for Plant Gene Research (Beijing), Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China [2]. ; State Key Laboratory of Plant Genomics and National Center for Plant Gene Research (Beijing), Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China. ; VARI-SIMM Center, Center for Structure and Function of Drug Targets, CAS-Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. ; Laboratory of Structural Sciences, Van Andel Research Institute, 333 Bostwick Avenue Northeast, Grand Rapids, Michigan 49503, USA. ; State Key Laboratory of Rice Biology, China National Rice Research Institute, Chinese Academy of Agricultural Sciences, Hangzhou 310006, China. ; 1] VARI-SIMM Center, Center for Structure and Function of Drug Targets, CAS-Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China [2] Laboratory of Structural Sciences, Van Andel Research Institute, 333 Bostwick Avenue Northeast, Grand Rapids, Michigan 49503, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24336200" target="_blank"〉PubMed〈/a〉
    Keywords: Cloning, Molecular ; Gene Expression Regulation, Plant ; Lactones/*antagonists & inhibitors/*metabolism ; Models, Biological ; Multiprotein Complexes/chemistry/metabolism ; Mutation/genetics ; Oryza/genetics/*metabolism ; Plant Growth Regulators/antagonists & inhibitors/*metabolism ; Plant Proteins/chemistry/genetics/*metabolism ; Proteasome Endopeptidase Complex/metabolism ; Protein Binding ; Proteolysis ; *Signal Transduction ; Ubiquitin/metabolism
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  • 48
    Publication Date: 2013-04-09
    Description: In vertebrate development, the body plan is determined by primordial morphogen gradients that suffuse the embryo. Retinoic acid (RA) is an important morphogen involved in patterning the anterior-posterior axis of structures, including the hindbrain and paraxial mesoderm. RA diffuses over long distances, and its activity is spatially restricted by synthesizing and degrading enzymes. However, gradients of endogenous morphogens in live embryos have not been directly observed; indeed, their existence, distribution and requirement for correct patterning remain controversial. Here we report a family of genetically encoded indicators for RA that we have termed GEPRAs (genetically encoded probes for RA). Using the principle of fluorescence resonance energy transfer we engineered the ligand-binding domains of RA receptors to incorporate cyan-emitting and yellow-emitting fluorescent proteins as fluorescence resonance energy transfer donor and acceptor, respectively, for the reliable detection of ambient free RA. We created three GEPRAs with different affinities for RA, enabling the quantitative measurement of physiological RA concentrations. Live imaging of zebrafish embryos at the gastrula and somitogenesis stages revealed a linear concentration gradient of endogenous RA in a two-tailed source-sink arrangement across the embryo. Modelling of the observed linear RA gradient suggests that the rate of RA diffusion exceeds the spatiotemporal dynamics of embryogenesis, resulting in stability to perturbation. Furthermore, we used GEPRAs in combination with genetic and pharmacological perturbations to resolve competing hypotheses on the structure of the RA gradient during hindbrain formation and somitogenesis. Live imaging of endogenous concentration gradients across embryonic development will allow the precise assignment of molecular mechanisms to developmental dynamics and will accelerate the application of approaches based on morphogen gradients to tissue engineering and regenerative medicine.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shimozono, Satoshi -- Iimura, Tadahiro -- Kitaguchi, Tetsuya -- Higashijima, Shin-Ichi -- Miyawaki, Atsushi -- England -- Nature. 2013 Apr 18;496(7445):363-6. doi: 10.1038/nature12037. Epub 2013 Apr 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Cell Function Dynamics, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-city, Saitama 351-0198, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23563268" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Body Patterning/physiology ; Embryo, Nonmammalian/embryology/metabolism ; Embryonic Development/*physiology ; Fibroblast Growth Factors/genetics/metabolism ; Fluorescence Resonance Energy Transfer ; Gastrula/embryology/metabolism ; HeLa Cells ; Humans ; Models, Biological ; Molecular Probes/analysis/genetics/metabolism ; Molecular Sequence Data ; Rhombencephalon/embryology/metabolism ; Somites/embryology/metabolism ; Substrate Specificity ; Tretinoin/analysis/*metabolism ; Zebrafish/*embryology/*metabolism ; Zebrafish Proteins/genetics/metabolism
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  • 49
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2013-04-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boehm, Thomas -- England -- Nature. 2013 Apr 18;496(7445):304-5. doi: 10.1038/496304a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23598335" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Genetic Variation ; Genome/*genetics ; *Heredity ; Ligands ; Major Histocompatibility Complex/genetics/immunology ; Mice ; Models, Biological ; Peptides/chemistry/genetics/urine ; Proteins/analysis/chemistry/genetics ; Proteolysis ; Sensory Receptor Cells/metabolism ; Smell/*physiology
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  • 50
    Publication Date: 2013-10-11
    Description: Cyanobacteria are photosynthetic organisms responsible for approximately 25% of organic carbon fixation on the Earth. These bacteria began to convert solar energy and carbon dioxide into bioenergy and oxygen more than two billion years ago. Cyanophages, which infect these bacteria, have an important role in regulating the marine ecosystem by controlling cyanobacteria community organization and mediating lateral gene transfer. Here we visualize the maturation process of cyanophage Syn5 inside its host cell, Synechococcus, using Zernike phase contrast electron cryo-tomography (cryoET). This imaging modality yields dramatic enhancement of image contrast over conventional cryoET and thus facilitates the direct identification of subcellular components, including thylakoid membranes, carboxysomes and polyribosomes, as well as phages, inside the congested cytosol of the infected cell. By correlating the structural features and relative abundance of viral progeny within cells at different stages of infection, we identify distinct Syn5 assembly intermediates. Our results indicate that the procapsid releases scaffolding proteins and expands its volume at an early stage of genome packaging. Later in the assembly process, we detected full particles with a tail either with or without an additional horn. The morphogenetic pathway we describe here is highly conserved and was probably established long before that of double-stranded DNA viruses infecting more complex organisms.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984937/" 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/PMC3984937/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dai, Wei -- Fu, Caroline -- Raytcheva, Desislava -- Flanagan, John -- Khant, Htet A -- Liu, Xiangan -- Rochat, Ryan H -- Haase-Pettingell, Cameron -- Piret, Jacqueline -- Ludtke, Steve J -- Nagayama, Kuniaki -- Schmid, Michael F -- King, Jonathan A -- Chiu, Wah -- AI0175208/AI/NIAID NIH HHS/ -- GM080139/GM/NIGMS NIH HHS/ -- P41 GM103832/GM/NIGMS NIH HHS/ -- P41GM123832/GM/NIGMS NIH HHS/ -- PN2 EY016525/EY/NEI NIH HHS/ -- PN2EY016525/EY/NEI NIH HHS/ -- R01 GM080139/GM/NIGMS NIH HHS/ -- R56 AI075208/AI/NIAID NIH HHS/ -- T15 LM007093/LM/NLM NIH HHS/ -- T15LM007093/LM/NLM NIH HHS/ -- T32GM007330/GM/NIGMS NIH HHS/ -- England -- Nature. 2013 Oct 31;502(7473):707-10. doi: 10.1038/nature12604. Epub 2013 Oct 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Center for Macromolecular Imaging, Verna and Marrs Mclean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24107993" target="_blank"〉PubMed〈/a〉
    Keywords: Aquatic Organisms/cytology/ultrastructure/virology ; Bacteriophages/*growth & development/*ultrastructure ; Cryoelectron Microscopy/*methods ; Electron Microscope Tomography/*methods ; Models, Biological ; Synechococcus/cytology/*ultrastructure/*virology ; *Virus Assembly
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  • 51
    Publication Date: 2013-06-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pongratz, Julia -- England -- Nature. 2013 Jun 6;498(7452):47-8. doi: 10.1038/498047a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23739422" target="_blank"〉PubMed〈/a〉
    Keywords: Atmosphere/chemistry ; Carbon Dioxide/metabolism ; *Carbon Sequestration ; Climate Change/statistics & numerical data ; Ecology/*methods ; *Forestry/methods ; Human Activities ; Models, Biological ; Nitrogen/analysis/*metabolism ; Nitrogen Fixation ; Soil Microbiology ; Trees/growth & development/*metabolism ; Uncertainty
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  • 52
    Publication Date: 2013-05-28
    Description: Fusing left and right eye images into a single view is dependent on precise ocular alignment, which relies on coordinated eye movements. During movements of the head this alignment is maintained by numerous reflexes. Although rodents share with other mammals the key components of eye movement control, the coordination of eye movements in freely moving rodents is unknown. Here we show that movements of the two eyes in freely moving rats differ fundamentally from the precisely controlled eye movements used by other mammals to maintain continuous binocular fusion. The observed eye movements serve to keep the visual fields of the two eyes continuously overlapping above the animal during free movement, but not continuously aligned. Overhead visual stimuli presented to rats freely exploring an open arena evoke an immediate shelter-seeking behaviour, but are ineffective when presented beside the arena. We suggest that continuously overlapping visual fields overhead would be of evolutionary benefit for predator detection by minimizing blind spots.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wallace, Damian J -- Greenberg, David S -- Sawinski, Juergen -- Rulla, Stefanie -- Notaro, Giuseppe -- Kerr, Jason N D -- England -- Nature. 2013 Jun 6;498(7452):65-9. doi: 10.1038/nature12153. Epub 2013 May 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Network Imaging Group, Max Planck Institute for Biological Cybernetics, Spemannstrasse 41, 72076 Tubingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23708965" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Escape Reaction/physiology ; Exploratory Behavior/physiology ; Eye Movements/physiology ; Head/physiology ; Models, Biological ; Movement/physiology ; Optic Disk/physiology ; Predatory Behavior ; Rats ; Retina/physiology ; Vision, Binocular/*physiology ; Visual Fields/*physiology
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  • 53
    Publication Date: 2013-11-29
    Description: Achieving the goal of malaria elimination will depend on targeting Plasmodium pathways essential across all life stages. Here we identify a lipid kinase, phosphatidylinositol-4-OH kinase (PI(4)K), as the target of imidazopyrazines, a new antimalarial compound class that inhibits the intracellular development of multiple Plasmodium species at each stage of infection in the vertebrate host. Imidazopyrazines demonstrate potent preventive, therapeutic, and transmission-blocking activity in rodent malaria models, are active against blood-stage field isolates of the major human pathogens P. falciparum and P. vivax, and inhibit liver-stage hypnozoites in the simian parasite P. cynomolgi. We show that imidazopyrazines exert their effect through inhibitory interaction with the ATP-binding pocket of PI(4)K, altering the intracellular distribution of phosphatidylinositol-4-phosphate. Collectively, our data define PI(4)K as a key Plasmodium vulnerability, opening up new avenues of target-based discovery to identify drugs with an ideal activity profile for the prevention, treatment and elimination of malaria.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3940870/" 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/PMC3940870/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McNamara, Case W -- Lee, Marcus C S -- Lim, Chek Shik -- Lim, Siau Hoi -- Roland, Jason -- Nagle, Advait -- Simon, Oliver -- Yeung, Bryan K S -- Chatterjee, Arnab K -- McCormack, Susan L -- Manary, Micah J -- Zeeman, Anne-Marie -- Dechering, Koen J -- Kumar, T R Santha -- Henrich, Philipp P -- Gagaring, Kerstin -- Ibanez, Maureen -- Kato, Nobutaka -- Kuhen, Kelli L -- Fischli, Christoph -- Rottmann, Matthias -- Plouffe, David M -- Bursulaya, Badry -- Meister, Stephan -- Rameh, Lucia -- Trappe, Joerg -- Haasen, Dorothea -- Timmerman, Martijn -- Sauerwein, Robert W -- Suwanarusk, Rossarin -- Russell, Bruce -- Renia, Laurent -- Nosten, Francois -- Tully, David C -- Kocken, Clemens H M -- Glynne, Richard J -- Bodenreider, Christophe -- Fidock, David A -- Diagana, Thierry T -- Winzeler, Elizabeth A -- 078285/Wellcome Trust/United Kingdom -- 089275/Wellcome Trust/United Kingdom -- 090534/Wellcome Trust/United Kingdom -- 096157/Wellcome Trust/United Kingdom -- R01 AI079709/AI/NIAID NIH HHS/ -- R01 AI085584/AI/NIAID NIH HHS/ -- R01 AI090141/AI/NIAID NIH HHS/ -- R01 AI103058/AI/NIAID NIH HHS/ -- R01079709/PHS HHS/ -- R01085584/PHS HHS/ -- R01AI090141/AI/NIAID NIH HHS/ -- WT078285/Wellcome Trust/United Kingdom -- WT096157/Wellcome Trust/United Kingdom -- England -- Nature. 2013 Dec 12;504(7479):248-53. doi: 10.1038/nature12782. Epub 2013 Nov 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA [2]. ; 1] Department of Microbiology & Immunology, Columbia University Medical Center, New York, New York 10032, USA [2]. ; Novartis Institutes for Tropical Disease, 138670 Singapore. ; Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA. ; Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA. ; Department of Parasitology, Biomedical Primate Research Centre, PO Box 3306, 2280 GH Rijswijk, The Netherlands. ; TropIQ Health Sciences, 6525 GA Nijmegen, The Netherlands. ; Department of Microbiology & Immunology, Columbia University Medical Center, New York, New York 10032, USA. ; Swiss Tropical and Public Health Institute, CH-4002 Basel, Switzerland. ; 1] Swiss Tropical and Public Health Institute, CH-4002 Basel, Switzerland [2] University of Basel, CH-4003 Basel, Switzerland. ; Department of Medicine, School of Medicine, Boston University, Boston, Massachusetts 02118, USA. ; Novartis Institutes for BioMedical Research, CH-4002 Basel, Switzerland. ; 1] TropIQ Health Sciences, 6525 GA Nijmegen, The Netherlands [2] Department of Medical Microbiology, Radboud University, Nijmegen Medical CentrePO Box 9101, 6500 HB Nijmegen, The Netherlands. ; Laboratory of Malaria Immunobiology, Singapore Immunology Network, Agency for Science Technology and Research (A*STAR), Biopolis, 138648 Singapore. ; 1] Laboratory of Malaria Immunobiology, Singapore Immunology Network, Agency for Science Technology and Research (A*STAR), Biopolis, 138648 Singapore [2] Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, 117545 Singapore. ; 1] Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK [2] Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot 63110, Thailand. ; 1] Department of Microbiology & Immunology, Columbia University Medical Center, New York, New York 10032, USA [2] Division of Infectious Diseases, Department of Medicine, Columbia University Medical Center, New York, New York 10032, USA. ; 1] Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA [2] Department of Pediatrics, School of Medicine, 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/24284631" target="_blank"〉PubMed〈/a〉
