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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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  • 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
    Publication Date: 2010-03-09
    Description: In the ovules of most sexual flowering plants female gametogenesis is initiated from a single surviving gametic cell, the functional megaspore, formed after meiosis of the somatically derived megaspore mother cell (MMC). Because some mutants and certain sexual species exhibit more than one MMC, and many others are able to form gametes without meiosis (by apomixis), it has been suggested that somatic cells in the ovule are competent to respond to a local signal likely to have an important function in determination. Here we show that the Arabidopsis protein ARGONAUTE 9 (AGO9) controls female gamete formation by restricting the specification of gametophyte precursors in a dosage-dependent, non-cell-autonomous manner. Mutations in AGO9 lead to the differentiation of multiple gametic cells that are able to initiate gametogenesis. The AGO9 protein is not expressed in the gamete lineage; instead, it is expressed in cytoplasmic foci of somatic companion cells. Mutations in SUPPRESSOR OF GENE SILENCING 3 and RNA-DEPENDENT RNA POLYMERASE 6 exhibit an identical defect to ago9 mutants, indicating that the movement of small RNA (sRNAs) silencing out of somatic companion cells is necessary for controlling the specification of gametic cells. AGO9 preferentially interacts with 24-nucleotide sRNAs derived from transposable elements (TEs), and its activity is necessary to silence TEs in female gametes and their accessory cells. Our results show that AGO9-dependent sRNA silencing is crucial to specify cell fate in the Arabidopsis ovule, and that epigenetic reprogramming in companion cells is necessary for sRNA-dependent silencing in plant gametes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613780/" 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/PMC4613780/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Olmedo-Monfil, Vianey -- Duran-Figueroa, Noe -- Arteaga-Vazquez, Mario -- Demesa-Arevalo, Edgar -- Autran, Daphne -- Grimanelli, Daniel -- Slotkin, R Keith -- Martienssen, Robert A -- Vielle-Calzada, Jean-Philippe -- R01 GM067014/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Mar 25;464(7288):628-32. doi: 10.1038/nature08828. Epub 2010 Mar 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Grupo de Desarrollo Reproductivo y Apomixis, Laboratorio Nacional de Genomica para la Biodiversidad y Departamento de Ingenieria Genetica de Plantas, Cinvestav Irapuato CP36500 Guanajuato, Mexico.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20208518" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/genetics/growth & development/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Argonaute Proteins ; DNA Transposable Elements/genetics ; Gametogenesis, Plant/*physiology ; Gene Expression Regulation, Plant ; Gene Silencing ; Meiosis ; Molecular Sequence Data ; Mutagenesis, Insertional/genetics ; Ovule/growth & development/*metabolism ; Phenotype ; RNA, Plant/*metabolism ; RNA-Binding Proteins/genetics/*metabolism
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  • 4
    Publication Date: 2010-02-19
    Description: E1 enzymes activate ubiquitin (Ub) and ubiquitin-like (Ubl) proteins in two steps by carboxy-terminal adenylation and thioester bond formation to a conserved catalytic cysteine in the E1 Cys domain. The structural basis for these intermediates remains unknown. Here we report crystal structures for human SUMO E1 in complex with SUMO adenylate and tetrahedral intermediate analogues at 2.45 and 2.6 A, respectively. These structures show that side chain contacts to ATP.Mg are released after adenylation to facilitate a 130 degree rotation of the Cys domain during thioester bond formation that is accompanied by remodelling of key structural elements including the helix that contains the E1 catalytic cysteine, the crossover and re-entry loops, and refolding of two helices that are required for adenylation. These changes displace side chains required for adenylation with side chains required for thioester bond formation. Mutational and biochemical analyses indicate these mechanisms are conserved in other E1s.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866016/" 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/PMC2866016/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Olsen, Shaun K -- Capili, Allan D -- Lu, Xuequan -- Tan, Derek S -- Lima, Christopher D -- F32 GM075695/GM/NIGMS NIH HHS/ -- F32 GM075695-03/GM/NIGMS NIH HHS/ -- R01 AI068038/AI/NIAID NIH HHS/ -- R01 AI068038-02/AI/NIAID NIH HHS/ -- R01 AI068038-03/AI/NIAID NIH HHS/ -- R01 GM065872/GM/NIGMS NIH HHS/ -- R01 GM065872-09/GM/NIGMS NIH HHS/ -- RR-15301/RR/NCRR NIH HHS/ -- England -- Nature. 2010 Feb 18;463(7283):906-12. doi: 10.1038/nature08765.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Biology, Sloan-Kettering Institute, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20164921" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Amino Acid Sequence ; *Biocatalysis ; Catalytic Domain/*physiology ; Conserved Sequence ; Crystallography, X-Ray ; Cysteine/chemistry/metabolism ; Humans ; Magnesium/metabolism ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; SUMO-1 Protein/*chemistry/*metabolism ; Saccharomyces cerevisiae ; Saccharomyces cerevisiae Proteins/metabolism ; Small Ubiquitin-Related Modifier Proteins/metabolism ; Sulfides/*metabolism ; Ubiquitin/metabolism ; Ubiquitin-Activating Enzymes/*chemistry/*metabolism ; Ubiquitins/metabolism
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  • 5
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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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  • 6
    Publication Date: 2010-05-21
    Description: Type II topoisomerases are required for the management of DNA tangles and supercoils, and are targets of clinical antibiotics and anti-cancer agents. These enzymes catalyse the ATP-dependent passage of one DNA duplex (the transport or T-segment) through a transient, double-stranded break in another (the gate or G-segment), navigating DNA through the protein using a set of dissociable internal interfaces, or 'gates'. For more than 20 years, it has been established that a pair of dimer-related tyrosines, together with divalent cations, catalyse G-segment cleavage. Recent efforts have proposed that strand scission relies on a 'two-metal mechanism', a ubiquitous biochemical strategy that supports vital cellular processes ranging from DNA synthesis to RNA self-splicing. Here we present the structure of the DNA-binding and cleavage core of Saccharomyces cerevisiae topoisomerase II covalently linked to DNA through its active-site tyrosine at 2.5A resolution, revealing for the first time the organization of a cleavage-competent type II topoisomerase configuration. Unexpectedly, metal-soaking experiments indicate that cleavage is catalysed by a novel variation of the classic two-metal approach. Comparative analyses extend this scheme to explain how distantly-related type IA topoisomerases cleave single-stranded DNA, unifying the cleavage mechanisms for these two essential enzyme families. The structure also highlights a hitherto undiscovered allosteric relay that actuates a molecular 'trapdoor' to prevent subunit dissociation during cleavage. This connection illustrates how an indispensable chromosome-disentangling machine auto-regulates DNA breakage to prevent the aberrant formation of mutagenic and cytotoxic genomic lesions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882514/" 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/PMC2882514/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schmidt, Bryan H -- Burgin, Alex B -- Deweese, Joseph E -- Osheroff, Neil -- Berger, James M -- CA077373/CA/NCI NIH HHS/ -- GM033944/GM/NIGMS NIH HHS/ -- GM053960/GM/NIGMS NIH HHS/ -- GM08295/GM/NIGMS NIH HHS/ -- R01 CA077373/CA/NCI NIH HHS/ -- R01 CA077373-11S1/CA/NCI NIH HHS/ -- R01 CA077373-12/CA/NCI NIH HHS/ -- R01 GM033944/GM/NIGMS NIH HHS/ -- T32 CA009592/CA/NCI NIH HHS/ -- T32CA09592/CA/NCI NIH HHS/ -- England -- Nature. 2010 Jun 3;465(7298):641-4. doi: 10.1038/nature08974.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20485342" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Base Sequence ; Catalytic Domain ; Crystallography, X-Ray ; DNA/*chemistry/genetics/*metabolism ; DNA Topoisomerases, Type I/*chemistry/*metabolism ; DNA Topoisomerases, Type II/*chemistry/*metabolism ; Kinetics ; Models, Molecular ; Molecular Sequence Data ; Saccharomyces cerevisiae/*enzymology ; Tyrosine
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  • 7
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    Nature Publishing Group (NPG)
    Publication Date: 2010-07-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Paterlini, Marta -- England -- Nature. 2010 May 27;465(7297):514-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20597184" target="_blank"〉PubMed〈/a〉
    Keywords: Denmark ; Education, Graduate/statistics & numerical data ; Emigration and Immigration/statistics & numerical data ; Foreign Professional Personnel/supply & distribution ; Personnel Selection ; Physics ; Research/economics/education/*manpower/standards
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  • 8
    Publication Date: 2010-02-26
    Description: The Red Queen hypothesis proposes that coevolution of interacting species (such as hosts and parasites) should drive molecular evolution through continual natural selection for adaptation and counter-adaptation. Although the divergence observed at some host-resistance and parasite-infectivity genes is consistent with this, the long time periods typically required to study coevolution have so far prevented any direct empirical test. Here we show, using experimental populations of the bacterium Pseudomonas fluorescens SBW25 and its viral parasite, phage Phi2 (refs 10, 11), that the rate of molecular evolution in the phage was far higher when both bacterium and phage coevolved with each other than when phage evolved against a constant host genotype. Coevolution also resulted in far greater genetic divergence between replicate populations, which was correlated with the range of hosts that coevolved phage were able to infect. Consistent with this, the most rapidly evolving phage genes under coevolution were those involved in host infection. These results demonstrate, at both the genomic and phenotypic level, that antagonistic coevolution is a cause of rapid and divergent evolution, and is likely to be a major driver of evolutionary change within species.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717453/" 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/PMC3717453/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Paterson, Steve -- Vogwill, Tom -- Buckling, Angus -- Benmayor, Rebecca -- Spiers, Andrew J -- Thomson, Nicholas R -- Quail, Mike -- Smith, Frances -- Walker, Danielle -- Libberton, Ben -- Fenton, Andrew -- Hall, Neil -- Brockhurst, Michael A -- 079643/Wellcome Trust/United Kingdom -- 098051/Wellcome Trust/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Mar 11;464(7286):275-8. doi: 10.1038/nature08798. Epub 2010 Feb 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Biological Sciences, Biosciences Building, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20182425" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteriophages/genetics/*physiology ; *Biological Evolution ; *Evolution, Molecular ; Genetic Variation ; Molecular Sequence Data ; Phenotype ; Pseudomonas fluorescens/*genetics/*virology ; Selection, Genetic/genetics
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  • 9
    Publication Date: 2010-09-25
    Description: Plasmodium falciparum is the most prevalent and lethal of the malaria parasites infecting humans, yet the origin and evolutionary history of this important pathogen remain controversial. Here we develop a single-genome amplification strategy to identify and characterize Plasmodium spp. DNA sequences in faecal samples from wild-living apes. Among nearly 3,000 specimens collected from field sites throughout central Africa, we found Plasmodium infection in chimpanzees (Pan troglodytes) and western gorillas (Gorilla gorilla), but not in eastern gorillas (Gorilla beringei) or bonobos (Pan paniscus). Ape plasmodial infections were highly prevalent, widely distributed and almost always made up of mixed parasite species. Analysis of more than 1,100 mitochondrial, apicoplast and nuclear gene sequences from chimpanzees and gorillas revealed that 99% grouped within one of six host-specific lineages representing distinct Plasmodium species within the subgenus Laverania. One of these from western gorillas comprised parasites that were nearly identical to P. falciparum. In phylogenetic analyses of full-length mitochondrial sequences, human P. falciparum formed a monophyletic lineage within the gorilla parasite radiation. These findings indicate that P. falciparum is of gorilla origin and not of chimpanzee, bonobo or ancient human origin.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997044/" 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/PMC2997044/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Weimin -- Li, Yingying -- Learn, Gerald H -- Rudicell, Rebecca S -- Robertson, Joel D -- Keele, Brandon F -- Ndjango, Jean-Bosco N -- Sanz, Crickette M -- Morgan, David B -- Locatelli, Sabrina -- Gonder, Mary K -- Kranzusch, Philip J -- Walsh, Peter D -- Delaporte, Eric -- Mpoudi-Ngole, Eitel -- Georgiev, Alexander V -- Muller, Martin N -- Shaw, George M -- Peeters, Martine -- Sharp, Paul M -- Rayner, Julian C -- Hahn, Beatrice H -- P30 AI 7767/AI/NIAID NIH HHS/ -- P30 AI027767/AI/NIAID NIH HHS/ -- P30 AI027767-21A1/AI/NIAID NIH HHS/ -- R01 AI058715/AI/NIAID NIH HHS/ -- R01 AI058715-06A1/AI/NIAID NIH HHS/ -- R01 AI058715-07/AI/NIAID NIH HHS/ -- R01 AI50529/AI/NIAID NIH HHS/ -- R01 I58715/PHS HHS/ -- R03 AI074778/AI/NIAID NIH HHS/ -- R03 AI074778-02/AI/NIAID NIH HHS/ -- R37 AI050529/AI/NIAID NIH HHS/ -- R37 AI050529-07/AI/NIAID NIH HHS/ -- R37 AI050529-08/AI/NIAID NIH HHS/ -- T32 AI007245/AI/NIAID NIH HHS/ -- T32 AI007245-26/AI/NIAID NIH HHS/ -- T32 GM008111/GM/NIGMS NIH HHS/ -- T32 GM008111-13/GM/NIGMS NIH HHS/ -- U19 AI 067854/AI/NIAID NIH HHS/ -- U19 AI067854/AI/NIAID NIH HHS/ -- U19 AI067854-06/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Sep 23;467(7314):420-5. doi: 10.1038/nature09442.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20864995" target="_blank"〉PubMed〈/a〉
