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  • 1
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    Nature Publishing Group (NPG)
    Publication Date: 2010-10-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaplan, Karen -- England -- Nature. 2010 Sep 23;467(7314):489-91.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20963934" target="_blank"〉PubMed〈/a〉
    Keywords: Age Factors ; Emigration and Immigration ; Europe ; European Union ; Faculty ; Income/statistics & numerical data ; Internationality ; *Pensions/statistics & numerical data ; Research Personnel/*economics/statistics & numerical data ; Retirement/*economics/statistics & numerical data ; Time Factors ; United States
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2010-11-26
    Description: In physiological settings, nucleic-acid translocases must act on substrates occupied by other proteins, and an increasingly appreciated role of translocases is to catalyse protein displacement from RNA and DNA. However, little is known regarding the inevitable collisions that must occur, and the fate of protein obstacles and the mechanisms by which they are evicted from DNA remain unexplored. Here we sought to establish the mechanistic basis for protein displacement from DNA using RecBCD as a model system. Using nanofabricated curtains of DNA and multicolour single-molecule microscopy, we visualized collisions between a model translocase and different DNA-bound proteins in real time. We show that the DNA translocase RecBCD can disrupt core RNA polymerase, holoenzymes, stalled elongation complexes and transcribing RNA polymerases in either head-to-head or head-to-tail orientations, as well as EcoRI(E111Q), lac repressor and even nucleosomes. RecBCD did not pause during collisions and often pushed proteins thousands of base pairs before evicting them from DNA. We conclude that RecBCD overwhelms obstacles through direct transduction of chemomechanical force with no need for specific protein-protein interactions, and that proteins can be removed from DNA through active disruption mechanisms that act on a transition state intermediate as they are pushed from one nonspecific site to the next.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230117/" 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/PMC3230117/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Finkelstein, Ilya J -- Visnapuu, Mari-Liis -- Greene, Eric C -- F32GM80864/GM/NIGMS NIH HHS/ -- GM074739/GM/NIGMS NIH HHS/ -- GM082848/GM/NIGMS NIH HHS/ -- R01 CA146940/CA/NCI NIH HHS/ -- R01 GM074739/GM/NIGMS NIH HHS/ -- R01 GM074739-01A1/GM/NIGMS NIH HHS/ -- R01 GM074739-05/GM/NIGMS NIH HHS/ -- R01 GM082848/GM/NIGMS NIH HHS/ -- R01 GM082848-01A1/GM/NIGMS NIH HHS/ -- R01 GM082848-04/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Dec 16;468(7326):983-7. doi: 10.1038/nature09561. Epub 2010 Nov 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21107319" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteriophage lambda/genetics ; Biocatalysis ; DNA/genetics/*metabolism ; DNA, Viral/genetics/metabolism ; DNA-Binding Proteins/*metabolism ; DNA-Directed RNA Polymerases/chemistry/metabolism ; Deoxyribonuclease EcoRI/metabolism ; Escherichia coli/enzymology ; Exodeoxyribonuclease V/*metabolism ; Holoenzymes/chemistry/metabolism ; Lac Repressors/metabolism ; Microscopy, Fluorescence ; *Movement ; Nucleosomes/metabolism ; Promoter Regions, Genetic/genetics ; Protein Binding ; Quantum Dots ; Time Factors
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  • 3
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    Nature Publishing Group (NPG)
    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
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  • 4
    Publication Date: 2010-04-16
    Description: Translation by the ribosome occurs by a complex mechanism involving the coordinated interaction of multiple nucleic acid and protein ligands. Here we use zero-mode waveguides (ZMWs) and sophisticated detection instrumentation to allow real-time observation of translation at physiologically relevant micromolar ligand concentrations. Translation at each codon is monitored by stable binding of transfer RNAs (tRNAs)-labelled with distinct fluorophores-to translating ribosomes, which allows direct detection of the identity of tRNA molecules bound to the ribosome and therefore the underlying messenger RNA (mRNA) sequence. We observe the transit of tRNAs on single translating ribosomes and determine the number of tRNA molecules simultaneously bound to the ribosome, at each codon of an mRNA molecule. Our results show that ribosomes are only briefly occupied by two tRNA molecules and that release of deacylated tRNA from the exit (E) site is uncoupled from binding of aminoacyl-tRNA site (A-site) tRNA and occurs rapidly after translocation. The methods outlined here have broad application to the study of mRNA sequences, and the mechanism and regulation of translation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466108/" 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/PMC4466108/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Uemura, Sotaro -- Aitken, Colin Echeverria -- Korlach, Jonas -- Flusberg, Benjamin A -- Turner, Stephen W -- Puglisi, Joseph D -- GM51266/GM/NIGMS NIH HHS/ -- R01 GM051266/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Apr 15;464(7291):1012-7. doi: 10.1038/nature08925.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Structural Biology, Stanford University School of Medicine, Stanford, California 94305-5126, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20393556" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Codon/*genetics ; Escherichia coli ; Fluorescence ; Kinetics ; Ligands ; Luminescent Measurements ; Optical Tweezers ; Protein Biosynthesis/genetics/*physiology ; RNA, Transfer/genetics/*metabolism ; Ribosomes/chemistry/genetics/*metabolism ; Time Factors
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  • 5
    Publication Date: 2010-04-23
    Description: The worldwide prevalence of chronic hepatitis C virus (HCV) infection is estimated to be approaching 200 million people. Current therapy relies upon a combination of pegylated interferon-alpha and ribavirin, a poorly tolerated regimen typically associated with less than 50% sustained virological response rate in those infected with genotype 1 virus. The development of direct-acting antiviral agents to treat HCV has focused predominantly on inhibitors of the viral enzymes NS3 protease and the RNA-dependent RNA polymerase NS5B. Here we describe the profile of BMS-790052, a small molecule inhibitor of the HCV NS5A protein that exhibits picomolar half-maximum effective concentrations (EC(50)) towards replicons expressing a broad range of HCV genotypes and the JFH-1 genotype 2a infectious virus in cell culture. In a phase I clinical trial in patients chronically infected with HCV, administration of a single 100-mg dose of BMS-790052 was associated with a 3.3 log(10) reduction in mean viral load measured 24 h post-dose that was sustained for an additional 120 h in two patients infected with genotype 1b virus. Genotypic analysis of samples taken at baseline, 24 and 144 h post-dose revealed that the major HCV variants observed had substitutions at amino-acid positions identified using the in vitro replicon system. These results provide the first clinical validation of an inhibitor of HCV NS5A, a protein with no known enzymatic function, as an approach to the suppression of virus replication that offers potential as part of a therapeutic regimen based on combinations of HCV inhibitors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gao, Min -- Nettles, Richard E -- Belema, Makonen -- Snyder, Lawrence B -- Nguyen, Van N -- Fridell, Robert A -- Serrano-Wu, Michael H -- Langley, David R -- Sun, Jin-Hua -- O'Boyle, Donald R 2nd -- Lemm, Julie A -- Wang, Chunfu -- Knipe, Jay O -- Chien, Caly -- Colonno, Richard J -- Grasela, Dennis M -- Meanwell, Nicholas A -- Hamann, Lawrence G -- England -- Nature. 2010 May 6;465(7294):96-100. doi: 10.1038/nature08960. Epub 2010 Apr 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20410884" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Animals ; Antiviral Agents/blood/chemistry/*pharmacology/therapeutic use ; Cell Line ; Cercopithecus aethiops ; Drug Resistance, Viral ; Female ; Genotype ; HeLa Cells ; Hepacivirus/*drug effects ; Hepatitis C/drug therapy/virology ; Humans ; Imidazoles/blood/chemistry/*pharmacology ; Inhibitory Concentration 50 ; Male ; Middle Aged ; Time Factors ; Vero Cells ; Viral Load/drug effects ; Viral Nonstructural Proteins/*antagonists & inhibitors ; Young Adult
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  • 6
    Publication Date: 2010-07-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Deborah -- Carter, Philip -- England -- Nature. 2010 Jul 15;466(7304):315. doi: 10.1038/466315a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20631779" target="_blank"〉PubMed〈/a〉
    Keywords: *Conflict of Interest ; *Drug Industry ; Humans ; *Influenza A Virus, H1N1 Subtype ; Influenza Vaccines/*supply & distribution ; Influenza, Human/*epidemiology/prevention & control/virology ; Reproducibility of Results ; Time Factors ; *Vaccination ; *World Health Organization
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  • 7
    Publication Date: 2010-01-29
    Description: Cellular differentiation and lineage commitment are considered to be robust and irreversible processes during development. Recent work has shown that mouse and human fibroblasts can be reprogrammed to a pluripotent state with a combination of four transcription factors. This raised the question of whether transcription factors could directly induce other defined somatic cell fates, and not only an undifferentiated state. We hypothesized that combinatorial expression of neural-lineage-specific transcription factors could directly convert fibroblasts into neurons. Starting from a pool of nineteen candidate genes, we identified a combination of only three factors, Ascl1, Brn2 (also called Pou3f2) and Myt1l, that suffice to rapidly and efficiently convert mouse embryonic and postnatal fibroblasts into functional neurons in vitro. These induced neuronal (iN) cells express multiple neuron-specific proteins, generate action potentials and form functional synapses. Generation of iN cells from non-neural lineages could have important implications for studies of neural development, neurological disease modelling and regenerative medicine.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829121/" 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/PMC2829121/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vierbuchen, Thomas -- Ostermeier, Austin -- Pang, Zhiping P -- Kokubu, Yuko -- Sudhof, Thomas C -- Wernig, Marius -- 1018438-142-PABCA/PHS HHS/ -- 5T32NS007280/NS/NINDS NIH HHS/ -- T32 CA009302/CA/NCI NIH HHS/ -- U01 HL100397/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Feb 25;463(7284):1035-41. doi: 10.1038/nature08797. Epub 2010 Jan 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Stem Cell Biology and Regenerative Medicine, Department of Pathology, Stanford University School of Medicine, 1050 Arastradero Road, Palo Alto, California 94304, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20107439" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism ; Biomarkers/analysis ; Cell Line ; *Cell Lineage ; *Cell Transdifferentiation ; Cells, Cultured ; Embryo, Mammalian/cytology ; Fibroblasts/*cytology ; Mice ; Nerve Tissue Proteins/genetics/metabolism ; Neurons/*cytology/metabolism/*physiology ; POU Domain Factors/genetics/metabolism ; Regenerative Medicine ; Synapses/metabolism ; Tail/cytology ; Time Factors ; Transcription Factors/genetics/metabolism
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  • 8
    Publication Date: 2010-12-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Collins, Francis -- England -- Nature. 2010 Dec 16;468(7326):877. doi: 10.1038/468877a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21164451" target="_blank"〉PubMed〈/a〉
    Keywords: Drug Industry ; National Institutes of Health (U.S.)/economics/*organization & administration ; Time Factors ; Translational Medical Research/economics/*organization & administration/trends ; United States
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  • 9
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    Nature Publishing Group (NPG)
    Publication Date: 2010-01-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Quirk, Gregory J -- Milad, Mohammed R -- England -- Nature. 2010 Jan 7;463(7277):36-7. doi: 10.1038/463036a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20054384" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Conditioning, Classical/*physiology ; Cues ; Electroshock ; Extinction, Psychological/*physiology ; Fear/*physiology/*psychology ; Humans ; Memory/*physiology ; Models, Neurological ; Models, Psychological ; Neuronal Plasticity/*physiology ; Photic Stimulation ; Rats ; Stress Disorders, Post-Traumatic/therapy ; Time Factors
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  • 10
    Publication Date: 2010-07-16
    Description: The translocation step of protein synthesis entails large-scale rearrangements of the ribosome-transfer RNA (tRNA) complex. Here we have followed tRNA movement through the ribosome during translocation by time-resolved single-particle electron cryomicroscopy (cryo-EM). Unbiased computational sorting of cryo-EM images yielded 50 distinct three-dimensional reconstructions, showing the tRNAs in classical, hybrid and various novel intermediate states that provide trajectories and kinetic information about tRNA movement through the ribosome. The structures indicate how tRNA movement is coupled with global and local conformational changes of the ribosome, in particular of the head and body of the small ribosomal subunit, and show that dynamic interactions between tRNAs and ribosomal residues confine the path of the tRNAs through the ribosome. The temperature dependence of ribosome dynamics reveals a surprisingly flat energy landscape of conformational variations at physiological temperature. The ribosome functions as a Brownian machine that couples spontaneous conformational changes driven by thermal energy to directed movement.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fischer, Niels -- Konevega, Andrey L -- Wintermeyer, Wolfgang -- Rodnina, Marina V -- Stark, Holger -- England -- Nature. 2010 Jul 15;466(7304):329-33. doi: 10.1038/nature09206.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉3D Electron Cryomicroscopy Group, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Gottingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20631791" target="_blank"〉PubMed〈/a〉
    Keywords: Cryoelectron Microscopy ; Escherichia coli ; Kinetics ; Models, Molecular ; Molecular Conformation ; *Movement ; *Protein Biosynthesis ; RNA, Transfer/genetics/*metabolism ; Ribosome Subunits, Large, Bacterial/chemistry/metabolism ; Ribosome Subunits, Small, Bacterial/chemistry/metabolism ; Ribosomes/chemistry/*metabolism ; Temperature ; Thermodynamics ; Time Factors
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  • 11
    Publication Date: 2010-05-14
    Description: Traditional robots rely for their function on computing, to store internal representations of their goals and environment and to coordinate sensing and any actuation of components required in response. Moving robotics to the single-molecule level is possible in principle, but requires facing the limited ability of individual molecules to store complex information and programs. One strategy to overcome this problem is to use systems that can obtain complex behaviour from the interaction of simple robots with their environment. A first step in this direction was the development of DNA walkers, which have developed from being non-autonomous to being capable of directed but brief motion on one-dimensional tracks. Here we demonstrate that previously developed random walkers-so-called molecular spiders that comprise a streptavidin molecule as an inert 'body' and three deoxyribozymes as catalytic 'legs'-show elementary robotic behaviour when interacting with a precisely defined environment. Single-molecule microscopy observations confirm that such walkers achieve directional movement by sensing and modifying tracks of substrate molecules laid out on a two-dimensional DNA origami landscape. When using appropriately designed DNA origami, the molecular spiders autonomously carry out sequences of actions such as 'start', 'follow', 'turn' and 'stop'. We anticipate that this strategy will result in more complex robotic behaviour at the molecular level if additional control mechanisms are incorporated. One example might be interactions between multiple molecular robots leading to collective behaviour; another might be the ability to read and transform secondary cues on the DNA origami landscape as a means of implementing Turing-universal algorithmic behaviour.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907518/" 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/PMC2907518/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lund, Kyle -- Manzo, Anthony J -- Dabby, Nadine -- Michelotti, Nicole -- Johnson-Buck, Alexander -- Nangreave, Jeanette -- Taylor, Steven -- Pei, Renjun -- Stojanovic, Milan N -- Walter, Nils G -- Winfree, Erik -- Yan, Hao -- P41 RR017573/RR/NCRR NIH HHS/ -- P41 RR017573-086704/RR/NCRR NIH HHS/ -- R01 GM062357/GM/NIGMS NIH HHS/ -- R01 GM062357-09/GM/NIGMS NIH HHS/ -- T32 EB005582/EB/NIBIB NIH HHS/ -- T32 EB005582-05/EB/NIBIB NIH HHS/ -- T32 GM008270/GM/NIGMS NIH HHS/ -- T32 GM008270-24/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 May 13;465(7295):206-10. doi: 10.1038/nature09012.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20463735" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Computers, Molecular ; DNA, Catalytic/*metabolism ; DNA, Single-Stranded/chemistry/*metabolism ; Microscopy, Atomic Force ; Microscopy, Fluorescence ; *Movement/drug effects ; Nanotechnology/*methods ; Robotics ; Streptavidin/*chemistry ; Surface Plasmon Resonance ; Time Factors ; Zinc/metabolism/pharmacology
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  • 12
    Publication Date: 2010-07-24
    Description: Environmental change has altered the phenology, morphological traits and population dynamics of many species. However, the links underlying these joint responses remain largely unknown owing to a paucity of long-term data and the lack of an appropriate analytical framework. Here we investigate the link between phenotypic and demographic responses to environmental change using a new methodology and a long-term (1976-2008) data set from a hibernating mammal (the yellow-bellied marmot) inhabiting a dynamic subalpine habitat. We demonstrate how earlier emergence from hibernation and earlier weaning of young has led to a longer growing season and larger body masses before hibernation. The resulting shift in both the phenotype and the relationship between phenotype and fitness components led to a decline in adult mortality, which in turn triggered an abrupt increase in population size in recent years. Direct and trait-mediated effects of environmental change made comparable contributions to the observed marked increase in population growth. Our results help explain how a shift in phenology can cause simultaneous phenotypic and demographic changes, and highlight the need for a theory integrating ecological and evolutionary dynamics in stochastic environments.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ozgul, Arpat -- Childs, Dylan Z -- Oli, Madan K -- Armitage, Kenneth B -- Blumstein, Daniel T -- Olson, Lucretia E -- Tuljapurkar, Shripad -- Coulson, Tim -- P01 AG022500/AG/NIA NIH HHS/ -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Jul 22;466(7305):482-5. doi: 10.1038/nature09210.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Life Sciences, Imperial College London, Ascot, Berkshire SL5 7PY, UK. a.ozgul@imperial.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20651690" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Evolution ; Body Weight/*physiology ; Colorado ; Female ; *Global Warming ; Hibernation/*physiology ; Marmota/*anatomy & histology/growth & development/*physiology ; Phenotype ; Population Dynamics ; Reproduction/physiology ; Survival Rate ; Time Factors ; Weaning
