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  • Molecular Sequence Data  (1,675)
  • Mice  (1,444)
  • American Association for the Advancement of Science (AAAS)  (2,863)
  • EMBO Press
  • Essen : Verl. Glückauf
  • Krefeld : Geologischer Dienst Nordhein-Westfalen
  • Oxford University Press
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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
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  • 2
    Publication Date: 2009-09-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Service, Robert F -- New York, N.Y. -- Science. 2009 Sep 4;325(5945):1200. doi: 10.1126/science.325_1200a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19729635" target="_blank"〉PubMed〈/a〉
    Keywords: Algal Proteins/*metabolism/*pharmacology ; Animals ; Anti-HIV Agents/metabolism/pharmacology ; Antiviral Agents/*metabolism/*pharmacology ; Ebolavirus/drug effects ; HIV/drug effects ; Humans ; Lectins/*metabolism/*pharmacology ; Mannose/*metabolism ; Mice ; Microbial Sensitivity Tests ; Plant Lectins ; SARS Virus/drug effects ; Virus Diseases/drug therapy ; Viruses/*drug effects
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  • 3
    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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  • 4
    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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  • 5
    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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  • 6
    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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  • 7
    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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  • 8
    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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  • 9
    Publication Date: 2009-02-07
    Description: Platelets play a critical role in the pathogenesis of malarial infections by encouraging the sequestration of infected red blood cells within the cerebral vasculature. But platelets also have well-established roles in innate protection against microbial infections. We found that purified human platelets killed Plasmodium falciparum parasites cultured in red blood cells. Inhibition of platelet function by aspirin and other platelet inhibitors abrogated the lethal effect human platelets exert on P. falciparum parasites. Likewise, platelet-deficient and aspirin-treated mice were more susceptible to death during erythrocytic infection with Plasmodium chabaudi. Both mouse and human platelets bind malarial-infected red cells and kill the parasite within. These results indicate a protective function for platelets in the early stages of erythrocytic infection distinct from their role in cerebral malaria.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McMorran, Brendan J -- Marshall, Vikki M -- de Graaf, Carolyn -- Drysdale, Karen E -- Shabbar, Meriam -- Smyth, Gordon K -- Corbin, Jason E -- Alexander, Warren S -- Foote, Simon J -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Feb 6;323(5915):797-800. doi: 10.1126/science.1166296.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Menzies Research Institute, University of Tasmania, Private Bag 23, Hobart, Tasmania 7000, Australia. brendan.mcmorran@utas.edu.au〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19197068" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Diphosphate/metabolism ; Animals ; Aspirin/pharmacology ; Blood Platelets/metabolism/*physiology ; Erythrocytes/*parasitology ; Female ; Humans ; In Situ Nick-End Labeling ; Malaria/*blood/immunology/*parasitology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Plasmodium chabaudi/*growth & development ; Plasmodium falciparum/*growth & development ; Platelet Activation ; Platelet Aggregation Inhibitors/pharmacology ; Platelet Count ; Receptors, Purinergic P2/metabolism ; Receptors, Purinergic P2Y1 ; Receptors, Thrombopoietin/genetics
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  • 10
    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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  • 11
    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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  • 12
    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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  • 13
    Publication Date: 2009-10-17
