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  • Articles  (429)
  • Models, Biological  (429)
  • 2010-2014  (429)
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  • 1
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    Palaeontology: Muddy tetrapod origins (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-01-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Janvier, Philippe -- Clement, Gael -- England -- Nature. 2010 Jan 7;463(7277):40-1. doi: 10.1038/463040a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20054387" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Chordata/anatomy & histology/classification/*physiology ; Extremities/anatomy & histology/physiology ; Fishes/anatomy & histology/physiology ; *Fossils ; Gait/physiology ; History, Ancient ; Models, Biological ; Phylogeny ; Poland
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
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    The key nickel enzyme of methanogenesis catalyses the anaerobic oxidation of methane (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-06-04
    Description: Large amounts (estimates range from 70 Tg per year to 300 Tg per year) of the potent greenhouse gas methane are oxidized to carbon dioxide in marine sediments by communities of methanotrophic archaea and sulphate-reducing bacteria, and thus are prevented from escaping into the atmosphere. Indirect evidence indicates that the anaerobic oxidation of methane might proceed as the reverse of archaeal methanogenesis from carbon dioxide with the nickel-containing methyl-coenzyme M reductase (MCR) as the methane-activating enzyme. However, experiments showing that MCR can catalyse the endergonic back reaction have been lacking. Here we report that purified MCR from Methanothermobacter marburgensis converts methane into methyl-coenzyme M under equilibrium conditions with apparent V(max) (maximum rate) and K(m) (Michaelis constant) values consistent with the observed in vivo kinetics of the anaerobic oxidation of methane with sulphate. This result supports the hypothesis of 'reverse methanogenesis' and is paramount to understanding the still-unknown mechanism of the last step of methanogenesis. The ability of MCR to cleave the particularly strong C-H bond of methane without the involvement of highly reactive oxygen-derived intermediates is directly relevant to catalytic C-H activation, currently an area of great interest in chemistry.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scheller, Silvan -- Goenrich, Meike -- Boecher, Reinhard -- Thauer, Rudolf K -- Jaun, Bernhard -- England -- Nature. 2010 Jun 3;465(7298):606-8. doi: 10.1038/nature09015.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Organic Chemistry, ETH Zurich, Wolfgang-Pauli-Str. 10, 8093 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20520712" target="_blank"〉PubMed〈/a〉
    Keywords: Anaerobiosis ; *Biocatalysis ; Gases/metabolism ; Kinetics ; Mesna/analogs & derivatives/metabolism ; Methane/*biosynthesis/*metabolism ; Methanobacteriaceae/*enzymology ; Methylation ; Models, Biological ; Nickel/*metabolism ; Oxidation-Reduction ; Oxidoreductases/*metabolism ; Temperature
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
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    A systems approach (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-05-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chi, Kelly Rae -- England -- Nature. 2010 Apr 15;464(7291):1090-1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20503480" target="_blank"〉PubMed〈/a〉
    Keywords: Breast Neoplasms/genetics/metabolism/pathology/therapy ; Computational Biology/education/manpower/trends ; Female ; Genetic Heterogeneity ; Humans ; Models, Biological ; Neoplasms/genetics/*metabolism/*pathology/therapy ; Research Personnel/education ; Systems Biology/education/manpower/*trends
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
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    Thousands of chemical starting points for antimalarial lead identification (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-05-21
    Description: Malaria is a devastating infection caused by protozoa of the genus Plasmodium. Drug resistance is widespread, no new chemical class of antimalarials has been introduced into clinical practice since 1996 and there is a recent rise of parasite strains with reduced sensitivity to the newest drugs. We screened nearly 2 million compounds in GlaxoSmithKline's chemical library for inhibitors of P. falciparum, of which 13,533 were confirmed to inhibit parasite growth by at least 80% at 2 microM concentration. More than 8,000 also showed potent activity against the multidrug resistant strain Dd2. Most (82%) compounds originate from internal company projects and are new to the malaria community. Analyses using historic assay data suggest several novel mechanisms of antimalarial action, such as inhibition of protein kinases and host-pathogen interaction related targets. Chemical structures and associated data are hereby made public to encourage additional drug lead identification efforts and further research into this disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gamo, Francisco-Javier -- Sanz, Laura M -- Vidal, Jaume -- de Cozar, Cristina -- Alvarez, Emilio -- Lavandera, Jose-Luis -- Vanderwall, Dana E -- Green, Darren V S -- Kumar, Vinod -- Hasan, Samiul -- Brown, James R -- Peishoff, Catherine E -- Cardon, Lon R -- Garcia-Bustos, Jose F -- England -- Nature. 2010 May 20;465(7296):305-10. doi: 10.1038/nature09107.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Tres Cantos Medicines Development Campus, GlaxoSmithKline, Severo Ochoa 2, 28760 Tres Cantos, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20485427" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antimalarials/*analysis/chemistry/*pharmacology/toxicity ; Cell Line, Tumor ; *Drug Discovery ; Drug Resistance, Multiple/drug effects ; Humans ; Malaria, Falciparum/*drug therapy/parasitology ; Models, Biological ; Phylogeny ; Plasmodium falciparum/*drug effects/enzymology/genetics/growth & development ; Small Molecule Libraries/*analysis/chemistry/*pharmacology/toxicity
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
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    Cancer: Genomic evolution of metastasis (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-10-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Luebeck, E Georg -- England -- Nature. 2010 Oct 28;467(7319):1053-5. doi: 10.1038/4671053a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20981088" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Lineage/genetics ; Clone Cells/metabolism/pathology ; DNA Mutational Analysis ; Disease Progression ; Early Detection of Cancer ; *Evolution, Molecular ; Genomic Instability/*genetics ; Humans ; Models, Biological ; Mutagenesis/*genetics ; Neoplasm Metastasis/*genetics/pathology ; Pancreatic Neoplasms/classification/*genetics/*pathology ; Time Factors
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
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    NINJA connects the co-repressor TOPLESS to jasmonate signalling (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-04-03
    Description: Jasmonoyl-isoleucine (JA-Ile) is a plant hormone that regulates a broad array of plant defence and developmental processes. JA-Ile-responsive gene expression is regulated by the transcriptional activator MYC2 that interacts physically with the jasmonate ZIM-domain (JAZ) repressor proteins. On perception of JA-Ile, JAZ proteins are degraded and JA-Ile-dependent gene expression is activated. The molecular mechanisms by which JAZ proteins repress gene expression remain unknown. Here we show that the Arabidopsis JAZ proteins recruit the Groucho/Tup1-type co-repressor TOPLESS (TPL) and TPL-related proteins (TPRs) through a previously uncharacterized adaptor protein, designated Novel Interactor of JAZ (NINJA). NINJA acts as a transcriptional repressor whose activity is mediated by a functional TPL-binding EAR repression motif. Accordingly, both NINJA and TPL proteins function as negative regulators of jasmonate responses. Our results point to TPL proteins as general co-repressors that affect multiple signalling pathways through the interaction with specific adaptor proteins. This new insight reveals how stress-related and growth-related signalling cascades use common molecular mechanisms to regulate gene expression in plants.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2849182/" 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/PMC2849182/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pauwels, Laurens -- Barbero, Gemma Fernandez -- Geerinck, Jan -- Tilleman, Sofie -- Grunewald, Wim -- Perez, Amparo Cuellar -- Chico, Jose Manuel -- Bossche, Robin Vanden -- Sewell, Jared -- Gil, Eduardo -- Garcia-Casado, Gloria -- Witters, Erwin -- Inze, Dirk -- Long, Jeff A -- De Jaeger, Geert -- Solano, Roberto -- Goossens, Alain -- R01 GM072764/GM/NIGMS NIH HHS/ -- R01 GM072764-06/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Apr 1;464(7289):788-91. doi: 10.1038/nature08854.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Systems Biology, Flanders Institute for Biotechnology (VIB), Technologiepark 927, B-9052 Gent, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360743" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/cytology/*drug effects/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Cyclopentanes/antagonists & inhibitors/*pharmacology ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; Models, Biological ; Oxylipins/antagonists & inhibitors/*pharmacology ; Plants, Genetically Modified ; Protein Binding ; Repressor Proteins/genetics/*metabolism ; Signal Transduction/*drug effects ; Two-Hybrid System Techniques
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  • 7
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    Evolutionary biology: Oh sibling, who art thou? (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-08-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cockburn, Andrew -- England -- Nature. 2010 Aug 19;466(7309):930-1. doi: 10.1038/466930a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20725030" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Birds/classification/genetics/*physiology ; *Cooperative Behavior ; Fathers ; Female ; Male ; Models, Biological ; Mothers ; Phylogeny ; Reproduction/genetics/physiology ; Sexual Behavior, Animal/*physiology ; *Siblings
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  • 8
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    RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-02-25
    Description: Tumours with mutant BRAF are dependent on the RAF-MEK-ERK signalling pathway for their growth. We found that ATP-competitive RAF inhibitors inhibit ERK signalling in cells with mutant BRAF, but unexpectedly enhance signalling in cells with wild-type BRAF. Here we demonstrate the mechanistic basis for these findings. We used chemical genetic methods to show that drug-mediated transactivation of RAF dimers is responsible for paradoxical activation of the enzyme by inhibitors. Induction of ERK signalling requires direct binding of the drug to the ATP-binding site of one kinase of the dimer and is dependent on RAS activity. Drug binding to one member of RAF homodimers (CRAF-CRAF) or heterodimers (CRAF-BRAF) inhibits one protomer, but results in transactivation of the drug-free protomer. In BRAF(V600E) tumours, RAS is not activated, thus transactivation is minimal and ERK signalling is inhibited in cells exposed to RAF inhibitors. These results indicate that RAF inhibitors will be effective in tumours in which BRAF is mutated. Furthermore, because RAF inhibitors do not inhibit ERK signalling in other cells, the model predicts that they would have a higher therapeutic index and greater antitumour activity than mitogen-activated protein kinase (MEK) inhibitors, but could also cause toxicity due to MEK/ERK activation. These predictions have been borne out in a recent clinical trial of the RAF inhibitor PLX4032 (refs 4, 5). The model indicates that promotion of RAF dimerization by elevation of wild-type RAF expression or RAS activity could lead to drug resistance in mutant BRAF tumours. In agreement with this prediction, RAF inhibitors do not inhibit ERK signalling in cells that coexpress BRAF(V600E) and mutant RAS.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3178447/" 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/PMC3178447/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Poulikakos, Poulikos I -- Zhang, Chao -- Bollag, Gideon -- Shokat, Kevan M -- Rosen, Neal -- 1P01CA129243-02/CA/NCI NIH HHS/ -- 2R01EB001987/EB/NIBIB NIH HHS/ -- P01 CA129243-010002/CA/NCI NIH HHS/ -- R01 EB001987/EB/NIBIB NIH HHS/ -- U01 CA091178/CA/NCI NIH HHS/ -- U01 CA091178-01/CA/NCI NIH HHS/ -- England -- Nature. 2010 Mar 18;464(7287):427-30. doi: 10.1038/nature08902.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Molecular Pharmacology and Chemistry and Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20179705" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Animals ; Catalytic Domain ; Cell Line ; Cell Line, Tumor ; Enzyme Activation/drug effects ; Extracellular Signal-Regulated MAP Kinases/*metabolism ; Humans ; Indoles/pharmacology ; MAP Kinase Signaling System/*drug effects ; Mice ; Mitogen-Activated Protein Kinase Kinases/metabolism ; Models, Biological ; Neoplasms/drug therapy/enzymology/genetics/metabolism ; Phosphorylation ; Protein Binding ; Protein Kinase Inhibitors/metabolism/*pharmacology/therapeutic use ; Protein Multimerization ; Proto-Oncogene Proteins B-raf/antagonists & ; inhibitors/chemistry/genetics/*metabolism ; Sulfonamides/pharmacology ; Transcriptional Activation/*drug effects ; raf Kinases/*antagonists & inhibitors/chemistry/genetics/*metabolism ; ras Proteins/genetics/metabolism
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  • 9
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    Higher rates of sex evolve in spatially heterogeneous environments (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-10-15
    Description: The evolution and maintenance of sexual reproduction has puzzled biologists for decades. Although this field is rich in hypotheses, experimental evidence is scarce. Some important experiments have demonstrated differences in evolutionary rates between sexual and asexual populations; other experiments have documented evolutionary changes in phenomena related to genetic mixing, such as recombination and selfing. However, direct experiments of the evolution of sex within populations are extremely rare (but see ref. 12). Here we use the rotifer, Brachionus calyciflorus, which is capable of both sexual and asexual reproduction, to test recent theory predicting that there is more opportunity for sex to evolve in spatially heterogeneous environments. Replicated experimental populations of rotifers were maintained in homogeneous environments, composed of either high- or low-quality food habitats, or in heterogeneous environments that consisted of a mix of the two habitats. For populations maintained in either type of homogeneous environment, the rate of sex evolves rapidly towards zero. In contrast, higher rates of sex evolve in populations experiencing spatially heterogeneous environments. The data indicate that the higher level of sex observed under heterogeneity is not due to sex being less costly or selection against sex being less efficient; rather sex is sufficiently advantageous in heterogeneous environments to overwhelm its inherent costs. Counter to some alternative theories for the evolution of sex, there is no evidence that genetic drift plays any part in the evolution of sex in these populations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Becks, Lutz -- Agrawal, Aneil F -- England -- Nature. 2010 Nov 4;468(7320):89-92. doi: 10.1038/nature09449. Epub 2010 Oct 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology & Evolutionary Biology, University of Toronto, Toronto, Ontario M5S 3B2, Canada. lutz.becks@utoronto.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20944628" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Migration/physiology ; Animals ; *Biological Evolution ; Diet/veterinary ; *Ecosystem ; Female ; *Food ; Genetic Drift ; Male ; Meiosis/genetics ; Models, Biological ; Ovum/physiology ; Population Density ; Reproduction/physiology ; Reproduction, Asexual/physiology ; Rotifera/cytology/genetics/*physiology ; Selection, Genetic ; *Sex
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
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    The trophic fingerprint of marine fisheries (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-11-19
    Description: Biodiversity indicators provide a vital window on the state of the planet, guiding policy development and management. The most widely adopted marine indicator is mean trophic level (MTL) from catches, intended to detect shifts from high-trophic-level predators to low-trophic-level invertebrates and plankton-feeders. This indicator underpins reported trends in human impacts, declining when predators collapse ("fishing down marine food webs") and when low-trophic-level fisheries expand ("fishing through marine food webs"). The assumption is that catch MTL measures changes in ecosystem MTL and biodiversity. Here we combine model predictions with global assessments of MTL from catches, trawl surveys and fisheries stock assessments and find that catch MTL does not reliably predict changes in marine ecosystems. Instead, catch MTL trends often diverge from ecosystem MTL trends obtained from surveys and assessments. In contrast to previous findings of rapid declines in catch MTL, we observe recent increases in catch, survey and assessment MTL. However, catches from most trophic levels are rising, which can intensify fishery collapses even when MTL trends are stable or increasing. To detect fishing impacts on marine biodiversity, we recommend greater efforts to measure true abundance trends for marine species, especially those most vulnerable to fishing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Branch, Trevor A -- Watson, Reg -- Fulton, Elizabeth A -- Jennings, Simon -- McGilliard, Carey R -- Pablico, Grace T -- Ricard, Daniel -- Tracey, Sean R -- England -- Nature. 2010 Nov 18;468(7322):431-5. doi: 10.1038/nature09528.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Aquatic and Fishery Sciences, Box 355020, University of Washington, Seattle, Washington 98195-5020, USA. tbranch@uw.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21085178" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aquatic Organisms/*isolation & purification/*metabolism ; Biodiversity ; Biomass ; Databases, Factual ; *Ecosystem ; Environmental Policy ; *Fisheries ; *Fishes/metabolism ; Food Chain ; Human Activities ; Invertebrates/metabolism ; Models, Biological ; Plankton/metabolism
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  • 11
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    The evolution of eusociality (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-08-27
    Description: Eusociality, in which some individuals reduce their own lifetime reproductive potential to raise the offspring of others, underlies the most advanced forms of social organization and the ecologically dominant role of social insects and humans. For the past four decades kin selection theory, based on the concept of inclusive fitness, has been the major theoretical attempt to explain the evolution of eusociality. Here we show the limitations of this approach. We argue that standard natural selection theory in the context of precise models of population structure represents a simpler and superior approach, allows the evaluation of multiple competing hypotheses, and provides an exact framework for interpreting empirical observations.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279739/" 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/PMC3279739/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nowak, Martin A -- Tarnita, Corina E -- Wilson, Edward O -- R01 GM078986/GM/NIGMS NIH HHS/ -- R01 GM078986-04/GM/NIGMS NIH HHS/ -- R01GM078986/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Aug 26;466(7310):1057-62. doi: 10.1038/nature09205.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program for Evolutionary Dynamics, Department of Mathematics, Harvard University, Cambridge, Massachusetts 02138, USA. martin_nowak@harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20740005" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal/*physiology ; *Biological Evolution ; Female ; Humans ; Insects/physiology ; Male ; Models, Biological ; Selection, Genetic ; *Social Behavior