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  • 13
    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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  • 14
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    Nature Publishing Group (NPG)
    Publication Date: 2010-10-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Oct 28;467(7319):1026-7. doi: 10.1038/4671026a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20981067" target="_blank"〉PubMed〈/a〉
    Keywords: Americas ; Asia ; Europe ; Genetic Predisposition to Disease ; Genetics, Population ; *Genome, Human ; Genomics/economics/*statistics & numerical data/trends ; Humans ; Precision Medicine/trends ; Sequence Analysis, DNA/economics/*statistics & numerical data/trends ; Time Factors
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  • 15
    Publication Date: 2010-12-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bonetta, Laura -- England -- Nature. 2010 Dec 9;468(7325):854. doi: 10.1038/468854a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21151000" target="_blank"〉PubMed〈/a〉
    Keywords: California ; Protein Binding ; Protein Interaction Mapping/*methods ; RNA, Transfer/metabolism ; Ribosomes/metabolism ; Sequence Analysis, DNA/methods ; Time Factors
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  • 16
    Publication Date: 2010-12-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schofield, Paul N -- Tapio, Soile -- Grosche, Bernd -- England -- Nature. 2010 Dec 2;468(7324):634. doi: 10.1038/468634a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21124436" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Archives/*history ; Databases, Factual/history ; Europe ; History, 20th Century ; Information Storage and Retrieval ; Japan ; Radiobiology/*history ; Time Factors ; United States
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  • 17
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    Nature Publishing Group (NPG)
    Publication Date: 2010-03-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dalton, Rex -- England -- Nature. 2010 Mar 18;464(7287):335. doi: 10.1038/464335a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20237533" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Archaeology ; Geography ; Hominidae/*classification ; Indonesia ; Paleontology ; *Phylogeny ; Time Factors
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  • 18
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    Nature Publishing Group (NPG)
    Publication Date: 2010-08-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jones, Rachel -- England -- Nature. 2010 Aug 26;466(7310):S11-2. doi: 10.1038/466S11a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20739930" target="_blank"〉PubMed〈/a〉
    Keywords: *Biomarkers ; Brain/pathology ; *Early Diagnosis ; Ethics, Medical ; Humans ; Parkinson Disease/*diagnosis/pathology ; Risk Factors ; Time Factors
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  • 19
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    Nature Publishing Group (NPG)
    Publication Date: 2010-09-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Persons, Derek A -- England -- Nature. 2010 Sep 16;467(7313):277-8. doi: 10.1038/467277a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20844523" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Blood Cells/cytology/metabolism ; Blood Transfusion ; Clone Cells/metabolism ; *Genetic Therapy ; HMGA2 Protein/genetics/*metabolism ; Humans ; Male ; Time Factors ; Transcriptional Activation ; Young Adult ; beta-Globins/*genetics/*metabolism ; beta-Thalassemia/*genetics/metabolism/*therapy
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  • 20
    Publication Date: 2010-07-03
    Description: The development of multicellular organisms relies on the coordinated control of cell divisions leading to proper patterning and growth. The molecular mechanisms underlying pattern formation, particularly the regulation of formative cell divisions, remain poorly understood. In Arabidopsis, formative divisions generating the root ground tissue are controlled by SHORTROOT (SHR) and SCARECROW (SCR). Here we show, using cell-type-specific transcriptional effects of SHR and SCR combined with data from chromatin immunoprecipitation-based microarray experiments, that SHR regulates the spatiotemporal activation of specific genes involved in cell division. Coincident with the onset of a specific formative division, SHR and SCR directly activate a D-type cyclin; furthermore, altering the expression of this cyclin resulted in formative division defects. Our results indicate that proper pattern formation is achieved through transcriptional regulation of specific cell-cycle genes in a cell-type- and developmental-stage-specific context. Taken together, we provide evidence for a direct link between developmental regulators, specific components of the cell-cycle machinery and organ patterning.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2967763/" 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/PMC2967763/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sozzani, R -- Cui, H -- Moreno-Risueno, M A -- Busch, W -- Van Norman, J M -- Vernoux, T -- Brady, S M -- Dewitte, W -- Murray, J A H -- Benfey, P N -- BB/E022383/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/E022383/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/E022383/2/Biotechnology and Biological Sciences Research Council/United Kingdom -- P50 GM081883/GM/NIGMS NIH HHS/ -- P50 GM081883-020003/GM/NIGMS NIH HHS/ -- P50 GM081883-030003/GM/NIGMS NIH HHS/ -- P50-GM081883/GM/NIGMS NIH HHS/ -- R01 GM043778/GM/NIGMS NIH HHS/ -- R01 GM043778-18/GM/NIGMS NIH HHS/ -- R01 GM043778-19/GM/NIGMS NIH HHS/ -- R01 GM043778-20/GM/NIGMS NIH HHS/ -- R01 GM043778-21/GM/NIGMS NIH HHS/ -- R01-GM043778/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Jul 1;466(7302):128-32. doi: 10.1038/nature09143.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology and IGSP Center for Systems Biology, Duke University, Durham, North Carolina 27708, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20596025" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/cytology/embryology/*genetics/*growth & development ; Arabidopsis Proteins/genetics/*metabolism ; Body Patterning/*genetics/*physiology ; Cell Cycle/genetics/physiology ; Cell Division/genetics ; Cyclin D/genetics/metabolism ; Cyclin-Dependent Kinases/metabolism ; Gene Expression Regulation, Plant ; Genes, cdc/*physiology ; Organogenesis/genetics/physiology ; Plant Roots/cytology/embryology/genetics/growth & development ; Time Factors ; Transcription Factors/genetics/*metabolism
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  • 21
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    Nature Publishing Group (NPG)
    Publication Date: 2010-09-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tollefson, Jeff -- England -- Nature. 2010 Sep 23;467(7314):386-7. doi: 10.1038/467386a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20864970" target="_blank"〉PubMed〈/a〉
    Keywords: Atmosphere/*chemistry ; Brazil ; Carbon Dioxide/*analysis/metabolism ; *Ecosystem ; Environmental Monitoring/economics/*instrumentation ; Forestry ; Germany ; Global Warming ; *Greenhouse Effect ; Time Factors ; Trees/growth & development/*metabolism ; Tropical Climate
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  • 22
    Publication Date: 2010-09-25
    Description: Origins of replication are activated throughout the S phase of the cell cycle such that some origins fire early and others fire late to ensure that each chromosome is completely replicated in a timely fashion. However, in response to DNA damage or replication fork stalling, eukaryotic cells block activation of unfired origins. Human cells derived from patients with ataxia telangiectasia are deficient in this process due to the lack of a functional ataxia telangiectasia mutated (ATM) kinase and elicit radioresistant DNA synthesis after gamma-irradiation(2). This effect is conserved in budding yeast, as yeast cells lacking the related kinase Mec1 (ATM and Rad3-related (ATR in humans)) also fail to inhibit DNA synthesis in the presence of DNA damage. This intra-S-phase checkpoint actively regulates DNA synthesis by inhibiting the firing of late replicating origins, and this inhibition requires both Mec1 and the downstream checkpoint kinase Rad53 (Chk2 in humans). However, the Rad53 substrate(s) whose phosphorylation is required to mediate this function has remained unknown. Here we show that the replication initiation protein Sld3 is phosphorylated by Rad53, and that this phosphorylation, along with phosphorylation of the Cdc7 kinase regulatory subunit Dbf4, blocks late origin firing in Saccharomyces cerevisiae. Upon exposure to DNA-damaging agents, cells expressing non-phosphorylatable alleles of SLD3 and DBF4 (SLD3-m25 and dbf4-m25, respectively) proceed through the S phase faster than wild-type cells by inappropriately firing late origins of replication. SLD3-m25 dbf4-m25 cells grow poorly in the presence of the replication inhibitor hydroxyurea and accumulate multiple Rad52 foci. Moreover, SLD3-m25 dbf4-m25 cells are delayed in recovering from transient blocks to replication and subsequently arrest at the DNA damage checkpoint. These data indicate that the intra-S-phase checkpoint functions to block late origin firing in adverse conditions to prevent genomic instability and maximize cell survival.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3393088/" 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/PMC3393088/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lopez-Mosqueda, Jaime -- Maas, Nancy L -- Jonsson, Zophonias O -- Defazio-Eli, Lisa G -- Wohlschlegel, James -- Toczyski, David P -- GM059691/GM/NIGMS NIH HHS/ -- R01 GM059691/GM/NIGMS NIH HHS/ -- R01 GM059691-09/GM/NIGMS NIH HHS/ -- R01 GM059691-10/GM/NIGMS NIH HHS/ -- R01 GM059691-11/GM/NIGMS NIH HHS/ -- R01 GM059691-12/GM/NIGMS NIH HHS/ -- R01 GM089778/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Sep 23;467(7314):479-83. doi: 10.1038/nature09377.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158-9001, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20865002" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Cycle Proteins/genetics/*metabolism ; Checkpoint Kinase 2 ; DNA Damage/*physiology ; DNA Replication/drug effects/*physiology ; DNA-Binding Proteins/deficiency/genetics/*metabolism ; Hydroxyurea/pharmacology ; Phosphorylation/drug effects ; Protein-Serine-Threonine Kinases ; Rad52 DNA Repair and Recombination Protein/metabolism ; Replication Origin/drug effects/*physiology ; *S Phase/drug effects/physiology ; Saccharomyces cerevisiae/cytology/drug effects/genetics/*metabolism ; Saccharomyces cerevisiae Proteins/genetics/*metabolism ; Time Factors
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  • 23
    Publication Date: 2010-11-16
    Description: The chemotaxis signalling network in Escherichia coli that controls the locomotion of bacteria is a classic model system for signal transduction. This pathway modulates the behaviour of flagellar motors to propel bacteria towards sources of chemical attractants. Although this system relaxes to a steady state in response to environmental changes, the signalling events within the chemotaxis network are noisy and cause large temporal variations of the motor behaviour even in the absence of stimulus. That the same signalling network governs both behavioural variability and cellular response raises the question of whether these two traits are independent. Here, we experimentally establish a fluctuation-response relationship in the chemotaxis system of living bacteria. Using this relationship, we demonstrate the possibility of inferring the cellular response from the behavioural variability measured before stimulus. In monitoring the pre- and post-stimulus switching behaviour of individual bacterial motors, we found that variability scales linearly with the response time for different functioning states of the cell. This study highlights that the fundamental relationship between fluctuation and response is not constrained to physical systems at thermodynamic equilibrium but is extensible to living cells. Such a relationship not only implies that behavioural variability and cellular response can be coupled traits, but it also provides a general framework within which we can examine how the selection of a network design shapes this interdependence.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230254/" 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/PMC3230254/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Park, Heungwon -- Pontius, William -- Guet, Calin C -- Marko, John F -- Emonet, Thierry -- Cluzel, Philippe -- 1U54CA143869-01/CA/NCI NIH HHS/ -- P50 GM081892/GM/NIGMS NIH HHS/ -- P50 GM081892-04/GM/NIGMS NIH HHS/ -- R01 AI059195-03/AI/NIAID NIH HHS/ -- R01AI059195-03/AI/NIAID NIH HHS/ -- U54 CA143869/CA/NCI NIH HHS/ -- U54 CA143869-01/CA/NCI NIH HHS/ -- England -- Nature. 2010 Dec 9;468(7325):819-23. doi: 10.1038/nature09551. Epub 2010 Nov 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The James Franck Institute, The Institute for Biophysical Dynamics, and The Department of Physics, University of Chicago, Chicago, Illinois 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21076396" target="_blank"〉PubMed〈/a〉
    Keywords: Aspartic Acid/metabolism/pharmacology ; Calibration ; Chemotaxis/drug effects/*physiology ; Chromatography, High Pressure Liquid ; *Environment ; Escherichia coli/*cytology/drug effects/*physiology ; Flagella/drug effects/physiology ; Molecular Motor Proteins/metabolism ; Rotation ; *Signal Transduction/drug effects ; Stochastic Processes ; Time Factors
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  • 24
    Publication Date: 2010-11-05
    Description: Stroke is a leading cause of disability, but no pharmacological therapy is currently available for promoting recovery. The brain region adjacent to stroke damage-the peri-infarct zone-is critical for rehabilitation, as it shows heightened neuroplasticity, allowing sensorimotor functions to re-map from damaged areas. Thus, understanding the neuronal properties constraining this plasticity is important for the development of new treatments. Here we show that after a stroke in mice, tonic neuronal inhibition is increased in the peri-infarct zone. This increased tonic inhibition is mediated by extrasynaptic GABA(A) receptors and is caused by an impairment in GABA (gamma-aminobutyric acid) transporter (GAT-3/GAT-4) function. To counteract the heightened inhibition, we administered in vivo a benzodiazepine inverse agonist specific for alpha5-subunit-containing extrasynaptic GABA(A) receptors at a delay after stroke. This treatment produced an early and sustained recovery of motor function. Genetically lowering the number of alpha5- or delta-subunit-containing GABA(A) receptors responsible for tonic inhibition also proved beneficial for recovery after stroke, consistent with the therapeutic potential of diminishing extrasynaptic GABA(A) receptor function. Together, our results identify new pharmacological targets and provide the rationale for a novel strategy to promote recovery after stroke and possibly other brain injuries.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058798/" 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/PMC3058798/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clarkson, Andrew N -- Huang, Ben S -- Macisaac, Sarah E -- Mody, Istvan -- Carmichael, S Thomas -- NS30549/NS/NINDS NIH HHS/ -- R01 NS030549/NS/NINDS NIH HHS/ -- R01 NS030549-18/NS/NINDS NIH HHS/ -- England -- Nature. 2010 Nov 11;468(7321):305-9. doi: 10.1038/nature09511. Epub 2010 Nov 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, The David Geffen School of Medicine at UCLA, 635 Charles Young Drive South, Los Angeles, California 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21048709" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Benzodiazepines/pharmacology ; Cerebral Infarction/metabolism/pathology/physiopathology ; Disease Models, Animal ; Drug Inverse Agonism ; GABA Antagonists/pharmacology ; GABA Plasma Membrane Transport Proteins/metabolism ; Imidazoles/pharmacology ; Male ; Membrane Potentials/drug effects ; Mice ; Mice, Inbred C57BL ; Motor Cortex/metabolism/pathology/*physiology/*physiopathology ; Neuronal Plasticity/physiology ; Receptors, GABA/deficiency/genetics/metabolism ; Recovery of Function/*physiology ; Stroke/drug therapy/*metabolism/pathology ; Synapses/metabolism ; Time Factors ; gamma-Aminobutyric Acid/*metabolism
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  • 25
    Publication Date: 2010-04-22
    Description: 'Brain training', or the goal of improved cognitive function through the regular use of computerized tests, is a multimillion-pound industry, yet in our view scientific evidence to support its efficacy is lacking. Modest effects have been reported in some studies of older individuals and preschool children, and video-game players outperform non-players on some tests of visual attention. However, the widely held belief that commercially available computerized brain-training programs improve general cognitive function in the wider population in our opinion lacks empirical support. The central question is not whether performance on cognitive tests can be improved by training, but rather, whether those benefits transfer to other untrained tasks or lead to any general improvement in the level of cognitive functioning. Here we report the results of a six-week online study in which 11,430 participants trained several times each week on cognitive tasks designed to improve reasoning, memory, planning, visuospatial skills and attention. Although improvements were observed in every one of the cognitive tasks that were trained, no evidence was found for transfer effects to untrained tasks, even when those tasks were cognitively closely related.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2884087/" 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/PMC2884087/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Owen, Adrian M -- Hampshire, Adam -- Grahn, Jessica A -- Stenton, Robert -- Dajani, Said -- Burns, Alistair S -- Howard, Robert J -- Ballard, Clive G -- MC_U105559837/Medical Research Council/United Kingdom -- MC_U105559847/Medical Research Council/United Kingdom -- U.1055.01.002.00001.01/Medical Research Council/United Kingdom -- U.1055.01.002.00001.01(80449)/Medical Research Council/United Kingdom -- U.1055.01.003.00001.01/Medical Research Council/United Kingdom -- England -- Nature. 2010 Jun 10;465(7299):775-8. doi: 10.1038/nature09042.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Cognition and Brain Sciences Unit, 15 Chaucer Road, Cambridge CB2 7EF, UK. adrian.owen@mrc-cbu.cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20407435" target="_blank"〉PubMed〈/a〉
