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  • Molecular Sequence Data  (496)
  • Cell Line  (341)
  • American Association for the Advancement of Science (AAAS)  (783)
  • Essen : Verl. Glückauf
  • 2005-2009  (783)
  • 1965-1969
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  • 1
    Publication Date: 2009-08-29
    Description: Coat color and type are essential characteristics of domestic dog breeds. Although the genetic basis of coat color has been well characterized, relatively little is known about the genes influencing coat growth pattern, length, and curl. We performed genome-wide association studies of more than 1000 dogs from 80 domestic breeds to identify genes associated with canine fur phenotypes. Taking advantage of both inter- and intrabreed variability, we identified distinct mutations in three genes, RSPO2, FGF5, and KRT71 (encoding R-spondin-2, fibroblast growth factor-5, and keratin-71, respectively), that together account for most coat phenotypes in purebred dogs in the United States. Thus, an array of varied and seemingly complex phenotypes can be reduced to the combinatorial effects of only a few genes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897713/" 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/PMC2897713/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cadieu, Edouard -- Neff, Mark W -- Quignon, Pascale -- Walsh, Kari -- Chase, Kevin -- Parker, Heidi G -- Vonholdt, Bridgett M -- Rhue, Alison -- Boyko, Adam -- Byers, Alexandra -- Wong, Aaron -- Mosher, Dana S -- Elkahloun, Abdel G -- Spady, Tyrone C -- Andre, Catherine -- Lark, K Gordon -- Cargill, Michelle -- Bustamante, Carlos D -- Wayne, Robert K -- Ostrander, Elaine A -- 1R01GM83606/GM/NIGMS NIH HHS/ -- GM063056/GM/NIGMS NIH HHS/ -- R01 GM063056/GM/NIGMS NIH HHS/ -- R01 GM063056-09/GM/NIGMS NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2009 Oct 2;326(5949):150-3. doi: 10.1126/science.1177808. Epub 2009 Aug 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19713490" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions ; Animals ; Dogs/*genetics ; Fibroblast Growth Factor 5/*genetics ; Genome-Wide Association Study ; *Hair/anatomy & histology/growth & development ; Haplotypes ; Keratins, Hair-Specific/*genetics ; Lod Score ; Molecular Sequence Data ; Mutation ; Oligonucleotide Array Sequence Analysis ; Phenotype ; *Polymorphism, Single Nucleotide ; Sequence Analysis, DNA ; Thrombospondins/*genetics ; United States
    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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  • 2
    Publication Date: 2009-08-15
    Description: Microbes are incredibly abundant and diverse and are key to ecosystem functioning, yet relatively little is known about the ecological and evolutionary mechanisms that shape their distributions. Bacteriophages, viral parasites that lyse their bacterial hosts, exert intense and spatially varying selection pressures on bacteria and vice versa. We measured local adaptation of bacteria and their associated phages in a centimeter-scale soil population. We first demonstrate that a large proportion of bacteria is sensitive to locally occurring phages. We then show that sympatric phages (isolated from the same 2-gram soil samples as the bacteria) are more infective than are phages from samples some distance away. This study demonstrates the importance of biotic interactions for the small-scale spatial structuring of microbial genetic diversity in soil.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vos, Michiel -- Birkett, Philip J -- Birch, Elizabeth -- Griffiths, Robert I -- Buckling, Angus -- New York, N.Y. -- Science. 2009 Aug 14;325(5942):833. doi: 10.1126/science.1174173.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Zoology, University of Oxford, Oxford OX1 3PS, UK. michiel.vos@nioo.knaw.nl〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19679806" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptation, Physiological ; Bacteria/genetics/*virology ; Bacterial Physiological Phenomena ; Bacteriophages/genetics/*physiology ; Biological Evolution ; Ecosystem ; Genetic Variation ; Molecular Sequence Data ; Selection, Genetic ; *Soil Microbiology ; Stenotrophomonas/genetics/physiology/*virology ; Viral Plaque Assay
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2009-04-11
    Description: Genetic exchange has not been shown to be a mechanism underlying the extensive diversity of Leishmania parasites. We report here evidence that the invertebrate stages of Leishmania are capable of having a sexual cycle consistent with a meiotic process like that described for African trypanosomes. Hybrid progeny were generated that bore full genomic complements from both parents, but kinetoplast DNA maxicircles from one parent. Mating occurred only in the sand fly vector, and hybrids were transmitted to the mammalian host by sand fly bite. Genetic exchange likely contributes to phenotypic diversity in natural populations, and analysis of hybrid progeny will be useful for positional cloning of the genes controlling traits such as virulence, tissue tropism, and drug resistance.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2729066/" 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/PMC2729066/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Akopyants, Natalia S -- Kimblin, Nicola -- Secundino, Nagila -- Patrick, Rachel -- Peters, Nathan -- Lawyer, Phillip -- Dobson, Deborah E -- Beverley, Stephen M -- Sacks, David L -- A1020941/PHS HHS/ -- A1029646/PHS HHS/ -- R01 AI029646/AI/NIAID NIH HHS/ -- R01 AI029646-20/AI/NIAID NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2009 Apr 10;324(5924):265-8. doi: 10.1126/science.1169464.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19359589" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antiprotozoal Agents/pharmacology ; DNA, Kinetoplast/genetics ; DNA, Protozoan/analysis/genetics ; Drug Resistance ; Female ; Genes, Protozoan ; *Hybridization, Genetic ; Insect Vectors/*parasitology ; Leishmania major/drug effects/*genetics/*growth & development/pathogenicity ; Leishmaniasis, Cutaneous/parasitology ; Meiosis ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; Phenotype ; Phlebotomus/*parasitology ; Polymorphism, Single Nucleotide
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  • 4
    Publication Date: 2009-08-15
    Description: Sleep deprivation can impair human health and performance. Habitual total sleep time and homeostatic sleep response to sleep deprivation are quantitative traits in humans. Genetic loci for these traits have been identified in model organisms, but none of these potential animal models have a corresponding human genotype and phenotype. We have identified a mutation in a transcriptional repressor (hDEC2-P385R) that is associated with a human short sleep phenotype. Activity profiles and sleep recordings of transgenic mice carrying this mutation showed increased vigilance time and less sleep time than control mice in a zeitgeber time- and sleep deprivation-dependent manner. These mice represent a model of human sleep homeostasis that provides an opportunity to probe the effect of sleep on human physical and mental health.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2884988/" 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/PMC2884988/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉He, Ying -- Jones, Christopher R -- Fujiki, Nobuhiro -- Xu, Ying -- Guo, Bin -- Holder, Jimmy L Jr -- Rossner, Moritz J -- Nishino, Seiji -- Fu, Ying-Hui -- HL059596/HL/NHLBI NIH HHS/ -- MH074924/MH/NIMH NIH HHS/ -- R01 HL059596/HL/NHLBI NIH HHS/ -- R01 HL059596-09/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2009 Aug 14;325(5942):866-70. doi: 10.1126/science.1174443.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, University of California at San Francisco, Mission Bay, 1550 Fourth Street, San Francisco, CA 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19679812" target="_blank"〉PubMed〈/a〉
    Keywords: Activity Cycles/genetics ; Adolescent ; Adult ; Aged ; Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Animals, Genetically Modified ; Basic Helix-Loop-Helix Transcription Factors/chemistry/*genetics/physiology ; Child ; Circadian Rhythm/genetics ; Drosophila/genetics ; Electroencephalography ; Electromyography ; Female ; Homeostasis ; Humans ; Male ; Mice ; Mice, Knockout ; Mice, Transgenic ; Middle Aged ; Molecular Sequence Data ; Pedigree ; Point Mutation ; Sleep/*genetics/physiology ; Sleep Deprivation ; Sleep, REM/genetics/physiology ; Transcription Factors/chemistry/genetics/physiology ; Wakefulness
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  • 5
    Publication Date: 2009-12-08
    Description: Fanconi anemia is a human cancer predisposition syndrome caused by mutations in 13 Fanc genes. The disorder is characterized by genomic instability and cellular hypersensitivity to chemicals that generate DNA interstrand cross-links (ICLs). A central event in the activation of the Fanconi anemia pathway is the mono-ubiquitylation of the FANCI-FANCD2 complex, but how this complex confers ICL resistance remains enigmatic. Using a cell-free system, we showed that FANCI-FANCD2 is required for replication-coupled ICL repair in S phase. Removal of FANCD2 from extracts inhibits both nucleolytic incisions near the ICL and translesion DNA synthesis past the lesion. Reversal of these defects requires ubiquitylated FANCI-FANCD2. Our results show that multiple steps of the essential S-phase ICL repair mechanism fail when the Fanconi anemia pathway is compromised.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2909596/" 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/PMC2909596/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Knipscheer, Puck -- Raschle, Markus -- Smogorzewska, Agata -- Enoiu, Milica -- Ho, The Vinh -- Scharer, Orlando D -- Elledge, Stephen J -- Walter, Johannes C -- GM62267/GM/NIGMS NIH HHS/ -- R01 GM062267/GM/NIGMS NIH HHS/ -- R01 GM062267-09/GM/NIGMS NIH HHS/ -- R37 GM044664/GM/NIGMS NIH HHS/ -- R37 GM044664-23/GM/NIGMS NIH HHS/ -- T32CA09216/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Dec 18;326(5960):1698-701. doi: 10.1126/science.1182372. Epub 2009 Nov 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965384" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell-Free System ; Chromatin/metabolism ; DNA/biosynthesis ; DNA Damage ; *DNA Repair ; *DNA Replication ; Fanconi Anemia/genetics/metabolism ; Fanconi Anemia Complementation Group D2 Protein/*metabolism ; Fanconi Anemia Complementation Group Proteins/*metabolism ; Molecular Sequence Data ; Recombinant Proteins/metabolism ; S Phase ; Signal Transduction ; Ubiquitinated Proteins/metabolism ; Ubiquitination ; Xenopus Proteins/*metabolism ; Xenopus laevis
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  • 6
    Publication Date: 2009-12-08
    Description: Loss-of-function genetic screens in model organisms have elucidated numerous biological processes, but the diploid genome of mammalian cells has precluded large-scale gene disruption. We used insertional mutagenesis to develop a screening method to generate null alleles in a human cell line haploid for all chromosomes except chromosome 8. Using this approach, we identified host factors essential for infection with influenza and genes encoding important elements of the biosynthetic pathway of diphthamide, which are required for the cytotoxic effects of diphtheria toxin and exotoxin A. We also identified genes needed for the action of cytolethal distending toxin, including a cell-surface protein that interacts with the toxin. This approach has both conceptual and practical parallels with genetic approaches in haploid yeast.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carette, Jan E -- Guimaraes, Carla P -- Varadarajan, Malini -- Park, Annie S -- Wuethrich, Irene -- Godarova, Alzbeta -- Kotecki, Maciej -- Cochran, Brent H -- Spooner, Eric -- Ploegh, Hidde L -- Brummelkamp, Thijn R -- New York, N.Y. -- Science. 2009 Nov 27;326(5957):1231-5. doi: 10.1126/science.1178955.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965467" target="_blank"〉PubMed〈/a〉
    Keywords: ADP Ribose Transferases/metabolism/toxicity ; Adenosine Diphosphate Ribose/metabolism ; Amino Acid Sequence ; Antigens, Bacterial/metabolism/toxicity ; Bacterial Toxins/*metabolism/toxicity ; Biosynthetic Pathways ; Cell Line, Tumor ; Diphtheria Toxin/metabolism/toxicity ; Exotoxins/metabolism/toxicity ; Genes ; *Genetic Testing ; *Haploidy ; Histidine/analogs & derivatives/biosynthesis ; *Host-Pathogen Interactions ; Humans ; Influenza A Virus, H1N1 Subtype/*pathogenicity ; Molecular Sequence Data ; Monosaccharide Transport Proteins/genetics/metabolism ; Mutagenesis, Insertional ; N-Acylneuraminate Cytidylyltransferase/genetics/metabolism ; Peptide Elongation Factor 2/metabolism ; Proteins/chemistry/genetics/metabolism ; Virulence Factors/metabolism/toxicity
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  • 7
    Publication Date: 2009-11-07
    Description: Ecological speciation occurs when ecologically based, divergent selection causes the evolution of reproductive isolation. There are many empirical examples of this process; however, there exists a poorly characterized stage during which the traits that distinguish species ecologically and reproductively segregate in a single population. By using a combination of genetic mapping, mate-choice experiments, field observations, and population genetics, we studied a butterfly population with a mimetic wing color polymorphism and found that the butterflies exhibited partial, color-based, assortative mate preference. These traits represent the divergent, ecologically based signal and preference components of sexual isolation that usually distinguish incipient and sibling species. The association between behavior and recognition trait in a single population may enhance the probability of speciation and provides an example of the missing link between an interbreeding population and isolated species.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875868/" 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/PMC2875868/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chamberlain, Nicola L -- Hill, Ryan I -- Kapan, Durrell D -- Gilbert, Lawrence E -- Kronforst, Marcus R -- GM068763/GM/NIGMS NIH HHS/ -- P50 GM068763/GM/NIGMS NIH HHS/ -- P50 GM068763-06/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Nov 6;326(5954):847-50. doi: 10.1126/science.1179141.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Faculty of Arts and Sciences Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19892982" target="_blank"〉PubMed〈/a〉
    Keywords: Amplified Fragment Length Polymorphism Analysis ; Animals ; Butterflies/anatomy & histology/*genetics/*physiology ; Color ; Ecosystem ; Female ; Genes, Insect ; Genetic Linkage ; *Genetic Speciation ; Linkage Disequilibrium ; Male ; *Mating Preference, Animal ; Molecular Sequence Data ; Phenotype ; *Pigmentation/genetics ; *Polymorphism, Genetic ; Reproduction ; Selection, Genetic ; Wings, Animal/*anatomy & histology
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  • 8
    Publication Date: 2009-12-08
    Description: Simocyclinones are bifunctional antibiotics that inhibit bacterial DNA gyrase by preventing DNA binding to the enzyme. We report the crystal structure of the complex formed between the N-terminal domain of the Escherichia coli gyrase A subunit and simocyclinone D8, revealing two binding pockets that separately accommodate the aminocoumarin and polyketide moieties of the antibiotic. These are close to, but distinct from, the quinolone-binding site, consistent with our observations that several mutations in this region confer resistance to both agents. Biochemical studies show that the individual moieties of simocyclinone D8 are comparatively weak inhibitors of gyrase relative to the parent compound, but their combination generates a more potent inhibitor. Our results should facilitate the design of drug molecules that target these unexploited binding pockets.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Edwards, Marcus J -- Flatman, Ruth H -- Mitchenall, Lesley A -- Stevenson, Clare E M -- Le, Tung B K -- Clarke, Thomas A -- McKay, Adam R -- Fiedler, Hans-Peter -- Buttner, Mark J -- Lawson, David M -- Maxwell, Anthony -- Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2009 Dec 4;326(5958):1415-8. doi: 10.1126/science.1179123.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry, John Innes Centre, Colney, Norwich NR4 7UH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965760" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Anti-Bacterial Agents/chemistry/metabolism/pharmacology ; Binding Sites ; Coumarins/chemistry/metabolism/pharmacology ; Crystallography, X-Ray ; DNA Gyrase/*chemistry/genetics/*metabolism ; DNA, Bacterial/metabolism ; Drug Resistance, Bacterial ; Escherichia coli/drug effects/*enzymology/genetics ; Glycosides/chemistry/metabolism/pharmacology ; Ligands ; Models, Molecular ; Molecular Sequence Data ; Molecular Weight ; Mutagenesis, Site-Directed ; Mutation ; Protein Multimerization ; Protein Structure, Tertiary ; Topoisomerase II Inhibitors
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  • 9
    Publication Date: 2009-02-07
    Description: Biodiversity hotspots, representing regions with high species endemism and conservation threat, have been mapped globally. Yet, biodiversity distribution data from within hotspots are too sparse for effective conservation in the face of rapid environmental change. Using frogs as indicators, ecological niche models under paleoclimates, and simultaneous Bayesian analyses of multispecies molecular data, we compare alternative hypotheses of assemblage-scale response to late Quaternary climate change. This reveals a hotspot within the Brazilian Atlantic forest hotspot. We show that the southern Atlantic forest was climatically unstable relative to the central region, which served as a large climatic refugium for neotropical species in the late Pleistocene. This sets new priorities for conservation in Brazil and establishes a validated approach to biodiversity prediction in other understudied, species-rich regions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carnaval, Ana Carolina -- Hickerson, Michael J -- Haddad, Celio F B -- Rodrigues, Miguel T -- Moritz, Craig -- New York, N.Y. -- Science. 2009 Feb 6;323(5915):785-9. doi: 10.1126/science.1166955.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Museum of Vertebrate Zoology, University of California, Berkeley, CA 94720-3160, USA. carnaval@berkeley.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19197066" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anura/classification/*genetics ; Bayes Theorem ; *Biodiversity ; Brazil ; Conservation of Natural Resources ; DNA, Mitochondrial/genetics ; Demography ; *Ecosystem ; Geography ; Molecular Sequence Data ; Mutation ; Phylogeny ; Population Dynamics ; Time ; *Trees ; *Tropical Climate
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  • 10
    Publication Date: 2009-11-11
    Description: Rapid antigenic evolution in the influenza A virus hemagglutinin precludes effective vaccination with existing vaccines. To understand this phenomenon, we passaged virus in mice immunized with influenza vaccine. Neutralizing antibodies selected mutants with single-amino acid hemagglutinin substitutions that increased virus binding to cell surface glycan receptors. Passaging these high-avidity binding mutants in naive mice, but not immune mice, selected for additional hemagglutinin substitutions that decreased cellular receptor binding avidity. Analyzing a panel of monoclonal antibody hemagglutinin escape mutants revealed a positive correlation between receptor binding avidity and escape from polyclonal antibodies. We propose that in response to variation in neutralizing antibody pressure between individuals, influenza A virus evolves by adjusting receptor binding avidity via amino acid substitutions throughout the hemagglutinin globular domain, many of which simultaneously alter antigenicity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784927/" 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/PMC2784927/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hensley, Scott E -- Das, Suman R -- Bailey, Adam L -- Schmidt, Loren M -- Hickman, Heather D -- Jayaraman, Akila -- Viswanathan, Karthik -- Raman, Rahul -- Sasisekharan, Ram -- Bennink, Jack R -- Yewdell, Jonathan W -- GM 57073/GM/NIGMS NIH HHS/ -- U54 GM62116/GM/NIGMS NIH HHS/ -- Z01 AI001014-01/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2009 Oct 30;326(5953):734-6. doi: 10.1126/science.1178258.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19900932" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Antigenic Variation/genetics/*immunology ; Cell Line ; Hemagglutinin Glycoproteins, Influenza Virus/genetics/immunology/*metabolism ; Influenza A Virus, H1N1 Subtype/genetics/*immunology ; Influenza Vaccines/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Models, Immunological ; Mutation ; Receptors, Virus/*metabolism ; Serial Passage
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  • 11
    Publication Date: 2009-12-08
    Description: Hepatitis delta virus (HDV) and cytoplasmic polyadenylation element-binding protein 3 (CPEB3) ribozymes form a family of self-cleaving RNAs characterized by a conserved nested double-pseudoknot and minimal sequence conservation. Secondary structure-based searches were used to identify sequences capable of forming this fold, and their self-cleavage activity was confirmed in vitro. Active sequences were uncovered in several marine organisms, two nematodes, an arthropod, a bacterium, and an insect virus, often in multiple sequence families and copies. Sequence searches based on identified ribozymes showed that plants, fungi, and a unicellular eukaryote also harbor the ribozymes. In Anopheles gambiae, the ribozymes were found differentially expressed and self-cleaved at basic developmental stages. Our results indicate that HDV-like ribozymes are abundant in nature and suggest that self-cleaving RNAs may play a variety of biological roles.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159031/" 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/PMC3159031/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Webb, Chiu-Ho T -- Riccitelli, Nathan J -- Ruminski, Dana J -- Luptak, Andrej -- R01 GM094929/GM/NIGMS NIH HHS/ -- R01 GM094929-01/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Nov 13;326(5955):953. doi: 10.1126/science.1178084.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697 USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965505" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anopheles/enzymology/*genetics/growth & development ; Base Sequence ; Catalysis ; Eukaryota/enzymology/*genetics ; Expressed Sequence Tags ; Hepatitis Delta Virus/enzymology/genetics ; Molecular Sequence Data ; Nucleic Acid Conformation ; RNA, Catalytic/*chemistry/*metabolism
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  • 12
    Publication Date: 2009-07-18
    Description: Amino acid, polyamine, and organocation (APC) transporters are secondary transporters that play essential roles in nutrient uptake, neurotransmitter recycling, ionic homeostasis, and regulation of cell volume. Here, we present the crystal structure of apo-ApcT, a proton-coupled broad-specificity amino acid transporter, at 2.35 angstrom resolution. The structure contains 12 transmembrane helices, with the first 10 consisting of an inverted structural repeat of 5 transmembrane helices like the leucine transporter LeuT. The ApcT structure reveals an inward-facing, apo state and an amine moiety of lysine-158 located in a position equivalent to the sodium ion site Na2 of LeuT. We propose that lysine-158 is central to proton-coupled transport and that the amine group serves the same functional role as the Na2 ion in LeuT, thus demonstrating common principles among proton- and sodium-coupled transporters.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851542/" 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/PMC2851542/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shaffer, Paul L -- Goehring, April -- Shankaranarayanan, Aruna -- Gouaux, Eric -- R01 MH070039/MH/NIMH NIH HHS/ -- R01 MH070039-05/MH/NIMH NIH HHS/ -- T32 GM008281/GM/NIGMS NIH HHS/ -- T32 GM008281-17/GM/NIGMS NIH HHS/ -- U54 GM075026/GM/NIGMS NIH HHS/ -- U54 GM075026-040002/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Aug 21;325(5943):1010-4. doi: 10.1126/science.1176088. Epub 2009 Jul 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vollum Institute, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19608859" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Transport Systems/*chemistry/*metabolism ; Amino Acids/metabolism ; Antiporters/chemistry ; Apoproteins/chemistry/metabolism ; Archaeal Proteins/*chemistry/*metabolism ; Crystallization ; Crystallography, X-Ray ; Escherichia coli Proteins/chemistry ; Methanococcus/*chemistry ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protons ; Sodium/metabolism ; Substrate Specificity
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  • 13
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-07-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holden, Constance -- New York, N.Y. -- Science. 2009 Jul 10;325(5937):131. doi: 10.1126/science.325_131.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19589969" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; *Embryo Research/economics ; *Embryonic Stem Cells ; Financing, Government ; *Guidelines as Topic ; Humans ; National Institutes of Health (U.S.) ; Registries ; *Research Support as Topic ; United States
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  • 14
    Publication Date: 2009-05-09
    Description: Despite tremendous progress in understanding the nature of the immune system, the full diversity of an organism's antibody repertoire is unknown. We used high-throughput sequencing of the variable domain of the antibody heavy chain from 14 zebrafish to analyze VDJ usage and antibody sequence. Zebrafish were found to use between 50 and 86% of all possible VDJ combinations and shared a similar frequency distribution, with some correlation of VDJ patterns between individuals. Zebrafish antibodies retained a few thousand unique heavy chains that also exhibited a shared frequency distribution. We found evidence of convergence, in which different individuals made the same antibody. This approach provides insight into the breadth of the expressed antibody repertoire and immunological diversity at the level of an individual organism.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086368/" 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/PMC3086368/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weinstein, Joshua A -- Jiang, Ning -- White, Richard A 3rd -- Fisher, Daniel S -- Quake, Stephen R -- DP1 OD000251/OD/NIH HHS/ -- DP1 OD000251-04/OD/NIH HHS/ -- DP1 OD000251-05/OD/NIH HHS/ -- DP1 OD000251-06/OD/NIH HHS/ -- New York, N.Y. -- Science. 2009 May 8;324(5928):807-10. doi: 10.1126/science.1170020.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biophysics Program, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19423829" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies/genetics ; Antibody Diversity ; Base Sequence ; Complementarity Determining Regions/*genetics ; Computational Biology ; Female ; Gene Library ; *Genes, Immunoglobulin Heavy Chain ; Immunoglobulin Heavy Chains/*genetics ; Immunoglobulin Joining Region/genetics ; Immunoglobulin M/*genetics ; Male ; Molecular Sequence Data ; Recombination, Genetic ; Sequence Analysis, DNA ; VDJ Exons ; Zebrafish/genetics/*immunology