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  • 12
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    Crystal structures of the CusA efflux pump suggest methionine-mediated metal transport (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-09-25
    Description: Gram-negative bacteria, such as Escherichia coli, frequently use tripartite efflux complexes in the resistance-nodulation-cell division (RND) family to expel various toxic compounds from the cell. The efflux system CusCBA is responsible for extruding biocidal Cu(I) and Ag(I) ions. No previous structural information was available for the heavy-metal efflux (HME) subfamily of the RND efflux pumps. Here we describe the crystal structures of the inner-membrane transporter CusA in the absence and presence of bound Cu(I) or Ag(I). These CusA structures provide new structural information about the HME subfamily of RND efflux pumps. The structures suggest that the metal-binding sites, formed by a three-methionine cluster, are located within the cleft region of the periplasmic domain. This cleft is closed in the apo-CusA form but open in the CusA-Cu(I) and CusA-Ag(I) structures, which directly suggests a plausible pathway for ion export. Binding of Cu(I) and Ag(I) triggers significant conformational changes in both the periplasmic and transmembrane domains. The crystal structure indicates that CusA has, in addition to the three-methionine metal-binding site, four methionine pairs-three located in the transmembrane region and one in the periplasmic domain. Genetic analysis and transport assays suggest that CusA is capable of actively picking up metal ions from the cytosol, using these methionine pairs or clusters to bind and export metal ions. These structures suggest a stepwise shuttle mechanism for transport between these sites.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946090/" 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/PMC2946090/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Long, Feng -- Su, Chih-Chia -- Zimmermann, Michael T -- Boyken, Scott E -- Rajashankar, Kanagalaghatta R -- Jernigan, Robert L -- Yu, Edward W -- GM 072014/GM/NIGMS NIH HHS/ -- GM 074027/GM/NIGMS NIH HHS/ -- GM 081680/GM/NIGMS NIH HHS/ -- GM 086431/GM/NIGMS NIH HHS/ -- R01 GM072014/GM/NIGMS NIH HHS/ -- R01 GM074027/GM/NIGMS NIH HHS/ -- R01 GM074027-05/GM/NIGMS NIH HHS/ -- R01 GM086431/GM/NIGMS NIH HHS/ -- R01 GM086431-01A2/GM/NIGMS NIH HHS/ -- RR-15301/RR/NCRR NIH HHS/ -- England -- Nature. 2010 Sep 23;467(7314):484-8. doi: 10.1038/nature09395.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular, Cellular and Developmental Biology Interdepartmental Graduate Program, Iowa State University, Iowa 50011, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20865003" target="_blank"〉PubMed〈/a〉
    Keywords: Apoproteins/chemistry/metabolism ; Binding Sites ; Cell Membrane/metabolism ; Copper/chemistry/*metabolism ; Crystallography, X-Ray ; Cytosol/metabolism ; Escherichia coli/*chemistry ; Escherichia coli Proteins/*chemistry/*metabolism ; Ion Transport ; Membrane Transport Proteins/*chemistry/*metabolism ; Methionine/*metabolism ; Models, Biological ; Models, Molecular ; Periplasm/metabolism ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; Silver/chemistry/*metabolism ; Structure-Activity Relationship
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    Sugar transporters for intercellular exchange and nutrition of pathogens (2010)
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    Publication Date: 2010-11-26
    Description: Sugar efflux transporters are essential for the maintenance of animal blood glucose levels, plant nectar production, and plant seed and pollen development. Despite broad biological importance, the identity of sugar efflux transporters has remained elusive. Using optical glucose sensors, we identified a new class of sugar transporters, named SWEETs, and show that at least six out of seventeen Arabidopsis, two out of over twenty rice and two out of seven homologues in Caenorhabditis elegans, and the single copy human protein, mediate glucose transport. Arabidopsis SWEET8 is essential for pollen viability, and the rice homologues SWEET11 and SWEET14 are specifically exploited by bacterial pathogens for virulence by means of direct binding of a bacterial effector to the SWEET promoter. Bacterial symbionts and fungal and bacterial pathogens induce the expression of different SWEET genes, indicating that the sugar efflux function of SWEET transporters is probably targeted by pathogens and symbionts for nutritional gain. The metazoan homologues may be involved in sugar efflux from intestinal, liver, epididymis and mammary cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3000469/" 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/PMC3000469/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Li-Qing -- Hou, Bi-Huei -- Lalonde, Sylvie -- Takanaga, Hitomi -- Hartung, Mara L -- Qu, Xiao-Qing -- Guo, Woei-Jiun -- Kim, Jung-Gun -- Underwood, William -- Chaudhuri, Bhavna -- Chermak, Diane -- Antony, Ginny -- White, Frank F -- Somerville, Shauna C -- Mudgett, Mary Beth -- Frommer, Wolf B -- 1R01DK079109/DK/NIDDK NIH HHS/ -- F32GM083439-02/GM/NIGMS NIH HHS/ -- R01 DK079109/DK/NIDDK NIH HHS/ -- R01 DK079109-01/DK/NIDDK NIH HHS/ -- R01 DK079109-02/DK/NIDDK NIH HHS/ -- R01 DK079109-03/DK/NIDDK NIH HHS/ -- R01 DK079109-03S1/DK/NIDDK NIH HHS/ -- R01 DK079109-04/DK/NIDDK NIH HHS/ -- R01 GM068886/GM/NIGMS NIH HHS/ -- ZR01GM06886-06A1/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Nov 25;468(7323):527-32. doi: 10.1038/nature09606.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Biology, Carnegie Institution for Science, 260 Panama St, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21107422" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arabidopsis/genetics/*metabolism/microbiology ; Arabidopsis Proteins/genetics/*metabolism ; Biological Transport/genetics ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; Glucose/*metabolism ; HEK293 Cells ; Host-Pathogen Interactions/*physiology ; Humans ; Membrane Transport Proteins/*metabolism ; Models, Biological ; Oryza/genetics/metabolism/microbiology ; RNA, Messenger/metabolism ; Saccharomyces cerevisiae/genetics ; Xenopus/genetics
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    Altruism researchers must cooperate (2010)
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    Publication Date: 2010-10-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Okasha, Samir -- England -- Nature. 2010 Oct 7;467(7316):653-5. doi: 10.1038/467653a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Philosophy, University of Bristol, Bristol BS8 1TB, UK. Samir.Okasha@bristol.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20930821" target="_blank"〉PubMed〈/a〉
    Keywords: *Altruism ; Animals ; Biological Evolution ; *Cooperative Behavior ; Female ; Group Processes ; Male ; Models, Biological ; *Research Personnel ; Selection, Genetic ; Social Behavior
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    Quantum physics: Hot entanglement (2010)
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    Publication Date: 2010-12-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vedral, Vlatko -- England -- Nature. 2010 Dec 9;468(7325):769-70. doi: 10.1038/468769a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21150986" target="_blank"〉PubMed〈/a〉
    Keywords: Hot Temperature ; Models, Biological ; Photosynthesis ; *Quantum Theory ; *Thermodynamics
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    Role of a ribosome-associated E3 ubiquitin ligase in protein quality control (2010)
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    Publication Date: 2010-09-14
    Description: Messenger RNA lacking stop codons ('non-stop mRNA') can arise from errors in gene expression, and encode aberrant proteins whose accumulation could be deleterious to cellular function. In bacteria, these 'non-stop proteins' become co-translationally tagged with a peptide encoded by ssrA/tmRNA (transfer-messenger RNA), which signals their degradation by energy-dependent proteases. How eukaryotic cells eliminate non-stop proteins has remained unknown. Here we show that the Saccharomyces cerevisiae Ltn1 RING-domain-type E3 ubiquitin ligase acts in the quality control of non-stop proteins, in a process that is mechanistically distinct but conceptually analogous to that performed by ssrA: Ltn1 is predominantly associated with ribosomes, and it marks nascent non-stop proteins with ubiquitin to signal their proteasomal degradation. Ltn1-mediated ubiquitylation of non-stop proteins seems to be triggered by their stalling in ribosomes on translation through the poly(A) tail. The biological relevance of this process is underscored by the finding that loss of Ltn1 function confers sensitivity to stress caused by increased non-stop protein production. We speculate that defective protein quality control may underlie the neurodegenerative phenotype that results from mutation of the mouse Ltn1 homologue Listerin.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988496/" 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/PMC2988496/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bengtson, Mario H -- Joazeiro, Claudio A P -- R01 GM083060/GM/NIGMS NIH HHS/ -- R01 GM083060-03/GM/NIGMS NIH HHS/ -- R01GM083060/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Sep 23;467(7314):470-3. doi: 10.1038/nature09371. Epub 2010 Sep 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, The Scripps Research Institute, CB168, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20835226" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Codon, Terminator/genetics ; Mice ; Models, Biological ; Peptide Chain Termination, Translational ; Polylysine/biosynthesis/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Protein Binding ; Protein Biosynthesis/*physiology ; Ribosomes/*enzymology/*metabolism ; Saccharomyces cerevisiae/cytology/enzymology/genetics/metabolism ; Saccharomyces cerevisiae Proteins/genetics/*metabolism ; Stress, Physiological ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligases/deficiency/genetics/*metabolism ; *Ubiquitination
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    Structural mechanism of C-type inactivation in K(+) channels (2010)
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    Publication Date: 2010-07-09
    Description: Interconversion between conductive and non-conductive forms of the K(+) channel selectivity filter underlies a variety of gating events, from flicker transitions (at the microsecond timescale) to C-type inactivation (millisecond to second timescale). Here we report the crystal structure of the Streptomyces lividans K(+) channel KcsA in its open-inactivated conformation and investigate the mechanism of C-type inactivation gating at the selectivity filter from channels 'trapped' in a series of partially open conformations. Five conformer classes were identified with openings ranging from 12 A in closed KcsA (Calpha-Calpha distances at Thr 112) to 32 A when fully open. They revealed a remarkable correlation between the degree of gate opening and the conformation and ion occupancy of the selectivity filter. We show that a gradual filter backbone reorientation leads first to a loss of the S2 ion binding site and a subsequent loss of the S3 binding site, presumably abrogating ion conduction. These structures indicate a molecular basis for C-type inactivation in K(+) channels.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033749/" 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/PMC3033749/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cuello, Luis G -- Jogini, Vishwanath -- Cortes, D Marien -- Perozo, Eduardo -- R01 GM057846/GM/NIGMS NIH HHS/ -- R01 GM057846-15/GM/NIGMS NIH HHS/ -- R01-GM57846/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Jul 8;466(7303):203-8. doi: 10.1038/nature09153.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, University of Chicago, Illinois 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20613835" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*antagonists & inhibitors/*chemistry/metabolism ; Binding Sites ; Crystallography, X-Ray ; Electrons ; *Ion Channel Gating ; Kinetics ; Models, Biological ; Models, Molecular ; Potassium/metabolism ; Potassium Channels/*chemistry/metabolism ; Protein Conformation ; Streptomyces lividans/*chemistry ; Structure-Activity Relationship
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    Climate-driven population divergence in sex-determining systems (2010)
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    Publication Date: 2010-10-29
    Description: Sex determination is a fundamental biological process, yet its mechanisms are remarkably diverse. In vertebrates, sex can be determined by inherited genetic factors or by the temperature experienced during embryonic development. However, the evolutionary causes of this diversity remain unknown. Here we show that live-bearing lizards at different climatic extremes of the species' distribution differ in their sex-determining mechanisms, with temperature-dependent sex determination in lowlands and genotypic sex determination in highlands. A theoretical model parameterized with field data accurately predicts this divergence in sex-determining systems and the consequence thereof for variation in cohort sex ratios among years. Furthermore, we show that divergent natural selection on sex determination across altitudes is caused by climatic effects on lizard life history and variation in the magnitude of between-year temperature fluctuations. Our results establish an adaptive explanation for intra-specific divergence in sex-determining systems driven by phenotypic plasticity and ecological selection, thereby providing a unifying framework for integrating the developmental, ecological and evolutionary basis for variation in vertebrate sex determination.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pen, Ido -- Uller, Tobias -- Feldmeyer, Barbara -- Harts, Anna -- While, Geoffrey M -- Wapstra, Erik -- England -- Nature. 2010 Nov 18;468(7322):436-8. doi: 10.1038/nature09512. Epub 2010 Oct 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Theoretical Biology Group, University of Groningen, PO Box 14, 9750 AA Haren, the Netherlands. i.r.pen@rug.nl〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20981009" target="_blank"〉PubMed〈/a〉
    Keywords: Altitude ; Animals ; Biological Evolution ; *Climate ; Female ; Genotype ; Lizards/*genetics/*physiology ; Male ; Models, Biological ; Phenotype ; Selection, Genetic ; Sex Chromosomes ; *Sex Determination Processes/genetics/physiology ; *Sex Differentiation/genetics/physiology ; Sex Ratio ; *Temperature ; Time Factors ; Viviparity, Nonmammalian/physiology
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    Germans cook up liver project (2010)
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    Publication Date: 2010-12-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abbott, Alison -- England -- Nature. 2010 Dec 16;468(7326):879. doi: 10.1038/468879a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21164453" target="_blank"〉PubMed〈/a〉
    Keywords: Cooperative Behavior ; Drug-Related Side Effects and Adverse Reactions ; Germany ; Hepatocytes/metabolism ; Humans ; Interdisciplinary Communication ; Liver/*physiology ; Models, Biological ; Pharmaceutical Preparations/metabolism ; Physics ; Research Personnel ; Systems Biology/economics/manpower/*trends
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    Negative plant-soil feedback predicts tree-species relative abundance in a tropical forest (2010)
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    Publication Date: 2010-06-29
    Description: The accumulation of species-specific enemies around adults is hypothesized to maintain plant diversity by limiting the recruitment of conspecific seedlings relative to heterospecific seedlings. Although previous studies in forested ecosystems have documented patterns consistent with the process of negative feedback, these studies are unable to address which classes of enemies (for example, pathogens, invertebrates, mammals) exhibit species-specific effects strong enough to generate negative feedback, and whether negative feedback at the level of the individual tree is sufficient to influence community-wide forest composition. Here we use fully reciprocal shade-house and field experiments to test whether the performance of conspecific tree seedlings (relative to heterospecific seedlings) is reduced when grown in the presence of enemies associated with adult trees. Both experiments provide strong evidence for negative plant-soil feedback mediated by soil biota. In contrast, above-ground enemies (mammals, foliar herbivores and foliar pathogens) contributed little to negative feedback observed in the field. In both experiments, we found that tree species that showed stronger negative feedback were less common as adults in the forest community, indicating that susceptibility to soil biota may determine species relative abundance in these tropical forests. Finally, our simulation models confirm that the strength of local negative feedback that we measured is sufficient to produce the observed community-wide patterns in tree-species relative abundance. Our findings indicate that plant-soil feedback is an important mechanism that can maintain species diversity and explain patterns of tree-species relative abundance in tropical forests.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mangan, Scott A -- Schnitzer, Stefan A -- Herre, Edward A -- Mack, Keenan M L -- Valencia, Mariana C -- Sanchez, Evelyn I -- Bever, James D -- R01 GM092660/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Aug 5;466(7307):752-5. doi: 10.1038/nature09273.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, University of Wisconsin-Milwaukee, Wisconsin 53201, USA. smangan37@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20581819" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biodiversity ; Biomass ; Computer Simulation ; Feedback, Physiological ; Food Chain ; Insects/physiology ; Models, Biological ; Panama ; Population Density ; Seedlings/growth & development ; Soil/*analysis ; *Soil Microbiology ; Species Specificity ; Trees/*classification/*growth & development/microbiology/parasitology ; *Tropical Climate ; Vertebrates/physiology
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    Intercalation of a new tier of transcription regulation into an ancient circuit (2010)
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    Publication Date: 2010-12-18