    Keywords: Attention/physiology ; Brain/*physiology ; Cognition/*physiology ; Computers ; Exercise/*physiology ; Humans ; Memory/physiology ; Task Performance and Analysis ; Thinking/physiology ; Time Factors
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  • 26
    Publication Date: 2010-01-30
    Description: The processes controlling the carbon flux and carbon storage of the atmosphere, ocean and terrestrial biosphere are temperature sensitive and are likely to provide a positive feedback leading to amplified anthropogenic warming. Owing to this feedback, at timescales ranging from interannual to the 20-100-kyr cycles of Earth's orbital variations, warming of the climate system causes a net release of CO(2) into the atmosphere; this in turn amplifies warming. But the magnitude of the climate sensitivity of the global carbon cycle (termed gamma), and thus of its positive feedback strength, is under debate, giving rise to large uncertainties in global warming projections. Here we quantify the median gamma as 7.7 p.p.m.v. CO(2) per degrees C warming, with a likely range of 1.7-21.4 p.p.m.v. CO(2) per degrees C. Sensitivity experiments exclude significant influence of pre-industrial land-use change on these estimates. Our results, based on the coupling of a probabilistic approach with an ensemble of proxy-based temperature reconstructions and pre-industrial CO(2) data from three ice cores, provide robust constraints for gamma on the policy-relevant multi-decadal to centennial timescales. By using an ensemble of 〉200,000 members, quantification of gamma is not only improved, but also likelihoods can be assigned, thereby providing a benchmark for future model simulations. Although uncertainties do not at present allow exclusion of gamma calculated from any of ten coupled carbon-climate models, we find that gamma is about twice as likely to fall in the lowermost than in the uppermost quartile of their range. Our results are incompatibly lower (P 〈 0.05) than recent pre-industrial empirical estimates of approximately 40 p.p.m.v. CO(2) per degrees C (refs 6, 7), and correspondingly suggest approximately 80% less potential amplification of ongoing global warming.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Frank, David C -- Esper, Jan -- Raible, Christoph C -- Buntgen, Ulf -- Trouet, Valerie -- Stocker, Benjamin -- Joos, Fortunat -- England -- Nature. 2010 Jan 28;463(7280):527-30. doi: 10.1038/nature08769.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Swiss Federal Research Institute WSL, Zurcherstrasse 111, CH-8903 Birmensdorf, Switzerland. david.frank@wsl.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20110999" target="_blank"〉PubMed〈/a〉
    Keywords: Carbon/*metabolism ; Carbon Dioxide/analysis ; *Climate Change ; Ice/analysis ; *Models, Theoretical ; Temperature ; Time Factors
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  • 27
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    Nature Publishing Group (NPG)
    Publication Date: 2010-04-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Apr 1;464(7289):649-50. doi: 10.1038/464649a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360688" target="_blank"〉PubMed〈/a〉
    Keywords: Data Collection ; Genetic Testing/trends ; Genetics, Medical/*trends ; Genome, Human/*genetics ; Genomics/economics/*history/trends ; Haplotypes/genetics ; History, 20th Century ; History, 21st Century ; Human Genome Project/*history ; Humans ; Time Factors
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  • 28
    Publication Date: 2010-04-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brakmann, Susanne -- England -- Nature. 2010 Apr 15;464(7291):987-8. doi: 10.1038/464987a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20393548" target="_blank"〉PubMed〈/a〉
    Keywords: Codon/*genetics ; Fluorescence ; Ligands ; Protein Biosynthesis/genetics/*physiology ; RNA, Transfer/genetics/*metabolism ; Ribosomes/chemistry/genetics/*metabolism ; Time Factors
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  • 29
    Publication Date: 2010-10-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Collins, Francis -- England -- Nature. 2010 Oct 7;467(7316):635. doi: 10.1038/467635a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20930798" target="_blank"〉PubMed〈/a〉
    Keywords: Age Factors ; Aptitude ; Awards and Prizes ; *Career Mobility ; Creativity ; Financing, Organized/economics ; *Freedom ; Humans ; Laboratories/economics/manpower ; National Institutes of Health (U.S.) ; Pilot Projects ; *Research/education/manpower ; *Research Personnel/education ; Research Support as Topic/economics/organization & administration ; Time Factors ; United States
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  • 30
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    Nature Publishing Group (NPG)
    Publication Date: 2010-07-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Visser, Marcel E -- England -- Nature. 2010 Jul 22;466(7305):445-7. doi: 10.1038/466445a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20651679" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Evolution ; Body Weight/*physiology ; Colorado ; *Global Warming ; Hibernation/*physiology ; Marmota/*anatomy & histology/growth & development/*physiology ; Population Dynamics ; Time Factors
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  • 31
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    Nature Publishing Group (NPG)
    Publication Date: 2010-08-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Aug 19;466(7309):903. doi: 10.1038/466903a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20724996" target="_blank"〉PubMed〈/a〉
    Keywords: Astronomy/economics/instrumentation/trends ; Budgets/trends ; *Data Collection ; Program Evaluation ; Research/economics/trends ; Time Factors ; United States ; United States National Aeronautics and Space Administration/*economics/trends
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  • 32
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    Nature Publishing Group (NPG)
    Publication Date: 2010-04-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Katsnelson, Alla -- England -- Nature. 2010 Apr 22;464(7292):1111. doi: 10.1038/4641111a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20414280" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Brain/*physiology ; Exercise/physiology ; Humans ; Mental Processes/*physiology ; Middle Aged ; Time Factors ; Treatment Failure ; *Video Games ; Young Adult
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  • 33
    Publication Date: 2010-01-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Khosla, Ashok -- Marton-Lefevre, Julia -- England -- Nature. 2010 Jan 7;463(7277):25. doi: 10.1038/463025c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20054377" target="_blank"〉PubMed〈/a〉
    Keywords: *Biodiversity ; Conservation of Natural Resources/*trends ; Extinction, Biological ; Politics ; Time Factors
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  • 34
    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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  • 35
    Publication Date: 2010-01-22
    Description: Robustness seems to be the opposite of evolvability. If phenotypes are robust against mutation, we might expect that a population will have difficulty adapting to an environmental change, as several studies have suggested. However, other studies contend that robust organisms are more adaptable. A quantitative understanding of the relationship between robustness and evolvability will help resolve these conflicting reports and will clarify outstanding problems in molecular and experimental evolution, evolutionary developmental biology and protein engineering. Here we demonstrate, using a general population genetics model, that mutational robustness can either impede or facilitate adaptation, depending on the population size, the mutation rate and the structure of the fitness landscape. In particular, neutral diversity in a robust population can accelerate adaptation as long as the number of phenotypes accessible to an individual by mutation is smaller than the total number of phenotypes in the fitness landscape. These results provide a quantitative resolution to a significant ambiguity in evolutionary theory.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071712/" 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/PMC3071712/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Draghi, Jeremy A -- Parsons, Todd L -- Wagner, Gunter P -- Plotkin, Joshua B -- 2U54AI057168/AI/NIAID NIH HHS/ -- U54 AI057168/AI/NIAID NIH HHS/ -- U54 AI057168-06S1/AI/NIAID NIH HHS/ -- England -- Nature. 2010 Jan 21;463(7279):353-5. doi: 10.1038/nature08694.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20090752" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological/*genetics ; *Biological Evolution ; Genetic Fitness/genetics ; Genetic Variation/genetics ; Genetics, Population ; Genotype ; Models, Genetic ; Mutagenesis/*genetics ; Mutation/*genetics ; Phenotype ; Population Density ; Time Factors
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  • 36
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    Nature Publishing Group (NPG)
    Publication Date: 2010-04-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2010 Apr 22;464(7292):1112-3. doi: 10.1038/4641112a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20414281" target="_blank"〉PubMed〈/a〉
    Keywords: Age Distribution ; Biomedical Research/*statistics & numerical data ; Disease Outbreaks/*statistics & numerical data ; Humans ; Influenza A Virus, H1N1 Subtype/immunology/isolation & ; purification/*pathogenicity ; Influenza B virus/genetics/immunology/isolation & purification/pathogenicity ; Influenza Vaccines/biosynthesis/immunology/supply & distribution ; Influenza, Human/*epidemiology/immunology/mortality/*virology ; Internationality ; Population Surveillance ; Time Factors ; United States/epidemiology ; Virulence
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  • 37
    Publication Date: 2010-04-30
    Description: The inflammatory nature of atherosclerosis is well established but the agent(s) that incite inflammation in the artery wall remain largely unknown. Germ-free animals are susceptible to atherosclerosis, suggesting that endogenous substances initiate the inflammation. Mature atherosclerotic lesions contain macroscopic deposits of cholesterol crystals in the necrotic core, but their appearance late in atherogenesis had been thought to disqualify them as primary inflammatory stimuli. However, using a new microscopic technique, we revealed that minute cholesterol crystals are present in early diet-induced atherosclerotic lesions and that their appearance in mice coincides with the first appearance of inflammatory cells. Other crystalline substances can induce inflammation by stimulating the caspase-1-activating NLRP3 (NALP3 or cryopyrin) inflammasome, which results in cleavage and secretion of interleukin (IL)-1 family cytokines. Here we show that cholesterol crystals activate the NLRP3 inflammasome in phagocytes in vitro in a process that involves phagolysosomal damage. Similarly, when injected intraperitoneally, cholesterol crystals induce acute inflammation, which is impaired in mice deficient in components of the NLRP3 inflammasome, cathepsin B, cathepsin L or IL-1 molecules. Moreover, when mice deficient in low-density lipoprotein receptor (LDLR) were bone-marrow transplanted with NLRP3-deficient, ASC (also known as PYCARD)-deficient or IL-1alpha/beta-deficient bone marrow and fed on a high-cholesterol diet, they had markedly decreased early atherosclerosis and inflammasome-dependent IL-18 levels. Minimally modified LDL can lead to cholesterol crystallization concomitant with NLRP3 inflammasome priming and activation in macrophages. Although there is the possibility that oxidized LDL activates the NLRP3 inflammasome in vivo, our results demonstrate that crystalline cholesterol acts as an endogenous danger signal and its deposition in arteries or elsewhere is an early cause rather than a late consequence of inflammation. These findings provide new insights into the pathogenesis of atherosclerosis and indicate new potential molecular targets for the therapy of this disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946640/" 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/PMC2946640/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Duewell, Peter -- Kono, Hajime -- Rayner, Katey J -- Sirois, Cherilyn M -- Vladimer, Gregory -- Bauernfeind, Franz G -- Abela, George S -- Franchi, Luigi -- Nunez, Gabriel -- Schnurr, Max -- Espevik, Terje -- Lien, Egil -- Fitzgerald, Katherine A -- Rock, Kenneth L -- Moore, Kathryn J -- Wright, Samuel D -- Hornung, Veit -- Latz, Eicke -- R01 AI075318/AI/NIAID NIH HHS/ -- R01 AI083713/AI/NIAID NIH HHS/ -- R01 AI083713-01/AI/NIAID NIH HHS/ -- R01 HL093262/HL/NHLBI NIH HHS/ -- R01 HL093262-01A1/HL/NHLBI NIH HHS/ -- England -- Nature. 2010 Apr 29;464(7293):1357-61. doi: 10.1038/nature08938.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20428172" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis Regulatory Proteins ; Atherosclerosis/chemically induced/*metabolism/*pathology ; Bone Marrow Transplantation ; Carrier Proteins/genetics/*metabolism ; Cathepsin B/metabolism ; Cathepsin L/metabolism ; Cholesterol/*chemistry/*metabolism/pharmacology ; Crystallization ; Cytoskeletal Proteins/deficiency ; Diet, Atherogenic ; Female ; Humans ; Inflammation/chemically induced/metabolism/pathology ; Interleukin-1/deficiency ; Interleukin-18/metabolism ; Lysosomes/drug effects/pathology ; Mice ; Mice, Inbred C57BL ; Peritoneal Cavity/pathology ; Phagocytes/drug effects/pathology/physiology ; Receptors, LDL/deficiency ; Time Factors
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  • 38
    Publication Date: 2010-03-30
    Description: Repair of DNA double-strand breaks (DSBs) by homologous recombination is crucial for cell proliferation and tumour suppression. However, despite its importance, the molecular intermediates of mitotic DSB repair remain undefined. The double Holliday junction (DHJ), presupposed to be the central intermediate for more than 25 years, has only been identified during meiotic recombination. Moreover, evidence has accumulated for alternative, DHJ-independent mechanisms, raising the possibility that DHJs are not formed during DSB repair in mitotically cycling cells. Here we identify intermediates of DSB repair by using a budding-yeast assay system designed to mimic physiological DSB repair. This system uses diploid cells and provides the possibility for allelic recombination either between sister chromatids or between homologues, as well as direct comparison with meiotic recombination at the same locus. In mitotically cycling cells, we detect inter-homologue joint molecule (JM) intermediates whose strand composition and size are identical to those of the canonical DHJ structures observed in meiosis. However, in contrast to meiosis, JMs between sister chromatids form in preference to those between homologues. Moreover, JMs seem to represent a minor pathway of DSB repair in mitotic cells, being detected at about tenfold lower levels (per DSB) than during meiotic recombination. Thus, although DHJs are identified as intermediates of DSB-promoted recombination in both mitotic and meiotic cells, their formation is distinctly regulated according to the specific dictates of the two cellular programs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851831/" 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/PMC2851831/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bzymek, Malgorzata -- Thayer, Nathaniel H -- Oh, Steve D -- Kleckner, Nancy -- Hunter, Neil -- GM025326/GM/NIGMS NIH HHS/ -- GM074223/GM/NIGMS NIH HHS/ -- R01 GM025326/GM/NIGMS NIH HHS/ -- R01 GM025326-31/GM/NIGMS NIH HHS/ -- R01 GM074223/GM/NIGMS NIH HHS/ -- R01 GM074223-05/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Apr 8;464(7290):937-41. doi: 10.1038/nature08868. Epub 2010 Mar 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, University of California Davis, Davis, California 95616, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20348905" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Chromatids/genetics/metabolism ; Crossing Over, Genetic/genetics ; *DNA Breaks, Double-Stranded ; *DNA Repair ; DNA, Cruciform/genetics/*metabolism ; Diploidy ; Meiosis/genetics ; Mitosis/genetics ; Models, Genetic ; RecQ Helicases/genetics/metabolism ; Saccharomyces cerevisiae/cytology/*genetics ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; Sister Chromatid Exchange/genetics ; Time Factors
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  • 39
    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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  • 40
    Publication Date: 2010-06-19
    Description: Functional receptive fields of neurons in sensory cortices undergo progressive refinement during development. Such refinement may be attributed to the pruning of non-optimal excitatory inputs, reshaping of the excitatory tuning profile through modifying the strengths of individual inputs, or strengthening of cortical inhibition. These models have not been directly tested because of the technical difficulties in assaying the spatiotemporal patterns of functional synaptic inputs during development. Here we apply in vivo whole-cell voltage-clamp recordings to the recipient layer 4 neurons in the rat primary auditory cortex (A1) to determine the developmental changes in the frequency-intensity tonal receptive fields (TRFs) of their excitatory and inhibitory inputs. Surprisingly, we observe co-tuned excitation and inhibition immediately after the onset of hearing, suggesting that a tripartite thalamocortical circuit with relatively strong feedforward inhibition is formed independently of auditory experience. The frequency ranges of tone-driven excitatory and inhibitory inputs first expand within a few days of the onset of hearing and then persist into adulthood. The latter phase is accompanied by a sharpening of the excitatory but not inhibitory frequency tuning profile, which results in relatively broader inhibitory tuning in adult A1 neurons. Thus the development of cortical synaptic TRFs after the onset of hearing is marked by a slight breakdown of previously formed excitation-inhibition balance. Our results suggest that functional refinement of cortical TRFs does not require a selective pruning of inputs, but may depend more on a fine adjustment of excitatory input strengths.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2909826/" 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/PMC2909826/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sun, Yujiao J -- Wu, Guangying K -- Liu, Bao-Hua -- Li, Pingyang -- Zhou, Mu -- Xiao, Zhongju -- Tao, Huizhong W -- Zhang, Li I -- EY018718/EY/NEI NIH HHS/ -- EY019049/EY/NEI NIH HHS/ -- R01 DC008983/DC/NIDCD NIH HHS/ -- R01 DC008983-01/DC/NIDCD NIH HHS/ -- R01 DC008983-02/DC/NIDCD NIH HHS/ -- R01 DC008983-03/DC/NIDCD NIH HHS/ -- R01 DC008983-04/DC/NIDCD NIH HHS/ -- R01 EY019049/EY/NEI NIH HHS/ -- R01 EY019049-02/EY/NEI NIH HHS/ -- R01DC008983/DC/NIDCD NIH HHS/ -- R03 DC006814/DC/NIDCD NIH HHS/ -- R03 DC006814-01A1/DC/NIDCD NIH HHS/ -- R03 DC006814-02/DC/NIDCD NIH HHS/ -- R03 DC006814-03/DC/NIDCD NIH HHS/ -- R21 DC008588/DC/NIDCD NIH HHS/ -- R21 DC008588-01/DC/NIDCD NIH HHS/ -- R21 DC008588-02/DC/NIDCD NIH HHS/ -- R21DC008588/DC/NIDCD NIH HHS/ -- UL1 RR025755/RR/NCRR NIH HHS/ -- England -- Nature. 2010 Jun 17;465(7300):927-31. doi: 10.1038/nature09079.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20559386" target="_blank"〉PubMed〈/a〉
