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  • Models, Biological  (178)
  • Cell & Developmental Biology
  • Chemical Engineering
  • Inorganic Chemistry
  • SPACE SCIENCES
  • American Association for the Advancement of Science (AAAS)  (181)
  • 2010-2014  (181)
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  • 1
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-01-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stokstad, Erik -- New York, N.Y. -- Science. 2014 Jan 17;343(6168):238. doi: 10.1126/science.343.6168.238.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24436398" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture ; Air Pollutants/*adverse effects/analysis ; Air Pollution/*adverse effects/prevention & control ; Ammonia/*adverse effects/analysis ; Animals ; Fertilizers/*adverse effects ; Health/*economics ; Heart Diseases/chemically induced ; Humans ; Livestock ; Models, Biological ; North Carolina ; Particulate Matter/*adverse effects/analysis ; Respiratory Tract Diseases/chemically induced ; United States ; United States Environmental Protection Agency
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-09-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kupferschmidt, Kai -- New York, N.Y. -- Science. 2014 Sep 5;345(6201):1108. doi: 10.1126/science.345.6201.1108.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25190771" target="_blank"〉PubMed〈/a〉
    Keywords: Africa, Western/epidemiology ; *Ebolavirus ; Epidemics ; Hemorrhagic Fever, Ebola/*epidemiology/*prevention & control ; Humans ; Models, Biological
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  • 3
    Publication Date: 2014-08-02
    Description: During limb development, digits emerge from the undifferentiated mesenchymal tissue that constitutes the limb bud. It has been proposed that this process is controlled by a self-organizing Turing mechanism, whereby diffusible molecules interact to produce a periodic pattern of digital and interdigital fates. However, the identities of the molecules remain unknown. By combining experiments and modeling, we reveal evidence that a Turing network implemented by Bmp, Sox9, and Wnt drives digit specification. We develop a realistic two-dimensional simulation of digit patterning and show that this network, when modulated by morphogen gradients, recapitulates the expression patterns of Sox9 in the wild type and in perturbation experiments. Our systems biology approach reveals how a combination of growth, morphogen gradients, and a self-organizing Turing network can achieve robust and reproducible pattern formation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Raspopovic, J -- Marcon, L -- Russo, L -- Sharpe, J -- New York, N.Y. -- Science. 2014 Aug 1;345(6196):566-70. doi: 10.1126/science.1252960.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Systems Biology Program, Centre for Genomic Regulation (CRG), and Universitat Pompeu Fabra (UPF), Dr. Aiguader 88, 08003 Barcelona, Spain. ; Systems Biology Program, Centre for Genomic Regulation (CRG), and Universitat Pompeu Fabra (UPF), Dr. Aiguader 88, 08003 Barcelona, Spain. Institucio Catalana de Recerca i Estudis Avancats (ICREA), Passeig Lluis Companys 23, 08010 Barcelona, Spain. james.sharpe@crg.eu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25082703" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Body Patterning/*genetics ; Bone Morphogenetic Proteins/*metabolism ; Computer Simulation ; Extremities/*embryology ; Female ; *Gene Expression Regulation, Developmental ; Gene Knockdown Techniques ; Green Fluorescent Proteins/genetics/metabolism ; Limb Buds/*embryology ; Mice ; Mice, Inbred Strains ; Models, Biological ; Oligonucleotide Array Sequence Analysis ; SOX9 Transcription Factor/genetics/*metabolism ; Wnt Proteins/*metabolism
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  • 4
    Publication Date: 2014-01-18
    Description: Cells need to adapt to dynamic environments. Yeast that fail to cope with dynamic changes in the abundance of glucose can undergo growth arrest. We show that this failure is caused by imbalanced reactions in glycolysis, the essential pathway in energy metabolism in most organisms. The imbalance arises largely from the fundamental design of glycolysis, making this state of glycolysis a generic risk. Cells with unbalanced glycolysis coexisted with vital cells. Spontaneous, nongenetic metabolic variability among individual cells determines which state is reached and, consequently, which cells survive. Transient ATP (adenosine 5'-triphosphate) hydrolysis through futile cycling reduces the probability of reaching the imbalanced state. Our results reveal dynamic behavior of glycolysis and indicate that cell fate can be determined by heterogeneity purely at the metabolic level.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉van Heerden, Johan H -- Wortel, Meike T -- Bruggeman, Frank J -- Heijnen, Joseph J -- Bollen, Yves J M -- Planque, Robert -- Hulshof, Josephus -- O'Toole, Tom G -- Wahl, S Aljoscha -- Teusink, Bas -- New York, N.Y. -- Science. 2014 Feb 28;343(6174):1245114. doi: 10.1126/science.1245114. Epub 2014 Jan 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Systems Bioinformatics/Amsterdam Institute for Molecules, Medicines and Systems (AIMMS)/Netherlands Institute for Systems Biology, VU University, De Boelelaan 1085, 1081 HV Amsterdam, Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24436182" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Energy Metabolism ; Glucose/*metabolism ; Glucosyltransferases/genetics/metabolism ; *Glycolysis ; Hydrogen-Ion Concentration ; Hydrolysis ; Models, Biological ; Saccharomyces cerevisiae/*growth & development/*metabolism ; Trehalose/metabolism
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  • 5
    Publication Date: 2014-05-31
    Description: Cells are active systems with molecular force generation that drives complex dynamics at the supramolecular scale. We present a quantitative study of molecular motions in cells over times from milliseconds to hours. Noninvasive tracking was accomplished by imaging highly stable near-infrared luminescence of single-walled carbon nanotubes targeted to kinesin-1 motor proteins in COS-7 cells. We observed a regime of active random "stirring" that constitutes an intermediate mode of transport, different from both thermal diffusion and directed motor activity. High-frequency motion was found to be thermally driven. At times greater than 100 milliseconds, nonequilibrium dynamics dominated. In addition to directed transport along microtubules, we observed strong random dynamics driven by myosins that result in enhanced nonspecific transport. We present a quantitative model connecting molecular mechanisms to mesoscopic fluctuations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fakhri, Nikta -- Wessel, Alok D -- Willms, Charlotte -- Pasquali, Matteo -- Klopfenstein, Dieter R -- MacKintosh, Frederick C -- Schmidt, Christoph F -- New York, N.Y. -- Science. 2014 May 30;344(6187):1031-5. doi: 10.1126/science.1250170.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Drittes Physikalisches Institut-Biophysik, Georg-August-Universitat, 37077 Gottingen, Germany. ; Department of Chemical and Biomolecular Engineering, Department of Chemistry, Smalley Institute for Nanoscale Science and Technology, Rice University, Houston, TX 77005, USA. ; Department of Physics and Astronomy, Vrije Universiteit, 1081 HV Amsterdam, Netherlands. christoph.schmidt@phys.uni-goettingen.de fcmack@gmail.com. ; Drittes Physikalisches Institut-Biophysik, Georg-August-Universitat, 37077 Gottingen, Germany. christoph.schmidt@phys.uni-goettingen.de fcmack@gmail.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24876498" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; COS Cells ; Cell Tracking/*methods ; Cercopithecus aethiops ; Kinesin/chemistry/metabolism ; Microtubules/metabolism ; Models, Biological ; Molecular Motor Proteins/chemistry/*metabolism ; Motion ; Myosins/chemistry/metabolism ; *Nanotubes, Carbon
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  • 6
    Publication Date: 2014-10-11
    Description: During animal cell division, the cleavage furrow is positioned by microtubules that signal to the actin cortex at the cell midplane. We developed a cell-free system to recapitulate cytokinesis signaling using cytoplasmic extract from Xenopus eggs. Microtubules grew out as asters from artificial centrosomes and met to organize antiparallel overlap zones. These zones blocked the interpenetration of neighboring asters and recruited cytokinesis midzone proteins, including the chromosomal passenger complex (CPC) and centralspindlin. The CPC was transported to overlap zones, which required two motor proteins, Kif4A and a Kif20A paralog. Using supported lipid bilayers to mimic the plasma membrane, we observed the recruitment of cleavage furrow markers, including an active RhoA reporter, at microtubule overlaps. This system opens further approaches to understanding the biophysics of cytokinesis signaling.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4281018/" 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/PMC4281018/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nguyen, Phuong A -- Groen, Aaron C -- Loose, Martin -- Ishihara, Keisuke -- Wuhr, Martin -- Field, Christine M -- Mitchison, Timothy J -- GM103785/GM/NIGMS NIH HHS/ -- GM39565/GM/NIGMS NIH HHS/ -- R01 GM039565/GM/NIGMS NIH HHS/ -- R01 GM103785/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Oct 10;346(6206):244-7. doi: 10.1126/science.1256773.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. Marine Biological Laboratory, Woods Hole, MA 02543, USA. ; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. ; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. Marine Biological Laboratory, Woods Hole, MA 02543, USA. Christine_Field@hms.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25301629" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Membrane/chemistry/*physiology ; *Cell-Free System ; Centrosome/physiology ; *Cytokinesis ; DNA-Binding Proteins/genetics/metabolism ; Guanosine Triphosphate/metabolism ; Kinesin/genetics/metabolism ; Lipid Bilayers ; Microtubules/physiology ; Models, Biological ; Nuclear Proteins/genetics/metabolism ; *Signal Transduction ; Xenopus laevis ; rhoA GTP-Binding Protein/metabolism
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  • 7
    Publication Date: 2014-02-01
    Description: Ecologists have long sought to understand the factors controlling the structure of savanna vegetation. Using data from 2154 sites in savannas across Africa, Australia, and South America, we found that increasing moisture availability drives increases in fire and tree basal area, whereas fire reduces tree basal area. However, among continents, the magnitude of these effects varied substantially, so that a single model cannot adequately represent savanna woody biomass across these regions. Historical and environmental differences drive the regional variation in the functional relationships between woody vegetation, fire, and climate. These same differences will determine the regional responses of vegetation to future climates, with implications for global carbon stocks.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lehmann, Caroline E R -- Anderson, T Michael -- Sankaran, Mahesh -- Higgins, Steven I -- Archibald, Sally -- Hoffmann, William A -- Hanan, Niall P -- Williams, Richard J -- Fensham, Roderick J -- Felfili, Jeanine -- Hutley, Lindsay B -- Ratnam, Jayashree -- San Jose, Jose -- Montes, Ruben -- Franklin, Don -- Russell-Smith, Jeremy -- Ryan, Casey M -- Durigan, Giselda -- Hiernaux, Pierre -- Haidar, Ricardo -- Bowman, David M J S -- Bond, William J -- New York, N.Y. -- Science. 2014 Jan 31;343(6170):548-52. doi: 10.1126/science.1247355.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Macquarie University, New South Wales 2109, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24482480" target="_blank"〉PubMed〈/a〉
    Keywords: Africa ; Australia ; *Climate ; *Ecosystem ; *Fires ; Humidity ; Models, Biological ; South America ; *Trees
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  • 8
    Publication Date: 2014-05-17
    Description: Nuclear magnetic resonance (NMR) spectroscopy is useful to determine molecular structure in tissues grown in vitro only if their fidelity, relative to native tissue, can be established. Here, we use multidimensional NMR spectra of animal and in vitro model tissues as fingerprints of their respective molecular structures, allowing us to compare the intact tissues at atomic length scales. To obtain spectra from animal tissues, we developed a heavy mouse enriched by about 20% in the NMR-active isotopes carbon-13 and nitrogen-15. The resulting spectra allowed us to refine an in vitro model of developing bone and to probe its detailed structure. The identification of an unexpected molecule, poly(adenosine diphosphate ribose), that may be implicated in calcification of the bone matrix, illustrates the analytical power of this approach.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chow, W Ying -- Rajan, Rakesh -- Muller, Karin H -- Reid, David G -- Skepper, Jeremy N -- Wong, Wai Ching -- Brooks, Roger A -- Green, Maggie -- Bihan, Dominique -- Farndale, Richard W -- Slatter, David A -- Shanahan, Catherine M -- Duer, Melinda J -- BB/G021392/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- G0500707/Medical Research Council/United Kingdom -- PG/08/011/24416/British Heart Foundation/United Kingdom -- PG/10/43/28390/British Heart Foundation/United Kingdom -- RG/09/003/27122/British Heart Foundation/United Kingdom -- RG/11/14/29056/British Heart Foundation/United Kingdom -- New York, N.Y. -- Science. 2014 May 16;344(6185):742-6. doi: 10.1126/science.1248167.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. ; Orthopaedic Research Unit, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK. ; Department of Physiology, Development, and Neuroscience, University of Cambridge, Downing Site, Cambridge CB2 3DY, UK. ; Central Biomedical Resources, University of Cambridge, School of Clinical Medicine, West Forvie Building, Forvie Site, Robinson Way, Cambridge CB2 0SZ, UK. ; Department of Biochemistry, University of Cambridge, Downing Site, Cambridge CB2 1QW, UK. ; British Heart Foundation Centre of Research Excellence, Cardiovascular Division, James Black Centre, King's College London, 125 Coldharbour Lane, London SE5 9NU, UK. ; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. mjd13@cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24833391" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Bone Development ; *Calcification, Physiologic ; Carbon Isotopes ; Extracellular Matrix/chemistry ; Growth Plate/growth & development ; Mice ; Models, Biological ; Nitrogen Isotopes ; Nuclear Magnetic Resonance, Biomolecular/*methods ; Poly Adenosine Diphosphate Ribose/*analysis ; Sheep
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  • 9
    Publication Date: 2014-04-26
    Description: Light is a source of energy and also a regulator of plant physiological adaptations. We show here that light/dark conditions affect alternative splicing of a subset of Arabidopsis genes preferentially encoding proteins involved in RNA processing. The effect requires functional chloroplasts and is also observed in roots when the communication with the photosynthetic tissues is not interrupted, suggesting that a signaling molecule travels through the plant. Using photosynthetic electron transfer inhibitors with different mechanisms of action, we deduce that the reduced pool of plastoquinones initiates a chloroplast retrograde signaling that regulates nuclear alternative splicing and is necessary for proper plant responses to varying light conditions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382720/" 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/PMC4382720/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Petrillo, Ezequiel -- Godoy Herz, Micaela A -- Fuchs, Armin -- Reifer, Dominik -- Fuller, John -- Yanovsky, Marcelo J -- Simpson, Craig -- Brown, John W S -- Barta, Andrea -- Kalyna, Maria -- Kornblihtt, Alberto R -- BB/G024979/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- P 26333/Austrian Science Fund FWF/Austria -- Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Apr 25;344(6182):427-30. doi: 10.1126/science.1250322. Epub 2014 Apr 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratorio de Fisiologia y Biologia Molecular, Departamento de Fisiologia, Biologia Molecular y Celular, IFIBYNE-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellon 2, C1428EHA Buenos Aires, Argentina.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24763593" target="_blank"〉PubMed〈/a〉
    Keywords: *Alternative Splicing ; Arabidopsis/*genetics/metabolism ; Arabidopsis Proteins/genetics/metabolism ; Cell Nucleus/genetics ; Chloroplasts/*metabolism ; Circadian Clocks ; Dibromothymoquinone/pharmacology ; Diuron/pharmacology ; Electron Transport/drug effects ; *Gene Expression Regulation, Plant ; Light ; Models, Biological ; Oxidation-Reduction ; Photosynthesis/drug effects ; Plant Leaves/metabolism ; Plant Roots/metabolism ; Plants, Genetically Modified ; Plastoquinone/*metabolism ; RNA Stability ; RNA, Messenger/genetics/metabolism ; RNA, Plant/genetics/metabolism ; Seedlings/genetics/metabolism ; Signal Transduction
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  • 10
    Publication Date: 2014-08-16
    Description: Natural interconversions between distinct somatic cell types have been reported in species as diverse as jellyfish and mice. The efficiency and reproducibility of some reprogramming events represent unexploited avenues in which to probe mechanisms that ensure robust cell conversion. We report that a conserved H3K27me3/me2 demethylase, JMJD-3.1, and the H3K4 methyltransferase Set1 complex cooperate to ensure invariant transdifferentiation (Td) of postmitotic Caenorhabditis elegans hindgut cells into motor neurons. At single-cell resolution, robust conversion requires stepwise histone-modifying activities, functionally partitioned into discrete phases of Td through nuclear degradation of JMJD-3.1 and phase-specific interactions with transcription factors that have conserved roles in cell plasticity and terminal fate selection. Our results draw parallels between epigenetic mechanisms underlying robust Td in nature and efficient cell reprogramming in vitro.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zuryn, Steven -- Ahier, Arnaud -- Portoso, Manuela -- White, Esther Redhouse -- Morin, Marie-Charlotte -- Margueron, Raphael -- Jarriault, Sophie -- New York, N.Y. -- Science. 2014 Aug 15;345(6198):826-9. doi: 10.1126/science.1255885.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Development and Stem Cells, Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS UMR 7104/INSERM U964, Universite de Strasbourg, 67404 Illkirch CU Strasbourg, France. ; Institut Curie, INSERM U934, CNRS UMR3215, 26, Rue d'Ulm, 75005 Paris, France. ; Department of Development and Stem Cells, Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS UMR 7104/INSERM U964, Universite de Strasbourg, 67404 Illkirch CU Strasbourg, France. sophie@igbmc.fr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25124442" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; Caenorhabditis elegans/*cytology/genetics ; Caenorhabditis elegans Proteins/chemistry/genetics/*metabolism ; Cell Dedifferentiation ; Cell Nucleus/metabolism/ultrastructure ; *Cell Transdifferentiation ; Digestive System/cytology ; Histone Demethylases/chemistry/genetics/*metabolism ; Histone-Lysine N-Methyltransferase/genetics/*metabolism ; Histones/*metabolism ; Lysine/metabolism ; Methylation ; Models, Biological ; Molecular Sequence Data ; Motor Neurons/*cytology ; Transcription Factors/metabolism
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  • 11
    Publication Date: 2014-09-27
    Description: Development requires tissue growth as well as cell diversification. To address how these processes are coordinated, we analyzed the development of molecularly distinct domains of neural progenitors in the mouse and chick neural tube. We show that during development, these domains undergo changes in size that do not scale with changes in overall tissue size. Our data show that domain proportions are first established by opposing morphogen gradients and subsequently controlled by domain-specific regulation of differentiation rate but not differences in proliferation rate. Regulation of differentiation rate is key to maintaining domain proportions while accommodating both intra- and interspecies variations in size. Thus, the sequential control of progenitor specification and differentiation elaborates pattern without requiring that signaling gradients grow as tissues expand.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4228193/" 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/PMC4228193/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kicheva, Anna -- Bollenbach, Tobias -- Ribeiro, Ana -- Valle, Helena Perez -- Lovell-Badge, Robin -- Episkopou, Vasso -- Briscoe, James -- 098326/Wellcome Trust/United Kingdom -- MC_U117560541/Medical Research Council/United Kingdom -- MC_U120074332/Medical Research Council/United Kingdom -- MR/J013331/1/Medical Research Council/United Kingdom -- R01 EB016629/EB/NIBIB NIH HHS/ -- U117560541/Medical Research Council/United Kingdom -- WT098326MA/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2014 Sep 26;345(6204):1254927. doi: 10.1126/science.1254927.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council (MRC), National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW71AA, UK. ; Institute of Science and Technology (IST) Austria, Am Campus 1, A - 3400 Klosterneuburg, Austria. ; Medical Research Council (MRC), National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW71AA, UK. Imperial College London, UK. ; Medical Research Council (MRC), National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW71AA, UK. Department of Biochemistry, The University of Hong Kong, 3/F Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Hong Kong. Division of Biosciences, Faculty of Life Sciences, University College London, UK. ; Division of Brain Sciences, Faculty of Medicine, Imperial College London, UK. ; Medical Research Council (MRC), National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW71AA, UK. jbrisco@nimr.mrc.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25258086" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Body Patterning ; *Cell Differentiation ; Chick Embryo ; Mice ; Models, Biological ; Neural Tube/cytology/*embryology ; Spinal Cord/*embryology ; Stem Cells/*cytology
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  • 12
    Publication Date: 2014-03-22
