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  • History, 20th Century  (570)
  • Protein Structure, Tertiary  (376)
  • Nature Publishing Group (NPG)  (946)
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  • 1
    Publication Date: 2010-04-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Check Hayden, Erika -- England -- Nature. 2010 Apr 1;464(7289):664-7. doi: 10.1038/464664a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360709" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Data Mining ; Gene Expression Regulation ; Genes/genetics ; Genome, Human/*genetics ; Genomics/history/trends ; History, 20th Century ; History, 21st Century ; Human Genome Project/history ; Humans ; *Models, Biological ; Molecular Biology/*history ; Neoplasms/genetics/therapy ; RNA, Untranslated/genetics/metabolism ; Sea Urchins/embryology/genetics ; Systems Biology/*trends ; Tumor Suppressor Protein p53/chemistry/genetics/metabolism ; *Uncertainty
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  • 2
    Publication Date: 2010-10-15
    Description: The pre-T-cell antigen receptor (pre-TCR), expressed by immature thymocytes, has a pivotal role in early T-cell development, including TCR beta-selection, survival and proliferation of CD4(-)CD8(-) double-negative thymocytes, and subsequent alphabeta T-cell lineage differentiation. Whereas alphabetaTCR ligation by the peptide-loaded major histocompatibility complex initiates T-cell signalling, pre-TCR-induced signalling occurs by means of a ligand-independent dimerization event. The pre-TCR comprises an invariant alpha-chain (pre-Talpha) that pairs with any TCR beta-chain (TCRbeta) following successful TCR beta-gene rearrangement. Here we provide the basis of pre-Talpha-TCRbeta assembly and pre-TCR dimerization. The pre-Talpha chain comprised a single immunoglobulin-like domain that is structurally distinct from the constant (C) domain of the TCR alpha-chain; nevertheless, the mode of association between pre-Talpha and TCRbeta mirrored that mediated by the Calpha-Cbeta domains of the alphabetaTCR. The pre-TCR had a propensity to dimerize in solution, and the molecular envelope of the pre-TCR dimer correlated well with the observed head-to-tail pre-TCR dimer. This mode of pre-TCR dimerization enabled the pre-Talpha domain to interact with the variable (V) beta domain through residues that are highly conserved across the Vbeta and joining (J) beta gene families, thus mimicking the interactions at the core of the alphabetaTCR's Valpha-Vbeta interface. Disruption of this pre-Talpha-Vbeta dimer interface abrogated pre-TCR dimerization in solution and impaired pre-TCR expression on the cell surface. Accordingly, we provide a mechanism of pre-TCR self-association that allows the pre-Talpha chain to simultaneously 'sample' the correct folding of both the V and C domains of any TCR beta-chain, regardless of its ultimate specificity, which represents a critical checkpoint in T-cell development. This unusual dual-chaperone-like sensing function of pre-Talpha represents a unique mechanism in nature whereby developmental quality control regulates the expression and signalling of an integral membrane receptor complex.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pang, Siew Siew -- Berry, Richard -- Chen, Zhenjun -- Kjer-Nielsen, Lars -- Perugini, Matthew A -- King, Glenn F -- Wang, Christina -- Chew, Sock Hui -- La Gruta, Nicole L -- Williams, Neal K -- Beddoe, Travis -- Tiganis, Tony -- Cowieson, Nathan P -- Godfrey, Dale I -- Purcell, Anthony W -- Wilce, Matthew C J -- McCluskey, James -- Rossjohn, Jamie -- England -- Nature. 2010 Oct 14;467(7317):844-8. doi: 10.1038/nature09448.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20944746" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography, X-Ray ; Gene Rearrangement, T-Lymphocyte/genetics ; Humans ; Models, Molecular ; Mutation ; Protein Folding ; *Protein Multimerization ; Protein Structure, Tertiary ; Receptors, Antigen, T-Cell/*chemistry/genetics/*metabolism ; Receptors, Antigen, T-Cell, alpha-beta/chemistry/metabolism ; Signal Transduction ; Solutions ; T-Lymphocytes/cytology/immunology/metabolism
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  • 3
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    Nature Publishing Group (NPG)
    Publication Date: 2010-11-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Olby, Robert -- England -- Nature. 2010 Nov 4;468(7320):37. doi: 10.1038/468037e.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21048750" target="_blank"〉PubMed〈/a〉
    Keywords: *Correspondence as Topic ; History, 20th Century
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  • 4
    Publication Date: 2010-05-21
    Description: MyD88, IRAK4 and IRAK2 are critical signalling mediators of the TLR/IL1-R superfamily. Here we report the crystal structure of the MyD88-IRAK4-IRAK2 death domain (DD) complex, which surprisingly reveals a left-handed helical oligomer that consists of 6 MyD88, 4 IRAK4 and 4 IRAK2 DDs. Assembly of this helical signalling tower is hierarchical, in which MyD88 recruits IRAK4 and the MyD88-IRAK4 complex recruits the IRAK4 substrates IRAK2 or the related IRAK1. Formation of these Myddosome complexes brings the kinase domains of IRAKs into proximity for phosphorylation and activation. Composite binding sites are required for recruitment of the individual DDs in the complex, which are confirmed by mutagenesis and previously identified signalling mutations. Specificities in Myddosome formation are dictated by both molecular complementarity and correspondence of surface electrostatics. The MyD88-IRAK4-IRAK2 complex provides a template for Toll signalling in Drosophila and an elegant mechanism for versatile assembly and regulation of DD complexes in signal transduction.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2888693/" 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/PMC2888693/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lin, Su-Chang -- Lo, Yu-Chih -- Wu, Hao -- P30 EB009998/EB/NIBIB NIH HHS/ -- R01 AI050872/AI/NIAID NIH HHS/ -- R01 AI050872-09/AI/NIAID NIH HHS/ -- England -- Nature. 2010 Jun 17;465(7300):885-90. doi: 10.1038/nature09121. Epub 2010 May 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Weill Cornell Medical College, New York, New York 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20485341" target="_blank"〉PubMed〈/a〉
    Keywords: Humans ; *Interleukin-1 Receptor-Associated Kinases/chemistry/metabolism ; *Models, Molecular ; *Myeloid Differentiation Factor 88/chemistry/metabolism ; Protein Structure, Tertiary ; Receptors, Interleukin-1/metabolism/*physiology ; *Signal Transduction ; Toll-Like Receptors/metabolism/*physiology
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  • 5
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    Nature Publishing Group (NPG)
    Publication Date: 2010-10-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Sep 30;467(7315):499-500. doi: 10.1038/467499b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20881967" target="_blank"〉PubMed〈/a〉
    Keywords: European Union ; Financing, Organized/economics ; Germany ; History, 20th Century ; History, 21st Century ; Internationality ; Politics ; Research Support as Topic/economics/history ; Science/economics/history/*standards/*trends
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  • 6
    Publication Date: 2010-01-16
    Description: Form I Rubisco (ribulose 1,5-bisphosphate carboxylase/oxygenase), a complex of eight large (RbcL) and eight small (RbcS) subunits, catalyses the fixation of atmospheric CO(2) in photosynthesis. The limited catalytic efficiency of Rubisco has sparked extensive efforts to re-engineer the enzyme with the goal of enhancing agricultural productivity. To facilitate such efforts we analysed the formation of cyanobacterial form I Rubisco by in vitro reconstitution and cryo-electron microscopy. We show that RbcL subunit folding by the GroEL/GroES chaperonin is tightly coupled with assembly mediated by the chaperone RbcX(2). RbcL monomers remain partially unstable and retain high affinity for GroEL until captured by RbcX(2). As revealed by the structure of a RbcL(8)-(RbcX(2))(8) assembly intermediate, RbcX(2) acts as a molecular staple in stabilizing the RbcL subunits as dimers and facilitates RbcL(8) core assembly. Finally, addition of RbcS results in RbcX(2) release and holoenzyme formation. Specific assembly chaperones may be required more generally in the formation of complex oligomeric structures when folding is closely coupled to assembly.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Cuimin -- Young, Anna L -- Starling-Windhof, Amanda -- Bracher, Andreas -- Saschenbrecker, Sandra -- Rao, Bharathi Vasudeva -- Rao, Karnam Vasudeva -- Berninghausen, Otto -- Mielke, Thorsten -- Hartl, F Ulrich -- Beckmann, Roland -- Hayer-Hartl, Manajit -- England -- Nature. 2010 Jan 14;463(7278):197-202. doi: 10.1038/nature08651.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20075914" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/chemistry/metabolism ; Chaperonin 10/metabolism ; Chaperonin 60/metabolism ; Cryoelectron Microscopy ; Holoenzymes/chemistry/metabolism ; Models, Molecular ; Molecular Chaperones/chemistry/*metabolism ; Protein Binding ; *Protein Folding ; *Protein Multimerization ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; Ribulose-Bisphosphate Carboxylase/*chemistry/*metabolism/ultrastructure ; Synechococcus/*chemistry/metabolism
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  • 7
    Publication Date: 2010-05-25
    Description: The three-dimensional structures of proteins often show a modular architecture comprised of discrete structural regions or domains. Cooperative communication between these regions is important for catalysis, regulation and efficient folding; lack of coupling has been implicated in the formation of fibrils and other misfolding pathologies. How different structural regions of a protein communicate and contribute to a protein's overall energetics and folding, however, is still poorly understood. Here we use a single-molecule optical tweezers approach to induce the selective unfolding of particular regions of T4 lysozyme and monitor the effect on other regions not directly acted on by force. We investigate how the topological organization of a protein (the order of structural elements along the sequence) affects the coupling and folding cooperativity between its domains. To probe the status of the regions not directly subjected to force, we determine the free energy changes during mechanical unfolding using Crooks' fluctuation theorem. We pull on topological variants (circular permutants) and find that the topological organization of the polypeptide chain critically determines the folding cooperativity between domains and thus what parts of the folding/unfolding landscape are explored. We speculate that proteins may have evolved to select certain topologies that increase coupling between regions to avoid areas of the landscape that lead to kinetic trapping and misfolding.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2911970/" 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/PMC2911970/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shank, Elizabeth A -- Cecconi, Ciro -- Dill, Jesse W -- Marqusee, Susan -- Bustamante, Carlos -- GM 32543/GM/NIGMS NIH HHS/ -- GM 50945/GM/NIGMS NIH HHS/ -- R01 GM050945/GM/NIGMS NIH HHS/ -- R01 GM050945-17/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Jun 3;465(7298):637-40. doi: 10.1038/nature09021. Epub 2010 May 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular & 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/20495548" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Bacteriophage T4/*enzymology ; Models, Molecular ; Mutant Proteins/chemistry/genetics/metabolism ; Optical Tweezers ; Probability ; Protein Denaturation ; *Protein Folding ; Protein Structure, Tertiary ; Viral Proteins/*chemistry/genetics/*metabolism
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  • 8
    Publication Date: 2010-02-09
    Description: Ca(2+) channels and calmodulin (CaM) are two prominent signalling hubs that synergistically affect functions as diverse as cardiac excitability, synaptic plasticity and gene transcription. It is therefore fitting that these hubs are in some sense coordinated, as the opening of Ca(V)1-2 Ca(2+) channels are regulated by a single CaM constitutively complexed with channels. The Ca(2+)-free form of CaM (apoCaM) is already pre-associated with the isoleucine-glutamine (IQ) domain on the channel carboxy terminus, and subsequent Ca(2+) binding to this 'resident' CaM drives conformational changes that then trigger regulation of channel opening. Another potential avenue for channel-CaM coordination could arise from the absence of Ca(2+) regulation in channels lacking a pre-associated CaM. Natural fluctuations in CaM concentrations might then influence the fraction of regulable channels and, thereby, the overall strength of Ca(2+) feedback. However, the prevailing view has been that the ultrastrong affinity of channels for apoCaM ensures their saturation with CaM, yielding a significant form of concentration independence between Ca(2+) channels and CaM. Here we show that significant exceptions to this autonomy exist, by combining electrophysiology (to characterize channel regulation) with optical fluorescence resonance energy transfer (FRET) sensor determination of free-apoCaM concentration in live cells. This approach translates quantitative CaM biochemistry from the traditional test-tube context into the realm of functioning holochannels within intact cells. From this perspective, we find that long splice forms of Ca(V)1.3 and Ca(V)1.4 channels include a distal carboxy tail that resembles an enzyme competitive inhibitor that retunes channel affinity for apoCaM such that natural CaM variations affect the strength of Ca(2+) feedback modulation. Given the ubiquity of these channels, the connection between ambient CaM levels and Ca(2+) entry through channels is broadly significant for Ca(2+) homeostasis. Strategies such as ours promise key advances for the in situ analysis of signalling molecules resistant to in vitro reconstitution, such as Ca(2+) channels.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553577/" 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/PMC3553577/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Xiaodong -- Yang, Philemon S -- Yang, Wanjun -- Yue, David T -- P30 DC005211/DC/NIDCD NIH HHS/ -- R01 DC000276/DC/NIDCD NIH HHS/ -- England -- Nature. 2010 Feb 18;463(7283):968-72. doi: 10.1038/nature08766. Epub 2010 Feb 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Calcium Signals Laboratory, Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Ross Building, Room 713, 720 Rutland Avenue, Baltimore, Maryland 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20139964" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing ; Animals ; Apoproteins/analysis/metabolism ; Binding, Competitive/drug effects ; Calcium/analysis/metabolism/pharmacology ; Calcium Channel Blockers/*chemistry/*metabolism ; Calcium Channels/*chemistry/genetics/*metabolism ; Calmodulin/analysis/*metabolism ; Cell Line ; Cell Survival ; Electrophysiology ; *Feedback, Physiological ; Fluorescence Resonance Energy Transfer ; Humans ; Protein Structure, Tertiary ; Rats ; Recombinant Fusion Proteins/chemistry/genetics/metabolism
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  • 9
    Publication Date: 2010-12-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bernado, Pau -- Blackledge, Martin -- England -- Nature. 2010 Dec 23;468(7327):1046-8. doi: 10.1038/4681046a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21179158" target="_blank"〉PubMed〈/a〉
    Keywords: *Biochemistry/methods ; Models, Chemical ; Protein Structure, Tertiary ; Proteins/*chemistry ; Proto-Oncogene Proteins c-hck/chemistry
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  • 10
    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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  • 11
    Publication Date: 2010-06-26
    Description: DNA polymerase eta (Poleta) is unique among eukaryotic polymerases in its proficient ability for error-free replication through ultraviolet-induced cyclobutane pyrimidine dimers, and inactivation of Poleta (also known as POLH) in humans causes the variant form of xeroderma pigmentosum (XPV). We present the crystal structures of Saccharomyces cerevisiae Poleta (also known as RAD30) in ternary complex with a cis-syn thymine-thymine (T-T) dimer and with undamaged DNA. The structures reveal that the ability of Poleta to replicate efficiently through the ultraviolet-induced lesion derives from a simple and yet elegant mechanism, wherein the two Ts of the T-T dimer are accommodated in an active site cleft that is much more open than in other polymerases. We also show by structural, biochemical and genetic analysis that the two Ts are maintained in a stable configuration in the active site via interactions with Gln 55, Arg 73 and Met 74. Together, these features define the basis for Poleta's action on ultraviolet-damaged DNA that is crucial in suppressing the mutagenic and carcinogenic consequences of sun exposure, thereby reducing the incidence of skin cancers in humans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3030469/" 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/PMC3030469/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Silverstein, Timothy D -- Johnson, Robert E -- Jain, Rinku -- Prakash, Louise -- Prakash, Satya -- Aggarwal, Aneel K -- P30 EB009998/EB/NIBIB NIH HHS/ -- R01 CA107650/CA/NCI NIH HHS/ -- R01 CA107650-39/CA/NCI NIH HHS/ -- R01 ES017767/ES/NIEHS NIH HHS/ -- R01 ES017767-01/ES/NIEHS NIH HHS/ -- England -- Nature. 2010 Jun 24;465(7301):1039-43. doi: 10.1038/nature09104.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Structural and Chemical Biology, Mount Sinai School of Medicine, Box 1677, 1425 Madison Avenue, New York, New York 10029, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20577207" target="_blank"〉PubMed〈/a〉