    Description: Changes in gene regulatory networks are a major source of evolutionary novelty. Here we describe a specific type of network rewiring event, one that intercalates a new level of transcriptional control into an ancient circuit. We deduce that, over evolutionary time, the direct ancestral connections between a regulator and its target genes were broken and replaced by indirect connections, preserving the overall logic of the ancestral circuit but producing a new behaviour. The example was uncovered through a series of experiments in three ascomycete yeasts: the bakers' yeast Saccharomyces cerevisiae, the dairy yeast Kluyveromyces lactis and the human pathogen Candida albicans. All three species have three cell types: two mating-competent cell forms (a and alpha) and the product of their mating (a/alpha), which is mating-incompetent. In the ancestral mating circuit, two homeodomain proteins, Mata1 and Matalpha2, form a heterodimer that directly represses four genes that are expressed only in a and alpha cells and are required for mating. In a relatively recent ancestor of K. lactis, a reorganization occurred. The Mata1-Matalpha2 heterodimer represses the same four genes (known as the core haploid-specific genes) but now does so indirectly through an intermediate regulatory protein, Rme1. The overall logic of the ancestral circuit is preserved (haploid-specific genes ON in a and alpha cells and OFF in a/alpha cells), but a new phenotype was produced by the rewiring: unlike S. cerevisiae and C. albicans, K. lactis integrates nutritional signals, by means of Rme1, into the decision of whether or not to mate.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3254258/" 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/PMC3254258/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Booth, Lauren N -- Tuch, Brian B -- Johnson, Alexander D -- R01 GM037049/GM/NIGMS NIH HHS/ -- R01 GM037049-26/GM/NIGMS NIH HHS/ -- R01 GM037049-27/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Dec 16;468(7326):959-63. doi: 10.1038/nature09560.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology and Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21164485" target="_blank"〉PubMed〈/a〉
    Keywords: Candida albicans/cytology/*genetics/metabolism/physiology ; *Evolution, Molecular ; Fungal Proteins/genetics/metabolism ; Gene Expression Profiling ; *Gene Expression Regulation, Fungal/genetics ; Genes, Fungal/genetics ; Homeodomain Proteins/genetics/metabolism ; Kluyveromyces/cytology/*genetics/physiology ; Models, Biological ; Phenotype ; Protein Precursors/genetics/metabolism ; Repressor Proteins/genetics/metabolism ; Saccharomyces cerevisiae/cytology/*genetics/metabolism/physiology ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; Transcription, Genetic/*genetics
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    Inferring echolocation in ancient bats (2010)
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    Publication Date: 2010-08-21
    Description: Laryngeal echolocation, used by most living bats to form images of their surroundings and to detect and capture flying prey, is considered to be a key innovation for the evolutionary success of bats, and palaeontologists have long sought osteological correlates of echolocation that can be used to infer the behaviour of fossil bats. Veselka et al. argued that the most reliable trait indicating echolocation capabilities in bats is an articulation between the stylohyal bone (part of the hyoid apparatus that supports the throat and larynx) and the tympanic bone, which forms the floor of the middle ear. They examined the oldest and most primitive known bat, Onychonycteris finneyi (early Eocene, USA), and argued that it showed evidence of this stylohyal-tympanic articulation, from which they concluded that O. finneyi may have been capable of echolocation. We disagree with their interpretation of key fossil data and instead argue that O. finneyi was probably not an echolocating bat.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Simmons, Nancy B -- Seymour, Kevin L -- Habersetzer, Jorg -- Gunnell, Gregg F -- England -- Nature. 2010 Aug 19;466(7309):E8; discussion E9. doi: 10.1038/nature09219.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉American Museum of Natural History, Central Park West at 79th Street, New York, New York 10024, USA. simmons@amnh.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20724993" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Structures/physiology ; Animals ; Bone and Bones/physiology ; Chiroptera/anatomy & histology/*physiology ; Echolocation/*physiology ; *Fossils ; Models, Biological ; Reproducibility of Results
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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    Fisheries: Measuring biodiversity in marine ecosystems (2010)
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    Publication Date: 2010-11-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Powers, Joseph E -- England -- Nature. 2010 Nov 18;468(7322):385-6. doi: 10.1038/468385a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21085170" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aquatic Organisms/*isolation & purification ; *Biodiversity ; Databases, Factual ; *Ecosystem ; *Fisheries ; *Fishes ; Food Chain ; Models, Biological
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    Ecology: Fish in Levy-flight foraging (2010)
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    Publication Date: 2010-06-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Viswanathan, Gandhimohan M -- England -- Nature. 2010 Jun 24;465(7301):1018-9. doi: 10.1038/4651018a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20577199" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Ecosystem ; Fishes/*physiology ; *Food ; Locomotion/*physiology ; Models, Biological ; Predatory Behavior/*physiology ; *Seawater ; Swimming/physiology
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    Structural biology: An alphavirus puzzle solved (2010)
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    Publication Date: 2010-12-03
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3088109/" 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/PMC3088109/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kielian, Margaret -- R01 AI075647/AI/NIAID NIH HHS/ -- R01 AI075647-17/AI/NIAID NIH HHS/ -- R01 GM057454/GM/NIGMS NIH HHS/ -- R01 GM057454-11/GM/NIGMS NIH HHS/ -- R21 AI067931/AI/NIAID NIH HHS/ -- R21 AI067931-02/AI/NIAID NIH HHS/ -- England -- Nature. 2010 Dec 2;468(7324):645-6. doi: 10.1038/468645a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21124448" target="_blank"〉PubMed〈/a〉
    Keywords: Chikungunya virus/*chemistry/physiology ; Crystallography, X-Ray ; Membrane Fusion ; Membrane Glycoproteins/*chemistry/metabolism ; Models, Biological ; Protein Multimerization ; Protein Structure, Quaternary ; Receptors, Virus/metabolism ; Sindbis Virus/*chemistry/*physiology ; Viral Envelope Proteins/*chemistry/*metabolism ; Viral Fusion Proteins/chemistry/metabolism ; Virion/chemistry/metabolism ; *Virus Internalization
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    Behavioural ecology: Learn to beat an identity cheat (2010)
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    Publication Date: 2010-01-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kilner, Rebecca -- England -- Nature. 2010 Jan 14;463(7278):165-7. doi: 10.1038/463165a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20075907" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Evolution ; Birds/*parasitology/*physiology ; Cues ; Discrimination Learning/*physiology ; Models, Biological ; Nesting Behavior/*physiology ; Pattern Recognition, Visual/physiology ; Survival Rate ; Time Factors
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    Promiscuity and the evolutionary transition to complex societies (2010)
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    Publication Date: 2010-08-21
    Description: Theory predicts that the evolution of cooperative behaviour is favoured by low levels of promiscuity leading to high within-group relatedness. However, in vertebrates, cooperation often occurs between non-relatives and promiscuity rates are among the highest recorded. Here we resolve this apparent inconsistency with a phylogenetic analysis of 267 bird species, demonstrating that cooperative breeding is associated with low promiscuity; that in cooperative species, helping is more common when promiscuity is low; and that intermediate levels of promiscuity favour kin discrimination. Overall, these results suggest that promiscuity is a unifying feature across taxa in explaining transitions to and from cooperative societies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cornwallis, Charlie K -- West, Stuart A -- Davis, Katie E -- Griffin, Ashleigh S -- England -- Nature. 2010 Aug 19;466(7309):969-72. doi: 10.1038/nature09335.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Edward Grey Institute, Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20725039" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Birds/classification/genetics/*physiology ; *Cooperative Behavior ; Fathers ; Female ; Male ; Models, Biological ; Mothers ; Phylogeny ; Reproduction/genetics/physiology ; Sexual Behavior, Animal/*physiology ; *Siblings
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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    Link communities reveal multiscale complexity in networks (2010)
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    Publication Date: 2010-06-22
    Description: Networks have become a key approach to understanding systems of interacting objects, unifying the study of diverse phenomena including biological organisms and human society. One crucial step when studying the structure and dynamics of networks is to identify communities: groups of related nodes that correspond to functional subunits such as protein complexes or social spheres. Communities in networks often overlap such that nodes simultaneously belong to several groups. Meanwhile, many networks are known to possess hierarchical organization, where communities are recursively grouped into a hierarchical structure. However, the fact that many real networks have communities with pervasive overlap, where each and every node belongs to more than one group, has the consequence that a global hierarchy of nodes cannot capture the relationships between overlapping groups. Here we reinvent communities as groups of links rather than nodes and show that this unorthodox approach successfully reconciles the antagonistic organizing principles of overlapping communities and hierarchy. In contrast to the existing literature, which has entirely focused on grouping nodes, link communities naturally incorporate overlap while revealing hierarchical organization. We find relevant link communities in many networks, including major biological networks such as protein-protein interaction and metabolic networks, and show that a large social network contains hierarchically organized community structures spanning inner-city to regional scales while maintaining pervasive overlap. Our results imply that link communities are fundamental building blocks that reveal overlap and hierarchical organization in networks to be two aspects of the same phenomenon.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ahn, Yong-Yeol -- Bagrow, James P -- Lehmann, Sune -- U01 A1070499-01/PHS HHS/ -- England -- Nature. 2010 Aug 5;466(7307):761-4. doi: 10.1038/nature09182. Epub 2010 Jun 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Complex Network Research, Department of Physics, Northeastern University, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20562860" target="_blank"〉PubMed〈/a〉
    Keywords: *Cell Phones/utilization ; Cities ; *Community Networks/statistics & numerical data ; Humans ; *Metabolic Networks and Pathways ; Models, Biological ; *Protein Interaction Mapping
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    Hierarchical group dynamics in pigeon flocks (2010)
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    Publication Date: 2010-04-09
    Description: Animals that travel together in groups display a variety of fascinating motion patterns thought to be the result of delicate local interactions among group members. Although the most informative way of investigating and interpreting collective movement phenomena would be afforded by the collection of high-resolution spatiotemporal data from moving individuals, such data are scarce and are virtually non-existent for long-distance group motion within a natural setting because of the associated technological difficulties. Here we present results of experiments in which track logs of homing pigeons flying in flocks of up to 10 individuals have been obtained by high-resolution lightweight GPS devices and analysed using a variety of correlation functions inspired by approaches common in statistical physics. We find a well-defined hierarchy among flock members from data concerning leading roles in pairwise interactions, defined on the basis of characteristic delay times between birds' directional choices. The average spatial position of a pigeon within the flock strongly correlates with its place in the hierarchy, and birds respond more quickly to conspecifics perceived primarily through the left eye-both results revealing differential roles for birds that assume different positions with respect to flock-mates. From an evolutionary perspective, our results suggest that hierarchical organization of group flight may be more efficient than an egalitarian one, at least for those flock sizes that permit regular pairwise interactions among group members, during which leader-follower relationships are consistently manifested.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nagy, Mate -- Akos, Zsuzsa -- Biro, Dora -- Vicsek, Tamas -- England -- Nature. 2010 Apr 8;464(7290):890-3. doi: 10.1038/nature08891.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Physics, Eotvos University, Pazmany Peter setany 1A, H-1117, Budapest, Hungary.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20376149" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Columbidae/*physiology ; Decision Making ; Flight, Animal/*physiology ; Geographic Information Systems ; *Group Processes ; *Hierarchy, Social ; Leadership ; Locomotion/physiology ; Models, Biological
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    Location of corneal epithelial stem cells (2010)
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    Publication Date: 2010-02-26
    Description: The longstanding concept that corneal epithelial stem cells reside mainly in the limbus is supported by the absence of major corneal epithelial differentiation markers, that is, K3 and K12 keratins, in limbal basal cells (these markers are expressed, however, in corneal basal cells, thus distinguishing the mode of keratin expression in corneal epithelium from that of all other stratified epithelia), the centripetal migration of corneal epithelial cells, the exclusive location of slow-cycling cells in the limbal basal layer, the superior in vitro proliferative potential of limbal epithelial cells, and the transplanted limbal cells' ability to reconstitute corneal epithelium in vivo (reviewed in refs 1-4). Moreover, previous data indicate that corneal and conjunctival epithelia represent two separate cell lineages (reviewed in refs 1-4). Majo et al. suggested, however, that corneal and conjunctival epithelia are equipotent, and that identical oligopotent stem cells are present throughout the corneal, limbal and conjunctival epithelia. We point out here that these suggestions are inconsistent with many known growth, differentiation and cell migration properties of the anterior ocular epithelia.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sun, Tung-Tien -- Tseng, Scheffer C -- Lavker, Robert M -- England -- Nature. 2010 Feb 25;463(7284):E10-1; discussion E11. doi: 10.1038/nature08805.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA. sunt01@nyumc.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20182462" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cattle ; Cell Differentiation ; Cell Lineage ; *Cell Movement ; Cell Proliferation ; Conjunctiva/cytology ; Epithelium, Corneal/*cytology ; Goblet Cells/cytology ; Humans ; Limbus Corneae/*cytology ; Mice ; Models, Biological ; Rabbits ; Reproducibility of Results ; Sheep ; Stem Cells/*cytology ; Swine
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    Distant metastasis occurs late during the genetic evolution of pancreatic cancer (2010)
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    Publication Date: 2010-10-29
    Description: Metastasis, the dissemination and growth of neoplastic cells in an organ distinct from that in which they originated, is the most common cause of death in cancer patients. This is particularly true for pancreatic cancers, where most patients are diagnosed with metastatic disease and few show a sustained response to chemotherapy or radiation therapy. Whether the dismal prognosis of patients with pancreatic cancer compared to patients with other types of cancer is a result of late diagnosis or early dissemination of disease to distant organs is not known. Here we rely on data generated by sequencing the genomes of seven pancreatic cancer metastases to evaluate the clonal relationships among primary and metastatic cancers. We find that clonal populations that give rise to distant metastases are represented within the primary carcinoma, but these clones are genetically evolved from the original parental, non-metastatic clone. Thus, genetic heterogeneity of metastases reflects that within the primary carcinoma. A quantitative analysis of the timing of the genetic evolution of pancreatic cancer was performed, indicating at least a decade between the occurrence of the initiating mutation and the birth of the parental, non-metastatic founder cell. At least five more years are required for the acquisition of metastatic ability and patients die an average of two years thereafter. These data provide novel insights into the genetic features underlying pancreatic cancer progression and define a broad time window of opportunity for early detection to prevent deaths from metastatic disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3148940/" 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/PMC3148940/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yachida, Shinichi -- Jones, Sian -- Bozic, Ivana -- Antal, Tibor -- Leary, Rebecca -- Fu, Baojin -- Kamiyama, Mihoko -- Hruban, Ralph H -- Eshleman, James R -- Nowak, Martin A -- Velculescu, Victor E -- Kinzler, Kenneth W -- Vogelstein, Bert -- Iacobuzio-Donahue, Christine A -- A62924/PHS HHS/ -- CA106610/CA/NCI NIH HHS/ -- CA121113/CA/NCI NIH HHS/ -- CA43460/CA/NCI NIH HHS/ -- CA57345/CA/NCI NIH HHS/ -- GM078986/GM/NIGMS NIH HHS/ -- K08 CA106610/CA/NCI NIH HHS/ -- K08 CA106610-04/CA/NCI NIH HHS/ -- K08 CA106610-05/CA/NCI NIH HHS/ -- P50 CA062924/CA/NCI NIH HHS/ -- P50 CA062924-10/CA/NCI NIH HHS/ -- P50 CA062924-11/CA/NCI NIH HHS/ -- P50 CA062924-12/CA/NCI NIH HHS/ -- R01 CA057345/CA/NCI NIH HHS/ -- R01 CA057345-08/CA/NCI NIH HHS/ -- R01 CA057345-09/CA/NCI NIH HHS/ -- R01 CA057345-10/CA/NCI NIH HHS/ -- R01 CA121113/CA/NCI NIH HHS/ -- R01 CA121113-03/CA/NCI NIH HHS/ -- R01 CA121113-04/CA/NCI NIH HHS/ -- R01 CA121113-05/CA/NCI NIH HHS/ -- R01 CA140599/CA/NCI NIH HHS/ -- R01 GM078986/GM/NIGMS NIH HHS/ -- R01 GM078986-02/GM/NIGMS NIH HHS/ -- R01 GM078986-03/GM/NIGMS NIH HHS/ -- R01 GM078986-04/GM/NIGMS NIH HHS/ -- R37 CA043460/CA/NCI NIH HHS/ -- R37 CA043460-24/CA/NCI NIH HHS/ -- R37 CA043460-25/CA/NCI NIH HHS/ -- R37 CA043460-26/CA/NCI NIH HHS/ -- R37 CA057345/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Oct 28;467(7319):1114-7. doi: 10.1038/nature09515.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20981102" target="_blank"〉PubMed〈/a〉
    Keywords: Adenocarcinoma/genetics/pathology ; Autopsy ; Cell Lineage/genetics ; Clone Cells/metabolism/pathology ; DNA Mutational Analysis ; *Disease Progression ; Early Detection of Cancer ; *Evolution, Molecular ; Humans ; Liver Neoplasms/genetics/secondary ; Lung Neoplasms/genetics/secondary ; Models, Biological ; Mutation/*genetics ; Neoplasm Metastasis/*genetics/pathology ; Pancreas/metabolism/pathology ; Pancreatic Neoplasms/*genetics/*pathology ; Peritoneal Neoplasms/genetics/secondary ; Time Factors
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    The Ndc80 kinetochore complex forms oligomeric arrays along microtubules (2010)