    Keywords: Acoustic Stimulation ; Animals ; Auditory Cortex/growth & development/*physiology ; Auditory Pathways/physiology ; Electrical Synapses/physiology ; Excitatory Postsynaptic Potentials/*physiology ; Hearing/physiology ; Neural Inhibition/*physiology ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; Sensory Receptor Cells/*physiology ; Time Factors
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  • 41
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    Nature Publishing Group (NPG)
    Publication Date: 2010-11-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nath, Deepa -- England -- Nature. 2010 Nov 4;468(7320):43. doi: 10.1038/468043a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21048755" target="_blank"〉PubMed〈/a〉
    Keywords: Actin Cytoskeleton/chemistry/metabolism/ultrastructure ; Animals ; Microscopy, Atomic Force/*methods ; Movement/*physiology ; Myosin Type V/chemistry/*metabolism/ultrastructure ; Protein Conformation ; Time Factors ; *Video Recording
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  • 42
    Publication Date: 2010-03-26
    Description: Learning from novel experiences is a major task of the central nervous system. In mammals, the medial temporal lobe is crucial for this rapid form of learning. The modification of synapses and neuronal circuits through plasticity is thought to underlie memory formation. The induction of synaptic plasticity is favoured by coordinated action-potential timing across populations of neurons. Such coordinated activity of neural populations can give rise to oscillations of different frequencies, recorded in local field potentials. Brain oscillations in the theta frequency range (3-8 Hz) are often associated with the favourable induction of synaptic plasticity as well as behavioural memory. Here we report the activity of single neurons recorded together with the local field potential in humans engaged in a learning task. We show that successful memory formation in humans is predicted by a tight coordination of spike timing with the local theta oscillation. More stereotyped spiking predicts better memory, as indicated by higher retrieval confidence reported by subjects. These findings provide a link between the known modulation of theta oscillations by many memory-modulating behaviours and circuit mechanisms of plasticity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rutishauser, Ueli -- Ross, Ian B -- Mamelak, Adam N -- Schuman, Erin M -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Apr 8;464(7290):903-7. doi: 10.1038/nature08860. Epub 2010 Mar 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Computation and Neural Systems and Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20336071" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials/physiology ; Amygdala/cytology/physiology ; Electrodes, Implanted ; Epilepsy ; Hippocampus/cytology/physiology ; Humans ; Memory/*physiology ; Models, Neurological ; Neuronal Plasticity/physiology ; Neurons/*physiology ; *Theta Rhythm ; Time Factors
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  • 43
    Publication Date: 2010-12-18
    Description: On the basis of projected losses of their essential sea-ice habitats, a United States Geological Survey research team concluded in 2007 that two-thirds of the world's polar bears (Ursus maritimus) could disappear by mid-century if business-as-usual greenhouse gas emissions continue. That projection, however, did not consider the possible benefits of greenhouse gas mitigation. A key question is whether temperature increases lead to proportional losses of sea-ice habitat, or whether sea-ice cover crosses a tipping point and irreversibly collapses when temperature reaches a critical threshold. Such a tipping point would mean future greenhouse gas mitigation would confer no conservation benefits to polar bears. Here we show, using a general circulation model, that substantially more sea-ice habitat would be retained if greenhouse gas rise is mitigated. We also show, with Bayesian network model outcomes, that increased habitat retention under greenhouse gas mitigation means that polar bears could persist throughout the century in greater numbers and more areas than in the business-as-usual case. Our general circulation model outcomes did not reveal thresholds leading to irreversible loss of ice; instead, a linear relationship between global mean surface air temperature and sea-ice habitat substantiated the hypothesis that sea-ice thermodynamics can overcome albedo feedbacks proposed to cause sea-ice tipping points. Our outcomes indicate that rapid summer ice losses in models and observations represent increased volatility of a thinning sea-ice cover, rather than tipping-point behaviour. Mitigation-driven Bayesian network outcomes show that previously predicted declines in polar bear distribution and numbers are not unavoidable. Because polar bears are sentinels of the Arctic marine ecosystem and trends in their sea-ice habitats foreshadow future global changes, mitigating greenhouse gas emissions to improve polar bear status would have conservation benefits throughout and beyond the Arctic.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Amstrup, Steven C -- Deweaver, Eric T -- Douglas, David C -- Marcot, Bruce G -- Durner, George M -- Bitz, Cecilia M -- Bailey, David A -- England -- Nature. 2010 Dec 16;468(7326):955-8. doi: 10.1038/nature09653.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉US Geological Survey, Alaska Science Center, 4210 University Drive, Anchorage, Alaska 99508, USA. samstrup@pbears.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21164484" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aquatic Organisms ; Arctic Regions ; Bayes Theorem ; Carbon Dioxide/analysis ; *Ecosystem ; Endangered Species/statistics & numerical data/*trends ; Environmental Monitoring ; Gases/analysis ; Global Warming/prevention & control/statistics & numerical data ; Greenhouse Effect/*prevention & control/statistics & numerical data ; *Ice Cover ; Models, Theoretical ; Population Density ; Predatory Behavior ; Seasons ; Seawater/analysis/chemistry ; Temperature ; Thermodynamics ; Time Factors ; Ursidae/*physiology
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  • 44
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    Nature Publishing Group (NPG)
    Publication Date: 2010-04-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ledford, Heidi -- England -- Nature. 2010 Apr 29;464(7293):1258. doi: 10.1038/4641258a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20428134" target="_blank"〉PubMed〈/a〉
    Keywords: Clinical Trials as Topic/economics/ethics/*methods ; Humans ; Neoplasms/drug therapy/genetics ; Precision Medicine/economics/*trends ; Time Factors ; United States ; United States Food and Drug Administration
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  • 45
    Publication Date: 2010-04-03
    Description: Despite our rapidly growing knowledge about the human genome, we do not know all of the genes required for some of the most basic functions of life. To start to fill this gap we developed a high-throughput phenotypic screening platform combining potent gene silencing by RNA interference, time-lapse microscopy and computational image processing. We carried out a genome-wide phenotypic profiling of each of the approximately 21,000 human protein-coding genes by two-day live imaging of fluorescently labelled chromosomes. Phenotypes were scored quantitatively by computational image processing, which allowed us to identify hundreds of human genes involved in diverse biological functions including cell division, migration and survival. As part of the Mitocheck consortium, this study provides an in-depth analysis of cell division phenotypes and makes the entire high-content data set available as a resource to the community.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3108885/" 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/PMC3108885/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Neumann, Beate -- Walter, Thomas -- Heriche, Jean-Karim -- Bulkescher, Jutta -- Erfle, Holger -- Conrad, Christian -- Rogers, Phill -- Poser, Ina -- Held, Michael -- Liebel, Urban -- Cetin, Cihan -- Sieckmann, Frank -- Pau, Gregoire -- Kabbe, Rolf -- Wunsche, Annelie -- Satagopam, Venkata -- Schmitz, Michael H A -- Chapuis, Catherine -- Gerlich, Daniel W -- Schneider, Reinhard -- Eils, Roland -- Huber, Wolfgang -- Peters, Jan-Michael -- Hyman, Anthony A -- Durbin, Richard -- Pepperkok, Rainer -- Ellenberg, Jan -- 077192/Wellcome Trust/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Apr 1;464(7289):721-7. doi: 10.1038/nature08869.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MitoCheck Project Group, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, D-69117 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360735" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Division/*genetics ; Cell Movement/genetics ; Cell Survival/genetics ; Color ; Gene Knockdown Techniques ; Genes/genetics ; Genome, Human/*genetics ; HeLa Cells ; Humans ; Kinetics ; Mice ; Microscopy, Fluorescence/*methods ; Mitosis/genetics ; *Phenotype ; RNA Interference ; Reproducibility of Results ; Spindle Apparatus/genetics/metabolism ; Time Factors
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  • 46
    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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  • 47
    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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  • 48
    Publication Date: 2010-08-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nicholls, Trevor -- England -- Nature. 2010 Aug 19;466(7309):920. doi: 10.1038/466920a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20725019" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/*education/*methods ; Food Supply/*statistics & numerical data ; Humans ; Time Factors
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  • 49
    Publication Date: 2010-01-08
    Description: Retroviruses are the only group of viruses known to have left a fossil record, in the form of endogenous proviruses, and approximately 8% of the human genome is made up of these elements. Although many other viruses, including non-retroviral RNA viruses, are known to generate DNA forms of their own genomes during replication, none has been found as DNA in the germline of animals. Bornaviruses, a genus of non-segmented, negative-sense RNA virus, are unique among RNA viruses in that they establish persistent infection in the cell nucleus. Here we show that elements homologous to the nucleoprotein (N) gene of bornavirus exist in the genomes of several mammalian species, including humans, non-human primates, rodents and elephants. These sequences have been designated endogenous Borna-like N (EBLN) elements. Some of the primate EBLNs contain an intact open reading frame (ORF) and are expressed as mRNA. Phylogenetic analyses showed that EBLNs seem to have been generated by different insertional events in each specific animal family. Furthermore, the EBLN of a ground squirrel was formed by a recent integration event, whereas those in primates must have been formed more than 40 million years ago. We also show that the N mRNA of a current mammalian bornavirus, Borna disease virus (BDV), can form EBLN-like elements in the genomes of persistently infected cultured cells. Our results provide the first evidence for endogenization of non-retroviral virus-derived elements in mammalian genomes and give novel insights not only into generation of endogenous elements, but also into a role of bornavirus as a source of genetic novelty in its host.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2818285/" 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/PMC2818285/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Horie, Masayuki -- Honda, Tomoyuki -- Suzuki, Yoshiyuki -- Kobayashi, Yuki -- Daito, Takuji -- Oshida, Tatsuo -- Ikuta, Kazuyoshi -- Jern, Patric -- Gojobori, Takashi -- Coffin, John M -- Tomonaga, Keizo -- R37 CA 089441/CA/NCI NIH HHS/ -- R37 CA089441/CA/NCI NIH HHS/ -- R37 CA089441-09/CA/NCI NIH HHS/ -- England -- Nature. 2010 Jan 7;463(7277):84-7. doi: 10.1038/nature08695.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Virology, Research Institute for Microbial Diseases (BIKEN), Osaka University, Osaka 565-0871, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20054395" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Borna disease virus/genetics/physiology ; Bornaviridae/*genetics/physiology ; Cell Line ; Conserved Sequence/genetics ; Evolution, Molecular ; Genes, Viral/*genetics ; Genome/*genetics ; Host-Pathogen Interactions/genetics ; Humans ; Mammals/*genetics/*virology ; Models, Genetic ; Molecular Sequence Data ; Open Reading Frames/genetics ; Phylogeny ; Reverse Transcription ; Time Factors ; Virus Integration/*genetics
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  • 50
    Publication Date: 2010-09-17
    Description: The beta-haemoglobinopathies are the most prevalent inherited disorders worldwide. Gene therapy of beta-thalassaemia is particularly challenging given the requirement for massive haemoglobin production in a lineage-specific manner and the lack of selective advantage for corrected haematopoietic stem cells. Compound beta(E)/beta(0)-thalassaemia is the most common form of severe thalassaemia in southeast Asian countries and their diasporas. The beta(E)-globin allele bears a point mutation that causes alternative splicing. The abnormally spliced form is non-coding, whereas the correctly spliced messenger RNA expresses a mutated beta(E)-globin with partial instability. When this is compounded with a non-functional beta(0) allele, a profound decrease in beta-globin synthesis results, and approximately half of beta(E)/beta(0)-thalassaemia patients are transfusion-dependent. The only available curative therapy is allogeneic haematopoietic stem cell transplantation, although most patients do not have a human-leukocyte-antigen-matched, geno-identical donor, and those who do still risk rejection or graft-versus-host disease. Here we show that, 33 months after lentiviral beta-globin gene transfer, an adult patient with severe beta(E)/beta(0)-thalassaemia dependent on monthly transfusions since early childhood has become transfusion independent for the past 21 months. Blood haemoglobin is maintained between 9 and 10 g dl(-1), of which one-third contains vector-encoded beta-globin. Most of the therapeutic benefit results from a dominant, myeloid-biased cell clone, in which the integrated vector causes transcriptional activation of HMGA2 in erythroid cells with further increased expression of a truncated HMGA2 mRNA insensitive to degradation by let-7 microRNAs. The clonal dominance that accompanies therapeutic efficacy may be coincidental and stochastic or result from a hitherto benign cell expansion caused by dysregulation of the HMGA2 gene in stem/progenitor cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355472/" 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/PMC3355472/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cavazzana-Calvo, Marina -- Payen, Emmanuel -- Negre, Olivier -- Wang, Gary -- Hehir, Kathleen -- Fusil, Floriane -- Down, Julian -- Denaro, Maria -- Brady, Troy -- Westerman, Karen -- Cavallesco, Resy -- Gillet-Legrand, Beatrix -- Caccavelli, Laure -- Sgarra, Riccardo -- Maouche-Chretien, Leila -- Bernaudin, Francoise -- Girot, Robert -- Dorazio, Ronald -- Mulder, Geert-Jan -- Polack, Axel -- Bank, Arthur -- Soulier, Jean -- Larghero, Jerome -- Kabbara, Nabil -- Dalle, Bruno -- Gourmel, Bernard -- Socie, Gerard -- Chretien, Stany -- Cartier, Nathalie -- Aubourg, Patrick -- Fischer, Alain -- Cornetta, Kenneth -- Galacteros, Frederic -- Beuzard, Yves -- Gluckman, Eliane -- Bushman, Frederick -- Hacein-Bey-Abina, Salima -- Leboulch, Philippe -- AI082020/AI/NIAID NIH HHS/ -- AI52845/AI/NIAID NIH HHS/ -- HL090921/HL/NHLBI NIH HHS/ -- R01 AI052845/AI/NIAID NIH HHS/ -- R01 AI082020/AI/NIAID NIH HHS/ -- England -- Nature. 2010 Sep 16;467(7313):318-22. doi: 10.1038/nature09328.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Clinical Investigation Center in Biotherapy, Groupe Hospitalier Universitaire Ouest, Inserm/Assistance Publique-Hopitaux de Paris, Paris 75015, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20844535" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Blood Cells/cytology/metabolism ; *Blood Transfusion ; Bone Marrow Cells/cytology/metabolism ; Child, Preschool ; Clone Cells/metabolism ; Gene Expression ; *Genetic Therapy ; Genetic Vectors/genetics ; HMGA2 Protein/genetics/*metabolism ; Homeostasis ; Humans ; Lentivirus/genetics ; Male ; MicroRNAs/genetics ; Organ Specificity ; RNA, Messenger/analysis/genetics ; Time Factors ; Transcriptional Activation ; Young Adult ; beta-Globins/*genetics/*metabolism ; beta-Thalassemia/*genetics/metabolism/*therapy
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  • 51
    Publication Date: 2010-10-29
    Description: Daily life continually confronts us with an exuberance of external, sensory stimuli competing with a rich stream of internal deliberations, plans and ruminations. The brain must select one or more of these for further processing. How this competition is resolved across multiple sensory and cognitive regions is not known; nor is it clear how internal thoughts and attention regulate this competition. Recording from single neurons in patients implanted with intracranial electrodes for clinical reasons, here we demonstrate that humans can regulate the activity of their neurons in the medial temporal lobe (MTL) to alter the outcome of the contest between external images and their internal representation. Subjects looked at a hybrid superposition of two images representing familiar individuals, landmarks, objects or animals and had to enhance one image at the expense of the other, competing one. Simultaneously, the spiking activity of their MTL neurons in different subregions and hemispheres was decoded in real time to control the content of the hybrid. Subjects reliably regulated, often on the first trial, the firing rate of their neurons, increasing the rate of some while simultaneously decreasing the rate of others. They did so by focusing onto one image, which gradually became clearer on the computer screen in front of their eyes, and thereby overriding sensory input. On the basis of the firing of these MTL neurons, the dynamics of the competition between visual images in the subject's mind was visualized on an external display.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010923/" 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/PMC3010923/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cerf, Moran -- Thiruvengadam, Nikhil -- Mormann, Florian -- Kraskov, Alexander -- Quiroga, Rodrigo Quian -- Koch, Christof -- Fried, Itzhak -- G0701038/Medical Research Council/United Kingdom -- R01 NS033221/NS/NINDS NIH HHS/ -- R01 NS033221-13/NS/NINDS NIH HHS/ -- England -- Nature. 2010 Oct 28;467(7319):1104-8. doi: 10.1038/nature09510.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Computation and Neural Systems, California Institute of Technology, Pasadena, California 91125, USA. moran@klab.caltech.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20981100" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Attention/*physiology ; Cognition/*physiology ; Electrodes, Implanted ; Epilepsy/physiopathology ; Humans ; Man-Machine Systems ; Microelectrodes ; Mind-Body Relations, Metaphysical/physiology ; Models, Neurological ; Neurons/*physiology ; Photic Stimulation ; Temporal Lobe/*cytology/*physiology ; Time Factors