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  • 15
    Publication Date: 2009-06-13
    Description: Rotavirus outer-layer protein VP7 is a principal target of protective antibodies. Removal of free calcium ions (Ca2+) dissociates VP7 trimers into monomers, releasing VP7 from the virion, and initiates penetration-inducing conformational changes in the other outer-layer protein, VP4. We report the crystal structure at 3.4 angstrom resolution of VP7 bound with the Fab fragment of a neutralizing monoclonal antibody. The Fab binds across the outer surface of the intersubunit contact, which contains two Ca2+ sites. Mutations that escape neutralization by other antibodies suggest that the same region bears the epitopes of most neutralizing antibodies. The monovalent Fab is sufficient to neutralize infectivity. We propose that neutralizing antibodies against VP7 act by stabilizing the trimer, thereby inhibiting the uncoating trigger for VP4 rearrangement. A disulfide-linked trimer is a potential subunit immunogen.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995306/" 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/PMC2995306/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aoki, Scott T -- Settembre, Ethan C -- Trask, Shane D -- Greenberg, Harry B -- Harrison, Stephen C -- Dormitzer, Philip R -- AI-21362/AI/NIAID NIH HHS/ -- CA-13202/CA/NCI NIH HHS/ -- DK-56339/DK/NIDDK NIH HHS/ -- R37 CA013202/CA/NCI NIH HHS/ -- R37 CA013202-38/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Jun 12;324(5933):1444-7. doi: 10.1126/science.1170481.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Medicine, Children's Hospital, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19520960" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Antibodies, Monoclonal/chemistry/immunology/metabolism ; Antibodies, Viral/chemistry/*immunology/metabolism ; Antigens, Viral/*chemistry/genetics/*immunology/metabolism ; Binding Sites ; Binding Sites, Antibody ; Calcium/metabolism ; Capsid Proteins/*chemistry/genetics/*immunology/metabolism ; Crystallography, X-Ray ; Epitopes/immunology ; Immunoglobulin Fab Fragments/chemistry/*immunology/metabolism ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Neutralization Tests ; Protein Folding ; Protein Multimerization ; Protein Structure, Tertiary ; Protein Subunits ; Recombinant Proteins/chemistry ; Rotavirus/*chemistry/immunology ; Serotyping
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  • 16
    Publication Date: 2009-03-28
    Description: P-glycoprotein (P-gp) detoxifies cells by exporting hundreds of chemically unrelated toxins but has been implicated in multidrug resistance (MDR) in the treatment of cancers. Substrate promiscuity is a hallmark of P-gp activity, thus a structural description of poly-specific drug-binding is important for the rational design of anticancer drugs and MDR inhibitors. The x-ray structure of apo P-gp at 3.8 angstroms reveals an internal cavity of approximately 6000 angstroms cubed with a 30 angstrom separation of the two nucleotide-binding domains. Two additional P-gp structures with cyclic peptide inhibitors demonstrate distinct drug-binding sites in the internal cavity capable of stereoselectivity that is based on hydrophobic and aromatic interactions. Apo and drug-bound P-gp structures have portals open to the cytoplasm and the inner leaflet of the lipid bilayer for drug entry. The inward-facing conformation represents an initial stage of the transport cycle that is competent for drug binding.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720052/" 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/PMC2720052/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aller, Stephen G -- Yu, Jodie -- Ward, Andrew -- Weng, Yue -- Chittaboina, Srinivas -- Zhuo, Rupeng -- Harrell, Patina M -- Trinh, Yenphuong T -- Zhang, Qinghai -- Urbatsch, Ina L -- Chang, Geoffrey -- F32 GM078914/GM/NIGMS NIH HHS/ -- F32 GM078914-03/GM/NIGMS NIH HHS/ -- GM073197/GM/NIGMS NIH HHS/ -- GM078914/GM/NIGMS NIH HHS/ -- GM61905/GM/NIGMS NIH HHS/ -- P50 GM073197/GM/NIGMS NIH HHS/ -- P50 GM073197-050002/GM/NIGMS NIH HHS/ -- R01 GM061905/GM/NIGMS NIH HHS/ -- R01 GM061905-09/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Mar 27;323(5922):1718-22. doi: 10.1126/science.1168750.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Scripps Research Institute, 10550 North Torrey Pines Road, CB105, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19325113" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Amino Acid Sequence ; Animals ; Apoproteins/chemistry/metabolism ; Binding Sites ; Cell Membrane/chemistry ; Crystallography, X-Ray ; Hydrophobic and Hydrophilic Interactions ; Lipid Bilayers/chemistry ; Mice ; Models, Molecular ; Molecular Sequence Data ; P-Glycoprotein/antagonists & inhibitors/*chemistry/*metabolism ; Peptides, Cyclic/*chemistry/*metabolism ; Protein Binding ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Stereoisomerism ; Verapamil/metabolism/pharmacology
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  • 17
    Publication Date: 2009-04-11
    Description: The nuclear factor kappaB (NF-kappaB) transcription factor regulates cellular stress responses and the immune response to infection. NF-kappaB activation results in oscillations in nuclear NF-kappaB abundance. To define the function of these oscillations, we treated cells with repeated short pulses of tumor necrosis factor-alpha at various intervals to mimic pulsatile inflammatory signals. At all pulse intervals that were analyzed, we observed synchronous cycles of NF-kappaB nuclear translocation. Lower frequency stimulations gave repeated full-amplitude translocations, whereas higher frequency pulses gave reduced translocation, indicating a failure to reset. Deterministic and stochastic mathematical models predicted how negative feedback loops regulate both the resetting of the system and cellular heterogeneity. Altering the stimulation intervals gave different patterns of NF-kappaB-dependent gene expression, which supports the idea that oscillation frequency has a functional role.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785900/" 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/PMC2785900/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ashall, Louise -- Horton, Caroline A -- Nelson, David E -- Paszek, Pawel -- Harper, Claire V -- Sillitoe, Kate -- Ryan, Sheila -- Spiller, David G -- Unitt, John F -- Broomhead, David S -- Kell, Douglas B -- Rand, David A -- See, Violaine -- White, Michael R H -- BB/C007158/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/C008219/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/C520471/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/D010748/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/E004210/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/E012965/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/F005938/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BBC0071581/Biotechnology and Biological Sciences Research Council/United Kingdom -- BBC0082191/Biotechnology and Biological Sciences Research Council/United Kingdom -- BBC5204711/Biotechnology and Biological Sciences Research Council/United Kingdom -- BBD0107481/Biotechnology and Biological Sciences Research Council/United Kingdom -- BBF0059381/Biotechnology and Biological Sciences Research Council/United Kingdom -- G0500346/Medical Research Council/United Kingdom -- G0500346(73596)/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2009 Apr 10;324(5924):242-6. doi: 10.1126/science.1164860.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Cell Imaging, School of Biological Sciences, Bioscience Research Building, Crown Street, Liverpool, L69 7ZB, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19359585" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Animals ; Cell Line ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Feedback, Physiological ; *Gene Expression ; Humans ; I-kappa B Proteins/metabolism ; Mice ; Models, Biological ; Models, Statistical ; NF-kappa B/*metabolism ; Phosphorylation ; Recombinant Fusion Proteins/metabolism ; Stochastic Processes ; Transcription Factor RelA/*metabolism ; *Transcription, Genetic ; Transfection ; Tumor Necrosis Factor-alpha/*metabolism
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  • 18
    Publication Date: 2009-03-03
    Description: Plants have distinct RNA polymerase complexes (Pol IV and Pol V) with largely unknown roles in maintaining small RNA-associated gene silencing. Curiously, the eudicot Arabidopsis thaliana is not affected when either function is lost. By use of mutation selection and positional cloning, we showed that the largest subunit of the presumed maize Pol IV is involved in paramutation, an inherited epigenetic change facilitated by an interaction between two alleles, as well as normal maize development. Bioinformatics analyses and nuclear run-on transcription assays indicate that Pol IV does not engage in the efficient RNA synthesis typical of the three major eukaryotic DNA-dependent RNA polymerases. These results indicate that Pol IV employs abnormal RNA polymerase activities to achieve genome-wide silencing and that its absence affects both maize development and heritable epigenetic changes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Erhard, Karl F Jr -- Stonaker, Jennifer L -- Parkinson, Susan E -- Lim, Jana P -- Hale, Christopher J -- Hollick, Jay B -- New York, N.Y. -- Science. 2009 Feb 27;323(5918):1201-5. doi: 10.1126/science.1164508.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant and Microbial Biology, 111 Koshland Hall, University of California, Berkeley, CA 94720-3102, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19251626" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Sequence ; Base Sequence ; Computational Biology ; DNA-Directed RNA Polymerases/chemistry/genetics/*metabolism ; *Epigenesis, Genetic ; Gene Silencing ; Genes, Plant ; Molecular Sequence Data ; *Mutation ; Phylogeny ; Protein Subunits/chemistry/genetics/metabolism ; RNA, Plant/genetics/metabolism ; RNA, Small Interfering/genetics/metabolism ; Transcription, Genetic ; Zea mays/*enzymology/*genetics/growth & development
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  • 19
    Publication Date: 2009-12-08
    Description: Primordial organisms of the putative RNA world would have required polymerase ribozymes able to replicate RNA. Known ribozymes with polymerase activity best approximating that needed for RNA replication contain at their catalytic core the class I RNA ligase, an artificial ribozyme with a catalytic rate among the fastest of known ribozymes. Here we present the 3.0 angstrom crystal structure of this ligase. The architecture resembles a tripod, its three legs converging near the ligation junction. Interacting with this tripod scaffold through a series of 10 minor-groove interactions (including two A-minor triads) is the unpaired segment that contributes to and organizes the active site. A cytosine nucleobase and two backbone phosphates abut the ligation junction; their location suggests a model for catalysis resembling that of proteinaceous polymerases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978776/" 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/PMC3978776/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shechner, David M -- Grant, Robert A -- Bagby, Sarah C -- Koldobskaya, Yelena -- Piccirilli, Joseph A -- Bartel, David P -- GM61835/GM/NIGMS NIH HHS/ -- R01 GM061835/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Nov 27;326(5957):1271-5. doi: 10.1126/science.1174676.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research and Howard Hughes Medical Institute, 9 Cambridge Center, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965478" target="_blank"〉PubMed〈/a〉
    Keywords: Base Pairing ; Base Sequence ; Catalysis ; Catalytic Domain ; Crystallization ; Crystallography, X-Ray ; DNA-Directed RNA Polymerases/chemistry/metabolism ; Hydrogen Bonding ; Hydrogen-Ion Concentration ; Magnesium/chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Polynucleotide Ligases/chemistry/metabolism ; RNA, Catalytic/*chemistry/metabolism ; Ribonucleotides/chemistry/metabolism
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  • 20
    Publication Date: 2009-02-21
    Description: Heat shock factor 1 (HSF1) is essential for protecting cells from protein-damaging stress associated with misfolded proteins and regulates the insulin-signaling pathway and aging. Here, we show that human HSF1 is inducibly acetylated at a critical residue that negatively regulates DNA binding activity. Activation of the deacetylase and longevity factor SIRT1 prolonged HSF1 binding to the heat shock promoter Hsp70 by maintaining HSF1 in a deacetylated, DNA-binding competent state. Conversely, down-regulation of SIRT1 accelerated the attenuation of the heat shock response (HSR) and release of HSF1 from its cognate promoter elements. These results provide a mechanistic basis for the requirement of HSF1 in the regulation of life span and establish a role for SIRT1 in protein homeostasis and the HSR.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3429349/" 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/PMC3429349/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Westerheide, Sandy D -- Anckar, Julius -- Stevens, Stanley M Jr -- Sistonen, Lea -- Morimoto, Richard I -- R01 AG026647/AG/NIA NIH HHS/ -- R01 AG026647-01/AG/NIA NIH HHS/ -- R01 AG026647-02/AG/NIA NIH HHS/ -- R01 AG026647-03/AG/NIA NIH HHS/ -- R01 AG026647-04/AG/NIA NIH HHS/ -- R01 GM038109/GM/NIGMS NIH HHS/ -- R37 GM038109/GM/NIGMS NIH HHS/ -- R37 GM038109-19/GM/NIGMS NIH HHS/ -- R37 GM038109-20/GM/NIGMS NIH HHS/ -- R37 GM038109-21/GM/NIGMS NIH HHS/ -- R37 GM038109-22/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Feb 20;323(5917):1063-6. doi: 10.1126/science.1165946.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Molecular Biology and Cell Biology, Rice Institute for Biomedical Research, Northwestern University, Evanston, IL, 60208, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19229036" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Amino Acid Sequence ; Animals ; Cell Aging/*physiology ; Chromatin Immunoprecipitation ; DNA/metabolism ; DNA-Binding Proteins/*metabolism ; Down-Regulation ; HSP70 Heat-Shock Proteins/*genetics ; HeLa Cells ; *Heat-Shock Response ; Homeostasis ; Humans ; Mice ; Molecular Sequence Data ; *Promoter Regions, Genetic ; RNA, Small Interfering ; Sirtuin 1 ; Sirtuins/genetics/*metabolism ; *Stress, Psychological ; Transcription Factors/*metabolism ; Transfection
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  • 21
    Publication Date: 2009-03-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holden, Constance -- New York, N.Y. -- Science. 2009 Mar 13;323(5920):1412-3. doi: 10.1126/science.323.5920.1412.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19286523" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; Embryo Research/economics/*legislation & jurisprudence ; *Embryonic Stem Cells ; Financing, Government/legislation & jurisprudence ; Guidelines as Topic ; Humans ; National Institutes of Health (U.S.) ; Pluripotent Stem Cells ; Research Support as Topic/*legislation & jurisprudence ; United States
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 22
    Publication Date: 2009-07-18
    Description: Genomic expansions of simple tandem repeats can give rise to toxic RNAs that contain expanded repeats. In myotonic dystrophy, the expression of expanded CUG repeats (CUGexp) causes abnormal regulation of alternative splicing and neuromuscular dysfunction. We used a transgenic mouse model to show that derangements of myotonic dystrophy are reversed by a morpholino antisense oligonucleotide, CAG25, that binds to CUGexp RNA and blocks its interaction with muscleblind-like 1 (MBNL1), a CUGexp-binding protein. CAG25 disperses nuclear foci of CUGexp RNA and reduces the overall burden of this toxic RNA. As MBNL1 is released from sequestration, the defect of alternative splicing regulation is corrected, thereby restoring ion channel function. These findings suggest an alternative use of antisense methods, to inhibit deleterious interactions of proteins with pathogenic RNAs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4109973/" 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/PMC4109973/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wheeler, Thurman M -- Sobczak, Krzysztof -- Lueck, John D -- Osborne, Robert J -- Lin, Xiaoyan -- Dirksen, Robert T -- Thornton, Charles A -- AR/NS48143/AR/NIAMS NIH HHS/ -- AR046806/AR/NIAMS NIH HHS/ -- K08 NS064293/NS/NINDS NIH HHS/ -- K24 AR048143/AR/NIAMS NIH HHS/ -- NIDCR-T32DE07202/DE/NIDCR NIH HHS/ -- R01 AR046806/AR/NIAMS NIH HHS/ -- R01 AR049077/AR/NIAMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Jul 17;325(5938):336-9. doi: 10.1126/science.1173110.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Neurology, Pharmacology and Physiology, University of Rochester, Rochester, NY 14642, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19608921" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions/genetics/*metabolism ; Actins/genetics ; Alternative Splicing ; Animals ; Cell Line ; Cell Nucleus/metabolism ; Chloride Channels/metabolism ; DNA-Binding Proteins/*metabolism ; Humans ; Mice ; Mice, Knockout ; Mice, Transgenic ; Myotonic Dystrophy/*drug therapy/*genetics/metabolism ; Myotonin-Protein Kinase ; Oligodeoxyribonucleotides, Antisense/*pharmacology/therapeutic use ; Protein-Serine-Threonine Kinases/genetics ; RNA, Messenger/genetics ; RNA-Binding Proteins/*metabolism ; Transcription, Genetic ; *Trinucleotide Repeat Expansion
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  • 23
    Publication Date: 2009-04-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holden, Constance -- Kaiser, Jocelyn -- New York, N.Y. -- Science. 2009 Apr 24;324(5926):446. doi: 10.1126/science.324_446.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19390007" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; Embryo Research/economics/*legislation & jurisprudence ; Embryonic Stem Cells ; Financing, Government/*legislation & jurisprudence ; Guidelines as Topic ; Humans ; National Institutes of Health (U.S.) ; Public Policy ; Research Support as Topic/*legislation & jurisprudence ; *Stem Cells ; United States
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 24
    Publication Date: 2009-09-12
    Description: Miniature inverted repeat transposable elements (MITEs) are widespread in eukaryotic genomes, where they can attain high copy numbers despite a lack of coding capacity. However, little is known about how they originate and amplify. We performed a genome-wide screen of functional interactions between Stowaway MITEs and potential transposases in the rice genome and identified a transpositionally active MITE that possesses key properties that enhance transposition. Although not directly related to its autonomous element, the MITE has less affinity for the transposase than does the autonomous element but lacks a motif repressing transposition in the autonomous element. The MITE contains internal sequences that enhance transposition. These findings suggest that MITEs achieve high transposition activity by scavenging transposases encoded by distantly related and self-restrained autonomous elements.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Guojun -- Nagel, Dawn Holligan -- Feschotte, Cedric -- Hancock, C Nathan -- Wessler, Susan R -- New York, N.Y. -- Science. 2009 Sep 11;325(5946):1391-4. doi: 10.1126/science.1175688.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Biology, University of Georgia, Athens, GA 30602, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19745152" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; *DNA Transposable Elements ; *Genome, Plant ; Inverted Repeat Sequences ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Oryza/*genetics/metabolism ; Transposases/genetics/*metabolism
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  • 25
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-07-11
    Description: Anaerobic methanotrophs help regulate Earth's climate and may have been an important part of the microbial ecosystem on the early Earth. The anaerobic oxidation of methane (AOM) is often thought of as a sulfate-dependent process, despite the fact that other electron acceptors are more energetically favorable. Here, we show that microorganisms from marine methane-seep sediment in the Eel River Basin in California are capable of using manganese (birnessite) and iron (ferrihydrite) to oxidize methane, revealing that marine AOM is coupled, either directly or indirectly, to a larger variety of oxidants than previously thought. Large amounts of manganese and iron are provided to oceans from rivers, indicating that manganese- and iron-dependent AOM have the potential to be globally important.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Beal, Emily J -- House, Christopher H -- Orphan, Victoria J -- New York, N.Y. -- Science. 2009 Jul 10;325(5937):184-7. doi: 10.1126/science.1169984.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Geosciences and Penn State Astrobiology Research Center, Pennsylvania State University, University Park, PA 16802, USA. ejbeal@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19589998" target="_blank"〉PubMed〈/a〉
    Keywords: Anaerobiosis ; Archaea/classification/genetics/isolation & purification/*metabolism ; Bacteria/classification/genetics/isolation & purification/*metabolism ; Bacteroides/classification/genetics/isolation & purification/metabolism ; California ; Carbon Dioxide/metabolism ; Crenarchaeota/classification/genetics/isolation & purification/metabolism ; Euryarchaeota/classification/genetics/isolation & purification/metabolism ; Ferric Compounds/*metabolism ; Geologic Sediments/*microbiology ; Manganese/*metabolism ; Methane/*metabolism ; Methanosarcinaceae/classification/genetics/isolation & purification/metabolism ; Molecular Sequence Data ; Oxidation-Reduction ; Oxides/*metabolism ; Phylogeny ; Proteobacteria/classification/genetics/isolation & purification/metabolism ; Thermodynamics
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  • 26
    Publication Date: 2009-04-04
    Description: Mitochondria continuously undergo two opposing processes, fission and fusion. The disruption of this dynamic equilibrium may herald cell injury or death and may contribute to developmental and neurodegenerative disorders. Nitric oxide functions as a signaling molecule, but in excess it mediates neuronal injury, in part via mitochondrial fission or fragmentation. However, the underlying mechanism for nitric oxide-induced pathological fission remains unclear. We found that nitric oxide produced in response to beta-amyloid protein, thought to be a key mediator of Alzheimer's disease, triggered mitochondrial fission, synaptic loss, and neuronal damage, in part via S-nitrosylation of dynamin-related protein 1 (forming SNO-Drp1). Preventing nitrosylation of Drp1 by cysteine mutation abrogated these neurotoxic events. SNO-Drp1 is increased in brains of human Alzheimer's disease patients and may thus contribute to the pathogenesis of neurodegeneration.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2823371/" 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/PMC2823371/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cho, Dong-Hyung -- Nakamura, Tomohiro -- Fang, Jianguo -- Cieplak, Piotr -- Godzik, Adam -- Gu, Zezong -- Lipton, Stuart A -- P01 ES016738/ES/NIEHS NIH HHS/ -- P01 ES016738-01/ES/NIEHS NIH HHS/ -- P01 ES016738-010003/ES/NIEHS NIH HHS/ -- P01 ES016738-02/ES/NIEHS NIH HHS/ -- P01 ES016738-020003/ES/NIEHS NIH HHS/ -- P01 HD029587/HD/NICHD NIH HHS/ -- P01 HD029587-16/HD/NICHD NIH HHS/ -- P01 HD29587/HD/NICHD NIH HHS/ -- P30 NS057096/NS/NINDS NIH HHS/ -- P30 NS057096-04/NS/NINDS NIH HHS/ -- R01 EY005477/EY/NEI NIH HHS/ -- R01 EY005477-25/EY/NEI NIH HHS/ -- R01 EY05477/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 2009 Apr 3;324(5923):102-5. doi: 10.1126/science.1171091.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Neuroscience, Aging, and Stem Cell Research, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19342591" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/metabolism/pathology ; Amino Acid Motifs ; Amyloid beta-Peptides/*metabolism/pharmacology ; Animals ; Cell Line ; Cell Line, Tumor ; Cerebral Cortex/cytology ; Cysteine/analogs & derivatives/genetics/metabolism/pharmacology ; Female ; GTP Phosphohydrolases/chemistry/*metabolism ; Humans ; Male ; Mice ; Mice, Transgenic ; Microtubule-Associated Proteins/chemistry/*metabolism ; Mitochondria/drug effects/physiology/*ultrastructure ; Mitochondrial Proteins/chemistry/*metabolism ; Models, Molecular ; Mutation ; Neurons/drug effects/*ultrastructure ; Nitric Oxide/*metabolism ; Peptide Fragments/metabolism/pharmacology ; Protein Multimerization ; Protein Structure, Tertiary ; S-Nitrosothiols/pharmacology
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  • 27
    Publication Date: 2009-02-21
    Description: Stripe rust is a devastating fungal disease that afflicts wheat in many regions of the world. New races of Puccinia striiformis, the pathogen responsible for this disease, have overcome most of the known race-specific resistance genes. We report the map-based cloning of the gene Yr36 (WKS1), which confers resistance to a broad spectrum of stripe rust races at relatively high temperatures (25 degrees to 35 degrees C). This gene includes a kinase and a putative START lipid-binding domain. Five independent mutations and transgenic complementation confirmed that both domains are necessary to confer resistance. Yr36 is present in wild wheat but is absent in modern pasta and bread wheat varieties, and therefore it can now be used to improve resistance to stripe rust in a broad set of varieties.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737487/" 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/PMC4737487/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fu, Daolin -- Uauy, Cristobal -- Distelfeld, Assaf -- Blechl, Ann -- Epstein, Lynn -- Chen, Xianming -- Sela, Hanan -- Fahima, Tzion -- Dubcovsky, Jorge -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Mar 6;323(5919):1357-60. doi: 10.1126/science.1166289. Epub 2009 Feb 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Sciences, University of California, Davis, CA 95616, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19228999" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Basidiomycota/*pathogenicity ; Cloning, Molecular ; Crosses, Genetic ; Down-Regulation ; *Genes, Plant ; Hot Temperature ; Immunity, Innate ; Molecular Sequence Data ; Phosphotransferases/chemistry/*genetics/metabolism ; Physical Chromosome Mapping ; *Plant Diseases/immunology/microbiology ; Plant Proteins/chemistry/genetics/metabolism ; Plants, Genetically Modified ; Triticum/*genetics/*microbiology