    Keywords: Africa/epidemiology ; Animals ; Animals, Wild/classification/parasitology ; Ape Diseases/epidemiology/*parasitology/transmission ; DNA, Mitochondrial/analysis/genetics ; Evolution, Molecular ; Feces/parasitology ; Genes, Mitochondrial/genetics ; Genetic Variation/genetics ; Genome, Protozoan/genetics ; Gorilla gorilla/classification/*parasitology ; Humans ; Malaria, Falciparum/epidemiology/*parasitology/transmission/*veterinary ; Molecular Sequence Data ; Pan paniscus/parasitology ; Pan troglodytes/parasitology ; Phylogeny ; Plasmodium/classification/genetics/isolation & purification ; Plasmodium falciparum/genetics/*isolation & purification ; Prevalence ; Zoonoses/parasitology/transmission
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  • 10
    Publication Date: 2010-01-16
    Description: Soybean (Glycine max) is one of the most important crop plants for seed protein and oil content, and for its capacity to fix atmospheric nitrogen through symbioses with soil-borne microorganisms. We sequenced the 1.1-gigabase genome by a whole-genome shotgun approach and integrated it with physical and high-density genetic maps to create a chromosome-scale draft sequence assembly. We predict 46,430 protein-coding genes, 70% more than Arabidopsis and similar to the poplar genome which, like soybean, is an ancient polyploid (palaeopolyploid). About 78% of the predicted genes occur in chromosome ends, which comprise less than one-half of the genome but account for nearly all of the genetic recombination. Genome duplications occurred at approximately 59 and 13 million years ago, resulting in a highly duplicated genome with nearly 75% of the genes present in multiple copies. The two duplication events were followed by gene diversification and loss, and numerous chromosome rearrangements. An accurate soybean genome sequence will facilitate the identification of the genetic basis of many soybean traits, and accelerate the creation of improved soybean varieties.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schmutz, Jeremy -- Cannon, Steven B -- Schlueter, Jessica -- Ma, Jianxin -- Mitros, Therese -- Nelson, William -- Hyten, David L -- Song, Qijian -- Thelen, Jay J -- Cheng, Jianlin -- Xu, Dong -- Hellsten, Uffe -- May, Gregory D -- Yu, Yeisoo -- Sakurai, Tetsuya -- Umezawa, Taishi -- Bhattacharyya, Madan K -- Sandhu, Devinder -- Valliyodan, Babu -- Lindquist, Erika -- Peto, Myron -- Grant, David -- Shu, Shengqiang -- Goodstein, David -- Barry, Kerrie -- Futrell-Griggs, Montona -- Abernathy, Brian -- Du, Jianchang -- Tian, Zhixi -- Zhu, Liucun -- Gill, Navdeep -- Joshi, Trupti -- Libault, Marc -- Sethuraman, Anand -- Zhang, Xue-Cheng -- Shinozaki, Kazuo -- Nguyen, Henry T -- Wing, Rod A -- Cregan, Perry -- Specht, James -- Grimwood, Jane -- Rokhsar, Dan -- Stacey, Gary -- Shoemaker, Randy C -- Jackson, Scott A -- England -- Nature. 2010 Jan 14;463(7278):178-83. doi: 10.1038/nature08670.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉HudsonAlpha Genome Sequencing Center, 601 Genome Way, Huntsville, Alabama 35806, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20075913" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/genetics ; Breeding ; Chromosomes, Plant/genetics ; Evolution, Molecular ; Gene Duplication ; Genes, Duplicate/genetics ; Genes, Plant/genetics ; Genome, Plant/*genetics ; *Genomics ; Molecular Sequence Data ; Multigene Family/genetics ; Phylogeny ; Plant Root Nodulation/genetics ; *Polyploidy ; Quantitative Trait Loci/genetics ; Recombination, Genetic ; Repetitive Sequences, Nucleic Acid/genetics ; Soybean Oil/biosynthesis ; Soybeans/*genetics ; Synteny/genetics ; Transcription Factors/genetics
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  • 11
    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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  • 12
    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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  • 13
    Publication Date: 2010-10-12
    Description: Jasmonates are a family of plant hormones that regulate plant growth, development and responses to stress. The F-box protein CORONATINE INSENSITIVE 1 (COI1) mediates jasmonate signalling by promoting hormone-dependent ubiquitylation and degradation of transcriptional repressor JAZ proteins. Despite its importance, the mechanism of jasmonate perception remains unclear. Here we present structural and pharmacological data to show that the true Arabidopsis jasmonate receptor is a complex of both COI1 and JAZ. COI1 contains an open pocket that recognizes the bioactive hormone (3R,7S)-jasmonoyl-l-isoleucine (JA-Ile) with high specificity. High-affinity hormone binding requires a bipartite JAZ degron sequence consisting of a conserved alpha-helix for COI1 docking and a loop region to trap the hormone in its binding pocket. In addition, we identify a third critical component of the jasmonate co-receptor complex, inositol pentakisphosphate, which interacts with both COI1 and JAZ adjacent to the ligand. Our results unravel the mechanism of jasmonate perception and highlight the ability of F-box proteins to evolve as multi-component signalling hubs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988090/" 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/PMC2988090/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sheard, Laura B -- Tan, Xu -- Mao, Haibin -- Withers, John -- Ben-Nissan, Gili -- Hinds, Thomas R -- Kobayashi, Yuichi -- Hsu, Fong-Fu -- Sharon, Michal -- Browse, John -- He, Sheng Yang -- Rizo, Josep -- Howe, Gregg A -- Zheng, Ning -- P30 DK056341/DK/NIDDK NIH HHS/ -- P30 DK056341-10/DK/NIDDK NIH HHS/ -- R01 AI068718/AI/NIAID NIH HHS/ -- R01 AI068718-04/AI/NIAID NIH HHS/ -- R01 CA107134/CA/NCI NIH HHS/ -- R01 CA107134-07/CA/NCI NIH HHS/ -- R01 GM057795/GM/NIGMS NIH HHS/ -- R01 GM057795-12/GM/NIGMS NIH HHS/ -- R01AI068718/AI/NIAID NIH HHS/ -- R01GM57795/GM/NIGMS NIH HHS/ -- T32 GM07270/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Nov 18;468(7322):400-5. doi: 10.1038/nature09430. Epub 2010 Oct 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Box 357280, University of Washington, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20927106" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acids/chemistry/metabolism ; Arabidopsis/chemistry/metabolism ; Arabidopsis Proteins/*chemistry/*metabolism ; Binding Sites ; Crystallography, X-Ray ; Cyclopentanes/chemistry/*metabolism ; F-Box Proteins/chemistry/metabolism ; Indenes/chemistry/metabolism ; Inositol Phosphates/*metabolism ; Isoleucine/analogs & derivatives/chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Oxylipins/chemistry/*metabolism ; Peptide Fragments/chemistry/metabolism ; Plant Growth Regulators/chemistry/*metabolism ; Protein Binding ; Protein Structure, Tertiary ; Repressor Proteins/*chemistry/*metabolism ; Signal Transduction
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  • 14
    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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  • 15
    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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  • 16
    Publication Date: 2010-01-08
    Description: The ability to silence the activity of genetically specified neurons in a temporally precise fashion would provide the opportunity to investigate the causal role of specific cell classes in neural computations, behaviours and pathologies. Here we show that members of the class of light-driven outward proton pumps can mediate powerful, safe, multiple-colour silencing of neural activity. The gene archaerhodopsin-3 (Arch) from Halorubrum sodomense enables near-100% silencing of neurons in the awake brain when virally expressed in the mouse cortex and illuminated with yellow light. Arch mediates currents of several hundred picoamps at low light powers, and supports neural silencing currents approaching 900 pA at light powers easily achievable in vivo. Furthermore, Arch spontaneously recovers from light-dependent inactivation, unlike light-driven chloride pumps that enter long-lasting inactive states in response to light. These properties of Arch are appropriate to mediate the optical silencing of significant brain volumes over behaviourally relevant timescales. Arch function in neurons is well tolerated because pH excursions created by Arch illumination are minimized by self-limiting mechanisms to levels comparable to those mediated by channelrhodopsins or natural spike firing. To highlight how proton pump ecological and genomic diversity may support new innovation, we show that the blue-green light-drivable proton pump from the fungus Leptosphaeria maculans (Mac) can, when expressed in neurons, enable neural silencing by blue light, thus enabling alongside other developed reagents the potential for independent silencing of two neural populations by blue versus red light. Light-driven proton pumps thus represent a high-performance and extremely versatile class of 'optogenetic' voltage and ion modulator, which will broadly enable new neuroscientific, biological, neurological and psychiatric investigations.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939492/" 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/PMC2939492/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chow, Brian Y -- Han, Xue -- Dobry, Allison S -- Qian, Xiaofeng -- Chuong, Amy S -- Li, Mingjie -- Henninger, Michael A -- Belfort, Gabriel M -- Lin, Yingxi -- Monahan, Patrick E -- Boyden, Edward S -- 1K99MH085944/MH/NIMH NIH HHS/ -- DP2 OD002002/OD/NIH HHS/ -- DP2 OD002002-01/OD/NIH HHS/ -- K99 MH085944/MH/NIMH NIH HHS/ -- K99 MH085944-01/MH/NIMH NIH HHS/ -- England -- Nature. 2010 Jan 7;463(7277):98-102. doi: 10.1038/nature08652.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The MIT Media Laboratory, Synthetic Neurobiology Group, and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20054397" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials/radiation effects ; Animals ; Ascomycota/metabolism/radiation effects ; Color ; Electric Conductivity ; Euryarchaeota/metabolism/radiation effects ; Genetic Engineering/*methods ; Hydrogen-Ion Concentration ; Mice ; Molecular Sequence Data ; Neocortex/cytology/physiology/radiation effects ; Neurons/*metabolism/*radiation effects ; Proton Pumps/classification/genetics/*metabolism/*radiation effects ; Rhodopsins, Microbial/antagonists & inhibitors/genetics/metabolism/radiation ; effects ; Wakefulness
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  • 17
    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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  • 18
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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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  • 19
    Publication Date: 2010-01-08
    Description: Archaea, one of three major evolutionary lineages of life, encode proteasomes highly related to those of eukaryotes. In contrast, archaeal ubiquitin-like proteins are less conserved and not known to function in protein conjugation. This has complicated our understanding of the origins of ubiquitination and its connection to proteasomes. Here we report two small archaeal modifier proteins, SAMP1 and SAMP2, with a beta-grasp fold and carboxy-terminal diglycine motif similar to ubiquitin, that form protein conjugates in the archaeon Haloferax volcanii. The levels of SAMP-conjugates were altered by nitrogen-limitation and proteasomal gene knockout and spanned various functions including components of the Urm1 pathway. LC-MS/MS-based collision-induced dissociation demonstrated isopeptide bonds between the C-terminal glycine of SAMP2 and the epsilon-amino group of lysines from a number of protein targets and Lys 58 of SAMP2 itself, revealing poly-SAMP chains. The widespread distribution and diversity of pathways modified by SAMPylation suggest that this type of protein conjugation is central to the archaeal lineage.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2872088/" 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/PMC2872088/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Humbard, Matthew A -- Miranda, Hugo V -- Lim, Jae-Min -- Krause, David J -- Pritz, Jonathan R -- Zhou, Guangyin -- Chen, Sixue -- Wells, Lance -- Maupin-Furlow, Julie A -- 1S10 RR025418-01/RR/NCRR NIH HHS/ -- P41 RR018502/RR/NCRR NIH HHS/ -- P41 RR018502-07/RR/NCRR NIH HHS/ -- R01 GM057498/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Jan 7;463(7277):54-60. doi: 10.1038/nature08659.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Cell Science, University of Florida, Gainesville, Florida 32611, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20054389" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Archaeal Proteins/chemistry/*metabolism ; Gene Deletion ; Glycylglycine/metabolism ; Haloferax volcanii/genetics/metabolism ; Immunoprecipitation ; Mass Spectrometry ; Molecular Sequence Data ; Nitrogen/metabolism ; Proteasome Endopeptidase Complex/genetics/metabolism ; Sequence Alignment ; Sulfur/metabolism ; Ubiquitination ; Ubiquitins/chemistry/*metabolism
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  • 20
    Publication Date: 2010-10-12