    Keywords: Biocatalysis ; Catalytic Domain ; Crystallography, X-Ray ; DNA/chemistry/metabolism ; DNA Damage ; DNA-Directed DNA Polymerase/*chemistry/genetics/*metabolism ; Humans ; Kinetics ; Models, Molecular ; Mutation, Missense ; Nucleic Acid Conformation ; Protein Structure, Tertiary ; Pyrimidine Dimers/chemistry/metabolism ; Saccharomyces cerevisiae/*enzymology/genetics ; Skin Neoplasms/*enzymology/genetics ; Structure-Activity Relationship ; Xeroderma Pigmentosum/enzymology/genetics
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  • 12
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    Nature Publishing Group (NPG)
    Publication Date: 2010-10-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Simmons, John Galbraith -- England -- Nature. 2010 Oct 14;467(7317):S14-5. doi: 10.1038/467S14a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20944614" target="_blank"〉PubMed〈/a〉
    Keywords: Age Factors ; Blogging ; Congresses as Topic/*history/*trends ; Conservation of Natural Resources/trends ; Germany ; History, 20th Century ; History, 21st Century ; *Nobel Prize ; Nuclear Warfare ; *Research Personnel/history/trends ; Science/*history/*trends
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  • 13
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    Nature Publishing Group (NPG)
    Publication Date: 2010-08-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wadman, Meredith -- England -- Nature. 2010 Aug 12;466(7308):808-10. doi: 10.1038/466808a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20703281" target="_blank"〉PubMed〈/a〉
    Keywords: American Recovery and Reinvestment Act/economics ; Biomedical Research/economics/organization & administration/trends ; Budgets/trends ; Comparative Effectiveness Research ; History, 20th Century ; History, 21st Century ; Human Genome Project/history ; Humans ; National Institutes of Health (U.S.)/*economics/*organization & ; administration/trends ; Religion and Science ; Translational Medical Research ; United States
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 14
    Publication Date: 2010-08-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mastrandrea, Michael D -- England -- Nature. 2010 Aug 19;466(7309):933. doi: 10.1038/466933a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Intergovernmental Panel on Climate Change Working Group II, Stanford University, Stanford, California 94305, USA. mikemas@stanford.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20725032" target="_blank"〉PubMed〈/a〉
    Keywords: Aerosols ; Climate Change/*history ; History, 20th Century ; History, 21st Century ; Policy Making ; United States
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  • 15
    Publication Date: 2010-01-22
    Description: In the lowermost layer of the atmosphere-the troposphere-ozone is an important source of the hydroxyl radical, an oxidant that breaks down most pollutants and some greenhouse gases. High concentrations of tropospheric ozone are toxic, however, and have a detrimental effect on human health and ecosystem productivity. Moreover, tropospheric ozone itself acts as an effective greenhouse gas. Much of the present tropospheric ozone burden is a consequence of anthropogenic emissions of ozone precursors resulting in widespread increases in ozone concentrations since the late 1800s. At present, east Asia has the fastest-growing ozone precursor emissions. Much of the springtime east Asian pollution is exported eastwards towards western North America. Despite evidence that the exported Asian pollution produces ozone, no previous study has found a significant increase in free tropospheric ozone concentrations above the western USA since measurements began in the late 1970s. Here we compile springtime ozone measurements from many different platforms across western North America. We show a strong increase in springtime ozone mixing ratios during 1995-2008 and we have some additional evidence that a similar rate of increase in ozone mixing ratio has occurred since 1984. We find that the rate of increase in ozone mixing ratio is greatest when measurements are more heavily influenced by direct transport from Asia. Our result agrees with previous modelling studies, which indicate that global ozone concentrations should be increasing during the early part of the twenty-first century as a result of increasing precursor emissions, especially at northern mid-latitudes, with western North America being particularly sensitive to rising Asian emissions. We suggest that the observed increase in springtime background ozone mixing ratio may hinder the USA's compliance with its ozone air quality standard.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cooper, O R -- Parrish, D D -- Stohl, A -- Trainer, M -- Nedelec, P -- Thouret, V -- Cammas, J P -- Oltmans, S J -- Johnson, B J -- Tarasick, D -- Leblanc, T -- McDermid, I S -- Jaffe, D -- Gao, R -- Stith, J -- Ryerson, T -- Aikin, K -- Campos, T -- Weinheimer, A -- Avery, M A -- England -- Nature. 2010 Jan 21;463(7279):344-8. doi: 10.1038/nature08708.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cooperative Institute for Research in Environmental Sciences, University of Colorado, Boulder, Colorado 80309, USA. owen.r.cooper@noaa.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20090751" target="_blank"〉PubMed〈/a〉
    Keywords: Air Pollutants/analysis/chemistry ; Asia ; Atmosphere/*chemistry ; Ecosystem ; Greenhouse Effect ; History, 20th Century ; History, 21st Century ; North America ; Ozone/*analysis/chemical synthesis/chemistry ; Sample Size ; Seasons
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  • 16
    Publication Date: 2010-08-10
    Description: Mitochondrial calcium uptake has a central role in cell physiology by stimulating ATP production, shaping cytosolic calcium transients and regulating cell death. The biophysical properties of mitochondrial calcium uptake have been studied in detail, but the underlying proteins remain elusive. Here we use an integrative strategy to predict human genes involved in mitochondrial calcium entry based on clues from comparative physiology, evolutionary genomics and organelle proteomics. RNA interference against 13 top candidates highlighted one gene, CBARA1, that we call hereafter mitochondrial calcium uptake 1 (MICU1). Silencing MICU1 does not disrupt mitochondrial respiration or membrane potential but abolishes mitochondrial calcium entry in intact and permeabilized cells, and attenuates the metabolic coupling between cytosolic calcium transients and activation of matrix dehydrogenases. MICU1 is associated with the mitochondrial inner membrane and has two canonical EF hands that are essential for its activity, indicating a role in calcium sensing. MICU1 represents the founding member of a set of proteins required for high-capacity mitochondrial calcium uptake. Its discovery may lead to the complete molecular characterization of mitochondrial calcium uptake pathways, and offers genetic strategies for understanding their contribution to normal physiology and disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2977980/" 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/PMC2977980/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Perocchi, Fabiana -- Gohil, Vishal M -- Girgis, Hany S -- Bao, X Robert -- McCombs, Janet E -- Palmer, Amy E -- Mootha, Vamsi K -- DK080261/DK/NIDDK NIH HHS/ -- GM0077465/GM/NIGMS NIH HHS/ -- GM084027/GM/NIGMS NIH HHS/ -- R01 GM077465/GM/NIGMS NIH HHS/ -- R01 GM077465-01A1/GM/NIGMS NIH HHS/ -- R01 GM077465-02/GM/NIGMS NIH HHS/ -- R01 GM077465-03/GM/NIGMS NIH HHS/ -- R01 GM077465-04/GM/NIGMS NIH HHS/ -- R01 GM077465-05/GM/NIGMS NIH HHS/ -- R01 GM077465-06/GM/NIGMS NIH HHS/ -- R01 GM084027/GM/NIGMS NIH HHS/ -- R24 DK080261/DK/NIDDK NIH HHS/ -- R24 DK080261-04/DK/NIDDK NIH HHS/ -- TR2 GM08759/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Sep 16;467(7313):291-6. doi: 10.1038/nature09358. Epub 2010 Aug 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20693986" target="_blank"〉PubMed〈/a〉
    Keywords: Allergens/*chemistry/genetics/*metabolism ; Amino Acid Sequence ; Antigens, Plant ; Calcium/*metabolism ; *Calcium Signaling ; Calcium-Binding Proteins/*chemistry/deficiency/genetics/*metabolism ; Cation Transport Proteins ; Cell Respiration ; Cytoplasm/metabolism ; DNA, Mitochondrial/analysis ; *EF Hand Motifs ; Endoplasmic Reticulum/metabolism ; Gene Knockdown Techniques ; HeLa Cells ; Homeostasis ; Humans ; Membrane Potentials ; Mitochondria/*metabolism ; Mitochondrial Membrane Transport Proteins ; Mitochondrial Proteins/*chemistry/deficiency/genetics/*metabolism ; NAD/metabolism ; NADP/metabolism ; Oxidative Phosphorylation ; Protein Structure, Tertiary ; Protein Transport ; RNA Interference
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  • 17
    Publication Date: 2010-01-30
    Description: Vitamin K epoxide reductase (VKOR) generates vitamin K hydroquinone to sustain gamma-carboxylation of many blood coagulation factors. Here, we report the 3.6 A crystal structure of a bacterial homologue of VKOR from Synechococcus sp. The structure shows VKOR in complex with its naturally fused redox partner, a thioredoxin-like domain, and corresponds to an arrested state of electron transfer. The catalytic core of VKOR is a four transmembrane helix bundle that surrounds a quinone, connected through an additional transmembrane segment with the periplasmic thioredoxin-like domain. We propose a pathway for how VKOR uses electrons from cysteines of newly synthesized proteins to reduce a quinone, a mechanism confirmed by in vitro reconstitution of vitamin K-dependent disulphide bridge formation. Our results have implications for the mechanism of the mammalian VKOR and explain how mutations can cause resistance to the VKOR inhibitor warfarin, the most commonly used oral anticoagulant.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2919313/" 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/PMC2919313/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Weikai -- Schulman, Sol -- Dutton, Rachel J -- Boyd, Dana -- Beckwith, Jon -- Rapoport, Tom A -- GMO41883/PHS HHS/ -- K99 HL097083/HL/NHLBI NIH HHS/ -- K99 HL097083-01/HL/NHLBI NIH HHS/ -- K991K99HL097083/HL/NHLBI NIH HHS/ -- R00 HL097083/HL/NHLBI NIH HHS/ -- R01 GM041883/GM/NIGMS NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Jan 28;463(7280):507-12. doi: 10.1038/nature08720.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA. weikai@crystal.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20110994" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anticoagulants ; Bacterial Proteins/chemistry ; Catalytic Domain ; Disulfides/chemistry ; Drug Resistance/genetics ; Electron Transport ; Humans ; Membrane Proteins/chemistry ; Mixed Function Oxygenases/*chemistry/genetics ; *Models, Molecular ; Protein Structure, Tertiary ; Synechococcus/*enzymology ; Vitamin K Epoxide Reductases ; Warfarin
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  • 18
    Publication Date: 2010-02-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ferry, Georgina -- England -- Nature. 2010 Feb 25;463(7284):1025. doi: 10.1038/4631025a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20182497" target="_blank"〉PubMed〈/a〉
    Keywords: Archives ; *Biography as Topic ; Electronic Mail ; History, 20th Century ; Nobel Prize ; Research Personnel/history ; Science/history ; *Writing
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  • 19
    Publication Date: 2010-09-25
    Description: Gram-negative bacteria, such as Escherichia coli, frequently use tripartite efflux complexes in the resistance-nodulation-cell division (RND) family to expel various toxic compounds from the cell. The efflux system CusCBA is responsible for extruding biocidal Cu(I) and Ag(I) ions. No previous structural information was available for the heavy-metal efflux (HME) subfamily of the RND efflux pumps. Here we describe the crystal structures of the inner-membrane transporter CusA in the absence and presence of bound Cu(I) or Ag(I). These CusA structures provide new structural information about the HME subfamily of RND efflux pumps. The structures suggest that the metal-binding sites, formed by a three-methionine cluster, are located within the cleft region of the periplasmic domain. This cleft is closed in the apo-CusA form but open in the CusA-Cu(I) and CusA-Ag(I) structures, which directly suggests a plausible pathway for ion export. Binding of Cu(I) and Ag(I) triggers significant conformational changes in both the periplasmic and transmembrane domains. The crystal structure indicates that CusA has, in addition to the three-methionine metal-binding site, four methionine pairs-three located in the transmembrane region and one in the periplasmic domain. Genetic analysis and transport assays suggest that CusA is capable of actively picking up metal ions from the cytosol, using these methionine pairs or clusters to bind and export metal ions. These structures suggest a stepwise shuttle mechanism for transport between these sites.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946090/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946090/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Long, Feng -- Su, Chih-Chia -- Zimmermann, Michael T -- Boyken, Scott E -- Rajashankar, Kanagalaghatta R -- Jernigan, Robert L -- Yu, Edward W -- GM 072014/GM/NIGMS NIH HHS/ -- GM 074027/GM/NIGMS NIH HHS/ -- GM 081680/GM/NIGMS NIH HHS/ -- GM 086431/GM/NIGMS NIH HHS/ -- R01 GM072014/GM/NIGMS NIH HHS/ -- R01 GM074027/GM/NIGMS NIH HHS/ -- R01 GM074027-05/GM/NIGMS NIH HHS/ -- R01 GM086431/GM/NIGMS NIH HHS/ -- R01 GM086431-01A2/GM/NIGMS NIH HHS/ -- RR-15301/RR/NCRR NIH HHS/ -- England -- Nature. 2010 Sep 23;467(7314):484-8. doi: 10.1038/nature09395.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular, Cellular and Developmental Biology Interdepartmental Graduate Program, Iowa State University, Iowa 50011, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20865003" target="_blank"〉PubMed〈/a〉
    Keywords: Apoproteins/chemistry/metabolism ; Binding Sites ; Cell Membrane/metabolism ; Copper/chemistry/*metabolism ; Crystallography, X-Ray ; Cytosol/metabolism ; Escherichia coli/*chemistry ; Escherichia coli Proteins/*chemistry/*metabolism ; Ion Transport ; Membrane Transport Proteins/*chemistry/*metabolism ; Methionine/*metabolism ; Models, Biological ; Models, Molecular ; Periplasm/metabolism ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; Silver/chemistry/*metabolism ; Structure-Activity Relationship
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  • 20
    Publication Date: 2010-09-30
    Description: Cell-cell signalling of semaphorin ligands through interaction with plexin receptors is important for the homeostasis and morphogenesis of many tissues and is widely studied for its role in neural connectivity, cancer, cell migration and immune responses. SEMA4D and Sema6A exemplify two diverse vertebrate, membrane-spanning semaphorin classes (4 and 6) that are capable of direct signalling through members of the two largest plexin classes, B and A, respectively. In the absence of any structural information on the plexin ectodomain or its interaction with semaphorins the extracellular specificity and mechanism controlling plexin signalling has remained unresolved. Here we present crystal structures of cognate complexes of the semaphorin-binding regions of plexins B1 and A2 with semaphorin ectodomains (human PLXNB1(1-2)-SEMA4D(ecto) and murine PlxnA2(1-4)-Sema6A(ecto)), plus unliganded structures of PlxnA2(1-4) and Sema6A(ecto). These structures, together with biophysical and cellular assays of wild-type and mutant proteins, reveal that semaphorin dimers independently bind two plexin molecules and that signalling is critically dependent on the avidity of the resulting bivalent 2:2 complex (monomeric semaphorin binds plexin but fails to trigger signalling). In combination, our data favour a cell-cell signalling mechanism involving semaphorin-stabilized plexin dimerization, possibly followed by clustering, which is consistent with previous functional data. Furthermore, the shared generic architecture of the complexes, formed through conserved contacts of the amino-terminal seven-bladed beta-propeller (sema) domains of both semaphorin and plexin, suggests that a common mode of interaction triggers all semaphorin-plexin based signalling, while distinct insertions within or between blades of the sema domains determine binding specificity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587840/" 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/PMC3587840/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Janssen, Bert J C -- Robinson, Ross A -- Perez-Branguli, Francesc -- Bell, Christian H -- Mitchell, Kevin J -- Siebold, Christian -- Jones, E Yvonne -- 082301/Wellcome Trust/United Kingdom -- 083111/Wellcome Trust/United Kingdom -- 10976/Cancer Research UK/United Kingdom -- A10976/Cancer Research UK/United Kingdom -- A3964/Cancer Research UK/United Kingdom -- A5261/Cancer Research UK/United Kingdom -- G0700232/Medical Research Council/United Kingdom -- G0700232(82098)/Medical Research Council/United Kingdom -- G0900084/Medical Research Council/United Kingdom -- G9900061/Medical Research Council/United Kingdom -- G9900061(69203)/Medical Research Council/United Kingdom -- Cancer Research UK/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Oct 28;467(7319):1118-22. doi: 10.1038/nature09468. Epub 2010 Sep 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20877282" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/chemistry/genetics/metabolism ; Binding Sites ; Cell Adhesion Molecules/*chemistry/genetics/*metabolism ; Cell Communication ; Crystallography, X-Ray ; Humans ; Ligands ; Mice ; Mice, Inbred C57BL ; Models, Molecular ; NIH 3T3 Cells ; 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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  • 21