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  • 28
    Publication Date: 2009-04-04
    Description: Most genes function at multiple stages of metazoan development, in dividing and nondividing cells. Generating mouse conditional knock-outs (cKO), where a gene can be eliminated in a temporally and spatially controlled manner, is a valuable technique because it allows study of gene function at any stage of life. In contrast and despite the development of many other powerful genetic tools, cKO has thus far been lacking in Drosophila. We combined several recent molecular and genetic technical advances in an approach termed integrase-mediated approach for gene knock-out (IMAGO). IMAGO allows the replacement of any genomic sequence, such as a gene, with another desired sequence, including cKO alleles that can be used to create positively marked mutant cells. IMAGO should also be applicable to other genetic model organisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Choi, Ching Man -- Vilain, Sven -- Langen, Marion -- Van Kelst, Sofie -- De Geest, Natalie -- Yan, Jiekun -- Verstreken, Patrik -- Hassan, Bassem A -- New York, N.Y. -- Science. 2009 Apr 3;324(5923):54. doi: 10.1126/science.1168275.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Developmental Genetics, VIB 3000 Leuven, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19342580" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Drosophila melanogaster/cytology/*genetics ; *Gene Knockout Techniques ; Genes, Insect ; Integrases/metabolism ; Molecular Sequence Data ; *Mutagenesis ; Nerve Tissue Proteins/genetics ; Photoreceptor Cells, Invertebrate/cytology/physiology ; Recombination, Genetic ; Sense Organs/cytology/physiology
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  • 29
    Publication Date: 2009-01-03
    Description: Chaperone-mediated autophagy controls the degradation of selective cytosolic proteins and may protect neurons against degeneration. In a neuronal cell line, we found that chaperone-mediated autophagy regulated the activity of myocyte enhancer factor 2D (MEF2D), a transcription factor required for neuronal survival. MEF2D was observed to continuously shuttle to the cytoplasm, interact with the chaperone Hsc70, and undergo degradation. Inhibition of chaperone-mediated autophagy caused accumulation of inactive MEF2D in the cytoplasm. MEF2D levels were increased in the brains of alpha-synuclein transgenic mice and patients with Parkinson's disease. Wild-type alpha-synuclein and a Parkinson's disease-associated mutant disrupted the MEF2D-Hsc70 binding and led to neuronal death. Thus, chaperone-mediated autophagy modulates the neuronal survival machinery, and dysregulation of this pathway is associated with Parkinson's disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2666000/" 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/PMC2666000/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Qian -- She, Hua -- Gearing, Marla -- Colla, Emanuela -- Lee, Michael -- Shacka, John J -- Mao, Zixu -- AG023695/AG/NIA NIH HHS/ -- NS038065/NS/NINDS NIH HHS/ -- NS048254/NS/NINDS NIH HHS/ -- NS055077/NS/NINDS NIH HHS/ -- NS47466/NS/NINDS NIH HHS/ -- NS57098/NS/NINDS NIH HHS/ -- P30 NS055077/NS/NINDS NIH HHS/ -- P30 NS055077-01A2/NS/NINDS NIH HHS/ -- P50 AG025688/AG/NIA NIH HHS/ -- P50 AG025688-03/AG/NIA NIH HHS/ -- R01 AG023695/AG/NIA NIH HHS/ -- R01 AG023695-02/AG/NIA NIH HHS/ -- R01 AG023695-03/AG/NIA NIH HHS/ -- R01 AG023695-04/AG/NIA NIH HHS/ -- R01 AG023695-05/AG/NIA NIH HHS/ -- R01 NS048254/NS/NINDS NIH HHS/ -- R01 NS048254-02/NS/NINDS NIH HHS/ -- R01 NS048254-03/NS/NINDS NIH HHS/ -- R01 NS048254-04/NS/NINDS NIH HHS/ -- R01 NS048254-05/NS/NINDS NIH HHS/ -- R01 NS048254-06/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2009 Jan 2;323(5910):124-7. doi: 10.1126/science.1166088.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19119233" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Ammonium Chloride/pharmacology ; Animals ; *Autophagy ; Brain/metabolism ; Cell Line ; Cell Nucleus/metabolism ; Cell Survival ; Cytoplasm/metabolism ; DNA/metabolism ; HSC70 Heat-Shock Proteins/metabolism ; Lysosomal-Associated Membrane Protein 2/metabolism ; Lysosomes/metabolism ; MADS Domain Proteins/*metabolism ; MEF2 Transcription Factors ; Mice ; Mice, Transgenic ; Molecular Chaperones/*metabolism ; Myogenic Regulatory Factors/chemistry/*metabolism ; Neurons/cytology/*metabolism ; Parkinson Disease/metabolism ; Protein Binding ; Protein Transport ; Rats ; Rats, Long-Evans ; alpha-Synuclein/genetics/metabolism
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  • 30
    Publication Date: 2009-09-26
    Description: To explore the mechanisms and evolution of cell-cycle control, we analyzed the position and conservation of large numbers of phosphorylation sites for the cyclin-dependent kinase Cdk1 in the budding yeast Saccharomyces cerevisiae. We combined specific chemical inhibition of Cdk1 with quantitative mass spectrometry to identify the positions of 547 phosphorylation sites on 308 Cdk1 substrates in vivo. Comparisons of these substrates with orthologs throughout the ascomycete lineage revealed that the position of most phosphorylation sites is not conserved in evolution; instead, clusters of sites shift position in rapidly evolving disordered regions. We propose that the regulation of protein function by phosphorylation often depends on simple nonspecific mechanisms that disrupt or enhance protein-protein interactions. The gain or loss of phosphorylation sites in rapidly evolving regions could facilitate the evolution of kinase-signaling circuits.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2813701/" 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/PMC2813701/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holt, Liam J -- Tuch, Brian B -- Villen, Judit -- Johnson, Alexander D -- Gygi, Steven P -- Morgan, David O -- GM037049/GM/NIGMS NIH HHS/ -- GM50684/GM/NIGMS NIH HHS/ -- HG3456/HG/NHGRI NIH HHS/ -- R01 GM069901/GM/NIGMS NIH HHS/ -- R01 GM069901-06/GM/NIGMS NIH HHS/ -- R01 HG003456/HG/NHGRI NIH HHS/ -- R01 HG003456-06/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2009 Sep 25;325(5948):1682-6. doi: 10.1126/science.1172867.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Physiology and Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19779198" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Ascomycota/chemistry/genetics/metabolism ; *Biological Evolution ; CDC2 Protein Kinase/antagonists & inhibitors/*metabolism ; *Cell Cycle ; Cell Physiological Processes ; Computational Biology ; *Evolution, Molecular ; Molecular Sequence Data ; Phosphopeptides/chemistry/*metabolism ; Phosphorylation ; Phylogeny ; Protein Conformation ; Protein Structure, Tertiary ; Saccharomyces cerevisiae/chemistry/genetics/metabolism ; Saccharomyces cerevisiae Proteins/chemistry/*metabolism ; *Signal Transduction ; Substrate Specificity
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  • 31
    Publication Date: 2009-08-29
    Description: To understand the process by which antibiotic resistance genes are acquired by human pathogens, we functionally characterized the resistance reservoir in the microbial flora of healthy individuals. Most of the resistance genes we identified using culture-independent sampling have not been previously identified and are evolutionarily distant from known resistance genes. By contrast, nearly half of the resistance genes we identified in cultured aerobic gut isolates (a small subset of the gut microbiome) are identical to resistance genes harbored by major pathogens. The immense diversity of resistance genes in the human microbiome could contribute to future emergence of antibiotic resistance in human pathogens.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4720503/" 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/PMC4720503/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sommer, Morten O A -- Dantas, Gautam -- Church, George M -- P50 HG003170/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2009 Aug 28;325(5944):1128-31. doi: 10.1126/science.1176950.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. sommer@genetics.med.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19713526" target="_blank"〉PubMed〈/a〉
    Keywords: Anti-Bacterial Agents/pharmacology ; Antiporters/genetics/metabolism ; Bacteria/drug effects/*genetics/isolation & purification ; Bacteria, Aerobic/classification/drug effects/*genetics/isolation & purification ; Bacterial Proteins/genetics/metabolism ; Digestive System/*microbiology ; Drug Resistance, Bacterial/*genetics ; Feces/microbiology ; *Genes, Bacterial ; Humans ; *Metagenome ; Microbial Sensitivity Tests ; Molecular Sequence Data ; Phylogeny ; Proteobacteria/classification/drug effects/genetics/isolation & purification ; Saliva/microbiology ; Transposases/genetics/metabolism ; beta-Lactamases/genetics/metabolism
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  • 32
    Publication Date: 2009-12-08
    Description: Although the nematode Caenorhabditis elegans produces self-fertile hermaphrodites, it descended from a male/female species, so hermaphroditism provides a model for the origin of novel traits. In the related species C. remanei, which has only male and female sexes, lowering the activity of tra-2 by RNA interference created XX animals that made spermatids as well as oocytes, but their spermatids could not activate without the addition of male seminal fluid. However, by lowering the expression of both tra-2 and swm-1, a gene that regulates sperm activation in C. elegans, we produced XX animals with active sperm that were self-fertile. Thus, the evolution of hermaphroditism in Caenorhabditis probably required two steps: a mutation in the sex-determination pathway that caused XX spermatogenesis and a mutation that allowed these spermatids to self-activate.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baldi, Chris -- Cho, Soochin -- Ellis, Ronald E -- New York, N.Y. -- Science. 2009 Nov 13;326(5955):1002-5. doi: 10.1126/science.1176013.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, Stratford, NJ 08084, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965511" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; *Biological Evolution ; Caenorhabditis/anatomy & histology/classification/*genetics/*physiology ; Caenorhabditis elegans/anatomy & histology/classification/*genetics/*physiology ; Caenorhabditis elegans Proteins/genetics/physiology ; Crosses, Genetic ; Disorders of Sex Development/genetics ; Female ; Genes, Helminth ; Germ Cells/physiology ; Male ; Membrane Proteins/genetics/physiology ; Molecular Sequence Data ; *Mutation ; Oogenesis ; Ovulation ; Phylogeny ; Reproduction ; Selection, Genetic ; Sex Determination Processes ; Spermatids/physiology ; Spermatogenesis
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  • 33
    Publication Date: 2009-09-04
    Description: The Hedgehog (Hh) signaling pathway is inappropriately activated in certain human cancers, including medulloblastoma, an aggressive brain tumor. GDC-0449, a drug that inhibits Hh signaling by targeting the serpentine receptor Smoothened (SMO), has produced promising anti-tumor responses in early clinical studies of cancers driven by mutations in this pathway. To evaluate the mechanism of resistance in a medulloblastoma patient who had relapsed after an initial response to GDC-0449, we determined the mutational status of Hh signaling genes in the tumor after disease progression. We identified an amino acid substitution at a conserved aspartic acid residue of SMO that had no effect on Hh signaling but disrupted the ability of GDC-0449 to bind SMO and suppress this pathway. A mutation altering the same amino acid also arose in a GDC-0449-resistant mouse model of medulloblastoma. These findings show that acquired mutations in a serpentine receptor with features of a G protein-coupled receptor can serve as a mechanism of drug resistance in human cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yauch, Robert L -- Dijkgraaf, Gerrit J P -- Alicke, Bruno -- Januario, Thomas -- Ahn, Christina P -- Holcomb, Thomas -- Pujara, Kanan -- Stinson, Jeremy -- Callahan, Christopher A -- Tang, Tracy -- Bazan, J Fernando -- Kan, Zhengyan -- Seshagiri, Somasekar -- Hann, Christine L -- Gould, Stephen E -- Low, Jennifer A -- Rudin, Charles M -- de Sauvage, Frederic J -- New York, N.Y. -- Science. 2009 Oct 23;326(5952):572-4. doi: 10.1126/science.1179386. Epub 2009 Sep 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genentech, South San Francisco, CA 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19726788" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Anilides/metabolism/pharmacology/*therapeutic use ; Animals ; Antineoplastic Agents/metabolism/pharmacology/*therapeutic use ; Brain Neoplasms/*drug therapy/*genetics/pathology ; Cell Line, Tumor ; Cinnamates/pharmacology ; Drug Resistance, Neoplasm ; Hedgehog Proteins/antagonists & inhibitors/genetics/*metabolism ; Humans ; Medulloblastoma/*drug therapy/*genetics/pathology ; Mice ; Molecular Sequence Data ; Mutant Proteins/antagonists & inhibitors/chemistry/metabolism ; Mutation, Missense ; Neoplasm Metastasis ; Protein Conformation ; Pyridines/metabolism/pharmacology/*therapeutic use ; Receptors, Cell Surface/genetics/metabolism ; Receptors, G-Protein-Coupled/antagonists & ; inhibitors/chemistry/*genetics/metabolism ; Signal Transduction ; Veratrum Alkaloids/pharmacology
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  • 34
    Publication Date: 2009-10-03
    Description: Mitochondria are integral components of cellular calcium (Ca2+) signaling. Calcium stimulates mitochondrial adenosine 5'-triphosphate production, but can also initiate apoptosis. In turn, cytoplasmic Ca2+ concentrations are regulated by mitochondria. Although several transporter and ion-channel mechanisms have been measured in mitochondria, the molecules that govern Ca2+ movement across the inner mitochondrial membrane are unknown. We searched for genes that regulate mitochondrial Ca2+ and H+ concentrations using a genome-wide Drosophila RNA interference (RNAi) screen. The mammalian homolog of one Drosophila gene identified in the screen, Letm1, was found to specifically mediate coupled Ca2+/H+ exchange. RNAi knockdown, overexpression, and liposome reconstitution of the purified Letm1 protein demonstrate that Letm1 is a mitochondrial Ca2+/H+ antiporter.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067766/" 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/PMC4067766/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jiang, Dawei -- Zhao, Linlin -- Clapham, David E -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Oct 2;326(5949):144-7. doi: 10.1126/science.1175145.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cardiology, Howard Hughes Medical Institute, Children's Hospital Boston, Manton Center for Orphan Disease, and Department of Neurobiology, Harvard Medical School, Enders Building 1309, 320 Longwood Avenue, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19797662" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antiporters/*genetics/metabolism ; Calcium/*metabolism ; Calcium-Binding Proteins/*genetics/*metabolism ; Cation Transport Proteins/genetics/metabolism ; Cell Line ; Drosophila Proteins/*genetics/metabolism ; Drosophila melanogaster/*genetics/metabolism ; Genome, Human ; Genome, Insect ; HeLa Cells ; Humans ; Hydrogen/metabolism ; Hydrogen-Ion Concentration ; Ion Transport ; Membrane Potential, Mitochondrial ; Membrane Proteins/*genetics/*metabolism ; Mitochondria/*metabolism ; Mitochondrial Membranes/metabolism ; Mitochondrial Proteins/genetics/*metabolism ; Proteolipids/metabolism ; *RNA Interference
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  • 35
    Publication Date: 2009-12-08
    Description: Bacteria-mediated acquisition of atmospheric N2 serves as a critical source of nitrogen in terrestrial ecosystems. Here we reveal that symbiotic nitrogen fixation facilitates the cultivation of specialized fungal crops by leaf-cutter ants. By using acetylene reduction and stable isotope experiments, we demonstrated that N2 fixation occurred in the fungus gardens of eight leaf-cutter ant species and, further, that this fixed nitrogen was incorporated into ant biomass. Symbiotic N2-fixing bacteria were consistently isolated from the fungus gardens of 80 leaf-cutter ant colonies collected in Argentina, Costa Rica, and Panama. The discovery of N2 fixation within the leaf-cutter ant-microbe symbiosis reveals a previously unrecognized nitrogen source in neotropical ecosystems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pinto-Tomas, Adrian A -- Anderson, Mark A -- Suen, Garret -- Stevenson, David M -- Chu, Fiona S T -- Cleland, W Wallace -- Weimer, Paul J -- Currie, Cameron R -- GM 18938/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Nov 20;326(5956):1120-3. doi: 10.1126/science.1173036.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bacteriology, University of Wisconsin-Madison, 1550 Linden Drive, Madison, WI 53706, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965433" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylene/metabolism ; Animals ; Ants/metabolism/microbiology/*physiology ; Argentina ; Costa Rica ; *Ecosystem ; Fungi/growth & development/*physiology ; Klebsiella/isolation & purification/*metabolism ; Molecular Sequence Data ; Nitrogen/analysis/metabolism ; *Nitrogen Fixation ; Oxidation-Reduction ; Panama ; Pantoea/isolation & purification/*metabolism ; Phylogeny ; Plant Leaves/chemistry ; *Symbiosis
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  • 36
    Publication Date: 2009-03-07
    Description: The mutation rates of viroids, plant pathogens with minimal non-protein-coding RNA genomes, are unknown. Their replication is mediated by host RNA polymerases and, in some cases, by hammerhead ribozymes, small self-cleaving motifs embedded in the viroid. By using the principle that the population frequency of nonviable genotypes equals the mutation rate, we screened for changes that inactivated the hammerheads of Chrysanthemum chlorotic mottle viroid. We obtained a mutation rate of 1/400 per site, the highest reported for any biological entity. Such error-prone replication can only be tolerated by extremely simple genomes such as those of viroids and, presumably, the primitive replicons of the RNA world. Our results suggest that the emergence of replication fidelity was critical for the evolution of complexity in the early history of life.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gago, Selma -- Elena, Santiago F -- Flores, Ricardo -- Sanjuan, Rafael -- New York, N.Y. -- Science. 2009 Mar 6;323(5919):1308. doi: 10.1126/science.1169202.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Instituto de Biologia Molecular y Celular de Plantas, Consejo Superior de Investigaciones Cientificas-Universidad Politecnica de Valencia, 46022 Valencia, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19265013" target="_blank"〉PubMed〈/a〉
    Keywords: Genome, Viral ; Molecular Sequence Data ; *Mutation ; Nucleic Acid Conformation ; RNA, Catalytic/chemistry/*genetics ; RNA, Viral/chemistry/*genetics ; Replicon ; Reverse Transcriptase Polymerase Chain Reaction ; Selection, Genetic ; Viroids/*genetics/physiology ; Virus Replication
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  • 37
    Publication Date: 2009-12-19
    Description: The evolution of cis regulatory elements (enhancers) of developmentally regulated genes plays a large role in the evolution of animal morphology. However, the mutational path of enhancer evolution--the number, origin, effect, and order of mutations that alter enhancer function--has not been elucidated. Here, we localized a suite of substitutions in a modular enhancer of the ebony locus responsible for adaptive melanism in a Ugandan Drosophila population. We show that at least five mutations with varied effects arose recently from a combination of standing variation and new mutations and combined to create an allele of large phenotypic effect. We underscore how enhancers are distinct macromolecular entities, subject to fundamentally different, and generally more relaxed, functional constraints relative to protein sequences.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3363996/" 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/PMC3363996/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rebeiz, Mark -- Pool, John E -- Kassner, Victoria A -- Aquadro, Charles F -- Carroll, Sean B -- F32GM78972/GM/NIGMS NIH HHS/ -- F32HG004182/HG/NHGRI NIH HHS/ -- GM036431/GM/NIGMS NIH HHS/ -- R01 GM036431/GM/NIGMS NIH HHS/ -- R01 GM036431-22/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Dec 18;326(5960):1663-7. doi: 10.1126/science.1178357.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Laboratory of Molecular Biology, University of Wisconsin, Madison, WI 53706, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20019281" target="_blank"〉PubMed〈/a〉
    Keywords: Abdomen ; Adaptation, Biological ; Alleles ; Animals ; Animals, Genetically Modified ; *Biological Evolution ; DNA-Binding Proteins/*genetics ; Drosophila Proteins/*genetics ; Drosophila melanogaster/*genetics/growth & development/physiology ; *Enhancer Elements, Genetic ; Evolution, Molecular ; Gene Expression Regulation, Developmental ; Haplotypes ; Molecular Sequence Data ; Mutation ; Pigmentation/*genetics ; Polymorphism, Genetic ; Uganda
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  • 38
    Publication Date: 2009-05-30
    Description: Virulent enteric pathogens such as Escherichia coli strain O157:H7 rely on acid-resistance (AR) systems to survive the acidic environment in the stomach. A major component of AR is an arginine-dependent arginine:agmatine antiporter that expels intracellular protons. Here, we report the crystal structure of AdiC, the arginine:agmatine antiporter from E. coli O157:H7 and a member of the amino acid/polyamine/organocation (APC) superfamily of transporters at 3.6 A resolution. The overall fold is similar to that of several Na+-coupled symporters. AdiC contains 12 transmembrane segments, forms a homodimer, and exists in an outward-facing, open conformation in the crystals. A conserved, acidic pocket opens to the periplasm. Structural and biochemical analysis reveals the essential ligand-binding residues, defines the transport route, and suggests a conserved mechanism for the antiporter activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gao, Xiang -- Lu, Feiran -- Zhou, Lijun -- Dang, Shangyu -- Sun, Linfeng -- Li, Xiaochun -- Wang, Jiawei -- Shi, Yigong -- New York, N.Y. -- Science. 2009 Jun 19;324(5934):1565-8. doi: 10.1126/science.1173654. Epub 2009 May 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Bio-membrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19478139" target="_blank"〉PubMed〈/a〉
    Keywords: Agmatine/metabolism ; Amino Acid Sequence ; Amino Acid Transport Systems/*chemistry/genetics/metabolism/physiology ; Antiporters/*chemistry/genetics/metabolism/physiology ; Arginine/metabolism ; Conserved Sequence ; Crystallography, X-Ray ; Escherichia coli O157/*chemistry/genetics/metabolism ; Escherichia coli Proteins/*chemistry/genetics/metabolism/physiology ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation
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  • 39
    Publication Date: 2009-11-07
    Description: The rice Xa21 gene confers immunity to most strains of the bacterium Xanthomonas oryzae pv. oryzae (Xoo). Liquid chromatography-tandem mass spectrometry analysis of biologically active fractions from Xoo supernatants led to the identification of a 194-amino acid protein designated Ax21 (activator of XA21-mediated immunity). A sulfated, 17-amino acid synthetic peptide (axY(S)22) derived from the N-terminal region of Ax21 is sufficient for activity, whereas peptides lacking tyrosine sulfation are biologically inactive. Using coimmunoprecipitation, we found that XA21 is required for axY(S)22 binding and recognition. axY(S)22 is 100% conserved in all analyzed Xanthomonas species, confirming that Ax21 is a pathogen-associated molecular pattern and that XA21 is a pattern recognition receptor.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Sang-Won -- Han, Sang-Wook -- Sririyanum, Malinee -- Park, Chang-Jin -- Seo, Young-Su -- Ronald, Pamela C -- GM55962/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Nov 6;326(5954):850-3. doi: 10.1126/science.1173438.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Pathology, University of California, Davis, CA 95616, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19892983" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Bacterial Proteins/chemistry/genetics/isolation & purification/*metabolism ; Conserved Sequence ; Genes, Bacterial ; Host-Pathogen Interactions ; Immunity, Innate ; Immunoprecipitation ; Molecular Sequence Data ; Oryza/*immunology/metabolism/*microbiology ; Peptide Fragments/chemistry/metabolism ; Plant Diseases/*immunology/microbiology ; Plant Leaves/metabolism ; Plant Proteins/*metabolism ; Protein-Serine-Threonine Kinases/*metabolism ; Receptors, Pattern Recognition/genetics/*metabolism ; Sulfates/metabolism ; Tyrosine/metabolism ; Xanthomonas/genetics/immunology/*metabolism
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  • 40
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-04-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leite, Marcelo -- New York, N.Y. -- Science. 2009 Apr 3;324(5923):26. doi: 10.1126/science.324.5923.26.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19342562" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/economics ; Bioreactors ; Brazil ; Cell Culture Techniques ; Cell Line ; *Embryo Research/economics ; *Embryonic Stem Cells/cytology ; Financing, Government ; Humans ; *Pluripotent Stem Cells/cytology ; Research Support as Topic
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  • 41
    Publication Date: 2009-04-11