    Description: Wnt/beta-catenin signaling is critical for tissue regeneration. However, it is unclear how beta-catenin controls stem cell behaviors to coordinate organized growth. Using live imaging, we show that activation of beta-catenin specifically within mouse hair follicle stem cells generates new hair growth through oriented cell divisions and cellular displacement. beta-Catenin activation is sufficient to induce hair growth independently of mesenchymal dermal papilla niche signals normally required for hair regeneration. Wild-type cells are co-opted into new hair growths by beta-catenin mutant cells, which non-cell autonomously activate Wnt signaling within the neighboring wild-type cells via Wnt ligands. This study demonstrates a mechanism by which Wnt/beta-catenin signaling controls stem cell-dependent tissue growth non-cell autonomously and advances our understanding of the mechanisms that drive coordinated regeneration.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096864/" 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/PMC4096864/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Deschene, Elizabeth R -- Myung, Peggy -- Rompolas, Panteleimon -- Zito, Giovanni -- Sun, Thomas Yang -- Taketo, Makoto M -- Saotome, Ichiko -- Greco, Valentina -- 1R01AR063663-01/AR/NIAMS NIH HHS/ -- 2P50CA121974/CA/NCI NIH HHS/ -- 5P30 AR053495-07/AR/NIAMS NIH HHS/ -- K08 AR066790/AR/NIAMS NIH HHS/ -- P30 CA016359/CA/NCI NIH HHS/ -- P50 CA121974/CA/NCI NIH HHS/ -- R01 AR063663/AR/NIAMS NIH HHS/ -- T32 GM007223/GM/NIGMS NIH HHS/ -- TG32 GM007223/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Mar 21;343(6177):1353-6. doi: 10.1126/science.1248373.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Yale Stem Cell Center, Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24653033" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation ; Cell Division ; Hair/*growth & development ; Hair Follicle/*cytology/*metabolism ; Ligands ; Mice ; Models, Biological ; Mutation ; Stem Cell Niche ; Stem Cells/cytology/*metabolism ; Tamoxifen/pharmacology ; Up-Regulation ; Wnt Proteins/genetics/metabolism ; *Wnt Signaling Pathway ; beta Catenin/genetics/*metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 13
    Publication Date: 2014-10-04
    Description: Ethanol toxicity in the yeast Saccharomyces cerevisiae limits titer and productivity in the industrial production of transportation bioethanol. We show that strengthening the opposing potassium and proton electrochemical membrane gradients is a mechanism that enhances general resistance to multiple alcohols. The elevation of extracellular potassium and pH physically bolsters these gradients, increasing tolerance to higher alcohols and ethanol fermentation in commercial and laboratory strains (including a xylose-fermenting strain) under industrial-like conditions. Production per cell remains largely unchanged, with improvements deriving from heightened population viability. Likewise, up-regulation of the potassium and proton pumps in the laboratory strain enhances performance to levels exceeding those of industrial strains. Although genetically complex, alcohol tolerance can thus be dominated by a single cellular process, one controlled by a major physicochemical component but amenable to biological augmentation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4401034/" 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/PMC4401034/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lam, Felix H -- Ghaderi, Adel -- Fink, Gerald R -- Stephanopoulos, Gregory -- R01 GM035010/GM/NIGMS NIH HHS/ -- R01-GM035010/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Oct 3;346(6205):71-5. doi: 10.1126/science.1257859. Epub 2014 Oct 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA. Whitehead Institute for Biomedical Research, Cambridge, MA, USA. ; Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA. ; Whitehead Institute for Biomedical Research, Cambridge, MA, USA. gfink@wi.mit.edu gregstep@mit.edu. ; Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA. gfink@wi.mit.edu gregstep@mit.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25278607" target="_blank"〉PubMed〈/a〉
    Keywords: *Biofuels ; Cation Transport Proteins/genetics ; Cell Culture Techniques ; Cell Membrane/metabolism ; Chemical Engineering ; *Drug Resistance, Fungal/genetics ; Ethanol/*metabolism/pharmacology ; Fermentation ; Genetic Engineering ; Glucose/metabolism ; Hydrogen-Ion Concentration ; Phosphates/*metabolism ; Potassium Compounds/*metabolism ; Proton Pumps/genetics ; Proton-Translocating ATPases/genetics ; Saccharomyces cerevisiae/drug effects/genetics/*metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Up-Regulation ; Xylose/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 14
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-11-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Langer, Robert S -- Gura, Trisha -- New York, N.Y. -- Science. 2014 Nov 28;346(6213):1146. doi: 10.1126/science.346.6213.1146.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Trisha Gura is a freelance writer who lives in Boston. For more on life and careers visit www.sciencecareers.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25430772" target="_blank"〉PubMed〈/a〉
    Keywords: Biotechnology ; *Career Choice ; Chemical Engineering ; *Entrepreneurship ; *Science
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  • 15
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-01-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roberts, Richard G -- New York, N.Y. -- Science. 2014 Jan 10;343(6167):142-3. doi: 10.1126/science.1248646.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Archaeological Science, School of Earth and Environmental Sciences, University of Wollongong, Wollongong, NSW 2522, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24408422" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Australia ; *Climate Change ; Engraving and Engravings/history ; *Extinction, Biological ; Food Chain ; History, Ancient ; Humans ; Models, Biological ; Paintings/history ; *Population Dynamics ; *Wolves
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  • 16
    Publication Date: 2014-05-03
    Description: Microbial reduction of ferric iron [Fe(III)] is an important biogeochemical process in anoxic aquifers. Depending on groundwater pH, dissimilatory metal-reducing bacteria can also respire alternative electron acceptors to survive, including elemental sulfur (S(0)). To understand the interplay of Fe/S cycling under alkaline conditions, we combined thermodynamic geochemical modeling with bioreactor experiments using Shewanella oneidensis MR-1. Under these conditions, S. oneidensis can enzymatically reduce S(0) but not goethite (alpha-FeOOH). The HS(-) produced subsequently reduces goethite abiotically. Because of the prevalence of alkaline conditions in many aquifers, Fe(III) reduction may thus proceed via S(0)-mediated electron-shuttling pathways.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Flynn, Theodore M -- O'Loughlin, Edward J -- Mishra, Bhoopesh -- DiChristina, Thomas J -- Kemner, Kenneth M -- HHSN272200900040C/PHS HHS/ -- New York, N.Y. -- Science. 2014 May 30;344(6187):1039-42. doi: 10.1126/science.1252066. Epub 2014 May 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biosciences Division, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439, USA. Computation Institute, University of Chicago, Chicago, IL 60637, USA. ; Biosciences Division, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439, USA. ; Biosciences Division, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439, USA. Physics Department, Illinois Institute of Technology, Chicago, IL 60616, USA. ; School of Biology, Georgia Institute of Technology, Atlanta, GA 30332, USA. ; Biosciences Division, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439, USA. kemner@anl.gov.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24789972" target="_blank"〉PubMed〈/a〉
    Keywords: Alkalies/chemistry ; Bioreactors ; Electron Transport ; Ferric Compounds/*metabolism ; Hydrogen-Ion Concentration ; Iron/*metabolism ; Iron Compounds/metabolism ; Metabolic Networks and Pathways ; Minerals/metabolism ; Models, Biological ; Mutation ; Oxidation-Reduction ; Shewanella/*enzymology/genetics ; Sulfur/*metabolism ; Thermodynamics
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  • 17
    Publication Date: 2014-03-22
    Description: Why some individuals develop AIDS rapidly whereas others remain healthy without treatment for many years remains a central question of HIV research. An evolutionary perspective reveals an apparent conflict between two levels of selection on the virus. On the one hand, there is rapid evolution of the virus in the host, and on the other, new observations indicate the existence of virus factors that affect the virulence of infection whose influence persists over years in infected individuals and across transmission events. Here, we review recent evidence that shows that viral genetic factors play a larger role in modulating disease severity than anticipated. We propose conceptual models that reconcile adaptive evolution at both levels of selection. Evolutionary analysis provides new insight into HIV pathogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fraser, Christophe -- Lythgoe, Katrina -- Leventhal, Gabriel E -- Shirreff, George -- Hollingsworth, T Deirdre -- Alizon, Samuel -- Bonhoeffer, Sebastian -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2014 Mar 21;343(6177):1243727. doi: 10.1126/science.1243727.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London SW7 2AZ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24653038" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological ; *Evolution, Molecular ; HIV Infections/transmission/*virology ; HIV-1/*genetics/*pathogenicity/physiology ; Host-Pathogen Interactions ; Humans ; Models, Biological ; Selection, Genetic ; Viral Load ; Virulence/genetics ; Virulence Factors/physiology ; Virus Replication
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  • 18
    Publication Date: 2013-11-23
    Description: Cancer is a disease in which cells accumulate genetic aberrations that are believed to confer a clonal advantage over cells in the surrounding tissue. However, the quantitative benefit of frequently occurring mutations during tumor development remains unknown. We quantified the competitive advantage of Apc loss, Kras activation, and P53 mutations in the mouse intestine. Our findings indicate that the fate conferred by these mutations is not deterministic, and many mutated stem cells are replaced by wild-type stem cells after biased, but still stochastic events. Furthermore, P53 mutations display a condition-dependent advantage, and especially in colitis-affected intestines, clones harboring mutations in this gene are favored. Our work confirms the previously theoretical notion that the tissue architecture of the intestine suppresses the accumulation of mutated lineages.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vermeulen, Louis -- Morrissey, Edward -- van der Heijden, Maartje -- Nicholson, Anna M -- Sottoriva, Andrea -- Buczacki, Simon -- Kemp, Richard -- Tavare, Simon -- Winton, Douglas J -- Cancer Research UK/United Kingdom -- New York, N.Y. -- Science. 2013 Nov 22;342(6161):995-8. doi: 10.1126/science.1243148.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research UK, Cambridge Institute, University of Cambridge, Robinson Way, Cambridge CB2 0RE, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24264992" target="_blank"〉PubMed〈/a〉
    Keywords: Adenomatous Polyposis Coli Protein/genetics ; Animals ; Cell Transformation, Neoplastic/*genetics/*pathology ; *Gene Expression Regulation, Neoplastic ; Intestinal Neoplasms/*genetics/*pathology ; Mice ; Mice, Mutant Strains ; Models, Biological ; Mutation ; Neoplastic Stem Cells/metabolism/*pathology ; Proto-Oncogene Proteins p21(ras)/genetics ; Transcriptional Activation ; Tumor Suppressor Protein p53/genetics
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  • 19
    Publication Date: 2013-04-27
    Description: Color patterns of bird plumage affect animal behavior and speciation. Diverse patterns are present in different species and within the individual. Here, we study the cellular and molecular basis of feather pigment pattern formation. Melanocyte progenitors are distributed as a horizontal ring in the proximal follicle, sending melanocytes vertically up into the epithelial cylinder, which gradually emerges as feathers grow. Different pigment patterns form by modulating the presence, arrangement, or differentiation of melanocytes. A layer of peripheral pulp further regulates pigmentation via patterned agouti expression. Lifetime feather cyclic regeneration resets pigment patterns for physiological needs. Thus, the evolution of stem cell niche topology allows complex pigment patterning through combinatorial co-option of simple regulatory mechanisms.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4144997/" 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/PMC4144997/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lin, S J -- Foley, J -- Jiang, T X -- Yeh, C Y -- Wu, P -- Foley, A -- Yen, C M -- Huang, Y C -- Cheng, H C -- Chen, C F -- Reeder, B -- Jee, S H -- Widelitz, R B -- Chuong, C M -- AR060306/AR/NIAMS NIH HHS/ -- AR42177/AR/NIAMS NIH HHS/ -- AR47364/AR/NIAMS NIH HHS/ -- R01 AR042177/AR/NIAMS NIH HHS/ -- R01 AR047364/AR/NIAMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Jun 21;340(6139):1442-5. doi: 10.1126/science.1230374. Epub 2013 Apr 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23618762" target="_blank"〉PubMed〈/a〉
    Keywords: Agouti Signaling Protein/metabolism ; Animals ; Birds/*anatomy & histology/physiology ; Cell Differentiation ; Cell Lineage ; Cell Proliferation ; Chickens/anatomy & histology/physiology ; Columbidae/anatomy & histology/physiology ; Feathers/*cytology/growth & development ; Female ; Galliformes/anatomy & histology/physiology ; Male ; Melanocytes/*cytology/physiology ; Models, Biological ; *Pigmentation ; Regeneration ; *Stem Cell Niche ; Stem Cells/*cytology/physiology
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  • 20
    Publication Date: 2013-08-03
    Description: Insects often undergo regular outbreaks in population density but identifying the causal mechanism for such outbreaks in any particular species has proven difficult. Here, we show that outbreak cycles in the tea tortrix Adoxophyes honmai can be explained by temperature-driven changes in system stability. Wavelet analysis of a 51-year time series spanning more than 200 outbreaks reveals a threshold in outbreak amplitude each spring when temperature exceeds 15 degrees C and a secession of outbreaks each fall as temperature decreases. This is in close agreement with our independently parameterized mathematical model that predicts the system crosses a Hopf bifurcation from stability to sustained cycles as temperature increases. These results suggest that temperature can alter system stability and provide an explanation for generation cycles in multivoltine insects.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nelson, William A -- Bjornstad, Ottar N -- Yamanaka, Takehiko -- New York, N.Y. -- Science. 2013 Aug 16;341(6147):796-9. doi: 10.1126/science.1238477. Epub 2013 Aug 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Queen's University, Kingston, Ontario, Canada. nelsonw@queensu.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23907532" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Life Cycle Stages ; Models, Biological ; Moths/growth & development/*physiology ; Population Density ; Population Dynamics ; *Seasons ; *Temperature ; Wavelet Analysis
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  • 21
    Publication Date: 2013-06-08
    Description: Genome-scale network reconstruction has enabled predictive modeling of metabolism for many systems. Traditionally, protein structural information has not been represented in such reconstructions. Expansion of a genome-scale model of Escherichia coli metabolism by including experimental and predicted protein structures enabled the analysis of protein thermostability in a network context. This analysis allowed the prediction of protein activities that limit network function at superoptimal temperatures and mechanistic interpretations of mutations found in strains adapted to heat. Predicted growth-limiting factors for thermotolerance were validated through nutrient supplementation experiments and defined metabolic sensitivities to heat stress, providing evidence that metabolic enzyme thermostability is rate-limiting at superoptimal temperatures. Inclusion of structural information expanded the content and predictive capability of genome-scale metabolic networks that enable structural systems biology of metabolism.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3777776/" 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/PMC3777776/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chang, Roger L -- Andrews, Kathleen -- Kim, Donghyuk -- Li, Zhanwen -- Godzik, Adam -- Palsson, Bernhard O -- R01 GM057089/GM/NIGMS NIH HHS/ -- R01 GM101457/GM/NIGMS NIH HHS/ -- R01GM101457/GM/NIGMS NIH HHS/ -- U54 GM094586/GM/NIGMS NIH HHS/ -- U54GM094586/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Jun 7;340(6137):1220-3. doi: 10.1126/science.1234012.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bioinformatics and Systems Biology Graduate Program, University of California San Diego, La Jolla, CA 92093-0412, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23744946" target="_blank"〉PubMed〈/a〉
    Keywords: Escherichia coli/*genetics/growth & development/*metabolism ; Escherichia coli Proteins/chemistry/genetics/*metabolism ; Gene Expression Regulation, Bacterial ; *Hot Temperature ; *Metabolic Networks and Pathways ; Models, Biological ; Protein Conformation ; Systems Biology ; Transcriptional Activation
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  • 22
    Publication Date: 2013-02-09
    Description: Mutations in IDH1 and IDH2, the genes coding for isocitrate dehydrogenases 1 and 2, are common in several human cancers, including leukemias, and result in overproduction of the (R)-enantiomer of 2-hydroxyglutarate [(R)-2HG]. Elucidation of the role of IDH mutations and (R)-2HG in leukemogenesis has been hampered by a lack of appropriate cell-based models. Here, we show that a canonical IDH1 mutant, IDH1 R132H, promotes cytokine independence and blocks differentiation in hematopoietic cells. These effects can be recapitulated by (R)-2HG, but not (S)-2HG, despite the fact that (S)-2HG more potently inhibits enzymes, such as the 5'-methylcytosine hydroxylase TET2, that have previously been linked to the pathogenesis of IDH mutant tumors. We provide evidence that this paradox relates to the ability of (S)-2HG, but not (R)-2HG, to inhibit the EglN prolyl hydroxylases. Additionally, we show that transformation by (R)-2HG is reversible.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836459/" 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/PMC3836459/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Losman, Julie-Aurore -- Looper, Ryan E -- Koivunen, Peppi -- Lee, Sungwoo -- Schneider, Rebekka K -- McMahon, Christine -- Cowley, Glenn S -- Root, David E -- Ebert, Benjamin L -- Kaelin, William G Jr -- P30 DK049216/DK/NIDDK NIH HHS/ -- R01 CA068490/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Mar 29;339(6127):1621-5. doi: 10.1126/science.1231677. Epub 2013 Feb 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23393090" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics/*metabolism ; Glutarates/*metabolism ; *Hematopoiesis ; Humans ; Isocitrate Dehydrogenase/genetics/*metabolism ; Leukemia/*enzymology/genetics ; Models, Biological ; Procollagen-Proline Dioxygenase/*antagonists & inhibitors
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  • 23
    Publication Date: 2013-03-23
    Description: Biological membrane fission requires protein-driven stress. The guanosine triphosphatase (GTPase) dynamin builds up membrane stress by polymerizing into a helical collar that constricts the neck of budding vesicles. How this curvature stress mediates nonleaky membrane remodeling is actively debated. Using lipid nanotubes as substrates to directly measure geometric intermediates of the fission pathway, we found that GTP hydrolysis limits dynamin polymerization into short, metastable collars that are optimal for fission. Collars as short as two rungs translated radial constriction to reversible hemifission via membrane wedging of the pleckstrin homology domains (PHDs) of dynamin. Modeling revealed that tilting of the PHDs to conform with membrane deformations creates the low-energy pathway for hemifission. This local coordination of dynamin and lipids suggests how membranes can be remodeled in cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3980720/" 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/PMC3980720/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shnyrova, Anna V -- Bashkirov, Pavel V -- Akimov, Sergey A -- Pucadyil, Thomas J -- Zimmerberg, Joshua -- Schmid, Sandra L -- Frolov, Vadim A -- GM42455/GM/NIGMS NIH HHS/ -- R01 GM042455/GM/NIGMS NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2013 Mar 22;339(6126):1433-6. doi: 10.1126/science.1233920.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biophysics Unit (CSIC, UPV/EHU) and Department of Biochemistry and Molecular Biology, University of the Basque Country, Leioa, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23520112" target="_blank"〉PubMed〈/a〉
    Keywords: Biocatalysis ; Dynamin I/*chemistry/*metabolism ; Guanosine Triphosphate/metabolism ; Hydrolysis ; Lipid Bilayers/chemistry/*metabolism ; Models, Biological ; Nanotubes ; Protein Conformation ; Protein Multimerization ; Protein Structure, Tertiary ; Thermodynamics
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  • 24
    Publication Date: 2013-06-08
    Description: Colonial breeding is widespread among animals. Some, such as eusocial insects, may use agonistic behavior to partition available foraging habitat into mutually exclusive territories; others, such as breeding seabirds, do not. We found that northern gannets, satellite-tracked from 12 neighboring colonies, nonetheless forage in largely mutually exclusive areas and that these colony-specific home ranges are determined by density-dependent competition. This segregation may be enhanced by individual-level public information transfer, leading to cultural evolution and divergence among colonies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wakefield, Ewan D -- Bodey, Thomas W -- Bearhop, Stuart -- Blackburn, Jez -- Colhoun, Kendrew -- Davies, Rachel -- Dwyer, Ross G -- Green, Jonathan A -- Gremillet, David -- Jackson, Andrew L -- Jessopp, Mark J -- Kane, Adam -- Langston, Rowena H W -- Lescroel, Amelie -- Murray, Stuart -- Le Nuz, Melanie -- Patrick, Samantha C -- Peron, Clara -- Soanes, Louise M -- Wanless, Sarah -- Votier, Stephen C -- Hamer, Keith C -- New York, N.Y. -- Science. 2013 Jul 5;341(6141):68-70. doi: 10.1126/science.1236077. Epub 2013 Jun 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Biology, University of Leeds, Leeds, UK. e.d.wakefield@leeds.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23744776" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Birds/*physiology ; Breeding ; *Feeding Behavior ; *Homing Behavior ; Models, Biological ; *Territoriality
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  • 25
    Publication Date: 2013-01-12