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2010-06-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clayton, Julie -- England -- Nature. 2010 Jun 24;465(7301):S4-5. doi: 10.1038/nature09220.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20571553" target="_blank"〉PubMed〈/a〉
    Keywords: Acute Disease ; Animals ; Carrier State/epidemiology/immunology/parasitology ; *Chagas Disease/drug therapy/epidemiology/parasitology/transmission ; Chronic Disease/drug therapy/epidemiology ; Clinical Trials as Topic ; History, 16th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; Humans ; Insect Vectors/parasitology ; Latin America/epidemiology/ethnology ; Neglected Diseases/economics ; Nitroimidazoles/pharmacology/therapeutic use ; Trypanocidal Agents/pharmacology/therapeutic use ; Trypanosoma cruzi/immunology/pathogenicity/physiology
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  • 22
    Publication Date: 2010-11-05
    Description: Many physiological events require transient increases in cytosolic Ca(2+) concentrations. Ryanodine receptors (RyRs) are ion channels that govern the release of Ca(2+) from the endoplasmic and sarcoplasmic reticulum. Mutations in RyRs can lead to severe genetic conditions that affect both cardiac and skeletal muscle, but locating the mutated residues in the full-length channel structure has been difficult. Here we show the 2.5 A resolution crystal structure of a region spanning three domains of RyR type 1 (RyR1), encompassing amino acid residues 1-559. The domains interact with each other through a predominantly hydrophilic interface. Docking in RyR1 electron microscopy maps unambiguously places the domains in the cytoplasmic portion of the channel, forming a 240-kDa cytoplasmic vestibule around the four-fold symmetry axis. We pinpoint the exact locations of more than 50 disease-associated mutations in full-length RyR1 and RyR2. The mutations can be classified into three groups: those that destabilize the interfaces between the three amino-terminal domains, disturb the folding of individual domains or affect one of six interfaces with other parts of the receptor. We propose a model whereby the opening of a RyR coincides with allosterically coupled motions within the N-terminal domains. This process can be affected by mutations that target various interfaces within and across subunits. The crystal structure provides a framework to understand the many disease-associated mutations in RyRs that have been studied using functional methods, and will be useful for developing new strategies to modulate RyR function in disease states.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tung, Ching-Chieh -- Lobo, Paolo A -- Kimlicka, Lynn -- Van Petegem, Filip -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2010 Nov 25;468(7323):585-8. doi: 10.1038/nature09471. Epub 2010 Nov 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21048710" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Models, Molecular ; Mutation/genetics ; Protein Structure, Tertiary ; Rabbits ; Ryanodine Receptor Calcium Release Channel/*chemistry/*genetics/metabolism
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  • 23
    Publication Date: 2010-08-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Oreskes, Naomi -- Conway, Erik M -- England -- Nature. 2010 Aug 12;466(7308):815. doi: 10.1038/466815d.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20703283" target="_blank"〉PubMed〈/a〉
    Keywords: Acid Rain/*statistics & numerical data ; Federal Government ; History, 20th Century ; Peer Review ; United States
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  • 24
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2010-04-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Venter, J Craig -- England -- Nature. 2010 Apr 1;464(7289):676-7. doi: 10.1038/464676a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉J. Craig Venter Institute, La Jolla, California 92121, USA. jcventer@jcvi.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360717" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Continental Population Groups/genetics ; Diploidy ; Female ; Genetic Predisposition to Disease/genetics ; Genetic Variation/genetics ; Genetics, Medical/*trends ; Genome, Human/*genetics ; Genomics/economics/history/*trends ; Haploidy ; Haplotypes/genetics ; History, 20th Century ; History, 21st Century ; Human Genome Project/economics/history ; Humans ; Male ; Phenotype ; Precision Medicine/*trends ; Sequence Analysis, DNA/economics/history/instrumentation/methods
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  • 25
    Publication Date: 2010-07-14
    Description: While reversible histone modifications are linked to an ever-expanding range of biological functions, the demethylases for histone H4 lysine 20 and their potential regulatory roles remain unknown. Here we report that the PHD and Jumonji C (JmjC) domain-containing protein, PHF8, while using multiple substrates, including H3K9me1/2 and H3K27me2, also functions as an H4K20me1 demethylase. PHF8 is recruited to promoters by its PHD domain based on interaction with H3K4me2/3 and controls G1-S transition in conjunction with E2F1, HCF-1 (also known as HCFC1) and SET1A (also known as SETD1A), at least in part, by removing the repressive H4K20me1 mark from a subset of E2F1-regulated gene promoters. Phosphorylation-dependent PHF8 dismissal from chromatin in prophase is apparently required for the accumulation of H4K20me1 during early mitosis, which might represent a component of the condensin II loading process. Accordingly, the HEAT repeat clusters in two non-structural maintenance of chromosomes (SMC) condensin II subunits, N-CAPD3 and N-CAPG2 (also known as NCAPD3 and NCAPG2, respectively), are capable of recognizing H4K20me1, and ChIP-Seq analysis demonstrates a significant overlap of condensin II and H4K20me1 sites in mitotic HeLa cells. Thus, the identification and characterization of an H4K20me1 demethylase, PHF8, has revealed an intimate link between this enzyme and two distinct events in cell cycle progression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3059551/" 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/PMC3059551/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Wen -- Tanasa, Bogdan -- Tyurina, Oksana V -- Zhou, Tian Yuan -- Gassmann, Reto -- Liu, Wei Ting -- Ohgi, Kenneth A -- Benner, Chris -- Garcia-Bassets, Ivan -- Aggarwal, Aneel K -- Desai, Arshad -- Dorrestein, Pieter C -- Glass, Christopher K -- Rosenfeld, Michael G -- R01 CA097134/CA/NCI NIH HHS/ -- R01 CA097134-09/CA/NCI NIH HHS/ -- R01 DK018477/DK/NIDDK NIH HHS/ -- R01 DK018477-35/DK/NIDDK NIH HHS/ -- R01 DK039949/DK/NIDDK NIH HHS/ -- R01 DK039949-18/DK/NIDDK NIH HHS/ -- R01 HL065445/HL/NHLBI NIH HHS/ -- R01 NS034934/NS/NINDS NIH HHS/ -- R01 NS034934-21/NS/NINDS NIH HHS/ -- R37 DK039949/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Jul 22;466(7305):508-12. doi: 10.1038/nature09272. Epub 2010 Jul 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, School of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20622854" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/chemistry/metabolism ; Cell Cycle/*physiology ; Cell Line ; Chromatin/metabolism ; Chromosomal Proteins, Non-Histone/chemistry/deficiency/genetics/*metabolism ; DNA-Binding Proteins/chemistry/metabolism ; HeLa Cells ; Histone Demethylases/chemistry/genetics/*metabolism ; Histone-Lysine N-Methyltransferase/metabolism ; Histones/chemistry/*metabolism ; Host Cell Factor C1/genetics/metabolism ; Humans ; Lysine/*metabolism ; Methylation ; Multiprotein Complexes/chemistry/metabolism ; Phosphorylation ; Promoter Regions, Genetic ; Protein Structure, Tertiary ; Transcription Factors/chemistry/deficiency/genetics/*metabolism
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  • 26
    Publication Date: 2010-07-30
    Description: The post-translational methylation of alpha-amino groups was first discovered over 30 years ago on the bacterial ribosomal proteins L16 and L33 (refs 1, 2), but almost nothing is known about the function or enzymology of this modification. Several other bacterial and eukaryotic proteins have since been shown to be alpha-N-methylated. However, the Ran guanine nucleotide-exchange factor, RCC1, is the only protein for which any biological function of alpha-N-methylation has been identified. Methylation-defective mutants of RCC1 have reduced affinity for DNA and cause mitotic defects, but further characterization of this modification has been hindered by ignorance of the responsible methyltransferase. All fungal and animal N-terminally methylated proteins contain a unique N-terminal motif, Met-(Ala/Pro/Ser)-Pro-Lys, indicating that they may be targets of the same, unknown enzyme. The initiating Met is cleaved, and the exposed alpha-amino group is mono-, di- or trimethylated. Here we report the discovery of the first alpha-N-methyltransferase, which we named N-terminal RCC1 methyltransferase (NRMT). Substrate docking and mutational analysis of RCC1 defined the NRMT recognition sequence and enabled the identification of numerous new methylation targets, including SET (also known as TAF-I or PHAPII) and the retinoblastoma protein, RB. Knockdown of NRMT recapitulates the multi-spindle phenotype seen with methylation-defective RCC1 mutants, demonstrating the importance of alpha-N-methylation for normal bipolar spindle formation and chromosome segregation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939154/" 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/PMC2939154/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tooley, Christine E Schaner -- Petkowski, Janusz J -- Muratore-Schroeder, Tara L -- Balsbaugh, Jeremy L -- Shabanowitz, Jeffrey -- Sabat, Michal -- Minor, Wladek -- Hunt, Donald F -- Macara, Ian G -- R01 GM050526/GM/NIGMS NIH HHS/ -- R01 GM050526-17/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Aug 26;466(7310):1125-8. doi: 10.1038/nature09343.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, Center for Cell Signaling, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA. ces5g@virginia.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20668449" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Cycle Proteins/*metabolism ; Cell Line ; Chromosome Segregation ; Gene Knockdown Techniques ; Guanine Nucleotide Exchange Factors/*metabolism ; HeLa Cells ; Histone Chaperones/metabolism ; Humans ; Methyltransferases/chemistry/genetics/*metabolism ; Models, Molecular ; Mutation/genetics ; Nuclear Proteins/*metabolism ; Protein Binding ; Protein Structure, Tertiary ; Retinoblastoma Protein/*metabolism ; Spindle Apparatus/metabolism ; Transcription Factors/metabolism
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  • 27
    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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  • 28
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    Nature Publishing Group (NPG)
    Publication Date: 2010-04-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Collins, Francis -- England -- Nature. 2010 Apr 1;464(7289):674-5. doi: 10.1038/464674a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Institutes of Health, Bethesda, Maryland 20892, USA. francis.collins@nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360716" target="_blank"〉PubMed〈/a〉
    Keywords: Access to Information ; Genetic Predisposition to Disease/genetics ; Genetics, Medical/*trends ; Genome, Human/*genetics ; Genome-Wide Association Study ; Genomics/economics/history/*trends ; Haplotypes/genetics ; History, 20th Century ; History, 21st Century ; Humans ; Precision Medicine/*trends ; Sequence Analysis, DNA/economics/history/trends
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  • 29
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    Nature Publishing Group (NPG)
    Publication Date: 2010-07-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schrope, Mark -- England -- Nature. 2010 Jul 15;466(7304):304-5. doi: 10.1038/466304a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20631769" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Disasters/history ; *Ecosystem ; Fisheries/history/statistics & numerical data ; History, 20th Century ; History, 21st Century ; Marine Biology/history/trends ; Mexico ; Oceans and Seas ; Ostreidae ; Petroleum/*analysis/*toxicity ; Population Dynamics ; Research/history/*statistics & numerical data/trends ; Seawater/*chemistry
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  • 30
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    Nature Publishing Group (NPG)
    Publication Date: 2010-08-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Briggs, Derek E G -- England -- Nature. 2010 Aug 5;466(7307):706. doi: 10.1038/466706a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Geology and Geophysics, and the Peabody Museum of Natural History, Yale University, New Haven, Connecticut 06520, USA. derek.briggs@yale.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20686564" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; British Columbia ; *Fossils ; Geologic Sediments/analysis/chemistry ; Great Britain ; History, 20th Century ; History, 21st Century ; Paleontology/*history ; United States
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  • 31
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    Nature Publishing Group (NPG)
    Publication Date: 2010-01-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dalton, Rex -- England -- Nature. 2010 Jan 7;463(7277):16. doi: 10.1038/463016a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20054370" target="_blank"〉PubMed〈/a〉
    Keywords: California ; Disasters/prevention & control/statistics & numerical data ; Earthquakes/history/*statistics & numerical data ; Floods/history/*statistics & numerical data ; Fresh Water ; History, 15th Century ; History, 18th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; *Risk Management ; Rivers ; Water Movements
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  • 32
    Publication Date: 2010-05-14
    Description: A huge variety of proteins are able to form fibrillar structures, especially at high protein concentrations. Hence, it is surprising that spider silk proteins can be stored in a soluble form at high concentrations and transformed into extremely stable fibres on demand. Silk proteins are reminiscent of amphiphilic block copolymers containing stretches of polyalanine and glycine-rich polar elements forming a repetitive core flanked by highly conserved non-repetitive amino-terminal and carboxy-terminal domains. The N-terminal domain comprises a secretion signal, but further functions remain unassigned. The C-terminal domain was implicated in the control of solubility and fibre formation initiated by changes in ionic composition and mechanical stimuli known to align the repetitive sequence elements and promote beta-sheet formation. However, despite recent structural data, little is known about this remarkable behaviour in molecular detail. Here we present the solution structure of the C-terminal domain of a spider dragline silk protein and provide evidence that the structural state of this domain is essential for controlled switching between the storage and assembly forms of silk proteins. In addition, the C-terminal domain also has a role in the alignment of secondary structural features formed by the repetitive elements in the backbone of spider silk proteins, which is known to be important for the mechanical properties of the fibre.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hagn, Franz -- Eisoldt, Lukas -- Hardy, John G -- Vendrely, Charlotte -- Coles, Murray -- Scheibel, Thomas -- Kessler, Horst -- England -- Nature. 2010 May 13;465(7295):239-42. doi: 10.1038/nature08936.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Integrated Protein Science (CIPSM), Technische Universitat Munchen, 85747 Garching, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20463741" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calorimetry, Differential Scanning ; Circular Dichroism ; *Conserved Sequence ; Hydrophobic and Hydrophilic Interactions ; Magnetic Resonance Spectroscopy ; Models, Molecular ; Protein Structure, Tertiary ; Silk/*chemistry/*metabolism ; Spectrometry, Fluorescence ; Spectroscopy, Fourier Transform Infrared ; Spiders/*chemistry