    Description: Picoeukaryotes are a taxonomically diverse group of organisms less than 2 micrometers in diameter. Photosynthetic marine picoeukaryotes in the genus Micromonas thrive in ecosystems ranging from tropical to polar and could serve as sentinel organisms for biogeochemical fluxes of modern oceans during climate change. These broadly distributed primary producers belong to an anciently diverged sister clade to land plants. Although Micromonas isolates have high 18S ribosomal RNA gene identity, we found that genomes from two isolates shared only 90% of their predicted genes. Their independent evolutionary paths were emphasized by distinct riboswitch arrangements as well as the discovery of intronic repeat elements in one isolate, and in metagenomic data, but not in other genomes. Divergence appears to have been facilitated by selection and acquisition processes that actively shape the repertoire of genes that are mutually exclusive between the two isolates differently than the core genes. Analyses of the Micromonas genomes offer valuable insights into ecological differentiation and the dynamic nature of early plant evolution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Worden, Alexandra Z -- Lee, Jae-Hyeok -- Mock, Thomas -- Rouze, Pierre -- Simmons, Melinda P -- Aerts, Andrea L -- Allen, Andrew E -- Cuvelier, Marie L -- Derelle, Evelyne -- Everett, Meredith V -- Foulon, Elodie -- Grimwood, Jane -- Gundlach, Heidrun -- Henrissat, Bernard -- Napoli, Carolyn -- McDonald, Sarah M -- Parker, Micaela S -- Rombauts, Stephane -- Salamov, Aasf -- Von Dassow, Peter -- Badger, Jonathan H -- Coutinho, Pedro M -- Demir, Elif -- Dubchak, Inna -- Gentemann, Chelle -- Eikrem, Wenche -- Gready, Jill E -- John, Uwe -- Lanier, William -- Lindquist, Erika A -- Lucas, Susan -- Mayer, Klaus F X -- Moreau, Herve -- Not, Fabrice -- Otillar, Robert -- Panaud, Olivier -- Pangilinan, Jasmyn -- Paulsen, Ian -- Piegu, Benoit -- Poliakov, Aaron -- Robbens, Steven -- Schmutz, Jeremy -- Toulza, Eve -- Wyss, Tania -- Zelensky, Alexander -- Zhou, Kemin -- Armbrust, E Virginia -- Bhattacharya, Debashish -- Goodenough, Ursula W -- Van de Peer, Yves -- Grigoriev, Igor V -- New York, N.Y. -- Science. 2009 Apr 10;324(5924):268-72. doi: 10.1126/science.1167222.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Monterey Bay Aquarium Research Institute, Moss Landing, CA 95039 USA. azworden@mbari.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19359590" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological ; *Biological Evolution ; Chlorophyta/classification/cytology/*genetics/physiology ; DNA Transposable Elements ; Ecosystem ; Gene Expression Regulation ; Genes ; Genetic Variation ; *Genome ; Introns ; Meiosis/genetics ; Molecular Sequence Data ; Oceans and Seas ; Photosynthesis/genetics ; Phylogeny ; Phytoplankton/classification/genetics ; Plants/*genetics ; RNA, Untranslated ; Repetitive Sequences, Nucleic Acid ; Sequence Analysis, DNA ; Transcription Factors/genetics
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  • 42
    Publication Date: 2009-02-14
    Description: The sigma-1 receptor is widely distributed in the central nervous system and periphery. Originally mischaracterized as an opioid receptor, the sigma-1 receptor binds a vast number of synthetic compounds but does not bind opioid peptides; it is currently considered an orphan receptor. The sigma-1 receptor pharmacophore includes an alkylamine core, also found in the endogenous compound N,N-dimethyltryptamine (DMT). DMT acts as a hallucinogen, but its receptor target has been unclear. DMT bound to sigma-1 receptors and inhibited voltage-gated sodium ion (Na+) channels in both native cardiac myocytes and heterologous cells that express sigma-1 receptors. DMT induced hypermobility in wild-type mice but not in sigma-1 receptor knockout mice. These biochemical, physiological, and behavioral experiments indicate that DMT is an endogenous agonist for the sigma-1 receptor.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947205/" 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/PMC2947205/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fontanilla, Dominique -- Johannessen, Molly -- Hajipour, Abdol R -- Cozzi, Nicholas V -- Jackson, Meyer B -- Ruoho, Arnold E -- F31 DA022932/DA/NIDA NIH HHS/ -- NS30016/NS/NINDS NIH HHS/ -- R01 MH065503/MH/NIMH NIH HHS/ -- R01 MH065503-01A1/MH/NIMH NIH HHS/ -- R01 NS030016/NS/NINDS NIH HHS/ -- R01 NS030016-08/NS/NINDS NIH HHS/ -- R01 NS030016-09/NS/NINDS NIH HHS/ -- T32 GM08688/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Feb 13;323(5916):934-7. doi: 10.1126/science.1166127.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19213917" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; COS Cells ; Cell Line ; Cells, Cultured ; Cercopithecus aethiops ; Guinea Pigs ; Hallucinogens/*metabolism ; Ligands ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myocardium/metabolism ; N,N-Dimethyltryptamine/*metabolism ; Rats ; Receptors, sigma/agonists/antagonists & inhibitors/*metabolism ; Tryptamines/metabolism
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  • 43
    Publication Date: 2009-02-07
    Description: A major cause for biodiversity may be biodiversity itself. As new species form, they may create new niches for others to exploit, potentially catalyzing a chain reaction of speciation events across trophic levels. We tested for such sequential radiation in the Rhagoletis pomonella (Diptera: Tephritidae) complex, a model for sympatric speciation via host plant shifting. We report that the parasitic wasp Diachasma alloeum (Hymenoptera: Braconidae) has formed new incipient species as a result of specializing on diversifying fly hosts, including the recently derived apple-infesting race of R. pomonella. Furthermore, we show that traits that differentially adapt R. pomonella flies to their host plants have also quickly evolved and serve as ecological barriers to reproduction, isolating the wasps. Speciation therefore cascades as the effects of new niche construction move across trophic levels.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Forbes, Andrew A -- Powell, Thomas H Q -- Stelinski, Lukasz L -- Smith, James J -- Feder, Jeffrey L -- New York, N.Y. -- Science. 2009 Feb 6;323(5915):776-9. doi: 10.1126/science.1166981.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, University of Notre Dame, Galvin Life Sciences Building, Notre Dame, IN 46556, USA. aaforbes@ucdavis.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19197063" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Biological ; Animals ; *Biodiversity ; Cues ; DNA, Mitochondrial/genetics ; Female ; Fruit ; Gene Flow ; Gene Frequency ; Genes, Insect ; *Genetic Speciation ; Genetic Variation ; Haplotypes ; Host-Parasite Interactions ; Male ; Microsatellite Repeats ; Molecular Sequence Data ; Odors ; Sexual Behavior, Animal ; Tephritidae/*genetics/growth & development/*parasitology/physiology ; Wasps/*genetics/growth & development/physiology
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  • 44
    Publication Date: 2009-11-07
    Description: The LKB1 tumor suppressor is a protein kinase that controls the activity of adenosine monophosphate-activated protein kinase (AMPK). LKB1 activity is regulated by the pseudokinase STRADalpha and the scaffolding protein MO25alpha through an unknown, phosphorylation-independent, mechanism. We describe the structure of the core heterotrimeric LKB1-STRADalpha-MO25alpha complex, revealing an unusual allosteric mechanism of LKB1 activation. STRADalpha adopts a closed conformation typical of active protein kinases and binds LKB1 as a pseudosubstrate. STRADalpha and MO25alpha promote the active conformation of LKB1, which is stabilized by MO25alpha interacting with the LKB1 activation loop. This previously undescribed mechanism of kinase activation may be relevant to understanding the evolution of other pseudokinases. The structure also reveals how mutations found in Peutz-Jeghers syndrome and in various sporadic cancers impair LKB1 function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518268/" 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/PMC3518268/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zeqiraj, Elton -- Filippi, Beatrice Maria -- Deak, Maria -- Alessi, Dario R -- van Aalten, Daan M F -- 087590/Wellcome Trust/United Kingdom -- C33794/A10969/Cancer Research UK/United Kingdom -- G0900138/Medical Research Council/United Kingdom -- MC_U127070193/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2009 Dec 18;326(5960):1707-11. doi: 10.1126/science.1178377. Epub 2009 Nov 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Molecular Microbiology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19892943" target="_blank"〉PubMed〈/a〉
    Keywords: AMP-Activated Protein Kinases/metabolism ; Adaptor Proteins, Vesicular Transport/*chemistry/metabolism ; Allosteric Regulation ; Amino Acid Sequence ; Binding Sites ; Calcium-Binding Proteins/*chemistry/metabolism ; Crystallography, X-Ray ; Enzyme Activation ; Humans ; Models, Molecular ; Molecular Sequence Data ; Multiprotein Complexes/chemistry/metabolism ; Mutant Proteins/chemistry/metabolism ; Mutation ; Phosphorylation ; Protein Binding ; Protein Conformation ; Protein Interaction Domains and Motifs ; Protein Structure, Tertiary ; Protein-Serine-Threonine Kinases/*chemistry/metabolism
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  • 45
    Publication Date: 2009-01-10
    Description: Expression and signaling of CD30, a tumor necrosis factor receptor family member, is up-regulated in numerous lymphoid-derived neoplasias, most notably anaplastic large-cell lymphoma (ALCL) and Hodgkin's lymphoma. To gain insight into the mechanism of CD30 signaling, we used an affinity purification strategy that led to the identification of the aryl hydrocarbon receptor nuclear translocator (ARNT) as a CD30-interacting protein that modulated the activity of the RelB subunit of the transcription factor nuclear factor kappaB (NF-kappaB). ALCL cells that were deficient in ARNT exhibited defects in RelB recruitment to NF-kappaB-responsive promoters, whereas RelA recruitment to the same sites was potentiated, resulting in the augmented expression of these NF-kappaB-responsive genes. These findings indicate that ARNT functions in concert with RelB in a CD30-induced negative feedback mechanism.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2682336/" 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/PMC2682336/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wright, Casey W -- Duckett, Colin S -- R01 GM067827/GM/NIGMS NIH HHS/ -- R01 GM067827-04/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Jan 9;323(5911):251-5. doi: 10.1126/science.1162818.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19131627" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Antigens, CD30/*metabolism ; Aryl Hydrocarbon Receptor Nuclear Translocator/chemistry/genetics/*metabolism ; Cell Line ; Cell Line, Tumor ; DNA/metabolism ; Feedback, Physiological ; Gene Expression Regulation ; Humans ; Lymphoma, Large-Cell, Anaplastic/genetics/metabolism ; Molecular Sequence Data ; NF-kappa B/genetics/metabolism ; Promoter Regions, Genetic ; Protein Structure, Tertiary ; Receptors, Tumor Necrosis Factor, Type II/metabolism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Transcription Factor RelB/genetics/*metabolism ; *Transcription, Genetic ; Transcriptional Activation
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  • 46
    Publication Date: 2009-08-01
    Description: Epac2, a guanine nucleotide exchange factor for the small guanosine triphosphatase Rap1, is activated by adenosine 3',5'-monophosphate. Fluorescence resonance energy transfer and binding experiments revealed that sulfonylureas, widely used antidiabetic drugs, interact directly with Epac2. Sulfonylureas activated Rap1 specifically through Epac2. Sulfonylurea-stimulated insulin secretion was reduced both in vitro and in vivo in mice lacking Epac2, and the glucose-lowering effect of the sulfonylurea tolbutamide was decreased in these mice. Epac2 thus contributes to the effect of sulfonylureas to promote insulin secretion. Because Epac2 is also required for the action of incretins, gut hormones crucial for potentiating insulin secretion, it may be a promising target for antidiabetic drug development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Chang-Liang -- Katoh, Megumi -- Shibasaki, Tadao -- Minami, Kohtaro -- Sunaga, Yasuhiro -- Takahashi, Harumi -- Yokoi, Norihide -- Iwasaki, Masahiro -- Miki, Takashi -- Seino, Susumu -- New York, N.Y. -- Science. 2009 Jul 31;325(5940):607-10. doi: 10.1126/science.1172256.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Cellular and Molecular Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19644119" target="_blank"〉PubMed〈/a〉
    Keywords: 8-Bromo Cyclic Adenosine Monophosphate/pharmacology ; Animals ; Blood Glucose/analysis ; COS Cells ; Carrier Proteins/genetics/*metabolism ; Cell Line ; Cercopithecus aethiops ; Cyclic AMP/*metabolism ; Fluorescence Resonance Energy Transfer ; Glucose/administration & dosage ; Glyburide/metabolism/pharmacology ; Guanine Nucleotide Exchange Factors/genetics/*metabolism ; Hypoglycemic Agents/chemistry/*metabolism/pharmacology ; Insulin/blood/secretion ; Islets of Langerhans/secretion ; Mice ; Mice, Inbred C57BL ; Sulfonylurea Compounds/chemistry/*metabolism/pharmacology ; Tolbutamide/metabolism/pharmacology ; rap1 GTP-Binding Proteins/metabolism
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  • 47
    Publication Date: 2009-06-06
    Description: Necrosis can be induced by stimulating death receptors with tumor necrosis factor (TNF) or other agonists; however, the underlying mechanism differentiating necrosis from apoptosis is largely unknown. We identified the protein kinase receptor-interacting protein 3 (RIP3) as a molecular switch between TNF-induced apoptosis and necrosis in NIH 3T3 cells and found that RIP3 was required for necrosis in other cells. RIP3 did not affect RIP1-mediated apoptosis but was required for RIP1-mediated necrosis and the enhancement of necrosis by the caspase inhibitor zVAD. By activating key enzymes of metabolic pathways, RIP3 regulates TNF-induced reactive oxygen species production, which partially accounts for RIP3's ability to promote necrosis. Our data suggest that modulation of energy metabolism in response to death stimuli has an important role in the choice between apoptosis and necrosis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Duan-Wu -- Shao, Jing -- Lin, Juan -- Zhang, Na -- Lu, Bao-Ju -- Lin, Sheng-Cai -- Dong, Meng-Qiu -- Han, Jiahuai -- New York, N.Y. -- Science. 2009 Jul 17;325(5938):332-6. doi: 10.1126/science.1172308. Epub 2009 Jun 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19498109" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Chloromethyl Ketones/pharmacology ; Animals ; *Apoptosis ; Cell Line ; Energy Metabolism ; Glutamate Dehydrogenase/metabolism ; Glutamate-Ammonia Ligase/metabolism ; Glycogen Phosphorylase/metabolism ; Mice ; NIH 3T3 Cells ; *Necrosis ; RNA Interference ; Reactive Oxygen Species/metabolism ; Receptor-Interacting Protein Serine-Threonine Kinases/genetics/*metabolism ; Tumor Necrosis Factor-alpha/*pharmacology
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  • 48
    Publication Date: 2009-05-13
    Description: A novel influenza A (H1N1) virus has spread rapidly across the globe. Judging its pandemic potential is difficult with limited data, but nevertheless essential to inform appropriate health responses. By analyzing the outbreak in Mexico, early data on international spread, and viral genetic diversity, we make an early assessment of transmissibility and severity. Our estimates suggest that 23,000 (range 6000 to 32,000) individuals had been infected in Mexico by late April, giving an estimated case fatality ratio (CFR) of 0.4% (range: 0.3 to 1.8%) based on confirmed and suspected deaths reported to that time. In a community outbreak in the small community of La Gloria, Veracruz, no deaths were attributed to infection, giving an upper 95% bound on CFR of 0.6%. Thus, although substantial uncertainty remains, clinical severity appears less than that seen in the 1918 influenza pandemic but comparable with that seen in the 1957 pandemic. Clinical attack rates in children in La Gloria were twice that in adults (〈15 years of age: 61%; 〉/=15 years: 29%). Three different epidemiological analyses gave basic reproduction number (R0) estimates in the range of 1.4 to 1.6, whereas a genetic analysis gave a central estimate of 1.2. This range of values is consistent with 14 to 73 generations of human-to-human transmission having occurred in Mexico to late April. Transmissibility is therefore substantially higher than that of seasonal flu, and comparable with lower estimates of R0 obtained from previous influenza pandemics.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3735127/" 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/PMC3735127/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fraser, Christophe -- Donnelly, Christl A -- Cauchemez, Simon -- Hanage, William P -- Van Kerkhove, Maria D -- Hollingsworth, T Deirdre -- Griffin, Jamie -- Baggaley, Rebecca F -- Jenkins, Helen E -- Lyons, Emily J -- Jombart, Thibaut -- Hinsley, Wes R -- Grassly, Nicholas C -- Balloux, Francois -- Ghani, Azra C -- Ferguson, Neil M -- Rambaut, Andrew -- Pybus, Oliver G -- Lopez-Gatell, Hugo -- Alpuche-Aranda, Celia M -- Chapela, Ietza Bojorquez -- Zavala, Ethel Palacios -- Guevara, Dulce Ma Espejo -- Checchi, Francesco -- Garcia, Erika -- Hugonnet, Stephane -- Roth, Cathy -- WHO Rapid Pandemic Assessment Collaboration -- G0600719/Medical Research Council/United Kingdom -- GR082623MA/Wellcome Trust/United Kingdom -- U54 GM088491/GM/NIGMS NIH HHS/ -- Biotechnology and Biological Sciences Research Council/United Kingdom -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2009 Jun 19;324(5934):1557-61. doi: 10.1126/science.1176062. Epub 2009 May 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, Faculty of Medicine, Norfolk Place, London W2 1PG, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19433588" target="_blank"〉PubMed〈/a〉
    Keywords: *Disease Outbreaks ; Global Health ; Humans ; *Influenza A Virus, H1N1 Subtype ; Influenza, Human/*epidemiology/mortality/transmission/virology ; Mexico/epidemiology ; Molecular Sequence Data ; Travel
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  • 49
    Publication Date: 2009-04-18
    Description: An active microbial assemblage cycles sulfur in a sulfate-rich, ancient marine brine beneath Taylor Glacier, an outlet glacier of the East Antarctic Ice Sheet, with Fe(III) serving as the terminal electron acceptor. Isotopic measurements of sulfate, water, carbonate, and ferrous iron and functional gene analyses of adenosine 5'-phosphosulfate reductase imply that a microbial consortium facilitates a catalytic sulfur cycle. These metabolic pathways result from a limited organic carbon supply because of the absence of contemporary photosynthesis, yielding a subglacial ferrous brine that is anoxic but not sulfidic. Coupled biogeochemical processes below the glacier enable subglacial microbes to grow in extended isolation, demonstrating how analogous organic-starved systems, such as Neoproterozoic oceans, accumulated Fe(II) despite the presence of an active sulfur cycle.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mikucki, Jill A -- Pearson, Ann -- Johnston, David T -- Turchyn, Alexandra V -- Farquhar, James -- Schrag, Daniel P -- Anbar, Ariel D -- Priscu, John C -- Lee, Peter A -- New York, N.Y. -- Science. 2009 Apr 17;324(5925):397-400. doi: 10.1126/science.1167350.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Earth and Planetary Sciences, Harvard University, Cambridge, MA 02138 USA. jill.a.mikucki@dartmouth.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19372431" target="_blank"〉PubMed〈/a〉
    Keywords: Anaerobiosis ; Antarctic Regions ; Autotrophic Processes ; Bacteria/growth & development/*metabolism ; *Ecosystem ; Ferric Compounds/*metabolism ; Ferrous Compounds/*metabolism ; Heterotrophic Processes ; *Ice Cover ; Metabolic Networks and Pathways ; Molecular Sequence Data ; Oxidation-Reduction ; Oxidoreductases Acting on Sulfur Group Donors/genetics/metabolism ; Oxygen/metabolism ; Oxygen Isotopes/analysis ; Phylogeny ; Seawater/chemistry/*microbiology ; Sulfates/metabolism ; Sulfites/metabolism ; Sulfur/*metabolism
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  • 50
    Publication Date: 2009-09-05
    Description: Actin filaments are key components of the eukaryotic cytoskeleton that provide mechanical structure and generate forces during cell shape changes, growth, and migration. Actin filaments are dynamically assembled into higher-order structures at specified locations to regulate diverse functions. The Rab family of small guanosine triphosphatases is evolutionarily conserved and mediates intracellular vesicle trafficking. We found that Rab35 regulates the assembly of actin filaments during bristle development in Drosophila and filopodia formation in cultured cells. These effects were mediated by the actin-bundling protein fascin, which directly associated with active Rab35. Targeting Rab35 to the outer mitochondrial membrane triggered actin recruitment, demonstrating a role for an intracellular trafficking protein in localized actin assembly.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Jun -- Fonovic, Marko -- Suyama, Kaye -- Bogyo, Matthew -- Scott, Matthew P -- U54 RR020843/RR/NCRR NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Sep 4;325(5945):1250-4. doi: 10.1126/science.1174921.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19729655" target="_blank"〉PubMed〈/a〉
    Keywords: Actin Cytoskeleton/*metabolism/ultrastructure ; Actins/*metabolism ; Animals ; Carrier Proteins/*metabolism ; Cell Line ; Cell Membrane/metabolism ; Drosophila/anatomy & histology/growth & development/metabolism ; Drosophila Proteins/genetics/*metabolism ; HeLa Cells ; Humans ; Mice ; Microfilament Proteins/*metabolism ; Mitochondrial Membranes/metabolism ; NIH 3T3 Cells ; Pseudopodia/metabolism/ultrastructure ; RNA Interference ; Recombinant Fusion Proteins/metabolism ; rab GTP-Binding Proteins/genetics/*metabolism
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  • 51
    Publication Date: 2009-02-14
    Description: Many species of parasitoid wasps inject polydnavirus particles in order to manipulate host defenses and development. Because the DNA packaged in these particles encodes almost no viral structural proteins, their relation to viruses has been debated. Characterization of complementary DNAs derived from braconid wasp ovaries identified genes encoding subunits of a viral RNA polymerase and structural components of polydnavirus particles related most closely to those of nudiviruses--a sister group of baculoviruses. The conservation of this viral machinery in different braconid wasp lineages sharing polydnaviruses suggests that parasitoid wasps incorporated a nudivirus-related genome into their own genetic material. We found that the nudiviral genes themselves are no longer packaged but are actively transcribed and produce particles used to deliver genes essential for successful parasitism in lepidopteran hosts.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bezier, Annie -- Annaheim, Marc -- Herbiniere, Juline -- Wetterwald, Christoph -- Gyapay, Gabor -- Bernard-Samain, Sylvie -- Wincker, Patrick -- Roditi, Isabel -- Heller, Manfred -- Belghazi, Maya -- Pfister-Wilhem, Rita -- Periquet, Georges -- Dupuy, Catherine -- Huguet, Elisabeth -- Volkoff, Anne-Nathalie -- Lanzrein, Beatrice -- Drezen, Jean-Michel -- New York, N.Y. -- Science. 2009 Feb 13;323(5916):926-30. doi: 10.1126/science.1166788.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Recherche sur la Biologie de l'Insecte, CNRS UMR 6035, Universite Francois Rabelais, Parc de Grandmont, 37200 Tours, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19213916" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Baculoviridae/genetics ; Biological Evolution ; *DNA, Viral/analysis ; Expressed Sequence Tags ; Female ; Genome, Insect ; Molecular Sequence Data ; Ovary/virology ; Polydnaviridae/*genetics/physiology ; Viral Structural Proteins/genetics ; Virion/genetics ; Virus Integration ; Wasps/*virology
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  • 52
    Publication Date: 2009-12-08
    Description: Holometabolous insects undergo complete metamorphosis to become sexually mature adults. Metamorphosis is initiated by brain-derived prothoracicotropic hormone (PTTH), which stimulates the production of the molting hormone ecdysone via an incompletely defined signaling pathway. Here we demonstrate that Torso, a receptor tyrosine kinase that regulates embryonic terminal cell fate in Drosophila, is the PTTH receptor. Trunk, the embryonic Torso ligand, is related to PTTH, and ectopic expression of PTTH in the embryo partially rescues trunk mutants. In larvae, torso is expressed specifically in the prothoracic gland (PG), and its loss phenocopies the removal of PTTH. The activation of Torso by PTTH stimulates extracellular signal-regulated kinase (ERK) phosphorylation, and the loss of ERK in the PG phenocopies the loss of PTTH and Torso. We conclude that PTTH initiates metamorphosis by activation of the Torso/ERK pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rewitz, Kim F -- Yamanaka, Naoki -- Gilbert, Lawrence I -- O'Connor, Michael B -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Dec 4;326(5958):1403-5. doi: 10.1126/science.1176450.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965758" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Bombyx/*genetics/metabolism ; Cell Line ; Drosophila Proteins/chemistry/genetics/*metabolism ; Drosophila melanogaster/embryology/genetics/*growth & development/metabolism ; Embryo, Nonmammalian/metabolism ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Insect Hormones/chemistry/*metabolism ; Larva/growth & development ; Ligands ; *Metamorphosis, Biological ; Molecular Sequence Data ; Neurons/metabolism ; Phosphorylation ; Pupa/growth & development ; RNA Interference ; Receptor Protein-Tyrosine Kinases/genetics/*metabolism ; Signal Transduction
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  • 53
    Publication Date: 2009-01-20