    Description: The relationship between phenotype and fitness can be visualized as a rugged landscape. Multiple fitness peaks on this landscape are predicted to drive early bursts of niche diversification during adaptive radiation. We measured the adaptive landscape in a nascent adaptive radiation of Cyprinodon pupfishes endemic to San Salvador Island, Bahamas, and found multiple coexisting high-fitness regions driven by increased competition at high densities, supporting the early burst model. Hybrids resembling the generalist phenotype were isolated on a local fitness peak separated by a valley from a higher-fitness region corresponding to trophic specialization. This complex landscape could explain both the rarity of specialists across many similar environments due to stabilizing selection on generalists and the rapid morphological diversification rate of specialists due to their higher fitness.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Martin, Christopher H -- Wainwright, Peter C -- New York, N.Y. -- Science. 2013 Jan 11;339(6116):208-11. doi: 10.1126/science.1227710.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Evolution and Ecology and Center for Population Biology, University of California, One Shields Avenue, Davis, CA, USA. chmartin@ucdavis.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23307743" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological/*genetics ; Animals ; Bahamas ; *Biological Evolution ; Crosses, Genetic ; Ecosystem ; Environment ; Female ; *Genetic Fitness ; Genetic Speciation ; Hybridization, Genetic ; Killifishes/*genetics/*physiology ; Lakes ; Male ; Models, Biological ; Phenotype ; Selection, Genetic
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  • 26
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-11-16
    Description: Experimental studies of evolution have increased greatly in number in recent years, stimulated by the growing power of genomic tools. However, organismal fitness remains the ultimate metric for interpreting these experiments, and the dynamics of fitness remain poorly understood over long time scales. Here, we examine fitness trajectories for 12 Escherichia coli populations during 50,000 generations. Mean fitness appears to increase without bound, consistent with a power law. We also derive this power-law relation theoretically by incorporating clonal interference and diminishing-returns epistasis into a dynamical model of changes in mean fitness over time.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wiser, Michael J -- Ribeck, Noah -- Lenski, Richard E -- New York, N.Y. -- Science. 2013 Dec 13;342(6164):1364-7. doi: 10.1126/science.1243357. Epub 2013 Nov 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉BEACON Center for the Study of Evolution in Action, Michigan State University, East Lansing, MI 48824, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24231808" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptation, Physiological ; Escherichia coli/*genetics/*physiology ; *Genetic Fitness ; Models, Biological ; *Reproduction, Asexual
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  • 27
    Publication Date: 2013-01-26
    Description: Signaling pathways can induce different dynamics of transcription factor (TF) activation. We explored how TFs process signaling inputs to generate diverse dynamic responses. The budding yeast general stress-responsive TF Msn2 acted as a tunable signal processor that could track, filter, or integrate signals in an input-dependent manner. This tunable signal processing appears to originate from dual regulation of both nuclear import and export by phosphorylation, as mutants with one form of regulation sustained only one signal-processing function. Versatile signal processing by Msn2 is crucial for generating distinct dynamic responses to different natural stresses. Our findings reveal how complex signal-processing functions are integrated into a single molecule and provide a guide for the design of TFs with "programmable" signal-processing functions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3746486/" 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/PMC3746486/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hao, Nan -- Budnik, Bogdan A -- Gunawardena, Jeremy -- O'Shea, Erin K -- R01 GM081578/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Jan 25;339(6118):460-4. doi: 10.1126/science.1227299.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Harvard University Faculty of Arts and Sciences Center for Systems Biology, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23349292" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Cell Nucleus/*metabolism ; Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors/genetics/metabolism ; Cytoplasm/metabolism ; DNA-Binding Proteins/*metabolism ; Models, Biological ; Nuclear Export Signals ; Nuclear Localization Signals ; Osmotic Pressure ; Oxidative Stress ; Phosphorylation ; Proteins/pharmacology ; Saccharomyces cerevisiae/genetics/*metabolism ; Saccharomyces cerevisiae Proteins/*metabolism ; *Signal Transduction ; Stress, Physiological ; Transcription Factors/*metabolism
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  • 28
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-07-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stone, Richard -- New York, N.Y. -- Science. 2013 Jul 19;341(6143):230-3. doi: 10.1126/science.341.6143.230.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23868998" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Armadillos ; *Extinction, Biological ; Marine Biology ; Marsupialia ; Models, Biological ; Panama ; *Phylogeography ; Porcupines
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  • 29
    Publication Date: 2013-10-19
    Description: The vast extent of the Amazon Basin has historically restricted the study of its tree communities to the local and regional scales. Here, we provide empirical data on the commonness, rarity, and richness of lowland tree species across the entire Amazon Basin and Guiana Shield (Amazonia), collected in 1170 tree plots in all major forest types. Extrapolations suggest that Amazonia harbors roughly 16,000 tree species, of which just 227 (1.4%) account for half of all trees. Most of these are habitat specialists and only dominant in one or two regions of the basin. We discuss some implications of the finding that a small group of species--less diverse than the North American tree flora--accounts for half of the world's most diverse tree community.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉ter Steege, Hans -- Pitman, Nigel C A -- Sabatier, Daniel -- Baraloto, Christopher -- Salomao, Rafael P -- Guevara, Juan Ernesto -- Phillips, Oliver L -- Castilho, Carolina V -- Magnusson, William E -- Molino, Jean-Francois -- Monteagudo, Abel -- Nunez Vargas, Percy -- Montero, Juan Carlos -- Feldpausch, Ted R -- Coronado, Euridice N Honorio -- Killeen, Tim J -- Mostacedo, Bonifacio -- Vasquez, Rodolfo -- Assis, Rafael L -- Terborgh, John -- Wittmann, Florian -- Andrade, Ana -- Laurance, William F -- Laurance, Susan G W -- Marimon, Beatriz S -- Marimon, Ben-Hur Jr -- Guimaraes Vieira, Ima Celia -- Amaral, Ieda Leao -- Brienen, Roel -- Castellanos, Hernan -- Cardenas Lopez, Dairon -- Duivenvoorden, Joost F -- Mogollon, Hugo F -- Matos, Francisca Dionizia de Almeida -- Davila, Nallarett -- Garcia-Villacorta, Roosevelt -- Stevenson Diaz, Pablo Roberto -- Costa, Flavia -- Emilio, Thaise -- Levis, Carolina -- Schietti, Juliana -- Souza, Priscila -- Alonso, Alfonso -- Dallmeier, Francisco -- Montoya, Alvaro Javier Duque -- Fernandez Piedade, Maria Teresa -- Araujo-Murakami, Alejandro -- Arroyo, Luzmila -- Gribel, Rogerio -- Fine, Paul V A -- Peres, Carlos A -- Toledo, Marisol -- Aymard C, Gerardo A -- Baker, Tim R -- Ceron, Carlos -- Engel, Julien -- Henkel, Terry W -- Maas, Paul -- Petronelli, Pascal -- Stropp, Juliana -- Zartman, Charles Eugene -- Daly, Doug -- Neill, David -- Silveira, Marcos -- Paredes, Marcos Rios -- Chave, Jerome -- Lima Filho, Diogenes de Andrade -- Jorgensen, Peter Moller -- Fuentes, Alfredo -- Schongart, Jochen -- Cornejo Valverde, Fernando -- Di Fiore, Anthony -- Jimenez, Eliana M -- Penuela Mora, Maria Cristina -- Phillips, Juan Fernando -- Rivas, Gonzalo -- van Andel, Tinde R -- von Hildebrand, Patricio -- Hoffman, Bruce -- Zent, Eglee L -- Malhi, Yadvinder -- Prieto, Adriana -- Rudas, Agustin -- Ruschell, Ademir R -- Silva, Natalino -- Vos, Vincent -- Zent, Stanford -- Oliveira, Alexandre A -- Schutz, Angela Cano -- Gonzales, Therany -- Trindade Nascimento, Marcelo -- Ramirez-Angulo, Hirma -- Sierra, Rodrigo -- Tirado, Milton -- Umana Medina, Maria Natalia -- van der Heijden, Geertje -- Vela, Cesar I A -- Vilanova Torre, Emilio -- Vriesendorp, Corine -- Wang, Ophelia -- Young, Kenneth R -- Baider, Claudia -- Balslev, Henrik -- Ferreira, Cid -- Mesones, Italo -- Torres-Lezama, Armando -- Urrego Giraldo, Ligia Estela -- Zagt, Roderick -- Alexiades, Miguel N -- Hernandez, Lionel -- Huamantupa-Chuquimaco, Isau -- Milliken, William -- Palacios Cuenca, Walter -- Pauletto, Daniela -- Valderrama Sandoval, Elvis -- Valenzuela Gamarra, Luis -- Dexter, Kyle G -- Feeley, Ken -- Lopez-Gonzalez, Gabriela -- Silman, Miles R -- New York, N.Y. -- Science. 2013 Oct 18;342(6156):1243092. doi: 10.1126/science.1243092.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Naturalis Biodiversity Center, Leiden, Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24136971" target="_blank"〉PubMed〈/a〉
    Keywords: *Biodiversity ; Models, Biological ; Population ; *Rivers ; South America ; Trees/*classification/*physiology
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  • 30
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-05-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Min -- Schekman, Randy -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 May 3;340(6132):559-61. doi: 10.1126/science.1234740.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720-3370, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23641104" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autophagy ; Carrier Proteins/metabolism ; Cell Membrane/metabolism/*secretion ; Exosomes/metabolism ; Lysosomes/metabolism ; Membrane Fusion ; Membrane Proteins/metabolism ; Membrane Transport Proteins/metabolism ; Models, Biological ; Phagosomes/metabolism ; Proteins/*metabolism/*secretion ; *Secretory Pathway ; Secretory Vesicles/metabolism
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  • 31
    Publication Date: 2013-08-31
    Description: The villi of the human and chick gut are formed in similar stepwise progressions, wherein the mesenchyme and attached epithelium first fold into longitudinal ridges, then a zigzag pattern, and lastly individual villi. We find that these steps of villification depend on the sequential differentiation of the distinct smooth muscle layers of the gut, which restrict the expansion of the growing endoderm and mesenchyme, generating compressive stresses that lead to their buckling and folding. A quantitative computational model, incorporating measured properties of the developing gut, recapitulates the morphological patterns seen during villification in a variety of species. These results provide a mechanistic understanding of the formation of these elaborations of the lining of the gut, essential for providing sufficient surface area for nutrient absorption.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4045245/" 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/PMC4045245/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shyer, Amy E -- Tallinen, Tuomas -- Nerurkar, Nandan L -- Wei, Zhiyan -- Gil, Eun Seok -- Kaplan, David L -- Tabin, Clifford J -- Mahadevan, L -- R01 HD047360/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2013 Oct 11;342(6155):212-8. doi: 10.1126/science.1238842. Epub 2013 Aug 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23989955" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chick Embryo ; Endoderm/growth & development ; Gastrointestinal Tract/*embryology/*ultrastructure ; Humans ; Mesoderm/growth & development ; Mice ; Models, Biological ; *Morphogenesis ; Muscle, Smooth/*embryology ; Xenopus
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  • 32
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-06-08
    Description: Epithelia are robust tissues that support the structure of embryos and organs and serve as effective barriers against pathogens. Epithelia also chemically separate different physiological environments. These vital functions require tight association between cells through the assembly of junctions that mechanically stabilize the tissue. Remarkably, epithelia are also dynamic and can display a fluid behavior. Cells continuously die or divide, thereby allowing functional tissue homeostasis. Epithelial cells can change shape or intercalate as tissues deform during morphogenesis. We review the mechanical basis of tissue robustness and fluidity, with an emphasis on the pivotal role of junction dynamics. Tissue fluidity emerges from local active stresses acting at cell interfaces and allows the maintenance of epithelial organization during morphogenesis and tissue renewal.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guillot, Charlene -- Lecuit, Thomas -- New York, N.Y. -- Science. 2013 Jun 7;340(6137):1185-9. doi: 10.1126/science.1235249.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Aix-Marseille Universite, CNRS UMR 7288, IBDM, Campus de Luminy, Marseille, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23744939" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cadherins/chemistry/ultrastructure ; Cell Division ; Chick Embryo ; Drosophila/cytology/embryology ; Epithelial Cells/cytology ; Epithelium/*growth & development ; *Homeostasis ; Intercellular Junctions ; Models, Biological ; *Morphogenesis ; Neural Tube/growth & development
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  • 33
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-06-08
    Description: Morphogenesis, the development of the shape of an organism, is a dynamic process on a multitude of scales, from fast subcellular rearrangements and cell movements to slow structural changes at the whole-organism level. Live-imaging approaches based on light microscopy reveal the intricate dynamics of this process and are thus indispensable for investigating the underlying mechanisms. This Review discusses emerging imaging techniques that can record morphogenesis at temporal scales from seconds to days and at spatial scales from hundreds of nanometers to several millimeters. To unlock their full potential, these methods need to be matched with new computational approaches and physical models that help convert highly complex image data sets into biological insights.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Keller, Philipp J -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Jun 7;340(6137):1234168. doi: 10.1126/science.1234168.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, VA 20147, USA. kellerp@janelia.hhmi.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23744952" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Drosophila/embryology ; Image Processing, Computer-Assisted/*methods ; Mice/embryology ; Microscopy/*methods ; Models, Biological ; *Morphogenesis ; Zebrafish/embryology
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  • 34
    Publication Date: 2013-11-30
    Description: To predict the emergence of antibiotic resistance, quantitative relations must be established between the fitness of drug-resistant organisms and the molecular mechanisms conferring resistance. These relations are often unknown and may depend on the state of bacterial growth. To bridge this gap, we have investigated Escherichia coli strains expressing resistance to translation-inhibiting antibiotics. We show that resistance expression and drug inhibition are linked in a positive feedback loop arising from an innate, global effect of drug-inhibited growth on gene expression. A quantitative model of bacterial growth based on this innate feedback accurately predicts the rich phenomena observed: a plateau-shaped fitness landscape, with an abrupt drop in the growth rates of cultures at a threshold drug concentration, and the coexistence of growing and nongrowing populations, that is, growth bistability, below the threshold.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059556/" 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/PMC4059556/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Deris, J Barrett -- Kim, Minsu -- Zhang, Zhongge -- Okano, Hiroyuki -- Hermsen, Rutger -- Groisman, Alexander -- Hwa, Terence -- 1 U54 CA143803/CA/NCI NIH HHS/ -- R01 GM095903/GM/NIGMS NIH HHS/ -- R01-GM095903/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Nov 29;342(6162):1237435. doi: 10.1126/science.1237435.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, University of California at San Diego, La Jolla, CA 92093-0374, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24288338" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptation, Physiological ; Chloramphenicol/metabolism/pharmacology ; Chloramphenicol O-Acetyltransferase/biosynthesis ; *Drug Resistance, Bacterial ; Escherichia coli/*drug effects/genetics/*growth & development ; Gene Expression Regulation, Bacterial/drug effects ; *Genetic Fitness ; Models, Biological ; Protein Biosynthesis/drug effects ; Protein Synthesis Inhibitors/metabolism/*pharmacology
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  • 35
    Publication Date: 2013-04-27
    Description: Broad-scale environmental changes are altering patterns of natural selection in the wild, but few empirical studies have quantified the demographic cost of sustained directional selection in response to these changes. We tested whether population growth in a wild bird is negatively affected by climate change-induced phenological mismatch, using almost four decades of individual-level life-history data from a great tit population. In this population, warmer springs have generated a mismatch between the annual breeding time and the seasonal food peak, intensifying directional selection for earlier laying dates. Interannual variation in population mismatch has not, however, affected population growth. We demonstrated a mechanism contributing to this uncoupling, whereby fitness losses associated with mismatch are counteracted by fitness gains due to relaxed competition. These findings imply that natural populations may be able to tolerate considerable maladaptation driven by shifting climatic conditions without undergoing immediate declines.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reed, Thomas E -- Grotan, Vidar -- Jenouvrier, Stephanie -- Saether, Bernt-Erik -- Visser, Marcel E -- New York, N.Y. -- Science. 2013 Apr 26;340(6131):488-91. doi: 10.1126/science.1232870.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Animal Ecology, Netherlands Institute of Ecology, Wageningen, Netherlands. t.reed@nioo.knaw.nl〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23620055" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Breeding ; *Climate Change ; Computer Simulation ; Female ; *Genetic Fitness ; Models, Biological ; Passeriformes/genetics/*physiology ; Population Growth ; *Selection, Genetic
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  • 36
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-07-03
    Description: Protein synthesis by the ribosome requires the translocation of transfer RNAs and messenger RNA by one codon after each peptide bond is formed, a reaction that requires ribosomal subunit rotation and is catalyzed by the guanosine triphosphatase (GTPase) elongation factor G (EF-G). We determined 3 angstrom resolution x-ray crystal structures of EF-G complexed with a nonhydrolyzable guanosine 5'-triphosphate (GTP) analog and bound to the Escherichia coli ribosome in different states of ribosomal subunit rotation. The structures reveal that EF-G binding to the ribosome stabilizes switch regions in the GTPase active site, resulting in a compact EF-G conformation that favors an intermediate state of ribosomal subunit rotation. These structures suggest that EF-G controls the translocation reaction by cycles of conformational rigidity and relaxation before and after GTP hydrolysis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4274944/" 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/PMC4274944/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pulk, Arto -- Cate, Jamie H D -- R01 GM065050/GM/NIGMS NIH HHS/ -- R01 GM105404/GM/NIGMS NIH HHS/ -- R01-GM65050/GM/NIGMS NIH HHS/ -- R01GM105404/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Jun 28;340(6140):1235970. doi: 10.1126/science.1235970.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23812721" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography, X-Ray ; Escherichia coli/*enzymology ; Guanosine Triphosphate/*chemistry ; Hydrolysis ; Models, Biological ; Peptide Elongation Factor G/*chemistry ; *Protein Biosynthesis ; Protein Conformation ; Protein Structure, Tertiary ; RNA, Messenger/chemistry ; RNA, Transfer/chemistry ; Ribosome Subunits, Large, Bacterial/*chemistry ; Rotation
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 37
    Publication Date: 2013-06-15
    Description: Extended breath-hold endurance enables the exploitation of the aquatic niche by numerous mammalian lineages and is accomplished by elevated body oxygen stores and adaptations that promote their economical use. However, little is known regarding the molecular and evolutionary underpinnings of the high muscle myoglobin concentration phenotype of divers. We used ancestral sequence reconstruction to trace the evolution of this oxygen-storing protein across a 130-species mammalian phylogeny and reveal an adaptive molecular signature of elevated myoglobin net surface charge in diving species that is mechanistically linked with maximal myoglobin concentration. This observation provides insights into the tempo and routes to enhanced dive capacity evolution within the ancestors of each major mammalian aquatic lineage and infers amphibious ancestries of echidnas, moles, hyraxes, and elephants, offering a fresh perspective on the evolution of this iconic respiratory pigment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mirceta, Scott -- Signore, Anthony V -- Burns, Jennifer M -- Cossins, Andrew R -- Campbell, Kevin L -- Berenbrink, Michael -- Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2013 Jun 14;340(6138):1234192. doi: 10.1126/science.1234192.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23766330" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; *Biological Evolution ; *Diving ; Evolution, Molecular ; Mammals/*genetics/*physiology ; Models, Biological ; Molecular Sequence Data ; Muscle, Skeletal/chemistry ; Myoglobin/analysis/*chemistry/*classification ; Phylogeny
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  • 38
    Publication Date: 2013-08-31