    Keywords: 1-Phosphatidylinositol 4-Kinase/*antagonists & ; inhibitors/chemistry/genetics/metabolism ; Adenosine Triphosphate/metabolism ; Animals ; Binding Sites ; Cytokinesis/drug effects ; Drug Resistance/drug effects/genetics ; Fatty Acids/metabolism ; Female ; Hepatocytes/parasitology ; Humans ; Imidazoles/metabolism/pharmacology ; Life Cycle Stages/drug effects ; Macaca mulatta ; Malaria/*drug therapy/*parasitology ; Male ; Models, Biological ; Models, Molecular ; Phosphatidylinositol Phosphates/metabolism ; Plasmodium/classification/*drug effects/*enzymology/growth & development ; Pyrazoles/metabolism/pharmacology ; Quinoxalines/metabolism/pharmacology ; Reproducibility of Results ; Schizonts/cytology/drug effects ; rab GTP-Binding Proteins/genetics/metabolism
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  • 54
    Publication Date: 2013-12-10
    Description: Respiratory surfaces are exposed to billions of particulates and pathogens daily. A protective mucus barrier traps and eliminates them through mucociliary clearance (MCC). However, excessive mucus contributes to transient respiratory infections and to the pathogenesis of numerous respiratory diseases. MUC5AC and MUC5B are evolutionarily conserved genes that encode structurally related mucin glycoproteins, the principal macromolecules in airway mucus. Genetic variants are linked to diverse lung diseases, but specific roles for MUC5AC and MUC5B in MCC, and the lasting effects of their inhibition, are unknown. Here we show that mouse Muc5b (but not Muc5ac) is required for MCC, for controlling infections in the airways and middle ear, and for maintaining immune homeostasis in mouse lungs, whereas Muc5ac is dispensable. Muc5b deficiency caused materials to accumulate in upper and lower airways. This defect led to chronic infection by multiple bacterial species, including Staphylococcus aureus, and to inflammation that failed to resolve normally. Apoptotic macrophages accumulated, phagocytosis was impaired, and interleukin-23 (IL-23) production was reduced in Muc5b(-/-) mice. By contrast, in mice that transgenically overexpress Muc5b, macrophage functions improved. Existing dogma defines mucous phenotypes in asthma and chronic obstructive pulmonary disease (COPD) as driven by increased MUC5AC, with MUC5B levels either unaffected or increased in expectorated sputum. However, in many patients, MUC5B production at airway surfaces decreases by as much as 90%. By distinguishing a specific role for Muc5b in MCC, and by determining its impact on bacterial infections and inflammation in mice, our results provide a refined framework for designing targeted therapies to control mucin secretion and restore MCC.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4001806/" 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/PMC4001806/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roy, Michelle G -- Livraghi-Butrico, Alessandra -- Fletcher, Ashley A -- McElwee, Melissa M -- Evans, Scott E -- Boerner, Ryan M -- Alexander, Samantha N -- Bellinghausen, Lindsey K -- Song, Alfred S -- Petrova, Youlia M -- Tuvim, Michael J -- Adachi, Roberto -- Romo, Irlanda -- Bordt, Andrea S -- Bowden, M Gabriela -- Sisson, Joseph H -- Woodruff, Prescott G -- Thornton, David J -- Rousseau, Karine -- De la Garza, Maria M -- Moghaddam, Seyed J -- Karmouty-Quintana, Harry -- Blackburn, Michael R -- Drouin, Scott M -- Davis, C William -- Terrell, Kristy A -- Grubb, Barbara R -- O'Neal, Wanda K -- Flores, Sonia C -- Cota-Gomez, Adela -- Lozupone, Catherine A -- Donnelly, Jody M -- Watson, Alan M -- Hennessy, Corinne E -- Keith, Rebecca C -- Yang, Ivana V -- Barthel, Lea -- Henson, Peter M -- Janssen, William J -- Schwartz, David A -- Boucher, Richard C -- Dickey, Burton F -- Evans, Christopher M -- CA016086/CA/NCI NIH HHS/ -- CA016672/CA/NCI NIH HHS/ -- CA046934/CA/NCI NIH HHS/ -- G1000450/Medical Research Council/United Kingdom -- K01 DK090285/DK/NIDDK NIH HHS/ -- P01 HL108808/HL/NHLBI NIH HHS/ -- P01 HL110873/HL/NHLBI NIH HHS/ -- P30 CA016086/CA/NCI NIH HHS/ -- P30 CA016672/CA/NCI NIH HHS/ -- P30 CA046934/CA/NCI NIH HHS/ -- P30 DK065988/DK/NIDDK NIH HHS/ -- P30DK065988/DK/NIDDK NIH HHS/ -- P50 HL107168/HL/NHLBI NIH HHS/ -- R01 AA008769/AA/NIAAA NIH HHS/ -- R01 HL080396/HL/NHLBI NIH HHS/ -- R01 HL097000/HL/NHLBI NIH HHS/ -- R01 HL109517/HL/NHLBI NIH HHS/ -- R01 HL114381/HL/NHLBI NIH HHS/ -- England -- Nature. 2014 Jan 16;505(7483):412-6. doi: 10.1038/nature12807. Epub 2013 Dec 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] University of Texas, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA [2]. ; 1] University of North Carolina-Chapel Hill, 7011 Thurston-Bowles Building, Chapel Hill, North Carolina 27599, USA [2]. ; 1] University of Colorado School of Medicine, 12700 East 19th Avenue, Aurora, Colorado 80045, USA [2]. ; University of Texas, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA. ; University of Texas Health Science Center-Houston Medical School, 6431 Fannin Street, Houston, Texas 77030, USA. ; 1] University of Texas, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA [2] Instituto Tecnologico y de Estudios Superiores de Monterrey, Avenida Eugenio Garza Sada 2501 Sur Colonia Tecnologico, Monterrey, Nuevo Leon 64849, Mexico. ; Texas A&M Health Science Center, 2121 W. Holcombe Boulevard, Houston, Texas 77030, USA. ; 1] Texas A&M Health Science Center, 2121 W. Holcombe Boulevard, Houston, Texas 77030, USA [2] University of Houston-Downtown, 1 Main Street, Houston, Texas 77002, USA. ; University of Nebraska Medical Center, 985910 Nebraska Medical Center, Omaha, Nebraska 68198, USA. ; University of California San Francisco, 505 Parnassus Avenue, San Francisco, California 27599, USA. ; University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK. ; University of North Carolina-Chapel Hill, 7011 Thurston-Bowles Building, Chapel Hill, North Carolina 27599, USA. ; University of Colorado School of Medicine, 12700 East 19th Avenue, Aurora, Colorado 80045, USA. ; 1] University of Colorado School of Medicine, 12700 East 19th Avenue, Aurora, Colorado 80045, USA [2] National Jewish Health, Denver, Colorado 80206, USA. ; 1] University of Texas, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA [2] University of Colorado School of Medicine, 12700 East 19th Avenue, Aurora, Colorado 80045, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24317696" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Asthma/immunology/metabolism ; Bacterial Infections/immunology/microbiology ; Cilia/physiology ; Ear, Middle/immunology/microbiology ; Female ; Inflammation/pathology ; Lung/*immunology/metabolism/microbiology ; Macrophages/immunology/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Models, Biological ; Mucin 5AC/deficiency/metabolism ; Mucin-5B/deficiency/genetics/*metabolism/secretion ; Phagocytosis ; Pulmonary Disease, Chronic Obstructive/immunology/microbiology ; Respiratory Mucosa/*immunology/*metabolism ; Staphylococcus aureus/immunology ; Survival Analysis
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  • 55
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2013-01-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vance, Erik -- England -- Nature. 2012 Nov 22;491(7425):S52-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23320285" target="_blank"〉PubMed〈/a〉
    Keywords: Biomarkers, Tumor/analysis ; Biomedical Research/*methods ; Computer Simulation ; *Data Mining ; Humans ; *Interdisciplinary Studies ; Models, Biological ; Neoplasm Proteins/genetics/metabolism ; *Neoplasms/diagnosis/drug therapy/mortality/pathology ; Precision Medicine ; Proteome/genetics/metabolism ; *Proteomics/methods ; United States
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  • 56
    Publication Date: 2013-04-23
    Description: Accurate segregation of the replicated genome requires chromosome biorientation on the spindle. Biorientation is ensured by Aurora B kinase (Ipl1), a member of the four-subunit chromosomal passenger complex (CPC). Localization of the CPC to the inner centromere is central to the current model for how tension ensures chromosome biorientation: kinetochore-spindle attachments that are not under tension remain close to the inner centromere and are destabilized by Aurora B phosphorylation, whereas kinetochores under tension are pulled away from the influence of Aurora B, stabilizing their microtubule attachments. Here we show that an engineered truncation of the Sli15 (known as INCENP in humans) subunit of budding yeast CPC that eliminates association with the inner centromere nevertheless supports proper chromosome segregation during both mitosis and meiosis. Truncated Sli15 suppresses the deletion phenotypes of the inner-centromere-targeting proteins survivin (Bir1), borealin (Nbl1), Bub1 and Sgo1 (ref. 6). Unlike wild-type Sli15, truncated Sli15 localizes to pre-anaphase spindle microtubules. Premature targeting of full-length Sli15 to microtubules by preventing Cdk1 (also known as Cdc28) phosphorylation also suppresses the inviability of Bir1 deletion. These results suggest that activation of Aurora B kinase by clustering either on chromatin or on microtubules is sufficient for chromosome biorientation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644022/" 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/PMC3644022/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Campbell, Christopher S -- Desai, Arshad -- GM074215/GM/NIGMS NIH HHS/ -- R01 GM074215/GM/NIGMS NIH HHS/ -- England -- Nature. 2013 May 2;497(7447):118-21. doi: 10.1038/nature12057. Epub 2013 Apr 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23604256" target="_blank"〉PubMed〈/a〉
    Keywords: Aurora Kinase B ; Aurora Kinases ; CDC2 Protein Kinase/antagonists & inhibitors/metabolism ; Carrier Proteins/genetics/metabolism ; Centromere/*metabolism ; Chromatin/metabolism ; Chromosome Segregation ; Intracellular Signaling Peptides and Proteins/*metabolism ; Kinetochores/metabolism ; Meiosis ; Microbial Viability ; Microtubule-Associated Proteins/deficiency/genetics/*metabolism ; Microtubules/metabolism ; Mitosis ; Models, Biological ; Movement ; Nuclear Proteins/metabolism ; Phosphorylation ; Protein-Serine-Threonine Kinases/*metabolism ; Saccharomyces cerevisiae/*cytology/enzymology/*metabolism ; Saccharomyces cerevisiae Proteins/genetics/*metabolism ; Sequence Deletion/genetics
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  • 57
    Publication Date: 2013-11-22
    Description: Genetically identical cells sharing an environment can display markedly different phenotypes. It is often unclear how much of this variation derives from chance, external signals, or attempts by individual cells to exert autonomous phenotypic programs. By observing thousands of cells for hundreds of consecutive generations under constant conditions, we dissect the stochastic decision between a solitary, motile state and a chained, sessile state in Bacillus subtilis. We show that the motile state is 'memoryless', exhibiting no autonomous control over the time spent in the state. In contrast, the time spent as connected chains of cells is tightly controlled, enforcing coordination among related cells in the multicellular state. We show that the three-protein regulatory circuit governing the decision is modular, as initiation and maintenance of chaining are genetically separable functions. As stimulation of the same initiating pathway triggers biofilm formation, we argue that autonomous timing allows a trial commitment to multicellularity that external signals could extend.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4019345/" 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/PMC4019345/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Norman, Thomas M -- Lord, Nathan D -- Paulsson, Johan -- Losick, Richard -- GM081563/GM/NIGMS NIH HHS/ -- GM18568/GM/NIGMS NIH HHS/ -- R01 GM018568/GM/NIGMS NIH HHS/ -- R01 GM081563/GM/NIGMS NIH HHS/ -- England -- Nature. 2013 Nov 28;503(7477):481-6. doi: 10.1038/nature12804. Epub 2013 Nov 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA [2].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24256735" target="_blank"〉PubMed〈/a〉
    Keywords: Bacillus subtilis/*cytology/genetics/*physiology ; Models, Biological ; Movement ; Phenotype ; Stochastic Processes ; Time Factors
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  • 58
    Publication Date: 2013-06-07
    Description: The hepatitis C virus (HCV) has developed a small membrane protein, p7, which remarkably can self-assemble into a large channel complex that selectively conducts cations. We wanted to examine the structural solution that the viroporin adopts in order to achieve selective cation conduction, because p7 has no homology with any of the known prokaryotic or eukaryotic channel proteins. The activity of p7 can be inhibited by amantadine and rimantadine, which are potent blockers of the influenza M2 channel and licensed drugs against influenza infections. The adamantane derivatives have been used in HCV clinical trials, but large variation in drug efficacy among the various HCV genotypes has been difficult to explain without detailed molecular structures. Here we determine the structures of this HCV viroporin as well as its drug-binding site using the latest nuclear magnetic resonance (NMR) technologies. The structure exhibits an unusual mode of hexameric assembly, where the individual p7 monomers, i, not only interact with their immediate neighbours, but also reach farther to associate with the i+2 and i+3 monomers, forming a sophisticated, funnel-like architecture. The structure also points to a mechanism of cation selection: an asparagine/histidine ring that constricts the narrow end of the funnel serves as a broad cation selectivity filter, whereas an arginine/lysine ring that defines the wide end of the funnel may selectively allow cation diffusion into the channel. Our functional investigation using whole-cell channel recording shows that these residues are critical for channel activity. NMR measurements of the channel-drug complex revealed six equivalent hydrophobic pockets between the peripheral and pore-forming helices to which amantadine or rimantadine binds, and compound binding specifically to this position may allosterically inhibit cation conduction by preventing the channel from opening. Our data provide a molecular explanation for p7-mediated cation conductance and its inhibition by adamantane derivatives.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3725310/" 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/PMC3725310/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉OuYang, Bo -- Xie, Shiqi -- Berardi, Marcelo J -- Zhao, Xinhao -- Dev, Jyoti -- Yu, Wenjing -- Sun, Bing -- Chou, James J -- GM094608/GM/NIGMS NIH HHS/ -- U54 GM094608/GM/NIGMS NIH HHS/ -- England -- Nature. 2013 Jun 27;498(7455):521-5. doi: 10.1038/nature12283. Epub 2013 Jun 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23739335" target="_blank"〉PubMed〈/a〉
    Keywords: Adamantane/analogs & derivatives/chemistry/metabolism/pharmacology ; Binding Sites ; Diffusion ; Hepacivirus/*chemistry ; Microscopy, Electron ; Models, Biological ; Models, Molecular ; Nuclear Magnetic Resonance, Biomolecular ; Porosity ; Rimantadine/chemistry/metabolism/pharmacology ; Structure-Activity Relationship ; Viral Proteins/antagonists & inhibitors/*chemistry/metabolism/ultrastructure
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  • 59
    Publication Date: 2013-07-12