    Description: Axon guidance proteins are critical for the correct wiring of the nervous system during development. Several axon guidance cues and their family members have been well characterized. More unidentified axon guidance cues are assumed to participate in the formation of the extremely complex nervous system. We identified a secreted protein, draxin, that shares no homology with known guidance cues. Draxin inhibited or repelled neurite outgrowth from dorsal spinal cord and cortical explants in vitro. Ectopically expressed draxin inhibited growth or caused misrouting of chick spinal cord commissural axons in vivo. draxin knockout mice showed defasciculation of spinal cord commissural axons and absence of all forebrain commissures. Thus, draxin is a previously unknown chemorepulsive axon guidance molecule required for the development of spinal cord and forebrain commissures.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Islam, Shahidul M -- Shinmyo, Yohei -- Okafuji, Tatsuya -- Su, Yuhong -- Naser, Iftekhar Bin -- Ahmed, Giasuddin -- Zhang, Sanbing -- Chen, Sandy -- Ohta, Kunimasa -- Kiyonari, Hiroshi -- Abe, Takaya -- Tanaka, Satomi -- Nishinakamura, Ryuichi -- Terashima, Toshio -- Kitamura, Toshio -- Tanaka, Hideaki -- New York, N.Y. -- Science. 2009 Jan 16;323(5912):388-93. doi: 10.1126/science.1165187.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Developmental Neurobiology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19150847" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Axons/*physiology ; COS Cells ; Cercopithecus aethiops ; Chick Embryo ; Coculture Techniques ; Corpus Callosum/embryology/metabolism ; Electroporation ; Growth Cones/metabolism/physiology ; Intercellular Signaling Peptides and ; Proteins/chemistry/genetics/metabolism/*physiology ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Neurites/metabolism/*physiology ; Neurogenesis ; Neuroglia/metabolism ; Prosencephalon/abnormalities/*embryology/metabolism ; Recombinant Proteins/metabolism ; Spinal Cord/*embryology/metabolism ; Tissue Culture Techniques
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  • 54
    Publication Date: 2009-01-20
    Description: Among cellular organisms, symbiotic bacteria provide the extreme examples of genome degradation and reduction. However, only isolated snapshots of eroding symbiont genomes have previously been available. We documented the dynamics of symbiont genome evolution by sequencing seven strains of Buchnera aphidicola from pea aphid hosts. We estimated a spontaneous mutation rate of at least 4 x 10(-9) substitutions per site per replication, which is more than 10 times as high as the rates previously estimated for any bacteria. We observed a high rate of small insertions and deletions associated with abundant DNA homopolymers, and occasional larger deletions. Although purifying selection eliminates many mutations, some persist, resulting in ongoing loss of genes and DNA from this already tiny genome. Our results provide a general model for the stepwise process leading to genome reduction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moran, Nancy A -- McLaughlin, Heather J -- Sorek, Rotem -- New York, N.Y. -- Science. 2009 Jan 16;323(5912):379-82. doi: 10.1126/science.1167140.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721, USA. nmoran@email.arizona.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19150844" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aphids/*microbiology/physiology ; Base Composition ; Buchnera/*genetics/*physiology ; Evolution, Molecular ; *Gene Silencing ; *Genome, Bacterial ; INDEL Mutation ; Models, Genetic ; Molecular Sequence Data ; *Mutation ; Phylogeny ; Polymorphism, Single Nucleotide ; Selection, Genetic ; Sequence Analysis, DNA ; Sequence Deletion ; *Symbiosis
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  • 55
    Publication Date: 2009-04-11
    Description: Heterozygous mutations in the gene encoding isocitrate dehydrogenase-1 (IDH1) occur in certain human brain tumors, but their mechanistic role in tumor development is unknown. We have shown that tumor-derived IDH1 mutations impair the enzyme's affinity for its substrate and dominantly inhibit wild-type IDH1 activity through the formation of catalytically inactive heterodimers. Forced expression of mutant IDH1 in cultured cells reduces formation of the enzyme product, alpha-ketoglutarate (alpha-KG), and increases the levels of hypoxia-inducible factor subunit HIF-1alpha, a transcription factor that facilitates tumor growth when oxygen is low and whose stability is regulated by alpha-KG. The rise in HIF-1alpha levels was reversible by an alpha-KG derivative. HIF-1alpha levels were higher in human gliomas harboring an IDH1 mutation than in tumors without a mutation. Thus, IDH1 appears to function as a tumor suppressor that, when mutationally inactivated, contributes to tumorigenesis in part through induction of the HIF-1 pathway.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3251015/" 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/PMC3251015/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhao, Shimin -- Lin, Yan -- Xu, Wei -- Jiang, Wenqing -- Zha, Zhengyu -- Wang, Pu -- Yu, Wei -- Li, Zhiqiang -- Gong, Lingling -- Peng, Yingjie -- Ding, Jianping -- Lei, Qunying -- Guan, Kun-Liang -- Xiong, Yue -- R01 CA068377/CA/NCI NIH HHS/ -- R01 CA068377-14/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Apr 10;324(5924):261-5. doi: 10.1126/science.1170944.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular and Cell Biology Laboratory, Institute of Biomedical Sciences, Fudan University, 130 Dong-An Road, Shanghai 200032, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19359588" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Aged ; Astrocytoma/genetics/metabolism ; Biocatalysis ; Brain Neoplasms/*genetics/metabolism ; Cell Line ; Child ; Female ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Glioblastoma/genetics/metabolism ; Glioma/*genetics/metabolism ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & ; inhibitors/genetics/*metabolism ; Isocitrate Dehydrogenase/chemistry/*genetics/*metabolism ; Ketoglutaric Acids/metabolism ; Male ; Middle Aged ; Mutant Proteins/chemistry/metabolism ; Oligodendroglioma/genetics/metabolism ; Oxalates/pharmacology ; Protein Multimerization
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  • 56
    Publication Date: 2009-07-25
    Description: The toolbox of rat genetics currently lacks the ability to introduce site-directed, heritable mutations into the genome to create knockout animals. By using engineered zinc-finger nucleases (ZFNs) designed to target an integrated reporter and two endogenous rat genes, Immunoglobulin M (IgM) and Rab38, we demonstrate that a single injection of DNA or messenger RNA encoding ZFNs into the one-cell rat embryo leads to a high frequency of animals carrying 25 to 100% disruption at the target locus. These mutations are faithfully and efficiently transmitted through the germline. Our data demonstrate the feasibility of targeted gene disruption in multiple rat strains within 4 months time, paving the way to a humanized monoclonal antibody platform and additional human disease models.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831805/" 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/PMC2831805/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Geurts, Aron M -- Cost, Gregory J -- Freyvert, Yevgeniy -- Zeitler, Bryan -- Miller, Jeffrey C -- Choi, Vivian M -- Jenkins, Shirin S -- Wood, Adam -- Cui, Xiaoxia -- Meng, Xiangdong -- Vincent, Anna -- Lam, Stephen -- Michalkiewicz, Mieczyslaw -- Schilling, Rebecca -- Foeckler, Jamie -- Kalloway, Shawn -- Weiler, Hartmut -- Menoret, Severine -- Anegon, Ignacio -- Davis, Gregory D -- Zhang, Lei -- Rebar, Edward J -- Gregory, Philip D -- Urnov, Fyodor D -- Jacob, Howard J -- Buelow, Roland -- 5P01HL082798-03/HL/NHLBI NIH HHS/ -- 5U01HL066579-08/HL/NHLBI NIH HHS/ -- P01 HL082798/HL/NHLBI NIH HHS/ -- P01 HL082798-03/HL/NHLBI NIH HHS/ -- U01 HL066579/HL/NHLBI NIH HHS/ -- U01 HL066579-08/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2009 Jul 24;325(5939):433. doi: 10.1126/science.1172447.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI 52336, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19628861" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Dna ; Embryo, Mammalian ; Endodeoxyribonucleases/genetics/*metabolism ; Feasibility Studies ; Female ; *Gene Knockout Techniques ; Green Fluorescent Proteins ; Immunoglobulin M/*genetics ; Male ; *Microinjections ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; RNA, Messenger ; Rats ; *Zinc Fingers/genetics ; rab GTP-Binding Proteins/*genetics
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  • 57
    Publication Date: 2009-10-03
    Description: Sex determination mechanisms differ among animal species, but it is not clear how these differences evolve. New sex determiners may arise in response to sexual conflicts, which occur when traits benefit one sex but hinder the other. We identified the genetic basis for the orange-blotch (OB) color pattern, a trait under sexually antagonistic selection in the cichlid fish of Lake Malawi, East Africa. The OB phenotype is due to a cis-regulatory mutation in the Pax7 gene. OB provides benefits of camouflage to females but disrupts the species-specific male color patterns used for mate recognition. We suggest that the resulting sexual conflict over the OB allele has been resolved by selection for a novel female sex determination locus that has invaded populations with an ancestral male sex determination system.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3174268/" 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/PMC3174268/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roberts, Reade B -- Ser, Jennifer R -- Kocher, Thomas D -- F32HD051383/HD/NICHD NIH HHS/ -- R01 HD058635/HD/NICHD NIH HHS/ -- R01 HD058635-04/HD/NICHD NIH HHS/ -- R01HD058635/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2009 Nov 13;326(5955):998-1001. doi: 10.1126/science.1174705. Epub 2009 Oct 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of Maryland, College Park, MD 20742, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19797625" target="_blank"〉PubMed〈/a〉
    Keywords: Africa, Eastern ; Animals ; Biological Evolution ; Chromosome Mapping ; Cichlids/*genetics/*physiology ; Female ; Fresh Water ; Gene Expression Regulation ; Genetic Fitness ; Genetic Speciation ; Haplotypes ; Linkage Disequilibrium ; Male ; *Mating Preference, Animal ; Melanophores/cytology/metabolism ; Microsatellite Repeats ; Molecular Sequence Data ; PAX7 Transcription Factor/*genetics ; Phenotype ; Pigmentation/*genetics ; Polymorphism, Single Nucleotide ; *Selection, Genetic ; Sex Characteristics ; *Sex Determination Processes ; Sexual Behavior, Animal
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  • 58
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-11-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2009 Nov 6;326(5954):780-1. doi: 10.1126/science.326_780a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19892950" target="_blank"〉PubMed〈/a〉
    Keywords: *Academies and Institutes ; Adult Stem Cells ; *Biological Therapy ; California ; Cell Line ; Embryonic Stem Cells ; Genetic Therapy ; Humans ; Induced Pluripotent Stem Cells ; National Institutes of Health (U.S.) ; *Research Support as Topic ; *Stem Cell Transplantation ; *Stem Cells ; United States
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  • 59
    Publication Date: 2009-04-25
    Description: The imprints of domestication and breed development on the genomes of livestock likely differ from those of companion animals. A deep draft sequence assembly of shotgun reads from a single Hereford female and comparative sequences sampled from six additional breeds were used to develop probes to interrogate 37,470 single-nucleotide polymorphisms (SNPs) in 497 cattle from 19 geographically and biologically diverse breeds. These data show that cattle have undergone a rapid recent decrease in effective population size from a very large ancestral population, possibly due to bottlenecks associated with domestication, selection, and breed formation. Domestication and artificial selection appear to have left detectable signatures of selection within the cattle genome, yet the current levels of diversity within breeds are at least as great as exists within humans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2735092/" 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/PMC2735092/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bovine HapMap Consortium -- Gibbs, Richard A -- Taylor, Jeremy F -- Van Tassell, Curtis P -- Barendse, William -- Eversole, Kellye A -- Gill, Clare A -- Green, Ronnie D -- Hamernik, Debora L -- Kappes, Steven M -- Lien, Sigbjorn -- Matukumalli, Lakshmi K -- McEwan, John C -- Nazareth, Lynne V -- Schnabel, Robert D -- Weinstock, George M -- Wheeler, David A -- Ajmone-Marsan, Paolo -- Boettcher, Paul J -- Caetano, Alexandre R -- Garcia, Jose Fernando -- Hanotte, Olivier -- Mariani, Paola -- Skow, Loren C -- Sonstegard, Tad S -- Williams, John L -- Diallo, Boubacar -- Hailemariam, Lemecha -- Martinez, Mario L -- Morris, Chris A -- Silva, Luiz O C -- Spelman, Richard J -- Mulatu, Woudyalew -- Zhao, Keyan -- Abbey, Colette A -- Agaba, Morris -- Araujo, Flabio R -- Bunch, Rowan J -- Burton, James -- Gorni, Chiara -- Olivier, Hanotte -- Harrison, Blair E -- Luff, Bill -- Machado, Marco A -- Mwakaya, Joel -- Plastow, Graham -- Sim, Warren -- Smith, Timothy -- Thomas, Merle B -- Valentini, Alessio -- Williams, Paul -- Womack, James -- Woolliams, John A -- Liu, Yue -- Qin, Xiang -- Worley, Kim C -- Gao, Chuan -- Jiang, Huaiyang -- Moore, Stephen S -- Ren, Yanru -- Song, Xing-Zhi -- Bustamante, Carlos D -- Hernandez, Ryan D -- Muzny, Donna M -- Patil, Shobha -- San Lucas, Anthony -- Fu, Qing -- Kent, Matthew P -- Vega, Richard -- Matukumalli, Aruna -- McWilliam, Sean -- Sclep, Gert -- Bryc, Katarzyna -- Choi, Jungwoo -- Gao, Hong -- Grefenstette, John J -- Murdoch, Brenda -- Stella, Alessandra -- Villa-Angulo, Rafael -- Wright, Mark -- Aerts, Jan -- Jann, Oliver -- Negrini, Riccardo -- Goddard, Mike E -- Hayes, Ben J -- Bradley, Daniel G -- Barbosa da Silva, Marcos -- Lau, Lilian P L -- Liu, George E -- Lynn, David J -- Panzitta, Francesca -- Dodds, Ken G -- R01 GM083606/GM/NIGMS NIH HHS/ -- R01 GM083606-02/GM/NIGMS NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2009 Apr 24;324(5926):528-32. doi: 10.1126/science.1167936.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19390050" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breeding ; Cattle/*genetics ; Female ; Gene Frequency ; *Genetic Variation ; *Genome ; Male ; Molecular Sequence Data ; Mutation ; *Polymorphism, Single Nucleotide ; Population Density
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  • 60
    Publication Date: 2009-01-20
    Description: Variation in the length of simple DNA triplet repeats has been linked to phenotypic variability in microbes and to several human disorders. Population-level forces driving triplet repeat contraction and expansion in multicellular organisms are, however, not well understood. We have identified a triplet repeat-associated genetic defect in an Arabidopsis thaliana variety collected from the wild. The Bur-0 strain carries a dramatically expanded TTC/GAA repeat in the intron of the ISOPROPYL MALATE ISOMERASE LARGE SUB UNIT1 (IIL1; At4g13430) gene. The repeat expansion causes an environment-dependent reduction in IIL1 activity and severely impairs growth of this strain, whereas contraction of the expanded repeat can reverse the detrimental phenotype. The Bur-0 IIL1 defect thus presents a genetically tractable model for triplet repeat expansions and their variability in natural populations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sureshkumar, Sridevi -- Todesco, Marco -- Schneeberger, Korbinian -- Harilal, Ramya -- Balasubramanian, Sureshkumar -- Weigel, Detlef -- New York, N.Y. -- Science. 2009 Feb 20;323(5917):1060-3. doi: 10.1126/science.1164014. Epub 2009 Jan 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Max Planck Institute for Developmental Biology, D-72076 Tubingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19150812" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Arabidopsis/*genetics/growth & development/metabolism ; Arabidopsis Proteins/*genetics/metabolism ; Genes, Plant ; Genetic Variation ; *Introns ; Isomerases/*genetics/metabolism ; Molecular Sequence Data ; Phenotype ; Plant Leaves/growth & development ; RNA, Plant/genetics/metabolism ; Temperature ; *Trinucleotide Repeat Expansion ; Trinucleotide Repeats
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  • 61
    Publication Date: 2009-04-18
    Description: DNA cytosine methylation is crucial for retrotransposon silencing and mammalian development. In a computational search for enzymes that could modify 5-methylcytosine (5mC), we identified TET proteins as mammalian homologs of the trypanosome proteins JBP1 and JBP2, which have been proposed to oxidize the 5-methyl group of thymine. We show here that TET1, a fusion partner of the MLL gene in acute myeloid leukemia, is a 2-oxoglutarate (2OG)- and Fe(II)-dependent enzyme that catalyzes conversion of 5mC to 5-hydroxymethylcytosine (hmC) in cultured cells and in vitro. hmC is present in the genome of mouse embryonic stem cells, and hmC levels decrease upon RNA interference-mediated depletion of TET1. Thus, TET proteins have potential roles in epigenetic regulation through modification of 5mC to hmC.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715015/" 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/PMC2715015/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tahiliani, Mamta -- Koh, Kian Peng -- Shen, Yinghua -- Pastor, William A -- Bandukwala, Hozefa -- Brudno, Yevgeny -- Agarwal, Suneet -- Iyer, Lakshminarayan M -- Liu, David R -- Aravind, L -- Rao, Anjana -- AI44432/AI/NIAID NIH HHS/ -- K08 HL089150/HL/NHLBI NIH HHS/ -- R01 GM065865/GM/NIGMS NIH HHS/ -- R01 GM065865-05A1/GM/NIGMS NIH HHS/ -- R01GM065865/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2009 May 15;324(5929):930-5. doi: 10.1126/science.1170116. Epub 2009 Apr 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Harvard Medical School and Immune Disease Institute, 200 Longwood Avenue, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19372391" target="_blank"〉PubMed〈/a〉
    Keywords: 5-Methylcytosine/*metabolism ; Amino Acid Sequence ; Animals ; Cell Line ; Cytosine/*analogs & derivatives/analysis/metabolism ; DNA/chemistry/*metabolism ; DNA Methylation ; DNA-Binding Proteins/chemistry/genetics/*metabolism ; Dinucleoside Phosphates/metabolism ; Embryonic Stem Cells/chemistry/metabolism ; Humans ; Hydroxylation ; Mass Spectrometry ; Mice ; Molecular Sequence Data ; Proto-Oncogene Proteins/chemistry/genetics/*metabolism ; RNA Interference ; Sequence Alignment ; Transfection
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  • 62
    Publication Date: 2009-07-04
    Description: Biogenic amines such as serotonin and dopamine are intercellular signaling molecules that function widely as neurotransmitters and neuromodulators. We have identified in the nematode Caenorhabditis elegans three ligand-gated chloride channels that are receptors for biogenic amines: LGC-53 is a high-affinity dopamine receptor, LGC-55 is a high-affinity tyramine receptor, and LGC-40 is a low-affinity serotonin receptor that is also gated by choline and acetylcholine. lgc-55 mutants are defective in a behavior that requires endogenous tyramine, which indicates that this ionotropic tyramine receptor functions in tyramine signaling in vivo. Our studies suggest that direct activation of membrane chloride conductances is a general mechanism of action for biogenic amines in the modulation of C. elegans behavior.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2963310/" 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/PMC2963310/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ringstad, Niels -- Abe, Namiko -- Horvitz, H Robert -- GM24663/GM/NIGMS NIH HHS/ -- R01 GM024663/GM/NIGMS NIH HHS/ -- R01 GM024663-32A1/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Jul 3;325(5936):96-100. doi: 10.1126/science.1169243.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Biology, and McGovern Institute for Brain Research, MIT, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19574391" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Biogenic Amines/*metabolism ; Caenorhabditis elegans/genetics/*metabolism ; Caenorhabditis elegans Proteins/chemistry/genetics/*metabolism ; Chloride Channels/chemistry/genetics/*metabolism ; Dopamine/metabolism ; Genes, Helminth ; Ligands ; Membrane Potentials/drug effects ; Molecular Sequence Data ; Mutant Proteins/metabolism ; Oocytes ; Patch-Clamp Techniques ; Receptors, Biogenic Amine/chemistry/genetics/*metabolism ; Serotonin/metabolism ; Tyramine/metabolism ; Xenopus
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  • 63
    Publication Date: 2009-01-24
    Description: We constructed a large-scale functional network model in Drosophila melanogaster built around two key transcription factors involved in the process of embryonic segmentation. Analysis of the model allowed the identification of a new role for the ubiquitin E3 ligase complex factor SPOP. In Drosophila, the gene encoding SPOP is a target of segmentation transcription factors. Drosophila SPOP mediates degradation of the Jun kinase phosphatase Puckered, thereby inducing tumor necrosis factor (TNF)/Eiger-dependent apoptosis. In humans, we found that SPOP plays a conserved role in TNF-mediated JNK signaling and was highly expressed in 99% of clear cell renal cell carcinomas (RCCs), the most prevalent form of kidney cancer. SPOP expression distinguished histological subtypes of RCC and facilitated identification of clear cell RCC as the primary tumor for metastatic lesions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756524/" 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/PMC2756524/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Jiang -- Ghanim, Murad -- Xue, Lei -- Brown, Christopher D -- Iossifov, Ivan -- Angeletti, Cesar -- Hua, Sujun -- Negre, Nicolas -- Ludwig, Michael -- Stricker, Thomas -- Al-Ahmadie, Hikmat A -- Tretiakova, Maria -- Camp, Robert L -- Perera-Alberto, Montse -- Rimm, David L -- Xu, Tian -- Rzhetsky, Andrey -- White, Kevin P -- P50 GM081892/GM/NIGMS NIH HHS/ -- P50 GM081892-01A1/GM/NIGMS NIH HHS/ -- R01 HG003012/HG/NHGRI NIH HHS/ -- R01 HG003012-04/HG/NHGRI NIH HHS/ -- UL1 RR024999/RR/NCRR NIH HHS/ -- UL1 RR024999-02/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2009 Feb 27;323(5918):1218-22. doi: 10.1126/science.1157669. Epub 2009 Jan 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Genomics and Systems Biology, University of Chicago and Argonne National Laboratory, Chicago, IL 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19164706" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Apoptosis ; Carcinoma, Renal Cell/*genetics/metabolism ; Cell Line ; Compound Eye, Arthropod/embryology/metabolism ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster/embryology/*genetics/metabolism ; Embryo, Nonmammalian/metabolism ; Fushi Tarazu Transcription Factors/genetics/metabolism ; Gene Expression Profiling ; Gene Regulatory Networks ; Homeodomain Proteins/genetics/metabolism ; Humans ; Janus Kinases/*metabolism ; Kidney/metabolism ; Kidney Neoplasms/*genetics/metabolism ; Molecular Sequence Data ; Nervous System/embryology ; Nuclear Proteins/*genetics/metabolism ; Phosphoprotein Phosphatases/metabolism ; Phosphorylation ; Repressor Proteins/*genetics/metabolism ; *Signal Transduction ; Transcription Factors/genetics/metabolism ; Transcription, Genetic
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  • 64
    Publication Date: 2009-02-07
    Description: Speciation often involves the evolution of incompatible gene interactions that cause sterility or lethality in hybrids between populations. These so-called hybrid incompatibilities occur between two or more functionally divergent loci. We show that the nucleoporin 160kDa (Nup160) gene of the fruitfly Drosophila simulans is incompatible with one or more factors on the D. melanogaster X chromosome, causing hybrid lethality. Nup160 encodes a nuclear pore complex protein and shows evidence of adaptive evolution. Furthermore, the protein encoded by Nup160 directly interacts with that of another hybrid lethality gene, Nup96, indicating that at least two lethal hybrid incompatibility genes have evolved as byproducts of divergent coevolution among interacting components of the Drosophila nuclear pore complex.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2826207/" 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/PMC2826207/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tang, Shanwu -- Presgraves, Daven C -- R01 GM079543/GM/NIGMS NIH HHS/ -- R01 GM079543-01A1/GM/NIGMS NIH HHS/ -- R01-GM079543/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Feb 6;323(5915):779-82. doi: 10.1126/science.1169123.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of Rochester, Rochester, NY 14627, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19197064" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chromosome Mapping ; Crosses, Genetic ; Drosophila/*genetics/*physiology ; Drosophila Proteins/*genetics/metabolism ; Drosophila melanogaster/genetics/*physiology ; *Evolution, Molecular ; Female ; Genes, Insect ; *Genetic Speciation ; Hybridization, Genetic ; Male ; Molecular Sequence Data ; Mutation ; Nuclear Pore Complex Proteins/*genetics/metabolism ; Selection, Genetic ; X Chromosome/*genetics
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  • 65
    Publication Date: 2009-12-19
    Description: Inward-rectifier potassium (K+) channels conduct K+ ions most efficiently in one direction, into the cell. Kir2 channels control the resting membrane voltage in many electrically excitable cells, and heritable mutations cause periodic paralysis and cardiac arrhythmia. We present the crystal structure of Kir2.2 from chicken, which, excluding the unstructured amino and carboxyl termini, is 90% identical to human Kir2.2. Crystals containing rubidium (Rb+), strontium (Sr2+), and europium (Eu3+) reveal binding sites along the ion conduction pathway that are both conductive and inhibitory. The sites correlate with extensive electrophysiological data and provide a structural basis for understanding rectification. The channel's extracellular surface, with large structured turrets and an unusual selectivity filter entryway, might explain the relative insensitivity of eukaryotic inward rectifiers to toxins. These same surface features also suggest a possible approach to the development of inhibitory agents specific to each member of the inward-rectifier K+ channel family.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819303/" 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/PMC2819303/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tao, Xiao -- Avalos, Jose L -- Chen, Jiayun -- MacKinnon, Roderick -- P30 EB009998/EB/NIBIB NIH HHS/ -- R01 GM043949/GM/NIGMS NIH HHS/ -- R01 GM043949-10/GM/NIGMS NIH HHS/ -- R01 GM043949-11/GM/NIGMS NIH HHS/ -- R01 GM043949-12/GM/NIGMS NIH HHS/ -- R01 GM043949-13/GM/NIGMS NIH HHS/ -- R01 GM043949-14/GM/NIGMS NIH HHS/ -- R01 GM043949-15/GM/NIGMS NIH HHS/ -- R01 GM043949-16/GM/NIGMS NIH HHS/ -- R01 GM043949-17/GM/NIGMS NIH HHS/ -- R01 GM043949-18/GM/NIGMS NIH HHS/ -- R01 GM043949-19/GM/NIGMS NIH HHS/ -- R01 GM043949-20/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Dec 18;326(5960):1668-74. doi: 10.1126/science.1180310.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20019282" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Binding Sites ; Chickens ; Cloning, Molecular ; Crystallography, X-Ray ; Europium/metabolism ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Models, Molecular ; Molecular Sequence Data ; Oocytes ; Patch-Clamp Techniques ; Potassium/metabolism ; Potassium Channel Blockers/pharmacology ; Potassium Channels, Inwardly Rectifying/antagonists & ; inhibitors/*chemistry/metabolism ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein Subunits/chemistry ; Rubidium/metabolism ; Sequence Alignment ; Strontium/metabolism ; Xenopus laevis