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  • 33
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    Nature Publishing Group (NPG)
    Publication Date: 2010-04-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉White, Craig R -- England -- Nature. 2010 Apr 1;464(7289):691-3. doi: 10.1038/464691a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360729" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basal Metabolism/*physiology ; Body Size/*physiology ; Body Temperature/physiology ; Fractals ; History, 19th Century ; History, 20th Century ; Hot Temperature ; Mammals/*anatomy & histology/*physiology ; *Models, Biological
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  • 34
    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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  • 35
    Publication Date: 2010-06-19
    Description: Transcription of eukaryotic messenger RNA (mRNA) encoding genes by RNA polymerase II (Pol II) is triggered by the binding of transactivating proteins to enhancer DNA, which stimulates the recruitment of general transcription factors (TFIIA, B, D, E, F, H) and Pol II on the cis-linked promoter, leading to pre-initiation complex formation and transcription. In TFIID-dependent activation pathways, this general transcription factor containing TATA-box-binding protein is first recruited on the promoter through interaction with activators and cooperates with TFIIA to form a committed pre-initiation complex. However, neither the mechanisms by which activation signals are communicated between these factors nor the structural organization of the activated pre-initiation complex are known. Here we used cryo-electron microscopy to determine the architecture of nucleoprotein complexes composed of TFIID, TFIIA, the transcriptional activator Rap1 and yeast enhancer-promoter DNA. These structures revealed the mode of binding of Rap1 and TFIIA to TFIID, as well as a reorganization of TFIIA induced by its interaction with Rap1. We propose that this change in position increases the exposure of TATA-box-binding protein within TFIID, consequently enhancing its ability to interact with the promoter. A large Rap1-dependent DNA loop forms between the activator-binding site and the proximal promoter region. This loop is topologically locked by a TFIIA-Rap1 protein bridge that folds over the DNA. These results highlight the role of TFIIA in transcriptional activation, define a molecular mechanism for enhancer-promoter communication and provide structural insights into the pathways of intramolecular communication that convey transcription activation signals through the TFIID complex.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2900199/" 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/PMC2900199/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Papai, Gabor -- Tripathi, Manish K -- Ruhlmann, Christine -- Layer, Justin H -- Weil, P Anthony -- Schultz, Patrick -- GM52461/GM/NIGMS NIH HHS/ -- R01 GM052461/GM/NIGMS NIH HHS/ -- R01 GM052461-14/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Jun 17;465(7300):956-60. doi: 10.1038/nature09080.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Structural Biology and Genomics, Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), 1 rue Laurent Fries, BP10142, 67404 Illkirch, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20559389" target="_blank"〉PubMed〈/a〉
    Keywords: Cryoelectron Microscopy ; *Models, Molecular ; Nucleoproteins/chemistry/ultrastructure ; Protein Structure, Tertiary ; Saccharomyces cerevisiae ; Saccharomyces cerevisiae Proteins/chemistry/*metabolism/ultrastructure ; Telomere-Binding Proteins/chemistry/*metabolism/ultrastructure ; Transcription Factor TFIIA/chemistry/*metabolism ; Transcription Factor TFIID/chemistry/*metabolism ; Transcription Factors/chemistry/*metabolism/ultrastructure ; *Transcriptional Activation
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  • 36
    Publication Date: 2010-12-18
    Description: Recognition of modified histone species by distinct structural domains within 'reader' proteins plays a critical role in the regulation of gene expression. Readers that simultaneously recognize histones with multiple marks allow transduction of complex chromatin modification patterns into specific biological outcomes. Here we report that chromatin regulator tripartite motif-containing 24 (TRIM24) functions in humans as a reader of dual histone marks by means of tandem plant homeodomain (PHD) and bromodomain (Bromo) regions. The three-dimensional structure of the PHD-Bromo region of TRIM24 revealed a single functional unit for combinatorial recognition of unmodified H3K4 (that is, histone H3 unmodified at lysine 4, H3K4me0) and acetylated H3K23 (histone H3 acetylated at lysine 23, H3K23ac) within the same histone tail. TRIM24 binds chromatin and oestrogen receptor to activate oestrogen-dependent genes associated with cellular proliferation and tumour development. Aberrant expression of TRIM24 negatively correlates with survival of breast cancer patients. The PHD-Bromo of TRIM24 provides a structural rationale for chromatin activation through a non-canonical histone signature, establishing a new route by which chromatin readers may influence cancer pathogenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058826/" 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/PMC3058826/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tsai, Wen-Wei -- Wang, Zhanxin -- Yiu, Teresa T -- Akdemir, Kadir C -- Xia, Weiya -- Winter, Stefan -- Tsai, Cheng-Yu -- Shi, Xiaobing -- Schwarzer, Dirk -- Plunkett, William -- Aronow, Bruce -- Gozani, Or -- Fischle, Wolfgang -- Hung, Mien-Chie -- Patel, Dinshaw J -- Barton, Michelle Craig -- GM079641/GM/NIGMS NIH HHS/ -- GM081627/GM/NIGMS NIH HHS/ -- P01 GM081627/GM/NIGMS NIH HHS/ -- P01 GM081627-010003/GM/NIGMS NIH HHS/ -- P01 GM081627-020003/GM/NIGMS NIH HHS/ -- P30 EB009998/EB/NIBIB NIH HHS/ -- P30DK078392-01/DK/NIDDK NIH HHS/ -- T32 HD07325/HD/NICHD NIH HHS/ -- U54 RR025216/RR/NCRR NIH HHS/ -- UL1 TR000077/TR/NCATS NIH HHS/ -- England -- Nature. 2010 Dec 16;468(7326):927-32. doi: 10.1038/nature09542.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Program in Genes and Development, Graduate School of Biomedical Sciences, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21164480" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Breast Neoplasms/*genetics/*metabolism/pathology ; Carrier Proteins/chemistry/genetics/*metabolism ; Cell Line, Tumor ; Chromatin/metabolism ; Chromatin Assembly and Disassembly ; Crystallography, X-Ray ; Estrogen Receptor alpha/metabolism ; Estrogens/metabolism ; *Gene Expression Regulation, Neoplastic/genetics ; HEK293 Cells ; Histones/chemistry/*metabolism ; Humans ; Methylation ; Protein Array Analysis ; Protein Binding ; Protein Structure, Tertiary ; Substrate Specificity ; Survival Rate
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  • 37
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    Publication Date: 2010-04-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ganellin, Robin -- Duncan, William -- England -- Nature. 2010 Apr 29;464(7293):1292. doi: 10.1038/4641292a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20428161" target="_blank"〉PubMed〈/a〉
    Keywords: Drug Industry/history ; History, 20th Century ; Nobel Prize ; Pharmacology/*history ; Scotland
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  • 38
    Publication Date: 2010-02-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Penders, Bart -- Vermeulen, Niki -- Parker, John N -- England -- Nature. 2010 Jan 14;463(7278):157. doi: 10.1038/463157d.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20075896" target="_blank"〉PubMed〈/a〉
    Keywords: Government ; History, 20th Century ; History, 21st Century ; *Learning ; Private Sector ; Public Policy ; Science/*history/*methods/trends ; *Search Engine ; Universities
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  • 39
    Publication Date: 2010-01-08
    Description: Eukaryotic DNA replication uses kinase regulatory pathways to facilitate coordination with other processes during cell division cycles and response to environmental cues. At least two cell cycle-regulated protein kinase systems, the S-phase-specific cyclin-dependent protein kinases (S-CDKs) and the Dbf4-Cdc7 kinase (DDK, Dbf4-dependent protein kinase) are essential activators for initiation of DNA replication. Although the essential mechanism of CDK activation of DNA replication in Saccharomyces cerevisiae has been established, exactly how DDK acts has been unclear. Here we show that the amino terminal serine/threonine-rich domain (NSD) of Mcm4 has both inhibitory and facilitating roles in DNA replication control and that the sole essential function of DDK is to relieve an inhibitory activity residing within the NSD. By combining an mcm4 mutant lacking the inhibitory activity with mutations that bypass the requirement for CDKs for initiation of DNA replication, we show that DNA synthesis can occur in G1 phase when CDKs and DDK are limited. However, DDK is still required for efficient S phase progression. In the absence of DDK, CDK phosphorylation at the distal part of the Mcm4 NSD becomes crucial. Moreover, DDK-null cells fail to activate the intra-S-phase checkpoint in the presence of hydroxyurea-induced DNA damage and are unable to survive this challenge. Our studies establish that the eukaryote-specific NSD of Mcm4 has evolved to integrate several protein kinase regulatory signals for progression through S phase.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2805463/" 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/PMC2805463/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sheu, Yi-Jun -- Stillman, Bruce -- R01 GM045436/GM/NIGMS NIH HHS/ -- R01 GM045436-18/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Jan 7;463(7277):113-7. doi: 10.1038/nature08647.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20054399" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Cycle Proteins/antagonists & inhibitors/chemistry/genetics/*metabolism ; Cell Proliferation/drug effects ; DNA Damage ; DNA-Binding Proteins/antagonists & inhibitors/chemistry/genetics/*metabolism ; G1 Phase/drug effects ; Genes, Essential ; Hydroxyurea/pharmacology ; Microbial Viability/drug effects ; Minichromosome Maintenance Complex Component 4 ; Phosphorylation ; Protein Structure, Tertiary ; Protein-Serine-Threonine Kinases/deficiency/genetics/*metabolism ; S Phase/drug effects/*physiology ; Saccharomyces cerevisiae/*cytology/enzymology/growth & development/*metabolism ; Saccharomyces cerevisiae Proteins/antagonists & ; inhibitors/chemistry/genetics/*metabolism ; Sequence Deletion ; Substrate Specificity
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  • 40
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    Nature Publishing Group (NPG)
    Publication Date: 2010-04-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Apr 1;464(7289):649-50. doi: 10.1038/464649a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360688" target="_blank"〉PubMed〈/a〉
    Keywords: Data Collection ; Genetic Testing/trends ; Genetics, Medical/*trends ; Genome, Human/*genetics ; Genomics/economics/*history/trends ; Haplotypes/genetics ; History, 20th Century ; History, 21st Century ; Human Genome Project/*history ; Humans ; Time Factors
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  • 41
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    Nature Publishing Group (NPG)
    Publication Date: 2010-11-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gomory, Ralph -- England -- Nature. 2010 Nov 18;468(7322):378. doi: 10.1038/468378a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21085164" target="_blank"〉PubMed〈/a〉
    Keywords: Fractals/*history ; France ; History, 20th Century ; History, 21st Century ; Mathematics/history ; Nature ; Poland ; United States
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  • 42
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    Nature Publishing Group (NPG)
    Publication Date: 2010-02-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dalton, Rex -- England -- Nature. 2010 Feb 11;463(7282):724-5. doi: 10.1038/463724a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20148008" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arctic Regions ; Cryopreservation ; DNA/genetics/isolation & purification ; DNA, Mitochondrial/analysis/genetics ; Denmark ; Emigration and Immigration/*history ; Feces ; Fossils ; Genetics, Medical/history ; Genome, Human/*genetics ; Greenland/ethnology ; History, 20th Century ; History, 21st Century ; History, Ancient ; Humans ; Inuits/*ethnology/*history ; Male ; Paleontology/*history ; Phylogeny ; Reproducibility of Results ; Sequence Analysis, DNA ; Siberia/ethnology
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  • 43
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    Nature Publishing Group (NPG)
    Publication Date: 2008-05-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ball, Philip -- England -- Nature. 2008 May 8;453(7192):160-2. doi: 10.1038/453160a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18464725" target="_blank"〉PubMed〈/a〉
    Keywords: Auditory Perception/physiology ; Brain/physiology ; History, 18th Century ; History, 20th Century ; History, Ancient ; History, Medieval ; Humans ; Mathematics ; *Music/history/psychology ; *Science/history
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  • 44
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    Nature Publishing Group (NPG)
    Publication Date: 2008-02-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Perry, Joseph W -- England -- Nature. 2008 Feb 7;451(7179):636-7. doi: 10.1038/451636a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18256651" target="_blank"〉PubMed〈/a〉
    Keywords: History, 20th Century ; Holography/history/*instrumentation/methods
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  • 45
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    Nature Publishing Group (NPG)
    Publication Date: 2008-10-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sharp, Paul M -- Hahn, Beatrice H -- England -- Nature. 2008 Oct 2;455(7213):605-6. doi: 10.1038/455605a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18833267" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Democratic Republic of the Congo/epidemiology ; *Evolution, Molecular ; Genetic Variation/*genetics ; HIV Infections/*epidemiology/*virology ; HIV-1/classification/*genetics/*isolation & purification ; History, 20th Century ; Humans ; Phylogeny
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  • 46
    Publication Date: 2008-02-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ball, Philip -- England -- Nature. 2008 Feb 28;451(7182):1065-6. doi: 10.1038/4511065a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18305535" target="_blank"〉PubMed〈/a〉
    Keywords: History, 20th Century ; Quinine/*chemical synthesis/chemistry/*history ; Reproducibility of Results
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  • 47
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    Nature Publishing Group (NPG)
    Publication Date: 2008-05-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huron, David -- England -- Nature. 2008 May 22;453(7194):456-7. doi: 10.1038/453456a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Music & Center for Cognitive Science, Ohio State University, Columbus, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18497806" target="_blank"〉PubMed〈/a〉
    Keywords: *Cultural Diversity ; *Cultural Evolution ; History, 17th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; Humans ; *Music/history ; *Neurosciences
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  • 48
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    Nature Publishing Group (NPG)
    Publication Date: 2008-11-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Nov 20;456(7220):281. doi: 10.1038/456281a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19020564" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anniversaries and Special Events ; *Biological Evolution ; Biological Science Disciplines/history ; Genetic Speciation ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; Selection, Genetic
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  • 49
    Publication Date: 2008-01-04