    Description: Blood pressure is critically controlled by angiotensins, which are vasopressor peptides specifically released by the enzyme renin from the tail of angiotensinogen-a non-inhibitory member of the serpin family of protease inhibitors. Although angiotensinogen has long been regarded as a passive substrate, the crystal structures solved here to 2.1 A resolution show that the angiotensin cleavage site is inaccessibly buried in its amino-terminal tail. The conformational rearrangement that makes this site accessible for proteolysis is revealed in our 4.4 A structure of the complex of human angiotensinogen with renin. The co-ordinated changes involved are seen to be critically linked by a conserved but labile disulphide bridge. Here we show that the reduced unbridged form of angiotensinogen is present in the circulation in a near 40:60 ratio with the oxidized sulphydryl-bridged form, which preferentially interacts with receptor-bound renin. We propose that this redox-responsive transition of angiotensinogen to a form that will more effectively release angiotensin at a cellular level contributes to the modulation of blood pressure. Specifically, we demonstrate the oxidative switch of angiotensinogen to its more active sulphydryl-bridged form in the maternal circulation in pre-eclampsia-the hypertensive crisis of pregnancy that threatens the health and survival of both mother and child.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024006/" 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/PMC3024006/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Aiwu -- Carrell, Robin W -- Murphy, Michael P -- Wei, Zhenquan -- Yan, Yahui -- Stanley, Peter L D -- Stein, Penelope E -- Broughton Pipkin, Fiona -- Read, Randy J -- 082961/Wellcome Trust/United Kingdom -- BS/05/002/18361/British Heart Foundation/United Kingdom -- MC_U105663142/Medical Research Council/United Kingdom -- PG/08/041/24818/British Heart Foundation/United Kingdom -- PG/09/072/27945/British Heart Foundation/United Kingdom -- British Heart Foundation/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Nov 4;468(7320):108-11. doi: 10.1038/nature09505. Epub 2010 Oct 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK. awz20@cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20927107" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Angiotensinogen/blood/*chemistry/*metabolism ; Angiotensins/chemistry/*metabolism/secretion ; Blood Pressure ; Crystallography, X-Ray ; Disulfides/chemistry/metabolism ; Female ; Humans ; Kinetics ; Models, Molecular ; Molecular Sequence Data ; Oxidation-Reduction ; Oxidative Stress ; Pre-Eclampsia/blood/metabolism ; Pregnancy ; Protein Conformation ; *Protein Processing, Post-Translational ; Renin/chemistry/metabolism
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  • 21
    Publication Date: 2010-04-29
    Description: The nucleolytic activity of animal Argonaute proteins is deeply conserved, despite its having no obvious role in microRNA-directed gene regulation. In mice, Ago2 (also known as Eif2c2) is uniquely required for viability, and only this family member retains catalytic competence. To investigate the evolutionary pressure to conserve Argonaute enzymatic activity, we engineered a mouse with catalytically inactive Ago2 alleles. Homozygous mutants died shortly after birth with an obvious anaemia. Examination of microRNAs and their potential targets revealed a loss of miR-451, a small RNA important for erythropoiesis. Though this microRNA is processed by Drosha (also known as Rnasen), its maturation does not require Dicer. Instead, the pre-miRNA becomes loaded into Ago and is cleaved by the Ago catalytic centre to generate an intermediate 3' end, which is then further trimmed. Our findings link the conservation of Argonaute catalysis to a conserved mechanism of microRNA biogenesis that is important for vertebrate development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995450/" 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/PMC2995450/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cheloufi, Sihem -- Dos Santos, Camila O -- Chong, Mark M W -- Hannon, Gregory J -- P01 CA013106/CA/NCI NIH HHS/ -- P01 CA013106-38/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Jun 3;465(7298):584-9. doi: 10.1038/nature09092.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cold Spring Harbor Laboratory, Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor, New York 11724, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20424607" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Anemia/genetics/metabolism ; Animals ; Argonaute Proteins ; Base Sequence ; *Biocatalysis ; Embryo, Mammalian/embryology/metabolism ; Eukaryotic Initiation Factor-2/genetics/*metabolism ; Homozygote ; MicroRNAs/*biosynthesis ; Molecular Sequence Data ; Ribonuclease III/metabolism
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  • 22
    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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  • 23
    Publication Date: 2010-04-20
    Description: Ever since Darwin's pioneering research, the evolution of self-fertilisation (selfing) has been regarded as one of the most prevalent evolutionary transitions in flowering plants. A major mechanism to prevent selfing is the self-incompatibility (SI) recognition system, which consists of male and female specificity genes at the S-locus and SI modifier genes. Under conditions that favour selfing, mutations disabling the male recognition component are predicted to enjoy a relative advantage over those disabling the female component, because male mutations would increase through both pollen and seeds whereas female mutations would increase only through seeds. Despite many studies on the genetic basis of loss of SI in the predominantly selfing plant Arabidopsis thaliana, it remains unknown whether selfing arose through mutations in the female specificity gene (S-receptor kinase, SRK), male specificity gene (S-locus cysteine-rich protein, SCR; also known as S-locus protein 11, SP11) or modifier genes, and whether any of them rose to high frequency across large geographic regions. Here we report that a disruptive 213-base-pair (bp) inversion in the SCR gene (or its derivative haplotypes with deletions encompassing the entire SCR-A and a large portion of SRK-A) is found in 95% of European accessions, which contrasts with the genome-wide pattern of polymorphism in European A. thaliana. Importantly, interspecific crossings using Arabidopsis halleri as a pollen donor reveal that some A. thaliana accessions, including Wei-1, retain the female SI reaction, suggesting that all female components including SRK are still functional. Moreover, when the 213-bp inversion in SCR was inverted and expressed in transgenic Wei-1 plants, the functional SCR restored the SI reaction. The inversion within SCR is the first mutation disrupting SI shown to be nearly fixed in geographically wide samples, and its prevalence is consistent with theoretical predictions regarding the evolutionary advantage of mutations in male components.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tsuchimatsu, Takashi -- Suwabe, Keita -- Shimizu-Inatsugi, Rie -- Isokawa, Sachiyo -- Pavlidis, Pavlos -- Stadler, Thomas -- Suzuki, Go -- Takayama, Seiji -- Watanabe, Masao -- Shimizu, Kentaro K -- England -- Nature. 2010 Apr 29;464(7293):1342-6. doi: 10.1038/nature08927. Epub 2010 Apr 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Plant Biology, University Research Priority Program in Systems Biology/Functional Genomics & Zurich-Basel Plant Science Center, University of Zurich, Zollikerstrasse 107, CH-8008 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20400945" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis/chemistry/classification/*genetics/*physiology ; *Biological Evolution ; Crosses, Genetic ; Genes, Plant/*genetics ; Haplotypes/genetics ; Hybridization, Genetic/genetics ; Molecular Sequence Data ; Mutation/*genetics ; Pollen/physiology ; Pollination ; Reproduction/genetics/physiology
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  • 24
    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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  • 25
    Publication Date: 2010-06-04
    Description: Brown algae (Phaeophyceae) are complex photosynthetic organisms with a very different evolutionary history to green plants, to which they are only distantly related. These seaweeds are the dominant species in rocky coastal ecosystems and they exhibit many interesting adaptations to these, often harsh, environments. Brown algae are also one of only a small number of eukaryotic lineages that have evolved complex multicellularity (Fig. 1). We report the 214 million base pair (Mbp) genome sequence of the filamentous seaweed Ectocarpus siliculosus (Dillwyn) Lyngbye, a model organism for brown algae, closely related to the kelps (Fig. 1). Genome features such as the presence of an extended set of light-harvesting and pigment biosynthesis genes and new metabolic processes such as halide metabolism help explain the ability of this organism to cope with the highly variable tidal environment. The evolution of multicellularity in this lineage is correlated with the presence of a rich array of signal transduction genes. Of particular interest is the presence of a family of receptor kinases, as the independent evolution of related molecules has been linked with the emergence of multicellularity in both the animal and green plant lineages. The Ectocarpus genome sequence represents an important step towards developing this organism as a model species, providing the possibility to combine genomic and genetic approaches to explore these and other aspects of brown algal biology further.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cock, J Mark -- Sterck, Lieven -- Rouze, Pierre -- Scornet, Delphine -- Allen, Andrew E -- Amoutzias, Grigoris -- Anthouard, Veronique -- Artiguenave, Francois -- Aury, Jean-Marc -- Badger, Jonathan H -- Beszteri, Bank -- Billiau, Kenny -- Bonnet, Eric -- Bothwell, John H -- Bowler, Chris -- Boyen, Catherine -- Brownlee, Colin -- Carrano, Carl J -- Charrier, Benedicte -- Cho, Ga Youn -- Coelho, Susana M -- Collen, Jonas -- Corre, Erwan -- Da Silva, Corinne -- Delage, Ludovic -- Delaroque, Nicolas -- Dittami, Simon M -- Doulbeau, Sylvie -- Elias, Marek -- Farnham, Garry -- Gachon, Claire M M -- Gschloessl, Bernhard -- Heesch, Svenja -- Jabbari, Kamel -- Jubin, Claire -- Kawai, Hiroshi -- Kimura, Kei -- Kloareg, Bernard -- Kupper, Frithjof C -- Lang, Daniel -- Le Bail, Aude -- Leblanc, Catherine -- Lerouge, Patrice -- Lohr, Martin -- Lopez, Pascal J -- Martens, Cindy -- Maumus, Florian -- Michel, Gurvan -- Miranda-Saavedra, Diego -- Morales, Julia -- Moreau, Herve -- Motomura, Taizo -- Nagasato, Chikako -- Napoli, Carolyn A -- Nelson, David R -- Nyvall-Collen, Pi -- Peters, Akira F -- Pommier, Cyril -- Potin, Philippe -- Poulain, Julie -- Quesneville, Hadi -- Read, Betsy -- Rensing, Stefan A -- Ritter, Andres -- Rousvoal, Sylvie -- Samanta, Manoj -- Samson, Gaelle -- Schroeder, Declan C -- Segurens, Beatrice -- Strittmatter, Martina -- Tonon, Thierry -- Tregear, James W -- Valentin, Klaus -- von Dassow, Peter -- Yamagishi, Takahiro -- Van de Peer, Yves -- Wincker, Patrick -- England -- Nature. 2010 Jun 3;465(7298):617-21. doi: 10.1038/nature09016.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉UPMC Universite Paris 6, The Marine Plants and Biomolecules Laboratory, UMR 7139, Station Biologique de Roscoff, Place Georges Teissier, BP74, 29682 Roscoff Cedex, France. cock@sb-roscoff.fr〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20520714" target="_blank"〉PubMed〈/a〉
    Keywords: Algal Proteins/*genetics ; Animals ; *Biological Evolution ; Eukaryota ; Evolution, Molecular ; Genome/*genetics ; Molecular Sequence Data ; Phaeophyta/*cytology/*genetics/metabolism ; Phylogeny ; Pigments, Biological/biosynthesis ; Signal Transduction/genetics
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  • 26
    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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  • 27
    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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  • 28
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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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  • 29
    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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  • 30
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2010-10-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Penzias, Arno Allan -- England -- Nature. 2010 Oct 14;467(7317):S4. doi: 10.1038/467S4a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20944619" target="_blank"〉PubMed〈/a〉
    Keywords: Computing Methodologies ; Genomics ; *Nobel Prize ; Physics ; Politics ; Private Sector ; Public Opinion ; Public Policy ; Research/trends ; *Research Personnel
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  • 31
    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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  • 32
    Publication Date: 2010-05-21
    Description: The need to maintain the structural and functional integrity of an evolving protein severely restricts the repertoire of acceptable amino-acid substitutions. However, it is not known whether these restrictions impose a global limit on how far homologous protein sequences can diverge from each other. Here we explore the limits of protein evolution using sequence divergence data. We formulate a computational approach to study the rate of divergence of distant protein sequences and measure this rate for ancient proteins, those that were present in the last universal common ancestor. We show that ancient proteins are still diverging from each other, indicating an ongoing expansion of the protein sequence universe. The slow rate of this divergence is imposed by the sparseness of functional protein sequences in sequence space and the ruggedness of the protein fitness landscape: approximately 98 per cent of sites cannot accept an amino-acid substitution at any given moment but a vast majority of all sites may eventually be permitted to evolve when other, compensatory, changes occur. Thus, approximately 3.5 x 10(9) yr has not been enough to reach the limit of divergent evolution of proteins, and for most proteins the limit of sequence similarity imposed by common function may not exceed that of random sequences.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Povolotskaya, Inna S -- Kondrashov, Fyodor A -- England -- Nature. 2010 Jun 17;465(7300):922-6. doi: 10.1038/nature09105. Epub 2010 May 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bioinformatics and Genomics Programme, Centre for Genomic Regulation, Calle Dr Aiguader 88, Barcelona Biomedical Research Park Building, 08003 Barcelona, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20485343" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Amino Acids/chemistry ; *Evolution, Molecular ; *Genetic Variation ; Molecular Sequence Data ; Mutation ; Prokaryotic Cells ; Protein Structure, Secondary ; Proteins/*chemistry ; Selection, Genetic/genetics ; Sequence Analysis, Protein ; Sequence Homology, Amino Acid
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  • 33
    Publication Date: 2010-01-15