    Description: The epiblast is the mammalian embryonic tissue that contains the pluripotent stem cells that generate the whole embryo. We have established a method for inducing functional genetic mosaics in the mouse. Using this system, here we show that induction of a mosaic imbalance of Myc expression in the epiblast provokes the expansion of cells with higher Myc levels through the apoptotic elimination of cells with lower levels, without disrupting development. In contrast, homogeneous shifts in Myc levels did not affect epiblast cell viability, indicating that the observed competition results from comparison of relative Myc levels between epiblast cells. During normal development we found that Myc levels are intrinsically heterogeneous among epiblast cells, and that endogenous cell competition refines the epiblast cell population through the elimination of cells with low relative Myc levels. These results show that natural cell competition in the early mammalian embryo contributes to the selection of the epiblast cell pool.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Claveria, Cristina -- Giovinazzo, Giovanna -- Sierra, Rocio -- Torres, Miguel -- England -- Nature. 2013 Aug 1;500(7460):39-44. doi: 10.1038/nature12389. Epub 2013 Jul 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departamento de Desarrollo y Reparacion Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares, Madrid E-28029, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23842495" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Cell Proliferation ; Embryo, Mammalian/*cytology/*metabolism ; Embryonic Stem Cells/cytology/metabolism ; Female ; Gene Expression ; Genes, myc ; Germ Layers/*cytology/metabolism ; Male ; Mice ; Models, Biological ; Mosaicism/embryology ; Proto-Oncogene Proteins c-myc/*metabolism
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  • 60
    Publication Date: 2013-04-02
    Description: Phosphate is crucial for structural and metabolic needs, including nucleotide and lipid synthesis, signalling and chemical energy storage. Proton-coupled transporters of the major facilitator superfamily (MFS) are essential for phosphate uptake in plants and fungi, and also have a function in sensing external phosphate levels as transceptors. Here we report the 2.9 A structure of a fungal (Piriformospora indica) high-affinity phosphate transporter, PiPT, in an inward-facing occluded state, with bound phosphate visible in the membrane-buried binding site. The structure indicates both proton and phosphate exit pathways and suggests a modified asymmetrical 'rocker-switch' mechanism of phosphate transport. PiPT is related to several human transporter families, most notably the organic cation and anion transporters of the solute carrier family (SLC22), which are implicated in cancer-drug resistance. We modelled representative cation and anion SLC22 transporters based on the PiPT structure to surmise the structural basis for substrate binding and charge selectivity in this important family. The PiPT structure demonstrates and expands on principles of substrate transport by the MFS transporters and illuminates principles of phosphate uptake in particular.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678552/" 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/PMC3678552/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pedersen, Bjorn P -- Kumar, Hemant -- Waight, Andrew B -- Risenmay, Aaron J -- Roe-Zurz, Zygy -- Chau, Bryant H -- Schlessinger, Avner -- Bonomi, Massimiliano -- Harries, William -- Sali, Andrej -- Johri, Atul K -- Stroud, Robert M -- F32 GM088991/GM/NIGMS NIH HHS/ -- GM073210/GM/NIGMS NIH HHS/ -- GM24485/GM/NIGMS NIH HHS/ -- P50 GM073210/GM/NIGMS NIH HHS/ -- R01 GM024485/GM/NIGMS NIH HHS/ -- R37 GM024485/GM/NIGMS NIH HHS/ -- U01 GM061390/GM/NIGMS NIH HHS/ -- U01 GM61390/GM/NIGMS NIH HHS/ -- U19 GM061390/GM/NIGMS NIH HHS/ -- U54 GM094625/GM/NIGMS NIH HHS/ -- England -- Nature. 2013 Apr 25;496(7446):533-6. doi: 10.1038/nature12042. Epub 2013 Mar 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23542591" target="_blank"〉PubMed〈/a〉
    Keywords: Basidiomycota/*chemistry ; Binding Sites ; Crystallography, X-Ray ; Eukaryotic Cells/*chemistry ; Humans ; Models, Biological ; Models, Molecular ; Phosphate Transport Proteins/*chemistry/metabolism ; Phosphates/metabolism ; Protein Conformation ; Protons ; Structure-Activity Relationship
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  • 61
    Publication Date: 2013-03-22
    Description: Photorhabdus luminescens is an insect pathogenic bacterium that is symbiotic with entomopathogenic nematodes. On invasion of insect larvae, P. luminescens is released from the nematodes and kills the insect through the action of a variety of virulence factors including large tripartite ABC-type toxin complexes (Tcs). Tcs are typically composed of TcA, TcB and TcC proteins and are biologically active only when complete. Functioning as ADP-ribosyltransferases, TcC proteins were identified as the actual functional components that induce actin-clustering, defects in phagocytosis and cell death. However, little is known about the translocation of TcC into the cell by the TcA and TcB components. Here we show that TcA in P. luminescens (TcdA1) forms a transmembrane pore and report its structure in the prepore and pore state determined by cryoelectron microscopy. We find that the TcdA1 prepore assembles as a pentamer forming an alpha-helical, vuvuzela-shaped channel less than 1.5 nanometres in diameter surrounded by a large outer shell. Membrane insertion is triggered not only at low pH as expected, but also at high pH, explaining Tc action directly through the midgut of insects. Comparisons with structures of the TcdA1 pore inserted into a membrane and in complex with TcdB2 and TccC3 reveal large conformational changes during membrane insertion, suggesting a novel syringe-like mechanism of protein translocation. Our results demonstrate how ABC-type toxin complexes bridge a membrane to insert their lethal components into the cytoplasm of the host cell. We believe that the proposed mechanism is characteristic of the whole ABC-type toxin family. This explanation of toxin translocation is a step towards understanding the host-pathogen interaction and the complex life cycle of P. luminescens and other pathogens, including human pathogenic bacteria, and serves as a strong foundation for the development of biopesticides.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gatsogiannis, Christos -- Lang, Alexander E -- Meusch, Dominic -- Pfaumann, Vanda -- Hofnagel, Oliver -- Benz, Roland -- Aktories, Klaus -- Raunser, Stefan -- England -- Nature. 2013 Mar 28;495(7442):520-3. doi: 10.1038/nature11987. Epub 2013 Mar 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physical Biochemistry, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23515159" target="_blank"〉PubMed〈/a〉
    Keywords: ADP Ribose Transferases/chemistry/metabolism/ultrastructure ; Animals ; Bacterial Proteins/chemistry/*metabolism/ultrastructure ; Bacterial Toxins/chemistry/*metabolism ; Cell Membrane/metabolism ; Cryoelectron Microscopy ; Cytoplasm/metabolism ; Host-Pathogen Interactions ; Insects/cytology/metabolism/microbiology ; Models, Biological ; Models, Molecular ; Photorhabdus/*metabolism/pathogenicity/ultrastructure ; Pore Forming Cytotoxic Proteins/chemistry/*metabolism/ultrastructure ; Protein Conformation ; Protein Transport
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  • 62
    Publication Date: 2013-04-16
    Description: The energy-coupling factor (ECF) transporters constitute a novel family of conserved membrane transporters in prokaryotes that have a similar domain organization to the ATP-binding cassette transporters. Each ECF transporter comprises a pair of cytosolic ATPases (the A and A' components, or EcfA and EcfA'), a membrane-embedded substrate-binding protein (the S component, or EcfS) and a transmembrane energy-coupling component (the T component, or EcfT) that links the EcfA-EcfA' subcomplex to EcfS. The structure and transport mechanism of the quaternary ECF transporter remain largely unknown. Here we report the crystal structure of a nucleotide-free ECF transporter from Lactobacillus brevis at a resolution of 3.5 A. The T component has a horseshoe-shaped open architecture, with five alpha-helices as transmembrane segments and two cytoplasmic alpha-helices as coupling modules connecting to the A and A' components. Strikingly, the S component, thought to be specific for hydroxymethyl pyrimidine, lies horizontally along the lipid membrane and is bound exclusively by the five transmembrane segments and the two cytoplasmic helices of the T component. These structural features suggest a plausible working model for the transport cycle of the ECF transporters.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Tingliang -- Fu, Guobin -- Pan, Xiaojing -- Wu, Jianping -- Gong, Xinqi -- Wang, Jiawei -- Shi, Yigong -- England -- Nature. 2013 May 9;497(7448):272-6. doi: 10.1038/nature12045. Epub 2013 Apr 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ministry of Education Key Laboratory of Protein Science, Tsinghua University, Beijing 100084, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23584587" target="_blank"〉PubMed〈/a〉
    Keywords: ATP-Binding Cassette Transporters/chemistry ; Anti-Bacterial Agents ; Bacterial Proteins/*chemistry/metabolism ; Crystallography, X-Ray ; Cytoplasm/chemistry/metabolism ; Lactobacillus brevis/*chemistry ; Models, Biological ; Models, Molecular ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein Subunits/chemistry/metabolism ; Pyrimidines/chemistry/metabolism ; Structure-Activity Relationship ; Substrate Specificity
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  • 63
    Publication Date: 2013-04-20
    Description: In bacteria, archaea, fungi and plants the Trk, Ktr and HKT ion transporters are key components of osmotic regulation, pH homeostasis and resistance to drought and high salinity. These ion transporters are functionally diverse: they can function as Na(+) or K(+) channels and possibly as cation/K(+) symporters. They are closely related to potassium channels both at the level of the membrane protein and at the level of the cytosolic regulatory domains. Here we describe the crystal structure of a Ktr K(+) transporter, the KtrAB complex from Bacillus subtilis. The structure shows the dimeric membrane protein KtrB assembled with a cytosolic octameric KtrA ring bound to ATP, an activating ligand. A comparison between the structure of KtrAB-ATP and the structures of the isolated full-length KtrA protein with ATP or ADP reveals a ligand-dependent conformational change in the octameric ring, raising new ideas about the mechanism of activation in these transporters.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vieira-Pires, Ricardo S -- Szollosi, Andras -- Morais-Cabral, Joao H -- England -- Nature. 2013 Apr 18;496(7445):323-8. doi: 10.1038/nature12055.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, Porto 4150-180, Portugal.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23598340" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Diphosphate/metabolism ; Adenosine Triphosphate/metabolism ; Bacillus subtilis/*chemistry ; Bacterial Proteins/*chemistry/*metabolism ; Cation Transport Proteins/*chemistry/*metabolism ; Crystallography, X-Ray ; Ion Transport ; Models, Biological ; Models, Molecular ; Potassium/*metabolism ; Protein Conformation ; Protein Subunits/chemistry/metabolism ; Structure-Activity Relationship
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  • 64
    Publication Date: 2013-10-18
    Description: The US National Cancer Institute (NCI), in collaboration with scientists representing multiple areas of expertise relevant to 'omics'-based test development, has developed a checklist of criteria that can be used to determine the readiness of omics-based tests for guiding patient care in clinical trials. The checklist criteria cover issues relating to specimens, assays, mathematical modelling, clinical trial design, and ethical, legal and regulatory aspects. Funding bodies and journals are encouraged to consider the checklist, which they may find useful for assessing study quality and evidence strength. The checklist will be used to evaluate proposals for NCI-sponsored clinical trials in which omics tests will be used to guide therapy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4180668/" 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/PMC4180668/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McShane, Lisa M -- Cavenagh, Margaret M -- Lively, Tracy G -- Eberhard, David A -- Bigbee, William L -- Williams, P Mickey -- Mesirov, Jill P -- Polley, Mei-Yin C -- Kim, Kelly Y -- Tricoli, James V -- Taylor, Jeremy M G -- Shuman, Deborah J -- Simon, Richard M -- Doroshow, James H -- Conley, Barbara A -- P30 CA046592/CA/NCI NIH HHS/ -- R01 CA129102/CA/NCI NIH HHS/ -- Z99 CA999999/Intramural NIH HHS/ -- England -- Nature. 2013 Oct 17;502(7471):317-20. doi: 10.1038/nature12564.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. mcshanel@ctep.nci.nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24132288" target="_blank"〉PubMed〈/a〉
    Keywords: Checklist ; Clinical Trials as Topic/economics/ethics/*methods/standards ; Evaluation Studies as Topic ; *Genomics/ethics ; Humans ; Models, Biological ; National Cancer Institute (U.S.)/economics ; Precision Medicine/ethics/methods/standards ; *Research Design/standards ; Specimen Handling ; United States
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  • 65
    Publication Date: 2013-11-26
    Description: Voltage-gated calcium (CaV) channels catalyse rapid, highly selective influx of Ca(2+) into cells despite a 70-fold higher extracellular concentration of Na(+). How CaV channels solve this fundamental biophysical problem remains unclear. Here we report physiological and crystallographic analyses of a calcium selectivity filter constructed in the homotetrameric bacterial NaV channel NaVAb. Our results reveal interactions of hydrated Ca(2+) with two high-affinity Ca(2+)-binding sites followed by a third lower-affinity site that would coordinate Ca(2+) as it moves inward. At the selectivity filter entry, Site 1 is formed by four carboxyl side chains, which have a critical role in determining Ca(2+) selectivity. Four carboxyls plus four backbone carbonyls form Site 2, which is targeted by the blocking cations Cd(2+) and Mn(2+), with single occupancy. The lower-affinity Site 3 is formed by four backbone carbonyls alone, which mediate exit into the central cavity. This pore architecture suggests a conduction pathway involving transitions between two main states with one or two hydrated Ca(2+) ions bound in the selectivity filter and supports a 'knock-off' mechanism of ion permeation through a stepwise-binding process. The multi-ion selectivity filter of our CaVAb model establishes a structural framework for understanding the mechanisms of ion selectivity and conductance by vertebrate CaV channels.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877713/" 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/PMC3877713/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tang, Lin -- Gamal El-Din, Tamer M -- Payandeh, Jian -- Martinez, Gilbert Q -- Heard, Teresa M -- Scheuer, Todd -- Zheng, Ning -- Catterall, William A -- R01 HL112808/HL/NHLBI NIH HHS/ -- R01 HL117896/HL/NHLBI NIH HHS/ -- R01 NS015751/NS/NINDS NIH HHS/ -- R01HL112808/HL/NHLBI NIH HHS/ -- R01NS015751/NS/NINDS NIH HHS/ -- T32 GM008268/GM/NIGMS NIH HHS/ -- T32GM008268/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jan 2;505(7481):56-61. doi: 10.1038/nature12775. Epub 2013 Nov 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA [2] Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA [3]. ; 1] Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA [2]. ; 1] Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA [2] Department of Structural Biology, Genentech Inc., South San Francisco, California 94080, USA. ; Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA. ; 1] Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA [2] Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24270805" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry/genetics/*metabolism ; Binding Sites ; Biocatalysis ; Calcium/metabolism ; Calcium Channels/*chemistry/genetics/*metabolism ; Cations, Divalent/metabolism ; Crystallography, X-Ray ; Electric Conductivity ; *Ion Channel Gating ; Models, Biological ; Models, Molecular ; Structure-Activity Relationship ; Substrate Specificity