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    Publication Date: 2010-10-15
    Description: The Ndc80 complex is a key site of regulated kinetochore-microtubule attachment (a process required for cell division), but the molecular mechanism underlying its function remains unknown. Here we present a subnanometre-resolution cryo-electron microscopy reconstruction of the human Ndc80 complex bound to microtubules, sufficient for precise docking of crystal structures of the component proteins. We find that the Ndc80 complex binds the microtubule with a tubulin monomer repeat, recognizing alpha- and beta-tubulin at both intra- and inter-tubulin dimer interfaces in a manner that is sensitive to tubulin conformation. Furthermore, Ndc80 complexes self-associate along protofilaments through interactions mediated by the amino-terminal tail of the NDC80 protein, which is the site of phospho-regulation by Aurora B kinase. The complex's mode of interaction with the microtubule and its oligomerization suggest a mechanism by which Aurora B could regulate the stability of load-bearing kinetochore-microtubule attachments.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2957311/" 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/PMC2957311/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alushin, Gregory M -- Ramey, Vincent H -- Pasqualato, Sebastiano -- Ball, David A -- Grigorieff, Nikolaus -- Musacchio, Andrea -- Nogales, Eva -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Oct 14;467(7317):805-10. doi: 10.1038/nature09423.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biophysics Graduate Group, University of California, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20944740" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Cryoelectron Microscopy ; Humans ; Kinetochores/*chemistry/ultrastructure ; Microtubules/chemistry/*metabolism/ultrastructure ; Mitosis ; Models, Biological ; Models, Molecular ; Nuclear Proteins/*chemistry/*metabolism/ultrastructure ; Protein Conformation ; Tubulin/chemistry/metabolism/ultrastructure
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    Geomicrobiology: Sediment reactions defy dogma (2010)
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    Publication Date: 2010-02-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nealson, Kenneth H -- England -- Nature. 2010 Feb 25;463(7284):1033-4. doi: 10.1038/4631033a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20182504" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteria/metabolism ; Diffusion ; *Electric Conductivity ; Electron Transport ; Geologic Sediments/*chemistry/*microbiology ; Humans ; Hydrogen Sulfide/analysis/metabolism ; Hydrogen-Ion Concentration ; Models, Biological ; Nanowires/microbiology ; Oxygen/analysis/metabolism ; Seawater/microbiology
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    Genomic and functional adaptation in surface ocean planktonic prokaryotes (2010)
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    Publication Date: 2010-11-05
    Description: The understanding of marine microbial ecology and metabolism has been hampered by the paucity of sequenced reference genomes. To this end, we report the sequencing of 137 diverse marine isolates collected from around the world. We analysed these sequences, along with previously published marine prokaryotic genomes, in the context of marine metagenomic data, to gain insights into the ecology of the surface ocean prokaryotic picoplankton (0.1-3.0 mum size range). The results suggest that the sequenced genomes define two microbial groups: one composed of only a few taxa that are nearly always abundant in picoplanktonic communities, and the other consisting of many microbial taxa that are rarely abundant. The genomic content of the second group suggests that these microbes are capable of slow growth and survival in energy-limited environments, and rapid growth in energy-rich environments. By contrast, the abundant and cosmopolitan picoplanktonic prokaryotes for which there is genomic representation have smaller genomes, are probably capable of only slow growth and seem to be relatively unable to sense or rapidly acclimate to energy-rich conditions. Their genomic features also lead us to propose that one method used to avoid predation by viruses and/or bacterivores is by means of slow growth and the maintenance of low biomass.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yooseph, Shibu -- Nealson, Kenneth H -- Rusch, Douglas B -- McCrow, John P -- Dupont, Christopher L -- Kim, Maria -- Johnson, Justin -- Montgomery, Robert -- Ferriera, Steve -- Beeson, Karen -- Williamson, Shannon J -- Tovchigrechko, Andrey -- Allen, Andrew E -- Zeigler, Lisa A -- Sutton, Granger -- Eisenstadt, Eric -- Rogers, Yu-Hui -- Friedman, Robert -- Frazier, Marvin -- Venter, J Craig -- England -- Nature. 2010 Nov 4;468(7320):60-6. doi: 10.1038/nature09530.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉J. Craig Venter Institute, Rockville, Maryland 20850, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21048761" target="_blank"〉PubMed〈/a〉
    Keywords: Aquatic Organisms/classification/*genetics/isolation & purification/virology ; Biodiversity ; Biomass ; Databases, Protein ; Genome, Bacterial/genetics ; *Genomics ; *Metagenome ; Models, Biological ; Oceans and Seas ; Phylogeny ; Plankton/*genetics/growth & development/isolation & purification/metabolism ; Prokaryotic Cells/classification/*metabolism/virology ; RNA, Ribosomal, 16S/genetics ; Water Microbiology
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    Experimentally assessing the relative importance of predation and competition as agents of selection (2010)
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    Publication Date: 2010-05-11
    Description: Field experiments that measure natural selection in response to manipulations of the selective regime are extremely rare, even in systems where the ecological basis of adaptation has been studied extensively. The adaptive radiation of Caribbean Anolis lizards has been studied for decades, leading to precise predictions about the influence of alternative agents of selection in the wild. Here we present experimental evidence for the relative importance of two putative agents of selection in shaping the adaptive landscape for a classic island radiation. We manipulated whole-island populations of the brown anole lizard, Anolis sagrei, to measure the relative importance of predation versus competition as agents of natural selection. We excluded or included bird and snake predators across six islands that ranged from low to high population densities of lizards, then measured subsequent differences in behaviour and natural selection in each population. Predators altered the lizards' perching behaviour and increased mortality, but predation treatments did not alter selection on phenotypic traits. By contrast, experimentally increasing population density dramatically increased the strength of viability selection favouring large body size, long relative limb length and high running stamina. Our results from A. sagrei are consistent with the hypothesis that intraspecific competition is more important than predation in shaping the selective landscape for traits central to the adaptive radiation of Anolis ecomorphs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Calsbeek, Ryan -- Cox, Robert M -- England -- Nature. 2010 Jun 3;465(7298):613-6. doi: 10.1038/nature09020. Epub 2010 May 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Dartmouth College, Hanover, New Hampshire 03755, USA. ryan.calsbeek@dartmouth.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20453837" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bahamas ; Behavior, Animal/physiology ; *Biological Evolution ; Birds/physiology ; Body Size/physiology ; Competitive Behavior/*physiology ; Extremities/anatomy & histology ; Geography ; Lizards/anatomy & histology/*physiology ; Models, Biological ; Organ Size/physiology ; Phenotype ; Population Density ; Predatory Behavior/*physiology ; Running/physiology ; Selection, Genetic/*physiology ; Snakes/physiology ; Survival Rate
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    Neural bases for addictive properties of benzodiazepines (2010)
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    Publication Date: 2010-02-12
    Description: Benzodiazepines are widely used in clinics and for recreational purposes, but will lead to addiction in vulnerable individuals. Addictive drugs increase the levels of dopamine and also trigger long-lasting synaptic adaptations in the mesolimbic reward system that ultimately may induce the pathological behaviour. The neural basis for the addictive nature of benzodiazepines, however, remains elusive. Here we show that benzodiazepines increase firing of dopamine neurons of the ventral tegmental area through the positive modulation of GABA(A) (gamma-aminobutyric acid type A) receptors in nearby interneurons. Such disinhibition, which relies on alpha1-containing GABA(A) receptors expressed in these cells, triggers drug-evoked synaptic plasticity in excitatory afferents onto dopamine neurons and underlies drug reinforcement. Taken together, our data provide evidence that benzodiazepines share defining pharmacological features of addictive drugs through cell-type-specific expression of alpha1-containing GABA(A) receptors in the ventral tegmental area. The data also indicate that subunit-selective benzodiazepines sparing alpha1 may be devoid of addiction liability.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2871668/" 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/PMC2871668/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tan, Kelly R -- Brown, Matthew -- Labouebe, Gwenael -- Yvon, Cedric -- Creton, Cyril -- Fritschy, Jean-Marc -- Rudolph, Uwe -- Luscher, Christian -- DA019022/DA/NIDA NIH HHS/ -- R01 DA019022/DA/NIDA NIH HHS/ -- R01 DA019022-04/DA/NIDA NIH HHS/ -- England -- Nature. 2010 Feb 11;463(7282):769-74. doi: 10.1038/nature08758.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Basic Neurosciences, Medical Faculty, University of Geneva, CH-1211 Geneva, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20148031" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials/drug effects ; Administration, Oral ; Animals ; Behavior, Addictive/*chemically induced/pathology/*physiopathology ; Benzodiazepines/administration & dosage/*adverse effects/*pharmacology ; Dopamine/metabolism ; Electric Conductivity ; Glutamic Acid/metabolism ; In Vitro Techniques ; Inhibitory Postsynaptic Potentials/drug effects/physiology ; Interneurons/drug effects/metabolism ; Mice ; Mice, Inbred C57BL ; Midazolam/administration & dosage/adverse effects/pharmacology ; Models, Biological ; Morphine/pharmacology ; Neuronal Plasticity/drug effects ; Neurons/*drug effects/metabolism ; Organ Specificity ; Receptors, AMPA/metabolism ; Receptors, GABA-A/deficiency/genetics/metabolism ; Substrate Specificity ; Ventral Tegmental Area/cytology/drug effects/metabolism ; gamma-Aminobutyric Acid/metabolism
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    Odorant reception in the malaria mosquito Anopheles gambiae (2010)
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    Publication Date: 2010-02-05
    Description: The mosquito Anopheles gambiae is the major vector of malaria in sub-Saharan Africa. It locates its human hosts primarily through olfaction, but little is known about the molecular basis of this process. Here we functionally characterize the Anopheles gambiae odorant receptor (AgOr) repertoire. We identify receptors that respond strongly to components of human odour and that may act in the process of human recognition. Some of these receptors are narrowly tuned, and some salient odorants elicit strong responses from only one or a few receptors, suggesting a central role for specific transmission channels in human host-seeking behaviour. This analysis of the Anopheles gambiae receptors permits a comparison with the corresponding Drosophila melanogaster odorant receptor repertoire. We find that odorants are differentially encoded by the two species in ways consistent with their ecological needs. Our analysis of the Anopheles gambiae repertoire identifies receptors that may be useful targets for controlling the transmission of malaria.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2833235/" 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/PMC2833235/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carey, Allison F -- Wang, Guirong -- Su, Chih-Ying -- Zwiebel, Laurence J -- Carlson, John R -- 2T32GM07205/GM/NIGMS NIH HHS/ -- R01 AI056402/AI/NIAID NIH HHS/ -- R01 AI056402-06A2/AI/NIAID NIH HHS/ -- R01 AI056402-07/AI/NIAID NIH HHS/ -- R01 DC002174/DC/NIDCD NIH HHS/ -- R01 DC002174-24/DC/NIDCD NIH HHS/ -- R01 DC004729/DC/NIDCD NIH HHS/ -- R01 DC004729-10/DC/NIDCD NIH HHS/ -- R01 GM063364/GM/NIGMS NIH HHS/ -- R01 GM063364-08/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Mar 4;464(7285):66-71. doi: 10.1038/nature08834. Epub 2010 Feb 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20130575" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anopheles gambiae/anatomy & histology/genetics/*metabolism ; Drosophila melanogaster/cytology/genetics/metabolism ; Electrophysiology ; Humans ; Insect Bites and Stings/prevention & control ; Insect Vectors/*metabolism ; *Malaria/prevention & control/transmission ; Models, Biological ; Odors/*analysis ; Olfactory Pathways/*metabolism ; Olfactory Receptor Neurons/metabolism ; Receptors, Odorant/genetics/*metabolism ; Time Factors
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    Single-cell NF-kappaB dynamics reveal digital activation and analogue information processing (2010)
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    Publication Date: 2010-06-29
    Description: Cells operate in dynamic environments using extraordinary communication capabilities that emerge from the interactions of genetic circuitry. The mammalian immune response is a striking example of the coordination of different cell types. Cell-to-cell communication is primarily mediated by signalling molecules that form spatiotemporal concentration gradients, requiring cells to respond to a wide range of signal intensities. Here we use high-throughput microfluidic cell culture and fluorescence microscopy, quantitative gene expression analysis and mathematical modelling to investigate how single mammalian cells respond to different concentrations of the signalling molecule tumour-necrosis factor (TNF)-alpha, and relay information to the gene expression programs by means of the transcription factor nuclear factor (NF)-kappaB. We measured NF-kappaB activity in thousands of live cells under TNF-alpha doses covering four orders of magnitude. We find, in contrast to population-level studies with bulk assays, that the activation is heterogeneous and is a digital process at the single-cell level with fewer cells responding at lower doses. Cells also encode a subtle set of analogue parameters to modulate the outcome; these parameters include NF-kappaB peak intensity, response time and number of oscillations. We developed a stochastic mathematical model that reproduces both the digital and analogue dynamics as well as most gene expression profiles at all measured conditions, constituting a broadly applicable model for TNF-alpha-induced NF-kappaB signalling in various types of cells. These results highlight the value of high-throughput quantitative measurements with single-cell resolution in understanding how biological systems operate.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3105528/" 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/PMC3105528/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tay, Savas -- Hughey, Jacob J -- Lee, Timothy K -- Lipniacki, Tomasz -- Quake, Stephen R -- Covert, Markus W -- K99CA125994/CA/NCI NIH HHS/ -- R00 CA125994/CA/NCI NIH HHS/ -- R00 CA125994-05/CA/NCI NIH HHS/ -- R01-GM086885/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Jul 8;466(7303):267-71. doi: 10.1038/nature09145. Epub 2010 Jun 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering, Stanford University, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20581820" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Active Transport, Cell Nucleus/drug effects ; Animals ; Cell Culture Techniques ; Cell Nucleus/drug effects/metabolism ; Cell Survival ; Dose-Response Relationship, Drug ; Gene Expression Profiling/*methods ; Gene Expression Regulation/*drug effects ; High-Throughput Screening Assays/*methods ; Mice ; Microfluidic Analytical Techniques ; Microscopy, Fluorescence ; Models, Biological ; NF-kappa B/*metabolism ; Signal Transduction/*drug effects/*physiology ; Stochastic Processes ; Substrate Specificity ; Time Factors ; Tumor Necrosis Factor-alpha/*pharmacology
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    Tetrapod trackways from the early Middle Devonian period of Poland (2010)
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    Publication Date: 2010-01-08
    Description: The fossil record of the earliest tetrapods (vertebrates with limbs rather than paired fins) consists of body fossils and trackways. The earliest body fossils of tetrapods date to the Late Devonian period (late Frasnian stage) and are preceded by transitional elpistostegids such as Panderichthys and Tiktaalik that still have paired fins. Claims of tetrapod trackways predating these body fossils have remained controversial with regard to both age and the identity of the track makers. Here we present well-preserved and securely dated tetrapod tracks from Polish marine tidal flat sediments of early Middle Devonian (Eifelian stage) age that are approximately 18 million years older than the earliest tetrapod body fossils and 10 million years earlier than the oldest elpistostegids. They force a radical reassessment of the timing, ecology and environmental setting of the fish-tetrapod transition, as well as the completeness of the body fossil record.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Niedzwiedzki, Grzegorz -- Szrek, Piotr -- Narkiewicz, Katarzyna -- Narkiewicz, Marek -- Ahlberg, Per E -- England -- Nature. 2010 Jan 7;463(7277):43-8. doi: 10.1038/nature08623.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Paleobiology and Evolution, Faculty of Biology, Warsaw University, 2S. Banacha Street, 02-097 Warsaw, Poland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20054388" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chordata/anatomy & histology/*physiology ; Extremities/anatomy & histology/physiology ; Fishes/anatomy & histology/physiology ; *Fossils ; Gait/*physiology ; History, Ancient ; Models, Biological ; Phylogeny ; Poland
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    The mutation spectrum revealed by paired genome sequences from a lung cancer patient (2010)
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    Publication Date: 2010-05-28