    Description: The carbon balance of terrestrial ecosystems is particularly sensitive to climatic changes in autumn and spring, with spring and autumn temperatures over northern latitudes having risen by about 1.1 degrees C and 0.8 degrees C, respectively, over the past two decades. A simultaneous greening trend has also been observed, characterized by a longer growing season and greater photosynthetic activity. These observations have led to speculation that spring and autumn warming could enhance carbon sequestration and extend the period of net carbon uptake in the future. Here we analyse interannual variations in atmospheric carbon dioxide concentration data and ecosystem carbon dioxide fluxes. We find that atmospheric records from the past 20 years show a trend towards an earlier autumn-to-winter carbon dioxide build-up, suggesting a shorter net carbon uptake period. This trend cannot be explained by changes in atmospheric transport alone and, together with the ecosystem flux data, suggest increasing carbon losses in autumn. We use a process-based terrestrial biosphere model and satellite vegetation greenness index observations to investigate further the observed seasonal response of northern ecosystems to autumnal warming. We find that both photosynthesis and respiration increase during autumn warming, but the increase in respiration is greater. In contrast, warming increases photosynthesis more than respiration in spring. Our simulations and observations indicate that northern terrestrial ecosystems may currently lose carbon dioxide in response to autumn warming, with a sensitivity of about 0.2 PgC degrees C(-1), offsetting 90% of the increased carbon dioxide uptake during spring. If future autumn warming occurs at a faster rate than in spring, the ability of northern ecosystems to sequester carbon may be diminished earlier than previously suggested.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Piao, Shilong -- Ciais, Philippe -- Friedlingstein, Pierre -- Peylin, Philippe -- Reichstein, Markus -- Luyssaert, Sebastiaan -- Margolis, Hank -- Fang, Jingyun -- Barr, Alan -- Chen, Anping -- Grelle, Achim -- Hollinger, David Y -- Laurila, Tuomas -- Lindroth, Anders -- Richardson, Andrew D -- Vesala, Timo -- England -- Nature. 2008 Jan 3;451(7174):49-52. doi: 10.1038/nature06444.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉LSCE, UMR CEA-CNRS, Batiment 709, CE, L'Orme des Merisiers, F-91191 Gif-sur-Yvette, France. slpiao@lsce.ipsl.fr〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18172494" target="_blank"〉PubMed〈/a〉
    Keywords: Atmosphere/chemistry ; Biomass ; Carbon Dioxide/analysis/*metabolism ; Cell Respiration ; *Ecosystem ; Fossil Fuels ; Geography ; Greenhouse Effect ; History, 20th Century ; History, 21st Century ; Oceans and Seas ; Photosynthesis ; Plant Transpiration ; Plants/metabolism ; Rain ; *Seasons ; Soil/analysis ; *Temperature ; Water/metabolism
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  • 50
    Publication Date: 2008-09-12
    Description: Old-growth forests remove carbon dioxide from the atmosphere at rates that vary with climate and nitrogen deposition. The sequestered carbon dioxide is stored in live woody tissues and slowly decomposing organic matter in litter and soil. Old-growth forests therefore serve as a global carbon dioxide sink, but they are not protected by international treaties, because it is generally thought that ageing forests cease to accumulate carbon. Here we report a search of literature and databases for forest carbon-flux estimates. We find that in forests between 15 and 800 years of age, net ecosystem productivity (the net carbon balance of the forest including soils) is usually positive. Our results demonstrate that old-growth forests can continue to accumulate carbon, contrary to the long-standing view that they are carbon neutral. Over 30 per cent of the global forest area is unmanaged primary forest, and this area contains the remaining old-growth forests. Half of the primary forests (6 x 10(8) hectares) are located in the boreal and temperate regions of the Northern Hemisphere. On the basis of our analysis, these forests alone sequester about 1.3 +/- 0.5 gigatonnes of carbon per year. Thus, our findings suggest that 15 per cent of the global forest area, which is currently not considered when offsetting increasing atmospheric carbon dioxide concentrations, provides at least 10 per cent of the global net ecosystem productivity. Old-growth forests accumulate carbon for centuries and contain large quantities of it. We expect, however, that much of this carbon, even soil carbon, will move back to the atmosphere if these forests are disturbed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Luyssaert, Sebastiaan -- Schulze, E-Detlef -- Borner, Annett -- Knohl, Alexander -- Hessenmoller, Dominik -- Law, Beverly E -- Ciais, Philippe -- Grace, John -- England -- Nature. 2008 Sep 11;455(7210):213-5. doi: 10.1038/nature07276.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of Antwerp, 2610 Wilrijk, Belgium. sebastiaan.luyssaert@ua.ac.be〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18784722" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Atmosphere/chemistry ; Biomass ; Carbon/*metabolism ; Carbon Dioxide/metabolism ; Databases, Factual ; Disasters ; *Ecosystem ; History, 15th Century ; History, 16th Century ; History, 17th Century ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; History, Medieval ; Human Activities ; Time Factors ; Trees/*metabolism
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  • 51
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    Publication Date: 2008-06-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barron, Michael -- England -- Nature. 2008 Jun 12;453(7197):859-60. doi: 10.1038/453859a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Architecture and Civil Engineering, University of Bath, BA2 7AY, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18548056" target="_blank"〉PubMed〈/a〉
    Keywords: Absorption ; *Acoustics ; Auditory Perception ; *Facility Design and Construction/history ; Hearing/physiology ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Humans ; *Music/history
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  • 52
    Publication Date: 2008-09-19
    Description: The use of small organic molecules as catalysts has been known for more than a century. But only in the past decade has organocatalysis become a thriving area of general concepts and widely applicable asymmetric reactions. Here I present my opinion on why the field of organocatalysis has blossomed so dramatically over the past decade.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉MacMillan, David W C -- R01 GM078201-01-01/GM/NIGMS NIH HHS/ -- England -- Nature. 2008 Sep 18;455(7211):304-8. doi: 10.1038/nature07367.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Merck Center for Catalysis at Princeton University, 116 Frick Laboratory, Princeton University, Princeton, New Jersey 08540, USA. dmacmill@princeton.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18800128" target="_blank"〉PubMed〈/a〉
    Keywords: Catalysis ; Chemistry, Organic/*history/*methods ; History, 20th Century ; History, 21st Century ; Hydrogen Bonding ; Ions/chemistry
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  • 53
    Publication Date: 2008-02-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Beccaloni, George W -- Smith, Vincent S -- England -- Nature. 2008 Feb 28;451(7182):1050. doi: 10.1038/4511050d.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18305520" target="_blank"〉PubMed〈/a〉
    Keywords: Biology/*history ; History, 19th Century ; History, 20th Century ; History, 21st Century ; *Selection, Genetic
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  • 54
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    Publication Date: 2008-02-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smaglik, Paul -- England -- Nature. 2008 Jan 24;451(7177):494-6. doi: 10.1038/nj7177-494a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18290265" target="_blank"〉PubMed〈/a〉
    Keywords: Argentina ; Emigration and Immigration/history/trends ; *Federal Government ; History, 20th Century ; History, 21st Century ; Politics ; Research Personnel/economics/history/*trends ; Research Support as Topic/economics/history ; Salaries and Fringe Benefits ; Science/*economics/history/manpower/*organization & administration
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  • 55
    Publication Date: 2008-01-04
    Description: Synthesis of proteins containing errors (mistranslation) is prevented by aminoacyl transfer RNA synthetases through their accurate aminoacylation of cognate tRNAs and their ability to correct occasional errors of aminoacylation by editing reactions. A principal source of mistranslation comes from mistaking glycine or serine for alanine, which can lead to serious cell and animal pathologies, including neurodegeneration. A single specific G.U base pair (G3.U70) marks a tRNA for aminoacylation by alanyl-tRNA synthetase. Mistranslation occurs when glycine or serine is joined to the G3.U70-containing tRNAs, and is prevented by the editing activity that clears the mischarged amino acid. Previously it was assumed that the specificity for recognition of tRNA(Ala) for editing was provided by the same structural determinants as used for aminoacylation. Here we show that the editing site of alanyl-tRNA synthetase, as an artificial recombinant fragment, targets mischarged tRNA(Ala) using a structural motif unrelated to that for aminoacylation so that, remarkably, two motifs (one for aminoacylation and one for editing) in the same enzyme independently can provide determinants for tRNA(Ala) recognition. The structural motif for editing is also found naturally in genome-encoded protein fragments that are widely distributed in evolution. These also recognize mischarged tRNA(Ala). Thus, through evolution, three different complexes with the same tRNA can guard against mistaking glycine or serine for alanine.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Beebe, Kirk -- Mock, Marissa -- Merriman, Eve -- Schimmel, Paul -- England -- Nature. 2008 Jan 3;451(7174):90-3. doi: 10.1038/nature06454.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18172502" target="_blank"〉PubMed〈/a〉
    Keywords: Alanine-tRNA Ligase/*chemistry/*metabolism ; Amino Acid Motifs ; *Base Pairing ; Binding Sites ; Escherichia coli/enzymology ; Peptide Fragments/chemistry/metabolism ; Protein Biosynthesis ; Protein Structure, Tertiary ; RNA, Transfer, Ala/*chemistry/genetics/*metabolism ; Substrate Specificity
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  • 56
    Publication Date: 2008-08-30
    Description: The slicer activity of the RNA-induced silencing complex is associated with argonaute, the RNase H-like PIWI domain of which catalyses guide-strand-mediated sequence-specific cleavage of target messenger RNA. Here we report on the crystal structure of Thermus thermophilus argonaute bound to a 5'-phosphorylated 21-base DNA guide strand, thereby identifying the nucleic-acid-binding channel positioned between the PAZ- and PIWI-containing lobes, as well as the pivot-like conformational changes associated with complex formation. The bound guide strand is anchored at both of its ends, with the solvent-exposed Watson-Crick edges of stacked bases 2 to 6 positioned for nucleation with the mRNA target, whereas two critically positioned arginines lock bases 10 and 11 at the cleavage site into an unanticipated orthogonal alignment. Biochemical studies indicate that key amino acid residues at the active site and those lining the 5'-phosphate-binding pocket made up of the Mid domain are critical for cleavage activity, whereas alterations of residues lining the 2-nucleotide 3'-end-binding pocket made up of the PAZ domain show little effect.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4689319/" 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/PMC4689319/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Yanli -- Sheng, Gang -- Juranek, Stefan -- Tuschl, Thomas -- Patel, Dinshaw J -- P30 CA008748/CA/NCI NIH HHS/ -- R01 AI068776/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Nov 13;456(7219):209-13. doi: 10.1038/nature07315. Epub 2008 Aug 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18754009" target="_blank"〉PubMed〈/a〉
    Keywords: Aptamers, Nucleotide/metabolism ; Bacterial Proteins/*chemistry/metabolism ; Crystallography, X-Ray ; *Gene Silencing ; Hydrogen Bonding ; *Models, Molecular ; Mutation ; Protein Structure, Tertiary ; RNA/metabolism ; Thermus thermophilus/*chemistry/genetics
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  • 57
    Publication Date: 2008-11-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Coulson, Tim -- Malo, Aurelio -- England -- Nature. 2008 Nov 6;456(7218):43-4. doi: 10.1038/456043a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18987726" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arvicolinae/*physiology ; *Ecosystem ; Female ; *Greenhouse Effect ; History, 20th Century ; History, 21st Century ; Norway ; Population Dynamics ; Seasons ; Snow ; Temperature
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  • 58
    Publication Date: 2008-09-02
    Description: A common hallmark of human cancers is the overexpression of telomerase, a ribonucleoprotein complex that is responsible for maintaining the length and integrity of chromosome ends. Telomere length deregulation and telomerase activation is an early, and perhaps necessary, step in cancer cell evolution. Here we present the high-resolution structure of the Tribolium castaneum catalytic subunit of telomerase, TERT. The protein consists of three highly conserved domains, organized into a ring-like structure that shares common features with retroviral reverse transcriptases, viral RNA polymerases and B-family DNA polymerases. Domain organization places motifs implicated in substrate binding and catalysis in the interior of the ring, which can accommodate seven to eight bases of double-stranded nucleic acid. Modelling of an RNA-DNA heteroduplex in the interior of this ring demonstrates a perfect fit between the protein and the nucleic acid substrate, and positions the 3'-end of the DNA primer at the active site of the enzyme, providing evidence for the formation of an active telomerase elongation complex.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gillis, Andrew J -- Schuller, Anthony P -- Skordalakes, Emmanuel -- England -- Nature. 2008 Oct 2;455(7213):633-7. doi: 10.1038/nature07283. Epub 2008 Aug 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gene Expression and Regulation Program, The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18758444" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Animals ; Binding Sites ; Catalysis ; Catalytic Domain ; Conserved Sequence ; Crystallization ; Crystallography, X-Ray ; Humans ; Models, Molecular ; Nucleotides/metabolism ; Protein Structure, Tertiary ; Telomerase/*chemistry/metabolism ; Tribolium/*enzymology
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  • 59
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    Nature Publishing Group (NPG)
    Publication Date: 2008-09-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Powell, Kendall -- England -- Nature. 2008 Sep 25;455(7212):455-8. doi: 10.1038/455455a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18818627" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Awards and Prizes ; Creativity ; Elephants/physiology ; *Foundations/economics ; Greenhouse Effect ; Hand/physiology ; History, 20th Century ; History, 21st Century ; Humans ; Hybridization, Genetic ; Illinois ; Neurosciences ; *Research Personnel/economics/psychology ; Robotics ; *Science/economics ; Selection, Genetic
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  • 60
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    Nature Publishing Group (NPG)
    Publication Date: 2008-12-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wassarman, Paul M -- England -- Nature. 2008 Dec 4;456(7222):586-7. doi: 10.1038/456586a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19052615" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Conserved Sequence ; Crystallography, X-Ray ; Egg Proteins/*chemistry/genetics/*metabolism ; Female ; Fertilization/physiology ; Male ; Membrane Glycoproteins/*chemistry/genetics/*metabolism ; Mice ; Ovum/*chemistry/*metabolism ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, Cell Surface/*chemistry/genetics/*metabolism ; Spermatozoa/metabolism
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  • 61
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    Nature Publishing Group (NPG)
    Publication Date: 2008-02-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Watson, Bob -- England -- Nature. 2008 Feb 7;451(7179):642. doi: 10.1038/451642a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Watson@defra.gsi.gov.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18256656" target="_blank"〉PubMed〈/a〉
    Keywords: Atmosphere/chemistry ; Carbon Dioxide/metabolism ; Ecosystem ; *Greenhouse Effect ; History, 20th Century ; History, 21st Century ; Sweden
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  • 62
    Publication Date: 2008-05-10
    Description: The Amazon rainforest plays a crucial role in the climate system, helping to drive atmospheric circulations in the tropics by absorbing energy and recycling about half of the rainfall that falls on it. This region (Amazonia) is also estimated to contain about one-tenth of the total carbon stored in land ecosystems, and to account for one-tenth of global, net primary productivity. The resilience of the forest to the combined pressures of deforestation and global warming is therefore of great concern, especially as some general circulation models (GCMs) predict a severe drying of Amazonia in the twenty-first century. Here we analyse these climate projections with reference to the 2005 drought in western Amazonia, which was associated with unusually warm North Atlantic sea surface temperatures (SSTs). We show that reduction of dry-season (July-October) rainfall in western Amazonia correlates well with an index of the north-south SST gradient across the equatorial Atlantic (the 'Atlantic N-S gradient'). Our climate model is unusual among current GCMs in that it is able to reproduce this relationship and also the observed twentieth-century multidecadal variability in the Atlantic N-S gradient, provided that the effects of aerosols are included in the model. Simulations for the twenty-first century using the same model show a strong tendency for the SST conditions associated with the 2005 drought to become much more common, owing to continuing reductions in reflective aerosol pollution in the Northern Hemisphere.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cox, Peter M -- Harris, Phil P -- Huntingford, Chris -- Betts, Richard A -- Collins, Matthew -- Jones, Chris D -- Jupp, Tim E -- Marengo, Jose A -- Nobre, Carlos A -- England -- Nature. 2008 May 8;453(7192):212-5. doi: 10.1038/nature06960.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Engineering, Computing and Mathematics, University of Exeter, Exeter EX4 4QF, UK. p.m.cox@exeter.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18464740" target="_blank"〉PubMed〈/a〉
