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  • 1
    Publication Date: 2009-09-11
    Description: Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement. To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population. Current annual worldwide potato crop losses due to late blight are conservatively estimated at $6.7 billion. Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars. Here we report the sequence of the P. infestans genome, which at approximately 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for approximately 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haas, Brian J -- Kamoun, Sophien -- Zody, Michael C -- Jiang, Rays H Y -- Handsaker, Robert E -- Cano, Liliana M -- Grabherr, Manfred -- Kodira, Chinnappa D -- Raffaele, Sylvain -- Torto-Alalibo, Trudy -- Bozkurt, Tolga O -- Ah-Fong, Audrey M V -- Alvarado, Lucia -- Anderson, Vicky L -- Armstrong, Miles R -- Avrova, Anna -- Baxter, Laura -- Beynon, Jim -- Boevink, Petra C -- Bollmann, Stephanie R -- Bos, Jorunn I B -- Bulone, Vincent -- Cai, Guohong -- Cakir, Cahid -- Carrington, James C -- Chawner, Megan -- Conti, Lucio -- Costanzo, Stefano -- Ewan, Richard -- Fahlgren, Noah -- Fischbach, Michael A -- Fugelstad, Johanna -- Gilroy, Eleanor M -- Gnerre, Sante -- Green, Pamela J -- Grenville-Briggs, Laura J -- Griffith, John -- Grunwald, Niklaus J -- Horn, Karolyn -- Horner, Neil R -- Hu, Chia-Hui -- Huitema, Edgar -- Jeong, Dong-Hoon -- Jones, Alexandra M E -- Jones, Jonathan D G -- Jones, Richard W -- Karlsson, Elinor K -- Kunjeti, Sridhara G -- Lamour, Kurt -- Liu, Zhenyu -- Ma, Lijun -- Maclean, Daniel -- Chibucos, Marcus C -- McDonald, Hayes -- McWalters, Jessica -- Meijer, Harold J G -- Morgan, William -- Morris, Paul F -- Munro, Carol A -- O'Neill, Keith -- Ospina-Giraldo, Manuel -- Pinzon, Andres -- Pritchard, Leighton -- Ramsahoye, Bernard -- Ren, Qinghu -- Restrepo, Silvia -- Roy, Sourav -- Sadanandom, Ari -- Savidor, Alon -- Schornack, Sebastian -- Schwartz, David C -- Schumann, Ulrike D -- Schwessinger, Ben -- Seyer, Lauren -- Sharpe, Ted -- Silvar, Cristina -- Song, Jing -- Studholme, David J -- Sykes, Sean -- Thines, Marco -- van de Vondervoort, Peter J I -- Phuntumart, Vipaporn -- Wawra, Stephan -- Weide, Rob -- Win, Joe -- Young, Carolyn -- Zhou, Shiguo -- Fry, William -- Meyers, Blake C -- van West, Pieter -- Ristaino, Jean -- Govers, Francine -- Birch, Paul R J -- Whisson, Stephen C -- Judelson, Howard S -- Nusbaum, Chad -- BB/E007120/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/G015244/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- G0400284/Medical Research Council/United Kingdom -- England -- Nature. 2009 Sep 17;461(7262):393-8. doi: 10.1038/nature08358. Epub 2009 Sep 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02141, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19741609" target="_blank"〉PubMed〈/a〉
    Keywords: Algal Proteins/genetics ; DNA Transposable Elements/genetics ; DNA, Intergenic/genetics ; Evolution, Molecular ; Genome/*genetics ; Host-Pathogen Interactions/genetics ; Humans ; Ireland ; Molecular Sequence Data ; Necrosis ; Phenotype ; Phytophthora infestans/*genetics/pathogenicity ; Plant Diseases/immunology/*microbiology ; Solanum tuberosum/immunology/*microbiology ; Starvation
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 1993-11-05
    Description: Pre-steady state kinetics of misincorporation were used to investigate the addition of single nucleotides to nascent RNA by Escherichia coli RNA polymerase during transcription elongation. The results were fit with a branched kinetic mechanism that permits conformational switching, at each template position, between an activated and an unactivated enzyme complex, both of which can bind nucleotide triphosphates (NTPs) from solution. The complex exists most often in the long-lived activated state, and only becomes unactivated when transcription is slowed. This model permits multiple levels of nucleotide discrimination in transcription, since the complex can be "kinetically trapped" in the unactivated state in the absence of the correct NTP or if the 3' terminal residue is incorrectly matched. The transcription cleavage factor GreA (or an activity enhanced by GreA) increased the fidelity of transcription by preferential cleavage of transcripts containing misincorporated residues in the unactivated state of the elongation complex. This cleavage mechanism by GreA may prevent the formation of "dead-end" transcription complexes in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Erie, D A -- Hajiseyedjavadi, O -- Young, M C -- von Hippel, P H -- GM-12915/GM/NIGMS NIH HHS/ -- GM-15792/GM/NIGMS NIH HHS/ -- GM-29158/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1993 Nov 5;262(5135):867-73.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Biology, University of Oregon, Eugene 97403.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8235608" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; DNA-Directed RNA Polymerases/*chemistry/metabolism ; Endoribonucleases/metabolism ; Escherichia coli/enzymology ; *Escherichia coli Proteins ; Kinetics ; Models, Genetic ; Molecular Sequence Data ; Nucleotides/metabolism ; Peptide Elongation Factors/*metabolism ; Protein Conformation ; RNA, Messenger/*biosynthesis/metabolism ; Templates, Genetic ; Transcription Factors/*metabolism ; *Transcription, Genetic ; Uridine Triphosphate/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2009-05-30