    Description: Tissues can be soft like fat, which bears little stress, or stiff like bone, which sustains high stress, but whether there is a systematic relationship between tissue mechanics and differentiation is unknown. Here, proteomics analyses revealed that levels of the nucleoskeletal protein lamin-A scaled with tissue elasticity, E, as did levels of collagens in the extracellular matrix that determine E. Stem cell differentiation into fat on soft matrix was enhanced by low lamin-A levels, whereas differentiation into bone on stiff matrix was enhanced by high lamin-A levels. Matrix stiffness directly influenced lamin-A protein levels, and, although lamin-A transcription was regulated by the vitamin A/retinoic acid (RA) pathway with broad roles in development, nuclear entry of RA receptors was modulated by lamin-A protein. Tissue stiffness and stress thus increase lamin-A levels, which stabilize the nucleus while also contributing to lineage determination.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3976548/" 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/PMC3976548/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Swift, Joe -- Ivanovska, Irena L -- Buxboim, Amnon -- Harada, Takamasa -- Dingal, P C Dave P -- Pinter, Joel -- Pajerowski, J David -- Spinler, Kyle R -- Shin, Jae-Won -- Tewari, Manorama -- Rehfeldt, Florian -- Speicher, David W -- Discher, Dennis E -- 8UL1TR000003/TR/NCATS NIH HHS/ -- CA010815/CA/NCI NIH HHS/ -- HL038794/HL/NHLBI NIH HHS/ -- P01DK032094/DK/NIDDK NIH HHS/ -- P30-DK090969/DK/NIDDK NIH HHS/ -- R01 EB007049/EB/NIBIB NIH HHS/ -- R01 HL062352/HL/NHLBI NIH HHS/ -- R01EB007049/EB/NIBIB NIH HHS/ -- R01HL062352/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2013 Aug 30;341(6149):1240104. doi: 10.1126/science.1240104.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular and Cell Biophysics Laboratory, University of Pennsylvania, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23990565" target="_blank"〉PubMed〈/a〉
    Keywords: Adipogenesis ; Animals ; *Cell Differentiation ; Collagen/analysis/chemistry/metabolism ; *Elasticity ; Extracellular Matrix/chemistry/metabolism ; Gene Expression Regulation, Developmental ; Humans ; Lamin Type A/chemistry/genetics/*metabolism ; Mesenchymal Stromal Cells/*cytology ; Mice ; Models, Biological ; Nuclear Lamina/metabolism ; *Osteogenesis/genetics ; Protein Conformation ; Proteome ; *Stress, Mechanical ; Transcription, Genetic ; Tretinoin/metabolism ; Vitamin A/metabolism
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  • 39
    Publication Date: 2013-07-06
    Description: A low-error 16S ribosomal RNA amplicon sequencing method, in combination with whole-genome sequencing of 〉500 cultured isolates, was used to characterize bacterial strain composition in the fecal microbiota of 37 U.S. adults sampled for up to 5 years. Microbiota stability followed a power-law function, which when extrapolated suggests that most strains in an individual are residents for decades. Shared strains were recovered from family members but not from unrelated individuals. Sampling of individuals who consumed a monotonous liquid diet for up to 32 weeks indicated that changes in strain composition were better predicted by changes in weight than by differences in sampling interval. This combination of stability and responsiveness to physiologic change confirms the potential of the gut microbiota as a diagnostic tool and therapeutic target.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3791589/" 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/PMC3791589/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Faith, Jeremiah J -- Guruge, Janaki L -- Charbonneau, Mark -- Subramanian, Sathish -- Seedorf, Henning -- Goodman, Andrew L -- Clemente, Jose C -- Knight, Rob -- Heath, Andrew C -- Leibel, Rudolph L -- Rosenbaum, Michael -- Gordon, Jeffrey I -- DK078669/DK/NIDDK NIH HHS/ -- DK30292/DK/NIDDK NIH HHS/ -- DK64774/DK/NIDDK NIH HHS/ -- DK70977/DK/NIDDK NIH HHS/ -- K05 AA017688/AA/NIAAA NIH HHS/ -- P01 DK078669/DK/NIDDK NIH HHS/ -- P30 DK026687/DK/NIDDK NIH HHS/ -- P60 DK020541/DK/NIDDK NIH HHS/ -- R01 DK064773/DK/NIDDK NIH HHS/ -- R01 DK070977/DK/NIDDK NIH HHS/ -- R37 DK030292/DK/NIDDK NIH HHS/ -- UL1TR000040/TR/NCATS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Jul 5;341(6141):1237439. doi: 10.1126/science.1237439.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23828941" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Bacteria/classification/genetics/isolation & purification ; Body Composition ; Caloric Restriction ; Family ; Feces/microbiology ; Female ; Gastrointestinal Tract/*microbiology ; Genome, Bacterial/genetics ; Genomic Instability ; Humans ; Male ; *Metagenome ; Models, Biological ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Time Factors ; Weight Loss ; Young Adult
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  • 40
    Publication Date: 2012-06-30
    Description: Metabolic engineering of plants can reduce the cost and environmental impact of agriculture while providing for the needs of a growing population. Although our understanding of plant metabolism continues to increase at a rapid pace, relatively few plant metabolic engineering projects with commercial potential have emerged, in part because of a lack of principles for the rational manipulation of plant phenotype. One underexplored approach to identifying such design principles derives from analysis of the dominant constraints on plant fitness, and the evolutionary innovations in response to those constraints, that gave rise to the enormous diversity of natural plant metabolic pathways.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Milo, Ron -- Last, Robert L -- 260392/European Research Council/International -- New York, N.Y. -- Science. 2012 Jun 29;336(6089):1663-7. doi: 10.1126/science.1217665.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Sciences, Weizmann Institute of Science, Rehovot 76100, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22745419" target="_blank"〉PubMed〈/a〉
    Keywords: *Biodiversity ; Evolution, Molecular ; Metabolic Engineering ; Models, Biological ; Plants/*metabolism
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  • 41
    Publication Date: 2012-03-31
    Description: The occurrence and magnitude of disease outbreaks can strongly influence host evolution. In particular, when hosts face a resistance-fecundity trade-off, they might evolve increased resistance to infection during larger epidemics but increased susceptibility during smaller ones. We tested this theoretical prediction by using a zooplankton-yeast host-parasite system in which ecological factors determine epidemic size. Lakes with high productivity and low predation pressure had large yeast epidemics; during these outbreaks, hosts became more resistant to infection. However, with low productivity and high predation, epidemics remained small and hosts evolved increased susceptibility. Thus, by modulating disease outbreaks, ecological context (productivity and predation) shaped host evolution during epidemics. Consequently, anthropogenic alteration of productivity and predation might strongly influence both ecological and evolutionary outcomes of disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Duffy, Meghan A -- Ochs, Jessica Housley -- Penczykowski, Rachel M -- Civitello, David J -- Klausmeier, Christopher A -- Hall, Spencer R -- New York, N.Y. -- Science. 2012 Mar 30;335(6076):1636-8. doi: 10.1126/science.1215429.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Biology, Georgia Institute of Technology, Atlanta, GA 30332-0230, USA. duffy@gatech.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22461614" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Daphnia/*microbiology/*physiology ; *Ecosystem ; Female ; Fishes ; *Host-Pathogen Interactions ; Indiana ; *Lakes ; Male ; Metschnikowia/*pathogenicity ; Models, Biological ; Population Dynamics ; Predatory Behavior ; Reproduction ; Zooplankton/microbiology/physiology
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  • 42
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2012-11-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Savage, Phillip E -- New York, N.Y. -- Science. 2012 Nov 23;338(6110):1039-40. doi: 10.1126/science.1224310.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Chemical Engineering Department, University of Michigan, Ann Arbor, MI 48109, USA. psavage@umich.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23180853" target="_blank"〉PubMed〈/a〉
    Keywords: *Biofuels ; Cell Culture Techniques ; Chemical Engineering ; Chlorophyta/*chemistry/growth & development ; *Hot Temperature ; *Hydrostatic Pressure ; *Water
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  • 43
    Publication Date: 2012-04-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vinson, Valda -- Purnell, Beverly A -- Zahn, Laura M -- Travis, John -- New York, N.Y. -- Science. 2012 Apr 13;336(6078):171. doi: 10.1126/science.336.6078.171.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22499935" target="_blank"〉PubMed〈/a〉
    Keywords: *Computational Biology ; Computer Simulation ; Genomics ; Models, Biological ; Morphogenesis
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  • 44
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2012-07-24
    Description: Ecological theory predicts that a complex community formed by a number of species is inherently unstable, guiding ecologists to identify what maintains species diversity in nature. Earlier studies often assumed a community with only one interaction type, either an antagonistic, competitive, or mutualistic interaction, leaving open the question of what the diversity of interaction types contributes to the community maintenance. We show theoretically that the multiple interaction types might hold the key to understanding community dynamics. A moderate mixture of antagonistic and mutualistic interactions can stabilize population dynamics. Furthermore, increasing complexity leads to increased stability in a "hybrid" community. We hypothesize that the diversity of species and interaction types may be the essential element of biodiversity that maintains ecological communities.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mougi, A -- Kondoh, M -- New York, N.Y. -- Science. 2012 Jul 20;337(6092):349-51. doi: 10.1126/science.1220529.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Environmental Solution Technology, Faculty of Science and Technology, Ryukoku University, 1-5 Yokoya, Seta Oe-cho, Otsu 520-2194, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22822151" target="_blank"〉PubMed〈/a〉
    Keywords: *Biodiversity ; *Biota ; Models, Biological ; Population Dynamics
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  • 45
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2012-09-08
    Description: Cells have developed ways to sense and control the size of their organelles. Size-sensing mechanisms range from direct measurements provided by dedicated reporters to indirect functional readouts, and they are used to modify organelle size under both normal and stress conditions. Organelle size can also be controlled in the absence of an identifiable size sensor. Studies on flagella have dissected principles of size sensing and control, and it will be exciting to see how these principles apply to other organelles.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3625396/" 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/PMC3625396/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chan, Yee-Hung M -- Marshall, Wallace F -- 1F32GM090442-01A1/GM/NIGMS NIH HHS/ -- P50 GM081879/GM/NIGMS NIH HHS/ -- P50GM081879/GM/NIGMS NIH HHS/ -- R01 GM097017/GM/NIGMS NIH HHS/ -- R01GM097017/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 Sep 7;337(6099):1186-9. doi: 10.1126/science.1223539.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, UCSF Center for Systems and Synthetic Biology, University of California, San Francisco, San Francisco, CA 94158, USA. yhmchan@ucsf.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22955827" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Transport ; *Cell Physiological Phenomena ; Flagella/metabolism/physiology/ultrastructure ; Humans ; Models, Biological ; *Organelle Size ; *Organelles/chemistry/metabolism/ultrastructure
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  • 46
    Publication Date: 2012-04-14
    Description: The mechanism of ion channel voltage gating-how channels open and close in response to voltage changes-has been debated since Hodgkin and Huxley's seminal discovery that the crux of nerve conduction is ion flow across cellular membranes. Using all-atom molecular dynamics simulations, we show how a voltage-gated potassium channel (KV) switches between activated and deactivated states. On deactivation, pore hydrophobic collapse rapidly halts ion flow. Subsequent voltage-sensing domain (VSD) relaxation, including inward, 15-angstrom S4-helix motion, completes the transition. On activation, outward S4 motion tightens the VSD-pore linker, perturbing linker-S6-helix packing. Fluctuations allow water, then potassium ions, to reenter the pore; linker-S6 repacking stabilizes the open pore. We propose a mechanistic model for the sodium/potassium/calcium voltage-gated ion channel superfamily that reconciles apparently conflicting experimental data.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jensen, Morten O -- Jogini, Vishwanath -- Borhani, David W -- Leffler, Abba E -- Dror, Ron O -- Shaw, David E -- New York, N.Y. -- Science. 2012 Apr 13;336(6078):229-33. doi: 10.1126/science.1216533.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉D E Shaw Research, New York, NY 10036, USA. morten.jensen@DEShawResearch.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22499946" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Hydrophobic and Hydrophilic Interactions ; *Ion Channel Gating ; Kv1.2 Potassium Channel/*chemistry/*metabolism ; Membrane Potentials ; Models, Biological ; Models, Molecular ; Molecular Dynamics Simulation ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Rats ; Recombinant Fusion Proteins/chemistry/metabolism ; Shab Potassium Channels/*chemistry/*metabolism
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  • 47
    Publication Date: 2012-05-05
    Description: Although the network topology of metabolism is well known, understanding the principles that govern the distribution of fluxes through metabolism lags behind. Experimentally, these fluxes can be measured by (13)C-flux analysis, and there has been a long-standing interest in understanding this functional network operation from an evolutionary perspective. On the basis of (13)C-determined fluxes from nine bacteria and multi-objective optimization theory, we show that metabolism operates close to the Pareto-optimal surface of a three-dimensional space defined by competing objectives. Consistent with flux data from evolved Escherichia coli, we propose that flux states evolve under the trade-off between two principles: optimality under one given condition and minimal adjustment between conditions. These principles form the forces by which evolution shapes metabolic fluxes in microorganisms' environmental context.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schuetz, Robert -- Zamboni, Nicola -- Zampieri, Mattia -- Heinemann, Matthias -- Sauer, Uwe -- New York, N.Y. -- Science. 2012 May 4;336(6081):601-4. doi: 10.1126/science.1216882.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Systems Biology, Eidgenossische Technische Hochschule Zurich, Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22556256" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological ; Adenosine Triphosphate/metabolism ; Aerobiosis ; Algorithms ; Bacteria/growth & development/*metabolism ; *Biological Evolution ; Biomass ; Computer Simulation ; Escherichia coli/genetics/growth & development/*metabolism ; Glucose/metabolism ; *Metabolic Networks and Pathways ; Models, Biological
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  • 48
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2012-11-03
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3705936/" 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/PMC3705936/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baudisch, Annette -- Vaupel, James W -- AG-031719/AG/NIA NIH HHS/ -- P01 AG031719/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2012 Nov 2;338(6107):618-9. doi: 10.1126/science.1226467.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Research Group for Modeling the Evolution of Aging, Rostock, Germany. baudisch@demogr.mpg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23118175" target="_blank"〉PubMed〈/a〉
    Keywords: *Aging ; Animals ; *Biological Evolution ; Fertility ; Humans ; Models, Biological ; Mortality ; Reproduction
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  • 49
    Publication Date: 2012-03-03
    Description: Over 90 capsular serotypes of Streptococcus pneumoniae, a common nasopharyngeal colonizer and major cause of pneumonia, bacteremia, and meningitis, are known. It is unclear why some serotypes can persist at all: They are more easily cleared from carriage and compete poorly in vivo. Serotype-specific immune responses, which could promote diversity in principle, are weak enough to allow repeated colonizations by the same type. We show that weak serotype-specific immunity and an acquired response not specific to the capsule can together reproduce observed diversity. Serotype-specific immunity stabilizes competition, and acquired immunity to noncapsular antigens reduces fitness differences. Our model can be used to explain the effects of pneumococcal vaccination and indicates general factors that regulate the diversity of pathogens.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3341938/" 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/PMC3341938/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cobey, Sarah -- Lipsitch, Marc -- 1F32GM097997/GM/NIGMS NIH HHS/ -- 5R01AI048935/AI/NIAID NIH HHS/ -- F32 GM097997/GM/NIGMS NIH HHS/ -- U54 GM088558/GM/NIGMS NIH HHS/ -- U54 GM088558-02/GM/NIGMS NIH HHS/ -- U54GM088558/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 Mar 16;335(6074):1376-80. doi: 10.1126/science.1215947. Epub 2012 Mar 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Communicable Disease Dynamics and Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA. scobey@hsph.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22383809" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptive Immunity ; Adult ; Antigenic Variation ; Antigens, Bacterial/*immunology ; Bacterial Capsules/immunology ; Carrier State/immunology/*microbiology ; Child ; Child, Preschool ; Computer Simulation ; Humans ; Immunity, Innate ; Infant ; Models, Biological ; Nasopharynx/*microbiology ; Pneumococcal Infections/immunology/*microbiology ; Pneumococcal Vaccines/immunology ; Serotyping ; Streptococcus pneumoniae/classification/*immunology/*physiology ; Time Factors
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  • 50
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2012-04-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kelly, Daniel P -- R01 DK045416/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2012 Apr 6;336(6077):42-3. doi: 10.1126/science.1221688.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL 32827, USA. dkelly@sanfordburnham.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22491843" target="_blank"〉PubMed〈/a〉
    Keywords: Adipocytes, Brown/metabolism ; Adipocytes, White/*metabolism ; Animals ; Energy Metabolism ; *Exercise ; Fibronectins/genetics/*metabolism ; Gene Expression Regulation ; Hormones/*metabolism ; Humans ; Mice ; Models, Biological ; Muscle Fibers, Skeletal/metabolism ; Muscle, Skeletal/*metabolism ; Oxygen Consumption ; Physical Conditioning, Animal ; Physical Endurance ; *Physical Exertion ; Thermogenesis ; Trans-Activators/*metabolism ; Transcription Factors
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 51
    Publication Date: 2012-04-28
    Description: Biological systems that perform multiple tasks face a fundamental trade-off: A given phenotype cannot be optimal at all tasks. Here we ask how trade-offs affect the range of phenotypes found in nature. Using the Pareto front concept from economics and engineering, we find that best-trade-off phenotypes are weighted averages of archetypes--phenotypes specialized for single tasks. For two tasks, phenotypes fall on the line connecting the two archetypes, which could explain linear trait correlations, allometric relationships, as well as bacterial gene-expression patterns. For three tasks, phenotypes fall within a triangle in phenotype space, whose vertices are the archetypes, as evident in morphological studies, including on Darwin's finches. Tasks can be inferred from measured phenotypes based on the behavior of organisms nearest the archetypes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shoval, O -- Sheftel, H -- Shinar, G -- Hart, Y -- Ramote, O -- Mayo, A -- Dekel, E -- Kavanagh, K -- Alon, U -- New York, N.Y. -- Science. 2012 Jun 1;336(6085):1157-60. doi: 10.1126/science.1217405. Epub 2012 Apr 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22539553" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Beak/anatomy & histology ; *Biological Evolution ; Body Size ; Escherichia coli/genetics/growth & development/metabolism ; Finches/anatomy & histology ; Gene Expression ; *Genetic Fitness ; Models, Biological ; Models, Statistical ; *Phenotype ; Selection, Genetic
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  • 52
    Publication Date: 2012-02-04
    Description: Eukaryotic secretory proteins exit the endoplasmic reticulum (ER) via transport vesicles generated by the essential coat protein complex II (COPII) proteins. The outer coat complex, Sec13-Sec31, forms a scaffold that is thought to enforce curvature. By exploiting yeast bypass-of-sec-thirteen (bst) mutants, where Sec13p is dispensable, we probed the relationship between a compromised COPII coat and the cellular context in which it could still function. Genetic and biochemical analyses suggested that Sec13p was required to generate vesicles from membranes that contained asymmetrically distributed cargoes that were likely to confer opposing curvature. Thus, Sec13p may rigidify the COPII cage and increase its membrane-bending capacity; this function could be bypassed when a bst mutation renders the membrane more deformable.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3306526/" 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/PMC3306526/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Copic, Alenka -- Latham, Catherine F -- Horlbeck, Max A -- D'Arcangelo, Jennifer G -- Miller, Elizabeth A -- GM078186/GM/NIGMS NIH HHS/ -- GM085089/GM/NIGMS NIH HHS/ -- R01 GM078186/GM/NIGMS NIH HHS/ -- R01 GM078186-05/GM/NIGMS NIH HHS/ -- R01 GM085089/GM/NIGMS NIH HHS/ -- R01 GM085089-04/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 Mar 16;335(6074):1359-62. doi: 10.1126/science.1215909. Epub 2012 Feb 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Columbia University, New York, NY 10027, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22300850" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; COP-Coated Vesicles/*chemistry/metabolism/ultrastructure ; Endoplasmic Reticulum/*metabolism ; Genes, Fungal ; Models, Biological ; Models, Molecular ; Mutant Proteins/chemistry/metabolism ; Mutation ; Nuclear Pore Complex Proteins/chemistry/genetics/*metabolism ; Protein Interaction Domains and Motifs ; Protein Structure, Tertiary ; Protein Transport ; Saccharomyces cerevisiae/genetics/*metabolism/ultrastructure ; Saccharomyces cerevisiae Proteins/chemistry/genetics/*metabolism ; Vesicular Transport Proteins/chemistry/metabolism
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  • 53
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2012-02-11