    Print ISSN: 0036-8075
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  • 66
    Publication Date: 2009-01-31
    Description: Schwann cells develop from multipotent neural crest cells and form myelin sheaths around axons that allow rapid transmission of action potentials. Neuregulin signaling through the ErbB receptor regulates Schwann cell development; however, the downstream pathways are not fully defined. We find that mice lacking calcineurin B1 in the neural crest have defects in Schwann cell differentiation and myelination. Neuregulin addition to Schwann cell precursors initiates an increase in cytoplasmic Ca2+, which activates calcineurin and the downstream transcription factors NFATc3 and c4. Purification of NFAT protein complexes shows that Sox10 is an NFAT nuclear partner and synergizes with NFATc4 to activate Krox20, which regulates genes necessary for myelination. Our studies demonstrate that calcineurin and NFAT are essential for neuregulin and ErbB signaling, neural crest diversification, and differentiation of Schwann cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2790385/" 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/PMC2790385/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kao, Shih-Chu -- Wu, Hai -- Xie, Jianming -- Chang, Ching-Pin -- Ranish, Jeffrey A -- Graef, Isabella A -- Crabtree, Gerald R -- AI60037/AI/NIAID NIH HHS/ -- HD55391/HD/NICHD NIH HHS/ -- NS046789/NS/NINDS NIH HHS/ -- R01 AI060037/AI/NIAID NIH HHS/ -- R01 AI060037-01/AI/NIAID NIH HHS/ -- R01 AI060037-02/AI/NIAID NIH HHS/ -- R01 AI060037-03/AI/NIAID NIH HHS/ -- R01 AI060037-04/AI/NIAID NIH HHS/ -- R01 AI060037-05/AI/NIAID NIH HHS/ -- R01 HD055391/HD/NICHD NIH HHS/ -- R01 NS046789/NS/NINDS NIH HHS/ -- R01 NS046789-01/NS/NINDS NIH HHS/ -- R01 NS046789-02/NS/NINDS NIH HHS/ -- R01 NS046789-03/NS/NINDS NIH HHS/ -- R01 NS046789-04/NS/NINDS NIH HHS/ -- R01 NS046789-05/NS/NINDS NIH HHS/ -- R21 NS061702/NS/NINDS NIH HHS/ -- R21 NS061702-01/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Jan 30;323(5914):651-4. doi: 10.1126/science.1166562.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19179536" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcineurin/*metabolism ; Calcium/metabolism ; Cell Differentiation ; Cell Line ; Coculture Techniques ; Early Growth Response Protein 2/metabolism ; Ganglia, Spinal/cytology ; Mice ; Myelin Sheath/physiology ; NFATC Transcription Factors/*metabolism ; Neural Crest/cytology/metabolism ; Neuregulins/*metabolism ; Phosphorylation ; Receptor, ErbB-2/metabolism ; Receptor, ErbB-3 ; SOXE Transcription Factors/metabolism ; Schwann Cells/*cytology/*metabolism ; *Signal Transduction
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  • 67
    Publication Date: 2009-01-24
    Description: Membrane fusion between vesicles and target membranes involves the zippering of a four-helix bundle generated by constituent helices derived from target- and vesicle-soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). In neurons, the protein complexin clamps otherwise spontaneous fusion by SNARE proteins, allowing neurotransmitters and other mediators to be secreted when and where they are needed as this clamp is released. The membrane-proximal accessory helix of complexin is necessary for clamping, but its mechanism of action is unknown. Here, we present experiments using a reconstituted fusion system that suggest a simple model in which the complexin accessory helix forms an alternative four-helix bundle with the target-SNARE near the membrane, preventing the vesicle-SNARE from completing its zippering.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736854/" 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/PMC3736854/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Giraudo, Claudio G -- Garcia-Diaz, Alejandro -- Eng, William S -- Chen, Yuhang -- Hendrickson, Wayne A -- Melia, Thomas J -- Rothman, James E -- R01 GM071458/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Jan 23;323(5913):512-6. doi: 10.1126/science.1166500.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology and Cellular Biophysics, Columbia University, College of Physicians and Surgeons, 1150 Saint Nicholas Avenue, Russ Berrie Building, Room 520, New York, NY 10032, USA. claudio.giraudo@yale.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19164750" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Vesicular Transport ; Amino Acid Motifs ; Amino Acid Sequence ; HeLa Cells ; Humans ; Hydrophobic and Hydrophilic Interactions ; *Membrane Fusion ; Models, Molecular ; Molecular Sequence Data ; Mutant Proteins/chemistry/metabolism ; Mutation ; Nerve Tissue Proteins/*chemistry/genetics/*metabolism ; Protein Binding ; Protein Structure, Secondary ; Recombinant Fusion Proteins/chemistry/metabolism ; SNARE Proteins/*chemistry/*metabolism ; Vesicle-Associated Membrane Protein 2/*chemistry/*metabolism
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  • 68
    Publication Date: 2009-03-17
    Description: Many metabolic and physiological processes display circadian oscillations. We have shown that the core circadian regulator, CLOCK, is a histone acetyltransferase whose activity is counterbalanced by the nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase SIRT1. Here we show that intracellular NAD+ levels cycle with a 24-hour rhythm, an oscillation driven by the circadian clock. CLOCK:BMAL1 regulates the circadian expression of NAMPT (nicotinamide phosphoribosyltransferase), an enzyme that provides a rate-limiting step in the NAD+ salvage pathway. SIRT1 is recruited to the Nampt promoter and contributes to the circadian synthesis of its own coenzyme. Using the specific inhibitor FK866, we demonstrated that NAMPT is required to modulate circadian gene expression. Our findings in mouse embryo fibroblasts reveal an interlocked transcriptional-enzymatic feedback loop that governs the molecular interplay between cellular metabolism and circadian rhythms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nakahata, Yasukazu -- Sahar, Saurabh -- Astarita, Giuseppe -- Kaluzova, Milota -- Sassone-Corsi, Paolo -- R01-GM081634/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 May 1;324(5927):654-7. doi: 10.1126/science.1170803. Epub 2009 Mar 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19286518" target="_blank"〉PubMed〈/a〉
    Keywords: ARNTL Transcription Factors ; Acrylamides/pharmacology ; Animals ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Biological Clocks ; CLOCK Proteins ; Cell Line ; Chromatin Assembly and Disassembly ; *Circadian Rhythm ; Cytokines/antagonists & inhibitors/genetics/*metabolism ; Enzyme Inhibitors/pharmacology ; *Feedback, Physiological ; *Gene Expression Regulation ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; NAD/*metabolism ; Niacinamide/metabolism ; Nicotinamide Phosphoribosyltransferase/antagonists & ; inhibitors/genetics/*metabolism ; Piperidines/pharmacology ; Promoter Regions, Genetic ; Sirtuin 1 ; Sirtuins/*metabolism ; Trans-Activators/genetics/*metabolism ; Transcription, Genetic
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  • 69
    Publication Date: 2009-01-31
    Description: Genetic incompatibilities resulting from interactions between two loci represent a potential source of postzygotic barriers and may be an important factor in evolution when they impair the outcome of interspecific crosses. We show that, in crosses between strains of the plant Arabidopsis thaliana, loci interact epistatically, controlling a recessive embryo lethality. This interaction is explained by divergent evolution occurring among paralogs of an essential duplicate gene, for which the functional copy is not located at the same locus in different accessions. These paralogs demonstrate genetic heterogeneity in their respective evolutionary trajectories, which results in widespread incompatibility among strains. Our data suggest that these passive mechanisms, gene duplication and extinction, could represent an important source of genetic incompatibilities across all taxa.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bikard, David -- Patel, Dhaval -- Le Mette, Claire -- Giorgi, Veronica -- Camilleri, Christine -- Bennett, Malcolm J -- Loudet, Olivier -- Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2009 Jan 30;323(5914):623-6. doi: 10.1126/science.1165917.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genetics and Plant Breeding, INRA, SGAP UR254, F-78026 Versailles, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19179528" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Arabidopsis/*genetics/growth & development/metabolism ; Chromosome Segregation ; Chromosomes, Plant/genetics ; Crosses, Genetic ; Epistasis, Genetic ; *Evolution, Molecular ; Gene Duplication ; Gene Expression ; *Genes, Duplicate ; Genes, Plant ; Genetic Speciation ; Histidine/metabolism ; Molecular Sequence Data ; Plant Roots/genetics/growth & development/metabolism ; Plant Shoots/genetics/growth & development/metabolism ; Polymorphism, Single Nucleotide ; Seeds/growth & development ; Transaminases/*genetics/metabolism
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  • 70
    Publication Date: 2009-08-08
    Description: The catalytic engine of RNA interference (RNAi) is the RNA-induced silencing complex (RISC), wherein the endoribonuclease Argonaute and single-stranded small interfering RNA (siRNA) direct target mRNA cleavage. We reconstituted long double-stranded RNA- and duplex siRNA-initiated RISC activities with the use of recombinant Drosophila Dicer-2, R2D2, and Ago2 proteins. We used this core reconstitution system to purify an RNAi regulator that we term C3PO (component 3 promoter of RISC), a complex of Translin and Trax. C3PO is a Mg2+-dependent endoribonuclease that promotes RISC activation by removing siRNA passenger strand cleavage products. These studies establish an in vitro RNAi reconstitution system and identify C3PO as a key activator of the core RNAi machinery.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2855623/" 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/PMC2855623/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Ying -- Ye, Xuecheng -- Jiang, Feng -- Liang, Chunyang -- Chen, Dongmei -- Peng, Junmin -- Kinch, Lisa N -- Grishin, Nick V -- Liu, Qinghua -- AG025688/AG/NIA NIH HHS/ -- GM078163/GM/NIGMS NIH HHS/ -- GM084010/GM/NIGMS NIH HHS/ -- R01 GM078163/GM/NIGMS NIH HHS/ -- R01 GM078163-03/GM/NIGMS NIH HHS/ -- R01 GM084010/GM/NIGMS NIH HHS/ -- R01 GM084010-02/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Aug 7;325(5941):750-3. doi: 10.1126/science.1176325.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19661431" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Argonaute Proteins ; Carrier Proteins/chemistry/genetics/isolation & purification/*metabolism ; Catalytic Domain ; Drosophila Proteins/chemistry/genetics/isolation & purification/*metabolism ; Drosophila melanogaster/chemistry/enzymology/*genetics ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Protein Conformation ; RNA Helicases/genetics/metabolism ; *RNA Interference ; RNA, Double-Stranded/chemistry/metabolism ; RNA, Small Interfering/chemistry/metabolism ; RNA-Binding Proteins/genetics/metabolism ; RNA-Induced Silencing Complex/genetics/*metabolism ; Recombinant Proteins/metabolism ; Ribonuclease III/genetics/metabolism
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  • 71
    Publication Date: 2009-03-21
    Description: New drugs are required to counter the tuberculosis (TB) pandemic. Here, we describe the synthesis and characterization of 1,3-benzothiazin-4-ones (BTZs), a new class of antimycobacterial agents that kill Mycobacterium tuberculosis in vitro, ex vivo, and in mouse models of TB. Using genetics and biochemistry, we identified the enzyme decaprenylphosphoryl-beta-d-ribose 2'-epimerase as a major BTZ target. Inhibition of this enzymatic activity abolishes the formation of decaprenylphosphoryl arabinose, a key precursor that is required for the synthesis of the cell-wall arabinans, thus provoking cell lysis and bacterial death. The most advanced compound, BTZ043, is a candidate for inclusion in combination therapies for both drug-sensitive and extensively drug-resistant TB.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3128490/" 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/PMC3128490/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Makarov, Vadim -- Manina, Giulia -- Mikusova, Katarina -- Mollmann, Ute -- Ryabova, Olga -- Saint-Joanis, Brigitte -- Dhar, Neeraj -- Pasca, Maria Rosalia -- Buroni, Silvia -- Lucarelli, Anna Paola -- Milano, Anna -- De Rossi, Edda -- Belanova, Martina -- Bobovska, Adela -- Dianiskova, Petronela -- Kordulakova, Jana -- Sala, Claudia -- Fullam, Elizabeth -- Schneider, Patricia -- McKinney, John D -- Brodin, Priscille -- Christophe, Thierry -- Waddell, Simon -- Butcher, Philip -- Albrethsen, Jakob -- Rosenkrands, Ida -- Brosch, Roland -- Nandi, Vrinda -- Bharath, Sowmya -- Gaonkar, Sheshagiri -- Shandil, Radha K -- Balasubramanian, Venkataraman -- Balganesh, Tanjore -- Tyagi, Sandeep -- Grosset, Jacques -- Riccardi, Giovanna -- Cole, Stewart T -- 062511/Wellcome Trust/United Kingdom -- 080039/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2009 May 8;324(5928):801-4. doi: 10.1126/science.1171583. Epub 2009 Mar 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉A. N. Bakh Institute of Biochemistry, Russian Academy of Science, 119071 Moscow, Russia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19299584" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antitubercular Agents/chemical synthesis/chemistry/*pharmacology/*therapeutic use ; Arabinose/metabolism ; Cell Wall/metabolism ; Drug Resistance, Bacterial ; Enzyme Inhibitors/cerebrospinal fluid/chemistry/pharmacology/therapeutic use ; Ethambutol/pharmacology ; Gene Expression Regulation, Bacterial/drug effects ; Genes, Bacterial ; Mice ; Mice, Inbred BALB C ; Microbial Sensitivity Tests ; Molecular Sequence Data ; Molecular Structure ; Mycobacterium/drug effects/genetics ; Mycobacterium tuberculosis/*drug effects/genetics/metabolism ; Polysaccharides/*biosynthesis ; Racemases and Epimerases/*antagonists & inhibitors/metabolism ; Spiro Compounds/chemical synthesis/chemistry/*pharmacology/*therapeutic use ; Thiazines/chemical synthesis/chemistry/*pharmacology/*therapeutic use ; Tuberculosis/*drug therapy/microbiology
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  • 72
    Publication Date: 2009-12-08
    Description: We report an improved draft nucleotide sequence of the 2.3-gigabase genome of maize, an important crop plant and model for biological research. Over 32,000 genes were predicted, of which 99.8% were placed on reference chromosomes. Nearly 85% of the genome is composed of hundreds of families of transposable elements, dispersed nonuniformly across the genome. These were responsible for the capture and amplification of numerous gene fragments and affect the composition, sizes, and positions of centromeres. We also report on the correlation of methylation-poor regions with Mu transposon insertions and recombination, and copy number variants with insertions and/or deletions, as well as how uneven gene losses between duplicated regions were involved in returning an ancient allotetraploid to a genetically diploid state. These analyses inform and set the stage for further investigations to improve our understanding of the domestication and agricultural improvements of maize.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schnable, Patrick S -- Ware, Doreen -- Fulton, Robert S -- Stein, Joshua C -- Wei, Fusheng -- Pasternak, Shiran -- Liang, Chengzhi -- Zhang, Jianwei -- Fulton, Lucinda -- Graves, Tina A -- Minx, Patrick -- Reily, Amy Denise -- Courtney, Laura -- Kruchowski, Scott S -- Tomlinson, Chad -- Strong, Cindy -- Delehaunty, Kim -- Fronick, Catrina -- Courtney, Bill -- Rock, Susan M -- Belter, Eddie -- Du, Feiyu -- Kim, Kyung -- Abbott, Rachel M -- Cotton, Marc -- Levy, Andy -- Marchetto, Pamela -- Ochoa, Kerri -- Jackson, Stephanie M -- Gillam, Barbara -- Chen, Weizu -- Yan, Le -- Higginbotham, Jamey -- Cardenas, Marco -- Waligorski, Jason -- Applebaum, Elizabeth -- Phelps, Lindsey -- Falcone, Jason -- Kanchi, Krishna -- Thane, Thynn -- Scimone, Adam -- Thane, Nay -- Henke, Jessica -- Wang, Tom -- Ruppert, Jessica -- Shah, Neha -- Rotter, Kelsi -- Hodges, Jennifer -- Ingenthron, Elizabeth -- Cordes, Matt -- Kohlberg, Sara -- Sgro, Jennifer -- Delgado, Brandon -- Mead, Kelly -- Chinwalla, Asif -- Leonard, Shawn -- Crouse, Kevin -- Collura, Kristi -- Kudrna, Dave -- Currie, Jennifer -- He, Ruifeng -- Angelova, Angelina -- Rajasekar, Shanmugam -- Mueller, Teri -- Lomeli, Rene -- Scara, Gabriel -- Ko, Ara -- Delaney, Krista -- Wissotski, Marina -- Lopez, Georgina -- Campos, David -- Braidotti, Michele -- Ashley, Elizabeth -- Golser, Wolfgang -- Kim, HyeRan -- Lee, Seunghee -- Lin, Jinke -- Dujmic, Zeljko -- Kim, Woojin -- Talag, Jayson -- Zuccolo, Andrea -- Fan, Chuanzhu -- Sebastian, Aswathy -- Kramer, Melissa -- Spiegel, Lori -- Nascimento, Lidia -- Zutavern, Theresa -- Miller, Beth -- Ambroise, Claude -- Muller, Stephanie -- Spooner, Will -- Narechania, Apurva -- Ren, Liya -- Wei, Sharon -- Kumari, Sunita -- Faga, Ben -- Levy, Michael J -- McMahan, Linda -- Van Buren, Peter -- Vaughn, Matthew W -- Ying, Kai -- Yeh, Cheng-Ting -- Emrich, Scott J -- Jia, Yi -- Kalyanaraman, Ananth -- Hsia, An-Ping -- Barbazuk, W Brad -- Baucom, Regina S -- Brutnell, Thomas P -- Carpita, Nicholas C -- Chaparro, Cristian -- Chia, Jer-Ming -- Deragon, Jean-Marc -- Estill, James C -- Fu, Yan -- Jeddeloh, Jeffrey A -- Han, Yujun -- Lee, Hyeran -- Li, Pinghua -- Lisch, Damon R -- Liu, Sanzhen -- Liu, Zhijie -- Nagel, Dawn Holligan -- McCann, Maureen C -- SanMiguel, Phillip -- Myers, Alan M -- Nettleton, Dan -- Nguyen, John -- Penning, Bryan W -- Ponnala, Lalit -- Schneider, Kevin L -- Schwartz, David C -- Sharma, Anupma -- Soderlund, Carol -- Springer, Nathan M -- Sun, Qi -- Wang, Hao -- Waterman, Michael -- Westerman, Richard -- Wolfgruber, Thomas K -- Yang, Lixing -- Yu, Yeisoo -- Zhang, Lifang -- Zhou, Shiguo -- Zhu, Qihui -- Bennetzen, Jeffrey L -- Dawe, R Kelly -- Jiang, Jiming -- Jiang, Ning -- Presting, Gernot G -- Wessler, Susan R -- Aluru, Srinivas -- Martienssen, Robert A -- Clifton, Sandra W -- McCombie, W Richard -- Wing, Rod A -- Wilson, Richard K -- New York, N.Y. -- Science. 2009 Nov 20;326(5956):1112-5. doi: 10.1126/science.1178534.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Plant Genomics, Iowa State University, Ames, IA 50011, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965430" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Centromere/genetics ; Chromosome Mapping ; Chromosomes, Plant/genetics ; Crops, Agricultural/genetics ; DNA Copy Number Variations ; DNA Methylation ; DNA Transposable Elements ; DNA, Plant/genetics ; Genes, Plant ; *Genetic Variation ; *Genome, Plant ; Inbreeding ; MicroRNAs/genetics ; Molecular Sequence Data ; Ploidies ; RNA, Plant/genetics ; Recombination, Genetic ; Retroelements ; *Sequence Analysis, DNA ; Zea mays/*genetics
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  • 73
    Publication Date: 2009-09-05
    Description: The magnitude of antigen-specific CD8+ T cell responses is not fixed but correlates with the severity of infection. Although by definition T cell response size is the product of both the capacity to recruit naive T cells (clonal selection) and their subsequent proliferation (clonal expansion), it remains undefined how these two factors regulate antigen-specific T cell responses. We determined the relative contribution of recruitment and expansion by labeling naive T cells with unique genetic tags and transferring them into mice. Under disparate infection conditions with different pathogens and doses, recruitment of antigen-specific T cells was near constant and close to complete. Thus, naive T cell recruitment is highly efficient, and the magnitude of antigen-specific CD8+ T cell responses is primarily controlled by clonal expansion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉van Heijst, Jeroen W J -- Gerlach, Carmen -- Swart, Erwin -- Sie, Daoud -- Nunes-Alves, Claudio -- Kerkhoven, Ron M -- Arens, Ramon -- Correia-Neves, Margarida -- Schepers, Koen -- Schumacher, Ton N M -- New York, N.Y. -- Science. 2009 Sep 4;325(5945):1265-9. doi: 10.1126/science.1175455.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19729659" target="_blank"〉PubMed〈/a〉
    Keywords: Adoptive Transfer ; Ampicillin/therapeutic use ; Animals ; Anti-Bacterial Agents/therapeutic use ; Antigens/*immunology ; Antigens, Bacterial/immunology ; Antigens, Viral/immunology ; CD8-Positive T-Lymphocytes/*immunology ; Dendritic Cells/immunology ; Epitopes/immunology ; Genes, T-Cell Receptor alpha ; Genes, T-Cell Receptor beta ; Influenza A virus/immunology ; Listeriosis/drug therapy/*immunology ; *Lymphocyte Activation ; Lymphocyte Count ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Molecular Sequence Data ; Orthomyxoviridae Infections/immunology ; Ovalbumin/immunology ; Receptors, Antigen, T-Cell, alpha-beta/chemistry/immunology ; Spleen/immunology ; Vaccinia/immunology ; Virus Diseases/*immunology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 74
    Publication Date: 2009-12-08
    Description: The thiol group of the amino acid cysteine can be modified to regulate protein activity. The Escherichia coli periplasm is an oxidizing environment in which most cysteine residues are involved in disulfide bonds. However, many periplasmic proteins contain single cysteine residues, which are vulnerable to oxidation to sulfenic acids and then irreversibly modified to sulfinic and sulfonic acids. We discovered that DsbG and DsbC, two thioredoxin-related proteins, control the global sulfenic acid content of the periplasm and protect single cysteine residues from oxidation. DsbG interacts with the YbiS protein and, along with DsbC, regulates oxidation of its catalytic cysteine residue. Thus, a potentially widespread mechanism controls sulfenic acid modification in the cellular environment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Depuydt, Matthieu -- Leonard, Stephen E -- Vertommen, Didier -- Denoncin, Katleen -- Morsomme, Pierre -- Wahni, Khadija -- Messens, Joris -- Carroll, Kate S -- Collet, Jean-Francois -- New York, N.Y. -- Science. 2009 Nov 20;326(5956):1109-11. doi: 10.1126/science.1179557.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉de Duve Institute, Universite catholique de Louvain, B-1200 Brussels, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965429" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Catalytic Domain ; Cysteine/chemistry/*metabolism ; Disulfides/chemistry/metabolism ; Escherichia coli/genetics/*metabolism ; Escherichia coli Proteins/chemistry/genetics/*metabolism ; Models, Biological ; Molecular Sequence Data ; Oxidation-Reduction ; Oxidoreductases/chemistry/genetics/*metabolism ; Periplasm/*metabolism ; Periplasmic Proteins/chemistry/genetics/*metabolism ; Protein Binding ; Protein Disulfide-Isomerases/chemistry/genetics/*metabolism ; Proteomics ; Substrate Specificity ; Sulfenic Acids/metabolism
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  • 75
    Publication Date: 2009-06-27
    Description: Escherichia coli diacylglycerol kinase (DAGK) represents a family of integral membrane enzymes that is unrelated to all other phosphotransferases. We have determined the three-dimensional structure of the DAGK homotrimer with the use of solution nuclear magnetic resonance. The third transmembrane helix from each subunit is domain-swapped with the first and second transmembrane segments from an adjacent subunit. Each of DAGK's three active sites resembles a portico. The cornice of the portico appears to be the determinant of DAGK's lipid substrate specificity and overhangs the site of phosphoryl transfer near the water-membrane interface. Mutations to cysteine that caused severe misfolding were located in or near the active site, indicating a high degree of overlap between sites responsible for folding and for catalysis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2764269/" 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/PMC2764269/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Van Horn, Wade D -- Kim, Hak-Jun -- Ellis, Charles D -- Hadziselimovic, Arina -- Sulistijo, Endah S -- Karra, Murthy D -- Tian, Changlin -- Sonnichsen, Frank D -- Sanders, Charles R -- R01 GM047485/GM/NIGMS NIH HHS/ -- R01 GM047485-17/GM/NIGMS NIH HHS/ -- R01 GM47485/GM/NIGMS NIH HHS/ -- T32 NS007491/NS/NINDS NIH HHS/ -- T32 NS007491-09/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2009 Jun 26;324(5935):1726-9. doi: 10.1126/science.1171716.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Center for Structural Biology, Vanderbilt University, Nashville, TN 37232, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19556511" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Amino Acid Sequence ; Biocatalysis ; Catalytic Domain ; Cell Membrane/enzymology ; Diacylglycerol Kinase/*chemistry/metabolism ; Escherichia coli/*enzymology ; Escherichia coli Proteins/*chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Nuclear Magnetic Resonance, Biomolecular ; Protein Conformation ; Protein Folding ; Protein Multimerization ; Protein Structure, Quaternary ; Protein Structure, Secondary ; Protein Structure, Tertiary
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  • 76
    Publication Date: 2009-09-05