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  • 52
    Publication Date: 2010-03-30
    Description: Cancer chemoprevention uses natural, synthetic, or biological substances to reverse, suppress, or prevent either the initial phase of carcinogenesis or the progression of neoplastic cells to cancer. It holds promise for overcoming problems associated with the treatment of late-stage cancers. However, the broad application of chemoprevention is compromised at present by limited effectiveness and potential toxicity. To overcome these challenges, here we developed a new chemoprevention approach that specifically targets premalignant tumour cells for apoptosis. We show that a deficiency in the adenomatous polyposis coli (APC) gene and subsequent activation of beta-catenin lead to the repression of cellular caspase-8 inhibitor c-FLIP (also known as CFLAR) expression through activation of c-Myc, and that all-trans-retinyl acetate (RAc) independently upregulates tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptors and suppresses decoy receptors. Thus, the combination of TRAIL and RAc induces apoptosis in APC-deficient premalignant cells without affecting normal cells in vitro. In addition, we show that short-term and non-continuous TRAIL and RAc treatment induce apoptosis specifically in intestinal polyps, strongly inhibit tumour growth, and prolong survival in multiple intestinal neoplasms C57BL/6J-Apc(Min)/J (Apc(Min)) mice. With our approach, we further demonstrate that TRAIL and RAc induce significant cell death in human colon polyps, providing a potentially selective approach for colorectal cancer chemoprevention by targeting APC-deficient cells for apoptosis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3425353/" 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/PMC3425353/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Ling -- Ren, Xiaoyang -- Alt, Eckhard -- Bai, Xiaowen -- Huang, Shaoyi -- Xu, Zhengming -- Lynch, Patrick M -- Moyer, Mary P -- Wen, Xian-Feng -- Wu, Xiangwei -- AI063063/AI/NIAID NIH HHS/ -- R01 AI063063/AI/NIAID NIH HHS/ -- England -- Nature. 2010 Apr 15;464(7291):1058-61. doi: 10.1038/nature08871. Epub 2010 Mar 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20348907" target="_blank"〉PubMed〈/a〉
    Keywords: Adenomatous Polyposis Coli Protein/*deficiency/genetics ; Animals ; Apoptosis/*drug effects ; CASP8 and FADD-Like Apoptosis Regulating Protein/metabolism ; Cell Proliferation/drug effects ; Colorectal Neoplasms/genetics/metabolism/*pathology/*prevention & control ; Gene Expression Regulation/drug effects ; Genes, APC ; Humans ; Intestinal Polyps/drug therapy/pathology ; Mice ; Mice, Inbred C57BL ; Precancerous Conditions/drug therapy/genetics/metabolism/pathology ; Proto-Oncogene Proteins c-myc/metabolism ; Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism ; Signal Transduction/drug effects ; Survival Rate ; TNF-Related Apoptosis-Inducing Ligand/administration & ; dosage/pharmacology/therapeutic use ; Time Factors ; Vitamin A/administration & dosage/*analogs & derivatives/pharmacology/therapeutic ; use ; beta Catenin/metabolism
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  • 53
    Publication Date: 2010-03-12
    Description: Halogen atoms and oxides are highly reactive and can profoundly affect atmospheric composition. Chlorine atoms can decrease the lifetimes of gaseous elemental mercury and hydrocarbons such as the greenhouse gas methane. Chlorine atoms also influence cycles that catalytically destroy or produce tropospheric ozone, a greenhouse gas potentially toxic to plant and animal life. Conversion of inorganic chloride into gaseous chlorine atom precursors within the troposphere is generally considered a coastal or marine air phenomenon. Here we report mid-continental observations of the chlorine atom precursor nitryl chloride at a distance of 1,400 km from the nearest coastline. We observe persistent and significant nitryl chloride production relative to the consumption of its nitrogen oxide precursors. Comparison of these findings to model predictions based on aerosol and precipitation composition data from long-term monitoring networks suggests nitryl chloride production in the contiguous USA alone is at a level similar to previous global estimates for coastal and marine regions. We also suggest that a significant fraction of tropospheric chlorine atoms may arise directly from anthropogenic pollutants.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thornton, Joel A -- Kercher, James P -- Riedel, Theran P -- Wagner, Nicholas L -- Cozic, Julie -- Holloway, John S -- Dube, William P -- Wolfe, Glenn M -- Quinn, Patricia K -- Middlebrook, Ann M -- Alexander, Becky -- Brown, Steven S -- England -- Nature. 2010 Mar 11;464(7286):271-4. doi: 10.1038/nature08905.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Atmospheric Sciences, University of Washington, Seattle, Washington 98195, USA. thornton@atmos.washington.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20220847" target="_blank"〉PubMed〈/a〉
    Keywords: Aerosols/chemistry ; Air/analysis ; Atmosphere/*chemistry ; Chlorine/*chemistry ; Colorado ; Models, Chemical ; Nitrites/analysis/*chemistry ; Nitrogen/*chemistry ; Nitrogen Oxides/chemistry ; Time Factors
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  • 54
    Publication Date: 2010-02-26
    Description: Tropical cyclones (also known as hurricanes and typhoons) are now believed to be an important component of the Earth's climate system. In particular, by vigorously mixing the upper ocean, they can affect the ocean's heat uptake, poleward heat transport, and hence global temperatures. Changes in the distribution and frequency of tropical cyclones could therefore become an important element of the climate response to global warming. A potential analogue to modern greenhouse conditions, the climate of the early Pliocene epoch (approximately 5 to 3 million years ago) can provide important clues to this response. Here we describe a positive feedback between hurricanes and the upper-ocean circulation in the tropical Pacific Ocean that may have been essential for maintaining warm, El Nino-like conditions during the early Pliocene. This feedback is based on the ability of hurricanes to warm water parcels that travel towards the Equator at shallow depths and then resurface in the eastern equatorial Pacific as part of the ocean's wind-driven circulation. In the present climate, very few hurricane tracks intersect the parcel trajectories; consequently, there is little heat exchange between waters at such depths and the surface. More frequent and/or stronger hurricanes in the central Pacific imply greater heating of the parcels, warmer temperatures in the eastern equatorial Pacific, warmer tropics and, in turn, even more hurricanes. Using a downscaling hurricane model, we show dramatic shifts in the tropical cyclone distribution for the early Pliocene that favour this feedback. Further calculations with a coupled climate model support our conclusions. The proposed feedback should be relevant to past equable climates and potentially to contemporary climate change.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fedorov, Alexey V -- Brierley, Christopher M -- Emanuel, Kerry -- England -- Nature. 2010 Feb 25;463(7284):1066-70. doi: 10.1038/nature08831.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Geology and Geophysics, Yale University, New Haven, Connecticut 06520, USA. alexey.fedorov@yale.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20182509" target="_blank"〉PubMed〈/a〉
    Keywords: Atlantic Ocean ; Atmosphere/chemistry ; Carbon Dioxide/analysis ; Cyclonic Storms/*history ; Global Warming ; History, Ancient ; Hot Temperature ; Pacific Ocean ; Seawater ; Time Factors ; *Tropical Climate ; Water Movements ; Wind
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  • 55
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    Nature Publishing Group (NPG)
    Publication Date: 2010-11-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sartorius, Norman -- England -- Nature. 2010 Nov 11;468(7321):163-5. doi: 10.1038/468163a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Association for the Improvement of Mental Health Programmes at 14 Chemin Colladon, 1209 Geneva, Switzerland. sartorius@normansartorius.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21068806" target="_blank"〉PubMed〈/a〉
    Keywords: *Health Knowledge, Attitudes, Practice ; Health Personnel/education ; Health Surveys ; Humans ; Internationality ; *Mental Disorders/diagnosis/economics/therapy ; *Prejudice ; *Public Opinion ; Surveys and Questionnaires ; Time Factors ; World Health Organization
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  • 56
    Publication Date: 2010-07-27
    Description: One of the detrimental effects of ultraviolet radiation on DNA is the formation of the (6-4) photoproduct, 6-4PP, between two adjacent pyrimidine rings. This lesion interferes with replication and transcription, and may result in mutation and cell death. In many organisms, a flavoenzyme called photolyase uses blue light energy to repair the 6-4PP (ref. 3). The molecular mechanism of the repair reaction is poorly understood. Here, we use ultrafast spectroscopy to show that the key step in the repair photocycle is acyclic proton transfer between the enzyme and the substrate. By femtosecond synchronization of the enzymatic dynamics with the repair function, we followed the function evolution and observed direct electron transfer from the excited flavin cofactor to the 6-4PP in 225 picoseconds, but surprisingly fast back electron transfer in 50 picoseconds without repair. We found that the catalytic proton transfer between a histidine residue in the active site and the 6-4PP, induced by the initial photoinduced electron transfer from the excited flavin cofactor to 6-4PP, occurs in 425 picoseconds and leads to 6-4PP repair in tens of nanoseconds. These key dynamics define the repair photocycle and explain the underlying molecular mechanism of the enzyme's modest efficiency.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018752/" 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/PMC3018752/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Jiang -- Liu, Zheyun -- Tan, Chuang -- Guo, Xunmin -- Wang, Lijuan -- Sancar, Aziz -- Zhong, Dongping -- GM074813/GM/NIGMS NIH HHS/ -- P30 ES010126/ES/NIEHS NIH HHS/ -- R01 GM031082/GM/NIGMS NIH HHS/ -- R01 GM074813/GM/NIGMS NIH HHS/ -- R01 GM074813-04/GM/NIGMS NIH HHS/ -- R01 HG002779-05/HG/NHGRI NIH HHS/ -- R01 HG002779-06/HG/NHGRI NIH HHS/ -- R01 LM006845/LM/NLM NIH HHS/ -- England -- Nature. 2010 Aug 12;466(7308):887-890. doi: 10.1038/nature09192.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, Program of Biophysics, The Ohio State University, Columbus, Ohio 43210, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20657578" target="_blank"〉PubMed〈/a〉
    Keywords: Absorption ; Animals ; Arabidopsis/*enzymology/genetics ; Biocatalysis ; DNA Damage ; *DNA Repair/radiation effects ; Deoxyribodipyrimidine Photo-Lyase/chemistry/genetics/*metabolism ; Drosophila melanogaster/enzymology ; Electrons ; Flavins/chemistry/metabolism ; Histidine/genetics/metabolism ; Kinetics ; Models, Molecular ; Protons ; Pyrimidine Dimers/chemistry/*metabolism/*radiation effects ; Time Factors ; *Ultraviolet Rays
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  • 57
    Publication Date: 2010-04-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chatterji, Biswa Prasun -- England -- Nature. 2010 Apr 8;464(7290):831. doi: 10.1038/464831c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20376126" target="_blank"〉PubMed〈/a〉
    Keywords: Career Mobility ; *Education, Graduate ; India ; Research Personnel/*education/*standards ; Time Factors
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  • 58
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    Nature Publishing Group (NPG)
    Publication Date: 2010-02-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Check Hayden, Erika -- England -- Nature. 2010 Feb 25;463(7284):1006. doi: 10.1038/4631006a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20182479" target="_blank"〉PubMed〈/a〉
    Keywords: Clinical Trials as Topic/trends ; *Disease Progression ; HIV Infections/*drug therapy/*epidemiology/prevention & control/transmission ; HIV Seropositivity/*drug therapy/*epidemiology/transmission/virology ; Humans ; Time Factors
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  • 59
    Publication Date: 2010-04-03
    Description: African sleeping sickness or human African trypanosomiasis, caused by Trypanosoma brucei spp., is responsible for approximately 30,000 deaths each year. Available treatments for this disease are poor, with unacceptable efficacy and safety profiles, particularly in the late stage of the disease when the parasite has infected the central nervous system. Here we report the validation of a molecular target and the discovery of associated lead compounds with the potential to address this lack of suitable treatments. Inhibition of this target-T. brucei N-myristoyltransferase-leads to rapid killing of trypanosomes both in vitro and in vivo and cures trypanosomiasis in mice. These high-affinity inhibitors bind into the peptide substrate pocket of the enzyme and inhibit protein N-myristoylation in trypanosomes. The compounds identified have promising pharmaceutical properties and represent an opportunity to develop oral drugs to treat this devastating disease. Our studies validate T. brucei N-myristoyltransferase as a promising therapeutic target for human African trypanosomiasis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917743/" 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/PMC2917743/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Frearson, Julie A -- Brand, Stephen -- McElroy, Stuart P -- Cleghorn, Laura A T -- Smid, Ondrej -- Stojanovski, Laste -- Price, Helen P -- Guther, M Lucia S -- Torrie, Leah S -- Robinson, David A -- Hallyburton, Irene -- Mpamhanga, Chidochangu P -- Brannigan, James A -- Wilkinson, Anthony J -- Hodgkinson, Michael -- Hui, Raymond -- Qiu, Wei -- Raimi, Olawale G -- van Aalten, Daan M F -- Brenk, Ruth -- Gilbert, Ian H -- Read, Kevin D -- Fairlamb, Alan H -- Ferguson, Michael A J -- Smith, Deborah F -- Wyatt, Paul G -- 077503/Wellcome Trust/United Kingdom -- 077705/Wellcome Trust/United Kingdom -- 085622/Wellcome Trust/United Kingdom -- 087590/Wellcome Trust/United Kingdom -- 1097737/Canadian Institutes of Health Research/Canada -- G0900138/Medical Research Council/United Kingdom -- G0900138(90614)/Medical Research Council/United Kingdom -- WT077503/Wellcome Trust/United Kingdom -- WT077705/Wellcome Trust/United Kingdom -- WT083481,/Wellcome Trust/United Kingdom -- WT085622/Wellcome Trust/United Kingdom -- England -- Nature. 2010 Apr 1;464(7289):728-32. doi: 10.1038/nature08893.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 5EH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360736" target="_blank"〉PubMed〈/a〉
    Keywords: Acyltransferases/*antagonists & inhibitors/metabolism ; Aminopyridines/chemistry/metabolism/pharmacology/therapeutic use ; Animals ; Antiparasitic Agents/chemistry/metabolism/*pharmacology/*therapeutic use ; Enzyme Assays ; Enzyme Inhibitors/chemistry/metabolism/pharmacology/therapeutic use ; Female ; Humans ; Mice ; Molecular Structure ; Pyrazoles/chemistry/metabolism/pharmacology/therapeutic use ; Rats ; Sulfonamides/chemistry/metabolism/pharmacology/therapeutic use ; Time Factors ; Trypanosoma brucei brucei/*drug effects/*enzymology/growth & development ; Trypanosomiasis, African/*drug therapy/*parasitology
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  • 60
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    Nature Publishing Group (NPG)
    Publication Date: 2010-01-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schiermeier, Quirin -- England -- Nature. 2010 Jan 21;463(7279):276-7. doi: 10.1038/463276a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20090719" target="_blank"〉PubMed〈/a〉
    Keywords: Ecology/*standards ; Environmental Monitoring ; Geography ; Global Warming ; *Ice Cover ; India ; Peer Review, Research/standards ; Tibet ; Time Factors ; Uncertainty ; Water Supply/analysis
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  • 61
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    Nature Publishing Group (NPG)
    Publication Date: 2010-10-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schiermeier, Quirin -- England -- Nature. 2010 Oct 28;467(7319):1018-9. doi: 10.1038/4671018a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20981064" target="_blank"〉PubMed〈/a〉
    Keywords: *Disasters/statistics & numerical data ; *Earthquakes/mortality/statistics & numerical data ; Haiti ; Humans ; Time Factors
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  • 62
    Publication Date: 2010-01-08
    Description: The Southern Ocean, with its large surface area and vigorous overturning circulation, is potentially a substantial sink of anthropogenic CO(2) (refs 1-4). Despite its importance, the mechanism and pathways of anthropogenic CO(2) uptake and transport are poorly understood. Regulation of the Southern Ocean carbon sink by the wind-driven Ekman flow, mesoscale eddies and their interaction is under debate. Here we use a high-resolution ocean circulation and carbon cycle model to address the mechanisms controlling the Southern Ocean sink of anthropogenic CO(2). The focus of our study is on the intra-annual variability in anthropogenic CO(2) over a two-year time period. We show that the pattern of carbon uptake is correlated with the oceanic vertical exchange. Zonally integrated carbon uptake peaks at the Antarctic polar front. The carbon is then advected away from the uptake regions by the circulation of the Southern Ocean, which is controlled by the interplay among Ekman flow, ocean eddies and subduction of water masses. Although lateral carbon fluxes are locally dominated by the imprint of mesoscale eddies, the Ekman transport is the primary mechanism for the zonally integrated, cross-frontal transport of anthropogenic CO(2). Intra-annual variability of the cross-frontal transport is dominated by the Ekman flow with little compensation from eddies. A budget analysis in the density coordinate highlights the importance of wind-driven transport across the polar front and subduction at the subtropical front. Our results suggest intimate connections between oceanic carbon uptake and climate variability through the temporal variability of Ekman transport.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ito, T -- Woloszyn, M -- Mazloff, M -- England -- Nature. 2010 Jan 7;463(7277):80-3. doi: 10.1038/nature08687.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Atmospheric Science, Colorado State University, 1371 Campus Delivery, Fort Collins, Colorado 80523-1371, USA. ito@atmos.colostate.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20054394" target="_blank"〉PubMed〈/a〉
