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  • Models, Biological  (417)
  • Dynamic
  • Elasticity
  • Fracture
  • Nature Publishing Group (NPG)  (429)
  • Am. Soc. Mech. Eng.
  • Institute of Physics
  • 51
    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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  • 52
    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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  • 53
    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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  • 54
    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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  • 55
    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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  • 56
    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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  • 57
    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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  • 58
    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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  • 59
    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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  • 60
    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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  • 61
    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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  • 62
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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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  • 63
    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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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 64
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    Unknown
    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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  • 65
    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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  • 66
    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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  • 67
    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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  • 68
    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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  • 69
    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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  • 70
    Publication Date: 2014-05-16
    Description: Groundwater use in California's San Joaquin Valley exceeds replenishment of the aquifer, leading to substantial diminution of this resource and rapid subsidence of the valley floor. The volume of groundwater lost over the past century and a half also represents a substantial reduction in mass and a large-scale unburdening of the lithosphere, with significant but unexplored potential impacts on crustal deformation and seismicity. Here we use vertical global positioning system measurements to show that a broad zone of rock uplift of up to 1-3 mm per year surrounds the southern San Joaquin Valley. The observed uplift matches well with predicted flexure from a simple elastic model of current rates of water-storage loss, most of which is caused by groundwater depletion. The height of the adjacent central Coast Ranges and the Sierra Nevada is strongly seasonal and peaks during the dry late summer and autumn, out of phase with uplift of the valley floor during wetter months. Our results suggest that long-term and late-summer flexural uplift of the Coast Ranges reduce the effective normal stress resolved on the San Andreas Fault. This process brings the fault closer to failure, thereby providing a viable mechanism for observed seasonality in microseismicity at Parkfield and potentially affecting long-term seismicity rates for fault systems adjacent to the valley. We also infer that the observed contemporary uplift of the southern Sierra Nevada previously attributed to tectonic or mantle-derived forces is partly a consequence of human-caused groundwater depletion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Amos, Colin B -- Audet, Pascal -- Hammond, William C -- Burgmann, Roland -- Johanson, Ingrid A -- Blewitt, Geoffrey -- England -- Nature. 2014 May 22;509(7501):483-6. doi: 10.1038/nature13275. Epub 2014 May 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Geology Department, Western Washington University, Bellingham, Washington 98225-9080, USA. ; Department of Earth Sciences, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada. ; Nevada Geodetic Laboratory, Nevada Bureau of Mines and Geology and Nevada Seismological Laboratory, University of Nevada, Reno, Nevada 89557, USA. ; 1] Berkeley Seismological Laboratory, University of California, Berkeley, California 94720-4760, USA [2] Department of Earth and Planetary Science, University of California, Berkeley, California 97720-4767, USA. ; Berkeley Seismological Laboratory, University of California, Berkeley, California 94720-4760, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24828048" target="_blank"〉PubMed〈/a〉
    Keywords: *Altitude ; California ; Earthquakes/*statistics & numerical data ; Elasticity ; Environmental Monitoring ; Geographic Information Systems ; Groundwater/*analysis ; *Models, Theoretical ; Seasons ; Water Supply/analysis/*statistics & numerical data
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  • 71
    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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  • 72
    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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  • 73
    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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  • 74
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2014-04-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Anthes, Emily -- England -- Nature. 2014 Apr 3;508(7494):S16-7. doi: 10.1038/508S16a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24695330" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Aged ; Aging, Premature/*complications/etiology/pathology/*physiopathology ; Antipsychotic Agents/adverse effects ; Brain/pathology/physiopathology ; Cardiovascular Diseases/complications ; Confounding Factors (Epidemiology) ; Diabetes Mellitus, Type 2/complications ; Glucose Intolerance/complications ; Health Surveys ; Humans ; Longevity/drug effects ; Middle Aged ; Models, Biological ; Schizophrenia/*complications/drug therapy/pathology/*physiopathology ; Telomere/metabolism ; Time Factors
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  • 75
    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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  • 76
    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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  • 77
    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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  • 78
    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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  • 79
    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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  • 80
    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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  • 81
    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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  • 82
    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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  • 83
    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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  • 84
    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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  • 85
    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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  • 86
    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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  • 87
    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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  • 88
    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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  • 89
    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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  • 90
    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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  • 91
    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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  • 92
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    Unknown
    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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  • 93
    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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  • 94
    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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  • 95
    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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  • 96
    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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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 97
    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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  • 98
    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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  • 99
    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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  • 100
    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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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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