    Description: Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small-cell lung carcinomas in smokers being the predominant form of the disease. Although previous studies have identified important common somatic mutations in lung cancers, they have primarily focused on a limited set of genes and have thus provided a constrained view of the mutational spectrum. Recent cancer sequencing efforts have used next-generation sequencing technologies to provide a genome-wide view of mutations in leukaemia, breast cancer and cancer cell lines. Here we present the complete sequences of a primary lung tumour (60x coverage) and adjacent normal tissue (46x). Comparing the two genomes, we identify a wide variety of somatic variations, including 〉50,000 high-confidence single nucleotide variants. We validated 530 somatic single nucleotide variants in this tumour, including one in the KRAS proto-oncogene and 391 others in coding regions, as well as 43 large-scale structural variations. These constitute a large set of new somatic mutations and yield an estimated 17.7 per megabase genome-wide somatic mutation rate. Notably, we observe a distinct pattern of selection against mutations within expressed genes compared to non-expressed genes and in promoter regions up to 5 kilobases upstream of all protein-coding genes. Furthermore, we observe a higher rate of amino acid-changing mutations in kinase genes. We present a comprehensive view of somatic alterations in a single lung tumour, and provide the first evidence, to our knowledge, of distinct selective pressures present within the tumour environment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, William -- Jiang, Zhaoshi -- Liu, Jinfeng -- Haverty, Peter M -- Guan, Yinghui -- Stinson, Jeremy -- Yue, Peng -- Zhang, Yan -- Pant, Krishna P -- Bhatt, Deepali -- Ha, Connie -- Johnson, Stephanie -- Kennemer, Michael I -- Mohan, Sankar -- Nazarenko, Igor -- Watanabe, Colin -- Sparks, Andrew B -- Shames, David S -- Gentleman, Robert -- de Sauvage, Frederic J -- Stern, Howard -- Pandita, Ajay -- Ballinger, Dennis G -- Drmanac, Radoje -- Modrusan, Zora -- Seshagiri, Somasekar -- Zhang, Zemin -- England -- Nature. 2010 May 27;465(7297):473-7. doi: 10.1038/nature09004.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioinformatics and Computational Biology, Genentech Inc., South San Francisco, California 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20505728" target="_blank"〉PubMed〈/a〉
    Keywords: Carcinoma, Non-Small-Cell Lung/*genetics ; DNA Mutational Analysis ; Genome, Human/*genetics ; Humans ; Lung Neoplasms/*genetics ; Male ; Middle Aged ; Models, Biological ; Point Mutation/*genetics ; Selection, Genetic/genetics
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    Loss of fish actinotrichia proteins and the fin-to-limb transition (2010)
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    Publication Date: 2010-06-25
    Description: The early development of teleost paired fins is strikingly similar to that of tetrapod limb buds and is controlled by similar mechanisms. One early morphological divergence between pectoral fins and limbs is in the fate of the apical ectodermal ridge (AER), the distal epidermis that rims the bud. Whereas the AER of tetrapods regresses after specification of the skeletal progenitors, the AER of teleost fishes forms a fold that elongates. Formation of the fin fold is accompanied by the synthesis of two rows of rigid, unmineralized fibrils called actinotrichia, which keep the fold straight and guide the migration of mesenchymal cells within the fold. The actinotrichia are made of elastoidin, the components of which, apart from collagen, are unknown. Here we show that two zebrafish proteins, which we name actinodin 1 and 2 (And1 and And2), are essential structural components of elastoidin. The presence of actinodin sequences in several teleost fishes and in the elephant shark (Callorhinchus milii, which occupies a basal phylogenetic position), but not in tetrapods, suggests that these genes have been lost during tetrapod species evolution. Double gene knockdown of and1 and and2 in zebrafish embryos results in the absence of actinotrichia and impaired fin folds. Gene expression profiles in embryos lacking and1 and and2 function are consistent with pectoral fin truncation and may offer a potential explanation for the polydactyly observed in early tetrapod fossils. We propose that the loss of both actinodins and actinotrichia during evolution may have led to the loss of lepidotrichia and may have contributed to the fin-to-limb transition.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Jing -- Wagh, Purva -- Guay, Danielle -- Sanchez-Pulido, Luis -- Padhi, Bhaja K -- Korzh, Vladimir -- Andrade-Navarro, Miguel A -- Akimenko, Marie-Andree -- MC_U137761446/Medical Research Council/United Kingdom -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2010 Jul 8;466(7303):234-7. doi: 10.1038/nature09137. Epub 2010 Jun 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CAREG, Department of Biology, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20574421" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Structures/*anatomy & histology/embryology/*physiology ; Animals ; *Biological Evolution ; Collagen/chemistry/metabolism ; Ectoderm/embryology/metabolism ; Embryo, Nonmammalian/anatomy & histology/embryology/metabolism ; Evolution, Molecular ; Extremities/anatomy & histology/embryology/*physiology ; Fish Proteins/*deficiency/genetics/metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Knockdown Techniques ; Limb Buds/anatomy & histology/embryology/metabolism ; Models, Biological ; Phylogeny ; Zebrafish/*anatomy & histology/embryology/genetics/*metabolism ; Zebrafish Proteins/deficiency/genetics/metabolism
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    Drug discovery: inhibitors that activate (2010)
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    Publication Date: 2010-03-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cichowski, Karen -- Janne, Pasi A -- England -- Nature. 2010 Mar 18;464(7287):358-9. doi: 10.1038/464358a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20237552" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Animals ; Enzyme Activation/drug effects ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Humans ; MAP Kinase Signaling System/*drug effects ; Melanoma/drug therapy/pathology ; Mitogen-Activated Protein Kinase Kinases/metabolism ; Models, Biological ; Neoplasms/*chemically induced/*drug therapy/enzymology/genetics ; Protein Kinase Inhibitors/adverse effects/*pharmacology/therapeutic use ; Proto-Oncogene Proteins B-raf/antagonists & inhibitors/*genetics/*metabolism ; raf Kinases/*antagonists & inhibitors/chemistry/genetics/*metabolism ; ras Proteins/genetics/metabolism
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    Cancer: Tumour stem cells switch sides (2010)
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    Publication Date: 2010-12-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bautch, Victoria L -- England -- Nature. 2010 Dec 9;468(7325):770-1. doi: 10.1038/468770a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21150987" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/metabolism ; Biomarkers, Tumor/metabolism ; *Cell Differentiation ; Cell Lineage ; Chromosome Aberrations ; Endothelial Cells/metabolism/*pathology ; Glioblastoma/*blood supply/genetics/*pathology ; Glycoproteins/metabolism ; Humans ; Models, Biological ; Neoplastic Stem Cells/metabolism/*pathology ; Neovascularization, Pathologic/genetics/*pathology ; Neural Stem Cells/metabolism/*pathology ; Peptides/metabolism ; Receptors, Notch/metabolism ; Vascular Endothelial Growth Factor A/metabolism
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    Reproductive ageing: Of worms and women (2010)
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    Publication Date: 2010-11-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Flurkey, Kevin -- Harrison, David E -- P30 AG025707/AG/NIA NIH HHS/ -- R01 AG026074/AG/NIA NIH HHS/ -- England -- Nature. 2010 Nov 18;468(7322):386-7. doi: 10.1038/468386a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21085171" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/genetics/*physiology ; Animals ; Caenorhabditis elegans/cytology/embryology/genetics/*physiology ; Caenorhabditis elegans Proteins/genetics/metabolism ; Embryo, Nonmammalian/cytology/embryology ; Female ; Fertility/genetics/*physiology ; Humans ; Insulin/metabolism ; Insulin-Like Growth Factor I/metabolism ; Longevity/genetics/*physiology ; Male ; Maternal Age ; Models, Animal ; Models, Biological ; Oocytes/growth & development/*physiology ; Receptor, Insulin/genetics/metabolism ; Signal Transduction/genetics/physiology ; Transforming Growth Factor beta/metabolism
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    Cross-species genomics matches driver mutations and cell compartments to model ependymoma (2010)
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    Publication Date: 2010-07-20
    Description: Understanding the biology that underlies histologically similar but molecularly distinct subgroups of cancer has proven difficult because their defining genetic alterations are often numerous, and the cellular origins of most cancers remain unknown. We sought to decipher this heterogeneity by integrating matched genetic alterations and candidate cells of origin to generate accurate disease models. First, we identified subgroups of human ependymoma, a form of neural tumour that arises throughout the central nervous system (CNS). Subgroup-specific alterations included amplifications and homozygous deletions of genes not yet implicated in ependymoma. To select cellular compartments most likely to give rise to subgroups of ependymoma, we matched the transcriptomes of human tumours to those of mouse neural stem cells (NSCs), isolated from different regions of the CNS at different developmental stages, with an intact or deleted Ink4a/Arf locus (that encodes Cdkn2a and b). The transcriptome of human supratentorial ependymomas with amplified EPHB2 and deleted INK4A/ARF matched only that of embryonic cerebral Ink4a/Arf(-/-) NSCs. Notably, activation of Ephb2 signalling in these, but not other, NSCs generated the first mouse model of ependymoma, which is highly penetrant and accurately models the histology and transcriptome of one subgroup of human supratentorial tumour. Further, comparative analysis of matched mouse and human tumours revealed selective deregulation in the expression and copy number of genes that control synaptogenesis, pinpointing disruption of this pathway as a critical event in the production of this ependymoma subgroup. Our data demonstrate the power of cross-species genomics to meticulously match subgroup-specific driver mutations with cellular compartments to model and interrogate cancer subgroups.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2912966/" 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/PMC2912966/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johnson, Robert A -- Wright, Karen D -- Poppleton, Helen -- Mohankumar, Kumarasamypet M -- Finkelstein, David -- Pounds, Stanley B -- Rand, Vikki -- Leary, Sarah E S -- White, Elsie -- Eden, Christopher -- Hogg, Twala -- Northcott, Paul -- Mack, Stephen -- Neale, Geoffrey -- Wang, Yong-Dong -- Coyle, Beth -- Atkinson, Jennifer -- DeWire, Mariko -- Kranenburg, Tanya A -- Gillespie, Yancey -- Allen, Jeffrey C -- Merchant, Thomas -- Boop, Fredrick A -- Sanford, Robert A -- Gajjar, Amar -- Ellison, David W -- Taylor, Michael D -- Grundy, Richard G -- Gilbertson, Richard J -- P01 CA096832/CA/NCI NIH HHS/ -- P01 CA096832-06A18120/CA/NCI NIH HHS/ -- P01 CA096832-078120/CA/NCI NIH HHS/ -- P01CA96832/CA/NCI NIH HHS/ -- P30 CA021765/CA/NCI NIH HHS/ -- P30 CA021765-319030/CA/NCI NIH HHS/ -- P30CA021765/CA/NCI NIH HHS/ -- R01 CA129541/CA/NCI NIH HHS/ -- R01 CA129541-01/CA/NCI NIH HHS/ -- R01 CA129541-02/CA/NCI NIH HHS/ -- R01 CA129541-03/CA/NCI NIH HHS/ -- R01 CA129541-04/CA/NCI NIH HHS/ -- R01CA129541/CA/NCI NIH HHS/ -- T32 CA070089/CA/NCI NIH HHS/ -- England -- Nature. 2010 Jul 29;466(7306):632-6. doi: 10.1038/nature09173. Epub 2010 Jul 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Neurobiology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20639864" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Compartmentation ; Central Nervous System/cytology/growth & development ; Central Nervous System Neoplasms/classification/genetics/pathology ; *Disease Models, Animal ; Ependymoma/classification/*genetics/*pathology ; Gene Deletion ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genes, p16 ; *Genomics ; Humans ; Mice ; Models, Biological ; Mutation/*genetics ; Polymorphism, Single Nucleotide/genetics ; Receptor, EphB2/genetics/metabolism ; Species Specificity ; Stem Cells/cytology/metabolism ; Synapses/metabolism
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    Q&A: Animal behaviour: Magnetic-field perception (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-04-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lohmann, Kenneth J -- England -- Nature. 2010 Apr 22;464(7292):1140-2. doi: 10.1038/4641140a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA. klohmann@email.unc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20414302" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Migration/physiology ; Animals ; Behavior, Animal/*physiology ; *Earth (Planet) ; Electromagnetic Phenomena ; Ferrosoferric Oxide/analysis/chemistry/metabolism ; *Magnetics ; Models, Biological ; Orientation/physiology ; Perception/*physiology ; Sensation/physiology
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    Structure of a fucose transporter in an outward-open conformation (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-09-30
    Description: The major facilitator superfamily (MFS) transporters are an ancient and widespread family of secondary active transporters. In Escherichia coli, the uptake of l-fucose, a source of carbon for microorganisms, is mediated by an MFS proton symporter, FucP. Despite intensive study of the MFS transporters, atomic structure information is only available on three proteins and the outward-open conformation has yet to be captured. Here we report the crystal structure of FucP at 3.1 A resolution, which shows that it contains an outward-open, amphipathic cavity. The similarly folded amino and carboxyl domains of FucP have contrasting surface features along the transport path, with negative electrostatic potential on the N domain and hydrophobic surface on the C domain. FucP only contains two acidic residues along the transport path, Asp 46 and Glu 135, which can undergo cycles of protonation and deprotonation. Their essential role in active transport is supported by both in vivo and in vitro experiments. Structure-based biochemical analyses provide insights into energy coupling, substrate recognition and the transport mechanism of FucP.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dang, Shangyu -- Sun, Linfeng -- Huang, Yongjian -- Lu, Feiran -- Liu, Yufeng -- Gong, Haipeng -- Wang, Jiawei -- Yan, Nieng -- England -- Nature. 2010 Oct 7;467(7316):734-8. doi: 10.1038/nature09406. Epub 2010 Sep 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Bio-membrane and Membrane Biotechnology, Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20877283" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography, X-Ray ; Escherichia coli/*chemistry ; Escherichia coli Proteins/*chemistry/metabolism ; Fucose/metabolism ; Hydrophobic and Hydrophilic Interactions ; Models, Biological ; Models, Molecular ; Monosaccharide Transport Proteins/*chemistry/metabolism ; Protein Conformation ; Protons ; Rotation ; Static Electricity ; Symporters/*chemistry/metabolism
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    Formate-driven growth coupled with H(2) production (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-09-17
    Description: Although a common reaction in anaerobic environments, the conversion of formate and water to bicarbonate and H(2) (with a change in Gibbs free energy of DeltaG degrees = +1.3 kJ mol(-1)) has not been considered energetic enough to support growth of microorganisms. Recently, experimental evidence for growth on formate was reported for syntrophic communities of Moorella sp. strain AMP and a hydrogen-consuming Methanothermobacter species and of Desulfovibrio sp. strain G11 and Methanobrevibacter arboriphilus strain AZ. The basis of the sustainable growth of the formate-users is explained by H(2) consumption by the methanogens, which lowers the H(2) partial pressure, thus making the pathway exergonic. However, it has not been shown that a single strain can grow on formate by catalysing its conversion to bicarbonate and H(2). Here we report that several hyperthermophilic archaea belonging to the Thermococcus genus are capable of formate-oxidizing, H(2)-producing growth. The actual DeltaG values for the formate metabolism are calculated to range between -8 and -20 kJ mol(-1) under the physiological conditions where Thermococcus onnurineus strain NA1 are grown. Furthermore, we detected ATP synthesis in the presence of formate as a sole energy source. Gene expression profiling and disruption identified the gene cluster encoding formate hydrogen lyase, cation/proton antiporter and formate transporter, which were responsible for the growth of T. onnurineus NA1 on formate. This work shows formate-driven growth by a single microorganism with protons as the electron acceptor, and reports the biochemical basis of this ability.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Yun Jae -- Lee, Hyun Sook -- Kim, Eun Sook -- Bae, Seung Seob -- Lim, Jae Kyu -- Matsumi, Rie -- Lebedinsky, Alexander V -- Sokolova, Tatyana G -- Kozhevnikova, Darya A -- Cha, Sun-Shin -- Kim, Sang-Jin -- Kwon, Kae Kyoung -- Imanaka, Tadayuki -- Atomi, Haruyuki -- Bonch-Osmolovskaya, Elizaveta A -- Lee, Jung-Hyun -- Kang, Sung Gyun -- England -- Nature. 2010 Sep 16;467(7313):352-5. doi: 10.1038/nature09375.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Korea Ocean Research & Development Institute, PO Box 29, Ansan 425-600, Korea.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20844539" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/analysis/biosynthesis ; Anaerobiosis ; Biocatalysis ; Carbon Dioxide/metabolism ; Electrons ; Formate Dehydrogenases ; Formates/*metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Archaeal/genetics ; Hydrogen/*metabolism ; Hydrogenase ; Lyases/metabolism ; Models, Biological ; Multienzyme Complexes ; Multigene Family/genetics ; Oxidation-Reduction ; Partial Pressure ; Protons ; Reverse Transcriptase Polymerase Chain Reaction ; Thermococcus/classification/genetics/*growth & development/*metabolism ; Water/metabolism
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    Translating cancer research into targeted therapeutics (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-10-01
    Description: The emphasis in cancer drug development has shifted from cytotoxic, non-specific chemotherapies to molecularly targeted, rationally designed drugs promising greater efficacy and less side effects. Nevertheless, despite some successes drug development remains painfully slow. Here, we highlight the issues involved and suggest ways in which this process can be improved and expedited. We envision an increasing shift to integrated cancer research and biomarker-driven adaptive and hypothesis testing clinical trials. The goal is the development of specific cancer medicines to treat the individual patient, with treatment selection being driven by a detailed understanding of the genetics and biology of the patient and their cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉de Bono, J S -- Ashworth, Alan -- England -- Nature. 2010 Sep 30;467(7315):543-9. doi: 10.1038/nature09339.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Institute of Cancer Research, Cotswold Road, Sutton, Surrey SM2 5NG, UK. johann.de-bono@icr.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20882008" target="_blank"〉PubMed〈/a〉
    Keywords: Biomarkers, Tumor/antagonists & inhibitors/genetics/metabolism ; Biomedical Research/*trends ; Clinical Trials as Topic ; Drug Approval ; Drug Design ; Female ; Humans ; Male ; Models, Biological ; Neoplasms/*drug therapy/genetics/metabolism/pathology ; Precision Medicine/*trends ; Tissue Banks ; Translational Medical Research/*trends
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    George C. Williams (1926-2010) (2010)
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    Publication Date: 2010-10-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meyer, Axel -- England -- Nature. 2010 Oct 14;467(7317):790. doi: 10.1038/467790a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology at the University of Konstanz, D78457 Konstanz, Germany. axel.meyer@uni-konstanz.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20944730" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/physiology ; *Biological Evolution ; History, 20th Century ; Models, Biological ; Reproduction/genetics/physiology ; *Selection, Genetic ; United States