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  • 66
    Publication Date: 2013-02-12
    Description: Ribosomes, the protein factories of living cells, translate genetic information carried by messenger RNAs into proteins, and are thus involved in virtually all aspects of cellular development and maintenance. The few available structures of the eukaryotic ribosome reveal that it is more complex than its prokaryotic counterpart, owing mainly to the presence of eukaryote-specific ribosomal proteins and additional ribosomal RNA insertions, called expansion segments. The structures also differ among species, partly in the size and arrangement of these expansion segments. Such differences are extreme in kinetoplastids, unicellular eukaryotic parasites often infectious to humans. Here we present a high-resolution cryo-electron microscopy structure of the ribosome of Trypanosoma brucei, the parasite that is transmitted by the tsetse fly and that causes African sleeping sickness. The atomic model reveals the unique features of this ribosome, characterized mainly by the presence of unusually large expansion segments and ribosomal-protein extensions leading to the formation of four additional inter-subunit bridges. We also find additional rRNA insertions, including one large rRNA domain that is not found in other eukaryotes. Furthermore, the structure reveals the five cleavage sites of the kinetoplastid large ribosomal subunit (LSU) rRNA chain, which is known to be cleaved uniquely into six pieces, and suggests that the cleavage is important for the maintenance of the T. brucei ribosome in the observed structure. We discuss several possible implications of the large rRNA expansion segments for the translation-regulation process. The structure could serve as a basis for future experiments aimed at understanding the functional importance of these kinetoplastid-specific ribosomal features in protein-translation regulation, an essential step towards finding effective and safe kinetoplastid-specific drugs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659406/" 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/PMC3659406/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hashem, Yaser -- des Georges, Amedee -- Fu, Jie -- Buss, Sarah N -- Jossinet, Fabrice -- Jobe, Amy -- Zhang, Qin -- Liao, Hstau Y -- Grassucci, Robert A -- Bajaj, Chandrajit -- Westhof, Eric -- Madison-Antenucci, Susan -- Frank, Joachim -- R01 GM029169/GM/NIGMS NIH HHS/ -- R01 GM29169/GM/NIGMS NIH HHS/ -- R01-EB004873/EB/NIBIB NIH HHS/ -- R01-GM074258/GM/NIGMS NIH HHS/ -- T32 GM008798/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Feb 21;494(7437):385-9. doi: 10.1038/nature11872. Epub 2013 Feb 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, 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/23395961" target="_blank"〉PubMed〈/a〉
    Keywords: *Cryoelectron Microscopy ; Models, Biological ; Models, Molecular ; Molecular Conformation ; Protein Biosynthesis ; RNA, Protozoan/genetics/metabolism ; RNA, Ribosomal/genetics/metabolism ; Ribosomes/chemistry/genetics/*ultrastructure ; Trypanosoma brucei brucei/chemistry/*cytology/genetics/*ultrastructure ; Yeasts/chemistry
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  • 67
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    Nature Publishing Group (NPG)
    Publication Date: 2013-06-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Willyard, Cassandra -- England -- Nature. 2013 Jun 27;498(7455):S12-3. doi: 10.1038/498S12a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23803943" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomarkers, Tumor/metabolism ; Cell Division/drug effects ; Chemokine CXCL12/biosynthesis/metabolism ; Granulocyte Colony-Stimulating Factor/pharmacology/therapeutic use ; Heterocyclic Compounds/therapeutic use ; Humans ; Leukemia/*drug therapy/genetics/metabolism/*pathology ; Leukemia, Myeloid, Acute/drug therapy/genetics/metabolism/pathology ; Mice ; Models, Biological ; Neoplastic Stem Cells/*drug effects/metabolism/*pathology ; Proto-Oncogene Proteins c-hck/antagonists & inhibitors/metabolism
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  • 68
    Publication Date: 2013-04-26
    Description: Locomotion in living birds (Neornithes) has two remarkable features: feather-assisted flight, and the use of unusually crouched hindlimbs for bipedal support and movement. When and how these defining functional traits evolved remains controversial. However, the advent of computer modelling approaches and the discoveries of exceptionally preserved key specimens now make it possible to use quantitative data on whole-body morphology to address the biomechanics underlying this issue. Here we use digital body reconstructions to quantify evolutionary trends in locomotor biomechanics (whole-body proportions and centre-of-mass position) across the clade Archosauria. We use three-dimensional digital reconstruction to estimate body shape from skeletal dimensions for 17 archosaurs along the ancestral bird line, including the exceptionally preserved, feathered taxa Microraptor, Archaeopteryx, Pengornis and Yixianornis, which represent key stages in the evolution of the avian body plan. Rather than a discrete transition from more-upright postures in the basal-most birds (Avialae) and their immediate outgroup deinonychosauria, our results support hypotheses of a gradual, stepwise acquisition of more-crouched limb postures across much of theropod evolution, although we find evidence of an accelerated change within the clade Maniraptora (birds and their closest relatives, such as deinonychosaurs). In addition, whereas reduction of the tail is widely accepted to be the primary morphological factor correlated with centre-of-mass position and, hence, evolution of hindlimb posture, we instead find that enlargement of the pectoral limb and several associated trends have a much stronger influence. Intriguingly, our support for the onset of accelerated morpho-functional trends within Maniraptora is closely correlated with the evolution of flight. Because we find that the evolution of enlarged forelimbs is strongly linked, via whole-body centre of mass, to hindlimb function during terrestrial locomotion, we suggest that the evolution of avian flight is linked to anatomical novelties in the pelvic limb as well as the pectoral.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Allen, Vivian -- Bates, Karl T -- Li, Zhiheng -- Hutchinson, John R -- England -- Nature. 2013 May 2;497(7447):104-7. doi: 10.1038/nature12059. Epub 2013 Apr 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut fur Spezielle Zoologie und Evolutionsbiologie, Friedrich-Schiller-University Jena, 07743 Jena, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23615616" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Biomechanical Phenomena ; Birds/*anatomy & histology/*physiology ; Dinosaurs/*anatomy & histology/*physiology ; Feathers ; Flight, Animal ; Hindlimb/anatomy & histology/physiology ; Locomotion/*physiology ; Models, Anatomic ; Models, Biological ; Phylogeny
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  • 69
    Publication Date: 2013-05-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Fusuo -- Chen, Xinping -- Vitousek, Peter -- England -- Nature. 2013 May 2;497(7447):33-5. doi: 10.1038/497033a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Resources, Environment and Food Security, China Agricultural University, Beijing, China. zhangfs@cau.edu.cn〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23636381" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/economics/methods/*statistics & numerical data/*trends ; Biomass ; China ; Crops, Agricultural/metabolism/radiation effects ; Ecosystem ; Fertilizers/adverse effects/utilization ; Food Supply/economics/*methods/*statistics & numerical data ; Food, Genetically Modified ; Models, Biological ; Plants, Genetically Modified ; Research/economics ; Soil/analysis/chemistry ; Sunlight ; Water Supply/statistics & numerical data
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  • 70
    Publication Date: 2013-03-22
    Description: A long-held tenet of molecular pharmacology is that canonical signal transduction mediated by G-protein-coupled receptor (GPCR) coupling to heterotrimeric G proteins is confined to the plasma membrane. Evidence supporting this traditional view is based on analytical methods that provide limited or no subcellular resolution. It has been subsequently proposed that signalling by internalized GPCRs is restricted to G-protein-independent mechanisms such as scaffolding by arrestins, or GPCR activation elicits a discrete form of persistent G protein signalling, or that internalized GPCRs can indeed contribute to the acute G-protein-mediated response. Evidence supporting these various latter hypotheses is indirect or subject to alternative interpretation, and it remains unknown if endosome-localized GPCRs are even present in an active form. Here we describe the application of conformation-specific single-domain antibodies (nanobodies) to directly probe activation of the beta2-adrenoceptor, a prototypical GPCR, and its cognate G protein, Gs (ref. 12), in living mammalian cells. We show that the adrenergic agonist isoprenaline promotes receptor and G protein activation in the plasma membrane as expected, but also in the early endosome membrane, and that internalized receptors contribute to the overall cellular cyclic AMP response within several minutes after agonist application. These findings provide direct support for the hypothesis that canonical GPCR signalling occurs from endosomes as well as the plasma membrane, and suggest a versatile strategy for probing dynamic conformational change in vivo.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3835555/" 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/PMC3835555/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Irannejad, Roshanak -- Tomshine, Jin C -- Tomshine, Jon R -- Chevalier, Michael -- Mahoney, Jacob P -- Steyaert, Jan -- Rasmussen, Soren G F -- Sunahara, Roger K -- El-Samad, Hana -- Huang, Bo -- von Zastrow, Mark -- DA010711/DA/NIDA NIH HHS/ -- DA012864/DA/NIDA NIH HHS/ -- F32 DA029993/DA/NIDA NIH HHS/ -- GM083118/GM/NIGMS NIH HHS/ -- P01 DA010154/DA/NIDA NIH HHS/ -- P01 NS053709/NS/NINDS NIH HHS/ -- R01 DA012864/DA/NIDA NIH HHS/ -- R01 GM068603/GM/NIGMS NIH HHS/ -- R01 GM083118/GM/NIGMS NIH HHS/ -- R29 DA010711/DA/NIDA NIH HHS/ -- R37 DA010711/DA/NIDA NIH HHS/ -- T32 GM007767/GM/NIGMS NIH HHS/ -- England -- Nature. 2013 Mar 28;495(7442):534-8. doi: 10.1038/nature12000. Epub 2013 Mar 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychiatry, University of California, San Francisco, California 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23515162" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenergic beta-2 Receptor Agonists/pharmacology ; Biosensing Techniques/*methods ; Cell Membrane/chemistry/metabolism ; Clathrin-Coated Vesicles ; Cyclic AMP/metabolism ; Endocytosis ; Endosomes/chemistry/*metabolism ; GTP-Binding Protein alpha Subunits, Gs/metabolism ; Green Fluorescent Proteins/analysis/genetics/metabolism ; HEK293 Cells ; Humans ; Isoproterenol/pharmacology ; Models, Biological ; Protein Conformation ; Receptors, Adrenergic, beta-2/*chemistry/immunology/*metabolism ; *Signal Transduction ; Single-Domain Antibodies/genetics/immunology
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  • 71
    Publication Date: 2013-02-15
    Description: Accelerating rates of species extinctions and disease emergence underscore the importance of understanding how changes in biodiversity affect disease outcomes. Over the past decade, a growing number of studies have reported negative correlations between host biodiversity and disease risk, prompting suggestions that biodiversity conservation could promote human and wildlife health. Yet the generality of the diversity-disease linkage remains conjectural, in part because empirical evidence of a relationship between host competence (the ability to maintain and transmit infections) and the order in which communities assemble has proven elusive. Here we integrate high-resolution field data with multi-scale experiments to show that host diversity inhibits transmission of the virulent pathogen Ribeiroia ondatrae and reduces amphibian disease as a result of consistent linkages among species richness, host composition and community competence. Surveys of 345 wetlands indicated that community composition changed nonrandomly with species richness, such that highly competent hosts dominated in species-poor assemblages whereas more resistant species became progressively more common in diverse assemblages. As a result, amphibian species richness strongly moderated pathogen transmission and disease pathology among 24,215 examined hosts, with a 78.4% decline in realized transmission in richer assemblages. Laboratory and mesocosm manipulations revealed an approximately 50% decrease in pathogen transmission and host pathology across a realistic diversity gradient while controlling for host density, helping to establish mechanisms underlying the diversity-disease relationship and their consequences for host fitness. By revealing a consistent link between species richness and community competence, these findings highlight the influence of biodiversity on infection risk and emphasize the benefit of a community-based approach to understanding infectious diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johnson, Pieter T J -- Preston, Daniel L -- Hoverman, Jason T -- Richgels, Katherine L D -- England -- Nature. 2013 Feb 14;494(7436):230-3. doi: 10.1038/nature11883.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ecology and Evolutionary Biology, University of Colorado, Boulder, Colorado 80309, USA. pieter.johnson@colorado.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23407539" target="_blank"〉PubMed〈/a〉
    Keywords: Amphibians/*parasitology ; Animals ; *Biodiversity ; California ; *Host-Parasite Interactions ; Models, Biological ; Trematoda/*pathogenicity ; Trematode Infections/prevention & control/transmission/veterinary ; *Wetlands
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  • 72
    Publication Date: 2013-02-15