    Keywords: Antarctic Regions ; Carbon/analysis/metabolism ; Carbon Dioxide/*analysis/metabolism ; Human Activities ; Models, Theoretical ; Oceans and Seas ; Reproducibility of Results ; Seawater/*chemistry ; Time Factors ; *Water Movements ; *Wind
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  • 63
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    Publication Date: 2010-03-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shadan, Sadaf -- England -- Nature. 2010 Mar 4;464(7285):43. doi: 10.1038/464043a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20203600" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Child, Preschool ; Female ; Finland ; Genome-Wide Association Study ; Great Britain ; Humans ; Infant ; Male ; Polymorphism, Single Nucleotide/*genetics ; Time Factors ; *Tooth, Deciduous/*growth & development
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  • 64
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    Nature Publishing Group (NPG)
    Publication Date: 2010-07-31
    Description: Unjustified and impractical legal requirements are stopping genetically engineered crops from saving millions from starvation and malnutrition, says Ingo Potrykus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Potrykus, Ingo -- England -- Nature. 2010 Jul 29;466(7306):561. doi: 10.1038/466561a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Golden Rice Humanitarian Board. ingo@potrykus.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20671692" target="_blank"〉PubMed〈/a〉
    Keywords: Consumer Product Safety/*legislation & jurisprudence ; Cost-Benefit Analysis ; Environment ; Food Supply/*statistics & numerical data ; Food, Genetically Modified/standards/*statistics & numerical data/utilization ; Genetic Engineering/*legislation & jurisprudence ; Humans ; Malnutrition/prevention & control ; Plants, Genetically Modified ; Public-Private Sector Partnerships ; Safety/legislation & jurisprudence/statistics & numerical data ; Time Factors
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  • 65
    Publication Date: 2010-06-26
    Description: Concentrations of dissolved inorganic carbon (DIC) decrease in the surface mixed layers during spring and summer in most of the oligotrophic ocean. Mass balance calculations require that the missing DIC is converted into particulate carbon by photosynthesis. This DIC uptake represents one of the largest components of net community production in the world ocean. However, mixed-layer waters in these regions of the ocean typically contain negligible concentrations of plant nutrients such as nitrate and phosphate. Combined nutrient supply mechanisms including nitrogen fixation, diffusive transport and vertical entrainment are believed to be insufficient to supply the required nutrients for photosynthesis. The basin-scale potential for episodic nutrient transport by eddy events is unresolved. As a result, it is not understood how biologically mediated DIC uptake can be supported in the absence of nutrients. Here we report on high-resolution measurements of nitrate (NO(3)(-)) and oxygen (O(2)) concentration made over 21 months using a profiling float deployed near the Hawaii Ocean Time-series station in the North Pacific subtropical gyre. Our measurements demonstrate that as O(2) was produced and DIC was consumed over two annual cycles, a corresponding seasonal deficit in dissolved NO(3)(-) appeared in water at depths from 100 to 250 m. The deep-water deficit in NO(3)(-) was in near-stoichiometric balance with the fixed nitrogen exported to depth. Thus, when the water column from the surface to 250 m is considered as a whole, there is near equivalence between nutrient supply and demand. Short-lived transport events (〈10 days) that connect deep stocks of nitrate to nutrient-poor surface waters were clearly present in 12 of the 127 vertical profiles.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johnson, Kenneth S -- Riser, Stephen C -- Karl, David M -- England -- Nature. 2010 Jun 24;465(7301):1062-5. doi: 10.1038/nature09170.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Monterey Bay Aquarium Research Institute, Moss Landing, California 95039, USA. johnson@mbari.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20577212" target="_blank"〉PubMed〈/a〉
    Keywords: Atmosphere/chemistry ; Carbon Dioxide/analysis/metabolism ; Ecosystem ; Hawaii ; Nitrates/*analysis/chemistry/*metabolism ; Nitrogen/analysis/chemistry/metabolism ; Oxygen/analysis/metabolism ; Pacific Ocean ; Salinity ; Seasons ; Seawater/*chemistry ; Ships ; Solubility ; Time Factors ; *Tropical Climate
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  • 66
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    Nature Publishing Group (NPG)
    Publication Date: 2010-04-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wadman, Meredith -- England -- Nature. 2010 Apr 15;464(7291):967. doi: 10.1038/464967a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20393530" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; *Embryonic Stem Cells ; *Federal Government ; Humans ; National Institutes of Health (U.S.)/legislation & jurisprudence ; Research Support as Topic/*economics ; Time Factors ; United States
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  • 67
    Publication Date: 2014-12-17
    Description: Nitrous oxide (N2O) is an important greenhouse gas and ozone-depleting substance that has anthropogenic as well as natural marine and terrestrial sources. The tropospheric N2O concentrations have varied substantially in the past in concert with changing climate on glacial-interglacial and millennial timescales. It is not well understood, however, how N2O emissions from marine and terrestrial sources change in response to varying environmental conditions. The distinct isotopic compositions of marine and terrestrial N2O sources can help disentangle the relative changes in marine and terrestrial N2O emissions during past climate variations. Here we present N2O concentration and isotopic data for the last deglaciation, from 16,000 to 10,000 years before present, retrieved from air bubbles trapped in polar ice at Taylor Glacier, Antarctica. With the help of our data and a box model of the N2O cycle, we find a 30 per cent increase in total N2O emissions from the late glacial to the interglacial, with terrestrial and marine emissions contributing equally to the overall increase and generally evolving in parallel over the last deglaciation, even though there is no a priori connection between the drivers of the two sources. However, we find that terrestrial emissions dominated on centennial timescales, consistent with a state-of-the-art dynamic global vegetation and land surface process model that suggests that during the last deglaciation emission changes were strongly influenced by temperature and precipitation patterns over land surfaces. The results improve our understanding of the drivers of natural N2O emissions and are consistent with the idea that natural N2O emissions will probably increase in response to anthropogenic warming.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schilt, Adrian -- Brook, Edward J -- Bauska, Thomas K -- Baggenstos, Daniel -- Fischer, Hubertus -- Joos, Fortunat -- Petrenko, Vasilii V -- Schaefer, Hinrich -- Schmitt, Jochen -- Severinghaus, Jeffrey P -- Spahni, Renato -- Stocker, Thomas F -- England -- Nature. 2014 Dec 11;516(7530):234-7. doi: 10.1038/nature13971.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] College of Earth, Ocean, and Atmospheric Sciences, Oregon State University, Corvallis, Oregon 97331, USA [2] Climate and Environmental Physics, Physics Institute, and Oeschger Centre for Climate Change Research, University of Bern, 3012 Bern, Switzerland. ; College of Earth, Ocean, and Atmospheric Sciences, Oregon State University, Corvallis, Oregon 97331, USA. ; Scripps Institution of Oceanography, University of California, San Diego, California 92037, USA. ; Climate and Environmental Physics, Physics Institute, and Oeschger Centre for Climate Change Research, University of Bern, 3012 Bern, Switzerland. ; Department of Earth and Environmental Sciences, University of Rochester, Rochester, New York 14627, USA. ; National Institute of Water and Atmospheric Research, Wellington 6021, New Zealand.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25503236" target="_blank"〉PubMed〈/a〉
    Keywords: Antarctic Regions ; Aquatic Organisms/*metabolism ; Atmosphere/*chemistry ; Global Warming ; History, Ancient ; *Ice Cover ; Nitrogen Isotopes/analysis ; Nitrous Oxide/analysis/history/*metabolism ; Oxygen Isotopes/analysis ; Rain ; Temperature ; Time Factors
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  • 68
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    Nature Publishing Group (NPG)
    Publication Date: 2010-04-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brown, Terence A -- England -- Nature. 2010 Apr 8;464(7290):838-9. doi: 10.1038/464838a. Epub 2010 Mar 24.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20376137" target="_blank"〉PubMed〈/a〉
    Keywords: Africa/ethnology ; Animals ; DNA, Mitochondrial/*genetics/isolation & purification ; Emigration and Immigration ; Extinction, Biological ; Finger Phalanges ; Genome, Mitochondrial/*genetics ; Hominidae/*classification/*genetics ; Humans ; *Phylogeny ; Siberia ; Time Factors
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  • 69
    Publication Date: 2010-12-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gruebele, Martin -- England -- Nature. 2010 Dec 2;468(7324):640-1. doi: 10.1038/468640a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21124444" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry/metabolism ; Hydrogen Peroxide/chemistry ; Kinetics ; Lasers ; Mass Spectrometry/*methods ; Protein Denaturation ; *Protein Folding ; Protein Refolding ; Temperature ; Thermodynamics ; Time Factors
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  • 70
    Publication Date: 2014-04-18
    Description: Fertilization occurs when sperm and egg recognize each other and fuse to form a new, genetically distinct organism. The molecular basis of sperm-egg recognition is unknown, but is likely to require interactions between receptor proteins displayed on their surface. Izumo1 is an essential sperm cell-surface protein, but its receptor on the egg has not been described. Here we identify folate receptor 4 (Folr4) as the receptor for Izumo1 on the mouse egg, and propose to rename it Juno. We show that the Izumo1-Juno interaction is conserved within several mammalian species, including humans. Female mice lacking Juno are infertile and Juno-deficient eggs do not fuse with normal sperm. Rapid shedding of Juno from the oolemma after fertilization suggests a mechanism for the membrane block to polyspermy, ensuring eggs normally fuse with just a single sperm. Our discovery of an essential receptor pair at the nexus of conception provides opportunities for the rational development of new fertility treatments and contraceptives.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998876/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998876/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bianchi, Enrica -- Doe, Brendan -- Goulding, David -- Wright, Gavin J -- 098051/Wellcome Trust/United Kingdom -- England -- Nature. 2014 Apr 24;508(7497):483-7. doi: 10.1038/nature13203. Epub 2014 Apr 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK. ; Mouse Production Team, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK. ; Electron and Advanced Light Microscopy Suite, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24739963" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Conserved Sequence ; Evolution, Molecular ; Female ; Fertility/genetics ; Fertilization/genetics/*physiology ; Genes, Essential ; Glycosylphosphatidylinositols/metabolism ; Humans ; Immunoglobulins/*metabolism ; Infertility, Female/genetics ; Male ; Mammals ; Membrane Proteins/*metabolism ; Mice ; Oocytes/cytology/metabolism ; Ovum/cytology/*metabolism ; Parthenogenesis ; Receptors, Cell Surface/deficiency/genetics/*metabolism ; Sperm Injections, Intracytoplasmic ; Spermatozoa/*metabolism ; Time Factors
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  • 71
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    Nature Publishing Group (NPG)
    Publication Date: 2010-10-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smoot, George F -- England -- Nature. 2010 Oct 14;467(7317):S12. doi: 10.1038/467S12a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20944612" target="_blank"〉PubMed〈/a〉
    Keywords: Biology/methods/trends ; *Elementary Particles ; Interdisciplinary Communication ; *Nobel Prize ; Physics/trends ; Research/organization & administration ; *Research Personnel/psychology/standards ; Time Factors
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  • 72
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    Nature Publishing Group (NPG)
    Publication Date: 2010-02-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Feb 4;463(7281):587. doi: 10.1038/463587a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20130607" target="_blank"〉PubMed〈/a〉
    Keywords: Epigenesis, Genetic/*genetics ; Genome, Human/*genetics ; Genomics/*trends ; Humans ; Internationality ; Reference Values ; Time Factors
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  • 73
    Publication Date: 2015-04-23
    Description: The current outbreak of Ebola virus in West Africa is unprecedented, causing more cases and fatalities than all previous outbreaks combined, and has yet to be controlled. Several post-exposure interventions have been employed under compassionate use to treat patients repatriated to Europe and the United States. However, the in vivo efficacy of these interventions against the new outbreak strain of Ebola virus is unknown. Here we show that lipid-nanoparticle-encapsulated short interfering RNAs (siRNAs) rapidly adapted to target the Makona outbreak strain of Ebola virus are able to protect 100% of rhesus monkeys against lethal challenge when treatment was initiated at 3 days after exposure while animals were viraemic and clinically ill. Although all infected animals showed evidence of advanced disease including abnormal haematology, blood chemistry and coagulopathy, siRNA-treated animals had milder clinical features and fully recovered, while the untreated control animals succumbed to the disease. These results represent the first, to our knowledge, successful demonstration of therapeutic anti-Ebola virus efficacy against the new outbreak strain in nonhuman primates and highlight the rapid development of lipid-nanoparticle-delivered siRNA as a countermeasure against this highly lethal human disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467030/" 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/PMC4467030/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thi, Emily P -- Mire, Chad E -- Lee, Amy C H -- Geisbert, Joan B -- Zhou, Joy Z -- Agans, Krystle N -- Snead, Nicholas M -- Deer, Daniel J -- Barnard, Trisha R -- Fenton, Karla A -- MacLachlan, Ian -- Geisbert, Thomas W -- U19 AI109711/AI/NIAID NIH HHS/ -- U19AI109711/AI/NIAID NIH HHS/ -- England -- Nature. 2015 May 21;521(7552):362-5. doi: 10.1038/nature14442. Epub 2015 Apr 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Tekmira Pharmaceuticals, Burnaby, British Columbia V5J 5J8, Canada. ; 1] Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas 77550, USA [2] Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 77550, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25901685" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Disease Models, Animal ; Ebolavirus/classification/*drug effects/*genetics ; Female ; Hemorrhagic Fever, Ebola/pathology/prevention & control/*therapy/*virology ; Humans ; Macaca mulatta/virology ; Male ; Nanoparticles/*administration & dosage ; RNA, Small Interfering/*administration & dosage/pharmacology/*therapeutic use ; Survival Analysis ; Time Factors ; Treatment Outcome ; Viral Load/drug effects
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  • 74
    Publication Date: 2010-10-12
    Description: The dynamic behaviour of myosin V molecules translocating along actin filaments has been mainly studied by optical microscopy. The processive hand-over-hand movement coupled with hydrolysis of adenosine triphosphate was thereby demonstrated. However, the protein molecules themselves are invisible in the observations and have therefore been visualized by electron microscopy in the stationary states. The concomitant assessment of structure and dynamics has been unfeasible, a situation prevailing throughout biological research. Here we directly visualize myosin V molecules walking along actin tracks, using high-speed atomic force microscopy. The high-resolution movies not only provide corroborative 'visual evidence' for previously speculated or demonstrated molecular behaviours, including lever-arm swing, but also reveal more detailed behaviours of the molecules, leading to a comprehensive understanding of the motor mechanism. Our direct and dynamic high-resolution visualization is a powerful new approach to studying the structure and dynamics of biomolecules in action.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kodera, Noriyuki -- Yamamoto, Daisuke -- Ishikawa, Ryoki -- Ando, Toshio -- England -- Nature. 2010 Nov 4;468(7320):72-6. doi: 10.1038/nature09450. Epub 2010 Oct 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20935627" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/chemistry/metabolism/ultrastructure ; Adenosine Diphosphate/metabolism ; Adenosine Triphosphate/metabolism ; Animals ; Biotinylation ; Chickens ; Immobilized Proteins/chemistry/metabolism/ultrastructure ; Microscopy, Atomic Force/*methods ; *Movement ; Myosin Type V/chemistry/*metabolism/*ultrastructure ; Protein Conformation ; Protein Unfolding ; Time Factors ; *Video Recording
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  • 75
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    Nature Publishing Group (NPG)
    Publication Date: 2015-11-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Geddes, Linda -- England -- Nature. 2015 Nov 5;527(7576):22-5. doi: 10.1038/527022a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26536940" target="_blank"〉PubMed〈/a〉
    Keywords: Attention Deficit Disorder with ; Hyperactivity/diagnosis/physiopathology/psychology ; Autism Spectrum Disorder/diagnosis/physiopathology/psychology ; Brain/blood supply/*growth & development/*physiology ; *Child Development ; Child, Preschool ; Electroencephalography ; Electromyography ; Eye Movements/physiology ; Female ; Humans ; Infant ; Infant Behavior/*physiology/*psychology ; *Laboratories ; London ; Magnetic Resonance Imaging ; Male ; Mirror Neurons ; Neuroimaging ; Personality ; Spectroscopy, Near-Infrared ; Time Factors
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  • 76
    Publication Date: 2010-03-12