    Description: Ocean warming occurs every year in seasonal cycles that can help us to understand long-term responses of plankton to climate change. Rhythmic seasonal patterns of microbial community turnover are revealed when high-resolution measurements of microbial plankton diversity are applied to samples collected in lengthy time series. Seasonal cycles in microbial plankton are complex, but the expansion of fixed ocean stations monitoring long-term change and the development of automated instrumentation are providing the time-series data needed to understand how these cycles vary across broad geographical scales. By accumulating data and using predictive modeling, we gain insights into changes that will occur as the ocean surface continues to warm and as the extent and duration of ocean stratification increase. These developments will enable marine scientists to predict changes in geochemical cycles mediated by microbial communities and to gauge their broader impacts.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Giovannoni, Stephen J -- Vergin, Kevin L -- New York, N.Y. -- Science. 2012 Feb 10;335(6069):671-6. doi: 10.1126/science.1198078.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, Oregon State University, Corvallis, OR 97331, USA. steve.giovannoni@oregonstate.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22323811" target="_blank"〉PubMed〈/a〉
    Keywords: Alphaproteobacteria/physiology ; Archaea/*physiology ; *Bacterial Physiological Phenomena ; Climate Change ; *Ecosystem ; Models, Biological ; Oceans and Seas ; Phytoplankton/growth & development/*physiology ; *Seasons ; Seawater/chemistry/*microbiology ; Temperature
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  • 54
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2012-09-22
    Description: The blood-testis barrier includes strands of tight junctions between somatic Sertoli cells that restricts solutes from crossing the paracellular space, creating a microenvironment within seminiferous tubules and providing immune privilege to meiotic and postmeiotic cells. Large cysts of germ cells transit the Sertoli cell tight junctions (SCTJs) without compromising their integrity. We used confocal microscopy to visualize SCTJ components during germ cell cyst migration across the SCTJs. Cysts become enclosed within a network of transient compartments fully bounded by old and new tight junctions. Dissolution of the old tight junctions releases the germ cells into the adluminal compartment, thus completing transit across the blood-testis barrier. Claudin 3, a tight junction protein, is transiently incorporated into new tight junctions and then replaced by claudin 11.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694388/" 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/PMC3694388/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smith, Benjamin E -- Braun, Robert E -- CA34196/CA/NCI NIH HHS/ -- HD12629/HD/NICHD NIH HHS/ -- P30 CA034196/CA/NCI NIH HHS/ -- U54 HD012629/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2012 Nov 9;338(6108):798-802. doi: 10.1126/science.1219969. Epub 2012 Sep 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22997133" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood-Testis Barrier/*ultrastructure ; *Cell Movement ; Claudin-3/analysis/metabolism ; Claudins/analysis/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Microscopy, Confocal ; Models, Biological ; Seminiferous Tubules/chemistry/ultrastructure ; Sertoli Cells/chemistry/physiology/*ultrastructure ; Spermatocytes/*physiology/ultrastructure ; Spermatogenesis ; Tight Junctions/chemistry/physiology/*ultrastructure
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  • 55
    Publication Date: 2012-08-11
    Description: Cells reuse signaling proteins in multiple pathways, raising the potential for improper cross talk. Scaffold proteins are thought to insulate against such miscommunication by sequestering proteins into distinct physical complexes. We show that the scaffold protein Ste5, which organizes the yeast mating mitogen-activated protein kinase (MAPK) pathway, does not use sequestration to prevent misactivation of the mating response. Instead, Ste5 appears to use a conformation mechanism: Under basal conditions, an intramolecular interaction of the pleckstrin homology (PH) domain with the von Willebrand type A (VWA) domain blocks the ability to coactivate the mating-specific MAPK Fus3. Pheromone-induced membrane binding of Ste5 triggers release of this autoinhibition. Thus, in addition to serving as a conduit guiding kinase communication, Ste5 directly receives input information to decide if and when signal can be transmitted to mating output.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3631425/" 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/PMC3631425/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zalatan, Jesse G -- Coyle, Scott M -- Rajan, Saravanan -- Sidhu, Sachdev S -- Lim, Wendell A -- MOPS-93725/Canadian Institutes of Health Research/Canada -- P41 RR001614/RR/NCRR NIH HHS/ -- P50 GM081879/GM/NIGMS NIH HHS/ -- PN2 EY016546/EY/NEI NIH HHS/ -- R01 GM055040/GM/NIGMS NIH HHS/ -- R01 GM55040/GM/NIGMS NIH HHS/ -- R01 GM62583/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Sep 7;337(6099):1218-22. doi: 10.1126/science.1220683. Epub 2012 Aug 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology, University of California, San Francisco, 600 16th Street, San Francisco, CA 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22878499" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/antagonists & ; inhibitors/*chemistry/*metabolism ; Enzyme Activation ; MAP Kinase Kinase Kinases/metabolism ; MAP Kinase Signaling System ; Mitogen-Activated Protein Kinase Kinases/metabolism ; Mitogen-Activated Protein Kinases/*metabolism ; Models, Biological ; Phosphorylation ; Protein Conformation ; Protein Interaction Domains and Motifs ; Protein Kinases/metabolism ; Protein Precursors/metabolism ; Saccharomyces cerevisiae/*metabolism/physiology ; Saccharomyces cerevisiae Proteins/antagonists & inhibitors/*chemistry/*metabolism
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  • 56
    Publication Date: 2012-06-16
    Description: Cells transmit information through molecular signals that often show complex dynamical patterns. The dynamic behavior of the tumor suppressor p53 varies depending on the stimulus; in response to double-strand DNA breaks, it shows a series of repeated pulses. Using a computational model, we identified a sequence of precisely timed drug additions that alter p53 pulses to instead produce a sustained p53 response. This leads to the expression of a different set of downstream genes and also alters cell fate: Cells that experience p53 pulses recover from DNA damage, whereas cells exposed to sustained p53 signaling frequently undergo senescence. Our results show that protein dynamics can be an important part of a signal, directly influencing cellular fate decisions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162876/" 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/PMC4162876/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Purvis, Jeremy E -- Karhohs, Kyle W -- Mock, Caroline -- Batchelor, Eric -- Loewer, Alexander -- Lahav, Galit -- F32 GM095168/GM/NIGMS NIH HHS/ -- F32GM095168/GM/NIGMS NIH HHS/ -- GM083303/GM/NIGMS NIH HHS/ -- K99 GM102372/GM/NIGMS NIH HHS/ -- R00 GM102372/GM/NIGMS NIH HHS/ -- R01 GM083303/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 Jun 15;336(6087):1440-4. doi: 10.1126/science.1218351.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22700930" target="_blank"〉PubMed〈/a〉
    Keywords: Apoptosis/genetics ; Cell Aging/*genetics ; Cell Cycle Checkpoints ; Cell Line, Tumor ; Cyclin-Dependent Kinase Inhibitor p21/genetics ; *DNA Breaks, Double-Stranded ; DNA Repair ; Gamma Rays ; Humans ; Imidazoles/metabolism/pharmacology ; Models, Biological ; Nuclear Proteins/genetics ; Piperazines/metabolism/pharmacology ; *Signal Transduction ; Single-Cell Analysis ; Transcription Factors/genetics ; Transcriptional Activation ; Tumor Suppressor Protein p53/*metabolism ; Tumor Suppressor Proteins/genetics
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  • 57
    Publication Date: 2012-12-22
    Description: Neurotransmitter release depends critically on Munc18-1, Munc13, the Ca(2+) sensor synaptotagmin-1, and the soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptors (SNAREs) syntaxin-1, synaptobrevin, and SNAP-25. In vitro reconstitutions have shown that syntaxin-1-SNAP-25 liposomes fuse efficiently with synaptobrevin liposomes in the presence of synaptotagmin-1-Ca(2+), but neurotransmitter release also requires Munc18-1 and Munc13 in vivo. We found that Munc18-1 could displace SNAP-25 from syntaxin-1 and that fusion of syntaxin-1-Munc18-1 liposomes with synaptobrevin liposomes required Munc13, in addition to SNAP-25 and synaptotagmin-1-Ca(2+). Moreover, when starting with syntaxin-1-SNAP-25 liposomes, NSF-alpha-SNAP disassembled the syntaxin-1-SNAP-25 heterodimers and abrogated fusion, which then required Munc18-1 and Munc13. We propose that fusion does not proceed through syntaxin-1-SNAP-25 heterodimers but starts with the syntaxin-1-Munc18-1 complex; Munc18-1 and Munc13 then orchestrate membrane fusion together with the SNAREs and synaptotagmin-1-Ca(2+) in an NSF- and SNAP-resistant manner.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3733786/" 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/PMC3733786/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ma, Cong -- Su, Lijing -- Seven, Alpay B -- Xu, Yibin -- Rizo, Josep -- NS37200/NS/NINDS NIH HHS/ -- NS40944/NS/NINDS NIH HHS/ -- R01 NS037200/NS/NINDS NIH HHS/ -- R01 NS040944/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2013 Jan 25;339(6118):421-5. doi: 10.1126/science.1230473. Epub 2012 Dec 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Key Laboratory of Molecular Biophysics, Ministry of Education, and Institute of Biophysics and Biochemistry, Huazhong University of Science and Technology, Wuhan 430074, China. cong.ma7@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23258414" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/metabolism ; Humans ; Liposomes ; *Membrane Fusion ; Models, Biological ; Munc18 Proteins/*metabolism ; Nerve Tissue Proteins/*metabolism ; Neurotransmitter Agents/*metabolism ; Protein Binding ; Protein Multimerization ; R-SNARE Proteins/metabolism ; Rats ; Synaptic Vesicles/*metabolism ; Synaptosomal-Associated Protein 25/metabolism ; Synaptotagmin I/metabolism ; Syntaxin 1/metabolism
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  • 58
    Publication Date: 2012-03-03
    Description: Adaptation of cells to environmental changes requires dynamic interactions between metabolic and regulatory networks, but studies typically address only one or a few layers of regulation. For nutritional shifts between two preferred carbon sources of Bacillus subtilis, we combined statistical and model-based data analyses of dynamic transcript, protein, and metabolite abundances and promoter activities. Adaptation to malate was rapid and primarily controlled posttranscriptionally compared with the slow, mainly transcriptionally controlled adaptation to glucose that entailed nearly half of the known transcription regulation network. Interactions across multiple levels of regulation were involved in adaptive changes that could also be achieved by controlling single genes. Our analysis suggests that global trade-offs and evolutionary constraints provide incentives to favor complex control programs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buescher, Joerg Martin -- Liebermeister, Wolfram -- Jules, Matthieu -- Uhr, Markus -- Muntel, Jan -- Botella, Eric -- Hessling, Bernd -- Kleijn, Roelco Jacobus -- Le Chat, Ludovic -- Lecointe, Francois -- Mader, Ulrike -- Nicolas, Pierre -- Piersma, Sjouke -- Rugheimer, Frank -- Becher, Dorte -- Bessieres, Philippe -- Bidnenko, Elena -- Denham, Emma L -- Dervyn, Etienne -- Devine, Kevin M -- Doherty, Geoff -- Drulhe, Samuel -- Felicori, Liza -- Fogg, Mark J -- Goelzer, Anne -- Hansen, Annette -- Harwood, Colin R -- Hecker, Michael -- Hubner, Sebastian -- Hultschig, Claus -- Jarmer, Hanne -- Klipp, Edda -- Leduc, Aurelie -- Lewis, Peter -- Molina, Frank -- Noirot, Philippe -- Peres, Sabine -- Pigeonneau, Nathalie -- Pohl, Susanne -- Rasmussen, Simon -- Rinn, Bernd -- Schaffer, Marc -- Schnidder, Julian -- Schwikowski, Benno -- Van Dijl, Jan Maarten -- Veiga, Patrick -- Walsh, Sean -- Wilkinson, Anthony J -- Stelling, Jorg -- Aymerich, Stephane -- Sauer, Uwe -- New York, N.Y. -- Science. 2012 Mar 2;335(6072):1099-103. doi: 10.1126/science.1206871.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22383848" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptation, Physiological ; Algorithms ; Bacillus subtilis/*genetics/*metabolism ; Bacterial Proteins/metabolism ; Computer Simulation ; Data Interpretation, Statistical ; Gene Expression Regulation, Bacterial ; *Gene Regulatory Networks ; Genome, Bacterial ; Glucose/*metabolism ; Malates/*metabolism ; Metabolic Networks and Pathways/*genetics ; Metabolome ; Metabolomics ; Models, Biological ; Operon ; Promoter Regions, Genetic ; Transcription Factors/metabolism ; Transcription, Genetic
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  • 59
    Publication Date: 2012-02-11
    Description: Apical constriction changes cell shapes, driving critical morphogenetic events, including gastrulation in diverse organisms and neural tube closure in vertebrates. Apical constriction is thought to be triggered by contraction of apical actomyosin networks. We found that apical actomyosin contractions began before cell shape changes in both Caenorhabitis elegans and Drosophila. In C. elegans, actomyosin networks were initially dynamic, contracting and generating cortical tension without substantial shrinking of apical surfaces. Apical cell-cell contact zones and actomyosin only later moved increasingly in concert, with no detectable change in actomyosin dynamics or cortical tension. Thus, apical constriction appears to be triggered not by a change in cortical tension, but by dynamic linking of apical cell-cell contact zones to an already contractile apical cortex.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3298882/" 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/PMC3298882/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roh-Johnson, Minna -- Shemer, Gidi -- Higgins, Christopher D -- McClellan, Joseph H -- Werts, Adam D -- Tulu, U Serdar -- Gao, Liang -- Betzig, Eric -- Kiehart, Daniel P -- Goldstein, Bob -- R01 GM033830/GM/NIGMS NIH HHS/ -- R01 GM083071/GM/NIGMS NIH HHS/ -- R01 GM083071-01A1/GM/NIGMS NIH HHS/ -- R01 GM083071-02/GM/NIGMS NIH HHS/ -- R01 GM083071-02S1/GM/NIGMS NIH HHS/ -- R01 GM083071-03/GM/NIGMS NIH HHS/ -- R01 GM083071-04/GM/NIGMS NIH HHS/ -- R01 GM33830/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Mar 9;335(6073):1232-5. doi: 10.1126/science.1217869. Epub 2012 Feb 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22323741" target="_blank"〉PubMed〈/a〉
    Keywords: Actomyosin/chemistry/*physiology ; Animals ; Caenorhabditis elegans/*cytology/*embryology ; Cell Membrane/physiology/ultrastructure ; *Cell Shape ; Computer Simulation ; Cytoskeleton/physiology/ultrastructure ; Drosophila melanogaster/*cytology/*embryology ; Embryo, Nonmammalian/cytology/physiology ; Fluorescence Recovery After Photobleaching ; *Gastrulation ; Intercellular Junctions/physiology/ultrastructure ; Mechanical Phenomena ; Models, Biological ; Morphogenesis ; Myosins/chemistry/physiology
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  • 60
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2012-05-19
    Description: Cells must balance the cost and benefit of protein expression to optimize organismal fitness. The lac operon of the bacterium Escherichia coli has been a model for quantifying the physiological impact of costly protein production and for elucidating the resulting regulatory mechanisms. We report quantitative fitness measurements in 27 redesigned operons that suggested that protein production is not the primary origin of fitness costs. Instead, we discovered that the lac permease activity, which relates linearly to cost, is the major physiological burden to the cell. These findings explain control points in the lac operon that minimize the cost of lac permease activity, not protein expression. Characterizing similar relationships in other systems will be important to map the impact of cost/benefit tradeoffs on cell physiology and regulation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Eames, Matt -- Kortemme, Tanja -- New York, N.Y. -- Science. 2012 May 18;336(6083):911-5. doi: 10.1126/science.1219083.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate Group in Biophysics, MC 2530, University of California, San Francisco, CA 94158-2330, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22605776" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Biocatalysis ; Biological Transport ; Escherichia coli/*genetics/growth & development/metabolism ; Escherichia coli Proteins/*genetics/*metabolism ; Gene Expression Regulation, Bacterial ; Gene Knockout Techniques ; Genetic Engineering ; Isopropyl Thiogalactoside/metabolism ; *Lac Operon ; Lac Repressors ; Lactose/metabolism ; Models, Biological ; Molecular Sequence Data ; Monosaccharide Transport Proteins/*genetics/*metabolism ; Mutation ; Symporters/*genetics/*metabolism ; beta-Galactosidase/*genetics/*metabolism
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  • 61
    Publication Date: 2012-06-23
    Description: Avian A/H5N1 influenza viruses pose a pandemic threat. As few as five amino acid substitutions, or four with reassortment, might be sufficient for mammal-to-mammal transmission through respiratory droplets. From surveillance data, we found that two of these substitutions are common in A/H5N1 viruses, and thus, some viruses might require only three additional substitutions to become transmissible via respiratory droplets between mammals. We used a mathematical model of within-host virus evolution to study factors that could increase and decrease the probability of the remaining substitutions evolving after the virus has infected a mammalian host. These factors, combined with the presence of some of these substitutions in circulating strains, make a virus evolving in nature a potentially serious threat. These results highlight critical areas in which more data are needed for assessing, and potentially averting, this threat.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3426314/" 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/PMC3426314/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Russell, Colin A -- Fonville, Judith M -- Brown, Andre E X -- Burke, David F -- Smith, David L -- James, Sarah L -- Herfst, Sander -- van Boheemen, Sander -- Linster, Martin -- Schrauwen, Eefje J -- Katzelnick, Leah -- Mosterin, Ana -- Kuiken, Thijs -- Maher, Eileen -- Neumann, Gabriele -- Osterhaus, Albert D M E -- Kawaoka, Yoshihiro -- Fouchier, Ron A M -- Smith, Derek J -- DP1 OD000490/OD/NIH HHS/ -- DP1-OD000490-01/OD/NIH HHS/ -- HHSN266200700010C/AI/NIAID NIH HHS/ -- HHSN266200700010C/PHS HHS/ -- R01 AI 069274/AI/NIAID NIH HHS/ -- R56 AI069274/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2012 Jun 22;336(6088):1541-7. doi: 10.1126/science.1222526.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Zoology, University of Cambridge, Cambridge, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22723414" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological ; Air Microbiology ; Amino Acid Substitution ; Animals ; Birds ; *Evolution, Molecular ; Genetic Fitness ; Glycosylation ; Hemagglutinin Glycoproteins, Influenza Virus/*genetics/metabolism ; High-Throughput Nucleotide Sequencing ; Humans ; Influenza A Virus, H5N1 Subtype/*genetics/*pathogenicity ; Influenza in Birds/virology ; Influenza, Human/immunology/transmission/*virology ; Mammals ; Models, Biological ; Mutation ; Orthomyxoviridae Infections/transmission/*virology ; Probability ; RNA Replicase/*genetics ; Receptors, Virus/metabolism ; Respiratory System/*virology ; Selection, Genetic ; Sialic Acids/metabolism ; Viral Proteins/*genetics
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  • 62
    Publication Date: 2012-04-14
    Description: Biological systems involving short-range activators and long-range inhibitors can generate complex patterns. Reaction-diffusion models postulate that differences in signaling range are caused by differential diffusivity of inhibitor and activator. Other models suggest that differential clearance underlies different signaling ranges. To test these models, we measured the biophysical properties of the Nodal/Lefty activator/inhibitor system during zebrafish embryogenesis. Analysis of Nodal and Lefty gradients revealed that Nodals have a shorter range than Lefty proteins. Pulse-labeling analysis indicated that Nodals and Leftys have similar clearance kinetics, whereas fluorescence recovery assays revealed that Leftys have a higher effective diffusion coefficient than Nodals. These results indicate that differential diffusivity is the major determinant of the differences in Nodal/Lefty range and provide biophysical support for reaction-diffusion models of activator/inhibitor-mediated patterning.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3525670/" 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/PMC3525670/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Muller, Patrick -- Rogers, Katherine W -- Jordan, Ben M -- Lee, Joon S -- Robson, Drew -- Ramanathan, Sharad -- Schier, Alexander F -- 5R01GM56211/GM/NIGMS NIH HHS/ -- R01 GM056211/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 May 11;336(6082):721-4. doi: 10.1126/science.1221920. Epub 2012 Apr 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA. pmueller@fas.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22499809" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blastula/*metabolism ; *Body Patterning ; Diffusion ; Embryonic Development ; Fluorescence Recovery After Photobleaching ; Half-Life ; Intracellular Signaling Peptides and Proteins/genetics/*metabolism ; Kinetics ; Left-Right Determination Factors/genetics/*metabolism ; Models, Biological ; Nodal Signaling Ligands/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Zebrafish/*embryology/metabolism ; Zebrafish Proteins/genetics/*metabolism
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  • 63
    Publication Date: 2012-04-21
    Description: A detailed understanding of the mechanisms that underlie antibiotic killing is important for the derivation of new classes of antibiotics and clinically useful adjuvants for current antimicrobial therapies. Our efforts to understand why DinB (DNA polymerase IV) overproduction is cytotoxic to Escherichia coli led to the unexpected insight that oxidation of guanine to 8-oxo-guanine in the nucleotide pool underlies much of the cell death caused by both DinB overproduction and bactericidal antibiotics. We propose a model in which the cytotoxicity of beta-lactams and quinolones predominantly results from lethal double-strand DNA breaks caused by incomplete repair of closely spaced 8-oxo-deoxyguanosine lesions, whereas the cytotoxicity of aminoglycosides might additionally result from mistranslation due to the incorporation of 8-oxo-guanine into newly synthesized RNAs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3357493/" 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/PMC3357493/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Foti, James J -- Devadoss, Babho -- Winkler, Jonathan A -- Collins, James J -- Walker, Graham C -- DP1 OD003644/OD/NIH HHS/ -- F32 GM079885/GM/NIGMS NIH HHS/ -- P30 ES002019/ES/NIEHS NIH HHS/ -- R01 CA021615/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Apr 20;336(6079):315-9. doi: 10.1126/science.1219192.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22517853" target="_blank"〉PubMed〈/a〉