    Description: Collagen IV networks are ancient proteins of basement membranes that underlie epithelia in metazoa from sponge to human. The networks provide structural integrity to tissues and serve as ligands for integrin cell-surface receptors. They are assembled by oligomerization of triple-helical protomers and are covalently crosslinked, a key reinforcement that stabilizes networks. We used Fourier-transform ion cyclotron resonance mass spectrometry and nuclear magnetic resonance spectroscopy to show that a sulfilimine bond (-S=N-) crosslinks hydroxylysine-211 and methionine-93 of adjoining protomers, a bond not previously found in biomolecules. This bond, the nitrogen analog of a sulfoxide, appears to have arisen at the divergence of sponge and cnidaria, an adaptation of the extracellular matrix in response to mechanical stress in metazoan evolution.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2876822/" 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/PMC2876822/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vanacore, Roberto -- Ham, Amy-Joan L -- Voehler, Markus -- Sanders, Charles R -- Conrads, Thomas P -- Veenstra, Timothy D -- Sharpless, K Barry -- Dawson, Philip E -- Hudson, Billy G -- DC007416/DC/NIDCD NIH HHS/ -- DK065123/DK/NIDDK NIH HHS/ -- DK18381/DK/NIDDK NIH HHS/ -- GM059380/GM/NIGMS NIH HHS/ -- P01 DK065123/DK/NIDDK NIH HHS/ -- P01 DK065123-07/DK/NIDDK NIH HHS/ -- R01 DC007416/DC/NIDCD NIH HHS/ -- R01 DC007416-05/DC/NIDCD NIH HHS/ -- R01 GM059380/GM/NIGMS NIH HHS/ -- R01 GM059380-09/GM/NIGMS NIH HHS/ -- R37 DK018381/DK/NIDDK NIH HHS/ -- R37 DK018381-37/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2009 Sep 4;325(5945):1230-4. doi: 10.1126/science.1176811.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Nephrology, Department of Medicine and Center for Matrix Biology, Vanderbilt University, Nashville, TN 37232, USA. roberto.vanacore@vanderbilt.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19729652" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cattle ; Collagen Type IV/*chemistry ; Humans ; Hydroxylysine/chemistry ; Mass Spectrometry ; Methionine/chemistry ; Models, Molecular ; Molecular Sequence Data ; Nitrogen/chemistry ; Nuclear Magnetic Resonance, Biomolecular ; Physicochemical Processes ; Protein Conformation ; Protein Multimerization ; Protein Subunits/chemistry ; Sequence Alignment ; Stress, Mechanical ; Sulfur/chemistry
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  • 77
    Publication Date: 2009-04-11
    Description: In vertebrates, the readily apparent left/right (L/R) anatomical asymmetries of the internal organs can be traced to molecular events initiated at or near the time of gastrulation. However, the earliest steps of this process do not seem to be universally conserved. In particular, how this axis is first defined in chicks has remained problematic. Here we show that asymmetric cell rearrangements take place within chick embryos, creating a leftward movement of cells around the node. It is the relative displacement of cells expressing sonic hedgehog (Shh) and fibroblast growth factor 8 (Fgf8) that is responsible for establishing their asymmetric expression patterns. The creation of asymmetric expression domains as a passive effect of cell movements represents an alternative strategy for breaking L/R symmetry in gene activity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2993078/" 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/PMC2993078/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gros, Jerome -- Feistel, Kerstin -- Viebahn, Christoph -- Blum, Martin -- Tabin, Clifford J -- R01 HD045499/HD/NICHD NIH HHS/ -- R01 HD045499-06/HD/NICHD NIH HHS/ -- R01-HD045499/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2009 May 15;324(5929):941-4. doi: 10.1126/science.1172478. Epub 2009 Apr 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19359542" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; *Body Patterning ; *Cell Movement ; Chick Embryo ; Fibroblast Growth Factor 8/genetics ; *Gastrulation ; *Gene Expression ; Gene Expression Profiling ; Hedgehog Proteins/genetics ; Molecular Sequence Data ; Organizers, Embryonic/*cytology/embryology/*metabolism ; Primitive Streak/*cytology/embryology/metabolism ; Swine/embryology ; Tissue Culture Techniques
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  • 78
    Publication Date: 2009-05-02
    Description: Molecular preservation in non-avian dinosaurs is controversial. We present multiple lines of evidence that endogenous proteinaceous material is preserved in bone fragments and soft tissues from an 80-million-year-old Campanian hadrosaur, Brachylophosaurus canadensis [Museum of the Rockies (MOR) 2598]. Microstructural and immunological data are consistent with preservation of multiple bone matrix and vessel proteins, and phylogenetic analyses of Brachylophosaurus collagen sequenced by mass spectrometry robustly support the bird-dinosaur clade, consistent with an endogenous source for these collagen peptides. These data complement earlier results from Tyrannosaurus rex (MOR 1125) and confirm that molecular preservation in Cretaceous dinosaurs is not a unique event.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schweitzer, Mary H -- Zheng, Wenxia -- Organ, Chris L -- Avci, Recep -- Suo, Zhiyong -- Freimark, Lisa M -- Lebleu, Valerie S -- Duncan, Michael B -- Vander Heiden, Matthew G -- Neveu, John M -- Lane, William S -- Cottrell, John S -- Horner, John R -- Cantley, Lewis C -- Kalluri, Raghu -- Asara, John M -- AA 13913/AA/NIAAA NIH HHS/ -- CA 125550/CA/NCI NIH HHS/ -- DK 55001/DK/NIDDK NIH HHS/ -- DK 61866/DK/NIDDK NIH HHS/ -- DK 62987/DK/NIDDK NIH HHS/ -- R01 AA013913/AA/NIAAA NIH HHS/ -- R01 CA125550/CA/NCI NIH HHS/ -- R01 DK055001/DK/NIDDK NIH HHS/ -- R01 DK062987/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2009 May 1;324(5927):626-31. doi: 10.1126/science.1165069.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉North Carolina State University, Raleigh, NC 27695, USA. schweitzer@ncsu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19407199" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Birds/classification ; Bone Demineralization Technique ; Bone Matrix/chemistry ; Collagen/analysis/*chemistry/isolation & purification ; *Dinosaurs/classification ; Elastin/analysis ; Femur/blood supply/*chemistry/ultrastructure ; *Fossils ; Hemoglobins/analysis ; Immunologic Techniques ; Laminin/analysis ; Mass Spectrometry ; Microscopy, Electron, Scanning ; Molecular Sequence Data ; Osteocytes/ultrastructure ; Peptide Fragments/chemistry/isolation & purification ; Phylogeny ; Proteins/analysis/*chemistry/isolation & purification ; Sequence Alignment
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  • 79
    Publication Date: 2009-05-02
    Description: The plant hormone abscisic acid (ABA) acts as a developmental signal and as an integrator of environmental cues such as drought and cold. Key players in ABA signal transduction include the type 2C protein phosphatases (PP2Cs) ABI1 and ABI2, which act by negatively regulating ABA responses. In this study, we identify interactors of ABI1 and ABI2 which we have named regulatory components of ABA receptor (RCARs). In Arabidopsis, RCARs belong to a family with 14 members that share structural similarity with class 10 pathogen-related proteins. RCAR1 was shown to bind ABA, to mediate ABA-dependent inactivation of ABI1 or ABI2 in vitro, and to antagonize PP2C action in planta. Other RCARs also mediated ABA-dependent regulation of ABI1 and ABI2, consistent with a combinatorial assembly of receptor complexes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ma, Yue -- Szostkiewicz, Izabela -- Korte, Arthur -- Moes, Daniele -- Yang, Yi -- Christmann, Alexander -- Grill, Erwin -- New York, N.Y. -- Science. 2009 May 22;324(5930):1064-8. doi: 10.1126/science.1172408. Epub 2009 Apr 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lehrstuhl fur Botanik, Technische Universitat Munchen, Am Hochanger 4, D-85354 Freising, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19407143" target="_blank"〉PubMed〈/a〉
    Keywords: Abscisic Acid/*metabolism/pharmacology ; Amino Acid Sequence ; Arabidopsis/genetics/*metabolism/physiology ; Arabidopsis Proteins/antagonists & inhibitors/chemistry/genetics/*metabolism ; Binding Sites ; Carrier Proteins/chemistry/genetics/*metabolism ; Gene Expression Regulation, Plant ; Germination ; Molecular Sequence Data ; Phosphoprotein Phosphatases/antagonists & ; inhibitors/chemistry/genetics/*metabolism ; Plant Roots/growth & development ; Plant Stomata/physiology ; Plants, Genetically Modified ; Point Mutation ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Stereoisomerism ; Up-Regulation
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  • 80
    Publication Date: 2009-12-08
    Description: To study basic principles of transcriptome organization in bacteria, we analyzed one of the smallest self-replicating organisms, Mycoplasma pneumoniae. We combined strand-specific tiling arrays, complemented by transcriptome sequencing, with more than 252 spotted arrays. We detected 117 previously undescribed, mostly noncoding transcripts, 89 of them in antisense configuration to known genes. We identified 341 operons, of which 139 are polycistronic; almost half of the latter show decaying expression in a staircase-like manner. Under various conditions, operons could be divided into 447 smaller transcriptional units, resulting in many alternative transcripts. Frequent antisense transcripts, alternative transcripts, and multiple regulators per gene imply a highly dynamic transcriptome, more similar to that of eukaryotes than previously thought.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guell, Marc -- van Noort, Vera -- Yus, Eva -- Chen, Wei-Hua -- Leigh-Bell, Justine -- Michalodimitrakis, Konstantinos -- Yamada, Takuji -- Arumugam, Manimozhiyan -- Doerks, Tobias -- Kuhner, Sebastian -- Rode, Michaela -- Suyama, Mikita -- Schmidt, Sabine -- Gavin, Anne-Claude -- Bork, Peer -- Serrano, Luis -- New York, N.Y. -- Science. 2009 Nov 27;326(5957):1268-71. doi: 10.1126/science.1176951.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Genomic Regulation (CRG), Universitat Pompeu Fabra, Barcelona, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965477" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; *Gene Expression Profiling ; *Gene Expression Regulation, Bacterial ; Genes, Bacterial ; *Genome, Bacterial ; Molecular Sequence Data ; Mycoplasma pneumoniae/*genetics/metabolism ; Oligonucleotide Array Sequence Analysis ; Operon ; RNA, Antisense/genetics/metabolism ; RNA, Bacterial/*genetics/metabolism ; RNA, Messenger/genetics/metabolism ; RNA, Untranslated/analysis/*genetics ; *Transcription, Genetic
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  • 81
    Publication Date: 2009-08-22
    Description: By using remotely operated vehicles, we found seven previously unknown species of swimming annelid worms below 1800 meters. Specimens were large and bore a variety of elaborate head appendages. In addition, five species have pairs of ellipsoidal organs homologous to branchiae that produce brilliant green bioluminescence when autotomized. Five genes were used to determine the evolutionary relationships of these worms within Cirratuliformia. These species form a clade within Acrocirridae and were not closely related to either of the two known pelagic cirratuliforms. Thus, this clade represents a third invasion of the pelagic realm from Cirratuliformia. This finding emphasizes the wealth of discoveries to be made in pelagic and deep demersal habitats.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Osborn, Karen J -- Haddock, Steven H D -- Pleijel, Fredrik -- Madin, Laurence P -- Rouse, Greg W -- New York, N.Y. -- Science. 2009 Aug 21;325(5943):964. doi: 10.1126/science.1172488.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Scripps Institution of Oceanography, La Jolla, CA 92093, USA. kjosborn@ucsd.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19696343" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Ecosystem ; Luminescence ; Molecular Sequence Data ; Polychaeta/*anatomy & histology/classification/genetics/*physiology ; *Seawater ; Swimming
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  • 82
    Publication Date: 2009-05-30
    Description: Intracellular trafficking of the glucose transporter GLUT4 from storage compartments to the plasma membrane is triggered in muscle and fat during the body's response to insulin. Clathrin is involved in intracellular trafficking, and in humans, the clathrin heavy-chain isoform CHC22 is highly expressed in skeletal muscle. We found a role for CHC22 in the formation of insulin-responsive GLUT4 compartments in human muscle and adipocytes. CHC22 also associated with expanded GLUT4 compartments in muscle from type 2 diabetic patients. Tissue-specific introduction of CHC22 in mice, which have only a pseudogene for this protein, caused aberrant localization of GLUT4 transport pathway components in their muscle, as well as features of diabetes. Thus, CHC22-dependent membrane trafficking constitutes a species-restricted pathway in human muscle and fat with potential implications for type 2 diabetes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2975026/" 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/PMC2975026/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vassilopoulos, Stephane -- Esk, Christopher -- Hoshino, Sachiko -- Funke, Birgit H -- Chen, Chih-Ying -- Plocik, Alex M -- Wright, Woodring E -- Kucherlapati, Raju -- Brodsky, Frances M -- GM038093/GM/NIGMS NIH HHS/ -- HD47863/HD/NICHD NIH HHS/ -- R01 GM038093/GM/NIGMS NIH HHS/ -- R01 GM038093-19/GM/NIGMS NIH HHS/ -- R01 GM038093-19S1/GM/NIGMS NIH HHS/ -- R01 GM038093-20A1/GM/NIGMS NIH HHS/ -- R01 HD047863/HD/NICHD NIH HHS/ -- R01 HD047863-01/HD/NICHD NIH HHS/ -- R01 HD047863-02/HD/NICHD NIH HHS/ -- R01 HD047863-03/HD/NICHD NIH HHS/ -- R01 HD047863-04/HD/NICHD NIH HHS/ -- R01 HD047863-05/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2009 May 29;324(5931):1192-6. doi: 10.1126/science.1171529.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering and Therapeutic Sciences, University of California, School of Pharmacy, San Francisco (UCSF), San Francisco, CA 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19478182" target="_blank"〉PubMed〈/a〉
    Keywords: Adipocytes/cytology/*metabolism/ultrastructure ; Animals ; Blood Glucose/metabolism ; Cell Differentiation ; Cell Line ; Cell Membrane/metabolism ; Clathrin/chemistry/*metabolism ; Clathrin Heavy Chains ; Clathrin-Coated Vesicles/*metabolism ; Diabetes Mellitus, Type 2/*metabolism ; Glucose/*metabolism ; Glucose Transporter Type 4/*metabolism ; Humans ; Insulin/blood/pharmacology ; Mice ; Mice, Transgenic ; Muscle Fibers, Skeletal/metabolism ; Muscle, Skeletal/*metabolism/ultrastructure ; Myoblasts/cytology/metabolism/ultrastructure ; Protein Isoforms/chemistry/metabolism ; Protein Transport ; Signal Transduction
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  • 83
    Publication Date: 2009-10-03
    Description: Intraspecific chemical communication is mediated by signals called pheromones. Caenorhabditis elegans secretes a mixture of small molecules (collectively termed dauer pheromone) that regulates entry into the alternate dauer larval stage and also modulates adult behavior via as yet unknown receptors. Here, we identify two heterotrimeric GTP-binding protein (G protein)-coupled receptors (GPCRs) that mediate dauer formation in response to a subset of dauer pheromone components. The SRBC-64 and SRBC-66 GPCRs are members of the large Caenorhabditis-specific SRBC subfamily and are expressed in the ASK chemosensory neurons, which are required for pheromone-induced dauer formation. Expression of both, but not each receptor alone, confers pheromone-mediated effects on heterologous cells. Identification of dauer pheromone receptors will allow a better understanding of the signaling cascades that transduce the context-dependent effects of ecologically important chemical signals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4448937/" 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/PMC4448937/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Kyuhyung -- Sato, Koji -- Shibuya, Mayumi -- Zeiger, Danna M -- Butcher, Rebecca A -- Ragains, Justin R -- Clardy, Jon -- Touhara, Kazushige -- Sengupta, Piali -- F32 GM077943/GM/NIGMS NIH HHS/ -- P30 NS045713/NS/NINDS NIH HHS/ -- P30 NS45713/NS/NINDS NIH HHS/ -- R01 CA024487/CA/NCI NIH HHS/ -- R01 CA24487/CA/NCI NIH HHS/ -- R01 GM056223/GM/NIGMS NIH HHS/ -- R01 GM56223/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Nov 13;326(5955):994-8. doi: 10.1126/science.1176331. Epub 2009 Oct 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19797623" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/genetics/*growth & development/*physiology ; Caenorhabditis elegans Proteins/genetics/physiology ; Calcium/metabolism ; Cell Line ; Chemoreceptor Cells/metabolism ; Cyclic AMP/metabolism ; Cyclic GMP/metabolism ; GTP-Binding Protein alpha Subunits, Gi-Go/physiology ; Gene Expression Regulation, Developmental ; Genes, Helminth ; Guanylate Cyclase/antagonists & inhibitors/metabolism ; Hexoses/chemistry/physiology ; Humans ; Mutation ; Pheromones/*physiology ; Receptors, G-Protein-Coupled ; Reproduction ; Signal Transduction ; Transfection
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 84
    Publication Date: 2009-12-17
    Description: Emerging evidence indicates that gene expression in higher organisms is regulated by RNA polymerase II stalling during early transcription elongation. To probe the mechanisms responsible for this regulation, we developed methods to isolate and characterize short RNAs derived from stalled RNA polymerase II in Drosophila cells. Significant levels of these short RNAs were generated from more than one-third of all genes, indicating that promoter-proximal stalling is a general feature of early polymerase elongation. Nucleotide composition of the initially transcribed sequence played an important role in promoting transcriptional stalling by rendering polymerase elongation complexes highly susceptible to backtracking and arrest. These results indicate that the intrinsic efficiency of early elongation can greatly affect gene expression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3435875/" 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/PMC3435875/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nechaev, Sergei -- Fargo, David C -- dos Santos, Gilberto -- Liu, Liwen -- Gao, Yuan -- Adelman, Karen -- ZIA ES101987-05/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2010 Jan 15;327(5963):335-8. doi: 10.1126/science.1181421. Epub 2009 Dec 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20007866" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Composition ; Cell Line ; Drosophila melanogaster ; *Gene Expression Regulation ; *Genes, Insect ; Genome, Insect ; Oligonucleotide Array Sequence Analysis ; *Promoter Regions, Genetic ; RNA/genetics/*metabolism ; RNA Caps/genetics/metabolism ; RNA Polymerase II/*metabolism ; RNA, Messenger/genetics/metabolism ; Transcription Initiation Site ; *Transcription, Genetic
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  • 85
    Publication Date: 2009-01-31
    Description: Telomerase is a ribonucleoprotein (RNP) complex that synthesizes telomere repeats in tissue progenitor cells and cancer cells. Active human telomerase consists of at least three principal subunits, including the telomerase reverse transcriptase, the telomerase RNA (TERC), and dyskerin. Here, we identify a holoenzyme subunit, TCAB1 (telomerase Cajal body protein 1), that is notably enriched in Cajal bodies, nuclear sites of RNP processing that are important for telomerase function. TCAB1 associates with active telomerase enzyme, established telomerase components, and small Cajal body RNAs that are involved in modifying splicing RNAs. Depletion of TCAB1 by using RNA interference prevents TERC from associating with Cajal bodies, disrupts telomerase-telomere association, and abrogates telomere synthesis by telomerase. Thus, TCAB1 controls telomerase trafficking and is required for telomere synthesis in human cancer cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2728071/" 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/PMC2728071/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Venteicher, Andrew S -- Abreu, Eladio B -- Meng, Zhaojing -- McCann, Kelly E -- Terns, Rebecca M -- Veenstra, Timothy D -- Terns, Michael P -- Artandi, Steven E -- CA104676/CA/NCI NIH HHS/ -- CA111691/CA/NCI NIH HHS/ -- CA125453/CA/NCI NIH HHS/ -- GM07365/GM/NIGMS NIH HHS/ -- N01-CO-12400/CO/NCI NIH HHS/ -- R01 CA111691/CA/NCI NIH HHS/ -- R01 CA111691-04/CA/NCI NIH HHS/ -- R01 CA125453/CA/NCI NIH HHS/ -- R01 CA125453-03/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Jan 30;323(5914):644-8. doi: 10.1126/science.1165357.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Stanford School of Medicine, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19179534" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cell Cycle Proteins/metabolism ; Cell Line, Tumor ; Coiled Bodies/*metabolism ; HeLa Cells ; Humans ; Immunoprecipitation ; Molecular Sequence Data ; Nuclear Proteins/metabolism ; RNA/metabolism ; RNA Interference ; Telomerase/chemistry/*metabolism ; Telomere/*metabolism
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  • 86
    Publication Date: 2009-08-01
    Description: Studies correlating genetic variation to gene expression facilitate the interpretation of common human phenotypes and disease. As functional variants may be operating in a tissue-dependent manner, we performed gene expression profiling and association with genetic variants (single-nucleotide polymorphisms) on three cell types of 75 individuals. We detected cell type-specific genetic effects, with 69 to 80% of regulatory variants operating in a cell type-specific manner, and identified multiple expressive quantitative trait loci (eQTLs) per gene, unique or shared among cell types and positively correlated with the number of transcripts per gene. Cell type-specific eQTLs were found at larger distances from genes and at lower effect size, similar to known enhancers. These data suggest that the complete regulatory variant repertoire can only be uncovered in the context of cell-type specificity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867218/" 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/PMC2867218/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dimas, Antigone S -- Deutsch, Samuel -- Stranger, Barbara E -- Montgomery, Stephen B -- Borel, Christelle -- Attar-Cohen, Homa -- Ingle, Catherine -- Beazley, Claude -- Gutierrez Arcelus, Maria -- Sekowska, Magdalena -- Gagnebin, Marilyne -- Nisbett, James -- Deloukas, Panos -- Dermitzakis, Emmanouil T -- Antonarakis, Stylianos E -- 077011/Wellcome Trust/United Kingdom -- 077046/Wellcome Trust/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2009 Sep 4;325(5945):1246-50. doi: 10.1126/science.1174148. Epub 2009 Jul 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, CB10 1HH, Cambridge, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19644074" target="_blank"〉PubMed〈/a〉
    Keywords: Allelic Imbalance ; B-Lymphocytes ; Cell Line ; Enhancer Elements, Genetic ; Fibroblasts ; Gene Expression Profiling ; *Gene Expression Regulation ; Gene Frequency ; Genotype ; Humans ; *Polymorphism, Single Nucleotide ; *Quantitative Trait Loci ; RNA, Messenger/genetics/metabolism ; *Regulatory Elements, Transcriptional ; Statistics, Nonparametric ; T-Lymphocytes
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  • 87
    Publication Date: 2009-06-06
    Description: To survive in hostile environments, organisms activate stress-responsive transcriptional regulators that coordinately increase production of protective factors. Hypoxia changes cellular metabolism and thus activates redox-sensitive as well as oxygen-dependent signal transducers. We demonstrate that Sirtuin 1 (Sirt1), a redox-sensing deacetylase, selectively stimulates activity of the transcription factor hypoxia-inducible factor 2 alpha (HIF-2alpha) during hypoxia. The effect of Sirt1 on HIF-2alpha required direct interaction of the proteins and intact deacetylase activity of Sirt1. Select lysine residues in HIF-2alpha that are acetylated during hypoxia confer repression of Sirt1 augmentation by small-molecule inhibitors. In cultured cells and mice, decreasing or increasing Sirt1 activity or levels affected expression of the HIF-2alpha target gene erythropoietin accordingly. Thus, Sirt1 promotes HIF-2 signaling during hypoxia and likely other environmental stresses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dioum, Elhadji M -- Chen, Rui -- Alexander, Matthew S -- Zhang, Quiyang -- Hogg, Richard T -- Gerard, Robert D -- Garcia, Joseph A -- I01 BX000446/BX/BLRD VA/ -- New York, N.Y. -- Science. 2009 Jun 5;324(5932):1289-93. doi: 10.1126/science.1169956.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Veterans Affairs North Texas Health Care System, Department of Medicine, 4500 South Lancaster Road, Dallas, TX 75216, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19498162" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Amino Acid Substitution ; Animals ; Basic Helix-Loop-Helix Transcription Factors/chemistry/genetics/*metabolism ; *Cell Hypoxia ; Cell Line ; Cell Line, Tumor ; Erythropoietin/genetics ; Gene Expression Regulation ; Humans ; Kidney/metabolism ; Liver/embryology/metabolism ; Mice ; Mice, Knockout ; Mutant Proteins/chemistry/metabolism ; Oxidation-Reduction ; *Signal Transduction ; Sirtuin 1 ; Sirtuins/genetics/*metabolism
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  • 88
    Publication Date: 2009-12-08
    Description: Maize domestication (Zea mays ssp. mays L.) resulted in a wide diversity of native landraces that represent an invaluable source of genetic information for exploring natural variation and genome evolution. We sequenced de novo the approximately 2-gigabase genome of the Mexican landrace Palomero Toluqueno (Palomero) and compared its features to those of the modern inbred line B73. We revealed differences concordant with its ancient origin and identified chromosomal regions of low nucleotide variability that contain domestication genes involved in heavy-metal detoxification. Our results indicate that environmental changes were important selective forces acting on maize domestication.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vielle-Calzada, Jean-Philippe -- Martinez de la Vega, Octavio -- Hernandez-Guzman, Gustavo -- Ibarra-Laclette, Enrique -- Alvarez-Mejia, Cesar -- Vega-Arreguin, Julio C -- Jimenez-Moraila, Beatriz -- Fernandez-Cortes, Araceli -- Corona-Armenta, Guillermo -- Herrera-Estrella, Luis -- Herrera-Estrella, Alfredo -- New York, N.Y. -- Science. 2009 Nov 20;326(5956):1078. doi: 10.1126/science.1178437.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratorio Nacional de Genomica para la Biodiversidad, CINVESTAV Irapuato, Km 9.6 Libramiento Norte Carretera Irapuato-Leon, 36500 Irapuato, Mexico.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965420" target="_blank"〉PubMed〈/a〉
    Keywords: Chromosome Mapping ; Chromosomes, Plant/genetics ; Crops, Agricultural/genetics/growth & development ; *Genes, Plant ; Genetic Variation ; *Genome, Plant ; Metals, Heavy/analysis/*metabolism/toxicity ; Molecular Sequence Data ; *Selection, Genetic ; Sequence Analysis, DNA ; Sequence Homology, Nucleic Acid ; Soil/analysis ; Zea mays/*genetics/growth & development/*metabolism
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  • 89