    Description: Carbonated beverages are commonly available and immensely popular, but little is known about the cellular and molecular mechanisms underlying the perception of carbonation in the mouth. In mammals, carbonation elicits both somatosensory and chemosensory responses, including activation of taste neurons. We have identified the cellular and molecular substrates for the taste of carbonation. By targeted genetic ablation and the silencing of synapses in defined populations of taste receptor cells, we demonstrated that the sour-sensing cells act as the taste sensors for carbonation, and showed that carbonic anhydrase 4, a glycosylphosphatidylinositol-anchored enzyme, functions as the principal CO2 taste sensor. Together, these studies reveal the basis of the taste of carbonation as well as the contribution of taste cells in the orosensory response to CO2.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3654389/" 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/PMC3654389/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chandrashekar, Jayaram -- Yarmolinsky, David -- von Buchholtz, Lars -- Oka, Yuki -- Sly, William -- Ryba, Nicholas J P -- Zuker, Charles S -- Z01 DE000561-15/Intramural NIH HHS/ -- Z01 DE000561-16/Intramural NIH HHS/ -- ZIA DE000561-17/Intramural NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Oct 16;326(5951):443-5. doi: 10.1126/science.1174601.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Departments of Neurobiology and Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19833970" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Benzolamide/pharmacology ; Bicarbonates/metabolism ; Calcium Channels/metabolism ; Carbon Dioxide/*metabolism ; *Carbonated Beverages ; Carbonic Anhydrase IV/antagonists & inhibitors/genetics/*metabolism ; Carbonic Anhydrase Inhibitors/pharmacology ; Carbonic Anhydrases/metabolism ; Chorda Tympani Nerve/physiology ; Gene Expression Profiling ; Mice ; Mice, Transgenic ; Protons ; Receptors, Cell Surface/metabolism ; Taste/*physiology ; Taste Buds/enzymology/*physiology ; *Taste Perception
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  • 14
    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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  • 15
    Publication Date: 2009-11-07
    Description: Pathogen recognition by T cells is dependent on their exquisite specificity for self-major histocompatibility complex (MHC) molecules presenting a bound peptide. Although this specificity results from positive and negative selection of developing T cells in the thymus, the relative contribution of these two processes remains controversial. To address the relation between the selecting peptide-MHC complex and the specificity of mature T cells, we generated transgenic mice that express a single peptide-MHC class I complex. We demonstrate that positive selection of CD8 T cells in these mice results in an MHC-specific repertoire. Although selection on a single complex is peptide promiscuous, mature T cells are highly peptide specific. Thus, positive selection imparts MHC and peptide specificity on the peripheral CD8 T cell repertoire.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828816/" 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/PMC2828816/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Baomei -- Primeau, Tina M -- Myers, Nancy -- Rohrs, Henry W -- Gross, Michael L -- Lybarger, Lonnie -- Hansen, Ted H -- Connolly, Janet M -- 2P41RR000954/RR/NCRR NIH HHS/ -- AI 027568/AI/NIAID NIH HHS/ -- AI 055849/AI/NIAID NIH HHS/ -- P41 GM103422/GM/NIGMS NIH HHS/ -- P41 RR000954/RR/NCRR NIH HHS/ -- P41 RR000954-32S1/RR/NCRR NIH HHS/ -- R01 AI027568/AI/NIAID NIH HHS/ -- R01 AI027568-17/AI/NIAID NIH HHS/ -- R01 AI055849/AI/NIAID NIH HHS/ -- R01 AI055849-05/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2009 Nov 6;326(5954):871-4. doi: 10.1126/science.1177627.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Immunology, 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/19892989" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CD8-Positive T-Lymphocytes/*immunology ; Cross Reactions ; Cytotoxicity, Immunologic ; H-2 Antigens/genetics/*immunology ; Lymphocyte Activation ; Major Histocompatibility Complex/*immunology ; Mice ; Mice, Knockout ; Mice, Transgenic ; Ovalbumin/immunology ; Peptides/*immunology ; Protein Multimerization ; Spleen/cytology/immunology ; T-Lymphocytes, Cytotoxic/*immunology ; Thymus Gland/cytology/immunology ; Vesiculovirus/immunology
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  • 16
    Publication Date: 2009-11-07