    Description: Human skin is a large, heterogeneous organ that protects the body from pathogens while sustaining microorganisms that influence human health and disease. Our analysis of 16S ribosomal RNA gene sequences obtained from 20 distinct skin sites of healthy humans revealed that physiologically comparable sites harbor similar bacterial communities. The complexity and stability of the microbial community are dependent on the specific characteristics of the skin site. This topographical and temporal survey provides a baseline for studies that examine the role of bacterial communities in disease states and the microbial interdependencies required to maintain healthy skin.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2805064/" 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/PMC2805064/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grice, Elizabeth A -- Kong, Heidi H -- Conlan, Sean -- Deming, Clayton B -- Davis, Joie -- Young, Alice C -- NISC Comparative Sequencing Program -- Bouffard, Gerard G -- Blakesley, Robert W -- Murray, Patrick R -- Green, Eric D -- Turner, Maria L -- Segre, Julia A -- Z01 HG000180-08/Intramural NIH HHS/ -- ZIA BC010938-02/Intramural NIH HHS/ -- ZIA HG000180-09/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2009 May 29;324(5931):1190-2. doi: 10.1126/science.1171700.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19478181" target="_blank"〉PubMed〈/a〉
    Keywords: Actinobacteria/classification/genetics/isolation & purification ; Adult ; Bacteria/classification/genetics/*isolation & purification ; Bacteroidetes/classification/genetics/isolation & purification ; Biodiversity ; Female ; Genes, rRNA ; Humans ; Male ; *Metagenome ; Molecular Sequence Data ; Phylogeny ; Proteobacteria/classification/genetics/isolation & purification ; RNA, Ribosomal, 16S ; Skin/*microbiology ; Time Factors ; Young Adult
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2015-12-19
    Description: Voltage-gated sodium (Nav) channels propagate action potentials in excitable cells. Accordingly, Nav channels are therapeutic targets for many cardiovascular and neurological disorders. Selective inhibitors have been challenging to design because the nine mammalian Nav channel isoforms share high sequence identity and remain recalcitrant to high-resolution structural studies. Targeting the human Nav1.7 channel involved in pain perception, we present a protein-engineering strategy that has allowed us to determine crystal structures of a novel receptor site in complex with isoform-selective antagonists. GX-936 and related inhibitors bind to the activated state of voltage-sensor domain IV (VSD4), where their anionic aryl sulfonamide warhead engages the fourth arginine gating charge on the S4 helix. By opposing VSD4 deactivation, these compounds inhibit Nav1.7 through a voltage-sensor trapping mechanism, likely by stabilizing inactivated states of the channel. Residues from the S2 and S3 helices are key determinants of isoform selectivity, and bound phospholipids implicate the membrane as a modulator of channel function and pharmacology. Our results help to elucidate the molecular basis of voltage sensing and establish structural blueprints to design selective Nav channel antagonists.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ahuja, Shivani -- Mukund, Susmith -- Deng, Lunbin -- Khakh, Kuldip -- Chang, Elaine -- Ho, Hoangdung -- Shriver, Stephanie -- Young, Clint -- Lin, Sophia -- Johnson, J P Jr -- Wu, Ping -- Li, Jun -- Coons, Mary -- Tam, Christine -- Brillantes, Bobby -- Sampang, Honorio -- Mortara, Kyle -- Bowman, Krista K -- Clark, Kevin R -- Estevez, Alberto -- Xie, Zhiwei -- Verschoof, Henry -- Grimwood, Michael -- Dehnhardt, Christoph -- Andrez, Jean-Christophe -- Focken, Thilo -- Sutherlin, Daniel P -- Safina, Brian S -- Starovasnik, Melissa A -- Ortwine, Daniel F -- Franke, Yvonne -- Cohen, Charles J -- Hackos, David H -- Koth, Christopher M -- Payandeh, Jian -- New York, N.Y. -- Science. 2015 Dec 18;350(6267):aac5464. doi: 10.1126/science.aac5464.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Structural Biology, Genentech Inc., South San Francisco, CA 94080, USA. ; Department of Neuroscience, Genentech Inc., South San Francisco, CA 94080, USA. ; Department of Biology, Xenon Pharmaceuticals Inc., Burnaby, British Columbia, V5G 4W8, Canada. ; Department of Discovery Chemistry, Genentech Inc., South San Francisco, CA 94080, USA. ; Department of Biochemical and Cellular Pharmacology, Genentech Inc., South San Francisco, CA 94080, USA. ; Department of Chemistry, Xenon Pharmaceuticals Inc., Burnaby, British Columbia, V5G 4W8, Canada. ; Department of Neuroscience, Genentech Inc., South San Francisco, CA 94080, USA. hackos.david@gene.com koth.christopher@gene.com payandeh.jian@gene.com. ; Department of Structural Biology, Genentech Inc., South San Francisco, CA 94080, USA. hackos.david@gene.com koth.christopher@gene.com payandeh.jian@gene.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26680203" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cell Membrane/chemistry ; Crystallization/methods ; Crystallography, X-Ray ; DNA Mutational Analysis ; Humans ; Models, Molecular ; Molecular Sequence Data ; NAV1.7 Voltage-Gated Sodium Channel/*chemistry/genetics ; Pain Perception/drug effects ; Protein Engineering ; Protein Isoforms/antagonists & inhibitors/chemistry ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Sodium Channel Blockers/*chemistry/*pharmacology ; Sulfonamides/*chemistry/*pharmacology ; Thiadiazoles/*chemistry/*pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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