    Keywords: Aerosols/*analysis ; Atlantic Ocean ; Carbon Dioxide/analysis ; Disasters/history/*statistics & numerical data ; *Ecosystem ; Environmental Pollution/*statistics & numerical data ; *Greenhouse Effect ; History, 20th Century ; History, 21st Century ; *Models, Theoretical ; Pacific Ocean ; Probability ; Rain ; Seasons ; South America ; Temperature ; Trees/*physiology
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  • 63
    Publication Date: 2008-09-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Berg, Paul -- England -- Nature. 2008 Sep 18;455(7211):290-1. doi: 10.1038/455290a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Beckman Center of Molecular and Genetic Medicine, at Stanford University, 279 Campus Drive, Stanford, California 94305, USA. pberg@stanford.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18800118" target="_blank"〉PubMed〈/a〉
    Keywords: Biotechnology/history/standards ; California ; Congresses as Topic/*history ; DNA, Recombinant/*history ; Ecosystem ; Genetic Engineering/*history/standards ; Guidelines as Topic ; History, 20th Century ; Humans ; Risk Assessment/history ; Safety/*standards ; Simian virus 40/genetics/physiology
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  • 64
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    Nature Publishing Group (NPG)
    Publication Date: 2008-01-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weinberger, Sharon -- England -- Nature. 2008 Jan 24;451(7177):390-3. doi: 10.1038/451390a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18216826" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bionics/trends ; History, 20th Century ; History, 21st Century ; Humans ; Internet ; Research/history/*trends ; Robotics/trends ; Security Measures/history/organization & administration/*trends ; Technology/history/*trends ; Terrorism/prevention & control ; United States ; United States Government Agencies/economics/history/organization & ; administration/*trends
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  • 65
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    Nature Publishing Group (NPG)
    Publication Date: 2008-06-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Berry, Andrew -- Browne, Janet -- England -- Nature. 2008 Jun 26;453(7199):1188-90. doi: 10.1038/4531188a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Harvard University, Biology Laboratories, 16 Divinity Avenue, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18580934" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; History, 19th Century ; History, 20th Century ; Selection, Genetic
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  • 66
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    Nature Publishing Group (NPG)
    Publication Date: 2008-02-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jones, Dan -- England -- Nature. 2008 Jan 31;451(7178):512-5. doi: 10.1038/451512a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18235473" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological ; Aggression/*physiology/psychology ; Altruism ; Anger/physiology ; Animals ; Antisocial Personality Disorder/physiopathology ; *Biological Evolution ; Conflict (Psychology) ; Female ; History, 15th Century ; History, 16th Century ; History, 17th Century ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Medieval ; *Homicide/history/psychology ; Humans ; Male ; Models, Biological ; Morals ; Pan troglodytes/physiology ; Prefrontal Cortex/anatomy & histology/physiology ; Sex Characteristics ; United Nations ; Violence/psychology ; Warfare
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  • 67
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    Nature Publishing Group (NPG)
    Publication Date: 2008-05-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wenner, Melinda -- England -- Nature. 2008 May 15;453(7193):271-3. doi: 10.1038/453271a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18480787" target="_blank"〉PubMed〈/a〉
    Keywords: *Apoptosis ; Caspases/metabolism ; History, 20th Century ; History, 21st Century ; Humans ; Immunity, Innate ; Kenya ; Neoplasms/pathology/therapy ; Signal Transduction ; Ubiquitin/metabolism ; United States
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  • 68
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    Nature Publishing Group (NPG)
    Publication Date: 2008-09-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Sep 11;455(7210):137-8. doi: 10.1038/455137b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18784666" target="_blank"〉PubMed〈/a〉
    Keywords: Congresses as Topic/*history ; Creativity ; History, 20th Century ; History, 21st Century ; Human Genome Project/history ; Humans ; Internationality ; Paris ; Physics/*history ; Research Personnel/history
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  • 69
    Publication Date: 2008-09-06
    Description: Human cancer cells typically harbour multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas (TCGA) pilot project aims to assess the value of large-scale multi-dimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas--the most common type of adult brain cancer--and nucleotide sequence aberrations in 91 of the 206 glioblastomas. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the phosphatidylinositol-3-OH kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of glioblastoma. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671642/" 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/PMC2671642/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cancer Genome Atlas Research Network -- R01 CA099041/CA/NCI NIH HHS/ -- R01 CA099041-05/CA/NCI NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- U24 CA126543-01/CA/NCI NIH HHS/ -- U24 CA126544/CA/NCI NIH HHS/ -- U24 CA126544-01/CA/NCI NIH HHS/ -- U24 CA126546/CA/NCI NIH HHS/ -- U24 CA126546-01/CA/NCI NIH HHS/ -- U24 CA126551-01/CA/NCI NIH HHS/ -- U24 CA126554/CA/NCI NIH HHS/ -- U24 CA126554-01/CA/NCI NIH HHS/ -- U24 CA126561/CA/NCI NIH HHS/ -- U24 CA126561-01/CA/NCI NIH HHS/ -- U24 CA126563/CA/NCI NIH HHS/ -- U24 CA126563-01/CA/NCI NIH HHS/ -- U24CA126543/CA/NCI NIH HHS/ -- U24CA126544/CA/NCI NIH HHS/ -- U24CA126546/CA/NCI NIH HHS/ -- U24CA126551/CA/NCI NIH HHS/ -- U24CA126554/CA/NCI NIH HHS/ -- U24CA126561/CA/NCI NIH HHS/ -- U24CA126563/CA/NCI NIH HHS/ -- U54 HG003067/HG/NHGRI NIH HHS/ -- U54 HG003067-01/HG/NHGRI NIH HHS/ -- U54 HG003079/HG/NHGRI NIH HHS/ -- U54 HG003079-05/HG/NHGRI NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- U54 HG003273-01/HG/NHGRI NIH HHS/ -- U54HG003067/HG/NHGRI NIH HHS/ -- U54HG003079/HG/NHGRI NIH HHS/ -- U54HG003273/HG/NHGRI NIH HHS/ -- England -- Nature. 2008 Oct 23;455(7216):1061-8. doi: 10.1038/nature07385. Epub 2008 Sep 4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18772890" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Aged ; Aged, 80 and over ; Brain Neoplasms/*genetics ; DNA Methylation ; DNA Modification Methylases/genetics ; DNA Repair/genetics ; DNA Repair Enzymes/genetics ; Female ; Gene Dosage ; *Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Genes, erbB-1/genetics ; Genome, Human/genetics ; *Genomics ; Glioblastoma/*genetics ; Humans ; Male ; Middle Aged ; Models, Molecular ; Mutation/genetics ; Neurofibromin 1/genetics ; Phosphatidylinositol 3-Kinases/genetics ; Protein Structure, Tertiary ; Retrospective Studies ; Signal Transduction/genetics ; Tumor Suppressor Proteins/genetics
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  • 70
    Publication Date: 2008-07-04
    Description: Neurotrophins (NTs) are important regulators for the survival, differentiation and maintenance of different peripheral and central neurons. NTs bind to two distinct classes of glycosylated receptor: the p75 neurotrophin receptor (p75(NTR)) and tyrosine kinase receptors (Trks). Whereas p75(NTR) binds to all NTs, the Trk subtypes are specific for each NT. The question of whether NTs stimulate p75(NTR) by inducing receptor homodimerization is still under debate. Here we report the 2.6-A resolution crystal structure of neurotrophin-3 (NT-3) complexed to the ectodomain of glycosylated p75(NTR). In contrast to the previously reported asymmetric complex structure, which contains a dimer of nerve growth factor (NGF) bound to a single ectodomain of deglycosylated p75(NTR) (ref. 3), we show that NT-3 forms a central homodimer around which two glycosylated p75(NTR) molecules bind symmetrically. Symmetrical binding occurs along the NT-3 interfaces, resulting in a 2:2 ligand-receptor cluster. A comparison of the symmetrical and asymmetric structures reveals significant differences in ligand-receptor interactions and p75(NTR) conformations. Biochemical experiments indicate that both NT-3 and NGF bind to p75(NTR) with 2:2 stoichiometry in solution, whereas the 2:1 complexes are the result of artificial deglycosylation. We therefore propose that the symmetrical 2:2 complex reflects a native state of p75(NTR) activation at the cell surface. These results provide a model for NTs-p75(NTR) recognition and signal generation, as well as insights into coordination between p75(NTR) and Trks.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gong, Yong -- Cao, Peng -- Yu, Hong-jun -- Jiang, Tao -- England -- Nature. 2008 Aug 7;454(7205):789-93. doi: 10.1038/nature07089. Epub 2008 Jul 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18596692" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Crystallography, X-Ray ; Dimerization ; Glycosylation ; Humans ; Ligands ; Models, Molecular ; Neurotrophin 3/*chemistry/genetics/*metabolism ; Protein Binding ; Protein Structure, Tertiary ; Rats ; Receptor, Nerve Growth Factor/*chemistry/genetics/*metabolism ; Spodoptera
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  • 71
    Publication Date: 2008-02-26
    Description: The psychosis associated with schizophrenia is characterized by alterations in sensory processing and perception. Some antipsychotic drugs were identified by their high affinity for serotonin 5-HT2A receptors (2AR). Drugs that interact with metabotropic glutamate receptors (mGluR) also have potential for the treatment of schizophrenia. The effects of hallucinogenic drugs, such as psilocybin and lysergic acid diethylamide, require the 2AR and resemble some of the core symptoms of schizophrenia. Here we show that the mGluR2 interacts through specific transmembrane helix domains with the 2AR, a member of an unrelated G-protein-coupled receptor family, to form functional complexes in brain cortex. The 2AR-mGluR2 complex triggers unique cellular responses when targeted by hallucinogenic drugs, and activation of mGluR2 abolishes hallucinogen-specific signalling and behavioural responses. In post-mortem human brain from untreated schizophrenic subjects, the 2AR is upregulated and the mGluR2 is downregulated, a pattern that could predispose to psychosis. These regulatory changes indicate that the 2AR-mGluR2 complex may be involved in the altered cortical processes of schizophrenia, and this complex is therefore a promising new target for the treatment of psychosis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743172/" 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/PMC2743172/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gonzalez-Maeso, Javier -- Ang, Rosalind L -- Yuen, Tony -- Chan, Pokman -- Weisstaub, Noelia V -- Lopez-Gimenez, Juan F -- Zhou, Mingming -- Okawa, Yuuya -- Callado, Luis F -- Milligan, Graeme -- Gingrich, Jay A -- Filizola, Marta -- Meana, J Javier -- Sealfon, Stuart C -- G9811527/Medical Research Council/United Kingdom -- P01 DA012923/DA/NIDA NIH HHS/ -- P01 DA012923-06A10004/DA/NIDA NIH HHS/ -- T32 DA007135/DA/NIDA NIH HHS/ -- T32 DA007135-25S1/DA/NIDA NIH HHS/ -- T32 GM062754/GM/NIGMS NIH HHS/ -- England -- Nature. 2008 Mar 6;452(7183):93-7. doi: 10.1038/nature06612. Epub 2008 Feb 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, Mount Sinai School of Medicine, New York, New York 10029, USA. javier.maeso@mssm.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18297054" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/cytology/metabolism ; Cell Line ; Cells, Cultured ; Down-Regulation ; Hallucinogens/metabolism/pharmacology ; Humans ; Mice ; Models, Molecular ; Multiprotein Complexes/chemistry/genetics/metabolism ; Protein Binding ; Protein Structure, Tertiary ; Psychotic Disorders/drug therapy/genetics/*metabolism ; Receptor, Serotonin, 5-HT2A/analysis/deficiency/genetics/*metabolism ; Receptors, Metabotropic Glutamate/analysis/antagonists & ; inhibitors/genetics/*metabolism ; Schizophrenia/metabolism ; Signal Transduction/drug effects ; Up-Regulation
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  • 72
    Publication Date: 2008-05-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goodman, Neville W -- England -- Nature. 2008 May 15;453(7193):281. doi: 10.1038/453281c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18480791" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/economics/history/*standards ; History, 20th Century ; Humans ; Lobbying ; *Politics ; *Public Opinion
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  • 73
    Publication Date: 2008-02-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bland, Phil -- England -- Nature. 2008 Feb 14;451(7180):768. doi: 10.1038/451768c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18272996" target="_blank"〉PubMed〈/a〉
    Keywords: Great Britain ; History, 20th Century ; History, 21st Century ; Research Support as Topic/*economics/history/*trends ; Science/*economics/history/trends
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  • 74
    Publication Date: 2008-09-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maseland, Robbert -- England -- Nature. 2008 Sep 11;455(7210):167. doi: 10.1038/455167c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18784701" target="_blank"〉PubMed〈/a〉
    Keywords: Competitive Behavior ; Creativity ; Europe ; History, 19th Century ; History, 20th Century ; History, 21st Century ; *Internationality ; Science/history/*standards/trends ; United States
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  • 75
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    Nature Publishing Group (NPG)
    Publication Date: 2008-11-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Blobel, Gunter -- England -- Nature. 2008 Nov 6;456(7218):52. doi: 10.1038/456052a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gunter Blobel is at the Rockefeller University, 1230 York Avenue, New York, New York 10021, USA. blobel@mail.rockefeller.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18987733" target="_blank"〉PubMed〈/a〉
    Keywords: *Cell Physiological Phenomena ; History, 20th Century ; Microscopy, Electron/history ; Organelles/ultrastructure ; Romania ; United States
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  • 76
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    Nature Publishing Group (NPG)
    Publication Date: 2008-06-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Steel, Duncan -- England -- Nature. 2008 Jun 26;453(7199):1157-9. doi: 10.1038/4531157a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18580919" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Ecosystem ; History, 20th Century ; *Meteoroids ; Siberia ; Trees
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  • 77
    Publication Date: 2008-08-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kanner, Baruch I -- England -- Nature. 2008 Jul 31;454(7204):593-4. doi: 10.1038/454593a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18668099" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry/*metabolism ; Galactose/metabolism ; *Ion Transport ; Models, Molecular ; Protein Structure, Tertiary ; Sodium/metabolism ; Sodium-Glucose Transport Proteins/*chemistry/*metabolism
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  • 78
    Publication Date: 2008-11-07