    Description: Several reports proposed that the extraordinary dominance of the SAR11 bacterial clade in ocean ecosystems could be a consequence of unusual mechanisms of resistance to bacteriophage infection, including 'cryptic escape' through reduced cell size and/or K-strategist defence specialism. Alternatively, the evolution of high surface-to-volume ratios coupled with minimal genomes containing high-affinity transporters enables unusually efficient metabolism for oxidizing dissolved organic matter in the world's oceans that could support vast population sizes despite phage susceptibility. These ideas are important for understanding plankton ecology because they emphasize the potentially important role of top-down mechanisms in predation, thus determining the size of SAR11 populations and their concomitant role in biogeochemical cycling. Here we report the isolation of diverse SAR11 viruses belonging to two virus families in culture, for which we propose the name 'pelagiphage', after their host. Notably, the pelagiphage genomes were highly represented in marine viral metagenomes, demonstrating their importance in nature. One of the new phages, HTVC010P, represents a new podovirus subfamily more abundant than any seen previously, in all data sets tested, and may represent one of the most abundant virus subfamilies in the biosphere. This discovery disproves the theory that SAR11 cells are immune to viral predation and is consistent with the interpretation that the success of this highly abundant microbial clade is the result of successfully evolved adaptation to resource competition.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhao, Yanlin -- Temperton, Ben -- Thrash, J Cameron -- Schwalbach, Michael S -- Vergin, Kevin L -- Landry, Zachary C -- Ellisman, Mark -- Deerinck, Tom -- Sullivan, Matthew B -- Giovannoni, Stephen J -- P41 RR004050/RR/NCRR NIH HHS/ -- England -- Nature. 2013 Feb 21;494(7437):357-60. doi: 10.1038/nature11921. Epub 2013 Feb 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, Oregon State University, Corvallis, Oregon 97331, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23407494" target="_blank"〉PubMed〈/a〉
    Keywords: Aquatic Organisms/genetics/*isolation & purification ; Bacteria/classification/isolation & purification/virology ; Bacteriophages/*classification/genetics/*isolation & purification/physiology ; Bermuda ; Biota ; Competitive Behavior ; Food Chain ; Genome, Viral/genetics ; Metagenome/genetics ; Models, Biological ; Molecular Sequence Data ; Oregon ; Pacific Ocean ; Plankton/physiology ; Seawater/microbiology/*virology
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  • 73
    Publication Date: 2013-08-09
    Description: The cyclic AMP (cAMP)-dependent catabolite repression effect in Escherichia coli is among the most intensely studied regulatory processes in biology. However, the physiological function(s) of cAMP signalling and its molecular triggers remain elusive. Here we use a quantitative physiological approach to show that cAMP signalling tightly coordinates the expression of catabolic proteins with biosynthetic and ribosomal proteins, in accordance with the cellular metabolic needs during exponential growth. The expression of carbon catabolic genes increased linearly with decreasing growth rates upon limitation of carbon influx, but decreased linearly with decreasing growth rate upon limitation of nitrogen or sulphur influx. In contrast, the expression of biosynthetic genes showed the opposite linear growth-rate dependence as the catabolic genes. A coarse-grained mathematical model provides a quantitative framework for understanding and predicting gene expression responses to catabolic and anabolic limitations. A scheme of integral feedback control featuring the inhibition of cAMP signalling by metabolic precursors is proposed and validated. These results reveal a key physiological role of cAMP-dependent catabolite repression: to ensure that proteomic resources are spent on distinct metabolic sectors as needed in different nutrient environments. Our findings underscore the power of quantitative physiology in unravelling the underlying functions of complex molecular signalling networks.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038431/" 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/PMC4038431/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉You, Conghui -- Okano, Hiroyuki -- Hui, Sheng -- Zhang, Zhongge -- Kim, Minsu -- Gunderson, Carl W -- Wang, Yi-Ping -- Lenz, Peter -- Yan, Dalai -- Hwa, Terence -- R01 GM095903/GM/NIGMS NIH HHS/ -- England -- Nature. 2013 Aug 15;500(7462):301-6. doi: 10.1038/nature12446. Epub 2013 Aug 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, University of California at San Diego, La Jolla, California 92093-0374, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23925119" target="_blank"〉PubMed〈/a〉
    Keywords: Cyclic AMP/*metabolism ; Escherichia coli/*genetics/*metabolism ; Escherichia coli Proteins/*genetics/*metabolism ; *Gene Expression Regulation, Bacterial ; Models, Biological ; *Proteome ; *Signal Transduction
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  • 74
    Publication Date: 2013-11-10
    Description: From the formation of animal flocks to the emergence of coordinated motion in bacterial swarms, populations of motile organisms at all scales display coherent collective motion. This consistent behaviour strongly contrasts with the difference in communication abilities between the individuals. On the basis of this universal feature, it has been proposed that alignment rules at the individual level could solely account for the emergence of unidirectional motion at the group level. This hypothesis has been supported by agent-based simulations. However, more complex collective behaviours have been systematically found in experiments, including the formation of vortices, fluctuating swarms, clustering and swirling. All these (living and man-made) model systems (bacteria, biofilaments and molecular motors, shaken grains and reactive colloids) predominantly rely on actual collisions to generate collective motion. As a result, the potential local alignment rules are entangled with more complex, and often unknown, interactions. The large-scale behaviour of the populations therefore strongly depends on these uncontrolled microscopic couplings, which are extremely challenging to measure and describe theoretically. Here we report that dilute populations of millions of colloidal rolling particles self-organize to achieve coherent motion in a unique direction, with very few density and velocity fluctuations. Quantitatively identifying the microscopic interactions between the rollers allows a theoretical description of this polar-liquid state. Comparison of the theory with experiment suggests that hydrodynamic interactions promote the emergence of collective motion either in the form of a single macroscopic 'flock', at low densities, or in that of a homogenous polar phase, at higher densities. Furthermore, hydrodynamics protects the polar-liquid state from the giant density fluctuations that were hitherto considered the hallmark of populations of self-propelled particles. Our experiments demonstrate that genuine physical interactions at the individual level are sufficient to set homogeneous active populations into stable directed motion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bricard, Antoine -- Caussin, Jean-Baptiste -- Desreumaux, Nicolas -- Dauchot, Olivier -- Bartolo, Denis -- England -- Nature. 2013 Nov 7;503(7474):95-8. doi: 10.1038/nature12673.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] PMMH, CNRS UMR7636, ESPCI-ParisTech, Universite Paris Diderot and Universite Pierre et Marie Curie, 10 rue Vauquelin, 75005 Paris, France [2].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24201282" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Colloids ; Hydrodynamics ; Mass Behavior ; Microspheres ; Models, Biological ; *Models, Theoretical ; *Motion
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  • 75
    Publication Date: 2013-05-31
    Description: Type 2 diabetes (T2D) is a result of complex gene-environment interactions, and several risk factors have been identified, including age, family history, diet, sedentary lifestyle and obesity. Statistical models that combine known risk factors for T2D can partly identify individuals at high risk of developing the disease. However, these studies have so far indicated that human genetics contributes little to the models, whereas socio-demographic and environmental factors have greater influence. Recent evidence suggests the importance of the gut microbiota as an environmental factor, and an altered gut microbiota has been linked to metabolic diseases including obesity, diabetes and cardiovascular disease. Here we use shotgun sequencing to characterize the faecal metagenome of 145 European women with normal, impaired or diabetic glucose control. We observe compositional and functional alterations in the metagenomes of women with T2D, and develop a mathematical model based on metagenomic profiles that identified T2D with high accuracy. We applied this model to women with impaired glucose tolerance, and show that it can identify women who have a diabetes-like metabolism. Furthermore, glucose control and medication were unlikely to have major confounding effects. We also applied our model to a recently described Chinese cohort and show that the discriminant metagenomic markers for T2D differ between the European and Chinese cohorts. Therefore, metagenomic predictive tools for T2D should be specific for the age and geographical location of the populations studied.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Karlsson, Fredrik H -- Tremaroli, Valentina -- Nookaew, Intawat -- Bergstrom, Goran -- Behre, Carl Johan -- Fagerberg, Bjorn -- Nielsen, Jens -- Backhed, Fredrik -- England -- Nature. 2013 Jun 6;498(7452):99-103. doi: 10.1038/nature12198. Epub 2013 May 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemical and Biological Engineering, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23719380" target="_blank"〉PubMed〈/a〉
    Keywords: Age Factors ; Aged ; Asian Continental Ancestry Group ; Bacteria/genetics/isolation & purification ; Biomarkers ; Blood Glucose/*metabolism ; Cluster Analysis ; Cohort Studies ; Confounding Factors (Epidemiology) ; Demography ; Diabetes Mellitus, Type 2/blood/drug therapy/genetics/*microbiology ; Environment ; European Continental Ancestry Group ; Feces/microbiology ; Female ; Gastrointestinal Tract/*microbiology ; Glucose Intolerance/blood/metabolism/*microbiology ; *Health ; Humans ; *Metagenome/genetics ; Middle Aged ; Models, Biological ; Prognosis ; Species Specificity ; Sweden
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  • 76
    Publication Date: 2013-12-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Greenwald, Noah -- Ando, Amy W -- Butchart, Stuart H M -- Tschirhart, John -- England -- Nature. 2013 Dec 19;504(7480):369-70.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24358508" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Conservation of Natural Resources/economics/*legislation & ; jurisprudence/*statistics & numerical data/trends ; Ecosystem ; Endangered Species/economics/legislation & jurisprudence/*statistics & numerical ; data ; Extinction, Biological ; Models, Biological ; Models, Economic ; United States
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  • 77
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2012-02-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2012 Feb 13;482(7385):289. doi: 10.1038/482289a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22337028" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Viral/analysis/immunology ; Humans ; Influenza A Virus, H5N1 Subtype/*genetics/immunology/isolation & ; purification/*pathogenicity ; Influenza, Human/epidemiology/immunology/*mortality/virology ; Models, Biological ; Poultry/virology ; Seroepidemiologic Studies ; Zoonoses/epidemiology/transmission/virology
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  • 78
    Publication Date: 2012-09-07
    Description: Animal and plant development starts with a constituting phase called embryogenesis, which evolved independently in both lineages. Comparative anatomy of vertebrate development--based on the Meckel-Serres law and von Baer's laws of embryology from the early nineteenth century--shows that embryos from various taxa appear different in early stages, converge to a similar form during mid-embryogenesis, and again diverge in later stages. This morphogenetic series is known as the embryonic 'hourglass', and its bottleneck of high conservation in mid-embryogenesis is referred to as the phylotypic stage. Recent analyses in zebrafish and Drosophila embryos provided convincing molecular support for the hourglass model, because during the phylotypic stage the transcriptome was dominated by ancient genes and global gene expression profiles were reported to be most conserved. Although extensively explored in animals, an embryonic hourglass has not been reported in plants, which represent the second major kingdom in the tree of life that evolved embryogenesis. Here we provide phylotranscriptomic evidence for a molecular embryonic hourglass in Arabidopsis thaliana, using two complementary approaches. This is particularly significant because the possible absence of an hourglass based on morphological features in plants suggests that morphological and molecular patterns might be uncoupled. Together with the reported developmental hourglass patterns in animals, these findings indicate convergent evolution of the molecular hourglass and a conserved logic of embryogenesis across kingdoms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Quint, Marcel -- Drost, Hajk-Georg -- Gabel, Alexander -- Ullrich, Kristian Karsten -- Bonn, Markus -- Grosse, Ivo -- England -- Nature. 2012 Oct 4;490(7418):98-101. doi: 10.1038/nature11394. Epub 2012 Sep 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Leibniz Institute of Plant Biochemistry, Department of Molecular Signal Processing, Weinberg 3, 06120 Halle (Saale), Germany. mquint@ipb-halle.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22951968" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arabidopsis/classification/*embryology/*genetics ; Brassicaceae/genetics ; Conserved Sequence/genetics ; Developmental Biology ; Drosophila/embryology/genetics ; Embryonic Development/genetics ; Evolution, Molecular ; Gene Expression Profiling ; Gene Expression Regulation, Plant/*genetics ; Genes, Plant/genetics ; Models, Biological ; Plant Development/*genetics ; Transcriptome/*genetics ; Zebrafish/embryology
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  • 79
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2012-02-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reinitz, John -- England -- Nature. 2012 Feb 22;482(7386):464. doi: 10.1038/482464a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Statistics, University of Chicago, Chicago, Illinois 60637, USA. reinitz@galton.uchicago.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22358813" target="_blank"〉PubMed〈/a〉
    Keywords: Computer Simulation ; Developmental Biology/*history ; Diffusion ; History, 19th Century ; History, 20th Century ; Models, Biological ; Morphogenesis/*physiology
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  • 80
    Publication Date: 2012-03-16