    Description: All immune systems must distinguish self from non-self to repel invaders without inducing autoimmunity. Clustered, regularly interspaced, short palindromic repeat (CRISPR) loci protect bacteria and archaea from invasion by phage and plasmid DNA through a genetic interference pathway. CRISPR loci are present in approximately 40% and approximately 90% of sequenced bacterial and archaeal genomes, respectively, and evolve rapidly, acquiring new spacer sequences to adapt to highly dynamic viral populations. Immunity requires a sequence match between the invasive DNA and the spacers that lie between CRISPR repeats. Each cluster is genetically linked to a subset of the cas (CRISPR-associated) genes that collectively encode 〉40 families of proteins involved in adaptation and interference. CRISPR loci encode small CRISPR RNAs (crRNAs) that contain a full spacer flanked by partial repeat sequences. CrRNA spacers are thought to identify targets by direct Watson-Crick pairing with invasive 'protospacer' DNA, but how they avoid targeting the spacer DNA within the encoding CRISPR locus itself is unknown. Here we have defined the mechanism of CRISPR self/non-self discrimination. In Staphylococcus epidermidis, target/crRNA mismatches at specific positions outside of the spacer sequence license foreign DNA for interference, whereas extended pairing between crRNA and CRISPR DNA repeats prevents autoimmunity. Hence, this CRISPR system uses the base-pairing potential of crRNAs not only to specify a target, but also to spare the bacterial chromosome from interference. Differential complementarity outside of the spacer sequence is a built-in feature of all CRISPR systems, indicating that this mechanism is a broadly applicable solution to the self/non-self dilemma that confronts all immune pathways.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2813891/" 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/PMC2813891/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marraffini, Luciano A -- Sontheimer, Erik J -- R03 AI079722/AI/NIAID NIH HHS/ -- R03 AI079722-01A1/AI/NIAID NIH HHS/ -- England -- Nature. 2010 Jan 28;463(7280):568-71. doi: 10.1038/nature08703. Epub 2010 Jan 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, 2205 Tech Drive, Evanston, Illinois 60208, USA. marraffini@northwestern.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20072129" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/genetics ; Base Pairing/genetics ; Base Sequence ; Conserved Sequence ; DNA, Intergenic/genetics ; Molecular Sequence Data ; Mutation/genetics ; RNA, Bacterial/*genetics/metabolism ; Repetitive Sequences, Nucleic Acid/*genetics/*immunology ; Staphylococcus epidermidis/*genetics/*immunology
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  • 34
    Publication Date: 2010-11-05
    Description: Bacteria and Archaea have developed several defence strategies against foreign nucleic acids such as viral genomes and plasmids. Among them, clustered regularly interspaced short palindromic repeats (CRISPR) loci together with cas (CRISPR-associated) genes form the CRISPR/Cas immune system, which involves partially palindromic repeats separated by short stretches of DNA called spacers, acquired from extrachromosomal elements. It was recently demonstrated that these variable loci can incorporate spacers from infecting bacteriophages and then provide immunity against subsequent bacteriophage infections in a sequence-specific manner. Here we show that the Streptococcus thermophilus CRISPR1/Cas system can also naturally acquire spacers from a self-replicating plasmid containing an antibiotic-resistance gene, leading to plasmid loss. Acquired spacers that match antibiotic-resistance genes provide a novel means to naturally select bacteria that cannot uptake and disseminate such genes. We also provide in vivo evidence that the CRISPR1/Cas system specifically cleaves plasmid and bacteriophage double-stranded DNA within the proto-spacer, at specific sites. Our data show that the CRISPR/Cas immune system is remarkably adapted to cleave invading DNA rapidly and has the potential for exploitation to generate safer microbial strains.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Garneau, Josiane E -- Dupuis, Marie-Eve -- Villion, Manuela -- Romero, Dennis A -- Barrangou, Rodolphe -- Boyaval, Patrick -- Fremaux, Christophe -- Horvath, Philippe -- Magadan, Alfonso H -- Moineau, Sylvain -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2010 Nov 4;468(7320):67-71. doi: 10.1038/nature09523.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departement de biochimie, de microbiologie et de bio-informatique, Faculte des sciences et de genie, Groupe de recherche en ecologie buccale, Faculte de medecine dentaire, Felix d'Herelle Reference Center for Bacterial Viruses, Universite Laval, Quebec City, Quebec G1V 0A6, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21048762" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteriophages/*genetics/metabolism ; Base Sequence ; DNA, Intergenic/genetics/metabolism ; DNA, Viral/genetics/*metabolism ; Drug Resistance, Bacterial/genetics ; Genetic Loci/*genetics/*immunology ; Interspersed Repetitive Sequences/genetics ; Molecular Sequence Data ; Mutation ; Plasmids/genetics/*metabolism ; RNA, Bacterial/genetics/immunology ; Streptococcus thermophilus/genetics/*immunology/*virology
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  • 35
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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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  • 36
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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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  • 37
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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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  • 38
    Publication Date: 2010-02-26
    Description: Despite the essential roles of sphingolipids both as structural components of membranes and critical signalling molecules, we have a limited understanding of how cells sense and regulate their levels. Here we reveal the function in sphingolipid metabolism of the ORM genes (known as ORMDL genes in humans)-a conserved gene family that includes ORMDL3, which has recently been identified as a potential risk factor for childhood asthma. Starting from an unbiased functional genomic approach in Saccharomyces cerevisiae, we identify Orm proteins as negative regulators of sphingolipid synthesis that form a conserved complex with serine palmitoyltransferase, the first and rate-limiting enzyme in sphingolipid production. We also define a regulatory pathway in which phosphorylation of Orm proteins relieves their inhibitory activity when sphingolipid production is disrupted. Changes in ORM gene expression or mutations to their phosphorylation sites cause dysregulation of sphingolipid metabolism. Our work identifies the Orm proteins as critical mediators of sphingolipid homeostasis and raises the possibility that sphingolipid misregulation contributes to the development of childhood asthma.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2877384/" 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/PMC2877384/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Breslow, David K -- Collins, Sean R -- Bodenmiller, Bernd -- Aebersold, Ruedi -- Simons, Kai -- Shevchenko, Andrej -- Ejsing, Christer S -- Weissman, Jonathan S -- N01-HV-28179/HV/NHLBI NIH HHS/ -- P50 GM073210/GM/NIGMS NIH HHS/ -- P50 GM073210-06/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Feb 25;463(7284):1048-53. doi: 10.1038/nature08787.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology, University of California, San Francisco, 1700 4th Street, San Francisco, California 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20182505" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Asthma/metabolism ; Cell Line ; Conserved Sequence ; Fatty Acids, Monounsaturated/pharmacology ; HeLa Cells ; *Homeostasis ; Humans ; Molecular Sequence Data ; *Multigene Family ; Multiprotein Complexes/chemistry/metabolism ; Phosphoric Monoester Hydrolases/genetics/metabolism ; Phosphorylation ; Protein Binding ; Saccharomyces cerevisiae/drug effects/enzymology/genetics/*metabolism ; Saccharomyces cerevisiae Proteins/classification/genetics/*metabolism ; Serine C-Palmitoyltransferase/genetics/metabolism ; Sphingolipids/biosynthesis/*metabolism
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  • 39
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    Nature Publishing Group (NPG)
    Publication Date: 2010-12-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abbott, Alison -- England -- Nature. 2010 Dec 16;468(7326):879. doi: 10.1038/468879a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21164453" target="_blank"〉PubMed〈/a〉
    Keywords: Cooperative Behavior ; Drug-Related Side Effects and Adverse Reactions ; Germany ; Hepatocytes/metabolism ; Humans ; Interdisciplinary Communication ; Liver/*physiology ; Models, Biological ; Pharmaceutical Preparations/metabolism ; Physics ; Research Personnel ; Systems Biology/economics/manpower/*trends
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  • 40
    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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  • 41
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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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  • 42
    Publication Date: 2010-03-09
    Description: The tumour suppressor ARF is specifically required for p53 activation under oncogenic stress. Recent studies showed that p53 activation mediated by ARF, but not that induced by DNA damage, acts as a major protection against tumorigenesis in vivo under certain biological settings, suggesting that the ARF-p53 axis has more fundamental functions in tumour suppression than originally thought. Because ARF is a very stable protein in most human cell lines, it has been widely assumed that ARF induction is mediated mainly at the transcriptional level and that activation of the ARF-p53 pathway by oncogenes is a much slower and largely irreversible process by comparison with p53 activation after DNA damage. Here we report that ARF is very unstable in normal human cells but that its degradation is inhibited in cancerous cells. Through biochemical purification, we identified a specific ubiquitin ligase for ARF and named it ULF. ULF interacts with ARF both in vitro and in vivo and promotes the lysine-independent ubiquitylation and degradation of ARF. ULF knockdown stabilizes ARF in normal human cells, triggering ARF-dependent, p53-mediated growth arrest. Moreover, nucleophosmin (NPM) and c-Myc, both of which are commonly overexpressed in cancer cells, are capable of abrogating ULF-mediated ARF ubiquitylation through distinct mechanisms, and thereby promote ARF stabilization in cancer cells. These findings reveal the dynamic feature of the ARF-p53 pathway and suggest that transcription-independent mechanisms are critically involved in ARF regulation during responses to oncogenic stress.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737736/" 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/PMC3737736/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Delin -- Shan, Jing -- Zhu, Wei-Guo -- Qin, Jun -- Gu, Wei -- P01 CA080058/CA/NCI NIH HHS/ -- P01 CA097403/CA/NCI NIH HHS/ -- R01 CA085533/CA/NCI NIH HHS/ -- R01 CA118561/CA/NCI NIH HHS/ -- R01 CA129627/CA/NCI NIH HHS/ -- R01 CA131439/CA/NCI NIH HHS/ -- England -- Nature. 2010 Mar 25;464(7288):624-7. doi: 10.1038/nature08820. Epub 2010 Mar 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Cancer Genetics, and Department of Pathology and Cell Biology College of Physicians & Surgeons, Columbia University, 1130 St Nicholas Avenue, New York, New York 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20208519" target="_blank"〉PubMed〈/a〉
    Keywords: ADP-Ribosylation Factors/*metabolism ; Cell Line ; Fibroblasts/metabolism ; *Gene Expression Regulation ; Humans ; Molecular Sequence Data ; Nuclear Proteins/metabolism ; Proto-Oncogene Proteins c-myc/metabolism ; Stress, Physiological/*physiology ; Tumor Suppressor Protein p53/*metabolism ; U937 Cells ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination
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  • 43
    Publication Date: 2010-02-02
    Description: The spectacular escalation in complexity in early bilaterian evolution correlates with a strong increase in the number of microRNAs. To explore the link between the birth of ancient microRNAs and body plan evolution, we set out to determine the ancient sites of activity of conserved bilaterian microRNA families in a comparative approach. We reason that any specific localization shared between protostomes and deuterostomes (the two major superphyla of bilaterian animals) should probably reflect an ancient specificity of that microRNA in their last common ancestor. Here, we investigate the expression of conserved bilaterian microRNAs in Platynereis dumerilii, a protostome retaining ancestral bilaterian features, in Capitella, another marine annelid, in the sea urchin Strongylocentrotus, a deuterostome, and in sea anemone Nematostella, representing an outgroup to the bilaterians. Our comparative data indicate that the oldest known animal microRNA, miR-100, and the related miR-125 and let-7 were initially active in neurosecretory cells located around the mouth. Other sets of ancient microRNAs were first present in locomotor ciliated cells, specific brain centres, or, more broadly, one of four major organ systems: central nervous system, sensory tissue, musculature and gut. These findings reveal that microRNA evolution and the establishment of tissue identities were closely coupled in bilaterian evolution. Also, they outline a minimum set of cell types and tissues that existed in the protostome-deuterostome ancestor.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981144/" 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/PMC2981144/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Christodoulou, Foteini -- Raible, Florian -- Tomer, Raju -- Simakov, Oleg -- Trachana, Kalliopi -- Klaus, Sebastian -- Snyman, Heidi -- Hannon, Gregory J -- Bork, Peer -- Arendt, Detlev -- P01 CA013106/CA/NCI NIH HHS/ -- P01 CA013106-38/CA/NCI NIH HHS/ -- P01 CA013106-39/CA/NCI NIH HHS/ -- England -- Nature. 2010 Feb 25;463(7284):1084-8. doi: 10.1038/nature08744. Epub 2010 Jan 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Developmental Biology Unit, European Molecular Biology Laboratory, D-69117 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20118916" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Annelida/anatomy & histology/cytology/genetics ; *Biological Evolution ; Brain/metabolism ; Cilia/physiology ; Conserved Sequence/genetics ; Digestive System/cytology/metabolism ; In Situ Hybridization ; MicroRNAs/*analysis/*genetics ; Molecular Sequence Data ; *Organ Specificity ; Phylogeny ; Polychaeta/*anatomy & histology/cytology/*genetics ; Sea Anemones/anatomy & histology/cytology/genetics ; Sea Urchins/anatomy & histology/cytology/genetics