    Keywords: Ampicillin/pharmacology ; Anti-Bacterial Agents/*pharmacology ; DNA Breaks, Double-Stranded ; DNA Glycosylases/genetics/metabolism ; DNA Polymerase I/genetics/metabolism ; DNA Polymerase II/genetics/metabolism ; DNA Polymerase beta/genetics/metabolism ; DNA, Bacterial/*metabolism ; DNA-Directed DNA Polymerase/genetics/metabolism ; Deoxyguanine Nucleotides/metabolism ; Escherichia coli/*drug effects/genetics/*metabolism ; Escherichia coli Proteins/genetics/metabolism ; Guanine/*analogs & derivatives/metabolism ; Guanine Nucleotides/*metabolism ; Hydroxyl Radical/metabolism ; Kanamycin/pharmacology ; Microbial Viability ; Models, Biological ; Norfloxacin/pharmacology ; Oxidation-Reduction ; Pyrophosphatases/genetics/metabolism ; RNA, Bacterial/*metabolism
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  • 64
    Publication Date: 2012-07-07
    Description: Springtime phytoplankton blooms photosynthetically fix carbon and export it from the surface ocean at globally important rates. These blooms are triggered by increased light exposure of the phytoplankton due to both seasonal light increase and the development of a near-surface vertical density gradient (stratification) that inhibits vertical mixing of the phytoplankton. Classically and in current climate models, that stratification is ascribed to a springtime warming of the sea surface. Here, using observations from the subpolar North Atlantic and a three-dimensional biophysical model, we show that the initial stratification and resulting bloom are instead caused by eddy-driven slumping of the basin-scale north-south density gradient, resulting in a patchy bloom beginning 20 to 30 days earlier than would occur by warming.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mahadevan, Amala -- D'Asaro, Eric -- Lee, Craig -- Perry, Mary Jane -- New York, N.Y. -- Science. 2012 Jul 6;337(6090):54-8. doi: 10.1126/science.1218740.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Woods Hole Oceanographic Institution, Woods Hole, MA 02543, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22767922" target="_blank"〉PubMed〈/a〉
    Keywords: Atlantic Ocean ; Climate ; *Eutrophication ; Models, Biological ; Models, Theoretical ; Phytoplankton/*growth & development ; Robotics ; Seasons ; *Seawater ; Sunlight ; Temperature ; *Water Movements
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  • 65
    Publication Date: 2012-03-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Garcia, S M -- Kolding, J -- Rice, J -- Rochet, M-J -- Zhou, S -- Arimoto, T -- Beyer, J E -- Borges, L -- Bundy, A -- Dunn, D -- Fulton, E A -- Hall, M -- Heino, M -- Law, R -- Makino, M -- Rijnsdorp, A D -- Simard, F -- Smith, A D M -- New York, N.Y. -- Science. 2012 Mar 2;335(6072):1045-7. doi: 10.1126/science.1214594.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Commission on Ecosystem Management, International Union for Conservation of Nature (IUCN-CEM), Fisheries Expert Group, Brussels, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22383833" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biodiversity ; Biomass ; Body Size ; *Conservation of Natural Resources ; *Ecosystem ; *Fisheries ; *Fishes ; Models, Biological ; Policy
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  • 66
    Publication Date: 2012-05-26
    Description: Plants use day-length information to coordinate flowering time with the appropriate season to maximize reproduction. In Arabidopsis, the long day-specific expression of CONSTANS (CO) protein is crucial for flowering induction. Although light signaling regulates CO protein stability, the mechanism by which CO is stabilized in the long-day afternoon has remained elusive. Here, we demonstrate that FLAVIN-BINDING, KELCH REPEAT, F-BOX 1 (FKF1) protein stabilizes CO protein in the afternoon in long days. FKF1 interacts with CO through its LOV domain, and blue light enhances this interaction. In addition, FKF1 simultaneously removes CYCLING DOF FACTOR 1 (CDF1), which represses CO and FLOWERING LOCUS T (FT) transcription. Together with CO transcriptional regulation, FKF1 protein controls robust FT mRNA induction through multiple feedforward mechanisms that accurately control flowering timing.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737243/" 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/PMC3737243/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Song, Young Hun -- Smith, Robert W -- To, Benjamin J -- Millar, Andrew J -- Imaizumi, Takato -- BB/F005237/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/F59011/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/G019621/Biotechnology and Biological Sciences Research Council/United Kingdom -- GM079712/GM/NIGMS NIH HHS/ -- R01 GM079712/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 May 25;336(6084):1045-9. doi: 10.1126/science.1219644.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of Washington, Seattle, WA 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22628657" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/genetics/growth & development/metabolism/*physiology ; Arabidopsis Proteins/chemistry/*genetics/*metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Flowers/*growth & development ; Gene Expression Regulation, Plant ; Light ; Models, Biological ; Mutation ; *Photoperiod ; Plants, Genetically Modified ; Promoter Regions, Genetic ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein Stability ; RNA, Messenger/genetics/metabolism ; RNA, Plant/genetics/metabolism ; Repressor Proteins/metabolism ; Transcription Factors/genetics/*metabolism ; Transcription, Genetic
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  • 67
    Publication Date: 2012-03-03
    Description: Although genetic control of morphogenesis is well established, elaboration of complex shapes requires changes in the mechanical properties of cells. In plants, the first visible sign of leaf formation is a bulge on the flank of the shoot apical meristem. Bulging results from local relaxation of cell walls, which causes them to yield to internal hydrostatic pressure. By manipulation of tissue tension in combination with quantitative live imaging and finite-element modeling, we found that the slow-growing area at the shoot tip is substantially strain-stiffened compared with surrounding fast-growing tissue. We propose that strain stiffening limits growth, restricts organ bulging, and contributes to the meristem's functional zonation. Thus, mechanical signals are not just passive readouts of gene action but feed back on morphogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kierzkowski, Daniel -- Nakayama, Naomi -- Routier-Kierzkowska, Anne-Lise -- Weber, Alain -- Bayer, Emmanuelle -- Schorderet, Martine -- Reinhardt, Didier -- Kuhlemeier, Cris -- Smith, Richard S -- New York, N.Y. -- Science. 2012 Mar 2;335(6072):1096-9. doi: 10.1126/science.1213100.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Plant Sciences, University of Bern, Bern, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22383847" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Wall/physiology/ultrastructure ; Elasticity ; Hydrostatic Pressure ; Lycopersicon esculentum/cytology/*growth & development ; Meristem/cytology/*growth & development ; Models, Biological ; *Morphogenesis ; Osmolar Concentration ; Osmotic Pressure ; Plant Shoots/cytology/*growth & development
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  • 68
    Publication Date: 2012-03-01
    Description: Understanding species' interactions and the robustness of interaction networks to species loss is essential to understand the effects of species' declines and extinctions. In most studies, different types of networks (such as food webs, parasitoid webs, seed dispersal networks, and pollination networks) have been studied separately. We sampled such multiple networks simultaneously in an agroecosystem. We show that the networks varied in their robustness; networks including pollinators appeared to be particularly fragile. We show that, overall, networks did not strongly covary in their robustness, which suggests that ecological restoration (for example, through agri-environment schemes) benefitting one functional group will not inevitably benefit others. Some individual plant species were disproportionately well linked to many other species. This type of information can be used in restoration management, because it identifies the plant taxa that can potentially lead to disproportionate gains in biodiversity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pocock, Michael J O -- Evans, Darren M -- Memmott, Jane -- BBD0156341/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2012 Feb 24;335(6071):973-7. doi: 10.1126/science.1214915.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Biological Sciences, University of Bristol, Woodland Road, Bristol BS8 1UG, UK. michael.pocock@ceh.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22363009" target="_blank"〉PubMed〈/a〉
    Keywords: *Agriculture ; Animals ; Biodiversity ; *Ecosystem ; Extinction, Biological ; *Food Chain ; Great Britain ; Insects/physiology ; Models, Biological ; Parasites/physiology ; *Plant Physiological Phenomena ; Pollination ; Vertebrates/physiology
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  • 69
    Publication Date: 2012-11-20
    Description: Analogies with inert soft condensed matter--such as viscoelastic liquids, pastes, foams, emulsions, colloids, and polymers--can be used to investigate the mechanical response of soft biological tissues to forces. A variety of experimental techniques and biophysical models have exploited these analogies allowing the quantitative characterization of the mechanical properties of model tissues, such as surface tension, elasticity, and viscosity. The framework of soft matter has been successful in explaining a number of dynamical tissue behaviors observed in physiology and development, such as cell sorting, tissue spreading, or the escape of individual cells from a tumor. However, living tissues also exhibit active responses, such as rigidity sensing or cell pulsation, that are absent in inert soft materials. The soft matter models reviewed here have provided valuable insight in understanding morphogenesis and cancer invasion and have set bases for using tissue engineering within medicine.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gonzalez-Rodriguez, David -- Guevorkian, Karine -- Douezan, Stephane -- Brochard-Wyart, Francoise -- New York, N.Y. -- Science. 2012 Nov 16;338(6109):910-7. doi: 10.1126/science.1226418.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratoire d'Hydrodynamique (LadHyX), CNRS UMR 7646, Ecole Polytechnique, 91128 Palaiseau, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23161991" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Adhesion ; Cell Culture Techniques ; Cell Separation ; *Elasticity ; *Embryo, Mammalian ; *Embryo, Nonmammalian ; Hardness ; Humans ; Mechanotransduction, Cellular ; Mice ; Models, Biological ; *Neoplasms ; Tissue Engineering/*methods ; Viscosity ; Xenopus
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  • 70
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2012-06-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zarnetske, Phoebe L -- Skelly, David K -- Urban, Mark C -- New York, N.Y. -- Science. 2012 Jun 22;336(6088):1516-8. doi: 10.1126/science.1222732.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Forestry and Environmental Studies, Yale University, New Haven, CT 06511, USA. phoebe.zarnetske@yale.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22723403" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Climate Change ; *Ecosystem ; Extinction, Biological ; *Food Chain ; Models, Biological ; Plants ; Population Dynamics
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  • 71
    Publication Date: 2012-05-19
    Description: Cells promote polarized growth by activation of Rho-family protein Cdc42 at the cell membrane. We combined experiments and modeling to study bipolar growth initiation in fission yeast. Concentrations of a fluorescent marker for active Cdc42, Cdc42 protein, Cdc42-activator Scd1, and scaffold protein Scd2 exhibited anticorrelated fluctuations and oscillations with a 5-minute average period at polarized cell tips. These dynamics indicate competition for active Cdc42 or its regulators and the presence of positive and delayed negative feedbacks. Cdc42 oscillations and spatial distribution were sensitive to the amounts of Cdc42-activator Gef1 and to the activity of Cdc42-dependent kinase Pak1, a negative regulator. Feedbacks regulating Cdc42 oscillations and spatial self-organization appear to provide a flexible mechanism for fission yeast cells to explore polarization states and to control their morphology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681419/" 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/PMC3681419/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Das, Maitreyi -- Drake, Tyler -- Wiley, David J -- Buchwald, Peter -- Vavylonis, Dimitrios -- Verde, Fulvia -- 1R01GM095867/GM/NIGMS NIH HHS/ -- R01 GM095867/GM/NIGMS NIH HHS/ -- R21 GM083928/GM/NIGMS NIH HHS/ -- R21GM083928/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 Jul 13;337(6091):239-43. doi: 10.1126/science.1218377. Epub 2012 May 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Pharmacology (R-189), University of Miami Miller School of Medicine, Post Office Box 016189, Miami, FL 33101, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22604726" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Cycle Proteins/metabolism ; Guanine Nucleotide Exchange Factors/metabolism ; Microscopy, Fluorescence ; Models, Biological ; Mutation ; Recombinant Fusion Proteins/metabolism ; Schizosaccharomyces/cytology/*enzymology/genetics/*growth & development ; Schizosaccharomyces pombe Proteins/*metabolism ; cdc42 GTP-Binding Protein/*metabolism ; p21-Activated Kinases/metabolism
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  • 72
    Publication Date: 2012-04-14
    Description: During animal development, several planar cell polarity (PCP) pathways control tissue shape by coordinating collective cell behavior. Here, we characterize by means of multiscale imaging epithelium morphogenesis in the Drosophila dorsal thorax and show how the Fat/Dachsous/Four-jointed PCP pathway controls morphogenesis. We found that the proto-cadherin Dachsous is polarized within a domain of its tissue-wide expression gradient. Furthermore, Dachsous polarizes the myosin Dachs, which in turn promotes anisotropy of junction tension. By combining physical modeling with quantitative image analyses, we determined that this tension anisotropy defines the pattern of local tissue contraction that contributes to shaping the epithelium mainly via oriented cell rearrangements. Our results establish how tissue planar polarization coordinates the local changes of cell mechanical properties to control tissue morphogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bosveld, Floris -- Bonnet, Isabelle -- Guirao, Boris -- Tlili, Sham -- Wang, Zhimin -- Petitalot, Ambre -- Marchand, Raphael -- Bardet, Pierre-Luc -- Marcq, Philippe -- Graner, Francois -- Bellaiche, Yohanns -- New York, N.Y. -- Science. 2012 May 11;336(6082):724-7. doi: 10.1126/science.1221071. Epub 2012 Apr 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Polarity, Division and Morphogenesis Team, Institut Curie, CNRS UMR 3215, INSERM U934, 26 Rue d'Ulm, 75248 Paris Cedex 05, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22499807" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anisotropy ; Cadherins/genetics/*metabolism ; Cell Adhesion Molecules/genetics/*metabolism ; *Cell Polarity ; Cell Shape ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/cytology/genetics/*growth & development/metabolism ; Epithelial Cells/cytology/metabolism ; Intercellular Junctions/metabolism/physiology ; Membrane Glycoproteins/genetics/*metabolism ; Metamorphosis, Biological ; Models, Biological ; *Morphogenesis ; Myosins/metabolism ; Pupa/growth & development/metabolism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Thorax/cytology/growth & development/metabolism
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  • 73
    Publication Date: 2011-09-24
    Description: The emergence of bacterial antibiotic resistance is a growing problem, yet the variables that influence the rate of emergence of resistance are not well understood. In a microfluidic device designed to mimic naturally occurring bacterial niches, resistance of Escherichia coli to the antibiotic ciprofloxacin developed within 10 hours. Resistance emerged with as few as 100 bacteria in the initial inoculation. Whole-genome sequencing of the resistant organisms revealed that four functional single-nucleotide polymorphisms attained fixation. Knowledge about the rapid emergence of antibiotic resistance in the heterogeneous conditions within the mammalian body may be helpful in understanding the emergence of drug resistance during cancer chemotherapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Qiucen -- Lambert, Guillaume -- Liao, David -- Kim, Hyunsung -- Robin, Kristelle -- Tung, Chih-kuan -- Pourmand, Nader -- Austin, Robert H -- U54CA143803/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2011 Sep 23;333(6050):1764-7. doi: 10.1126/science.1208747.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, Princeton University, Princeton, NJ 08544, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21940899" target="_blank"〉PubMed〈/a〉
    Keywords: Anti-Bacterial Agents/analysis/*pharmacology ; Ciprofloxacin/analysis/*pharmacology ; DNA Gyrase/genetics/metabolism ; Drug Resistance, Bacterial/*genetics ; Escherichia coli K12/*drug effects/genetics/growth & development/physiology ; Escherichia coli Proteins/genetics/metabolism ; *Evolution, Molecular ; Genes, Bacterial ; Genome, Bacterial ; Membrane Transport Proteins/genetics/metabolism ; Microbial Sensitivity Tests ; Microfluidic Analytical Techniques ; Models, Biological ; Movement ; Mutation, Missense ; *Polymorphism, Single Nucleotide ; Repressor Proteins/genetics/metabolism
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  • 74
    Publication Date: 2011-09-10
    Description: The mechanisms that generate dynamic spatial patterns within proliferating tissues are poorly understood, largely because of difficulties in unravelling interactions between cell specification, polarity, asymmetric division, rearrangements, and growth. We address this problem for stomatal spacing in plants, which offer the simplifying advantage that cells do not rearrange. By tracking lineages and gene activities over extended periods, we show that limited stem cell behavior of stomatal precursors depends on maintenance of the SPEECHLESS (SPCH) transcription factor in single daughter cells. Modeling shows how this property can lead to observed stereotypical stomata lineages through a postmitotic polarity-switching mechanism. The model predicts the location of a polarity determinant BASL over multiple divisions, which we validate experimentally. Our results highlight the dynamic two-way interactions between stem cells and their neighborhood during developmental patterning.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3383840/" 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/PMC3383840/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Robinson, Sarah -- Barbier de Reuille, Pierre -- Chan, Jordi -- Bergmann, Dominique -- Prusinkiewicz, Przemyslaw -- Coen, Enrico -- 1R01GM086632-02/GM/NIGMS NIH HHS/ -- BB/F005997/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- R01 GM086632/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2011 Sep 9;333(6048):1436-40. doi: 10.1126/science.1202185.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉John Innes Centre, Norwich Research Park, Colney, Norwich NR4 7UH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21903812" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/*cytology/genetics ; Arabidopsis Proteins/genetics/*metabolism ; Basic Helix-Loop-Helix Transcription Factors/genetics/*metabolism ; Cell Cycle Proteins/genetics/metabolism ; Cell Differentiation ; Cell Division ; Cell Lineage ; *Cell Polarity ; Cell Size ; Meristem/*cytology ; Microscopy, Confocal ; Models, Biological ; Plant Epidermis/cytology ; Plant Leaves/cytology ; Plant Stomata/*cytology ; Recombinant Fusion Proteins/metabolism
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  • 75
    Publication Date: 2011-11-15
    Description: Intestinal epithelial stem cell identity and location have been the subject of substantial research. Cells in the +4 niche are slow-cycling and label-retaining, whereas a different stem cell niche located at the crypt base is occupied by crypt base columnar (CBC) cells. CBCs are distinct from +4 cells, and the relationship between them is unknown, though both give rise to all intestinal epithelial lineages. We demonstrate that Hopx, an atypical homeobox protein, is a specific marker of +4 cells. Hopx-expressing cells give rise to CBCs and all mature intestinal epithelial lineages. Conversely, CBCs can give rise to +4 Hopx-positive cells. These findings demonstrate a bidirectional lineage relationship between active and quiescent stem cells in their niches.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3705713/" 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/PMC3705713/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takeda, Norifumi -- Jain, Rajan -- LeBoeuf, Matthew R -- Wang, Qiaohong -- Lu, Min Min -- Epstein, Jonathan A -- R01 HL071546/HL/NHLBI NIH HHS/ -- U01 HL100405/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2011 Dec 9;334(6061):1420-4. doi: 10.1126/science.1213214. Epub 2011 Nov 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22075725" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Cycle ; Cell Differentiation ; Cell Lineage ; Cell Proliferation ; Cells, Cultured ; Epithelial Cells/*cytology ; Homeodomain Proteins/analysis/genetics ; Intestinal Mucosa/*cytology/drug effects ; Intestine, Small/*cytology/drug effects ; Mice ; Models, Biological ; Multipotent Stem Cells/*cytology/physiology ; Paneth Cells/cytology ; *Stem Cell Niche ; Tamoxifen/pharmacology
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  • 76
    Publication Date: 2011-07-19