    Description: Derivatives of vitamin B(12) are used in methyl group transfer in biological processes as diverse as methionine synthesis in humans and CO(2) fixation in acetogenic bacteria. This seemingly straightforward reaction requires large, multimodular enzyme complexes that adopt multiple conformations to alternately activate, protect and perform catalysis on the reactive B(12) cofactor. Crystal structures determined thus far have provided structural information for only fragments of these complexes, inspiring speculation about the overall protein assembly and conformational movements inherent to activity. Here we present X-ray crystal structures of a complete 220 kDa complex that contains all enzymes responsible for B(12)-dependent methyl transfer, namely the corrinoid iron-sulphur protein and its methyltransferase from the model acetogen Moorella thermoacetica. These structures provide the first three-dimensional depiction of all protein modules required for the activation, protection and catalytic steps of B(12)-dependent methyl transfer. In addition, the structures capture B(12) at multiple locations between its 'resting' and catalytic positions, allowing visualization of the dramatic protein rearrangements that enable methyl transfer and identification of the trajectory for B(12) movement within the large enzyme scaffold. The structures are also presented alongside in crystallo spectroscopic data, which confirm enzymatic activity within crystals and demonstrate the largest known conformational movements of proteins in a crystalline state. Taken together, this work provides a model for the molecular juggling that accompanies turnover and helps explain why such an elaborate protein framework is required for such a simple, yet biologically essential reaction.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3326194/" 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/PMC3326194/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kung, Yan -- Ando, Nozomi -- Doukov, Tzanko I -- Blasiak, Leah C -- Bender, Gunes -- Seravalli, Javier -- Ragsdale, Stephen W -- Drennan, Catherine L -- GM39451/GM/NIGMS NIH HHS/ -- GM69857/GM/NIGMS NIH HHS/ -- R01 GM039451/GM/NIGMS NIH HHS/ -- R01 GM039451-25/GM/NIGMS NIH HHS/ -- R01 GM069857/GM/NIGMS NIH HHS/ -- R37 GM039451/GM/NIGMS NIH HHS/ -- RR-15301/RR/NCRR NIH HHS/ -- T32 GM008334/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Mar 14;484(7393):265-9. doi: 10.1038/nature10916.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22419154" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Biocatalysis ; Corrinoids/metabolism ; Crystallography, X-Ray ; Folic Acid/metabolism ; Iron-Sulfur Proteins/*chemistry/*metabolism ; Methylation ; Methyltransferases/*chemistry/*metabolism ; Models, Biological ; Models, Molecular ; Moorella/chemistry/*enzymology ; Protein Multimerization ; Protein Structure, Tertiary ; Vitamin B 12/*metabolism
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  • 81
    Publication Date: 2012-03-23
    Description: Spontaneous collective motion, as in some flocks of bird and schools of fish, is an example of an emergent phenomenon. Such phenomena are at present of great interest and physicists have put forward a number of theoretical results that so far lack experimental verification. In animal behaviour studies, large-scale data collection is now technologically possible, but data are still scarce and arise from observations rather than controlled experiments. Multicellular biological systems, such as bacterial colonies or tissues, allow more control, but may have many hidden variables and interactions, hindering proper tests of theoretical ideas. However, in systems on the subcellular scale such tests may be possible, particularly in in vitro experiments with only few purified components. Motility assays, in which protein filaments are driven by molecular motors grafted to a substrate in the presence of ATP, can show collective motion for high densities of motors and attached filaments. This was demonstrated recently for the actomyosin system, but a complete understanding of the mechanisms at work is still lacking. Here we report experiments in which microtubules are propelled by surface-bound dyneins. In this system it is possible to study the local interaction: we find that colliding microtubules align with each other with high probability. At high densities, this alignment results in self-organization of the microtubules, which are on average 15 microm long, into vortices with diameters of around 400 microm. Inside the vortices, the microtubules circulate both clockwise and anticlockwise. On longer timescales, the vortices form a lattice structure. The emergence of these structures, as verified by a mathematical model, is the result of the smooth, reptation-like motion of single microtubules in combination with local interactions (the nematic alignment due to collisions)--there is no need for long-range interactions. Apart from its potential relevance to cortical arrays in plant cells and other biological situations, our study provides evidence for the existence of previously unsuspected universality classes of collective motion phenomena.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sumino, Yutaka -- Nagai, Ken H -- Shitaka, Yuji -- Tanaka, Dan -- Yoshikawa, Kenichi -- Chate, Hugues -- Oiwa, Kazuhiro -- England -- Nature. 2012 Mar 21;483(7390):448-52. doi: 10.1038/nature10874.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Aichi University of Education, Aichi 448-8542, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22437613" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chlamydomonas ; Dyneins/metabolism ; Flagella ; Microtubules/*metabolism ; Models, Biological ; *Movement
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  • 82
    Publication Date: 2012-07-06
    Description: It is possible that anthropogenic climate change will drive the Earth system into a qualitatively different state. Although different types of uncertainty limit our capacity to assess this risk, Earth system scientists are particularly concerned about tipping elements, large-scale components of the Earth system that can be switched into qualitatively different states by small perturbations. Despite growing evidence that tipping elements exist in the climate system, whether large-scale vegetation systems can tip into alternative states is poorly understood. Here we show that tropical grassland, savanna and forest ecosystems, areas large enough to have powerful impacts on the Earth system, are likely to shift to alternative states. Specifically, we show that increasing atmospheric CO2 concentration will force transitions to vegetation states characterized by higher biomass and/or woody-plant dominance. The timing of these critical transitions varies as a result of between-site variance in the rate of temperature increase, as well as a dependence on stochastic variation in fire severity and rainfall. We further show that the locations of bistable vegetation zones (zones where alternative vegetation states can exist) will shift as climate changes. We conclude that even though large-scale directional regime shifts in terrestrial ecosystems are likely, asynchrony in the timing of these shifts may serve to dampen, but not nullify, the shock that these changes may represent to the Earth system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Higgins, Steven I -- Scheiter, Simon -- England -- Nature. 2012 Aug 9;488(7410):209-12. doi: 10.1038/nature11238.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut fur Physische Geographie, Goethe Universitat Frankfurt am Main, 60438 Frankfurt am Main, Germany. higgins@em.uni-frankfurt.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22763447" target="_blank"〉PubMed〈/a〉
    Keywords: Africa ; Atmosphere/*chemistry ; Biomass ; Carbon/metabolism ; Carbon Dioxide/analysis/*metabolism ; Climate Change/*statistics & numerical data ; *Ecosystem ; Fires ; Geography ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Hot Temperature ; Models, Biological ; Photosynthesis/physiology ; Poaceae/growth & development/metabolism ; Probability ; Rain ; Stochastic Processes ; Time Factors ; Trees/*growth & development/metabolism ; Wood
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  • 83
    Publication Date: 2012-01-06
    Description: In 1969, a palaeontologist proposed that theropod dinosaurs used their tails as dynamic stabilizers during rapid or irregular movements, contributing to their depiction as active and agile predators. Since then the inertia of swinging appendages has been implicated in stabilizing human walking, aiding acrobatic manoeuvres by primates and rodents, and enabling cats to balance on branches. Recent studies on geckos suggest that active tail stabilization occurs during climbing, righting and gliding. By contrast, studies on the effect of lizard tail loss show evidence of a decrease, an increase or no change in performance. Application of a control-theoretic framework could advance our general understanding of inertial appendage use in locomotion. Here we report that lizards control the swing of their tails in a measured manner to redirect angular momentum from their bodies to their tails, stabilizing body attitude in the sagittal plane. We video-recorded Red-Headed Agama lizards (Agama agama) leaping towards a vertical surface by first vaulting onto an obstacle with variable traction to induce a range of perturbations in body angular momentum. To examine a known controlled tail response, we built a lizard-sized robot with an active tail that used sensory feedback to stabilize pitch as it drove off a ramp. Our dynamics model revealed that a body swinging its tail experienced less rotation than a body with a rigid tail, a passively compliant tail or no tail. To compare a range of tails, we calculated tail effectiveness as the amount of tailless body rotation a tail could stabilize. A model Velociraptor mongoliensis supported the initial tail stabilization hypothesis, showing as it did a greater tail effectiveness than the Agama lizards. Leaping lizards show that inertial control of body attitude can advance our understanding of appendage evolution and provide biological inspiration for the next generation of manoeuvrable search-and-rescue robots.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Libby, Thomas -- Moore, Talia Y -- Chang-Siu, Evan -- Li, Deborah -- Cohen, Daniel J -- Jusufi, Ardian -- Full, Robert J -- England -- Nature. 2012 Jan 4;481(7380):181-4. doi: 10.1038/nature10710.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Interdisciplinary Bio-Inspiration in Education and Research, University of California, Berkeley, California 94720-3140, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22217942" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Evolution ; Biomechanical Phenomena ; Computer Simulation ; Dinosaurs/*anatomy & histology/*physiology ; Feedback, Sensory/physiology ; Lizards/*anatomy & histology/*physiology ; Models, Biological ; Posture/physiology ; *Robotics/instrumentation ; Rotation ; Tail/*physiology
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  • 84
    Publication Date: 2012-06-09
    Description: Evidence is mounting that extinctions are altering key processes important to the productivity and sustainability of Earth's ecosystems. Further species loss will accelerate change in ecosystem processes, but it is unclear how these effects compare to the direct effects of other forms of environmental change that are both driving diversity loss and altering ecosystem function. Here we use a suite of meta-analyses of published data to show that the effects of species loss on productivity and decomposition--two processes important in all ecosystems--are of comparable magnitude to the effects of many other global environmental changes. In experiments, intermediate levels of species loss (21-40%) reduced plant production by 5-10%, comparable to previously documented effects of ultraviolet radiation and climate warming. Higher levels of extinction (41-60%) had effects rivalling those of ozone, acidification, elevated CO(2) and nutrient pollution. At intermediate levels, species loss generally had equal or greater effects on decomposition than did elevated CO(2) and nitrogen addition. The identity of species lost also had a large effect on changes in productivity and decomposition, generating a wide range of plausible outcomes for extinction. Despite the need for more studies on interactive effects of diversity loss and environmental changes, our analyses clearly show that the ecosystem consequences of local species loss are as quantitatively significant as the direct effects of several global change stressors that have mobilized major international concern and remediation efforts.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hooper, David U -- Adair, E Carol -- Cardinale, Bradley J -- Byrnes, Jarrett E K -- Hungate, Bruce A -- Matulich, Kristin L -- Gonzalez, Andrew -- Duffy, J Emmett -- Gamfeldt, Lars -- O'Connor, Mary I -- England -- Nature. 2012 May 2;486(7401):105-8. doi: 10.1038/nature11118.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Western Washington University, Bellingham, Washington 98225-9160, USA. hooper@biol.wwu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22678289" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biodiversity ; Ecology ; *Ecosystem ; *Extinction, Biological ; Models, Biological
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  • 85
    Publication Date: 2012-02-03
    Description: Natural materials are renowned for exquisite designs that optimize function, as illustrated by the elasticity of blood vessels, the toughness of bone and the protection offered by nacre. Particularly intriguing are spider silks, with studies having explored properties ranging from their protein sequence to the geometry of a web. This material system, highly adapted to meet a spider's many needs, has superior mechanical properties. In spite of much research into the molecular design underpinning the outstanding performance of silk fibres, and into the mechanical characteristics of web-like structures, it remains unknown how the mechanical characteristics of spider silk contribute to the integrity and performance of a spider web. Here we report web deformation experiments and simulations that identify the nonlinear response of silk threads to stress--involving softening at a yield point and substantial stiffening at large strain until failure--as being crucial to localize load-induced deformation and resulting in mechanically robust spider webs. Control simulations confirmed that a nonlinear stress response results in superior resistance to structural defects in the web compared to linear elastic or elastic-plastic (softening) material behaviour. We also show that under distributed loads, such as those exerted by wind, the stiff behaviour of silk under small deformation, before the yield point, is essential in maintaining the web's structural integrity. The superior performance of silk in webs is therefore not due merely to its exceptional ultimate strength and strain, but arises from the nonlinear response of silk threads to strain and their geometrical arrangement in a web.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cranford, Steven W -- Tarakanova, Anna -- Pugno, Nicola M -- Buehler, Markus J -- England -- Nature. 2012 Feb 1;482(7383):72-6. doi: 10.1038/nature10739.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Atomistic and Molecular Mechanics, Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22297972" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomechanical Phenomena ; Elasticity ; Hardness ; Models, Biological ; Silk/*chemistry ; *Spiders/physiology ; *Tensile Strength ; Wind
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  • 86
    Publication Date: 2012-10-30