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  • 44
    Publication Date: 2010-09-28
    Description: Epigenetic proteins are intently pursued targets in ligand discovery. So far, successful efforts have been limited to chromatin modifying enzymes, or so-called epigenetic 'writers' and 'erasers'. Potent inhibitors of histone binding modules have not yet been described. Here we report a cell-permeable small molecule (JQ1) that binds competitively to acetyl-lysine recognition motifs, or bromodomains. High potency and specificity towards a subset of human bromodomains is explained by co-crystal structures with bromodomain and extra-terminal (BET) family member BRD4, revealing excellent shape complementarity with the acetyl-lysine binding cavity. Recurrent translocation of BRD4 is observed in a genetically-defined, incurable subtype of human squamous carcinoma. Competitive binding by JQ1 displaces the BRD4 fusion oncoprotein from chromatin, prompting squamous differentiation and specific antiproliferative effects in BRD4-dependent cell lines and patient-derived xenograft models. These data establish proof-of-concept for targeting protein-protein interactions of epigenetic 'readers', and provide a versatile chemical scaffold for the development of chemical probes more broadly throughout the bromodomain family.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010259/" 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/PMC3010259/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Filippakopoulos, Panagis -- Qi, Jun -- Picaud, Sarah -- Shen, Yao -- Smith, William B -- Fedorov, Oleg -- Morse, Elizabeth M -- Keates, Tracey -- Hickman, Tyler T -- Felletar, Ildiko -- Philpott, Martin -- Munro, Shonagh -- McKeown, Michael R -- Wang, Yuchuan -- Christie, Amanda L -- West, Nathan -- Cameron, Michael J -- Schwartz, Brian -- Heightman, Tom D -- La Thangue, Nicholas -- French, Christopher A -- Wiest, Olaf -- Kung, Andrew L -- Knapp, Stefan -- Bradner, James E -- 13058/Cancer Research UK/United Kingdom -- G0500905/Medical Research Council/United Kingdom -- G1000807/Medical Research Council/United Kingdom -- G9400953/Medical Research Council/United Kingdom -- K08 CA128972/CA/NCI NIH HHS/ -- K08 CA128972-03/CA/NCI NIH HHS/ -- T32-075762/PHS HHS/ -- Canadian Institutes of Health Research/Canada -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Dec 23;468(7327):1067-73. doi: 10.1038/nature09504. Epub 2010 Sep 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20871596" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Azirines/chemical synthesis/chemistry/*pharmacology ; Binding Sites ; Carcinoma, Squamous Cell/physiopathology ; Cell Differentiation/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Chromatin/metabolism ; Dihydropyridines/chemical synthesis/chemistry/*pharmacology ; Female ; Humans ; Mice ; Mice, Nude ; *Models, Molecular ; Molecular Sequence Data ; Nuclear Proteins/*antagonists & inhibitors/*metabolism ; Protein Binding/drug effects ; Protein Structure, Tertiary ; Recombinant Proteins/metabolism ; Sequence Alignment ; Skin Neoplasms/physiopathology ; Stereoisomerism ; Transcription Factors/*antagonists & inhibitors/*metabolism
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  • 45
    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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  • 46
    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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  • 47
    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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  • 48
    Publication Date: 2010-08-13
    Description: The use of homologous recombination to modify genes in embryonic stem (ES) cells provides a powerful means to elucidate gene function and create disease models. Application of this technology to engineer genes in rats has not previously been possible because of the absence of germline-competent ES cells in this species. We have recently established authentic rat ES cells. Here we report the generation of gene knockout rats using the ES-cell-based gene targeting technology. We designed a targeting vector to disrupt the tumour suppressor gene p53 (also known as Tp53) in rat ES cells by means of homologous recombination. p53 gene-targeted rat ES cells can be routinely generated. Furthermore, the p53 gene-targeted mutation in the rat ES-cell genome can transmit through the germ line via ES-cell rat chimaeras to create p53 gene knockout rats. The rat is the most widely used animal model in biological research. The establishment of gene targeting technology in rat ES cells, in combination with advances in genomics and the vast amount of research data on physiology and pharmacology in this species, now provide a powerful new platform for the study of human disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2937076/" 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/PMC2937076/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tong, Chang -- Li, Ping -- Wu, Nancy L -- Yan, Youzhen -- Ying, Qi-Long -- 1R01 RR025881/RR/NCRR NIH HHS/ -- R01 OD010926/OD/NIH HHS/ -- R01 RR025881/RR/NCRR NIH HHS/ -- R01 RR025881-01A2/RR/NCRR NIH HHS/ -- England -- Nature. 2010 Sep 9;467(7312):211-3. doi: 10.1038/nature09368. Epub 2010 Aug 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20703227" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Culture Techniques ; Embryo, Mammalian/cytology ; Embryonic Stem Cells/*cytology ; Female ; Gene Knockout Techniques/*methods ; *Genes, p53 ; Germ-Line Mutation ; Male ; Mice ; Molecular Sequence Data ; Rats/*genetics ; Rats, Inbred F344 ; Rats, Sprague-Dawley ; Recombination, Genetic
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  • 49
    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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  • 50
    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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  • 51
    Publication Date: 2010-09-03
    Description: The structures of RNA molecules are often important for their function and regulation, yet there are no experimental techniques for genome-scale measurement of RNA structure. Here we describe a novel strategy termed parallel analysis of RNA structure (PARS), which is based on deep sequencing fragments of RNAs that were treated with structure-specific enzymes, thus providing simultaneous in vitro profiling of the secondary structure of thousands of RNA species at single nucleotide resolution. We apply PARS to profile the secondary structure of the messenger RNAs (mRNAs) of the budding yeast Saccharomyces cerevisiae and obtain structural profiles for over 3,000 distinct transcripts. Analysis of these profiles reveals several RNA structural properties of yeast transcripts, including the existence of more secondary structure over coding regions compared with untranslated regions, a three-nucleotide periodicity of secondary structure across coding regions and an anti-correlation between the efficiency with which an mRNA is translated and the structure over its translation start site. PARS is readily applicable to other organisms and to profiling RNA structure in diverse conditions, thus enabling studies of the dynamics of secondary structure at a genomic scale.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3847670/" 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/PMC3847670/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kertesz, Michael -- Wan, Yue -- Mazor, Elad -- Rinn, John L -- Nutter, Robert C -- Chang, Howard Y -- Segal, Eran -- R01 HG004361/HG/NHGRI NIH HHS/ -- R01HG004361/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Sep 2;467(7311):103-7. doi: 10.1038/nature09322.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20811459" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; *Genetic Techniques ; Genome-Wide Association Study ; Molecular Sequence Data ; *Nucleic Acid Conformation ; RNA, Fungal/*chemistry ; RNA, Messenger/*chemistry ; Saccharomyces cerevisiae/*chemistry/*genetics ; Transcription, Genetic
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  • 52
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    Unknown
    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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  • 53
    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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  • 54
    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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  • 55
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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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  • 56
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    Unknown
    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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  • 57
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    Unknown
    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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  • 58
    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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  • 59
    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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  • 60
    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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  • 61
    Publication Date: 2010-07-02
    Description: Pheromone-based behaviours are crucial in animals from insects to mammals, and reproductive isolation is often based on pheromone differences. However, the genetic mechanisms by which pheromone signals change during the evolution of new species are largely unknown. In the sexual communication system of moths (Insecta: Lepidoptera), females emit a species-specific pheromone blend that attracts males over long distances. The European corn borer, Ostrinia nubilalis, consists of two sex pheromone races, Z and E, that use different ratios of the cis and trans isomers of acetate pheromone components. This subtle difference leads to strong reproductive isolation in the field between the two races, which could represent a first step in speciation. Female sex pheromone production and male behavioural response are under the control of different major genes, but the identity of these genes is unknown. Here we show that allelic variation in a fatty-acyl reductase gene essential for pheromone biosynthesis accounts for the phenotypic variation in female pheromone production, leading to race-specific signals. Both the cis and trans isomers of the pheromone precursors are produced by both races, but the precursors are differentially reduced to yield opposite ratios in the final pheromone blend as a result of the substrate specificity of the enzymes encoded by the Z and E alleles. This is the first functional characterization of a gene contributing to intraspecific behavioural reproductive isolation in moths, highlighting the importance of evolutionary diversification in a lepidopteran-specific family of reductases. Accumulation of substitutions in the coding region of a single biosynthetic enzyme can produce pheromone differences resulting in reproductive isolation, with speciation as a potential end result.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lassance, Jean-Marc -- Groot, Astrid T -- Lienard, Marjorie A -- Antony, Binu -- Borgwardt, Christin -- Andersson, Fredrik -- Hedenstrom, Erik -- Heckel, David G -- Lofstedt, Christer -- England -- Nature. 2010 Jul 22;466(7305):486-9. doi: 10.1038/nature09058. Epub 2010 Jun 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Lund University, 22362 Lund, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20592730" target="_blank"〉PubMed〈/a〉
    Keywords: *Alleles ; Animals ; Female ; Isomerism ; Male ; Molecular Sequence Data ; Moths/classification/enzymology/genetics/*physiology ; Oxidoreductases/*genetics/*metabolism ; Phylogeny ; RNA/analysis/genetics/metabolism ; Sex Attractants/biosynthesis/chemistry/*metabolism ; Substrate Specificity
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  • 62
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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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  • 63
    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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  • 64
    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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  • 65
    Publication Date: 2010-03-12
    Description: Domestic animals are excellent models for genetic studies of phenotypic evolution. They have evolved genetic adaptations to a new environment, the farm, and have been subjected to strong human-driven selection leading to remarkable phenotypic changes in morphology, physiology and behaviour. Identifying the genetic changes underlying these developments provides new insight into general mechanisms by which genetic variation shapes phenotypic diversity. Here we describe the use of massively parallel sequencing to identify selective sweeps of favourable alleles and candidate mutations that have had a prominent role in the domestication of chickens (Gallus gallus domesticus) and their subsequent specialization into broiler (meat-producing) and layer (egg-producing) chickens. We have generated 44.5-fold coverage of the chicken genome using pools of genomic DNA representing eight different populations of domestic chickens as well as red jungle fowl (Gallus gallus), the major wild ancestor. We report more than 7,000,000 single nucleotide polymorphisms, almost 1,300 deletions and a number of putative selective sweeps. One of the most striking selective sweeps found in all domestic chickens occurred at the locus for thyroid stimulating hormone receptor (TSHR), which has a pivotal role in metabolic regulation and photoperiod control of reproduction in vertebrates. Several of the selective sweeps detected in broilers overlapped genes associated with growth, appetite and metabolic regulation. We found little evidence that selection for loss-of-function mutations had a prominent role in chicken domestication, but we detected two deletions in coding sequences that we suggest are functionally important. This study has direct application to animal breeding and enhances the importance of the domestic chicken as a model organism for biomedical research.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rubin, Carl-Johan -- Zody, Michael C -- Eriksson, Jonas -- Meadows, Jennifer R S -- Sherwood, Ellen -- Webster, Matthew T -- Jiang, Lin -- Ingman, Max -- Sharpe, Ted -- Ka, Sojeong -- Hallbook, Finn -- Besnier, Francois -- Carlborg, Orjan -- Bed'hom, Bertrand -- Tixier-Boichard, Michele -- Jensen, Per -- Siegel, Paul -- Lindblad-Toh, Kerstin -- Andersson, Leif -- England -- Nature. 2010 Mar 25;464(7288):587-91. doi: 10.1038/nature08832. Epub 2010 Mar 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Biochemistry and Microbiology, Uppsala University, Box 582, SE-75123 Uppsala, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20220755" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Biological Evolution ; Chickens/*genetics ; Female ; Genetic Loci/*genetics ; Genome/*genetics ; Male ; Molecular Sequence Data ; Polymorphism, Single Nucleotide ; Selection, Genetic/*genetics ; Sequence Alignment ; Sequence Analysis, DNA ; Sequence Deletion