    Description: Measures to prevent sexual mucosal transmission of human immunodeficiency virus (HIV)-1 are urgently needed to curb the growth of the acquired immunodeficiency syndrome (AIDS) pandemic and ultimately bring it to an end. Studies in animal models and acute HIV-1 infection reviewed here reveal potential viral vulnerabilities at the mucosal portal of entry in the earliest stages of infection that might be most effectively targeted by vaccines and microbicides, thereby preventing acquisition and averting systemic infection, CD4 T-cell depletion and pathologies that otherwise rapidly ensue.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haase, Ashley T -- AI 38565/AI/NIAID NIH HHS/ -- AI 48484/AI/NIAID NIH HHS/ -- AI 71976/AI/NIAID NIH HHS/ -- England -- Nature. 2010 Mar 11;464(7286):217-23. doi: 10.1038/nature08757.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, University of Minnesota, Minnesota 55455, USA. haase001@umn.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20220840" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/*immunology/*prevention & control/transmission ; Animals ; Disease Models, Animal ; HIV-1/*immunology ; Humans ; Immunity, Mucosal ; Mucous Membrane/*immunology/virology ; Simian Acquired Immunodeficiency Syndrome/immunology/transmission ; Simian Immunodeficiency Virus/immunology ; Time Factors
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  • 77
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    Nature Publishing Group (NPG)
    Publication Date: 2015-05-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2015 May 28;521(7553):394. doi: 10.1038/521394a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26017406" target="_blank"〉PubMed〈/a〉
    Keywords: *Bibliometrics/history ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Research/*history ; Time Factors
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  • 78
    Publication Date: 2015-10-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉de Oliveira, Joao Ricardo Mendes -- England -- Nature. 2015 Oct 22;526(7574):506. doi: 10.1038/526506e.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Federal University of Pernambuco, Recife, Brazil.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26490608" target="_blank"〉PubMed〈/a〉
    Keywords: Brazil ; Financing, Organized/*economics/*organization & administration ; Research Personnel/*economics ; Research Support as Topic/*economics/*organization & administration ; Time Factors
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  • 79
    Publication Date: 2015-05-29
    Description: Robots have transformed many industries, most notably manufacturing, and have the power to deliver tremendous benefits to society, such as in search and rescue, disaster response, health care and transportation. They are also invaluable tools for scientific exploration in environments inaccessible to humans, from distant planets to deep oceans. A major obstacle to their widespread adoption in more complex environments outside factories is their fragility. Whereas animals can quickly adapt to injuries, current robots cannot 'think outside the box' to find a compensatory behaviour when they are damaged: they are limited to their pre-specified self-sensing abilities, can diagnose only anticipated failure modes, and require a pre-programmed contingency plan for every type of potential damage, an impracticality for complex robots. A promising approach to reducing robot fragility involves having robots learn appropriate behaviours in response to damage, but current techniques are slow even with small, constrained search spaces. Here we introduce an intelligent trial-and-error algorithm that allows robots to adapt to damage in less than two minutes in large search spaces without requiring self-diagnosis or pre-specified contingency plans. Before the robot is deployed, it uses a novel technique to create a detailed map of the space of high-performing behaviours. This map represents the robot's prior knowledge about what behaviours it can perform and their value. When the robot is damaged, it uses this prior knowledge to guide a trial-and-error learning algorithm that conducts intelligent experiments to rapidly discover a behaviour that compensates for the damage. Experiments reveal successful adaptations for a legged robot injured in five different ways, including damaged, broken, and missing legs, and for a robotic arm with joints broken in 14 different ways. This new algorithm will enable more robust, effective, autonomous robots, and may shed light on the principles that animals use to adapt to injury.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cully, Antoine -- Clune, Jeff -- Tarapore, Danesh -- Mouret, Jean-Baptiste -- England -- Nature. 2015 May 28;521(7553):503-7. doi: 10.1038/nature14422.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Sorbonne Universites, Universite Pierre et Marie Curie (UPMC), Paris 06, UMR 7222, Institut des Systemes Intelligents et de Robotique (ISIR), F-75005, Paris, France [2] CNRS, UMR 7222, Institut des Systemes Intelligents et de Robotique (ISIR), F-75005, Paris, France. ; Department of Computer Science, University of Wyoming, Laramie, Wyoming 82071, USA. ; 1] Sorbonne Universites, Universite Pierre et Marie Curie (UPMC), Paris 06, UMR 7222, Institut des Systemes Intelligents et de Robotique (ISIR), F-75005, Paris, France [2] CNRS, UMR 7222, Institut des Systemes Intelligents et de Robotique (ISIR), F-75005, Paris, France [3] Inria, Team Larsen, Villers-les-Nancy, F-54600, France [4] CNRS, Loria, UMR 7503, Vandoeuvre-les-Nancy, F-54500, France [5] Universite de Lorraine, Loria, UMR 7503, Vandoeuvre-les-Nancy, F-54500, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26017452" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptation, Physiological ; Algorithms ; Animals ; *Artificial Intelligence ; Behavior, Animal ; Biomimetics/*methods ; Dogs ; Extremities/*injuries/physiopathology ; Motor Skills ; Robotics/*instrumentation/*methods ; Time Factors
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  • 80
    Publication Date: 2015-09-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tollefson, Jeff -- England -- Nature. 2015 Sep 24;525(7570):434-5. doi: 10.1038/525434a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26399805" target="_blank"〉PubMed〈/a〉
    Keywords: Conservation of Natural Resources/legislation & jurisprudence/*trends ; *Goals ; Humans ; *International Cooperation ; Poverty/legislation & jurisprudence/*prevention & control/trends ; Time Factors ; *United Nations/legislation & jurisprudence
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  • 81
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    Nature Publishing Group (NPG)
    Publication Date: 2015-03-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jones, Dan -- England -- Nature. 2015 Mar 12;519(7542):148-50. doi: 10.1038/519148a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25762265" target="_blank"〉PubMed〈/a〉
    Keywords: *Computer Simulation ; *Conflict (Psychology) ; Feedback ; Humans ; Mathematics ; *Models, Theoretical ; Negotiating/psychology ; Psychology, Social/*methods ; *Research ; Time Factors ; Violence/prevention & control ; *Warfare
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  • 82
    Publication Date: 2014-12-18
    Description: Endocytosis is required for internalization of micronutrients and turnover of membrane components. Endophilin has been assigned as a component of clathrin-mediated endocytosis. Here we show in mammalian cells that endophilin marks and controls a fast-acting tubulovesicular endocytic pathway that is independent of AP2 and clathrin, activated upon ligand binding to cargo receptors, inhibited by inhibitors of dynamin, Rac, phosphatidylinositol-3-OH kinase, PAK1 and actin polymerization, and activated upon Cdc42 inhibition. This pathway is prominent at the leading edges of cells where phosphatidylinositol-3,4-bisphosphate-produced by the dephosphorylation of phosphatidylinositol-3,4,5-triphosphate by SHIP1 and SHIP2-recruits lamellipodin, which in turn engages endophilin. This pathway mediates the ligand-triggered uptake of several G-protein-coupled receptors such as alpha2a- and beta1-adrenergic, dopaminergic D3 and D4 receptors and muscarinic acetylcholine receptor 4, the receptor tyrosine kinases EGFR, HGFR, VEGFR, PDGFR, NGFR and IGF1R, as well as interleukin-2 receptor. We call this new endocytic route fast endophilin-mediated endocytosis (FEME).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boucrot, Emmanuel -- Ferreira, Antonio P A -- Almeida-Souza, Leonardo -- Debard, Sylvain -- Vallis, Yvonne -- Howard, Gillian -- Bertot, Laetitia -- Sauvonnet, Nathalie -- McMahon, Harvey T -- U105178805/Medical Research Council/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- England -- Nature. 2015 Jan 22;517(7535):460-5. doi: 10.1038/nature14067. Epub 2014 Dec 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK [2] Institute of Structural and Molecular Biology, University College London &Birkbeck College, London WC1E 6BT, UK. ; Institute of Structural and Molecular Biology, University College London &Birkbeck College, London WC1E 6BT, UK. ; MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. ; 1] Institute of Structural and Molecular Biology, University College London &Birkbeck College, London WC1E 6BT, UK [2] Department of Biology, Ecole Normale Superieure de Cachan, 94235 Cachan, France. ; Institut Pasteur, Unite de Pathogenie Moleculaire Microbienne, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25517094" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/metabolism ; Acyltransferases/*metabolism ; Cell Line ; Clathrin ; Dynamins/metabolism ; *Endocytosis ; Humans ; Ligands ; Phosphatidylinositol Phosphates/metabolism ; Pseudopodia/metabolism ; Receptor Protein-Tyrosine Kinases/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Receptors, Interleukin-2/metabolism ; Signal Transduction ; Time Factors
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  • 83
    Publication Date: 2015-04-10
    Description: Continuing degradation of coral reef ecosystems has generated substantial interest in how management can support reef resilience. Fishing is the primary source of diminished reef function globally, leading to widespread calls for additional marine reserves to recover fish biomass and restore key ecosystem functions. Yet there are no established baselines for determining when these conservation objectives have been met or whether alternative management strategies provide similar ecosystem benefits. Here we establish empirical conservation benchmarks and fish biomass recovery timelines against which coral reefs can be assessed and managed by studying the recovery potential of more than 800 coral reefs along an exploitation gradient. We show that resident reef fish biomass in the absence of fishing (B0) averages approximately 1,000 kg ha(-1), and that the vast majority (83%) of fished reefs are missing more than half their expected biomass, with severe consequences for key ecosystem functions such as predation. Given protection from fishing, reef fish biomass has the potential to recover within 35 years on average and less than 60 years when heavily depleted. Notably, alternative fisheries restrictions are largely (64%) successful at maintaining biomass above 50% of B0, sustaining key functions such as herbivory. Our results demonstrate that crucial ecosystem functions can be maintained through a range of fisheries restrictions, allowing coral reef managers to develop recovery plans that meet conservation and livelihood objectives in areas where marine reserves are not socially or politically feasible solutions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉MacNeil, M Aaron -- Graham, Nicholas A J -- Cinner, Joshua E -- Wilson, Shaun K -- Williams, Ivor D -- Maina, Joseph -- Newman, Steven -- Friedlander, Alan M -- Jupiter, Stacy -- Polunin, Nicholas V C -- McClanahan, Tim R -- England -- Nature. 2015 Apr 16;520(7547):341-4. doi: 10.1038/nature14358. Epub 2015 Apr 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Australian Institute of Marine Science, PMB 3 Townsville MC, Townsville, Queensland 4810, Australia [2] Department of Mathematics and Statistics, Dalhousie University, Halifax, Nova Scotia B3H 3J5, Canada [3] Australian Research Council Centre of Excellence for Coral Reef Studies, James Cook University, Townsville, Queensland 4811, Australia. ; Australian Research Council Centre of Excellence for Coral Reef Studies, James Cook University, Townsville, Queensland 4811, Australia. ; 1] Department of Parks and Wildlife, Kensington, Perth, Western Australia 6151, Australia [2] Oceans Institute, University of Western Australia, Crawley, Western Australia 6009, Australia. ; Coral Reef Ecosystems Division, NOAA Pacific Islands Fisheries Science Center, Honolulu, Hawaii 96818, USA. ; 1] Australian Research Council Centre of Excellence for Environmental Decisions (CEED), University of Queensland, Brisbane, St Lucia, Queensland 4074, Australia [2] Wildlife Conservation Society, Marine Programs, Bronx, New York 10460, USA. ; School of Marine Science and Technology, Newcastle University, Newcastle upon Tyne NE1 7RU, UK. ; 1] Fisheries Ecology Research Lab, Department of Biology, University of Hawaii, Honolulu, Hawaii 96822, USA [2] Pristine Seas-National Geographic, Washington DC 20036, USA. ; Wildlife Conservation Society, Marine Programs, Bronx, New York 10460, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25855298" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biodiversity ; Biomass ; Conservation of Natural Resources/*methods/statistics & numerical data/*trends ; *Coral Reefs ; *Ecosystem ; Fisheries/*methods/standards/*statistics & numerical data ; Fishes/*physiology ; Herbivory ; Population Dynamics ; Predatory Behavior ; Time Factors
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  • 84
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    Nature Publishing Group (NPG)
    Publication Date: 2015-01-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gong, Zhaohui -- England -- Nature. 2015 Jan 8;517(7533):145. doi: 10.1038/517145c.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ningbo University School of Medicine, Ningbo, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25567273" target="_blank"〉PubMed〈/a〉
    Keywords: Air Pollution/adverse effects/*prevention & control ; China ; Climate Change ; Congresses as Topic ; Humans ; Public Health ; Time Factors
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  • 85
    Publication Date: 2015-09-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Hong -- Thompson, Julian R -- Flower, Roger J -- England -- Nature. 2015 Sep 24;525(7570):455. doi: 10.1038/525455e.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Oslo, Norway. ; University College London, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26399818" target="_blank"〉PubMed〈/a〉
    Keywords: China ; Electric Power Supplies/utilization ; Rain ; *Seasons ; Snow ; *Snow Sports/economics ; Time Factors ; Water Supply/economics/*statistics & numerical data
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  • 86
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    Nature Publishing Group (NPG)
    Publication Date: 2015-12-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gould, Julie -- England -- Nature. 2015 Dec 3;528(7580):22-5. doi: 10.1038/528022a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26632571" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/education/manpower ; Career Choice ; *Career Mobility ; Education, Graduate/methods/*statistics & numerical data/*trends ; Employment/*statistics & numerical data ; Engineering/education/manpower ; Research Personnel/*education/*statistics & numerical data ; Time Factors
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  • 87
    Publication Date: 2015-10-28
    Description: Growing evidence demonstrates that climatic conditions can have a profound impact on the functioning of modern human societies, but effects on economic activity appear inconsistent. Fundamental productive elements of modern economies, such as workers and crops, exhibit highly non-linear responses to local temperature even in wealthy countries. In contrast, aggregate macroeconomic productivity of entire wealthy countries is reported not to respond to temperature, while poor countries respond only linearly. Resolving this conflict between micro and macro observations is critical to understanding the role of wealth in coupled human-natural systems and to anticipating the global impact of climate change. Here we unify these seemingly contradictory results by accounting for non-linearity at the macro scale. We show that overall economic productivity is non-linear in temperature for all countries, with productivity peaking at an annual average temperature of 13 degrees C and declining strongly at higher temperatures. The relationship is globally generalizable, unchanged since 1960, and apparent for agricultural and non-agricultural activity in both rich and poor countries. These results provide the first evidence that economic activity in all regions is coupled to the global climate and establish a new empirical foundation for modelling economic loss in response to climate change, with important implications. If future adaptation mimics past adaptation, unmitigated warming is expected to reshape the global economy by reducing average global incomes roughly 23% by 2100 and widening global income inequality, relative to scenarios without climate change. In contrast to prior estimates, expected global losses are approximately linear in global mean temperature, with median losses many times larger than leading models indicate.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burke, Marshall -- Hsiang, Solomon M -- Miguel, Edward -- England -- Nature. 2015 Nov 12;527(7577):235-9. doi: 10.1038/nature15725. Epub 2015 Oct 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Earth System Science, Stanford University, California 94305, USA. ; Center on Food Security and the Environment, Stanford University, California 94305, USA. ; Goldman School of Public Policy, University of California, Berkeley, California 94720, USA. ; National Bureau of Economic Research. ; Department of Economics, University of California, Berkeley, California, 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26503051" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/economics/statistics & numerical data ; *Climate ; Developed Countries/economics ; Developing Countries/economics ; Efficiency ; Global Warming/*economics ; Income/statistics & numerical data/trends ; *Internationality ; *Models, Economic ; *Nonlinear Dynamics ; *Temperature ; Time Factors
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  • 88
    Publication Date: 2015-04-02