    Description: Escherichia coli RecA is the defining member of a ubiquitous class of DNA strand-exchange proteins that are essential for homologous recombination, a pathway that maintains genomic integrity by repairing broken DNA. To function, filaments of RecA must nucleate and grow on single-stranded DNA (ssDNA) in direct competition with ssDNA-binding protein (SSB), which rapidly binds and continuously sequesters ssDNA, kinetically blocking RecA assembly. This dynamic self-assembly on a DNA lattice, in competition with another protein, is unique for the RecA family compared to other filament-forming proteins such as actin and tubulin. The complexity of this process has hindered our understanding of RecA filament assembly because ensemble measurements cannot reliably distinguish between the nucleation and growth phases, despite extensive and diverse attempts. Previous single-molecule assays have measured the nucleation and growth of RecA--and its eukaryotic homologue RAD51--on naked double-stranded DNA and ssDNA; however, the template for RecA self-assembly in vivo is SSB-coated ssDNA. Using single-molecule microscopy, here we directly visualize RecA filament assembly on single molecules of SSB-coated ssDNA, simultaneously measuring nucleation and growth. We establish that a dimer of RecA is required for nucleation, followed by growth of the filament through monomer addition, consistent with the finding that nucleation, but not growth, is modulated by nucleotide and magnesium ion cofactors. Filament growth is bidirectional, albeit faster in the 5'--〉3' direction. Both nucleation and growth are repressed at physiological conditions, highlighting the essential role of recombination mediators in potentiating assembly in vivo. We define a two-step kinetic mechanism in which RecA nucleates on transiently exposed ssDNA during SSB sliding and/or partial dissociation (DNA unwrapping) and then the RecA filament grows. We further demonstrate that the recombination mediator protein pair, RecOR (RecO and RecR), accelerates both RecA nucleation and filament growth, and that the introduction of RecF further stimulates RecA nucleation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4112059/" 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/PMC4112059/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bell, Jason C -- Plank, Jody L -- Dombrowski, Christopher C -- Kowalczykowski, Stephen C -- CA136103/CA/NCI NIH HHS/ -- F32 CA136103/CA/NCI NIH HHS/ -- GM62653/GM/NIGMS NIH HHS/ -- GM64745/GM/NIGMS NIH HHS/ -- R01 GM062653/GM/NIGMS NIH HHS/ -- R01 GM064745/GM/NIGMS NIH HHS/ -- T32 CA10052159/CA/NCI NIH HHS/ -- T32 CA108459/CA/NCI NIH HHS/ -- T32 GM007377/GM/NIGMS NIH HHS/ -- England -- Nature. 2012 Nov 8;491(7423):274-8. doi: 10.1038/nature11598. Epub 2012 Oct 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, University of California, Davis, California 95616, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23103864" target="_blank"〉PubMed〈/a〉
    Keywords: DNA, Single-Stranded/chemistry/*metabolism ; DNA-Binding Proteins/*metabolism ; Escherichia coli/*chemistry/enzymology ; Escherichia coli Proteins/*metabolism ; Hydrogen-Ion Concentration ; Ligands ; Microscopy, Fluorescence/*methods ; Models, Biological ; Models, Molecular ; Molecular Conformation ; Protein Multimerization ; Rec A Recombinases/*chemistry/*metabolism
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  • 87
    Publication Date: 2012-10-13
    Description: Calcium-dependent exocytosis of synaptic vesicles mediates the release of neurotransmitters. Important proteins in this process have been identified such as the SNAREs, synaptotagmins, complexins, Munc18 and Munc13. Structural and functional studies have yielded a wealth of information about the physiological role of these proteins. However, it has been surprisingly difficult to arrive at a unified picture of the molecular sequence of events from vesicle docking to calcium-triggered membrane fusion. Using mainly a biochemical and biophysical perspective, we briefly survey the molecular mechanisms in an attempt to functionally integrate the key proteins into the emerging picture of the neuronal fusion machine.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4461657/" 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/PMC4461657/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jahn, Reinhard -- Fasshauer, Dirk -- 3P01GM072694-05S1/GM/NIGMS NIH HHS/ -- P01 GM072694/GM/NIGMS NIH HHS/ -- England -- Nature. 2012 Oct 11;490(7419):201-7. doi: 10.1038/nature11320.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Max-Planck-Institute for Biophysical Chemistry, 37077 Gottingen, Germany. rjahn@gwdg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23060190" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/metabolism ; Exocytosis/*physiology ; Humans ; Lipid Metabolism ; Models, Biological ; SNARE Proteins/chemistry/metabolism ; Synaptic Vesicles/*physiology
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  • 88
    Publication Date: 2012-03-13
    Description: The hydrosulphide ion (HS(-)) and its undissociated form, hydrogen sulphide (H(2)S), which are believed to have been critical to the origin of life on Earth, remain important in physiology and cellular signalling. As a major metabolite in anaerobic bacterial growth, hydrogen sulphide is a product of both assimilatory and dissimilatory sulphate reduction. These pathways can reduce various oxidized sulphur compounds including sulphate, sulphite and thiosulphate. The dissimilatory sulphate reduction pathway uses this molecule as the terminal electron acceptor for anaerobic respiration, in which process it produces excess amounts of H(2)S (ref. 4). The reduction of sulphite is a key intermediate step in all sulphate reduction pathways. In Clostridium and Salmonella, an inducible sulphite reductase is directly linked to the regeneration of NAD(+), which has been suggested to have a role in energy production and growth, as well as in the detoxification of sulphite. Above a certain concentration threshold, both H(2)S and HS(-) inhibit cell growth by binding the metal centres of enzymes and cytochrome oxidase, necessitating a release mechanism for the export of this toxic metabolite from the cell. Here we report the identification of a hydrosulphide ion channel in the pathogen Clostridium difficile through a combination of genetic, biochemical and functional approaches. The HS(-) channel is a member of the formate/nitrite transport family, in which about 50 hydrosulphide ion channels form a third subfamily alongside those for formate (FocA) and for nitrite (NirC). The hydrosulphide ion channel is permeable to formate and nitrite as well as to HS(-) ions. Such polyspecificity can be explained by the conserved ion selectivity filter observed in the channel's crystal structure. The channel has a low open probability and is tightly regulated, to avoid decoupling of the membrane proton gradient.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711795/" 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/PMC3711795/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Czyzewski, Bryan K -- Wang, Da-Neng -- F31 AI086072/AI/NIAID NIH HHS/ -- F31-AI086072/AI/NIAID NIH HHS/ -- R01 DK053973/DK/NIDDK NIH HHS/ -- R01 GM093825/GM/NIGMS NIH HHS/ -- R01 MH083840/MH/NIMH NIH HHS/ -- R01-DK053973-08A1S1/DK/NIDDK NIH HHS/ -- R01-DK073973/DK/NIDDK NIH HHS/ -- R01-GM093825/GM/NIGMS NIH HHS/ -- R01-MH083840/MH/NIMH NIH HHS/ -- U54 GM075026/GM/NIGMS NIH HHS/ -- U54-GM075026/GM/NIGMS NIH HHS/ -- England -- Nature. 2012 Mar 11;483(7390):494-7. doi: 10.1038/nature10881.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Helen L. and Martin S. Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22407320" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/chemistry/genetics/isolation & purification/metabolism ; *Clostridium difficile/chemistry/drug effects/genetics ; Crystallography, X-Ray ; Formates/metabolism ; Ion Channel Gating ; Ion Channels/chemistry/genetics/*isolation & purification/*metabolism ; Ion Transport ; Models, Biological ; Models, Molecular ; Nitrites/metabolism ; Operon/genetics ; Proteolipids/metabolism ; Proton-Motive Force ; Structure-Activity Relationship ; Substrate Specificity ; Sulfides/*metabolism/toxicity
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  • 89
    Publication Date: 2012-02-18
    Description: Species diversity can be lost through two different but potentially interacting extinction processes: demographic decline and speciation reversal through introgressive hybridization. To investigate the relative contribution of these processes, we analysed historical and contemporary data of replicate whitefish radiations from 17 pre-alpine European lakes and reconstructed changes in genetic species differentiation through time using historical samples. Here we provide evidence that species diversity evolved in response to ecological opportunity, and that eutrophication, by diminishing this opportunity, has driven extinctions through speciation reversal and demographic decline. Across the radiations, the magnitude of eutrophication explains the pattern of species loss and levels of genetic and functional distinctiveness among remaining species. We argue that extinction by speciation reversal may be more widespread than currently appreciated. Preventing such extinctions will require that conservation efforts not only target existing species but identify and protect the ecological and evolutionary processes that generate and maintain species.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vonlanthen, P -- Bittner, D -- Hudson, A G -- Young, K A -- Muller, R -- Lundsgaard-Hansen, B -- Roy, D -- Di Piazza, S -- Largiader, C R -- Seehausen, O -- England -- Nature. 2012 Feb 15;482(7385):357-62. doi: 10.1038/nature10824.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Aquatic Ecology and Evolution, Institute of Ecology and Evolution, University of Bern, Baltzerstrasse 6, CH-3012 Bern, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22337055" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biodiversity ; *Biological Evolution ; Europe ; Eutrophication/*physiology ; *Extinction, Biological ; *Genetic Speciation ; Lakes ; Models, Biological ; Phenotype ; Salmonidae/genetics/*physiology
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  • 90
    Publication Date: 2012-04-17
    Description: The development and maintenance of an epithelium requires finely balanced rates of growth and cell death. However, the mechanical and biochemical mechanisms that ensure proper feedback control of tissue growth, which when deregulated contribute to tumorigenesis, are poorly understood. Here we use the fly notum as a model system to identify a novel process of crowding-induced cell delamination that balances growth to ensure the development of well-ordered cell packing. In crowded regions of the tissue, a proportion of cells undergo a serial loss of cell-cell junctions and a progressive loss of apical area, before being squeezed out by their neighbours. This path of delamination is recapitulated by a simple computational model of epithelial mechanics, in which stochastic cell loss relieves overcrowding as the system tends towards equilibrium. We show that this process of delamination is mechanistically distinct from apoptosis-mediated cell extrusion and precedes the first signs of cell death. Overall, this analysis reveals a simple mechanism that buffers epithelia against variations in growth. Because live-cell delamination constitutes a mechanistic link between epithelial hyperplasia and cell invasion, this is likely to have important implications for our understanding of the early stages of cancer development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marinari, Eliana -- Mehonic, Aida -- Curran, Scott -- Gale, Jonathan -- Duke, Thomas -- Baum, Buzz -- 9786/Cancer Research UK/United Kingdom -- Cancer Research UK/United Kingdom -- England -- Nature. 2012 Apr 15;484(7395):542-5. doi: 10.1038/nature10984.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council Laboratory of Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22504180" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Cell Communication ; Cell Count ; Cell Death ; Cell Growth Processes ; Cell Survival ; Drosophila melanogaster/*cytology ; Epithelial Cells/*cytology ; Female ; Male ; Models, Biological ; Neoplasms/pathology ; Stochastic Processes
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  • 91
    Publication Date: 2012-06-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Polymenis, Michael -- Kennedy, Brian K -- England -- Nature. 2012 Jun 6;486(7401):37-8. doi: 10.1038/486037a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22678274" target="_blank"〉PubMed〈/a〉
    Keywords: Automation ; *Cell Aging ; Cell Biology/instrumentation ; Cell Culture Techniques/*instrumentation ; Microfluidic Analytical Techniques/*instrumentation ; Miniaturization ; Models, Biological ; Saccharomyces cerevisiae/*cytology ; Single-Cell Analysis/*instrumentation/*methods
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  • 92
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    Nature Publishing Group (NPG)
    Publication Date: 2012-09-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maxmen, Amy -- England -- Nature. 2012 Sep 20;489(7416):349-50. doi: 10.1038/489349a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22996526" target="_blank"〉PubMed〈/a〉
    Keywords: Humans ; Kidney/pathology/virology ; Kidney Diseases/*etiology/pathology/prevention & control/*virology ; Models, Biological ; RNA, Viral/urine ; Reproducibility of Results ; United States/epidemiology ; West Nile Fever/*complications/epidemiology/therapy ; West Nile virus/genetics/isolation & purification/*pathogenicity
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  • 93
    Publication Date: 2012-08-03
    Description: Recent studies using the isolation of a subpopulation of tumour cells followed by their transplantation into immunodeficient mice provide evidence that certain tumours, including squamous skin tumours, contain cells with high clonogenic potential that have been referred to as cancer stem cells (CSCs). Until now, CSC properties have only been investigated by transplantation assays, and their existence in unperturbed tumour growth is unproven. Here we make use of clonal analysis of squamous skin tumours using genetic lineage tracing to unravel the mode of tumour growth in vivo in its native environment. To this end, we used a genetic labelling strategy that allows individual tumour cells to be marked and traced over time at different stages of tumour progression. Surprisingly, we found that the majority of labelled tumour cells in benign papilloma have only limited proliferative potential, whereas a fraction has the capacity to persist long term, giving rise to progeny that occupy a significant part of the tumour. As well as confirming the presence of two distinct proliferative cell compartments within the papilloma, mirroring the composition, hierarchy and fate behaviour of normal tissue, quantitative analysis of clonal fate data indicates that the more persistent population has stem-cell-like characteristics and cycles twice per day, whereas the second represents a slower cycling transient population that gives rise to terminally differentiated tumour cells. Such behaviour is shown to be consistent with double-labelling experiments and detailed clonal fate characteristics. By contrast, measurements of clone size and proliferative potential in invasive squamous cell carcinoma show a different pattern of behaviour, consistent with geometric expansion of a single CSC population with limited potential for terminal differentiation. This study presents the first experimental evidence for the existence of CSCs during unperturbed solid tumour growth.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Driessens, Gregory -- Beck, Benjamin -- Caauwe, Amelie -- Simons, Benjamin D -- Blanpain, Cedric -- 079249/Wellcome Trust/United Kingdom -- 092096/Wellcome Trust/United Kingdom -- England -- Nature. 2012 Aug 23;488(7412):527-30. doi: 10.1038/nature11344.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Universite Libre de Bruxelles, IRIBHM, Brussels B-1070, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22854777" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carcinoma, Squamous Cell/genetics/pathology ; Cell Count ; Cell Differentiation ; *Cell Lineage ; Cell Proliferation ; *Cell Tracking ; Clone Cells/metabolism/pathology ; Disease Models, Animal ; Humans ; Mice ; Models, Biological ; Neoplastic Stem Cells/metabolism/pathology ; Skin Neoplasms/genetics/*pathology ; Stochastic Processes ; Tumor Microenvironment