    Description: Some organs in animals display left-right (LR) asymmetry. To better understand LR asymmetric morphogenesis in Drosophila, we studied LR directional rotation of the hindgut epithelial tube. Hindgut epithelial cells adopt a LR asymmetric (chiral) cell shape within their plane, and we refer to this cell behavior as planar cell-shape chirality (PCC). Drosophila E-cadherin (DE-Cad) is distributed to cell boundaries with LR asymmetry, which is responsible for the PCC formation. Myosin ID switches the LR polarity found in PCC and in DE-Cad distribution, which coincides with the direction of rotation. An in silico simulation showed that PCC is sufficient to induce the directional rotation of this tissue. Thus, the intrinsic chirality of epithelial cells in vivo is an underlying mechanism for LR asymmetric tissue morphogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Taniguchi, Kiichiro -- Maeda, Reo -- Ando, Tadashi -- Okumura, Takashi -- Nakazawa, Naotaka -- Hatori, Ryo -- Nakamura, Mitsutoshi -- Hozumi, Shunya -- Fujiwara, Hiroo -- Matsuno, Kenji -- New York, N.Y. -- Science. 2011 Jul 15;333(6040):339-41. doi: 10.1126/science.1200940.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21764746" target="_blank"〉PubMed〈/a〉
    Keywords: Adherens Junctions ; Animals ; Body Patterning ; Cadherins/*metabolism ; Cell Polarity ; *Cell Shape ; Computer Simulation ; Drosophila/cytology/*embryology/genetics ; Drosophila Proteins/genetics/*metabolism ; Epithelial Cells/*cytology ; Intestines/cytology/embryology ; Models, Biological ; Morphogenesis ; Myosin Type I/genetics/*metabolism ; Rotation
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  • 77
    Publication Date: 2011-06-18
    Description: The bacterial pathogen Legionella pneumophila exploits host cell vesicle transport by transiently manipulating the activity of the small guanosine triphosphatase (GTPase) Rab1. The effector protein SidM recruits Rab1 to the Legionella-containing vacuole (LCV), where it activates Rab1 and then AMPylates it by covalently adding adenosine monophosphate (AMP). L. pneumophila GTPase-activating protein LepB inactivates Rab1 before its removal from LCVs. Because LepB cannot bind AMPylated Rab1, the molecular events leading to Rab1 inactivation are unknown. We found that the effector protein SidD from L. pneumophila catalyzed AMP release from Rab1, generating de-AMPylated Rab1 accessible for inactivation by LepB. L. pneumophila mutants lacking SidD were defective for Rab1 removal from LCVs, identifying SidD as the missing link connecting the processes of early Rab1 accumulation and subsequent Rab1 removal during infection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3209958/" 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/PMC3209958/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Neunuebel, M Ramona -- Chen, Yang -- Gaspar, Andrew H -- Backlund, Peter S Jr -- Yergey, Alfred -- Machner, Matthias P -- ZIA HD008893-01/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2011 Jul 22;333(6041):453-6. doi: 10.1126/science.1207193. Epub 2011 Jun 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21680813" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Monophosphate/*metabolism ; Animals ; Bacterial Proteins/genetics/*metabolism ; COS Cells ; Cercopithecus aethiops ; Golgi Apparatus/metabolism ; Guanine Nucleotide Exchange Factors/metabolism ; Guanosine Monophosphate/metabolism ; Guanosine Triphosphate/metabolism ; Humans ; Legionella pneumophila/*metabolism/pathogenicity ; Ligands ; Macrophages/metabolism/microbiology ; Mice ; Mice, Inbred A ; Models, Biological ; Mutant Proteins/metabolism ; U937 Cells ; Vacuoles/metabolism/*microbiology ; rab1 GTP-Binding Proteins/*metabolism
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  • 78
    Publication Date: 2011-09-24
    Description: Nonhexameric helicases use adenosine triphosphate (ATP) to unzip base pairs in double-stranded nucleic acids (dsNAs). Studies have suggested that these helicases unzip dsNAs in single-base pair increments, consuming one ATP molecule per base pair, but direct evidence for this mechanism is lacking. We used optical tweezers to follow the unwinding of double-stranded RNA by the hepatitis C virus NS3 helicase. Single-base pair steps by NS3 were observed, along with nascent nucleotide release that was asynchronous with base pair opening. Asynchronous release of nascent nucleotides rationalizes various observations of its dsNA unwinding and may be used to coordinate the translocation speed of NS3 along the RNA during viral replication.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172460/" 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/PMC4172460/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cheng, Wei -- Arunajadai, Srikesh G -- Moffitt, Jeffrey R -- Tinoco, Ignacio Jr -- Bustamante, Carlos -- 5R01GM010840/GM/NIGMS NIH HHS/ -- 5R01GM032543/GM/NIGMS NIH HHS/ -- R01 GM010840/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Sep 23;333(6050):1746-9. doi: 10.1126/science.1206023.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA. chengwe@umich.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21940894" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Algorithms ; Base Pairing ; Hepacivirus/*enzymology ; Kinetics ; Models, Biological ; Nucleic Acid Conformation ; Optical Tweezers ; RNA Helicases/*metabolism ; RNA, Double-Stranded/chemistry/*metabolism ; RNA, Viral/chemistry/*metabolism ; Viral Nonstructural Proteins/*metabolism
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  • 79
    Publication Date: 2011-04-30
    Description: Catastrophic ecological regime shifts may be announced in advance by statistical early warning signals such as slowing return rates from perturbation and rising variance. The theoretical background for these indicators is rich, but real-world tests are rare, especially for whole ecosystems. We tested the hypothesis that these statistics would be early warning signals for an experimentally induced regime shift in an aquatic food web. We gradually added top predators to a lake over 3 years to destabilize its food web. An adjacent lake was monitored simultaneously as a reference ecosystem. Warning signals of a regime shift were evident in the manipulated lake during reorganization of the food web more than a year before the food web transition was complete, corroborating theory for leading indicators of ecological regime shifts.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carpenter, S R -- Cole, J J -- Pace, M L -- Batt, R -- Brock, W A -- Cline, T -- Coloso, J -- Hodgson, J R -- Kitchell, J F -- Seekell, D A -- Smith, L -- Weidel, B -- New York, N.Y. -- Science. 2011 May 27;332(6033):1079-82. doi: 10.1126/science.1203672. Epub 2011 Apr 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Limnology, University of Wisconsin, Madison, WI 53706, USA. srcarpen@wisc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21527677" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bass ; Biomass ; Chlorophyll/analysis ; *Ecosystem ; *Fishes ; *Food Chain ; *Fresh Water/chemistry ; Models, Biological ; Nonlinear Dynamics ; *Phytoplankton ; Population Dynamics ; *Zooplankton
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  • 80
    Publication Date: 2011-04-23
    Description: Mucosal surfaces constantly encounter microbes. Toll-like receptors (TLRs) mediate recognition of microbial patterns to eliminate pathogens. By contrast, we demonstrate that the prominent gut commensal Bacteroides fragilis activates the TLR pathway to establish host-microbial symbiosis. TLR2 on CD4(+) T cells is required for B. fragilis colonization of a unique mucosal niche in mice during homeostasis. A symbiosis factor (PSA, polysaccharide A) of B. fragilis signals through TLR2 directly on Foxp3(+) regulatory T cells to promote immunologic tolerance. B. fragilis lacking PSA is unable to restrain T helper 17 cell responses and is defective in niche-specific mucosal colonization. Therefore, commensal bacteria exploit the TLR pathway to actively suppress immunity. We propose that the immune system can discriminate between pathogens and the microbiota through recognition of symbiotic bacterial molecules in a process that engenders commensal colonization.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164325/" 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/PMC3164325/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Round, June L -- Lee, S Melanie -- Li, Jennifer -- Tran, Gloria -- Jabri, Bana -- Chatila, Talal A -- Mazmanian, Sarkis K -- AI 080002/AI/NIAID NIH HHS/ -- AI 088626/AI/NIAID NIH HHS/ -- DK 078938/DK/NIDDK NIH HHS/ -- DK 083633/DK/NIDDK NIH HHS/ -- R01 AI085090/AI/NIAID NIH HHS/ -- R01 AI085090-01/AI/NIAID NIH HHS/ -- R01 AI085090-01S1/AI/NIAID NIH HHS/ -- R01 AI085090-02/AI/NIAID NIH HHS/ -- R01 AI085090-03/AI/NIAID NIH HHS/ -- R01 DK078938/DK/NIDDK NIH HHS/ -- R01 DK078938-01A2/DK/NIDDK NIH HHS/ -- R01 DK078938-02/DK/NIDDK NIH HHS/ -- R01 DK078938-03/DK/NIDDK NIH HHS/ -- R01 DK078938-04/DK/NIDDK NIH HHS/ -- R21 AI080002/AI/NIAID NIH HHS/ -- R21 AI080002-01/AI/NIAID NIH HHS/ -- R21 AI080002-02/AI/NIAID NIH HHS/ -- R21 AI088626/AI/NIAID NIH HHS/ -- R21 AI088626-01/AI/NIAID NIH HHS/ -- R21 AI088626-02/AI/NIAID NIH HHS/ -- R21 DK083633/DK/NIDDK NIH HHS/ -- R21 DK083633-01A1/DK/NIDDK NIH HHS/ -- R21 DK083633-02/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2011 May 20;332(6032):974-7. doi: 10.1126/science.1206095. Epub 2011 Apr 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA. jround@caltech.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21512004" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacteroides fragilis/*growth & development/*immunology ; Colon/immunology/microbiology ; Germ-Free Life ; Homeostasis ; Humans ; *Immune Tolerance ; Immunity, Mucosal ; Interleukin-10/metabolism ; Intestinal Mucosa/*immunology/*microbiology ; Metagenome ; Mice ; Mice, Inbred C57BL ; Models, Biological ; Polysaccharides, Bacterial/immunology/*metabolism ; Signal Transduction ; Specific Pathogen-Free Organisms ; Symbiosis ; T-Lymphocytes, Regulatory/immunology ; Th17 Cells/immunology ; Toll-Like Receptor 2/immunology/*metabolism
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  • 81
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2011-01-22
    Description: Animal migrations are often spectacular, and migratory species harbor zoonotic pathogens of importance to humans. Animal migrations are expected to enhance the global spread of pathogens and facilitate cross-species transmission. This does happen, but new research has also shown that migration allows hosts to escape from infected habitats, reduces disease levels when infected animals do not migrate successfully, and may lead to the evolution of less-virulent pathogens. Migratory demands can also reduce immune function, with consequences for host susceptibility and mortality. Studies of pathogen dynamics in migratory species and how these will respond to global change are urgently needed to predict future disease risks for wildlife and humans alike.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Altizer, Sonia -- Bartel, Rebecca -- Han, Barbara A -- New York, N.Y. -- Science. 2011 Jan 21;331(6015):296-302. doi: 10.1126/science.1194694.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Odum School of Ecology, University of Georgia, Athens, GA 30602, USA. saltizer@uga.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21252339" target="_blank"〉PubMed〈/a〉
    Keywords: *Animal Migration ; Animals ; Biological Evolution ; Climate Change ; *Communicable Diseases/epidemiology/immunology/transmission/veterinary ; Disease Susceptibility ; Ecosystem ; Human Activities ; Humans ; Immunity ; Models, Biological ; Risk
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  • 82
    Publication Date: 2011-10-15
    Description: Periodic stripe patterns are ubiquitous in living organisms, yet the underlying developmental processes are complex and difficult to disentangle. We describe a synthetic genetic circuit that couples cell density and motility. This system enabled programmed Escherichia coli cells to form periodic stripes of high and low cell densities sequentially and autonomously. Theoretical and experimental analyses reveal that the spatial structure arises from a recurrent aggregation process at the front of the continuously expanding cell population. The number of stripes formed could be tuned by modulating the basal expression of a single gene. The results establish motility control as a simple route to establishing recurrent structures without requiring an extrinsic pacemaker.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Chenli -- Fu, Xiongfei -- Liu, Lizhong -- Ren, Xiaojing -- Chau, Carlos K L -- Li, Sihong -- Xiang, Lu -- Zeng, Hualing -- Chen, Guanhua -- Tang, Lei-Han -- Lenz, Peter -- Cui, Xiaodong -- Huang, Wei -- Hwa, Terence -- Huang, Jian-Dong -- New York, N.Y. -- Science. 2011 Oct 14;334(6053):238-41. doi: 10.1126/science.1209042.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, The University of Hong Kong, Pokfulam, Hong Kong, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21998392" target="_blank"〉PubMed〈/a〉
    Keywords: Acyl-Butyrolactones/metabolism ; Bacterial Load ; Cell Proliferation ; Culture Media ; Diffusion ; Escherichia coli K12/cytology/genetics/*growth & development/*physiology ; Gene Expression Regulation, Bacterial ; Gene Regulatory Networks ; Kinetics ; Models, Biological ; Movement ; Quorum Sensing ; Synthetic Biology
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  • 83
    Publication Date: 2011-11-19
    Description: Both human and nonhuman decision-makers can deviate from optimal choice by making context-dependent choices. Because ignoring context information can be beneficial, this is called a "less-is-more effect." The fact that organisms are so sensitive to the context is thus paradoxical and calls for the inclusion of an ecological perspective. In an experiment with starlings, adding cues that identified the context impaired performance in simultaneous prey choices but improved it in sequential prey encounters, in which subjects could reject opportunities in order to search instead in the background. Because sequential prey encounters are likely to be more frequent in nature, storing and using contextual information appears to be ecologically rational on balance by conditioning acceptance of each opportunity to the relative richness of the background, even if this causes context-dependent suboptimal preferences in (less-frequent) simultaneous choices. In ecologically relevant scenarios, more information seems to be more.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Freidin, Esteban -- Kacelnik, Alex -- BB/G007144/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2011 Nov 18;334(6058):1000-2. doi: 10.1126/science.1209626.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Zoology, University of Oxford, Oxford, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22096203" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Appetitive Behavior ; *Behavior, Animal ; *Choice Behavior ; Cues ; Decision Making ; Feeding Behavior ; Food ; Memory ; Models, Biological ; Starlings/*physiology
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  • 84
    Publication Date: 2011-04-02
    Description: Heparan and chondroitin sulfate proteoglycans (HSPGs and CSPGs, respectively) regulate numerous cell surface signaling events, with typically opposite effects on cell function. CSPGs inhibit nerve regeneration through receptor protein tyrosine phosphatase sigma (RPTPsigma). Here we report that RPTPsigma acts bimodally in sensory neuron extension, mediating CSPG inhibition and HSPG growth promotion. Crystallographic analyses of a shared HSPG-CSPG binding site reveal a conformational plasticity that can accommodate diverse glycosaminoglycans with comparable affinities. Heparan sulfate and analogs induced RPTPsigma ectodomain oligomerization in solution, which was inhibited by chondroitin sulfate. RPTPsigma and HSPGs colocalize in puncta on sensory neurons in culture, whereas CSPGs occupy the extracellular matrix. These results lead to a model where proteoglycans can exert opposing effects on neuronal extension by competing to control the oligomerization of a common receptor.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3154093/" 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/PMC3154093/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Coles, Charlotte H -- Shen, Yingjie -- Tenney, Alan P -- Siebold, Christian -- Sutton, Geoffrey C -- Lu, Weixian -- Gallagher, John T -- Jones, E Yvonne -- Flanagan, John G -- Aricescu, A Radu -- 090532/Wellcome Trust/United Kingdom -- 10976/Cancer Research UK/United Kingdom -- EY11559/EY/NEI NIH HHS/ -- G0700232/Medical Research Council/United Kingdom -- G0900084/Medical Research Council/United Kingdom -- HD29417/HD/NICHD NIH HHS/ -- R01 EY011559/EY/NEI NIH HHS/ -- R01 EY011559-19/EY/NEI NIH HHS/ -- R37 HD029417/HD/NICHD NIH HHS/ -- R37 HD029417-20/HD/NICHD NIH HHS/ -- Cancer Research UK/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2011 Apr 22;332(6028):484-8. doi: 10.1126/science.1200840. Epub 2011 Mar 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21454754" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Axons/*physiology ; Binding Sites ; Cell Membrane/metabolism ; Cells, Cultured ; Chondroitin Sulfate Proteoglycans/chemistry/*metabolism ; Chondroitin Sulfates/chemistry/metabolism ; Crystallography, X-Ray ; Extracellular Matrix ; Ganglia, Spinal ; Glypicans/metabolism ; Growth Cones/metabolism ; Heparan Sulfate Proteoglycans/chemistry/*metabolism ; Heparitin Sulfate/analogs & derivatives/chemistry/metabolism ; Humans ; Mice ; Models, Biological ; Models, Molecular ; Molecular Sequence Data ; Neurites/physiology ; Neurocan/metabolism ; Protein Conformation ; Protein Multimerization ; Protein Structure, Tertiary ; Receptor-Like Protein Tyrosine Phosphatases, Class 2/*chemistry/*metabolism ; Sensory Receptor Cells/*physiology
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  • 85
    Publication Date: 2011-09-24
    Description: We studied the mechanical process of seed pods opening in Bauhinia variegate and found a chirality-creating mechanism, which turns an initially flat pod valve into a helix. We studied con fi gurations of strips cut from pod valve tissue and from composite elastic materials that mimic its structure. The experiments reveal various helical con fi gurations with sharp morphological transitions between them. Using the mathematical framework of "incompatible elasticity," we modeled the pod as a thin strip with a flat intrinsic metric and a saddle-like intrinsic curvature. Our theoretical analysis quantitatively predicts all observed con fi gurations, thus linking the pod's microscopic structure and macroscopic conformation. We suggest that this type of incompatible strip is likely to play a role in the self-assembly of chiral macromolecules and could be used for the engineering of synthetic self-shaping devices.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Armon, Shahaf -- Efrati, Efi -- Kupferman, Raz -- Sharon, Eran -- New York, N.Y. -- Science. 2011 Sep 23;333(6050):1726-30. doi: 10.1126/science.1203874.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Racah Institute of Physics, Hebrew University of Jerusalem, Jerusalem 91904, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21940888" target="_blank"〉PubMed〈/a〉
    Keywords: Bauhinia/*anatomy & histology/physiology ; Biomimetic Materials ; Elasticity ; *Latex ; Mathematical Concepts ; Models, Biological ; Physical Phenomena ; Seeds/*anatomy & histology/*physiology
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  • 86
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2011-07-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arner, Peter -- New York, N.Y. -- Science. 2011 Jul 8;333(6039):163-4. doi: 10.1126/science.1209418.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden. peter.arner@ki.se〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21737725" target="_blank"〉PubMed〈/a〉
    Keywords: Adipocytes/*enzymology ; Adipose Tissue/*enzymology/pathology ; Animals ; Cachexia/*enzymology/etiology/pathology/prevention & control ; Humans ; Lipase/deficiency/*metabolism ; *Lipolysis ; Lung Neoplasms/complications/enzymology/metabolism/pathology ; Melanoma, Experimental/complications/enzymology/metabolism/pathology ; Mice ; Models, Biological ; Muscle, Skeletal/metabolism/pathology ; Neoplasms/complications/*enzymology/metabolism/pathology ; Oxidation-Reduction ; Sterol Esterase/antagonists & inhibitors/deficiency/*metabolism ; Triglycerides/metabolism
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  • 87
    Publication Date: 2011-06-04
    Description: Rod-shaped bacteria elongate by the action of cell wall synthesis complexes linked to underlying dynamic MreB filaments. To understand how the movements of these filaments relate to cell wall synthesis, we characterized the dynamics of MreB and the cell wall elongation machinery using high-precision particle tracking in Bacillus subtilis. We found that MreB and the elongation machinery moved circumferentially around the cell, perpendicular to its length, with nearby synthesis complexes and MreB filaments moving independently in both directions. Inhibition of cell wall synthesis by various methods blocked the movement of MreB. Thus, bacteria elongate by the uncoordinated, circumferential movements of synthetic complexes that insert radial hoops of new peptidoglycan during their transit, possibly driving the motion of the underlying MreB filaments.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235694/" 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/PMC3235694/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Garner, Ethan C -- Bernard, Remi -- Wang, Wenqin -- Zhuang, Xiaowei -- Rudner, David Z -- Mitchison, Tim -- R01 GM039565/GM/NIGMS NIH HHS/ -- R01 GM039565-24/GM/NIGMS NIH HHS/ -- R01 GM073831/GM/NIGMS NIH HHS/ -- R01 GM096450/GM/NIGMS NIH HHS/ -- R01-GM073831/GM/NIGMS NIH HHS/ -- R01-GM096450/GM/NIGMS NIH HHS/ -- R01-GM39565/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Jul 8;333(6039):222-5. doi: 10.1126/science.1203285. Epub 2011 Jun 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. ethan.garner@hms.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21636745" target="_blank"〉PubMed〈/a〉
    Keywords: Anti-Bacterial Agents/pharmacology ; Bacillus subtilis/drug effects/*growth & development/*metabolism/ultrastructure ; Bacterial Proteins/chemistry/genetics/*metabolism ; Cell Wall/*metabolism ; Models, Biological ; Morphogenesis ; Motion ; Mutation ; Peptidoglycan/chemistry/*metabolism ; Polymerization ; Recombinant Fusion Proteins/chemistry/metabolism
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  • 88
    Publication Date: 2011-02-19