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  • 66
    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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  • 67
    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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  • 68
    Publication Date: 2010-02-05
    Description: The M2 protein of influenza A virus is a membrane-spanning tetrameric proton channel targeted by the antiviral drugs amantadine and rimantadine. Resistance to these drugs has compromised their effectiveness against many influenza strains, including pandemic H1N1. A recent crystal structure of M2(22-46) showed electron densities attributed to a single amantadine in the amino-terminal half of the pore, indicating a physical occlusion mechanism for inhibition. However, a solution NMR structure of M2(18-60) showed four rimantadines bound to the carboxy-terminal lipid-facing surface of the helices, suggesting an allosteric mechanism. Here we show by solid-state NMR spectroscopy that two amantadine-binding sites exist in M2 in phospholipid bilayers. The high-affinity site, occupied by a single amantadine, is located in the N-terminal channel lumen, surrounded by residues mutated in amantadine-resistant viruses. Quantification of the protein-amantadine distances resulted in a 0.3 A-resolution structure of the high-affinity binding site. The second, low-affinity, site was observed on the C-terminal protein surface, but only when the drug reaches high concentrations in the bilayer. The orientation and dynamics of the drug are distinct in the two sites, as shown by (2)H NMR. These results indicate that amantadine physically occludes the M2 channel, thus paving the way for developing new antiviral drugs against influenza viruses. The study demonstrates the ability of solid-state NMR to elucidate small-molecule interactions with membrane proteins and determine high-resolution structures of their complexes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2818718/" 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/PMC2818718/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cady, Sarah D -- Schmidt-Rohr, Klaus -- Wang, Jun -- Soto, Cinque S -- Degrado, William F -- Hong, Mei -- AI74571/AI/NIAID NIH HHS/ -- GM088204/GM/NIGMS NIH HHS/ -- GM56423/GM/NIGMS NIH HHS/ -- R01 GM056423/GM/NIGMS NIH HHS/ -- R01 GM056423-12/GM/NIGMS NIH HHS/ -- R01 GM088204/GM/NIGMS NIH HHS/ -- R01 GM088204-01/GM/NIGMS NIH HHS/ -- U01 AI074571/AI/NIAID NIH HHS/ -- U01 AI074571-02/AI/NIAID NIH HHS/ -- England -- Nature. 2010 Feb 4;463(7281):689-92. doi: 10.1038/nature08722.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Iowa State University, Ames, Iowa 50011 2, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20130653" target="_blank"〉PubMed〈/a〉
    Keywords: Amantadine/chemistry/*metabolism/pharmacology ; Amino Acid Sequence ; Antiviral Agents/chemistry/*metabolism/pharmacology ; Binding Sites ; Crystallography, X-Ray ; Dimyristoylphosphatidylcholine/chemistry/metabolism ; Hydrogen-Ion Concentration ; Influenza A virus/*chemistry/drug effects ; Lipid Bilayers/chemistry/*metabolism ; Models, Molecular ; Molecular Sequence Data ; Nuclear Magnetic Resonance, Biomolecular ; Protein Conformation ; Structure-Activity Relationship ; Temperature ; Viral Matrix Proteins/antagonists & inhibitors/*chemistry/*metabolism
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  • 69
    Publication Date: 2010-07-09
    Description: Large-conductance, voltage- and calcium-activated potassium (BK, or K(Ca)1.1) channels are ubiquitously expressed in electrically excitable and non-excitable cells, either as alpha-subunit (BKalpha) tetramers or together with tissue specific auxiliary beta-subunits (beta1-beta4). Activation of BK channels typically requires coincident membrane depolarization and elevation in free cytosolic Ca(2+) concentration ([Ca(2+)](i)), which are not physiological conditions for most non-excitable cells. Here we present evidence that in non-excitable LNCaP prostate cancer cells, BK channels can be activated at negative voltages without rises in [Ca(2+)](i) through their complex with an auxiliary protein, leucine-rich repeat (LRR)-containing protein 26 (LRRC26). LRRC26 modulates the gating of a BK channel by enhancing the allosteric coupling between voltage-sensor activation and the channel's closed-open transition. This finding reveals a novel auxiliary protein of a voltage-gated ion channel that gives an unprecedentedly large negative shift ( approximately -140 mV) in voltage dependence and provides a molecular basis for activation of BK channels at physiological voltages and calcium levels in non-excitable cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yan, Jiusheng -- Aldrich, Richard W -- England -- Nature. 2010 Jul 22;466(7305):513-6. doi: 10.1038/nature09162. Epub 2010 Jul 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Neurobiology, Center for Learning and Memory, University of Texas, Austin, Texas 78712, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20613726" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Amino Acid Sequence ; Animals ; *Calcium/analysis ; Cell Line, Tumor ; Humans ; Ion Channel Gating/*physiology ; Large-Conductance Calcium-Activated Potassium Channels/genetics/*metabolism ; Male ; Membrane Potentials ; Mice ; Molecular Sequence Data ; Neoplasm Proteins/chemistry/genetics/*metabolism ; Prostatic Neoplasms/metabolism ; Rats
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  • 70
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    Unknown
    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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  • 71
    Publication Date: 2010-10-15
    Description: Eukaryotes and archaea use a protease called the proteasome that has an integral role in maintaining cellular function through the selective degradation of proteins. Proteolysis occurs in a barrel-shaped 20S core particle, which in Thermoplasma acidophilum is built from four stacked homoheptameric rings of subunits, alpha and beta, arranged alpha(7)beta(7)beta(7)alpha(7) (ref. 5). These rings form three interconnected cavities, including a pair of antechambers (formed by alpha(7)beta(7)) through which substrates are passed before degradation and a catalytic chamber (beta(7)beta(7)) where the peptide-bond hydrolysis reaction occurs. Although it is clear that substrates must be unfolded to enter through narrow, gated passageways (13 A in diameter) located on the alpha-rings, the structural and dynamical properties of substrates inside the proteasome antechamber remain unclear. Confinement in the antechamber might be expected to promote folding and thus impede proteolysis. Here we investigate the folding, stability and dynamics of three small protein substrates in the antechamber by methyl transverse-relaxation-optimized NMR spectroscopy. We show that these substrates interact actively with the antechamber walls and have drastically altered kinetic and equilibrium properties that maintain them in unstructured states so as to be accessible for hydrolysis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ruschak, Amy M -- Religa, Tomasz L -- Breuer, Sarah -- Witt, Susanne -- Kay, Lewis E -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2010 Oct 14;467(7317):868-71. doi: 10.1038/nature09444.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Molecular Genetics, Biochemistry and Chemistry, The University of Toronto, Toronto, Ontario M5S 1A8, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20944750" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Hydrolysis ; Kinetics ; Magnetic Resonance Spectroscopy ; Models, Molecular ; Molecular Sequence Data ; Proteasome Endopeptidase Complex/*chemistry/*metabolism ; Protein Folding ; *Protein Processing, Post-Translational ; Protein Stability ; Protein Subunits/chemistry/metabolism ; *Protein Unfolding ; Thermodynamics ; Thermoplasma/enzymology
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  • 72
    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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  • 73
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2010-10-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉't Hooft, Gerardus -- England -- Nature. 2010 Oct 14;467(7317):S7. doi: 10.1038/467S7a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20944622" target="_blank"〉PubMed〈/a〉
    Keywords: Artificial Intelligence ; Computers ; Exploratory Behavior ; Mentors ; Motivation ; *Nobel Prize ; Peer Review, Research/methods ; Physics ; Public Opinion ; Publishing/economics ; *Research Personnel/psychology ; Software/trends
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  • 74
    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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  • 75
    Publication Date: 2010-06-11
    Description: Regulation of the expression of the human immunodeficiency virus (HIV) genome is accomplished in large part by controlling transcription elongation. The viral protein Tat hijacks the host cell's RNA polymerase II elongation control machinery through interaction with the positive transcription elongation factor, P-TEFb, and directs the factor to promote productive elongation of HIV mRNA. Here we describe the crystal structure of the Tat.P-TEFb complex containing HIV-1 Tat, human Cdk9 (also known as CDK9), and human cyclin T1 (also known as CCNT1). Tat adopts a structure complementary to the surface of P-TEFb and makes extensive contacts, mainly with the cyclin T1 subunit of P-TEFb, but also with the T-loop of the Cdk9 subunit. The structure provides a plausible explanation for the tolerance of Tat to sequence variations at certain sites. Importantly, Tat induces significant conformational changes in P-TEFb. This finding lays a foundation for the design of compounds that would specifically inhibit the Tat.P-TEFb complex and block HIV replication.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885016/" 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/PMC2885016/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tahirov, Tahir H -- Babayeva, Nigar D -- Varzavand, Katayoun -- Cooper, Jeffrey J -- Sedore, Stanley C -- Price, David H -- AI074392/AI/NIAID NIH HHS/ -- GM082923/GM/NIGMS NIH HHS/ -- GM35500/GM/NIGMS NIH HHS/ -- P30CA036727/CA/NCI NIH HHS/ -- P41 RR015301/RR/NCRR NIH HHS/ -- P41 RR015301-075443/RR/NCRR NIH HHS/ -- R01 GM035500/GM/NIGMS NIH HHS/ -- R01 GM035500-20/GM/NIGMS NIH HHS/ -- R01 GM035500-21/GM/NIGMS NIH HHS/ -- R01 GM035500-22/GM/NIGMS NIH HHS/ -- R01 GM035500-23/GM/NIGMS NIH HHS/ -- R01 GM035500-24/GM/NIGMS NIH HHS/ -- R01 GM082923/GM/NIGMS NIH HHS/ -- R01 GM082923-01A2/GM/NIGMS NIH HHS/ -- R01 GM082923-02/GM/NIGMS NIH HHS/ -- R01 GM082923-02S1/GM/NIGMS NIH HHS/ -- R21 AI074392/AI/NIAID NIH HHS/ -- R21 AI074392-01A1/AI/NIAID NIH HHS/ -- R21 AI074392-02/AI/NIAID NIH HHS/ -- R33 AI074392/AI/NIAID NIH HHS/ -- R33 AI074392-03/AI/NIAID NIH HHS/ -- RR-15301/RR/NCRR NIH HHS/ -- England -- Nature. 2010 Jun 10;465(7299):747-51. doi: 10.1038/nature09131.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198-7696, USA. ttahirov@unmc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20535204" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Amino Acid Sequence ; Animals ; Binding Sites ; Crystallography, X-Ray ; Cyclin T/chemistry/metabolism ; Cyclin-Dependent Kinase 9/chemistry/metabolism ; Enzyme Activation ; HIV-1/*chemistry ; Humans ; Models, Molecular ; Molecular Sequence Data ; Positive Transcriptional Elongation Factor B/*chemistry/*metabolism ; Protein Binding ; Protein Conformation ; tat Gene Products, Human Immunodeficiency Virus/*chemistry/genetics/*metabolism
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  • 76
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    Unknown
    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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  • 77
    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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  • 78
    Publication Date: 2010-02-19
    Description: Local adaptations within species are often governed by several interacting genes scattered throughout the genome. Single-locus models of selection cannot explain the maintenance of such complex variation because recombination separates co-adapted alleles. Here we report a previously unrecognized type of intraspecific multi-locus genetic variation that has been maintained over a vast period. The galactose (GAL) utilization gene network of Saccharomyces kudriavzevii, a relative of brewer's yeast, exists in two distinct states: a functional gene network in Portuguese strains and, in Japanese strains, a non-functional gene network of allelic pseudogenes. Genome sequencing of all available S. kudriavzevii strains revealed that none of the functional GAL genes were acquired from other species. Rather, these polymorphisms have been maintained for nearly the entire history of the species, despite more recent gene flow genome-wide. Experimental evidence suggests that inactivation of the GAL3 and GAL80 regulatory genes facilitated the origin and long-term maintenance of the two gene network states. This striking example of a balanced unlinked gene network polymorphism introduces a remarkable type of intraspecific variation that may be widespread.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834422/" 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/PMC2834422/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hittinger, Chris Todd -- Goncalves, Paula -- Sampaio, Jose Paulo -- Dover, Jim -- Johnston, Mark -- Rokas, Antonis -- 2T32HG00045/HG/NHGRI NIH HHS/ -- 5R01GM032540/GM/NIGMS NIH HHS/ -- R01 GM032540/GM/NIGMS NIH HHS/ -- R01 GM032540-27/GM/NIGMS NIH HHS/ -- T32 HG000045/HG/NHGRI NIH HHS/ -- T32 HG000045-10/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Mar 4;464(7285):54-8. doi: 10.1038/nature08791. Epub 2010 Feb 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado 80045, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20164837" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; *Evolution, Molecular ; Galactose/metabolism ; Gene Regulatory Networks/*genetics ; Genes, Fungal/*genetics ; Genome, Fungal ; Japan ; Molecular Sequence Data ; Phylogeny ; Polymorphism, Genetic/*genetics ; Portugal ; Pseudogenes/genetics ; Repressor Proteins/genetics/metabolism ; Saccharomyces/classification/*genetics/metabolism ; Saccharomyces cerevisiae Proteins/genetics