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    Microtubule nucleating gamma-TuSC assembles structures with 13-fold microtubule-like symmetry (2010)
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    Publication Date: 2010-07-16
    Description: Microtubules are nucleated in vivo by gamma-tubulin complexes. The 300-kDa gamma-tubulin small complex (gamma-TuSC), consisting of two molecules of gamma-tubulin and one copy each of the accessory proteins Spc97 and Spc98, is the conserved, essential core of the microtubule nucleating machinery. In metazoa multiple gamma-TuSCs assemble with other proteins into gamma-tubulin ring complexes (gamma-TuRCs). The structure of gamma-TuRC indicated that it functions as a microtubule template. Because each gamma-TuSC contains two molecules of gamma-tubulin, it was assumed that the gamma-TuRC-specific proteins are required to organize gamma-TuSCs to match 13-fold microtubule symmetry. Here we show that Saccharomyces cerevisiae gamma-TuSC forms rings even in the absence of other gamma-TuRC components. The yeast adaptor protein Spc110 stabilizes the rings into extended filaments and is required for oligomer formation under physiological buffer conditions. The 8-A cryo-electron microscopic reconstruction of the filament reveals 13 gamma-tubulins per turn, matching microtubule symmetry, with plus ends exposed for interaction with microtubules, implying that one turn of the filament constitutes a microtubule template. The domain structures of Spc97 and Spc98 suggest functions for conserved sequence motifs, with implications for the gamma-TuRC-specific proteins. The gamma-TuSC filaments nucleate microtubules at a low level, and the structure provides a strong hypothesis for how nucleation is regulated, converting this less active form to a potent nucleator.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2921000/" 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/PMC2921000/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kollman, Justin M -- Polka, Jessica K -- Zelter, Alex -- Davis, Trisha N -- Agard, David A -- F32 GM078790-03/GM/NIGMS NIH HHS/ -- R01 GM031627/GM/NIGMS NIH HHS/ -- R01 GM031627-27/GM/NIGMS NIH HHS/ -- R01 GM040506/GM/NIGMS NIH HHS/ -- R01 GM040506-21/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Aug 12;466(7308):879-82. doi: 10.1038/nature09207. Epub 2010 Jul 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, Howard Hughes Medical Institute, and Keck Advanced Microscopy Center, University of California, San Francisco, San Francisco, California 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20631709" target="_blank"〉PubMed〈/a〉
    Keywords: Buffers ; Cryoelectron Microscopy ; Cytoskeletal Proteins/chemistry/metabolism ; Microtubule-Associated Proteins/chemistry/metabolism ; Microtubules/*chemistry/metabolism/*ultrastructure ; Models, Biological ; Models, Molecular ; Multiprotein Complexes/chemistry/metabolism/ultrastructure ; Nuclear Proteins/chemistry/metabolism ; Saccharomyces cerevisiae/chemistry/*cytology/*ultrastructure ; Saccharomyces cerevisiae Proteins/chemistry/metabolism ; Tubulin/*chemistry/metabolism/*ultrastructure
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    Ecology. Structure and dynamics of ecological networks (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-08-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bascompte, Jordi -- New York, N.Y. -- Science. 2010 Aug 13;329(5993):765-6. doi: 10.1126/science.1194255.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Integrative Ecology Group, Estacion Biologica de Donana, Consejo Superior de Investigaciones Cientificas, Americo Vespucio s/n, E-41092 Sevilla, Spain. bascompte@ebd.csic.es〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20705836" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Ecosystem ; Food Chain ; Insects/*physiology ; Models, Biological ; *Plant Physiological Phenomena ; Pollination ; *Symbiosis
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    A novel miRNA processing pathway independent of Dicer requires Argonaute2 catalytic activity (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-05-08
    Description: Dicer is a central enzyme in microRNA (miRNA) processing. We identified a Dicer-independent miRNA biogenesis pathway that uses Argonaute2 (Ago2) slicer catalytic activity. In contrast to other miRNAs, miR-451 levels were refractory to dicer loss of function but were reduced in MZago2 (maternal-zygotic) mutants. We found that pre-miR-451 processing requires Ago2 catalytic activity in vivo. MZago2 mutants showed delayed erythropoiesis that could be rescued by wild-type Ago2 or miR-451-duplex but not by catalytically dead Ago2. Changing the secondary structure of Dicer-dependent miRNAs to mimic that of pre-miR-451 restored miRNA function and rescued developmental defects in MZdicer mutants, indicating that the pre-miRNA secondary structure determines the processing pathway in vivo. We propose that Ago2-mediated cleavage of pre-miRNAs, followed by uridylation and trimming, generates functional miRNAs independently of Dicer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093307/" 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/PMC3093307/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cifuentes, Daniel -- Xue, Huiling -- Taylor, David W -- Patnode, Heather -- Mishima, Yuichiro -- Cheloufi, Sihem -- Ma, Enbo -- Mane, Shrikant -- Hannon, Gregory J -- Lawson, Nathan D -- Wolfe, Scot A -- Giraldez, Antonio J -- P01 CA013106/CA/NCI NIH HHS/ -- P01 CA013106-38/CA/NCI NIH HHS/ -- R01 GM081602/GM/NIGMS NIH HHS/ -- R01 GM081602-01/GM/NIGMS NIH HHS/ -- R01 GM081602-02/GM/NIGMS NIH HHS/ -- R01 GM081602-03/GM/NIGMS NIH HHS/ -- R01 GM081602-03S1/GM/NIGMS NIH HHS/ -- R01 GM081602-04/GM/NIGMS NIH HHS/ -- R01 GM101108/GM/NIGMS NIH HHS/ -- R01 HL093766/HL/NHLBI NIH HHS/ -- R01 HL093766-04/HL/NHLBI NIH HHS/ -- R01GM081602-03/03S1/GM/NIGMS NIH HHS/ -- R01HL093766/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Jun 25;328(5986):1694-8. doi: 10.1126/science.1190809. Epub 2010 May 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, 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/20448148" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Argonaute Proteins ; Biocatalysis ; Embryo, Nonmammalian/metabolism ; Embryonic Development ; Erythropoiesis ; Eukaryotic Initiation Factor-2/genetics/*metabolism ; Humans ; MicroRNAs/*chemistry/*metabolism ; Models, Biological ; Morphogenesis ; Nucleic Acid Conformation ; RNA Precursors/metabolism ; RNA Processing, Post-Transcriptional ; Recombinant Proteins/metabolism ; Ribonuclease III/metabolism ; Zebrafish/embryology/genetics/*metabolism ; Zebrafish Proteins/genetics/*metabolism
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    Covering a broad dynamic range: information processing at the erythropoietin receptor (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-05-22
    Description: Cell surface receptors convert extracellular cues into receptor activation, thereby triggering intracellular signaling networks and controlling cellular decisions. A major unresolved issue is the identification of receptor properties that critically determine processing of ligand-encoded information. We show by mathematical modeling of quantitative data and experimental validation that rapid ligand depletion and replenishment of the cell surface receptor are characteristic features of the erythropoietin (Epo) receptor (EpoR). The amount of Epo-EpoR complexes and EpoR activation integrated over time corresponds linearly to ligand input; this process is carried out over a broad range of ligand concentrations. This relation depends solely on EpoR turnover independent of ligand binding, which suggests an essential role of large intracellular receptor pools. These receptor properties enable the system to cope with basal and acute demand in the hematopoietic system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Becker, Verena -- Schilling, Marcel -- Bachmann, Julie -- Baumann, Ute -- Raue, Andreas -- Maiwald, Thomas -- Timmer, Jens -- Klingmuller, Ursula -- New York, N.Y. -- Science. 2010 Jun 11;328(5984):1404-8. doi: 10.1126/science.1184913. Epub 2010 May 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division Systems Biology of Signal Transduction, DKFZ-ZMBH Alliance, German Cancer Research Center, 69120 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20488988" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cell Membrane/*metabolism ; Computer Simulation ; Endocytosis ; Epoetin Alfa ; Erythropoietin/metabolism/pharmacology ; Kinetics ; Ligands ; Mice ; Models, Biological ; Protein Binding ; Receptors, Erythropoietin/*metabolism ; Recombinant Proteins ; Signal Transduction
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    Cell signaling. Signaling through cooperation (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-05-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Levy, Emmanuel D -- Landry, Christian R -- Michnick, Stephen W -- New York, N.Y. -- Science. 2010 May 21;328(5981):983-4. doi: 10.1126/science.1190993.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departement de Biochimie, Universite de Montreal, Montreal, Quebec, Canada H3T 1J4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20489011" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Mass Spectrometry ; Metabolic Networks and Pathways ; Models, Biological ; Phosphoprotein Phosphatases/*metabolism ; Phosphorylation ; Protein Interaction Mapping ; Protein Kinases/*metabolism ; Saccharomyces cerevisiae/enzymology/*metabolism ; Saccharomyces cerevisiae Proteins/*metabolism ; *Signal Transduction
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    Cell type-specific loss of BDNF signaling mimics optogenetic control of cocaine reward (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-10-16
    Description: The nucleus accumbens is a key mediator of cocaine reward, but the distinct roles of the two subpopulations of nucleus accumbens projection neurons, those expressing dopamine D1 versus D2 receptors, are poorly understood. We show that deletion of TrkB, the brain-derived neurotrophic factor (BDNF) receptor, selectively from D1+ or D2+ neurons oppositely affects cocaine reward. Because loss of TrkB in D2+ neurons increases their neuronal excitability, we next used optogenetic tools to control selectively the firing rate of D1+ and D2+ nucleus accumbens neurons and studied consequent effects on cocaine reward. Activation of D2+ neurons, mimicking the loss of TrkB, suppresses cocaine reward, with opposite effects induced by activation of D1+ neurons. These results provide insight into the molecular control of D1+ and D2+ neuronal activity as well as the circuit-level contribution of these cell types to cocaine reward.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3011229/" 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/PMC3011229/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lobo, Mary Kay -- Covington, Herbert E 3rd -- Chaudhury, Dipesh -- Friedman, Allyson K -- Sun, HaoSheng -- Damez-Werno, Diane -- Dietz, David M -- Zaman, Samir -- Koo, Ja Wook -- Kennedy, Pamela J -- Mouzon, Ezekiell -- Mogri, Murtaza -- Neve, Rachael L -- Deisseroth, Karl -- Han, Ming-Hu -- Nestler, Eric J -- P01 DA008227/DA/NIDA NIH HHS/ -- P01 DA008227-20/DA/NIDA NIH HHS/ -- R01 DA007359/DA/NIDA NIH HHS/ -- R01 DA007359-22/DA/NIDA NIH HHS/ -- R01 DA014133/DA/NIDA NIH HHS/ -- R01 DA014133-10/DA/NIDA NIH HHS/ -- R01 DA014133-11/DA/NIDA NIH HHS/ -- R01 DA014133-12/DA/NIDA NIH HHS/ -- R01 MH051399/MH/NIMH NIH HHS/ -- R01 MH051399-19/MH/NIMH NIH HHS/ -- R01 MH051399-20/MH/NIMH NIH HHS/ -- T32 DA007135-26A2/DA/NIDA NIH HHS/ -- New York, N.Y. -- Science. 2010 Oct 15;330(6002):385-90. doi: 10.1126/science.1188472.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Fishberg Department of Neuroscience, Mount Sinai School of Medicine, New York, NY 10029, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20947769" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal/drug effects ; Brain-Derived Neurotrophic Factor/*metabolism ; Cocaine/*pharmacology ; Cocaine-Related Disorders/*metabolism ; Conditioning (Psychology) ; Light ; Mice ; Mice, Transgenic ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Models, Biological ; Motor Activity/drug effects ; Neurons/*metabolism ; Nucleus Accumbens/cytology/*metabolism ; RNA, Messenger/genetics/metabolism ; Receptor, trkB/genetics/*metabolism ; Receptors, Dopamine D1/metabolism ; Receptors, Dopamine D2/metabolism ; *Reward ; Rhodopsin/genetics/metabolism ; *Signal Transduction
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    Interdependence of cell growth and gene expression: origins and consequences (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-11-26
    Description: In bacteria, the rate of cell proliferation and the level of gene expression are intimately intertwined. Elucidating these relations is important both for understanding the physiological functions of endogenous genetic circuits and for designing robust synthetic systems. We describe a phenomenological study that reveals intrinsic constraints governing the allocation of resources toward protein synthesis and other aspects of cell growth. A theory incorporating these constraints can accurately predict how cell proliferation and gene expression affect one another, quantitatively accounting for the effect of translation-inhibiting antibiotics on gene expression and the effect of gratuitous protein expression on cell growth. The use of such empirical relations, analogous to phenomenological laws, may facilitate our understanding and manipulation of complex biological systems before underlying regulatory circuits are elucidated.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scott, Matthew -- Gunderson, Carl W -- Mateescu, Eduard M -- Zhang, Zhongge -- Hwa, Terence -- R01GM77298/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Nov 19;330(6007):1099-102. doi: 10.1126/science.1192588.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Theoretical Biological Physics, Department of Physics, University of California, San Diego, La Jolla, CA 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21097934" target="_blank"〉PubMed〈/a〉
    Keywords: *Cell Proliferation ; Escherichia coli K12/*genetics/*growth & development ; Escherichia coli Proteins/genetics ; Gene Expression/*physiology ; Models, Biological ; Protein Biosynthesis ; RNA, Bacterial/genetics
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    Nonlinear elasticity and an 8-nm working stroke of single myosin molecules in myofilaments (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-08-07
    Description: Using optical trapping and fluorescence imaging techniques, we measured the step size and stiffness of single skeletal myosins interacting with actin filaments and arranged on myosin-rod cofilaments that approximate myosin mechanics during muscle contraction. Stiffness is dramatically lower for negatively compared to positively strained myosins, consistent with buckling of myosin's subfragment 2 rod domain. Low stiffness minimizes drag of negatively strained myosins during contraction at loaded conditions. Myosin's elastic portion is stretched during active force generation, reducing apparent step size with increasing load, even though the working stroke is approximately constant at about 8 nanometers. Taking account of the nonlinear nature of myosin elasticity is essential to relate myosin's internal structural changes to physiological force generation and filament sliding.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaya, Motoshi -- Higuchi, Hideo -- New York, N.Y. -- Science. 2010 Aug 6;329(5992):686-9. doi: 10.1126/science.1191484.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyou-ku, Tokyo, 113-0033 Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20689017" target="_blank"〉PubMed〈/a〉
    Keywords: Actin Cytoskeleton/*physiology ; Actomyosin/chemistry/physiology ; Adenosine Diphosphate/metabolism ; Adenosine Triphosphate/metabolism ; Animals ; Compliance ; Elasticity ; Models, Biological ; *Muscle Contraction ; Muscle Fibers, Skeletal/chemistry/physiology ; Muscle, Skeletal ; Myosin Subfragments/physiology ; Myosins/chemistry/*physiology ; Quantum Dots ; Rabbits
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    Btbd7 regulates epithelial cell dynamics and branching morphogenesis (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-07-31
    Description: During embryonic development, many organs form by extensive branching of epithelia through the formation of clefts and buds. In cleft formation, buds are delineated by the conversion of epithelial cell-cell adhesions to cell-matrix adhesions, but the mechanisms of cleft formation are not clear. We have identified Btbd7 as a dynamic regulator of branching morphogenesis. Btbd7 provides a mechanistic link between the extracellular matrix and cleft propagation through its highly focal expression leading to local regulation of Snail2 (Slug), E-cadherin, and epithelial cell motility. Inhibition experiments show that Btbd7 is required for branching of embryonic mammalian salivary glands and lungs. Hence, Btbd7 is a regulatory gene that promotes epithelial tissue remodeling and formation of branched organs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3412157/" 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/PMC3412157/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Onodera, Tomohiro -- Sakai, Takayoshi -- Hsu, Jeff Chi-feng -- Matsumoto, Kazue -- Chiorini, John A -- Yamada, Kenneth M -- ZIA DE000525-20/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2010 Jul 30;329(5991):562-5. doi: 10.1126/science.1191880.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-4370, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20671187" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cadherins/metabolism ; Cell Adhesion ; Cell Line ; Cell Movement ; Dogs ; Epithelial Cells/*physiology ; Fibronectins/genetics/metabolism ; Genes, Regulator ; Lung/*embryology/metabolism ; Mice ; Mice, Inbred ICR ; Models, Biological ; Molecular Sequence Data ; *Morphogenesis ; Nuclear Proteins ; Organ Culture Techniques ; Proteins/chemistry/*genetics/*physiology ; RNA, Small Interfering ; Salivary Glands/*embryology/metabolism ; Submandibular Gland/embryology ; Transcription Factors/genetics/metabolism ; Transfection
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    Cell signaling. Anchors away for ubiquitin chains (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-06-05
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3023166/" 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/PMC3023166/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Parvatiyar, Kislay -- Harhaj, Edward W -- R01 GM083143/GM/NIGMS NIH HHS/ -- R01 GM083143-03/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Jun 4;328(5983):1244-5. doi: 10.1126/science.1192296.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20522767" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/*metabolism ; Cell-Free System ; DEAD-box RNA Helicases/chemistry/*metabolism ; Humans ; Interferon Regulatory Factor-3/*metabolism ; Models, Biological ; Polyubiquitin/*metabolism ; Protein Binding ; RNA, Viral/*metabolism ; *Signal Transduction ; Transcription Factors/metabolism ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination ; Virus Diseases/immunology/metabolism
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    The onset of collective behavior in social amoebae (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-04-24