    Description: Cotranslational targeting of membrane and secretory proteins is mediated by the universally conserved signal recognition particle (SRP). Together with its receptor (SR), SRP mediates the guanine triphosphate (GTP)-dependent delivery of translating ribosomes bearing signal sequences to translocons on the target membrane. Here, we present the crystal structure of the SRP:SR complex at 3.9 angstrom resolution and biochemical data revealing that the activated SRP:SR guanine triphosphatase (GTPase) complex binds the distal end of the SRP hairpin RNA where GTP hydrolysis is stimulated. Combined with previous findings, these results suggest that the SRP:SR GTPase complex initially assembles at the tetraloop end of the SRP RNA and then relocalizes to the opposite end of the RNA. This rearrangement provides a mechanism for coupling GTP hydrolysis to the handover of cargo to the translocon.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3758919/" 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/PMC3758919/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ataide, Sandro F -- Schmitz, Nikolaus -- Shen, Kuang -- Ke, Ailong -- Shan, Shu-ou -- Doudna, Jennifer A -- Ban, Nenad -- GM078024/GM/NIGMS NIH HHS/ -- R01 GM078024/GM/NIGMS NIH HHS/ -- R01 GM086766/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Feb 18;331(6019):881-6. doi: 10.1126/science.1196473.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Biology and Biophysics, Eidgenossische Technische Hochschule Zurich (ETH Zurich), Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21330537" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry/metabolism ; Base Sequence ; Binding Sites ; Crystallization ; Crystallography, X-Ray ; Enzyme Activation ; Escherichia coli/chemistry/metabolism ; Escherichia coli Proteins/*chemistry/metabolism ; GTP Phosphohydrolases/chemistry/metabolism ; Guanosine Triphosphate/analogs & derivatives/chemistry/metabolism ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Models, Biological ; Models, Molecular ; Nucleic Acid Conformation ; Protein Conformation ; Protein Multimerization ; Protein Structure, Tertiary ; Protein Transport ; RNA, Bacterial/*chemistry/metabolism ; Receptors, Cytoplasmic and Nuclear/*chemistry/metabolism ; Ribosomal Proteins/chemistry/metabolism ; Ribosomes/metabolism ; Signal Recognition Particle/*chemistry/metabolism
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  • 89
    Publication Date: 2011-04-30
    Description: Using a regionally calibrated model, Sinervo et al. (Reports, 14 May 2010, p. 894) predicted potential climate change impacts on lizard populations and estimated that many extinctions are under way. We argue that this model is not sufficient for predicting global losses in lizard species in response to anthropogenic climate change.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clusella-Trullas, Susana -- Chown, Steven L -- New York, N.Y. -- Science. 2011 Apr 29;332(6029):537; author reply 537. doi: 10.1126/science.1195193.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Invasion Biology, Department of Botany and Zoology, Stellenbosch University, Stellenbosch 7602, South Africa. sct333@sun.ac.za〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21527699" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Body Temperature ; Body Temperature Regulation ; *Climate Change ; *Ecosystem ; *Extinction, Biological ; Forecasting ; *Lizards ; Models, Biological ; Population Dynamics ; Temperature
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  • 90
    Publication Date: 2011-05-14
    Description: Adenosine triphosphate (ATP)-binding cassette (ABC) transporters convert chemical energy from ATP hydrolysis to mechanical work for substrate translocation. They function by alternating between two states, exposing the substrate-binding site to either side of the membrane. A key question that remains to be addressed is how substrates initiate the transport cycle. Using x-ray crystallography, we have captured the maltose transporter in an intermediate step between the inward- and outward-facing states. We show that interactions with substrate-loaded maltose-binding protein in the periplasm induce a partial closure of the MalK dimer in the cytoplasm. ATP binding to this conformation then promotes progression to the outward-facing state. These results, interpreted in light of biochemical and functional studies, provide a structural basis to understand allosteric communication in ABC transporters.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Oldham, Michael L -- Chen, Jue -- GM070515/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Jun 3;332(6034):1202-5. doi: 10.1126/science.1200767. Epub 2011 May 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Purdue University, Howard Hughes Medical Institute, West Lafayette, IN 47907, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21566157" target="_blank"〉PubMed〈/a〉
    Keywords: ATP-Binding Cassette Transporters/*chemistry/metabolism ; Adenosine Triphosphate/metabolism ; Amino Acid Motifs ; Binding Sites ; Biological Transport, Active ; Catalytic Domain ; Crystallization ; Crystallography, X-Ray ; Escherichia coli/*chemistry/metabolism ; Escherichia coli Proteins/*chemistry/metabolism ; Hydrogen Bonding ; Maltose/metabolism ; Maltose-Binding Proteins/chemistry/metabolism ; Models, Biological ; Models, Molecular ; Monosaccharide Transport Proteins/*chemistry/metabolism ; Periplasm/metabolism ; Protein Conformation ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary
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  • 91
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2011-01-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gibbons, Ann -- New York, N.Y. -- Science. 2011 Jan 28;331(6016):392-4. doi: 10.1126/science.331.6016.392.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21273464" target="_blank"〉PubMed〈/a〉
    Keywords: Africa ; Animals ; *Anthropology ; *Biological Evolution ; Breeding ; *Genome ; *Genome, Human ; *Hominidae/genetics ; Humans ; *Hybridization, Genetic ; Models, Biological
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  • 92
    Publication Date: 2011-12-14
    Description: Plant resistance proteins detect the presence of specific pathogen effectors and initiate effector-triggered immunity. Few immune regulators downstream of resistance proteins have been identified, none of which are known virulence targets of effectors. We show that Arabidopsis ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1), a positive regulator of basal resistance and of effector-triggered immunity specifically mediated by Toll-interleukin-1 receptor-nucleotide binding-leucine-rich repeat (TIR-NB-LRR) resistance proteins, forms protein complexes with the TIR-NB-LRR disease resistance proteins RPS4 and RPS6 and with the negative immune regulator SRFR1 at a cytoplasmic membrane. Further, the cognate bacterial effectors AvrRps4 and HopA1 disrupt these EDS1 complexes. Tight association of EDS1 with TIR-NB-LRR-mediated immunity may therefore derive mainly from being guarded by TIR-NB-LRR proteins, and activation of this branch of effector-triggered immunity may directly connect to the basal resistance signaling pathway via EDS1.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bhattacharjee, Saikat -- Halane, Morgan K -- Kim, Sang Hee -- Gassmann, Walter -- New York, N.Y. -- Science. 2011 Dec 9;334(6061):1405-8. doi: 10.1126/science.1211592.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Plant Sciences, Christopher S. Bond Life Sciences Center and Interdisciplinary Plant Group, University of Missouri, Columbia, MO 65211, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22158819" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/genetics/*immunology/*metabolism/microbiology ; Arabidopsis Proteins/genetics/*metabolism ; Bacterial Proteins/*metabolism ; Cell Membrane/metabolism ; Cell Nucleus/metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Gene Expression Regulation, Plant ; Genes, Plant ; *Immunity, Innate ; Models, Biological ; Plant Diseases/immunology/microbiology ; Plant Proteins/*metabolism ; Plants, Genetically Modified ; Pseudomonas syringae/growth & development ; Signal Transduction ; Tobacco/genetics/metabolism
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  • 93
    Publication Date: 2011-06-11
    Description: Active nuclear import of soluble cargo involves transport factors that shuttle cargo through the nuclear pore complex (NPC) by binding to phenylalanine-glycine (FG) domains. How nuclear membrane proteins cross through the NPC to reach the inner membrane is presently unclear. We found that at least a 120-residue-long intrinsically disordered linker was required for the import of membrane proteins carrying a nuclear localization signal for the transport factor karyopherin-alpha. We propose an import mechanism for membrane proteins in which an unfolded linker slices through the NPC scaffold to enable binding between the transport factor and the FG domains in the center of the NPC.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meinema, Anne C -- Laba, Justyna K -- Hapsari, Rizqiya A -- Otten, Renee -- Mulder, Frans A A -- Kralt, Annemarie -- van den Bogaart, Geert -- Lusk, C Patrick -- Poolman, Bert -- Veenhoff, Liesbeth M -- New York, N.Y. -- Science. 2011 Jul 1;333(6038):90-3. doi: 10.1126/science.1205741. Epub 2011 Jun 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute, Netherlands Proteomics Centre, Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21659568" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Amino Acid Sequence ; Endoplasmic Reticulum/metabolism ; Karyopherins/chemistry/metabolism ; Membrane Proteins/*chemistry/genetics/*metabolism ; Models, Biological ; Molecular Sequence Data ; Nuclear Envelope/*metabolism ; Nuclear Localization Signals ; Nuclear Pore/*metabolism ; Nuclear Pore Complex Proteins/chemistry/genetics/*metabolism ; Nuclear Proteins/chemistry/genetics/metabolism ; Protein Folding ; Protein Structure, Tertiary ; Recombinant Fusion Proteins/chemistry/metabolism ; Saccharomyces cerevisiae/*metabolism ; Saccharomyces cerevisiae Proteins/chemistry/genetics/metabolism
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  • 94
    Publication Date: 2011-04-09
    Description: Cytotoxic T lymphocyte antigen 4 (CTLA-4) is an essential negative regulator of T cell immune responses whose mechanism of action is the subject of debate. CTLA-4 shares two ligands (CD80 and CD86) with a stimulatory receptor, CD28. Here, we show that CTLA-4 can capture its ligands from opposing cells by a process of trans-endocytosis. After removal, these costimulatory ligands are degraded inside CTLA-4-expressing cells, resulting in impaired costimulation via CD28. Acquisition of CD86 from antigen-presenting cells is stimulated by T cell receptor engagement and observed in vitro and in vivo. These data reveal a mechanism of immune regulation in which CTLA-4 acts as an effector molecule to inhibit CD28 costimulation by the cell-extrinsic depletion of ligands, accounting for many of the known features of the CD28-CTLA-4 system.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3198051/" 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/PMC3198051/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Qureshi, Omar S -- Zheng, Yong -- Nakamura, Kyoko -- Attridge, Kesley -- Manzotti, Claire -- Schmidt, Emily M -- Baker, Jennifer -- Jeffery, Louisa E -- Kaur, Satdip -- Briggs, Zoe -- Hou, Tie Z -- Futter, Clare E -- Anderson, Graham -- Walker, Lucy S K -- Sansom, David M -- 17851/Arthritis Research UK/United Kingdom -- BB/D011000/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/H013598/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- G0400931/Medical Research Council/United Kingdom -- G0401620/Medical Research Council/United Kingdom -- G0802382/Medical Research Council/United Kingdom -- G1000213/Medical Research Council/United Kingdom -- G9818340/Medical Research Council/United Kingdom -- Arthritis Research UK/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2011 Apr 29;332(6029):600-3. doi: 10.1126/science.1202947. Epub 2011 Apr 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council (MRC) Centre for Immune Regulation, School of Immunity and Infection, Institute of Biomedical Research, University of Birmingham Medical School, Birmingham B15 2TT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21474713" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/*immunology/metabolism ; Antigens, CD28/*immunology ; Antigens, CD80/*immunology/metabolism ; Antigens, CD86/*immunology/metabolism ; CHO Cells ; CTLA-4 Antigen ; Cricetinae ; Cricetulus ; Dendritic Cells/immunology ; *Endocytosis ; Humans ; Jurkat Cells ; Ligands ; Lymphocyte Activation ; Mice ; Mice, Transgenic ; Models, Biological ; Ovalbumin/immunology ; Receptors, Antigen, T-Cell/immunology ; Recombinant Fusion Proteins/metabolism ; T-Lymphocyte Subsets/*immunology/metabolism ; T-Lymphocytes, Regulatory/immunology/metabolism
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  • 95
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2011-03-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Raiborg, Camilla -- Stenmark, Harald -- New York, N.Y. -- Science. 2011 Mar 25;331(6024):1533-4. doi: 10.1126/science.1204208.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Montebello, Oslo, Norway.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21436431" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/metabolism ; Calcium-Binding Proteins/metabolism ; Cell Cycle Proteins/metabolism ; *Cell Division ; Cell Membrane/metabolism ; Endosomal Sorting Complexes Required for Transport/*chemistry/*metabolism ; Humans ; Microscopy, Electron ; Microtubules/*metabolism/*ultrastructure ; Models, Biological ; Nuclear Proteins/metabolism ; Protein Conformation ; Protein Multimerization
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 96
    Publication Date: 2011-08-20
    Description: Immune clearance and resource limitation (via red blood cell depletion) shape the peaks and troughs of malaria parasitemia, which in turn affect disease severity and transmission. Quantitatively partitioning the relative roles of these effects through time is challenging. Using data from rodent malaria, we estimated the effective propagation number, which reflects the relative importance of contrasting within-host control mechanisms through time and is sensitive to the inoculating parasite dose. Our analysis showed that the capacity of innate responses to restrict initial parasite growth saturates with parasite dose and that experimentally enhanced innate immunity can affect parasite density indirectly via resource depletion. Such a statistical approach offers a tool to improve targeting of drugs or vaccines for human therapy by revealing the dynamics and interactions of within-host regulatory mechanisms.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891600/" 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/PMC3891600/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Metcalf, C J E -- Graham, A L -- Huijben, S -- Barclay, V C -- Long, G H -- Grenfell, B T -- Read, A F -- Bjornstad, O N -- R01 GM089932/GM/NIGMS NIH HHS/ -- R01GM089932/GM/NIGMS NIH HHS/ -- R24 HD047879/HD/NICHD NIH HHS/ -- Biotechnology and Biological Sciences Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2011 Aug 19;333(6045):984-8. doi: 10.1126/science.1204588.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Zoology, Oxford University, Oxford OX1 3PS, UK. charlotte.metcalf@zoo.ox.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21852493" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptive Immunity ; Animals ; Antibodies/immunology ; CD4-Positive T-Lymphocytes/immunology ; Erythrocyte Aging ; Erythrocyte Count ; Erythrocytes/*parasitology/physiology ; Host-Parasite Interactions ; Humans ; Immunity, Innate ; Interleukin-10/immunology/metabolism ; Malaria/blood/*immunology/*parasitology ; Mice ; Models, Biological ; Models, Statistical ; *Parasitemia/blood/immunology/parasitology ; Plasmodium chabaudi/immunology/*physiology ; Receptors, Interleukin-10/immunology ; Regression Analysis
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 97
    Publication Date: 2011-07-23
    Description: Low-trophic level species account for more than 30% of global fisheries production and contribute substantially to global food security. We used a range of ecosystem models to explore the effects of fishing low-trophic level species on marine ecosystems, including marine mammals and seabirds, and on other commercially important species. In five well-studied ecosystems, we found that fishing these species at conventional maximum sustainable yield (MSY) levels can have large impacts on other parts of the ecosystem, particularly when they constitute a high proportion of the biomass in the ecosystem or are highly connected in the food web. Halving exploitation rates would result in much lower impacts on marine ecosystems while still achieving 80% of MSY.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smith, Anthony D M -- Brown, Christopher J -- Bulman, Catherine M -- Fulton, Elizabeth A -- Johnson, Penny -- Kaplan, Isaac C -- Lozano-Montes, Hector -- Mackinson, Steven -- Marzloff, Martin -- Shannon, Lynne J -- Shin, Yunne-Jai -- Tam, Jorge -- New York, N.Y. -- Science. 2011 Aug 26;333(6046):1147-50. doi: 10.1126/science.1209395. Epub 2011 Jul 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Commonwealth Scientific and Industrial Research Organization, Wealth from Oceans Flagship, Hobart, TAS 7001, Australia. tony.d.smith@csiro.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21778363" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Aquatic Organisms ; Biodiversity ; Biomass ; Birds ; *Ecosystem ; *Fisheries ; *Fishes ; *Food Chain ; Mammals ; Models, Biological ; Oceans and Seas ; Population Dynamics
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 98
    Publication Date: 2011-09-24
    Description: For more than 30 years, the relationship between net primary productivity and species richness has generated intense debate in ecology about the processes regulating local diversity. The original view, which is still widely accepted, holds that the relationship is hump-shaped, with richness first rising and then declining with increasing productivity. Although recent meta-analyses questioned the generality of hump-shaped patterns, these syntheses have been criticized for failing to account for methodological differences among studies. We addressed such concerns by conducting standardized sampling in 48 herbaceous-dominated plant communities on five continents. We found no clear relationship between productivity and fine-scale (meters(-2)) richness within sites, within regions, or across the globe. Ecologists should focus on fresh, mechanistic approaches to understanding the multivariate links between productivity and richness.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Adler, Peter B -- Seabloom, Eric W -- Borer, Elizabeth T -- Hillebrand, Helmut -- Hautier, Yann -- Hector, Andy -- Harpole, W Stanley -- O'Halloran, Lydia R -- Grace, James B -- Anderson, T Michael -- Bakker, Jonathan D -- Biederman, Lori A -- Brown, Cynthia S -- Buckley, Yvonne M -- Calabrese, Laura B -- Chu, Cheng-Jin -- Cleland, Elsa E -- Collins, Scott L -- Cottingham, Kathryn L -- Crawley, Michael J -- Damschen, Ellen I -- Davies, Kendi F -- DeCrappeo, Nicole M -- Fay, Philip A -- Firn, Jennifer -- Frater, Paul -- Gasarch, Eve I -- Gruner, Daniel S -- Hagenah, Nicole -- Hille Ris Lambers, Janneke -- Humphries, Hope -- Jin, Virginia L -- Kay, Adam D -- Kirkman, Kevin P -- Klein, Julia A -- Knops, Johannes M H -- La Pierre, Kimberly J -- Lambrinos, John G -- Li, Wei -- MacDougall, Andrew S -- McCulley, Rebecca L -- Melbourne, Brett A -- Mitchell, Charles E -- Moore, Joslin L -- Morgan, John W -- Mortensen, Brent -- Orrock, John L -- Prober, Suzanne M -- Pyke, David A -- Risch, Anita C -- Schuetz, Martin -- Smith, Melinda D -- Stevens, Carly J -- Sullivan, Lauren L -- Wang, Gang -- Wragg, Peter D -- Wright, Justin P -- Yang, Louie H -- New York, N.Y. -- Science. 2011 Sep 23;333(6050):1750-3. doi: 10.1126/science.1204498.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Wildland Resources and the Ecology Center, Utah State University, 5230 Old Main, Logan, UT 84322, USA. peter.adler@usu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21940895" target="_blank"〉PubMed〈/a〉
    Keywords: Africa ; Australia ; *Biodiversity ; *Biomass ; China ; *Ecosystem ; Europe ; Models, Biological ; Models, Statistical ; North America ; Plant Development ; Plant Physiological Processes ; *Plants ; Regression Analysis
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 99
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2011-10-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lane, Nick -- New York, N.Y. -- Science. 2011 Oct 14;334(6053):184-5. doi: 10.1126/science.1214012.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Evolution and Environment, University College London, London, UK. nick.lane@ucl.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21998376" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological ; Adenosine Triphosphate/metabolism ; Aging ; Animals ; Apoptosis ; *Biological Evolution ; Cell Nucleus/*genetics/metabolism ; *Cell Respiration ; Cytochromes c/metabolism ; Electron Transport ; Embryonic Development ; Fertility ; *Genes, Mitochondrial ; Genetic Fitness ; Longevity ; Mitochondria/*metabolism ; Models, Biological ; Mutation ; Reactive Oxygen Species/*metabolism ; *Selection, Genetic ; Species Specificity
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 100
    Publication Date: 2011-07-19
    Description: During early lung development, airway tubes change shape. Tube length increases more than circumference as a large proportion of lung epithelial cells divide parallel to the airway longitudinal axis. We show that this bias is lost in mutants with increased extracellular signal-regulated kinase 1 (ERK1) and ERK2 activity, revealing a link between the ERK1/2 signaling pathway and the control of mitotic spindle orientation. Using a mathematical model, we demonstrate that change in airway shape can occur as a function of spindle angle distribution determined by ERK1/2 signaling, independent of effects on cell proliferation or cell size and shape. We identify sprouty genes, which encode negative regulators of fibroblast growth factor 10 (FGF10)-mediated RAS-regulated ERK1/2 signaling, as essential for controlling airway shape change during development through an effect on mitotic spindle orientation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260627/" 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/PMC4260627/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tang, Nan -- Marshall, Wallace F -- McMahon, Martin -- Metzger, Ross J -- Martin, Gail R -- 5T32HL007185/HL/NHLBI NIH HHS/ -- R01 CA131201/CA/NCI NIH HHS/ -- R01 CA131261/CA/NCI NIH HHS/ -- R01 CA78711/CA/NCI NIH HHS/ -- R01 DE17744/DE/NIDCR NIH HHS/ -- R01 GM077004/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2011 Jul 15;333(6040):342-5. doi: 10.1126/science.1204831.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anatomy, University of California, San Francisco, CA 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21764747" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Animals ; Cell Polarity ; Cell Proliferation ; Cell Shape ; Cell Size ; Epithelial Cells/cytology ; Fibroblast Growth Factor 10/genetics/metabolism ; Intracellular Signaling Peptides and Proteins ; Lung/cytology/*embryology/metabolism ; *MAP Kinase Signaling System ; Membrane Proteins/genetics/metabolism ; Mice ; Mice, Knockout ; Mitogen-Activated Protein Kinase 1/*metabolism ; Mitogen-Activated Protein Kinase 3/*metabolism ; Mitosis ; Models, Biological ; *Morphogenesis ; Mutation ; Organogenesis ; Phosphoproteins/genetics/metabolism ; Phosphorylation ; Proto-Oncogene Proteins p21(ras)/genetics/*metabolism ; Respiratory Mucosa/cytology/*embryology ; Spindle Apparatus/*physiology/ultrastructure
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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