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  • 94
    Publication Date: 2012-04-17
    Description: For an epithelium to provide a protective barrier, it must maintain homeostatic cell numbers by matching the number of dividing cells with the number of dying cells. Although compensatory cell division can be triggered by dying cells, it is unknown how cell death might relieve overcrowding due to proliferation. When we trigger apoptosis in epithelia, dying cells are extruded to preserve a functional barrier. Extrusion occurs by cells destined to die signalling to surrounding epithelial cells to contract an actomyosin ring that squeezes the dying cell out. However, it is not clear what drives cell death during normal homeostasis. Here we show in human, canine and zebrafish cells that overcrowding due to proliferation and migration induces extrusion of live cells to control epithelial cell numbers. Extrusion of live cells occurs at sites where the highest crowding occurs in vivo and can be induced by experimentally overcrowding monolayers in vitro. Like apoptotic cell extrusion, live cell extrusion resulting from overcrowding also requires sphingosine 1-phosphate signalling and Rho-kinase-dependent myosin contraction, but is distinguished by signalling through stretch-activated channels. Moreover, disruption of a stretch-activated channel, Piezo1, in zebrafish prevents extrusion and leads to the formation of epithelial cell masses. Our findings reveal that during homeostatic turnover, growth and division of epithelial cells on a confined substratum cause overcrowding that leads to their extrusion and consequent death owing to the loss of survival factors. These results suggest that live cell extrusion could be a tumour-suppressive mechanism that prevents the accumulation of excess epithelial cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4593481/" 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/PMC4593481/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Eisenhoffer, George T -- Loftus, Patrick D -- Yoshigi, Masaaki -- Otsuna, Hideo -- Chien, Chi-Bin -- Morcos, Paul A -- Rosenblatt, Jody -- 1DP2OD002056-01/OD/NIH HHS/ -- 5T32 CA03247-8/CA/NCI NIH HHS/ -- DP2 OD002056/OD/NIH HHS/ -- EB-4443/EB/NIBIB NIH HHS/ -- P30 CA042014/CA/NCI NIH HHS/ -- R01 MH092256/MH/NIMH NIH HHS/ -- England -- Nature. 2012 Apr 15;484(7395):546-9. doi: 10.1038/nature10999.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope Drive, Salt Lake City, Utah 84112, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22504183" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Fins/anatomy & histology/cytology/embryology ; Animals ; Apoptosis ; Cell Count ; Cell Death ; Cell Line ; Cell Movement ; Cell Proliferation ; Cell Survival ; Colon/cytology ; Dogs ; Embryo, Nonmammalian/cytology/embryology ; Epidermis/cytology/embryology ; Epithelial Cells/*cytology ; *Homeostasis ; Humans ; Ion Channels/deficiency/genetics/metabolism ; Lysophospholipids/metabolism ; Models, Biological ; Neoplasms/pathology ; Sphingosine/analogs & derivatives/metabolism ; Zebrafish/anatomy & histology/embryology ; Zebrafish Proteins/deficiency/genetics/metabolism
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  • 95
    Publication Date: 2012-03-09
    Description: Dyneins are microtubule-based AAA(+) motor complexes that power ciliary beating, cell division, cell migration and intracellular transport. Here we report the most complete structure obtained so far, to our knowledge, of the 380-kDa motor domain of Dictyostelium discoideum cytoplasmic dynein at 2.8 A resolution; the data are reliable enough to discuss the structure and mechanism at the level of individual amino acid residues. Features that can be clearly visualized at this resolution include the coordination of ADP in each of four distinct nucleotide-binding sites in the ring-shaped AAA(+) ATPase unit, a newly identified interaction interface between the ring and mechanical linker, and junctional structures between the ring and microtubule-binding stalk, all of which should be critical for the mechanism of dynein motility. We also identify a long-range allosteric communication pathway between the primary ATPase and the microtubule-binding sites. Our work provides a framework for understanding the mechanism of dynein-based motility.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kon, Takahide -- Oyama, Takuji -- Shimo-Kon, Rieko -- Imamula, Kenji -- Shima, Tomohiro -- Sutoh, Kazuo -- Kurisu, Genji -- England -- Nature. 2012 Mar 7;484(7394):345-50. doi: 10.1038/nature10955.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan. takahide.kon@protein.osaka-u.ac.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22398446" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Diphosphate/metabolism ; Adenosine Triphosphate/metabolism ; Allosteric Regulation ; Binding Sites ; Crystallography, X-Ray ; Cytoplasmic Dyneins/*chemistry/metabolism ; Dictyostelium/*chemistry ; Hydrolysis ; Microtubules/metabolism ; Models, Biological ; Models, Molecular ; Movement ; Protein Structure, Tertiary ; Structure-Activity Relationship
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  • 96
    Publication Date: 2012-04-03
    Description: Empirical data indicate that sexual preferences are critical for maintaining species boundaries, yet theoretical work has suggested that, on their own, they can have only a minimal role in maintaining biodiversity. This is because long-term coexistence within overlapping ranges is thought to be unlikely in the absence of ecological differentiation. Here we challenge this widely held view by generalizing a standard model of sexual selection to include two ubiquitous features of populations with sexual selection: spatial variation in local carrying capacity, and mate-search costs in females. We show that, when these two features are combined, sexual preferences can single-handedly maintain coexistence, even when spatial variation in local carrying capacity is so slight that it might go unnoticed empirically. This theoretical study demonstrates that sexual selection alone can promote the long-term coexistence of ecologically equivalent species with overlapping ranges, and it thus provides a novel explanation for the maintenance of species diversity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉M'Gonigle, Leithen K -- Mazzucco, Rupert -- Otto, Sarah P -- Dieckmann, Ulf -- England -- Nature. 2012 Apr 26;484(7395):506-9. doi: 10.1038/nature10971.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Zoology, University of British Columbia, 6270 University Boulevard, Vancouver, British Columbia, Canada. mgonigle@zoology.ubc.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22466286" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; *Biodiversity ; Cichlids/genetics/*physiology ; Female ; *Lakes ; Male ; Mating Preference, Animal/*physiology ; Models, Biological ; Species Specificity ; Time Factors
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  • 97
    Publication Date: 2012-07-28
    Description: Malnutrition affects up to one billion people in the world and is a major cause of mortality. In many cases, malnutrition is associated with diarrhoea and intestinal inflammation, further contributing to morbidity and death. The mechanisms by which unbalanced dietary nutrients affect intestinal homeostasis are largely unknown. Here we report that deficiency in murine angiotensin I converting enzyme (peptidyl-dipeptidase A) 2 (Ace2), which encodes a key regulatory enzyme of the renin-angiotensin system (RAS), results in highly increased susceptibility to intestinal inflammation induced by epithelial damage. The RAS is known to be involved in acute lung failure, cardiovascular functions and SARS infections. Mechanistically, ACE2 has a RAS-independent function, regulating intestinal amino acid homeostasis, expression of antimicrobial peptides, and the ecology of the gut microbiome. Transplantation of the altered microbiota from Ace2 mutant mice into germ-free wild-type hosts was able to transmit the increased propensity to develop severe colitis. ACE2-dependent changes in epithelial immunity and the gut microbiota can be directly regulated by the dietary amino acid tryptophan. Our results identify ACE2 as a key regulator of dietary amino acid homeostasis, innate immunity, gut microbial ecology, and transmissible susceptibility to colitis. These results provide a molecular explanation for how amino acid malnutrition can cause intestinal inflammation and diarrhoea.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hashimoto, Tatsuo -- Perlot, Thomas -- Rehman, Ateequr -- Trichereau, Jean -- Ishiguro, Hiroaki -- Paolino, Magdalena -- Sigl, Verena -- Hanada, Toshikatsu -- Hanada, Reiko -- Lipinski, Simone -- Wild, Birgit -- Camargo, Simone M R -- Singer, Dustin -- Richter, Andreas -- Kuba, Keiji -- Fukamizu, Akiyoshi -- Schreiber, Stefan -- Clevers, Hans -- Verrey, Francois -- Rosenstiel, Philip -- Penninger, Josef M -- England -- Nature. 2012 Jul 25;487(7408):477-81. doi: 10.1038/nature11228.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22837003" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biocatalysis ; Colitis/drug therapy/*etiology/*microbiology/pathology ; Dextran Sulfate ; Diarrhea/complications ; Dietary Proteins/metabolism/pharmacology ; Female ; Gene Deletion ; Genetic Predisposition to Disease ; Germ-Free Life ; Homeostasis ; Immunity, Innate ; Intestines/*microbiology/pathology ; Male ; Malnutrition/*complications/metabolism ; *Metagenome ; Mice ; Models, Biological ; Niacinamide/metabolism/pharmacology/therapeutic use ; Peptidyl-Dipeptidase A/deficiency/genetics/*metabolism ; Renin-Angiotensin System/physiology ; TOR Serine-Threonine Kinases/metabolism ; Trinitrobenzenesulfonic Acid ; Tryptophan/*metabolism/pharmacology/therapeutic use
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  • 98
    Publication Date: 2012-03-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hill, Kim -- Hurtado, A Magdalena -- England -- Nature. 2012 Mar 7;483(7388):160-1. doi: 10.1038/483160a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22398548" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/physiology ; *Biological Evolution ; Competitive Behavior/physiology ; *Cooperative Behavior ; Emigration and Immigration ; *Family Characteristics ; Female ; Fertility/physiology ; Gambia ; Humans ; Male ; Menopause/*physiology ; Models, Biological ; Reproduction/*physiology ; *Reproductive Behavior
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  • 99
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    Nature Publishing Group (NPG)
    Publication Date: 2012-02-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Trivedi, Bijal P -- England -- Nature. 2012 Feb 15;482(7385):294-6. doi: 10.1038/482294a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22337030" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/drug therapy/metabolism/prevention & control ; Amyloid beta-Peptides/metabolism ; Animals ; *Biological Evolution ; Clinical Trials as Topic ; Drosophila Proteins/deficiency/genetics/metabolism ; Drosophila melanogaster/genetics/metabolism ; Genetic Variation/genetics ; HSP90 Heat-Shock Proteins/antagonists & inhibitors/*metabolism ; Heat-Shock Proteins/deficiency/genetics/metabolism ; Heat-Shock Response/physiology ; History, 20th Century ; History, 21st Century ; Humans ; Models, Biological ; Neoplasms/drug therapy/metabolism ; Peptide Termination Factors/metabolism ; Prions/chemistry/*metabolism ; Protein Folding ; Saccharomyces cerevisiae/genetics/growth & development/metabolism ; Saccharomyces cerevisiae Proteins/metabolism
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  • 100
    Publication Date: 2012-01-27
    Description: Our understanding of Alzheimer's disease pathogenesis is currently limited by difficulties in obtaining live neurons from patients and the inability to model the sporadic form of the disease. It may be possible to overcome these challenges by reprogramming primary cells from patients into induced pluripotent stem cells (iPSCs). Here we reprogrammed primary fibroblasts from two patients with familial Alzheimer's disease, both caused by a duplication of the amyloid-beta precursor protein gene (APP; termed APP(Dp)), two with sporadic Alzheimer's disease (termed sAD1, sAD2) and two non-demented control individuals into iPSC lines. Neurons from differentiated cultures were purified with fluorescence-activated cell sorting and characterized. Purified cultures contained more than 90% neurons, clustered with fetal brain messenger RNA samples by microarray criteria, and could form functional synaptic contacts. Virtually all cells exhibited normal electrophysiological activity. Relative to controls, iPSC-derived, purified neurons from the two APP(Dp) patients and patient sAD2 exhibited significantly higher levels of the pathological markers amyloid-beta(1-40), phospho-tau(Thr 231) and active glycogen synthase kinase-3beta (aGSK-3beta). Neurons from APP(Dp) and sAD2 patients also accumulated large RAB5-positive early endosomes compared to controls. Treatment of purified neurons with beta-secretase inhibitors, but not gamma-secretase inhibitors, caused significant reductions in phospho-Tau(Thr 231) and aGSK-3beta levels. These results suggest a direct relationship between APP proteolytic processing, but not amyloid-beta, in GSK-3beta activation and tau phosphorylation in human neurons. Additionally, we observed that neurons with the genome of one sAD patient exhibited the phenotypes seen in familial Alzheimer's disease samples. More generally, we demonstrate that iPSC technology can be used to observe phenotypes relevant to Alzheimer's disease, even though it can take decades for overt disease to manifest in patients.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338985/" 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/PMC3338985/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Israel, Mason A -- Yuan, Shauna H -- Bardy, Cedric -- Reyna, Sol M -- Mu, Yangling -- Herrera, Cheryl -- Hefferan, Michael P -- Van Gorp, Sebastiaan -- Nazor, Kristopher L -- Boscolo, Francesca S -- Carson, Christian T -- Laurent, Louise C -- Marsala, Martin -- Gage, Fred H -- Remes, Anne M -- Koo, Edward H -- Goldstein, Lawrence S B -- K12 HD001259/HD/NICHD NIH HHS/ -- P30 NS047101/NS/NINDS NIH HHS/ -- P50 AG005131/AG/NIA NIH HHS/ -- RC1 NS068705/NS/NINDS NIH HHS/ -- RC1 NS068705-01/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Jan 25;482(7384):216-20. doi: 10.1038/nature10821.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Cellular and Molecular Medicine, 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/22278060" target="_blank"〉PubMed〈/a〉
    Keywords: Aged, 80 and over ; Alzheimer Disease/*metabolism/*pathology ; Amyloid Precursor Protein Secretases/antagonists & inhibitors/metabolism ; Amyloid beta-Peptides/metabolism/secretion ; Amyloid beta-Protein Precursor/genetics/metabolism/secretion ; Astrocytes/cytology ; Biomarkers/metabolism ; Cells, Cultured ; Cellular Reprogramming ; Coculture Techniques ; Endosomes/metabolism ; Enzyme Activation ; Female ; Fibroblasts/cytology/metabolism ; Glycogen Synthase Kinase 3/metabolism ; Humans ; Induced Pluripotent Stem Cells/*metabolism/*pathology ; Male ; Middle Aged ; Models, Biological ; Neurons/drug effects/*metabolism/pathology ; Peptide Fragments/metabolism/secretion ; Phosphoproteins/metabolism ; Phosphorylation/drug effects ; Protease Inhibitors/pharmacology ; Proteolysis ; Synapsins/metabolism ; tau Proteins/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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