    Description: In the social amoebae Dictyostelium discoideum, periodic synthesis and release of extracellular cyclic adenosine 3',5'-monophosphate (cAMP) guide cell aggregation and commitment to form fruiting bodies. It is unclear whether these oscillations are an intrinsic property of individual cells or if they exist only as a population-level phenomenon. Here, we showed by live-cell imaging of intact cell populations that pulses originate from a discrete location despite constant exchange of cells to and from the region. In a perfusion chamber, both isolated single cells and cell populations switched from quiescence to rhythmic activity depending on the concentration of extracellular cAMP. A quantitative analysis showed that stochastic pulsing of individual cells below the threshold concentration of extracellular cAMP plays a critical role in the onset of collective behavior.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3120019/" 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/PMC3120019/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gregor, Thomas -- Fujimoto, Koichi -- Masaki, Noritaka -- Sawai, Satoshi -- P50 GM071508/GM/NIGMS NIH HHS/ -- P50 GM071508-08/GM/NIGMS NIH HHS/ -- R01 GM098407/GM/NIGMS NIH HHS/ -- R01 GM098407-01A1/GM/NIGMS NIH HHS/ -- R01 GM098407-02/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 May 21;328(5981):1021-5. doi: 10.1126/science.1183415. Epub 2010 Apr 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate School of Arts and Sciences, University of Tokyo, Tokyo 153-8902, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20413456" target="_blank"〉PubMed〈/a〉
    Keywords: 3',5'-Cyclic-AMP Phosphodiesterases/metabolism ; Adenylyl Cyclases/metabolism ; Cell Aggregation ; Cell Count ; Cyclic AMP/*metabolism/pharmacology ; Cyclic AMP-Dependent Protein Kinases/genetics/metabolism ; Cytosol/metabolism ; Dictyostelium/cytology/genetics/growth & development/*physiology ; Fluorescence Resonance Energy Transfer ; Models, Biological ; Periodicity ; Protozoan Proteins/genetics/metabolism ; Quorum Sensing ; Signal Transduction ; Stochastic Processes
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    The evolution of maximum body size of terrestrial mammals (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-11-27
    Description: The extinction of dinosaurs at the Cretaceous/Paleogene (K/Pg) boundary was the seminal event that opened the door for the subsequent diversification of terrestrial mammals. Our compilation of maximum body size at the ordinal level by sub-epoch shows a near-exponential increase after the K/Pg. On each continent, the maximum size of mammals leveled off after 40 million years ago and thereafter remained approximately constant. There was remarkable congruence in the rate, trajectory, and upper limit across continents, orders, and trophic guilds, despite differences in geological and climatic history, turnover of lineages, and ecological variation. Our analysis suggests that although the primary driver for the evolution of giant mammals was diversification to fill ecological niches, environmental temperature and land area may have ultimately constrained the maximum size achieved.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smith, Felisa A -- Boyer, Alison G -- Brown, James H -- Costa, Daniel P -- Dayan, Tamar -- Ernest, S K Morgan -- Evans, Alistair R -- Fortelius, Mikael -- Gittleman, John L -- Hamilton, Marcus J -- Harding, Larisa E -- Lintulaakso, Kari -- Lyons, S Kathleen -- McCain, Christy -- Okie, Jordan G -- Saarinen, Juha J -- Sibly, Richard M -- Stephens, Patrick R -- Theodor, Jessica -- Uhen, Mark D -- New York, N.Y. -- Science. 2010 Nov 26;330(6008):1216-9. doi: 10.1126/science.1194830.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, MSC03 2020, University of New Mexico, Albuquerque, NM 87131, USA. fasmith@unm.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21109666" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Atmosphere ; *Biological Evolution ; *Body Size ; Ecosystem ; Environment ; Extinction, Biological ; Fossils ; Geography ; Mammals/*anatomy & histology/classification/growth & development ; Models, Biological ; Oxygen ; Phylogeny ; Temperature
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    Structural sources of robustness in biochemical reaction networks (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-03-13
    Description: In vivo variations in the concentrations of biomolecular species are inevitable. These variations in turn propagate along networks of chemical reactions and modify the concentrations of still other species, which influence biological activity. Because excessive variations in the amounts of certain active species might hamper cell function, regulation systems have evolved that act to maintain concentrations within tight bounds. We identify simple yet subtle structural attributes that impart concentration robustness to any mass-action network possessing them. We thereby describe a large class of robustness-inducing networks that already embraces two quite different biochemical modules for which concentration robustness has been observed experimentally: the Escherichia coli osmoregulation system EnvZ-OmpR and the glyoxylate bypass control system isocitrate dehydrogenase kinase-phosphatase-isocitrate dehydrogenase. The structural attributes identified here might confer robustness far more broadly.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shinar, Guy -- Feinberg, Martin -- 1R01GM086881-01/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Mar 12;327(5971):1389-91. doi: 10.1126/science.1183372.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20223989" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Outer Membrane Proteins/*metabolism ; Bacterial Proteins/*metabolism ; Escherichia coli/*metabolism ; Escherichia coli Proteins/*metabolism ; Glyoxylates/metabolism ; Isocitrate Dehydrogenase/*metabolism ; *Metabolic Networks and Pathways ; Models, Biological ; Models, Chemical ; Multienzyme Complexes/*metabolism ; Osmolar Concentration ; Phosphorylation ; Signal Transduction ; Trans-Activators/*metabolism
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    Biochemistry. An ensemble view of allostery (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-02-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hilser, Vincent J -- GM63747/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Feb 5;327(5966):653-4. doi: 10.1126/science.1186121.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, and Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA. vjhilser@utmb.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20133562" target="_blank"〉PubMed〈/a〉
    Keywords: *Allosteric Regulation ; Allosteric Site ; Ligands ; Models, Biological ; Models, Molecular ; Molecular Motor Proteins/chemistry/metabolism ; Protein Conformation ; Protein Subunits/*chemistry/*metabolism ; Proteins/*chemistry/*metabolism ; *Signal Transduction
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    A peroxidase/dual oxidase system modulates midgut epithelial immunity in Anopheles gambiae (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-03-13
    Description: Extracellular matrices in diverse biological systems are cross-linked by dityrosine covalent bonds catalyzed by the peroxidase/oxidase system. We show that a peroxidase, secreted by the Anopheles gambiae midgut, and dual oxidase form a dityrosine network that decreases gut permeability to immune elicitors. This network protects the microbiota by preventing activation of epithelial immunity. It also provides a suitable environment for malaria parasites to develop within the midgut lumen without inducing nitric oxide synthase expression. Disruption of this barrier results in strong and effective pathogen-specific immune responses.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3510679/" 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/PMC3510679/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kumar, Sanjeev -- Molina-Cruz, Alvaro -- Gupta, Lalita -- Rodrigues, Janneth -- Barillas-Mury, Carolina -- ZIA AI000947-08/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2010 Mar 26;327(5973):1644-8. doi: 10.1126/science.1184008. Epub 2010 Mar 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20223948" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anopheles gambiae/*enzymology/*immunology/microbiology/parasitology ; Anti-Bacterial Agents/pharmacology ; Bacteria/immunology ; Bacterial Physiological Phenomena ; Blood ; Digestive System/enzymology/immunology/microbiology/parasitology ; Enzyme Induction ; Epithelial Cells/immunology/microbiology/parasitology ; Extracellular Matrix/metabolism ; Female ; Gene Expression Regulation ; Insect Proteins/metabolism ; Models, Biological ; NADPH Oxidase/genetics/*metabolism ; Nitric Oxide Synthase/biosynthesis ; Permeability ; Peroxidase/genetics/*metabolism ; Plasmodium berghei/immunology/physiology ; Plasmodium falciparum/immunology/physiology ; RNA Interference ; Tyrosine/analogs & derivatives/metabolism
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    Iron-clad fibers: a metal-based biological strategy for hard flexible coatings (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-03-06
    Description: The extensible byssal threads of marine mussels are shielded from abrasion in wave-swept habitats by an outer cuticle that is largely proteinaceous and approximately fivefold harder than the thread core. Threads from several species exhibit granular cuticles containing a protein that is rich in the catecholic amino acid 3,4-dihydroxyphenylalanine (dopa) as well as inorganic ions, notably Fe3+. Granular cuticles exhibit a remarkable combination of high hardness and high extensibility. We explored byssus cuticle chemistry by means of in situ resonance Raman spectroscopy and demonstrated that the cuticle is a polymeric scaffold stabilized by catecholato-iron chelate complexes having an unusual clustered distribution. Consistent with byssal cuticle chemistry and mechanics, we present a model in which dense cross-linking in the granules provides hardness, whereas the less cross-linked matrix provides extensibility.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3087814/" 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/PMC3087814/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Harrington, Matthew J -- Masic, Admir -- Holten-Andersen, Niels -- Waite, J Herbert -- Fratzl, Peter -- R01 DE015415/DE/NIDCR NIH HHS/ -- R01 DE015415-04/DE/NIDCR NIH HHS/ -- R01 DE018468/DE/NIDCR NIH HHS/ -- R01 DE018468-01A1/DE/NIDCR NIH HHS/ -- R01 DE018468-02/DE/NIDCR NIH HHS/ -- R01 DE018468-03/DE/NIDCR NIH HHS/ -- R01 DE018468-04/DE/NIDCR NIH HHS/ -- R01DE018468/DE/NIDCR NIH HHS/ -- New York, N.Y. -- Science. 2010 Apr 9;328(5975):216-20. doi: 10.1126/science.1181044. Epub 2010 Mar 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biomaterials, Max Planck Institute for Colloids and Interfaces, Potsdam 14424, Germany. Matt.Harrington@mpikg.mpg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20203014" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Structures/chemistry ; Animals ; Biomechanical Phenomena ; Dihydroxyphenylalanine/*chemistry ; Ferric Compounds/*chemistry ; Hardness ; Iron/chemistry ; Models, Biological ; Mytilus/*chemistry/physiology ; Physicochemical Processes ; Proteins/*chemistry/metabolism ; Repetitive Sequences, Amino Acid ; Spectrum Analysis, Raman
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    Scenarios for global biodiversity in the 21st century (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-10-28
    Description: Quantitative scenarios are coming of age as a tool for evaluating the impact of future socioeconomic development pathways on biodiversity and ecosystem services. We analyze global terrestrial, freshwater, and marine biodiversity scenarios using a range of measures including extinctions, changes in species abundance, habitat loss, and distribution shifts, as well as comparing model projections to observations. Scenarios consistently indicate that biodiversity will continue to decline over the 21st century. However, the range of projected changes is much broader than most studies suggest, partly because there are major opportunities to intervene through better policies, but also because of large uncertainties in projections.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pereira, Henrique M -- Leadley, Paul W -- Proenca, Vania -- Alkemade, Rob -- Scharlemann, Jorn P W -- Fernandez-Manjarres, Juan F -- Araujo, Miguel B -- Balvanera, Patricia -- Biggs, Reinette -- Cheung, William W L -- Chini, Louise -- Cooper, H David -- Gilman, Eric L -- Guenette, Sylvie -- Hurtt, George C -- Huntington, Henry P -- Mace, Georgina M -- Oberdorff, Thierry -- Revenga, Carmen -- Rodrigues, Patricia -- Scholes, Robert J -- Sumaila, Ussif Rashid -- Walpole, Matt -- New York, N.Y. -- Science. 2010 Dec 10;330(6010):1496-501. doi: 10.1126/science.1196624. Epub 2010 Oct 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centro de Biologia Ambiental, Faculdade de Ciencias da Universidade de Lisboa, 1749-016 Lisboa, Portugal. hpereira@fc.ul.pt〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20978282" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aquatic Organisms ; *Biodiversity ; Conservation of Natural Resources ; *Ecosystem ; Extinction, Biological ; Forecasting ; Models, Biological ; Plants ; Policy ; Population Dynamics
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    Immunology. A guardian of T cell fate (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-07-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Di Santo, James P -- R01 AR060723/AR/NIAMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Jul 2;329(5987):44-5. doi: 10.1126/science.1191664.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Innate Immunity Unit, Institut Pasteur, Paris F-75724, France. james.di-santo@pasteur.fr〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20595605" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Lineage ; Cells, Cultured ; Cytokines/metabolism ; Gene Deletion ; Gene Expression Regulation ; Interleukin-7/physiology ; Killer Cells, Natural/cytology/immunology/*physiology ; *Lymphopoiesis/genetics ; Mice ; Models, Biological ; Precursor Cells, T-Lymphoid/cytology/physiology ; Repressor Proteins/*genetics/*metabolism ; Signal Transduction ; T-Lymphocytes/cytology/immunology/*physiology ; Tumor Suppressor Proteins/*genetics/*metabolism
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    Target RNA-directed trimming and tailing of small silencing RNAs (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-06-19
    Description: In Drosophila, microRNAs (miRNAs) typically guide Argonaute1 to repress messenger RNA (mRNA), whereas small interfering RNAs (siRNAs) guide Argonaute2 to destroy viral and transposon RNA. Unlike siRNAs, miRNAs rarely form extensive numbers of base pairs to the mRNAs they regulate. We find that extensive complementarity between a target RNA and an Argonaute1-bound miRNA triggers miRNA tailing and 3'-to-5' trimming. In flies, Argonaute2-bound small RNAs--but not those bound to Argonaute1--bear a 2'-O-methyl group at their 3' ends. This modification blocks target-directed small RNA remodeling: In flies lacking Hen1, the enzyme that adds the 2'-O-methyl group, Argonaute2-associated siRNAs are tailed and trimmed. Target complementarity also affects small RNA stability in human cells. These results provide an explanation for the partial complementarity between animal miRNAs and their targets.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902985/" 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/PMC2902985/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ameres, Stefan L -- Horwich, Michael D -- Hung, Jui-Hung -- Xu, Jia -- Ghildiyal, Megha -- Weng, Zhiping -- Zamore, Phillip D -- F30AG030283/AG/NIA NIH HHS/ -- GM62862/GM/NIGMS NIH HHS/ -- GM65236/GM/NIGMS NIH HHS/ -- J 2832/Austrian Science Fund FWF/Austria -- R01 GM065236/GM/NIGMS NIH HHS/ -- R01 GM065236-08/GM/NIGMS NIH HHS/ -- R37 GM062862/GM/NIGMS NIH HHS/ -- R37 GM062862-10/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Jun 18;328(5985):1534-9. doi: 10.1126/science.1187058.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20558712" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Argonaute Proteins ; *Base Pairing ; Cell Line ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster/embryology/genetics ; Eukaryotic Initiation Factors/metabolism ; Green Fluorescent Proteins/genetics ; Humans ; Methylation ; Methyltransferases/genetics/metabolism ; MicroRNAs/chemistry/genetics/*metabolism ; Models, Biological ; RNA Caps ; *RNA Stability ; RNA, Complementary ; RNA, Messenger/chemistry/genetics/*metabolism ; RNA, Small Interfering/chemistry/genetics/*metabolism ; RNA-Induced Silencing Complex/metabolism
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    Comment on "Patterns of diversity in marine phytoplankton" (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-07-31
    Description: Barton et al. (Reports, 19 March 2010, p. 1509) argued that stable conditions enable neutral coexistence of many phytoplankton species in the tropical oceans, whereas seasonal variation causes low biodiversity in subpolar oceans. However, their model prediction is not robust. A minor deviation from the neutrality assumption favors coexistence in fluctuating rather than stable environments.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huisman, Jef -- New York, N.Y. -- Science. 2010 Jul 30;329(5991):512; author reply 512. doi: 10.1126/science.1189880.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Aquatic Microbiology, Institute for Biodiversity and Ecosystem Dynamics, University of Amsterdam, Post Office Box 94248, 1090 GE Amsterdam, Netherlands. j.huisman@uva.nl〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20671171" target="_blank"〉PubMed〈/a〉
    Keywords: *Biodiversity ; *Ecosystem ; Environment ; Geography ; Models, Biological ; Oceans and Seas ; *Phytoplankton/growth & development/physiology ; Population Dynamics ; Seasons ; *Seawater
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    Ecosystem management. Science meets politics off California's coast (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-03-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stokstad, Erik -- New York, N.Y. -- Science. 2010 Mar 26;327(5973):1574-5. doi: 10.1126/science.327.5973.1574.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20339047" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; California ; *Conservation of Natural Resources/economics/legislation & jurisprudence ; *Ecosystem ; Fisheries ; *Fishes ; Guidelines as Topic ; Models, Biological ; Models, Economic ; Pacific Ocean ; Politics
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    Circadian gating of the cell cycle revealed in single cyanobacterial cells (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-03-20
    Description: Although major progress has been made in uncovering the machinery that underlies individual biological clocks, much less is known about how multiple clocks coordinate their oscillations. We simultaneously tracked cell division events and circadian phases of individual cells of the cyanobacterium Synechococcus elongatus and fit the data to a model to determine when cell cycle progression slows as a function of circadian and cell cycle phases. We infer that cell cycle progression in cyanobacteria slows during a specific circadian interval but is uniform across cell cycle phases. Our model is applicable to the quantification of the coupling between biological oscillators in other organisms.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3118046/" 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/PMC3118046/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Qiong -- Pando, Bernardo F -- Dong, Guogang -- Golden, Susan S -- van Oudenaarden, Alexander -- R01 GM062419/GM/NIGMS NIH HHS/ -- R01 GM062419-05A2/GM/NIGMS NIH HHS/ -- R01 GM062419-06/GM/NIGMS NIH HHS/ -- R01 GM062419-07/GM/NIGMS NIH HHS/ -- R01 GM068957/GM/NIGMS NIH HHS/ -- R01 GM068957-07/GM/NIGMS NIH HHS/ -- R01 GM068957-08/GM/NIGMS NIH HHS/ -- R01-GM062419/GM/NIGMS NIH HHS/ -- R01-GM068957/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Mar 19;327(5972):1522-6. doi: 10.1126/science.1181759.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, 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/20299597" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/genetics/metabolism ; *Biological Clocks ; *Cell Cycle ; *Circadian Rhythm ; Circadian Rhythm Signaling Peptides and Proteins/genetics/metabolism ; Computer Simulation ; Light ; Luminescent Proteins/metabolism ; Microscopy, Fluorescence ; Models, Biological ; Monte Carlo Method ; Synechococcus/*cytology/genetics/metabolism/*physiology