    Description: The population cycles of rodents at northern latitudes have puzzled people for centuries, and their impact is manifest throughout the alpine ecosystem. Climate change is known to be able to drive animal population dynamics between stable and cyclic phases, and has been suggested to cause the recent changes in cyclic dynamics of rodents and their predators. But although predator-rodent interactions are commonly argued to be the cause of the Fennoscandian rodent cycles, the role of the environment in the modulation of such dynamics is often poorly understood in natural systems. Hence, quantitative links between climate-driven processes and rodent dynamics have so far been lacking. Here we show that winter weather and snow conditions, together with density dependence in the net population growth rate, account for the observed population dynamics of the rodent community dominated by lemmings (Lemmus lemmus) in an alpine Norwegian core habitat between 1970 and 1997, and predict the observed absence of rodent peak years after 1994. These local rodent dynamics are coherent with alpine bird dynamics both locally and over all of southern Norway, consistent with the influence of large-scale fluctuations in winter conditions. The relationship between commonly available meteorological data and snow conditions indicates that changes in temperature and humidity, and thus conditions in the subnivean space, seem to markedly affect the dynamics of alpine rodents and their linked groups. The pattern of less regular rodent peaks, and corresponding changes in the overall dynamics of the alpine ecosystem, thus seems likely to prevail over a growing area under projected climate change.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kausrud, Kyrre L -- Mysterud, Atle -- Steen, Harald -- Vik, Jon Olav -- Ostbye, Eivind -- Cazelles, Bernard -- Framstad, Erik -- Eikeset, Anne Maria -- Mysterud, Ivar -- Solhoy, Torstein -- Stenseth, Nils Chr -- England -- Nature. 2008 Nov 6;456(7218):93-7. doi: 10.1038/nature07442.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Ecological and Evolutionary Synthesis, University of Oslo, PO Box 1066 Blindern, N-0316 Oslo, Norway.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18987742" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arvicolinae/*physiology ; Birds/physiology ; *Ecosystem ; *Greenhouse Effect ; History, 20th Century ; History, 21st Century ; Humidity ; Models, Biological ; Norway ; Population Dynamics ; Seasons ; Snow ; Temperature
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  • 79
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    Nature Publishing Group (NPG)
    Publication Date: 2008-03-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Blumberg, Baruch S -- England -- Nature. 2008 Mar 27;452(7186):422. doi: 10.1038/452422a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Baruch S. Blumberg is at the Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111-2497, USA.baruch.blumberg@fccc.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18368111" target="_blank"〉PubMed〈/a〉
    Keywords: Exobiology/history ; History, 20th Century ; Humans ; Molecular Biology/*history ; Nobel Prize ; Plasmids/genetics/history ; Transduction, Genetic/history ; United States
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  • 80
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    Nature Publishing Group (NPG)
    Publication Date: 2008-01-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mayorga, Emilio -- England -- Nature. 2008 Jan 24;451(7177):405-6. doi: 10.1038/451405a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18216839" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/*history/methods ; Atmosphere/chemistry ; Bicarbonates/analysis/chemistry ; Carbon/*analysis ; Carbon Dioxide/analysis/metabolism ; Greenhouse Effect ; History, 20th Century ; History, 21st Century ; Human Activities/*history ; Louisiana ; Mississippi ; Rain ; Rivers/*chemistry
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  • 81
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    Nature Publishing Group (NPG)
    Publication Date: 2008-07-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Winchester, Simon -- England -- Nature. 2008 Jul 24;454(7203):409-11. doi: 10.1038/454409a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉simonwinchester@mac.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18650901" target="_blank"〉PubMed〈/a〉
    Keywords: *Authorship ; China ; Culture ; England ; History, 20th Century ; History, 21st Century ; History, Ancient ; Literature, Modern/*history ; Technology/education/*history
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  • 82
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    Nature Publishing Group (NPG)
    Publication Date: 2008-09-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dalton, Rex -- England -- Nature. 2008 Sep 11;455(7210):153-5. doi: 10.1038/455153a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18784695" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Argentina ; *Biological Evolution ; Dinosaurs ; *Fossils ; History, 20th Century ; History, 21st Century ; *Mammals/anatomy & histology/classification ; Paleontology/history ; Plants ; Politics
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  • 83
    Publication Date: 2008-11-07
    Description: The recent emergence of highly pathogenic avian (H5N1) influenza viruses, their epizootic and panzootic nature, and their association with lethal human infections have raised significant global health concerns. Several studies have underlined the importance of non-structural protein NS1 in the increased pathogenicity and virulence of these strains. NS1, which consists of two domains-a double-stranded RNA (dsRNA) binding domain and the effector domain, separated through a linker-is an antagonist of antiviral type-I interferon response in the host. Here we report the X-ray structure of the full-length NS1 from an H5N1 strain (A/Vietnam/1203/2004) that was associated with 60% of human deaths in an outbreak in Vietnam. Compared to the individually determined structures of the RNA binding domain and the effector domain from non-H5N1 strains, the RNA binding domain within H5N1 NS1 exhibits modest structural changes, while the H5N1 effector domain shows significant alteration, particularly in the dimeric interface. Although both domains in the full-length NS1 individually participate in dimeric interactions, an unexpected finding is that these interactions result in the formation of a chain of NS1 molecules instead of distinct dimeric units. Three such chains in the crystal interact with one another extensively to form a tubular organization of similar dimensions to that observed in the cryo-electron microscopy images of NS1 in the presence of dsRNA. The tubular oligomeric organization of NS1, in which residues implicated in dsRNA binding face a 20-A-wide central tunnel, provides a plausible mechanism for how NS1 sequesters varying lengths of dsRNA, to counter cellular antiviral dsRNA response pathways, while simultaneously interacting with other cellular ligands during an infection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2798118/" 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/PMC2798118/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bornholdt, Zachary A -- Prasad, B V Venkataram -- AI36040/AI/NIAID NIH HHS/ -- R37 AI036040/AI/NIAID NIH HHS/ -- R37 AI036040-21/AI/NIAID NIH HHS/ -- RR002250/RR/NCRR NIH HHS/ -- England -- Nature. 2008 Dec 18;456(7224):985-8. doi: 10.1038/nature07444. Epub 2008 Nov 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18987632" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Cryoelectron Microscopy ; Crystallography, X-Ray ; Humans ; Influenza A Virus, H5N1 Subtype/*chemistry/*pathogenicity ; Influenza, Human/epidemiology/virology ; Models, Molecular ; Protein Multimerization ; Protein Structure, Tertiary ; Vietnam/epidemiology ; Viral Nonstructural Proteins/*chemistry/ultrastructure ; Virulence ; Virulence Factors
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  • 84
    Publication Date: 2008-01-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Raymo, Maureen E -- Huybers, Peter -- England -- Nature. 2008 Jan 17;451(7176):284-5. doi: 10.1038/nature06589.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Earth Sciences, Boston University, 685 Commonwealth Avenue, Boston, Massachusetts 02215, USA. raymo@bu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18202644" target="_blank"〉PubMed〈/a〉
    Keywords: *Climate ; Fossils ; History, 19th Century ; History, 20th Century ; History, Ancient ; *Ice Cover ; *Models, Theoretical ; Solar Activity ; Time Factors
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  • 85
    Publication Date: 2008-01-25
    Description: The water and dissolved inorganic carbon exported by rivers are important net fluxes that connect terrestrial and oceanic water and carbon reservoirs. For most rivers, the majority of dissolved inorganic carbon is in the form of bicarbonate. The riverine bicarbonate flux originates mainly from the dissolution of rock minerals by soil water carbon dioxide, a process called chemical weathering, which controls the buffering capacity and mineral content of receiving streams and rivers. Here we introduce an unprecedented high-temporal-resolution, 100-year data set from the Mississippi River and couple it with sub-watershed and precipitation data to reveal that the large increase in bicarbonate flux that has occurred over the past 50 years (ref. 3) is clearly anthropogenically driven. We show that the increase in bicarbonate and water fluxes is caused mainly by an increase in discharge from agricultural watersheds that has not been balanced by a rise in precipitation, which is also relevant to nutrient and pesticide fluxes to the Gulf of Mexico. These findings demonstrate that alterations in chemical weathering are relevant to improving contemporary biogeochemical budgets. Furthermore, land use change and management were arguably more important than changes in climate and plant CO2 fertilization to increases in riverine water and carbon export from this large region over the past 50 years.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Raymond, Peter A -- Oh, Neung-Hwan -- Turner, R Eugene -- Broussard, Whitney -- England -- Nature. 2008 Jan 24;451(7177):449-52. doi: 10.1038/nature06505.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Yale School of Forestry and Environmental Studies, 21 Sachem Street, New Haven, Connecticut 06511, USA. peter.raymond@yale.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18216851" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/history ; Bicarbonates/*analysis/chemistry ; Carbon/*analysis ; Carbon Dioxide/analysis/metabolism ; Geologic Sediments/analysis/chemistry ; Greenhouse Effect ; History, 20th Century ; History, 21st Century ; *Human Activities/history ; Mississippi ; Rain ; Rivers/*chemistry ; Time Factors
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  • 86
    Publication Date: 2008-11-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wong, Min-Liang -- England -- Nature. 2008 Nov 27;456(7221):443. doi: 10.1038/456443a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19037293" target="_blank"〉PubMed〈/a〉
    Keywords: *Awards and Prizes ; *Congresses as Topic/history ; History, 20th Century ; Nobel Prize ; PubMed ; *Publishing/history ; *Research/history ; Research Personnel/history
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  • 87
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    Publication Date: 2008-07-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Jul 3;454(7200):2. doi: 10.1038/454002a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18596752" target="_blank"〉PubMed〈/a〉
    Keywords: Berlin ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Humans ; *Museums/history ; Schools, Medical/economics/organization & administration
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  • 88
    Publication Date: 2008-09-17
    Description: Hedgehog (Hh) proteins specify tissue pattern in metazoan embryos by forming gradients that emanate from discrete sites of expression and elicit concentration-dependent cellular differentiation or proliferation responses. Cellular responses to Hh and the movement of Hh through tissues are both precisely regulated, and abnormal Hh signalling has been implicated in human birth defects and cancer. Hh signalling is mediated by its amino-terminal domain (HhN), which is dually lipidated and secreted as part of a multivalent lipoprotein particle. Reception of the HhN signal is modulated by several cell-surface proteins on responding cells, including Patched (Ptc), Smoothened (Smo), Ihog (known as CDO or CDON in mammals) and the vertebrate-specific proteins Hip (also known as Hhip) and Gas1 (ref. 11). Drosophila Ihog and its vertebrate homologues CDO and BOC contain multiple immunoglobulin and fibronectin type III (FNIII) repeats, and the first FNIII repeat of Ihog binds Drosophila HhN in a heparin-dependent manner. Surprisingly, pull-down experiments suggest that a mammalian Sonic hedgehog N-terminal domain (ShhN) binds a non-orthologous FNIII repeat of CDO. Here we report biochemical, biophysical and X-ray structural studies of a complex between ShhN and the third FNIII repeat of CDO. We show that the ShhN-CDO interaction is completely unlike the HhN-Ihog interaction and requires calcium, which binds at a previously undetected site on ShhN. This site is conserved in nearly all Hh proteins and is a hotspot for mediating interactions between ShhN and CDO, Ptc, Hip and Gas1. Mutations in vertebrate Hh proteins causing holoprosencephaly and brachydactyly type A1 map to this calcium-binding site and disrupt interactions with these partners.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2679680/" 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/PMC2679680/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McLellan, Jason S -- Zheng, Xiaoyan -- Hauk, Glenn -- Ghirlando, Rodolfo -- Beachy, Philip A -- Leahy, Daniel J -- R01 HD055545/HD/NICHD NIH HHS/ -- Z99 DK999999/Intramural NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Oct 16;455(7215):979-83. doi: 10.1038/nature07358. Epub 2008 Sep 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18794898" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Calcium/metabolism ; Cell Adhesion Molecules/chemistry/metabolism ; Cell Cycle Proteins/chemistry/metabolism ; Cell Line ; *Conserved Sequence ; Crystallography, X-Ray ; Drosophila Proteins/*chemistry/*metabolism ; Drosophila melanogaster/chemistry ; Fibronectins/chemistry ; GPI-Linked Proteins ; Hedgehog Proteins/*chemistry/genetics/*metabolism ; Humans ; Immunoglobulin G/chemistry/metabolism ; Membrane Glycoproteins/*chemistry/*metabolism ; Membrane Proteins/chemistry/metabolism ; Mice ; Models, Molecular ; Protein Binding/genetics ; Protein Structure, Tertiary ; Receptors, Cell Surface/*chemistry/*metabolism ; *Sequence Homology, Amino Acid ; Signal Transduction ; Tumor Suppressor Proteins/chemistry/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 89
    Publication Date: 2008-10-04
    Description: Human immunodeficiency virus type 1 (HIV-1) sequences that pre-date the recognition of AIDS are critical to defining the time of origin and the timescale of virus evolution. A viral sequence from 1959 (ZR59) is the oldest known HIV-1 infection. Other historically documented sequences, important calibration points to convert evolutionary distance into time, are lacking, however; ZR59 is the only one sampled before 1976. Here we report the amplification and characterization of viral sequences from a Bouin's-fixed paraffin-embedded lymph node biopsy specimen obtained in 1960 from an adult female in Leopoldville, Belgian Congo (now Kinshasa, Democratic Republic of the Congo (DRC)), and we use them to conduct the first comparative evolutionary genetic study of early pre-AIDS epidemic HIV-1 group M viruses. Phylogenetic analyses position this viral sequence (DRC60) closest to the ancestral node of subtype A (excluding A2). Relaxed molecular clock analyses incorporating DRC60 and ZR59 date the most recent common ancestor of the M group to near the beginning of the twentieth century. The sizeable genetic distance between DRC60 and ZR59 directly demonstrates that diversification of HIV-1 in west-central Africa occurred long before the recognized AIDS pandemic. The recovery of viral gene sequences from decades-old paraffin-embedded tissues opens the door to a detailed palaeovirological investigation of the evolutionary history of HIV-1 that is not accessible by other methods.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682493/" 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/PMC3682493/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Worobey, Michael -- Gemmel, Marlea -- Teuwen, Dirk E -- Haselkorn, Tamara -- Kunstman, Kevin -- Bunce, Michael -- Muyembe, Jean-Jacques -- Kabongo, Jean-Marie M -- Kalengayi, Raphael M -- Van Marck, Eric -- Gilbert, M Thomas P -- Wolinsky, Steven M -- R21 AI065371/AI/NIAID NIH HHS/ -- England -- Nature. 2008 Oct 2;455(7213):661-4. doi: 10.1038/nature07390.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ecology and Evolutionary Biology, University of Arizona, Tucson, Arizona 85721, USA. worobey@email.arizona.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18833279" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Canada ; Democratic Republic of the Congo/epidemiology ; *Evolution, Molecular ; Female ; Genetic Variation/*genetics ; HIV Infections/*epidemiology/pathology/*virology ; HIV-1/classification/*genetics/*isolation & purification ; History, 20th Century ; Humans ; Male ; Microtomy ; Molecular Sequence Data ; Paraffin Embedding ; Phylogeny ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA
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  • 90
    Publication Date: 2008-06-13