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  • 79
    Publication Date: 2010-08-21
    Description: A diploid organism has two copies of each gene, one inherited from each parent. The expression of two inherited alleles is sometimes biased by the effects known as dominant/recessive relationships, which determine the final phenotype of the organism. To explore the mechanisms underlying these relationships, we have examined the monoallelic expression of S-locus protein 11 genes (SP11), which encode the male determinants of self-incompatibility in Brassica. We previously reported that SP11 expression was monoallelic in some S heterozygotes, and that the promoter regions of recessive SP11 alleles were specifically methylated in the anther tapetum. Here we show that this methylation is controlled by trans-acting small non-coding RNA (sRNA). We identified inverted genomic sequences that were similar to the recessive SP11 promoters in the flanking regions of dominant SP11 alleles. These sequences were specifically expressed in the anther tapetum and processed into 24-nucleotide sRNA, named SP11 methylation inducer (Smi). Introduction of the Smi genomic region into the recessive S homozygotes triggered the methylation of the promoter of recessive SP11 alleles and repressed their transcription. This is an example showing sRNA encoded in the flanking region of a dominant allele acts in trans to induce transcriptional silencing of the recessive allele. Our finding may provide new insights into the widespread monoallelic gene expression systems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tarutani, Yoshiaki -- Shiba, Hiroshi -- Iwano, Megumi -- Kakizaki, Tomohiro -- Suzuki, Go -- Watanabe, Masao -- Isogai, Akira -- Takayama, Seiji -- England -- Nature. 2010 Aug 19;466(7309):983-6. doi: 10.1038/nature09308.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma 630-0192, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20725042" target="_blank"〉PubMed〈/a〉
    Keywords: *Alleles ; Base Sequence ; Brassica/*genetics/physiology ; DNA Methylation ; Diploidy ; Flowers/genetics ; Gene Expression Regulation, Plant/genetics ; *Gene Silencing ; Genes, Dominant/*genetics ; Genes, Plant/*genetics ; Genes, Recessive/genetics ; Haplotypes/genetics ; Heterozygote ; Homozygote ; Molecular Sequence Data ; Phenotype ; Plant Infertility/*genetics/physiology ; Plant Proteins/genetics ; Plants, Genetically Modified ; Pollen/genetics/metabolism ; Pollination/genetics ; Promoter Regions, Genetic/genetics ; RNA, Plant/*genetics ; RNA, Untranslated/*genetics ; Reproduction/genetics/physiology ; Transcription, Genetic/genetics ; Transgenes/genetics
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  • 80
    Publication Date: 2010-11-19
    Description: Bacteria have developed mechanisms to communicate and compete with one another in diverse environments. A new form of intercellular communication, contact-dependent growth inhibition (CDI), was discovered recently in Escherichia coli. CDI is mediated by the CdiB/CdiA two-partner secretion (TPS) system. CdiB facilitates secretion of the CdiA 'exoprotein' onto the cell surface. An additional small immunity protein (CdiI) protects CDI(+) cells from autoinhibition. The mechanisms by which CDI blocks cell growth and by which CdiI counteracts this growth arrest are unknown. Moreover, the existence of CDI activity in other bacteria has not been explored. Here we show that the CDI growth inhibitory activity resides within the carboxy-terminal region of CdiA (CdiA-CT), and that CdiI binds and inactivates cognate CdiA-CT, but not heterologous CdiA-CT. Bioinformatic and experimental analyses show that multiple bacterial species encode functional CDI systems with high sequence variability in the CdiA-CT and CdiI coding regions. CdiA-CT heterogeneity implies that a range of toxic activities are used during CDI. Indeed, CdiA-CTs from uropathogenic E. coli and the plant pathogen Dickeya dadantii have different nuclease activities, each providing a distinct mechanism of growth inhibition. Finally, we show that bacteria lacking the CdiA-CT and CdiI coding regions are unable to compete with isogenic wild-type CDI(+) cells both in laboratory media and on a eukaryotic host. Taken together, these results suggest that CDI systems constitute an intricate immunity network with an important function in bacterial competition.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058911/" 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/PMC3058911/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aoki, Stephanie K -- Diner, Elie J -- de Roodenbeke, Claire T'kint -- Burgess, Brandt R -- Poole, Stephen J -- Braaten, Bruce A -- Jones, Allison M -- Webb, Julia S -- Hayes, Christopher S -- Cotter, Peggy A -- Low, David A -- AI043986/AI/NIAID NIH HHS/ -- GM078634/GM/NIGMS NIH HHS/ -- R01 GM078634/GM/NIGMS NIH HHS/ -- U54 AI065359/AI/NIAID NIH HHS/ -- U54 AI065359-056074/AI/NIAID NIH HHS/ -- U54 AI065359-066074/AI/NIAID NIH HHS/ -- U54 AI065359-07/AI/NIAID NIH HHS/ -- U54AI065359/AI/NIAID NIH HHS/ -- England -- Nature. 2010 Nov 18;468(7322):439-42. doi: 10.1038/nature09490.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cellular, and Developmental Biology, University of California - Santa Barbara (UCSB), Santa Barbara, California 93106-9625, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21085179" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Toxins/chemistry/genetics/immunology/*metabolism ; Contact Inhibition/immunology/physiology ; Enterobacteriaceae/enzymology/genetics/metabolism ; Escherichia coli Proteins/antagonists & inhibitors/chemistry/genetics/metabolism ; Membrane Proteins/antagonists & inhibitors/chemistry/genetics/metabolism ; Molecular Sequence Data ; Uropathogenic Escherichia coli/enzymology/genetics/growth & ; development/*metabolism
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  • 81
    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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  • 82
    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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  • 83
    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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  • 84
    Publication Date: 2010-05-14
    Description: Nature's high-performance polymer, spider silk, consists of specific proteins, spidroins, with repetitive segments flanked by conserved non-repetitive domains. Spidroins are stored as a highly concentrated fluid dope. On silk formation, intermolecular interactions between repeat regions are established that provide strength and elasticity. How spiders manage to avoid premature spidroin aggregation before self-assembly is not yet established. A pH drop to 6.3 along the spider's spinning apparatus, altered salt composition and shear forces are believed to trigger the conversion to solid silk, but no molecular details are known. Miniature spidroins consisting of a few repetitive spidroin segments capped by the carboxy-terminal domain form metre-long silk-like fibres irrespective of pH. We discovered that incorporation of the amino-terminal domain of major ampullate spidroin 1 from the dragline of the nursery web spider Euprosthenops australis (NT) into mini-spidroins enables immediate, charge-dependent self-assembly at pH values around 6.3, but delays aggregation above pH 7. The X-ray structure of NT, determined to 1.7 A resolution, shows a homodimer of dipolar, antiparallel five-helix bundle subunits that lack homologues. The overall dimeric structure and observed charge distribution of NT is expected to be conserved through spider evolution and in all types of spidroins. Our results indicate a relay-like mechanism through which the N-terminal domain regulates spidroin assembly by inhibiting precocious aggregation during storage, and accelerating and directing self-assembly as the pH is lowered along the spider's silk extrusion duct.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Askarieh, Glareh -- Hedhammar, My -- Nordling, Kerstin -- Saenz, Alejandra -- Casals, Cristina -- Rising, Anna -- Johansson, Jan -- Knight, Stefan D -- England -- Nature. 2010 May 13;465(7295):236-8. doi: 10.1038/nature08962.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Oslo University, 1033 Blindern, 0315 Oslo, Norway.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20463740" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Circular Dichroism ; Conserved Sequence ; Crystallography, X-Ray ; Hydrogen-Ion Concentration ; Models, Molecular ; Molecular Sequence Data ; Protein Structure, Tertiary ; Sequence Alignment ; Silk/*chemistry/*metabolism/ultrastructure ; Spiders/*chemistry ; Static Electricity
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  • 85
    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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  • 86
    Publication Date: 2010-03-26
    Description: Only three biological pathways are known to produce oxygen: photosynthesis, chlorate respiration and the detoxification of reactive oxygen species. Here we present evidence for a fourth pathway, possibly of considerable geochemical and evolutionary importance. The pathway was discovered after metagenomic sequencing of an enrichment culture that couples anaerobic oxidation of methane with the reduction of nitrite to dinitrogen. The complete genome of the dominant bacterium, named 'Candidatus Methylomirabilis oxyfera', was assembled. This apparently anaerobic, denitrifying bacterium encoded, transcribed and expressed the well-established aerobic pathway for methane oxidation, whereas it lacked known genes for dinitrogen production. Subsequent isotopic labelling indicated that 'M. oxyfera' bypassed the denitrification intermediate nitrous oxide by the conversion of two nitric oxide molecules to dinitrogen and oxygen, which was used to oxidize methane. These results extend our understanding of hydrocarbon degradation under anoxic conditions and explain the biochemical mechanism of a poorly understood freshwater methane sink. Because nitrogen oxides were already present on early Earth, our finding opens up the possibility that oxygen was available to microbial metabolism before the evolution of oxygenic photosynthesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ettwig, Katharina F -- Butler, Margaret K -- Le Paslier, Denis -- Pelletier, Eric -- Mangenot, Sophie -- Kuypers, Marcel M M -- Schreiber, Frank -- Dutilh, Bas E -- Zedelius, Johannes -- de Beer, Dirk -- Gloerich, Jolein -- Wessels, Hans J C T -- van Alen, Theo -- Luesken, Francisca -- Wu, Ming L -- van de Pas-Schoonen, Katinka T -- Op den Camp, Huub J M -- Janssen-Megens, Eva M -- Francoijs, Kees-Jan -- Stunnenberg, Henk -- Weissenbach, Jean -- Jetten, Mike S M -- Strous, Marc -- England -- Nature. 2010 Mar 25;464(7288):543-8. doi: 10.1038/nature08883.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Radboud University Nijmegen, IWWR, Department of Microbiology, Heyendaalseweg 135, 6525 AJ, Nijmegen, The Netherlands. k.ettwig@science.ru.nl〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20336137" target="_blank"〉PubMed〈/a〉
    Keywords: *Anaerobiosis ; Bacteria/classification/enzymology/genetics/*metabolism ; Genome, Bacterial/genetics ; Methane/*metabolism ; Molecular Sequence Data ; Nitrites/*metabolism ; Oxidation-Reduction ; Oxygen/metabolism ; Oxygenases/genetics ; Phylogeny ; Soil Microbiology
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  • 87
    Publication Date: 2010-08-03
    Description: The flagellar motor drives the rotation of flagellar filaments at hundreds of revolutions per second, efficiently propelling bacteria through viscous media. The motor uses the potential energy from an electrochemical gradient of cations across the cytoplasmic membrane to generate torque. A rapid switch from anticlockwise to clockwise rotation determines whether a bacterium runs smoothly forward or tumbles to change its trajectory. A protein called FliG forms a ring in the rotor of the flagellar motor that is involved in the generation of torque through an interaction with the cation-channel-forming stator subunit MotA. FliG has been suggested to adopt distinct conformations that induce switching but these structural changes and the molecular mechanism of switching are unknown. Here we report the molecular structure of the full-length FliG protein, identify conformational changes that are involved in rotational switching and uncover the structural basis for the formation of the FliG torque ring. This allows us to propose a model of the complete ring and switching mechanism in which conformational changes in FliG reverse the electrostatic charges involved in torque generation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159035/" 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/PMC3159035/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Lawrence K -- Ginsburg, Michael A -- Crovace, Claudia -- Donohoe, Mhairi -- Stock, Daniela -- MC_U105170645/Medical Research Council/United Kingdom -- P41 RR007707/RR/NCRR NIH HHS/ -- P41 RR007707-17/RR/NCRR NIH HHS/ -- RR007707/RR/NCRR NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- Medical Research Council/United Kingdom -- England -- Nature. 2010 Aug 19;466(7309):996-1000. doi: 10.1038/nature09300. Epub 2010 Aug 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural and Computational Biology Division, The Victor Chang Cardiac Research Institute, Lowy Packer Building, 405 Liverpool Street, Darlinghurst, New South Wales 2010, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20676082" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Proteins/*chemistry/genetics/*metabolism ; Flagella/*chemistry/genetics/*physiology ; Models, Molecular ; Molecular Motor Proteins/*chemistry/genetics/metabolism ; Molecular Sequence Data ; Mutation ; Protein Conformation ; Protein Multimerization ; Protein Structure, Tertiary ; *Rotation ; Static Electricity ; Structure-Activity Relationship ; Thermotoga maritima/chemistry ; *Torque