    Description: The cave infills at Sterkfontein contain one of the richest assemblages of Australopithecus fossils in the world, including the nearly complete skeleton StW 573 ('Little Foot') in its lower section, as well as early stone tools in higher sections. However, the chronology of the site remains controversial owing to the complex history of cave infilling. Much of the existing chronology based on uranium-lead dating and palaeomagnetic stratigraphy has recently been called into question by the recognition that dated flowstones fill cavities formed within previously cemented breccias and therefore do not form a stratigraphic sequence. Earlier dating with cosmogenic nuclides suffered a high degree of uncertainty and has been questioned on grounds of sediment reworking. Here we use isochron burial dating with cosmogenic aluminium-26 and beryllium-10 to show that the breccia containing StW 573 did not undergo significant reworking, and that it was deposited 3.67 +/- 0.16 million years ago, far earlier than the 2.2 million year flowstones found within it. The skeleton is thus coeval with early Australopithecus afarensis in eastern Africa. We also date the earliest stone tools at Sterkfontein to 2.18 +/- 0.21 million years ago, placing them in the Oldowan at a time similar to that found elsewhere in South Africa at Swartkans and Wonderwerk.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Granger, Darryl E -- Gibbon, Ryan J -- Kuman, Kathleen -- Clarke, Ronald J -- Bruxelles, Laurent -- Caffee, Marc W -- England -- Nature. 2015 Jun 4;522(7554):85-8. doi: 10.1038/nature14268. Epub 2015 Apr 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Earth, Atmospheric, and Planetary Sciences, Purdue University, West Lafayette, Indiana 47907, USA. ; Department of Anthropology, University of New Brunswick, Fredericton, New Brunswick E3B 5A3, Canada. ; 1] Evolutionary Studies Institute, University of the Witwatersrand, WITS 2050, Johannesburg, South Africa [2] School of Geography, Archaeology and Environmental Studies, University of the Witwatersrand, WITS 2050, Johannesburg, South Africa. ; Evolutionary Studies Institute, University of the Witwatersrand, WITS 2050, Johannesburg, South Africa. ; 1] School of Geography, Archaeology and Environmental Studies, University of the Witwatersrand, WITS 2050, Johannesburg, South Africa [2] French National Institute for Preventive Archaeological Research (Inrap), 561 rue Etienne Lenoir, km delta, 30900 Nimes, France [3] University of Toulouse Jean Jaures, UMR 5608 du CNRS (TRACES), Maison de la Recherche, 5 Allees Antonio Matchado, F-31058 Toulouse, France. ; 1] Department of Earth, Atmospheric, and Planetary Sciences, Purdue University, West Lafayette, Indiana 47907, USA [2] Department of Physics and Astronomy, Purdue University, West Lafayette, Indiana 47907, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25830884" target="_blank"〉PubMed〈/a〉
    Keywords: Africa, Eastern ; Aluminum ; Animals ; Beryllium ; Burial ; *Fossils ; Geologic Sediments/analysis/chemistry ; *Hominidae/anatomy & histology/classification ; Paleontology/*methods ; Radioisotopes ; Radiometric Dating/*methods ; *Skeleton ; Skull/anatomy & histology ; South Africa ; Time Factors ; Tool Use Behavior
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  • 89
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    Nature Publishing Group (NPG)
    Publication Date: 2015-05-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2015 May 21;521(7552):269. doi: 10.1038/nature.2015.17560.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25993935" target="_blank"〉PubMed〈/a〉
    Keywords: Bangladesh ; Ethiopia ; Evaluation Studies as Topic ; Humans ; *International Cooperation ; Pilot Projects ; Poverty/*economics/*prevention & control/statistics & numerical data/trends ; Program Evaluation ; Random Allocation ; Time Factors
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  • 90
    Publication Date: 2015-01-30
    Description: Most present-generation climate models simulate an increase in global-mean surface temperature (GMST) since 1998, whereas observations suggest a warming hiatus. It is unclear to what extent this mismatch is caused by incorrect model forcing, by incorrect model response to forcing or by random factors. Here we analyse simulations and observations of GMST from 1900 to 2012, and show that the distribution of simulated 15-year trends shows no systematic bias against the observations. Using a multiple regression approach that is physically motivated by surface energy balance, we isolate the impact of radiative forcing, climate feedback and ocean heat uptake on GMST--with the regression residual interpreted as internal variability--and assess all possible 15- and 62-year trends. The differences between simulated and observed trends are dominated by random internal variability over the shorter timescale and by variations in the radiative forcings used to drive models over the longer timescale. For either trend length, spread in simulated climate feedback leaves no traceable imprint on GMST trends or, consequently, on the difference between simulations and observations. The claim that climate models systematically overestimate the response to radiative forcing from increasing greenhouse gas concentrations therefore seems to be unfounded.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marotzke, Jochem -- Forster, Piers M -- England -- Nature. 2015 Jan 29;517(7536):565-70. doi: 10.1038/nature14117.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute for Meteorology, Bundesstrasse 53, 20146 Hamburg, Germany. ; School of Earth and Environment, University of Leeds, Leeds LS2 9JT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25631444" target="_blank"〉PubMed〈/a〉
    Keywords: Bias (Epidemiology) ; *Feedback ; Global Warming/history/*statistics & numerical data ; History, 20th Century ; History, 21st Century ; *Models, Theoretical ; Multivariate Analysis ; Regression Analysis ; Reproducibility of Results ; *Temperature ; Time Factors
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  • 91
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    Nature Publishing Group (NPG)
    Publication Date: 2015-01-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2015 Jan 1;517(7532):5. doi: 10.1038/517005a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25557694" target="_blank"〉PubMed〈/a〉
    Keywords: Natural Science Disciplines ; *Policy Making ; Social Sciences/*trends ; Time Factors
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  • 92
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    Nature Publishing Group (NPG)
    Publication Date: 2015-02-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Knight, Rob -- England -- Nature. 2015 Feb 26;518(7540):S5. doi: 10.1038/518S5a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of California, San Diego.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25715279" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Computer Simulation ; Crowdsourcing ; Disease Models, Animal ; Germ-Free Life ; Humans ; Kwashiorkor/etiology/genetics/microbiology/therapy ; Mice ; Microbiota/genetics/*physiology ; Obesity/etiology/*microbiology/*therapy ; Sequence Analysis, DNA ; Thinness/microbiology ; Time Factors
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  • 93
    Publication Date: 2015-01-21
    Description: Appropriate responses to an imminent threat brace us for adversities. The ability to sense and predict threatening or stressful events is essential for such adaptive behaviour. In the mammalian brain, one putative stress sensor is the paraventricular nucleus of the thalamus (PVT), an area that is readily activated by both physical and psychological stressors. However, the role of the PVT in the establishment of adaptive behavioural responses remains unclear. Here we show in mice that the PVT regulates fear processing in the lateral division of the central amygdala (CeL), a structure that orchestrates fear learning and expression. Selective inactivation of CeL-projecting PVT neurons prevented fear conditioning, an effect that can be accounted for by an impairment in fear-conditioning-induced synaptic potentiation onto somatostatin-expressing (SOM(+)) CeL neurons, which has previously been shown to store fear memory. Consistently, we found that PVT neurons preferentially innervate SOM(+) neurons in the CeL, and stimulation of PVT afferents facilitated SOM(+) neuron activity and promoted intra-CeL inhibition, two processes that are critical for fear learning and expression. Notably, PVT modulation of SOM(+) CeL neurons was mediated by activation of the brain-derived neurotrophic factor (BDNF) receptor tropomysin-related kinase B (TrkB). As a result, selective deletion of either Bdnf in the PVT or Trkb in SOM(+) CeL neurons impaired fear conditioning, while infusion of BDNF into the CeL enhanced fear learning and elicited unconditioned fear responses. Our results demonstrate that the PVT-CeL pathway constitutes a novel circuit essential for both the establishment of fear memory and the expression of fear responses, and uncover mechanisms linking stress detection in PVT with the emergence of adaptive behaviour.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376633/" 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/PMC4376633/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Penzo, Mario A -- Robert, Vincent -- Tucciarone, Jason -- De Bundel, Dimitri -- Wang, Minghui -- Van Aelst, Linda -- Darvas, Martin -- Parada, Luis F -- Palmiter, Richard D -- He, Miao -- Huang, Z Josh -- Li, Bo -- R01 MH082808/MH/NIMH NIH HHS/ -- R01 MH094705/MH/NIMH NIH HHS/ -- R01 MH101214/MH/NIMH NIH HHS/ -- R01 NS082266/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Mar 26;519(7544):455-9. doi: 10.1038/nature13978. Epub 2015 Jan 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. ; 1] Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA [2] Ecole Normale Superieure de Cachan, 94230 Cachan, France. ; 1] Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA [2] Medical Scientist Training Program &Program in Neuroscience, Stony Brook University, Stony Brook, New York 11790, USA. ; CNRS, UMR-5203, INSERM U661, Institut de Genomique Fonctionnelle, 34090 Montpellier, France. ; Department of Pathology, University of Washington, Seattle, Washington 98104, USA. ; Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. ; Howard Hughes Medical Institute; Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA. ; Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25600269" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain-Derived Neurotrophic Factor/metabolism ; Central Amygdaloid Nucleus/cytology/*physiology ; Conditioning (Psychology)/physiology ; Fear/*physiology/psychology ; Female ; Male ; Memory/physiology ; Mice ; Neural Pathways/cytology/*physiology ; Neuronal Plasticity ; Neurons/metabolism ; Receptor, trkB/metabolism ; Somatostatin/metabolism ; Thalamus/cytology/*physiology ; Time Factors
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  • 94
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    Publication Date: 2015-04-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marris, Emma -- England -- Nature. 2015 Apr 23;520(7548):415. doi: 10.1038/nature.2015.17263.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25903602" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Deer/*physiology ; *Ecology/methods/trends ; Great Lakes Region ; *Islands ; Population Dynamics ; *Predatory Behavior ; Research/*trends ; Time Factors ; Wolves/*physiology
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  • 95
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    Nature Publishing Group (NPG)
    Publication Date: 2015-12-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Yingying -- England -- Nature. 2015 Dec 17;528(7582):S170-3. doi: 10.1038/528S170a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26673023" target="_blank"〉PubMed〈/a〉
    Keywords: Biological Science Disciplines ; Chemistry ; China ; Diffusion of Innovation ; Ecology ; Economic Recession ; Humans ; International Cooperation ; Nobel Prize ; Physics ; Research/economics/manpower/standards/*statistics & numerical data ; Research Personnel/education/standards/supply & distribution ; Time Factors
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  • 96
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    Publication Date: 2015-03-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dolgin, Elie -- England -- Nature. 2015 Mar 19;519(7543):276-8. doi: 10.1038/519276a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25788077" target="_blank"〉PubMed〈/a〉
    Keywords: Child ; *Darkness ; Humans ; *Lighting ; Myopia/*epidemiology/*etiology/prevention & control ; *Sunlight ; Time Factors
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  • 97
    Publication Date: 2015-01-21
    Description: Fear memories allow animals to avoid danger, thereby increasing their chances of survival. Fear memories can be retrieved long after learning, but little is known about how retrieval circuits change with time. Here we show that the dorsal midline thalamus of rats is required for the retrieval of auditory conditioned fear at late (24 hours, 7 days, 28 days), but not early (0.5 hours, 6 hours) time points after learning. Consistent with this, the paraventricular nucleus of the thalamus (PVT), a subregion of the dorsal midline thalamus, showed increased c-Fos expression only at late time points, indicating that the PVT is gradually recruited for fear retrieval. Accordingly, the conditioned tone responses of PVT neurons increased with time after training. The prelimbic (PL) prefrontal cortex, which is necessary for fear retrieval, sends dense projections to the PVT. Retrieval at late time points activated PL neurons projecting to the PVT, and optogenetic silencing of these projections impaired retrieval at late, but not early, time points. In contrast, silencing of PL inputs to the basolateral amygdala impaired retrieval at early, but not late, time points, indicating a time-dependent shift in retrieval circuits. Retrieval at late time points also activated PVT neurons projecting to the central nucleus of the amygdala, and silencing these projections at late, but not early, time points induced a persistent attenuation of fear. Thus, the PVT may act as a crucial thalamic node recruited into cortico-amygdalar networks for retrieval and maintenance of long-term fear memories.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376623/" 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/PMC4376623/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Do-Monte, Fabricio H -- Quinones-Laracuente, Kelvin -- Quirk, Gregory J -- G12 MD007600/MD/NIMHD NIH HHS/ -- K99 MH105549/MH/NIMH NIH HHS/ -- P50 MH086400/MH/NIMH NIH HHS/ -- P50-MH086400/MH/NIMH NIH HHS/ -- R01-MH058883/MH/NIMH NIH HHS/ -- R25 GM061838/GM/NIGMS NIH HHS/ -- R25-GM061838/GM/NIGMS NIH HHS/ -- R37 MH058883/MH/NIMH NIH HHS/ -- England -- Nature. 2015 Mar 26;519(7544):460-3. doi: 10.1038/nature14030. Epub 2015 Jan 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Psychiatry, University of Puerto Rico School of Medicine, PO Box 365067, San Juan 00936, Puerto Rico [2] Department of Anatomy &Neurobiology, University of Puerto Rico School of Medicine, P.O. Box 365067, San Juan 00936, Puerto Rico.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25600268" target="_blank"〉PubMed〈/a〉
    Keywords: Amygdala/cytology/physiology ; Animals ; Conditioning (Psychology)/physiology ; Fear/*physiology ; Male ; Memory/*physiology ; Neural Pathways/cytology/*physiology ; Neurons/physiology ; Optogenetics ; Prefrontal Cortex/cytology/physiology ; Proto-Oncogene Proteins c-fos/metabolism ; Rats ; Rats, Sprague-Dawley ; Thalamus/cytology/physiology ; Time Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 98
    Publication Date: 2015-04-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Victor, David G -- England -- Nature. 2015 Apr 2;520(7545):27-9. doi: 10.1038/520027a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory on International Law and Regulation, University of California, San Diego, USA. He is also chairman of the Global Agenda Council on Governance for Sustainability at the World Economic Forum.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25832390" target="_blank"〉PubMed〈/a〉
    Keywords: Advisory Committees/*organization & administration ; *Climate Change/statistics & numerical data ; Consensus ; Environmental Policy/legislation & jurisprudence/*trends ; *Policy Making ; Reproducibility of Results ; *Research Report ; Social Sciences/*trends ; Time Factors ; Uncertainty
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 99
    Publication Date: 2015-11-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Victor, David G -- Leape, James P -- England -- Nature. 2015 Nov 26;527(7579):439-41. doi: 10.1038/527439a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26607527" target="_blank"〉PubMed〈/a〉
    Keywords: Brazil ; Carbon Dioxide/analysis/isolation & purification ; *Congresses as Topic ; Conservation of Natural Resources/economics/legislation & jurisprudence/trends ; Developing Countries/economics ; Diplomacy ; Environmental Policy/economics/legislation & jurisprudence/*trends ; Forestry/economics/legislation & jurisprudence/trends ; Global Warming/economics/legislation & jurisprudence/*prevention & control ; Goals ; International Cooperation/*legislation & jurisprudence ; Methane/analysis ; Negotiating ; Optimism ; Paris ; Temperature ; Time Factors ; United Nations/legislation & jurisprudence
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 100
    Publication Date: 2015-02-06
    Description: Theory and climate modelling suggest that the sensitivity of Earth's climate to changes in radiative forcing could depend on the background climate. However, palaeoclimate data have thus far been insufficient to provide a conclusive test of this prediction. Here we present atmospheric carbon dioxide (CO2) reconstructions based on multi-site boron-isotope records from the late Pliocene epoch (3.3 to 2.3 million years ago). We find that Earth's climate sensitivity to CO2-based radiative forcing (Earth system sensitivity) was half as strong during the warm Pliocene as during the cold late Pleistocene epoch (0.8 to 0.01 million years ago). We attribute this difference to the radiative impacts of continental ice-volume changes (the ice-albedo feedback) during the late Pleistocene, because equilibrium climate sensitivity is identical for the two intervals when we account for such impacts using sea-level reconstructions. We conclude that, on a global scale, no unexpected climate feedbacks operated during the warm Pliocene, and that predictions of equilibrium climate sensitivity (excluding long-term ice-albedo feedbacks) for our Pliocene-like future (with CO2 levels up to maximum Pliocene levels of 450 parts per million) are well described by the currently accepted range of an increase of 1.5 K to 4.5 K per doubling of CO2.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Martinez-Boti, M A -- Foster, G L -- Chalk, T B -- Rohling, E J -- Sexton, P F -- Lunt, D J -- Pancost, R D -- Badger, M P S -- Schmidt, D N -- England -- Nature. 2015 Feb 5;518(7537):49-54. doi: 10.1038/nature14145.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ocean and Earth Science, University of Southampton, National Oceanography Centre Southampton, Southampton, SO14 3ZH, UK. ; 1] Ocean and Earth Science, University of Southampton, National Oceanography Centre Southampton, Southampton, SO14 3ZH, UK [2] Research School of Earth Sciences, The Australian National University, Canberra, Australian Capital Territory 2601, Australia. ; Centre for Earth, Planetary, Space and Astronomical Research, The Open University, Milton Keynes, MK7 6AA, UK. ; 1] School of Geographical Sciences, University of Bristol, University Road, Bristol, BS8 1SS, UK [2] The Cabot Institute, University of Bristol, Bristol BS8 1UJ, UK. ; 1] The Cabot Institute, University of Bristol, Bristol BS8 1UJ, UK [2] Organic Geochemistry Unit, School of Chemistry, University of Bristol, Bristol BS8 1TS, UK. ; 1] The Cabot Institute, University of Bristol, Bristol BS8 1UJ, UK [2] School of Earth Sciences, University of Bristol, Wills Memorial Building, Bristol, BS8 1RJ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25652996" target="_blank"〉PubMed〈/a〉
    Keywords: Atmosphere/chemistry ; Boron/analysis/chemistry ; Carbon Dioxide/*analysis ; *Climate ; *Feedback ; Foraminifera/metabolism ; Geologic Sediments/chemistry ; History, Ancient ; Hydrogen-Ion Concentration ; Ice Cover ; Oceans and Seas ; Oxygen Isotopes ; Temperature ; Time Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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