    Description: In modern organisms, protein enzymes are solely responsible for the aminoacylation of transfer RNA. However, the evolution of protein synthesis in the RNA world required RNAs capable of catalysing this reaction. Ribozymes that aminoacylate RNA by using activated amino acids have been discovered through selection in vitro. Flexizyme is a 45-nucleotide ribozyme capable of charging tRNA in trans with various activated l-phenylalanine derivatives. In addition to a more than 10(5) rate enhancement and more than 10(4)-fold discrimination against some non-cognate amino acids, this ribozyme achieves good regioselectivity: of all the hydroxyl groups of a tRNA, it exclusively aminoacylates the terminal 3'-OH. Here we report the 2.8-A resolution structure of flexizyme fused to a substrate RNA. Together with randomization of ribozyme core residues and reselection, this structure shows that very few nucleotides are needed for the aminoacylation of specific tRNAs. Although it primarily recognizes tRNA through base-pairing with the CCA terminus of the tRNA molecule, flexizyme makes numerous local interactions to position the acceptor end of tRNA precisely. A comparison of two crystallographically independent flexizyme conformations, only one of which appears capable of binding activated phenylalanine, suggests that this ribozyme may achieve enhanced specificity by coupling active-site folding to tRNA docking. Such a mechanism would be reminiscent of the mutually induced fit of tRNA and protein employed by some aminoacyl-tRNA synthetases to increase specificity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xiao, Hong -- Murakami, Hiroshi -- Suga, Hiroaki -- Ferre-D'Amare, Adrian R -- England -- Nature. 2008 Jul 17;454(7202):358-61. doi: 10.1038/nature07033. Epub 2008 Jun 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109-1024, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18548004" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acyl-tRNA Synthetases/chemistry/metabolism ; Base Sequence ; Binding Sites ; Escherichia coli/enzymology ; Models, Molecular ; Nucleic Acid Conformation ; Protein Folding ; Protein Structure, Tertiary ; RNA, Catalytic/chemistry/genetics/*metabolism ; RNA, Transfer/chemistry/genetics/*metabolism ; *Transfer RNA Aminoacylation
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  • 91
    Publication Date: 2008-01-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grosshans, Helge -- Filipowicz, Witold -- England -- Nature. 2008 Jan 24;451(7177):414-6. doi: 10.1038/451414a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18216846" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; History, 20th Century ; History, 21st Century ; Humans ; Models, Genetic ; Molecular Biology/history ; Organ Specificity ; Protein Biosynthesis ; RNA Interference ; RNA, Double-Stranded/biosynthesis/genetics/metabolism ; RNA, Messenger/biosynthesis/genetics/metabolism ; RNA, Untranslated/biosynthesis/classification/*genetics/*metabolism ; Species Specificity ; Substrate Specificity ; Viruses/genetics/immunology
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 92
    Publication Date: 2008-10-17
    Description: Diatoms are photosynthetic secondary endosymbionts found throughout marine and freshwater environments, and are believed to be responsible for around one-fifth of the primary productivity on Earth. The genome sequence of the marine centric diatom Thalassiosira pseudonana was recently reported, revealing a wealth of information about diatom biology. Here we report the complete genome sequence of the pennate diatom Phaeodactylum tricornutum and compare it with that of T. pseudonana to clarify evolutionary origins, functional significance and ubiquity of these features throughout diatoms. In spite of the fact that the pennate and centric lineages have only been diverging for 90 million years, their genome structures are dramatically different and a substantial fraction of genes ( approximately 40%) are not shared by these representatives of the two lineages. Analysis of molecular divergence compared with yeasts and metazoans reveals rapid rates of gene diversification in diatoms. Contributing factors include selective gene family expansions, differential losses and gains of genes and introns, and differential mobilization of transposable elements. Most significantly, we document the presence of hundreds of genes from bacteria. More than 300 of these gene transfers are found in both diatoms, attesting to their ancient origins, and many are likely to provide novel possibilities for metabolite management and for perception of environmental signals. These findings go a long way towards explaining the incredible diversity and success of the diatoms in contemporary oceans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bowler, Chris -- Allen, Andrew E -- Badger, Jonathan H -- Grimwood, Jane -- Jabbari, Kamel -- Kuo, Alan -- Maheswari, Uma -- Martens, Cindy -- Maumus, Florian -- Otillar, Robert P -- Rayko, Edda -- Salamov, Asaf -- Vandepoele, Klaas -- Beszteri, Bank -- Gruber, Ansgar -- Heijde, Marc -- Katinka, Michael -- Mock, Thomas -- Valentin, Klaus -- Verret, Frederic -- Berges, John A -- Brownlee, Colin -- Cadoret, Jean-Paul -- Chiovitti, Anthony -- Choi, Chang Jae -- Coesel, Sacha -- De Martino, Alessandra -- Detter, J Chris -- Durkin, Colleen -- Falciatore, Angela -- Fournet, Jerome -- Haruta, Miyoshi -- Huysman, Marie J J -- Jenkins, Bethany D -- Jiroutova, Katerina -- Jorgensen, Richard E -- Joubert, Yolaine -- Kaplan, Aaron -- Kroger, Nils -- Kroth, Peter G -- La Roche, Julie -- Lindquist, Erica -- Lommer, Markus -- Martin-Jezequel, Veronique -- Lopez, Pascal J -- Lucas, Susan -- Mangogna, Manuela -- McGinnis, Karen -- Medlin, Linda K -- Montsant, Anton -- Oudot-Le Secq, Marie-Pierre -- Napoli, Carolyn -- Obornik, Miroslav -- Parker, Micaela Schnitzler -- Petit, Jean-Louis -- Porcel, Betina M -- Poulsen, Nicole -- Robison, Matthew -- Rychlewski, Leszek -- Rynearson, Tatiana A -- Schmutz, Jeremy -- Shapiro, Harris -- Siaut, Magali -- Stanley, Michele -- Sussman, Michael R -- Taylor, Alison R -- Vardi, Assaf -- von Dassow, Peter -- Vyverman, Wim -- Willis, Anusuya -- Wyrwicz, Lucjan S -- Rokhsar, Daniel S -- Weissenbach, Jean -- Armbrust, E Virginia -- Green, Beverley R -- Van de Peer, Yves -- Grigoriev, Igor V -- England -- Nature. 2008 Nov 13;456(7219):239-44. doi: 10.1038/nature07410. Epub 2008 Oct 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CNRS UMR8186, Department of Biology, Ecole Normale Superieure, 46 rue d'Ulm, 75005 Paris, France. cbowler@biologie.ens.fr〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18923393" target="_blank"〉PubMed〈/a〉
    Keywords: DNA, Algal/analysis ; Diatoms/*genetics ; *Evolution, Molecular ; Genes, Bacterial/genetics ; Genome/*genetics ; Molecular Sequence Data ; Protein Structure, Tertiary ; Sequence Homology, Amino Acid ; Signal Transduction
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  • 93
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    Nature Publishing Group (NPG)
    Publication Date: 2008-12-19
    Description: The detection of electrical potentials across lipid bilayers by specialized membrane proteins is required for many fundamental cellular processes such as the generation and propagation of nerve impulses. These membrane proteins possess modular voltage-sensing domains, a notable example being the S1-S4 domains of voltage-activated ion channels. Ground-breaking structural studies on these domains explain how voltage sensors are designed and reveal important interactions with the surrounding lipid membrane. Although further structures are needed to understand the conformational changes that occur during voltage sensing, the available data help to frame several key concepts that are fundamental to the mechanism of voltage sensing.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2629456/" 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/PMC2629456/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Swartz, Kenton J -- ZIA NS002945-13/Intramural NIH HHS/ -- England -- Nature. 2008 Dec 18;456(7224):891-7. doi: 10.1038/nature07620.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Porter Neuroscience Research Center, Molecular Physiology and Biophysics Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. swartzk@ninds.nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19092925" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Membrane/*metabolism ; Humans ; *Ion Channel Gating ; Membrane Lipids/*metabolism ; Membrane Proteins/*chemistry/*metabolism ; Movement ; Protein Structure, Tertiary
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  • 94
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2008-01-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dando, Paul R -- England -- Nature. 2008 Jan 3;451(7174):28. doi: 10.1038/451028a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Paul R. Dando, of the Marine Biological Association of the United Kingdom, is at the School of Ocean Sciences, Bangor University, Menai Bridge LL59 5AB, UK.oss109@bangor.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18172490" target="_blank"〉PubMed〈/a〉
    Keywords: Ecosystem ; Great Britain ; History, 20th Century ; Marine Biology/*history
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  • 95
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2008-06-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Jun 5;453(7196):697. doi: 10.1038/453697a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18528339" target="_blank"〉PubMed〈/a〉
    Keywords: Genome, Human ; Genomics/*trends ; History, 20th Century ; History, 21st Century ; Human Genome Project/history ; Humans ; National Human Genome Research Institute (U.S.)/history/*organization & ; administration/trends ; United States
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  • 96
    Publication Date: 2008-02-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Klagsbrun, Michael -- Moses, Marsha A -- England -- Nature. 2008 Feb 14;451(7180):781. doi: 10.1038/451781a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Surgery, Children's Hospital Boston and Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA. michael.klagsbrun@childrens.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18273010" target="_blank"〉PubMed〈/a〉
    Keywords: Angiogenesis Inhibitors/therapeutic use ; Awards and Prizes ; Biomarkers ; History, 20th Century ; History, 21st Century ; Humans ; Neoplasms/*blood supply/drug therapy ; *Neovascularization, Pathologic/drug therapy ; United States
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  • 97
    Publication Date: 2008-12-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Richerson, Peter J -- Boyd, Robert -- England -- Nature. 2008 Dec 18;456(7224):877. doi: 10.1038/456877a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Peter J. Richerson is in the Department of Environmental Science and Policy, University of California, Davis, California 95616, USA. pjricherson@ucdavis.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19092915" target="_blank"〉PubMed〈/a〉
    Keywords: Conflict (Psychology) ; *Cultural Evolution ; *Emigration and Immigration/history ; History, 20th Century ; History, 21st Century ; History, Ancient ; Internationality/history
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  • 98
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2008-04-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meulmeester, Erik -- Melchior, Frauke -- England -- Nature. 2008 Apr 10;452(7188):709-11. doi: 10.1038/452709a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18401402" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Eukaryotic Cells/metabolism ; History, 20th Century ; Humans ; Protein Binding ; Small Ubiquitin-Related Modifier Proteins/history/*metabolism ; Substrate Specificity ; Viruses/metabolism
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  • 99
    Publication Date: 2008-05-27
    Description: Members of the epidermal growth factor receptor (EGFR) or ErbB/HER family and their activating ligands are essential regulators of diverse developmental processes. Inappropriate activation of these receptors is a key feature of many human cancers, and its reversal is an important clinical goal. A natural secreted antagonist of EGFR signalling, called Argos, was identified in Drosophila. We showed previously that Argos functions by directly binding (and sequestering) growth factor ligands that activate EGFR. Here we describe the 1.6-A resolution crystal structure of Argos bound to an EGFR ligand. Contrary to expectations, Argos contains no EGF-like domain. Instead, a trio of closely related domains (resembling a three-finger toxin fold) form a clamp-like structure around the bound EGF ligand. Although structurally unrelated to the receptor, Argos mimics EGFR by using a bipartite binding surface to entrap EGF. The individual Argos domains share unexpected structural similarities with the extracellular ligand-binding regions of transforming growth factor-beta family receptors. The three-domain clamp of Argos also resembles the urokinase-type plasminogen activator (uPA) receptor, which uses a similar mechanism to engulf the EGF-like module of uPA. Our results indicate that undiscovered mammalian counterparts of Argos may exist among other poorly characterized structural homologues. In addition, the structures presented here define requirements for the design of artificial EGF-sequestering proteins that would be valuable anti-cancer therapeutics.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2526102/" 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/PMC2526102/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Klein, Daryl E -- Stayrook, Steven E -- Shi, Fumin -- Narayan, Kartik -- Lemmon, Mark A -- R01 CA079992/CA/NCI NIH HHS/ -- R01 CA079992-10/CA/NCI NIH HHS/ -- R01 CA125432/CA/NCI NIH HHS/ -- R01 CA125432-01A1/CA/NCI NIH HHS/ -- England -- Nature. 2008 Jun 26;453(7199):1271-5. doi: 10.1038/nature06978. Epub 2008 May 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, 809C Stellar-Chance Laboratories, 422 Curie Boulevard, Philadelphia, Pennsylvania 19104-6059, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18500331" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Cell Line ; Crystallography, X-Ray ; Drosophila Proteins/*chemistry/*metabolism ; Drosophila melanogaster/*chemistry/cytology ; Epidermal Growth Factor/*chemistry/*metabolism ; Eye Proteins/*chemistry/*metabolism ; Humans ; Ligands ; Membrane Proteins/*chemistry/*metabolism ; Models, Molecular ; Nerve Tissue Proteins/*chemistry/*metabolism ; Protein Structure, Tertiary ; Receptor, Epidermal Growth Factor/antagonists & inhibitors/chemistry/*metabolism ; Receptors, Transforming Growth Factor beta/chemistry/metabolism ; Spodoptera
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  • 100
    Publication Date: 2008-10-04
    Description: HIV-1 protease processes the Gag and Gag-Pol polyproteins into mature structural and functional proteins, including itself, and is therefore indispensable for viral maturation. The mature protease is active only as a dimer with each subunit contributing catalytic residues. The full-length transframe region protease precursor appears to be monomeric yet undergoes maturation via intramolecular cleavage of a putative precursor dimer, concomitant with the appearance of mature-like catalytic activity. How such intramolecular cleavage can occur when the amino and carboxy termini of the mature protease are part of an intersubunit beta-sheet located distal from the active site is unclear. Here we visualize the early events in N-terminal autoprocessing using an inactive mini-precursor with a four-residue N-terminal extension that mimics the transframe region protease precursor. Using paramagnetic relaxation enhancement, a technique that is exquisitely sensitive to the presence of minor species, we show that the mini-precursor forms highly transient, lowly populated (3-5%) dimeric encounter complexes that involve the mature dimer interface but occupy a wide range of subunit orientations relative to the mature dimer. Furthermore, the occupancy of the mature dimer configuration constitutes a very small fraction of the self-associated species (accounting for the very low enzymatic activity of the protease precursor), and the N-terminal extension makes transient intra- and intersubunit contacts with the substrate binding site and is therefore available for autocleavage when the correct dimer orientation is sampled within the encounter complex ensemble.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2798589/" 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/PMC2798589/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tang, Chun -- Louis, John M -- Aniana, Annie -- Suh, Jeong-Yong -- Clore, G Marius -- ZIA DK029023-19/Intramural NIH HHS/ -- England -- Nature. 2008 Oct 2;455(7213):693-6. doi: 10.1038/nature07342.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Chemical Physics, Building 5, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18833280" target="_blank"〉PubMed〈/a〉
    Keywords: Dimerization ; HIV Protease/*chemistry/genetics/*metabolism ; HIV-1/*enzymology/genetics ; Models, Molecular ; Nuclear Magnetic Resonance, Biomolecular ; Protein Precursors/*chemistry/genetics/*metabolism ; *Protein Processing, Post-Translational ; Protein Structure, Tertiary ; Spin Labels ; gag Gene Products, Human Immunodeficiency Virus/chemistry/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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