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  • 88
    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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  • 89
    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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  • 90
    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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  • 91
    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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  • 92
    Publication Date: 2010-10-01
    Description: Semaphorins and their receptor plexins constitute a pleiotropic cell-signalling system that is used in a wide variety of biological processes, and both protein families have been implicated in numerous human diseases. The binding of soluble or membrane-anchored semaphorins to the membrane-distal region of the plexin ectodomain activates plexin's intrinsic GTPase-activating protein (GAP) at the cytoplasmic region, ultimately modulating cellular adhesion behaviour. However, the structural mechanism underlying the receptor activation remains largely unknown. Here we report the crystal structures of the semaphorin 6A (Sema6A) receptor-binding fragment and the plexin A2 (PlxnA2) ligand-binding fragment in both their pre-signalling (that is, before binding) and signalling (after complex formation) states. Before binding, the Sema6A ectodomain was in the expected 'face-to-face' homodimer arrangement, similar to that adopted by Sema3A and Sema4D, whereas PlxnA2 was in an unexpected 'head-on' homodimer arrangement. In contrast, the structure of the Sema6A-PlxnA2 signalling complex revealed a 2:2 heterotetramer in which the two PlxnA2 monomers dissociated from one another and docked onto the top face of the Sema6A homodimer using the same interface as the head-on homodimer, indicating that plexins undergo 'partner exchange'. Cell-based activity measurements using mutant ligands/receptors confirmed that the Sema6A face-to-face dimer arrangement is physiologically relevant and is maintained throughout signalling events. Thus, homodimer-to-heterodimer transitions of cell-surface plexin that result in a specific orientation of its molecular axis relative to the membrane may constitute the structural mechanism by which the ligand-binding 'signal' is transmitted to the cytoplasmic region, inducing GAP domain rearrangements and activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nogi, Terukazu -- Yasui, Norihisa -- Mihara, Emiko -- Matsunaga, Yukiko -- Noda, Masanori -- Yamashita, Naoya -- Toyofuku, Toshihiko -- Uchiyama, Susumu -- Goshima, Yoshio -- Kumanogoh, Atsushi -- Takagi, Junichi -- England -- Nature. 2010 Oct 28;467(7319):1123-7. doi: 10.1038/nature09473. Epub 2010 Sep 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Protein Synthesis and Expression, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20881961" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Crystallography, X-Ray ; HEK293 Cells ; Humans ; Ligands ; Mice ; Models, Molecular ; Molecular Sequence Data ; Nerve Tissue Proteins/*chemistry/genetics/*metabolism ; Protein Binding ; Protein Structure, Tertiary ; Receptors, Cell Surface/*chemistry/genetics/*metabolism ; Semaphorins/*chemistry/genetics/*metabolism ; *Signal Transduction ; Structure-Activity Relationship
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  • 93
    Publication Date: 2010-06-04
    Description: Plants can defend themselves against a wide array of enemies, from microbes to large animals, yet there is great variability in the effectiveness of such defences, both within and between species. Some of this variation can be explained by conflicting pressures from pathogens with different modes of attack. A second explanation comes from an evolutionary 'tug of war', in which pathogens adapt to evade detection, until the plant has evolved new recognition capabilities for pathogen invasion. If selection is, however, sufficiently strong, susceptible hosts should remain rare. That this is not the case is best explained by costs incurred from constitutive defences in a pest-free environment. Using a combination of forward genetics and genome-wide association analyses, we demonstrate that allelic diversity at a single locus, ACCELERATED CELL DEATH 6 (ACD6), underpins marked pleiotropic differences in both vegetative growth and resistance to microbial infection and herbivory among natural Arabidopsis thaliana strains. A hyperactive ACD6 allele, compared to the reference allele, strongly enhances resistance to a broad range of pathogens from different phyla, but at the same time slows the production of new leaves and greatly reduces the biomass of mature leaves. This allele segregates at intermediate frequency both throughout the worldwide range of A. thaliana and within local populations, consistent with this allele providing substantial fitness benefits despite its marked impact on growth.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3055268/" 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/PMC3055268/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Todesco, Marco -- Balasubramanian, Sureshkumar -- Hu, Tina T -- Traw, M Brian -- Horton, Matthew -- Epple, Petra -- Kuhns, Christine -- Sureshkumar, Sridevi -- Schwartz, Christopher -- Lanz, Christa -- Laitinen, Roosa A E -- Huang, Yu -- Chory, Joanne -- Lipka, Volker -- Borevitz, Justin O -- Dangl, Jeffery L -- Bergelson, Joy -- Nordborg, Magnus -- Weigel, Detlef -- F23-GM65032-1/GM/NIGMS NIH HHS/ -- GM057171/GM/NIGMS NIH HHS/ -- GM057994/GM/NIGMS NIH HHS/ -- GM073822/GM/NIGMS NIH HHS/ -- GM62932/GM/NIGMS NIH HHS/ -- R01 GM062932/GM/NIGMS NIH HHS/ -- R01 GM062932-08/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Jun 3;465(7298):632-6. doi: 10.1038/nature09083.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Max Planck Institute for Developmental Biology, 72076 Tubingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20520716" target="_blank"〉PubMed〈/a〉
    Keywords: *Alleles ; Ankyrins/genetics/metabolism ; Arabidopsis/*genetics/growth & development/metabolism/microbiology ; Arabidopsis Proteins/genetics/metabolism ; Biomass ; Gene Expression Regulation, Plant ; Genes, Plant ; Genetic Fitness/*genetics ; Genetic Variation/*genetics ; Genome-Wide Association Study ; Molecular Sequence Data ; Phenotype ; Plant Diseases/genetics/microbiology ; Plant Leaves/anatomy & histology/genetics/growth & development/parasitology ; Quantitative Trait Loci
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  • 94
    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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  • 95
    Publication Date: 2010-03-17
    Description: The freshwater cnidarian Hydra was first described in 1702 and has been the object of study for 300 years. Experimental studies of Hydra between 1736 and 1744 culminated in the discovery of asexual reproduction of an animal by budding, the first description of regeneration in an animal, and successful transplantation of tissue between animals. Today, Hydra is an important model for studies of axial patterning, stem cell biology and regeneration. Here we report the genome of Hydra magnipapillata and compare it to the genomes of the anthozoan Nematostella vectensis and other animals. The Hydra genome has been shaped by bursts of transposable element expansion, horizontal gene transfer, trans-splicing, and simplification of gene structure and gene content that parallel simplification of the Hydra life cycle. We also report the sequence of the genome of a novel bacterium stably associated with H. magnipapillata. Comparisons of the Hydra genome to the genomes of other animals shed light on the evolution of epithelia, contractile tissues, developmentally regulated transcription factors, the Spemann-Mangold organizer, pluripotency genes and the neuromuscular junction.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479502/" 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/PMC4479502/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chapman, Jarrod A -- Kirkness, Ewen F -- Simakov, Oleg -- Hampson, Steven E -- Mitros, Therese -- Weinmaier, Thomas -- Rattei, Thomas -- Balasubramanian, Prakash G -- Borman, Jon -- Busam, Dana -- Disbennett, Kathryn -- Pfannkoch, Cynthia -- Sumin, Nadezhda -- Sutton, Granger G -- Viswanathan, Lakshmi Devi -- Walenz, Brian -- Goodstein, David M -- Hellsten, Uffe -- Kawashima, Takeshi -- Prochnik, Simon E -- Putnam, Nicholas H -- Shu, Shengquiang -- Blumberg, Bruce -- Dana, Catherine E -- Gee, Lydia -- Kibler, Dennis F -- Law, Lee -- Lindgens, Dirk -- Martinez, Daniel E -- Peng, Jisong -- Wigge, Philip A -- Bertulat, Bianca -- Guder, Corina -- Nakamura, Yukio -- Ozbek, Suat -- Watanabe, Hiroshi -- Khalturin, Konstantin -- Hemmrich, Georg -- Franke, Andre -- Augustin, Rene -- Fraune, Sebastian -- Hayakawa, Eisuke -- Hayakawa, Shiho -- Hirose, Mamiko -- Hwang, Jung Shan -- Ikeo, Kazuho -- Nishimiya-Fujisawa, Chiemi -- Ogura, Atshushi -- Takahashi, Toshio -- Steinmetz, Patrick R H -- Zhang, Xiaoming -- Aufschnaiter, Roland -- Eder, Marie-Kristin -- Gorny, Anne-Kathrin -- Salvenmoser, Willi -- Heimberg, Alysha M -- Wheeler, Benjamin M -- Peterson, Kevin J -- Bottger, Angelika -- Tischler, Patrick -- Wolf, Alexander -- Gojobori, Takashi -- Remington, Karin A -- Strausberg, Robert L -- Venter, J Craig -- Technau, Ulrich -- Hobmayer, Bert -- Bosch, Thomas C G -- Holstein, Thomas W -- Fujisawa, Toshitaka -- Bode, Hans R -- David, Charles N -- Rokhsar, Daniel S -- Steele, Robert E -- P 21108/Austrian Science Fund FWF/Austria -- R24 RR015088/RR/NCRR NIH HHS/ -- England -- Nature. 2010 Mar 25;464(7288):592-6. doi: 10.1038/nature08830. Epub 2010 Mar 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉US Department of Energy Joint Genome Institute, Walnut Creek, California 94598, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20228792" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anthozoa/genetics ; Comamonadaceae/genetics ; DNA Transposable Elements/genetics ; Gene Transfer, Horizontal/genetics ; Genome/*genetics ; Genome, Bacterial/genetics ; Hydra/*genetics/microbiology/ultrastructure ; Molecular Sequence Data ; Neuromuscular Junction/ultrastructure
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 96
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    Unknown
    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
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 97
    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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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 98
    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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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 99
    Publication Date: 2010-01-15
    Description: The human Y chromosome began to evolve from an autosome hundreds of millions of years ago, acquiring a sex-determining function and undergoing a series of inversions that suppressed crossing over with the X chromosome. Little is known about the recent evolution of the Y chromosome because only the human Y chromosome has been fully sequenced. Prevailing theories hold that Y chromosomes evolve by gene loss, the pace of which slows over time, eventually leading to a paucity of genes, and stasis. These theories have been buttressed by partial sequence data from newly emergent plant and animal Y chromosomes, but they have not been tested in older, highly evolved Y chromosomes such as that of humans. Here we finished sequencing of the male-specific region of the Y chromosome (MSY) in our closest living relative, the chimpanzee, achieving levels of accuracy and completion previously reached for the human MSY. By comparing the MSYs of the two species we show that they differ radically in sequence structure and gene content, indicating rapid evolution during the past 6 million years. The chimpanzee MSY contains twice as many massive palindromes as the human MSY, yet it has lost large fractions of the MSY protein-coding genes and gene families present in the last common ancestor. We suggest that the extraordinary divergence of the chimpanzee and human MSYs was driven by four synergistic factors: the prominent role of the MSY in sperm production, 'genetic hitchhiking' effects in the absence of meiotic crossing over, frequent ectopic recombination within the MSY, and species differences in mating behaviour. Although genetic decay may be the principal dynamic in the evolution of newly emergent Y chromosomes, wholesale renovation is the paramount theme in the continuing evolution of chimpanzee, human and perhaps other older MSYs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653425/" 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/PMC3653425/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hughes, Jennifer F -- Skaletsky, Helen -- Pyntikova, Tatyana -- Graves, Tina A -- van Daalen, Saskia K M -- Minx, Patrick J -- Fulton, Robert S -- McGrath, Sean D -- Locke, Devin P -- Friedman, Cynthia -- Trask, Barbara J -- Mardis, Elaine R -- Warren, Wesley C -- Repping, Sjoerd -- Rozen, Steve -- Wilson, Richard K -- Page, David C -- R01 HG000257/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Jan 28;463(7280):536-9. doi: 10.1038/nature08700. Epub 2010 Jan 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Whitehead Institute, and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20072128" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chromosomes, Human, Pair 21/genetics ; Chromosomes, Human, Y/*genetics ; DNA/chemistry/genetics ; Genes/*genetics ; Humans ; Male ; Molecular Sequence Data ; *Nucleic Acid Conformation ; Pan troglodytes/*genetics ; Sequence Homology, Nucleic Acid ; Y Chromosome/*genetics
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 100
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    Unknown
    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
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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