    Publication Date: 2009-07-18
    Description: Selenocysteine is the only genetically encoded amino acid in humans whose biosynthesis occurs on its cognate transfer RNA (tRNA). O-Phosphoseryl-tRNA:selenocysteinyl-tRNA synthase (SepSecS) catalyzes the final step of selenocysteine formation by a poorly understood tRNA-dependent mechanism. The crystal structure of human tRNA(Sec) in complex with SepSecS, phosphoserine, and thiophosphate, together with in vivo and in vitro enzyme assays, supports a pyridoxal phosphate-dependent mechanism of Sec-tRNA(Sec) formation. Two tRNA(Sec) molecules, with a fold distinct from other canonical tRNAs, bind to each SepSecS tetramer through their 13-base pair acceptor-TPsiC arm (where Psi indicates pseudouridine). The tRNA binding is likely to induce a conformational change in the enzyme's active site that allows a phosphoserine covalently attached to tRNA(Sec), but not free phosphoserine, to be oriented properly for the reaction to occur.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857584/" 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/PMC2857584/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Palioura, Sotiria -- Sherrer, R Lynn -- Steitz, Thomas A -- Soll, Dieter -- Simonovic, Miljan -- R01 GM022854/GM/NIGMS NIH HHS/ -- R01 GM022854-33/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Jul 17;325(5938):321-5. doi: 10.1126/science.1173755.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19608919" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acyl-tRNA Synthetases/*chemistry/*metabolism ; Base Sequence ; Biocatalysis ; Catalytic Domain ; Crystallography, X-Ray ; Humans ; Hydrogen Bonding ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Phosphates/chemistry/metabolism ; Phosphoserine/chemistry/metabolism ; Protein Conformation ; Protein Multimerization ; Protein Structure, Secondary ; RNA, Transfer, Amino Acid-Specific/*chemistry/*metabolism ; RNA, Transfer, Amino Acyl/*metabolism ; Selenocysteine/*biosynthesis/genetics
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  • 90
    Publication Date: 2009-12-08
    Description: Previous x-ray crystal structures have given insight into the mechanism of transcription and the role of general transcription factors in the initiation of the process. A structure of an RNA polymerase II-general transcription factor TFIIB complex at 4.5 angstrom resolution revealed the amino-terminal region of TFIIB, including a loop termed the "B finger," reaching into the active center of the polymerase where it may interact with both DNA and RNA, but this structure showed little of the carboxyl-terminal region. A new crystal structure of the same complex at 3.8 angstrom resolution obtained under different solution conditions is complementary with the previous one, revealing the carboxyl-terminal region of TFIIB, located above the polymerase active center cleft, but showing none of the B finger. In the new structure, the linker between the amino- and carboxyl-terminal regions can also be seen, snaking down from above the cleft toward the active center. The two structures, taken together with others previously obtained, dispel long-standing mysteries of the transcription initiation process.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2813267/" 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/PMC2813267/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Xin -- Bushnell, David A -- Wang, Dong -- Calero, Guillermo -- Kornberg, Roger D -- AI21144/AI/NIAID NIH HHS/ -- GM049985/GM/NIGMS NIH HHS/ -- K99 GM085136/GM/NIGMS NIH HHS/ -- K99 GM085136-02/GM/NIGMS NIH HHS/ -- R00 GM085136/GM/NIGMS NIH HHS/ -- R01 AI021144/AI/NIAID NIH HHS/ -- R01 AI021144-25/AI/NIAID NIH HHS/ -- R01 GM036659/GM/NIGMS NIH HHS/ -- R01 GM049985/GM/NIGMS NIH HHS/ -- R01 GM049985-16/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Jan 8;327(5962):206-9. doi: 10.1126/science.1182015. Epub 2009 Nov 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965383" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Catalytic Domain ; Crystallography, X-Ray ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Interaction Domains and Motifs ; Protein Structure, Secondary ; Protein Structure, Tertiary ; RNA Polymerase II/*chemistry/*metabolism ; Repetitive Sequences, Amino Acid ; Saccharomyces cerevisiae/chemistry/genetics/metabolism ; Saccharomyces cerevisiae Proteins/*chemistry/*metabolism ; Transcription Factor TFIIB/*chemistry/*metabolism ; *Transcription, Genetic
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  • 91
    Publication Date: 2009-12-17
    Description: The molecular mechanisms underlying major phenotypic changes that have evolved repeatedly in nature are generally unknown. Pelvic loss in different natural populations of threespine stickleback fish has occurred through regulatory mutations deleting a tissue-specific enhancer of the Pituitary homeobox transcription factor 1 (Pitx1) gene. The high prevalence of deletion mutations at Pitx1 may be influenced by inherent structural features of the locus. Although Pitx1 null mutations are lethal in laboratory animals, Pitx1 regulatory mutations show molecular signatures of positive selection in pelvic-reduced populations. These studies illustrate how major expression and morphological changes can arise from single mutational leaps in natural populations, producing new adaptive alleles via recurrent regulatory alterations in a key developmental control gene.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109066/" 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/PMC3109066/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chan, Yingguang Frank -- Marks, Melissa E -- Jones, Felicity C -- Villarreal, Guadalupe Jr -- Shapiro, Michael D -- Brady, Shannon D -- Southwick, Audrey M -- Absher, Devin M -- Grimwood, Jane -- Schmutz, Jeremy -- Myers, Richard M -- Petrov, Dmitri -- Jonsson, Bjarni -- Schluter, Dolph -- Bell, Michael A -- Kingsley, David M -- P50 HG002568/HG/NHGRI NIH HHS/ -- P50 HG002568-09/HG/NHGRI NIH HHS/ -- P50 HG02568/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Jan 15;327(5963):302-5. doi: 10.1126/science.1182213. Epub 2009 Dec 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20007865" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; *Biological Evolution ; Chromosome Fragile Sites ; Chromosome Mapping ; Crosses, Genetic ; DNA, Intergenic ; *Enhancer Elements, Genetic ; Fish Proteins/*genetics ; Molecular Sequence Data ; Mutation ; Paired Box Transcription Factors/*genetics ; Pelvis/anatomy & histology ; Selection, Genetic ; *Sequence Deletion ; Smegmamorpha/*anatomy & histology/*genetics/growth & development
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  • 92
    Publication Date: 2009-08-08
    Description: Posttranslational modifications play key roles in regulating chromatin plasticity. Although various chromatin-remodeling enzymes have been described that respond to specific histone modifications, little is known about the role of poly[adenosine 5'-diphosphate (ADP)-ribose] in chromatin remodeling. Here, we identify a chromatin-remodeling enzyme, ALC1 (Amplified in Liver Cancer 1, also known as CHD1L), that interacts with poly(ADP-ribose) and catalyzes PARP1-stimulated nucleosome sliding. Our results define ALC1 as a DNA damage-response protein whose role in this process is sustained by its association with known DNA repair factors and its rapid poly(ADP-ribose)-dependent recruitment to DNA damage sites. Furthermore, we show that depletion or overexpression of ALC1 results in sensitivity to DNA-damaging agents. Collectively, these results provide new insights into the mechanisms by which poly(ADP-ribose) regulates DNA repair.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3443743/" 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/PMC3443743/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ahel, Dragana -- Horejsi, Zuzana -- Wiechens, Nicola -- Polo, Sophie E -- Garcia-Wilson, Elisa -- Ahel, Ivan -- Flynn, Helen -- Skehel, Mark -- West, Stephen C -- Jackson, Stephen P -- Owen-Hughes, Tom -- Boulton, Simon J -- 064414/Wellcome Trust/United Kingdom -- 11224/Cancer Research UK/United Kingdom -- A3549/Cancer Research UK/United Kingdom -- A5290/Cancer Research UK/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- Cancer Research UK/United Kingdom -- Department of Health/United Kingdom -- New York, N.Y. -- Science. 2009 Sep 4;325(5945):1240-3. doi: 10.1126/science.1177321. Epub 2009 Aug 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉DNA Damage Response Laboratory, Clare Hall, London Research Institute, South Mimms EN6 3LD, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19661379" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/metabolism ; Adenosine Triphosphate/metabolism ; Cell Line ; Chromatin/*metabolism ; *Chromatin Assembly and Disassembly ; DNA Damage ; DNA Helicases/chemistry/genetics/*metabolism ; *DNA Repair ; DNA-Binding Proteins/chemistry/genetics/*metabolism ; Humans ; Hydrogen Peroxide/pharmacology ; Immunoprecipitation ; Kinetics ; Mutant Proteins/chemistry/metabolism ; Nucleosomes/metabolism ; Phleomycins/pharmacology ; Poly Adenosine Diphosphate Ribose/*metabolism ; Poly(ADP-ribose) Polymerase Inhibitors ; Poly(ADP-ribose) Polymerases/metabolism ; Protein Structure, Tertiary ; Radiation, Ionizing ; Recombinant Proteins/chemistry/metabolism
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  • 93
    Publication Date: 2009-03-21
    Description: Cyclic nucleotide-gated (CNG) channels localize exclusively to the plasma membrane of photosensitive outer segments of rod photoreceptors where they generate the electrical response to light. Here, we report the finding that targeting of CNG channels to the rod outer segment required their interaction with ankyrin-G. Ankyrin-G localized exclusively to rod outer segments, coimmunoprecipitated with the CNG channel, and bound to the C-terminal domain of the channel beta1 subunit. Ankyrin-G depletion in neonatal mouse retinas markedly reduced CNG channel expression. Transgenic expression of CNG channel beta-subunit mutants in Xenopus rods showed that ankyrin-G binding was necessary and sufficient for targeting of the beta1 subunit to outer segments. Thus, ankyrin-G is required for transport of CNG channels to the plasma membrane of rod outer segments.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2792576/" 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/PMC2792576/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kizhatil, Krishnakumar -- Baker, Sheila A -- Arshavsky, Vadim Y -- Bennett, Vann -- EY12859/EY/NEI NIH HHS/ -- P30 EY005722/EY/NEI NIH HHS/ -- P30 EY005722-23/EY/NEI NIH HHS/ -- R01 EY012859/EY/NEI NIH HHS/ -- R01 EY012859-10/EY/NEI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Mar 20;323(5921):1614-7. doi: 10.1126/science.1169789.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19299621" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; Ankyrins/*metabolism ; Cattle ; Cell Line ; Cell Membrane/metabolism ; Cilia/*metabolism ; Cyclic Nucleotide-Gated Cation Channels/*metabolism ; Humans ; Mice ; Molecular Sequence Data ; Nerve Tissue Proteins/metabolism ; Recombinant Fusion Proteins/metabolism ; Rod Cell Outer Segment/*metabolism ; Xenopus laevis
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  • 94
    Publication Date: 2009-11-07
    Description: We report a high-quality draft sequence of the genome of the horse (Equus caballus). The genome is relatively repetitive but has little segmental duplication. Chromosomes appear to have undergone few historical rearrangements: 53% of equine chromosomes show conserved synteny to a single human chromosome. Equine chromosome 11 is shown to have an evolutionary new centromere devoid of centromeric satellite DNA, suggesting that centromeric function may arise before satellite repeat accumulation. Linkage disequilibrium, showing the influences of early domestication of large herds of female horses, is intermediate in length between dog and human, and there is long-range haplotype sharing among breeds.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785132/" 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/PMC3785132/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wade, C M -- Giulotto, E -- Sigurdsson, S -- Zoli, M -- Gnerre, S -- Imsland, F -- Lear, T L -- Adelson, D L -- Bailey, E -- Bellone, R R -- Blocker, H -- Distl, O -- Edgar, R C -- Garber, M -- Leeb, T -- Mauceli, E -- MacLeod, J N -- Penedo, M C T -- Raison, J M -- Sharpe, T -- Vogel, J -- Andersson, L -- Antczak, D F -- Biagi, T -- Binns, M M -- Chowdhary, B P -- Coleman, S J -- Della Valle, G -- Fryc, S -- Guerin, G -- Hasegawa, T -- Hill, E W -- Jurka, J -- Kiialainen, A -- Lindgren, G -- Liu, J -- Magnani, E -- Mickelson, J R -- Murray, J -- Nergadze, S G -- Onofrio, R -- Pedroni, S -- Piras, M F -- Raudsepp, T -- Rocchi, M -- Roed, K H -- Ryder, O A -- Searle, S -- Skow, L -- Swinburne, J E -- Syvanen, A C -- Tozaki, T -- Valberg, S J -- Vaudin, M -- White, J R -- Zody, M C -- Broad Institute Genome Sequencing Platform -- Broad Institute Whole Genome Assembly Team -- Lander, E S -- Lindblad-Toh, K -- 098051/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2009 Nov 6;326(5954):865-7. doi: 10.1126/science.1178158.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Broad Institute, 7 Cambridge Center, Cambridge, MA 02142, USA. c.wade@usyd.edu.au〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19892987" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Domestic/genetics ; Centromere/genetics ; Chromosome Mapping ; Chromosomes, Mammalian/*genetics ; Computational Biology ; DNA Copy Number Variations ; Dogs ; Evolution, Molecular ; Female ; Genes ; *Genome ; Haplotypes ; Horses/*genetics ; Humans ; Molecular Sequence Data ; Phylogeny ; Repetitive Sequences, Nucleic Acid ; *Sequence Analysis, DNA ; Synteny
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  • 95
    Publication Date: 2009-10-17
    Description: The mammalian heart is formed from distinct sets of first and second heart field (FHF and SHF, respectively) progenitors. Although multipotent progenitors have previously been shown to give rise to cardiomyocytes, smooth muscle, and endothelial cells, the mechanism governing the generation of large numbers of differentiated progeny remains poorly understood. We have employed a two-colored fluorescent reporter system to isolate FHF and SHF progenitors from developing mouse embryos and embryonic stem cells. Genome-wide profiling of coding and noncoding transcripts revealed distinct molecular signatures of these progenitor populations. We further identify a committed ventricular progenitor cell in the Islet 1 lineage that is capable of limited in vitro expansion, differentiation, and assembly into functional ventricular muscle tissue, representing a combination of tissue engineering and stem cell biology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2895998/" 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/PMC2895998/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Domian, Ibrahim J -- Chiravuri, Murali -- van der Meer, Peter -- Feinberg, Adam W -- Shi, Xi -- Shao, Ying -- Wu, Sean M -- Parker, Kevin Kit -- Chien, Kenneth R -- K08 HL081086/HL/NHLBI NIH HHS/ -- K08 HL081086-01/HL/NHLBI NIH HHS/ -- K08 HL091209/HL/NHLBI NIH HHS/ -- R01 HL079126/HL/NHLBI NIH HHS/ -- R01 HL079126-01A1/HL/NHLBI NIH HHS/ -- T32 HL002807/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2009 Oct 16;326(5951):426-9. doi: 10.1126/science.1177350.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cardiovascular Research Center, Massachusetts General Hospital, Charles River Plaza, CPZN 3200, 185 Cambridge Street, Boston, MA 02114-2790, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19833966" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Cell Cycle ; Cell Differentiation ; Cell Line ; Cell Lineage ; Cells, Cultured ; Embryonic Stem Cells/*cytology/physiology ; Gene Expression ; Heart/embryology ; Heart Ventricles/*cytology/embryology ; Mice ; Mice, Transgenic ; Muscle Development ; Myocardial Contraction ; Myocytes, Cardiac/*cytology/physiology ; Oligonucleotide Array Sequence Analysis ; *Tissue Engineering ; *Ventricular Function
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  • 96
    Publication Date: 2009-02-14
    Description: Infection by human rhinovirus (HRV) is a major cause of upper and lower respiratory tract disease worldwide and displays considerable phenotypic variation. We examined diversity by completing the genome sequences for all known serotypes (n = 99). Superimposition of capsid crystal structure and optimal-energy RNA configurations established alignments and phylogeny. These revealed conserved motifs; clade-specific diversity, including a potential newly identified species (HRV-D); mutations in field isolates; and recombination. In analogy with poliovirus, a hypervariable 5' untranslated region tract may affect virulence. A configuration consistent with nonscanning internal ribosome entry was found in all HRVs and may account for rapid translation. The data density from complete sequences of the reference HRVs provided high resolution for this degree of modeling and serves as a platform for full genome-based epidemiologic studies and antiviral or vaccine development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3923423/" 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/PMC3923423/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Palmenberg, Ann C -- Spiro, David -- Kuzmickas, Ryan -- Wang, Shiliang -- Djikeng, Appolinaire -- Rathe, Jennifer A -- Fraser-Liggett, Claire M -- Liggett, Stephen B -- R01 HL091490/HL/NHLBI NIH HHS/ -- U19 AI070503/AI/NIAID NIH HHS/ -- U19-AI070503/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2009 Apr 3;324(5923):55-9. doi: 10.1126/science.1165557. Epub 2009 Feb 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Molecular Virology, University of Wisconsin, Madison, WI 53706, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19213880" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions ; 5' Untranslated Regions ; Base Composition ; Base Sequence ; Codon, Terminator ; *Evolution, Molecular ; *Genome, Viral ; Humans ; Molecular Sequence Data ; Mutation ; Nucleic Acid Conformation ; Open Reading Frames ; Phylogeny ; Picornaviridae Infections/virology ; Polyproteins/biosynthesis/chemistry/genetics ; RNA, Viral/chemistry/*genetics ; Recombination, Genetic ; Respiratory Tract Infections/virology ; Rhinovirus/classification/*genetics/ultrastructure ; Sequence Alignment ; Sequence Analysis, RNA ; Serotyping ; Viral Proteins/biosynthesis/chemistry/genetics
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  • 97
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-03-17
    Description: As fundamental units of neuronal communication, chemical synapses are composed of presynaptic and postsynaptic specializations that form at specific locations with defined shape and size. Synaptic assembly must be tightly regulated to prevent overgrowth of the synapse size and number, but the molecular mechanisms that inhibit synapse assembly are poorly understood. We identified regulator of synaptogenesis-1 (RSY-1) as an evolutionarily conserved molecule that locally antagonized presynaptic assembly. The loss of RSY-1 in Caenorhabditis elegans led to formation of extra synapses and recruitment of excessive synaptic material to presynaptic sites. RSY-1 directly interacted with and negatively regulated SYD-2/liprin-alpha, a master assembly molecule that recruits numerous synaptic components to presynaptic sites. RSY-1 also bound and regulated SYD-1, a synaptic protein required for proper functioning of SYD-2. Thus, local inhibitory mechanisms govern synapse formation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3087376/" 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/PMC3087376/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Patel, Maulik R -- Shen, Kang -- 1R01NS048392/NS/NINDS NIH HHS/ -- R01 NS048392/NS/NINDS NIH HHS/ -- R01 NS048392-05/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Mar 13;323(5920):1500-3. doi: 10.1126/science.1169025.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Neurosciences Program, Stanford University, 385 Serra Mall, Herrin Labs, Room 144, Stanford University, Stanford,CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19286562" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Caenorhabditis elegans/genetics/*physiology ; Caenorhabditis elegans Proteins/chemistry/genetics/*metabolism ; Carrier Proteins/metabolism ; Cell Line ; Cell Nucleus/metabolism ; Humans ; Mutation ; Nerve Tissue Proteins/metabolism ; Nuclear Proteins/chemistry/genetics/*metabolism ; Phosphoproteins/genetics/metabolism ; Protein Binding ; Protein Interaction Mapping ; Protein Isoforms/chemistry/genetics/metabolism ; Protein Structure, Tertiary ; Recombinant Fusion Proteins/metabolism ; Synapses/metabolism/*physiology
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  • 98
    Publication Date: 2009-01-10
    Description: Sex determination in maize is controlled by a developmental cascade leading to the formation of unisexual florets derived from an initially bisexual floral meristem. Abortion of pistil primordia in staminate florets is controlled by a tasselseed-mediated cell death process. We positionally cloned and characterized the function of the sex determination gene tasselseed1 (ts1). The TS1 protein encodes a plastid-targeted lipoxygenase with predicted 13-lipoxygenase specificity, which suggests that TS1 may be involved in the biosynthesis of the plant hormone jasmonic acid. In the absence of a functional ts1 gene, lipoxygenase activity was missing and endogenous jasmonic acid concentrations were reduced in developing inflorescences. Application of jasmonic acid to developing inflorescences rescued stamen development in mutant ts1 and ts2 inflorescences, revealing a role for jasmonic acid in male flower development in maize.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Acosta, Ivan F -- Laparra, Helene -- Romero, Sandra P -- Schmelz, Eric -- Hamberg, Mats -- Mottinger, John P -- Moreno, Maria A -- Dellaporta, Stephen L -- R01 GM038148/GM/NIGMS NIH HHS/ -- R01 GM038148-19/GM/NIGMS NIH HHS/ -- R01 GM38148/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Jan 9;323(5911):262-5. doi: 10.1126/science.1164645.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19131630" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cloning, Molecular ; Cyclopentanes/*metabolism/pharmacology ; Flowers/growth & development ; Genes, Plant ; Lipoxygenase/chemistry/genetics/*metabolism ; Molecular Sequence Data ; Mutation ; Oxylipins/*metabolism/pharmacology ; Plant Proteins/chemistry/*genetics/*metabolism ; Plastids/enzymology ; *Signal Transduction ; Zea mays/enzymology/*genetics/growth & development/*metabolism
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  • 99
    Publication Date: 2009-11-11
    Description: Oxygen minimum zones, also known as oceanic "dead zones," are widespread oceanographic features currently expanding because of global warming. Although inhospitable to metazoan life, they support a cryptic microbiota whose metabolic activities affect nutrient and trace gas cycling within the global ocean. Here, we report metagenomic analyses of a ubiquitous and abundant but uncultivated oxygen minimum zone microbe (SUP05) related to chemoautotrophic gill symbionts of deep-sea clams and mussels. The SUP05 metagenome harbors a versatile repertoire of genes mediating autotrophic carbon assimilation, sulfur oxidation, and nitrate respiration responsive to a wide range of water-column redox states. Our analysis provides a genomic foundation for understanding the ecological and biogeochemical role of pelagic SUP05 in oxygen-deficient oceanic waters and its potential sensitivity to environmental changes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Walsh, David A -- Zaikova, Elena -- Howes, Charles G -- Song, Young C -- Wright, Jody J -- Tringe, Susannah G -- Tortell, Philippe D -- Hallam, Steven J -- New York, N.Y. -- Science. 2009 Oct 23;326(5952):578-82. doi: 10.1126/science.1175309.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19900896" target="_blank"〉PubMed〈/a〉
    Keywords: Biomass ; British Columbia ; Carbon/metabolism ; *Chemoautotrophic Growth ; *Ecosystem ; Energy Metabolism ; Gammaproteobacteria/*genetics/metabolism/physiology ; Genes, rRNA ; *Genome, Bacterial ; *Metagenome ; Molecular Sequence Data ; Nitrates/metabolism ; Oxidation-Reduction ; Oxygen/*analysis ; Pacific Ocean ; Phylogeny ; Seasons ; Seawater/chemistry/*microbiology ; Sulfur/metabolism ; Symbiosis
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  • 100
    Publication Date: 2009-05-09
    Description: Visibly fluorescent proteins (FPs) from jellyfish and corals have revolutionized many areas of molecular and cell biology, but the use of FPs in intact animals, such as mice, has been handicapped by poor penetration of excitation light. We now show that a bacteriophytochrome from Deinococcus radiodurans, incorporating biliverdin as the chromophore, can be engineered into monomeric, infrared-fluorescent proteins (IFPs), with excitation and emission maxima of 684 and 708 nm, respectively; extinction coefficient 〉90,000 M(-1) cm(-1); and quantum yield of 0.07. IFPs express well in mammalian cells and mice and spontaneously incorporate biliverdin, which is ubiquitous as the initial intermediate in heme catabolism but has negligible fluorescence by itself. Because their wavelengths penetrate tissue well, IFPs are suitable for whole-body imaging. The IFPs developed here provide a scaffold for further engineering.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2763207/" 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/PMC2763207/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shu, Xiaokun -- Royant, Antoine -- Lin, Michael Z -- Aguilera, Todd A -- Lev-Ram, Varda -- Steinbach, Paul A -- Tsien, Roger Y -- R01 CA158448/CA/NCI NIH HHS/ -- R01 GM086197/GM/NIGMS NIH HHS/ -- R01 GM086197-01/GM/NIGMS NIH HHS/ -- R01 NS027177/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 May 8;324(5928):804-7. doi: 10.1126/science.1168683.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0647, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19423828" target="_blank"〉PubMed〈/a〉
    Keywords: Adenoviridae/genetics ; Amino Acid Sequence ; Animals ; *Biliverdine/chemistry/metabolism ; Cell Line ; Deinococcus/*chemistry ; Diagnostic Imaging ; Fluorescence ; Humans ; Liver/anatomy & histology ; *Luminescent Proteins/chemistry/metabolism ; Mice ; Molecular Sequence Data ; *Phytochrome/chemistry/genetics/metabolism ; *Protein Engineering ; Recombinant Fusion Proteins/chemistry/metabolism ; Spectrophotometry, Infrared ; Whole Body Imaging
    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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