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    BID, BIM, and PUMA are essential for activation of the BAX- and BAK-dependent cell death program (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-12-04
    Description: Although the proteins BAX and BAK are required for initiation of apoptosis at the mitochondria, how BAX and BAK are activated remains unsettled. We provide in vivo evidence demonstrating an essential role of the proteins BID, BIM, and PUMA in activating BAX and BAK. Bid, Bim, and Puma triple-knockout mice showed the same developmental defects that are associated with deficiency of Bax and Bak, including persistent interdigital webs and imperforate vaginas. Genetic deletion of Bid, Bim, and Puma prevented the homo-oligomerization of BAX and BAK, and thereby cytochrome c-mediated activation of caspases in response to diverse death signals in neurons and T lymphocytes, despite the presence of other BH3-only molecules. Thus, many forms of apoptosis require direct activation of BAX and BAK at the mitochondria by a member of the BID, BIM, or PUMA family of proteins.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3163443/" 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/PMC3163443/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ren, Decheng -- Tu, Ho-Chou -- Kim, Hyungjin -- Wang, Gary X -- Bean, Gregory R -- Takeuchi, Osamu -- Jeffers, John R -- Zambetti, Gerard P -- Hsieh, James J-D -- Cheng, Emily H-Y -- P30CA21765/CA/NCI NIH HHS/ -- R01 CA125562/CA/NCI NIH HHS/ -- R01 CA125562-02/CA/NCI NIH HHS/ -- R01 CA125562-03/CA/NCI NIH HHS/ -- R01 CA125562-04/CA/NCI NIH HHS/ -- R01CA125562/CA/NCI NIH HHS/ -- R01GM083159/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Dec 3;330(6009):1390-3. doi: 10.1126/science.1190217.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21127253" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; Apoptosis Regulatory Proteins/deficiency/genetics/*metabolism ; BH3 Interacting Domain Death Agonist Protein/deficiency/genetics/*metabolism ; Caspases/metabolism ; Cells, Cultured ; Cerebellum/cytology ; Cytochromes c/metabolism ; Intracellular Membranes/metabolism ; Membrane Proteins/deficiency/genetics/*metabolism ; Mice ; Mice, Knockout ; Mitochondria/metabolism ; Models, Biological ; Neurons/*physiology ; Permeability ; Protein Multimerization ; Proto-Oncogene Proteins/deficiency/genetics/*metabolism ; Stress, Physiological ; T-Lymphocytes/physiology ; Tumor Suppressor Proteins/deficiency/genetics/*metabolism ; bcl-2 Homologous Antagonist-Killer Protein/chemistry/genetics/*metabolism ; bcl-2-Associated X Protein/chemistry/genetics/*metabolism
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    The shifting balance of diversity among major marine animal groups (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-09-04
    Description: The fossil record demonstrates that each major taxonomic group has a consistent net rate of diversification and a limit to its species richness. It has been thought that long-term changes in the dominance of major taxonomic groups can be predicted from these characteristics. However, new analyses show that diversity limits may rise or fall in response to adaptive radiations or extinctions. These changes are idiosyncratic and occur at different times in each taxa. For example, the end-Permian mass extinction permanently reduced the diversity of important, previously dominant groups such as brachiopods and crinoids. The current global crisis may therefore permanently alter the biosphere's taxonomic composition by changing the rules of evolution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alroy, J -- New York, N.Y. -- Science. 2010 Sep 3;329(5996):1191-4. doi: 10.1126/science.1189910.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Paleobiology Database, University of California, 735 State Street, Santa Barbara, CA 93101, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20813951" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Biological ; Animals ; Anthozoa ; *Biodiversity ; Biological Evolution ; Data Interpretation, Statistical ; *Databases, Factual ; Extinction, Biological ; *Fossils ; *Invertebrates ; Marine Biology ; Models, Biological ; *Mollusca ; Oceans and Seas ; Paleontology ; Population Dynamics ; Statistics as Topic ; Time
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    Stoichiometry and architecture of active DNA replication machinery in Escherichia coli (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-04-24
    Description: The multiprotein replisome complex that replicates DNA has been extensively characterized in vitro, but its composition and architecture in vivo is unknown. Using millisecond single-molecule fluorescence microscopy in living cells expressing fluorescent derivatives of replisome components, we have examined replisome stoichiometry and architecture. Active Escherichia coli replisomes contain three molecules of the replicative polymerase, rather than the historically accepted two. These are associated with three molecules of tau, a clamp loader component that trimerizes polymerase. Only two of the three sliding clamps are always associated with the core replisome. Single-strand binding protein has a broader spatial distribution than the core components, with 5 to 11 tetramers per replisome. This in vivo technique could provide single-molecule insight into other molecular machines.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2859602/" 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/PMC2859602/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reyes-Lamothe, Rodrigo -- Sherratt, David J -- Leake, Mark C -- 083469/Wellcome Trust/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2010 Apr 23;328(5977):498-501. doi: 10.1126/science.1185757.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20413500" target="_blank"〉PubMed〈/a〉
    Keywords: DNA Polymerase III/*analysis/metabolism ; *DNA Replication ; DNA, Bacterial/analysis/chemistry/*metabolism ; DNA-Binding Proteins/analysis/metabolism ; DNA-Directed DNA Polymerase/*analysis/metabolism ; Escherichia coli/*chemistry/metabolism ; Escherichia coli Proteins/*analysis/metabolism ; Microscopy, Fluorescence ; Models, Biological ; Multienzyme Complexes/*analysis/metabolism ; Nucleic Acid Conformation
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    Conformational spread as a mechanism for cooperativity in the bacterial flagellar switch (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-02-06
    Description: The bacterial flagellar switch that controls the direction of flagellar rotation during chemotaxis has a highly cooperative response. This has previously been understood in terms of the classic two-state, concerted model of allosteric regulation. Here, we used high-resolution optical microscopy to observe switching of single motors and uncover the stochastic multistate nature of the switch. Our observations are in detailed quantitative agreement with a recent general model of allosteric cooperativity that exhibits conformational spread--the stochastic growth and shrinkage of domains of adjacent subunits sharing a particular conformational state. We expect that conformational spread will be important in explaining cooperativity in other large signaling complexes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bai, Fan -- Branch, Richard W -- Nicolau, Dan V Jr -- Pilizota, Teuta -- Steel, Bradley C -- Maini, Philip K -- Berry, Richard M -- BB/E00458X/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/H01991X/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2010 Feb 5;327(5966):685-9. doi: 10.1126/science.1182105.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Clarendon Laboratory, Department of Physics, University of Oxford, Parks Road, Oxford OX1 3PU, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20133571" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Bacterial Proteins/chemistry/metabolism ; Binding Sites ; Escherichia coli/metabolism ; Escherichia coli Proteins/*chemistry/*metabolism ; Flagella/*chemistry ; Membrane Proteins/chemistry/metabolism ; Models, Biological ; Models, Molecular ; Molecular Motor Proteins/*chemistry/*metabolism ; Monte Carlo Method ; Protein Binding ; Protein Conformation ; Protein Subunits/*chemistry/*metabolism ; Signal Transduction ; Thermodynamics
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    Structure of a eukaryotic CLC transporter defines an intermediate state in the transport cycle (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-10-12
    Description: CLC proteins transport chloride (Cl(-)) ions across cell membranes to control the electrical potential of muscle cells, transfer electrolytes across epithelia, and control the pH and electrolyte composition of intracellular organelles. Some members of this protein family are Cl(-) ion channels, whereas others are secondary active transporters that exchange Cl(-) ions and protons (H(+)) with a 2:1 stoichiometry. We have determined the structure of a eukaryotic CLC transporter at 3.5 angstrom resolution. Cytoplasmic cystathionine beta-synthase (CBS) domains are strategically positioned to regulate the ion-transport pathway, and many disease-causing mutations in human CLCs reside on the CBS-transmembrane interface. Comparison with prokaryotic CLC shows that a gating glutamate residue changes conformation and suggests a basis for 2:1 Cl(-)/H(+) exchange and a simple mechanistic connection between CLC channels and transporters.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079386/" 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/PMC3079386/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Feng, Liang -- Campbell, Ernest B -- Hsiung, Yichun -- MacKinnon, Roderick -- P30 EB009998/EB/NIBIB NIH HHS/ -- R01 GM043949/GM/NIGMS NIH HHS/ -- R01 GM043949-20/GM/NIGMS NIH HHS/ -- R01 GM043949-21/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Oct 29;330(6004):635-41. doi: 10.1126/science.1195230. Epub 2010 Sep 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20929736" target="_blank"〉PubMed〈/a〉
    Keywords: Algal Proteins/chemistry/metabolism ; Animals ; Antiporters/*chemistry/metabolism ; Binding Sites ; Cell Line ; Cell Membrane/chemistry ; Chloride Channels/*chemistry/metabolism ; Chlorides/*metabolism ; Crystallization ; Crystallography, X-Ray ; Cystathionine beta-Synthase/chemistry ; Cytoplasm/chemistry ; Glutamic Acid/metabolism ; Ion Channel Gating ; Ion Transport ; Models, Biological ; Models, Molecular ; Protein Conformation ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein Subunits/chemistry ; Protons ; Rhodophyta/*chemistry/metabolism
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    Acceleration of emergence of bacterial antibiotic resistance in connected microenvironments (2011)
    American Association for the Advancement of Science (AAAS)
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    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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    Generation of spatial patterns through cell polarity switching (2011)
    American Association for the Advancement of Science (AAAS)
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    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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    Interconversion between intestinal stem cell populations in distinct niches (2011)
    American Association for the Advancement of Science (AAAS)
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    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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    Chirality in planar cell shape contributes to left-right asymmetric epithelial morphogenesis (2011)
    American Association for the Advancement of Science (AAAS)
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    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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    Rotational movement of the formin mDia1 along the double helical strand of an actin filament (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-12-15
    Description: Formin homology proteins (formins) elongate actin filaments (F-actin) by continuously associating with filament tips, potentially harnessing actin-generated pushing forces. During this processive elongation, formins are predicted to rotate along the axis of the double helical F-actin structure (referred to here as helical rotation), although this has not yet been definitively shown. We demonstrated helical rotation of the formin mDia1 by single-molecule fluorescence polarization (FL(P)). FL(P) of labeled F-actin, both elongating and depolymerizing from immobilized mDia1, oscillated with a periodicity corresponding to that of the F-actin long-pitch helix, and this was not altered by actin-bound nucleotides or the actin-binding protein profilin. Thus, helical rotation is an intrinsic property of formins. To harness pushing forces from growing F-actin, formins must be anchored flexibly to cell structures.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mizuno, Hiroaki -- Higashida, Chiharu -- Yuan, Yunfeng -- Ishizaki, Toshimasa -- Narumiya, Shuh -- Watanabe, Naoki -- New York, N.Y. -- Science. 2011 Jan 7;331(6013):80-3. doi: 10.1126/science.1197692. Epub 2010 Dec 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Single-Molecule Cell Biology, Tohoku University Graduate School of Life Sciences, 6-3 Aoba, Aramaki-Aza, Aoba-ku, Sendai, Miyagi 980-8578, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21148346" target="_blank"〉PubMed〈/a〉
    Keywords: Actin Cytoskeleton/chemistry/*metabolism/ultrastructure ; Actins/chemistry/*metabolism ; Adenosine Diphosphate/metabolism ; Adenosine Triphosphate/metabolism ; Animals ; Carrier Proteins/chemistry/*metabolism ; Fluorescence Polarization ; Mice ; Models, Biological ; Profilins/metabolism ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein Multimerization ; Protein Structure, Secondary ; Rabbits ; Recombinant Fusion Proteins/chemistry/metabolism ; Rotation
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    De-AMPylation of the small GTPase Rab1 by the pathogen Legionella pneumophila (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    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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    Single-base pair unwinding and asynchronous RNA release by the hepatitis C virus NS3 helicase (2011)
    American Association for the Advancement of Science (AAAS)
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    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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    Early warnings of regime shifts: a whole-ecosystem experiment (2011)
    American Association for the Advancement of Science (AAAS)
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    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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    The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    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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    Animal migration and infectious disease risk (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    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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  • 88
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    Sequential establishment of stripe patterns in an expanding cell population (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    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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  • 89
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    Rational choice, context dependence, and the value of information in European starlings (Sturnus vulgaris) (2011)
    American Association for the Advancement of Science (AAAS)
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    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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  • 90
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    Proteoglycan-specific molecular switch for RPTPsigma clustering and neuronal extension (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    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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  • 91
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    Geometry and mechanics in the opening of chiral seed pods (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    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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  • 92
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    Medicine. Lipases in cachexia (2011)
    American Association for the Advancement of Science (AAAS)
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    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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  • 93
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    Coupled, circumferential motions of the cell wall synthesis machinery and MreB filaments in B. subtilis (2011)
    American Association for the Advancement of Science (AAAS)
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    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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    The crystal structure of the signal recognition particle in complex with its receptor (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    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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  • 95
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    Comment on "Erosion of lizard diversity by climate change and altered thermal niches" (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    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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    Crystal structure of the maltose transporter in a pretranslocation intermediate state (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    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
    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
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    Anthropology. A new view of the birth of Homo sapiens (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    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
    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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  • 98
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    Pathogen effectors target Arabidopsis EDS1 and alter its interactions with immune regulators (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    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
    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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  • 99
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    Long unfolded linkers facilitate membrane protein import through the nuclear pore complex (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    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
    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
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    Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4 (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    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
    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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