    Description: X-linked adrenoleukodystrophy (ALD) is a severe brain demyelinating disease in boys that is caused by a deficiency in ALD protein, an adenosine triphosphate-binding cassette transporter encoded by the ABCD1 gene. ALD progression can be halted by allogeneic hematopoietic cell transplantation (HCT). We initiated a gene therapy trial in two ALD patients for whom there were no matched donors. Autologous CD34+ cells were removed from the patients, genetically corrected ex vivo with a lentiviral vector encoding wild-type ABCD1, and then re-infused into the patients after they had received myeloablative treatment. Over a span of 24 to 30 months of follow-up, we detected polyclonal reconstitution, with 9 to 14% of granulocytes, monocytes, and T and B lymphocytes expressing the ALD protein. These results strongly suggest that hematopoietic stem cells were transduced in the patients. Beginning 14 to 16 months after infusion of the genetically corrected cells, progressive cerebral demyelination in the two patients stopped, a clinical outcome comparable to that achieved by allogeneic HCT. Thus, lentiviral-mediated gene therapy of hematopoietic stem cells can provide clinical benefits in ALD.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cartier, Nathalie -- Hacein-Bey-Abina, Salima -- Bartholomae, Cynthia C -- Veres, Gabor -- Schmidt, Manfred -- Kutschera, Ina -- Vidaud, Michel -- Abel, Ulrich -- Dal-Cortivo, Liliane -- Caccavelli, Laure -- Mahlaoui, Nizar -- Kiermer, Veronique -- Mittelstaedt, Denice -- Bellesme, Celine -- Lahlou, Najiba -- Lefrere, Francois -- Blanche, Stephane -- Audit, Muriel -- Payen, Emmanuel -- Leboulch, Philippe -- l'Homme, Bruno -- Bougneres, Pierre -- Von Kalle, Christof -- Fischer, Alain -- Cavazzana-Calvo, Marina -- Aubourg, Patrick -- New York, N.Y. -- Science. 2009 Nov 6;326(5954):818-23. doi: 10.1126/science.1171242.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉INSERM UMR745, University Paris-Descartes, 75279 Paris, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19892975" target="_blank"〉PubMed〈/a〉
    Keywords: ATP-Binding Cassette Transporters/*genetics ; Adrenoleukodystrophy/genetics/pathology/*therapy ; Animals ; Brain/pathology ; Cell Differentiation ; Cell Lineage ; Child ; Disease Progression ; Fatty Acids/blood ; Female ; Gene Expression ; *Genetic Therapy ; *Genetic Vectors ; HIV-1/*genetics ; Hematopoiesis ; *Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/*physiology/virology ; Humans ; Leukocytes, Mononuclear/metabolism ; Male ; Mice ; Microglia/cytology/metabolism ; Myeloablative Agonists/therapeutic use ; Transduction, Genetic ; Transplantation Conditioning ; Transplantation, Autologous ; Virus Integration
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  • 17
    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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  • 18
    Publication Date: 2009-01-10
    Description: Cytokines such as interleukin-6 induce tyrosine and serine phosphorylation of Stat3 that results in activation of Stat3-responsive genes. We provide evidence that Stat3 is present in the mitochondria of cultured cells and primary tissues, including the liver and heart. In Stat3(-/-) cells, the activities of complexes I and II of the electron transport chain (ETC) were significantly decreased. We identified Stat3 mutants that selectively restored the protein's function as a transcription factor or its functions within the ETC. In mice that do not express Stat3 in the heart, there were also selective defects in the activities of complexes I and II of the ETC. These data indicate that Stat3 is required for optimal function of the ETC, which may allow it to orchestrate responses to cellular homeostasis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2758306/" 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/PMC2758306/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wegrzyn, Joanna -- Potla, Ramesh -- Chwae, Yong-Joon -- Sepuri, Naresh B V -- Zhang, Qifang -- Koeck, Thomas -- Derecka, Marta -- Szczepanek, Karol -- Szelag, Magdalena -- Gornicka, Agnieszka -- Moh, Akira -- Moghaddas, Shadi -- Chen, Qun -- Bobbili, Santha -- Cichy, Joanna -- Dulak, Jozef -- Baker, Darren P -- Wolfman, Alan -- Stuehr, Dennis -- Hassan, Medhat O -- Fu, Xin-Yuan -- Avadhani, Narayan -- Drake, Jennifer I -- Fawcett, Paul -- Lesnefsky, Edward J -- Larner, Andrew C -- CA098924/CA/NCI NIH HHS/ -- P01AG15885/AG/NIA NIH HHS/ -- R01 AI059710/AI/NIAID NIH HHS/ -- R01 AI059710-03/AI/NIAID NIH HHS/ -- R01 AI059710-04/AI/NIAID NIH HHS/ -- R01 CA098924/CA/NCI NIH HHS/ -- R01 CA098924-03/CA/NCI NIH HHS/ -- R01 CA098924-04/CA/NCI NIH HHS/ -- R01 CA098924-05/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Feb 6;323(5915):793-7. doi: 10.1126/science.1164551. Epub 2009 Jan 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19131594" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Respiration ; Cells, Cultured ; Electron Transport Complex I/metabolism ; Electron Transport Complex II/metabolism ; Homeostasis ; Mice ; Mitochondria/*metabolism ; Mitochondria, Heart/metabolism ; Mitochondria, Liver/metabolism ; Mitochondrial Membranes/metabolism ; NADH, NADPH Oxidoreductases/metabolism ; Oxidative Phosphorylation ; Phosphorylation ; Precursor Cells, B-Lymphoid/metabolism ; STAT3 Transcription Factor/chemistry/*metabolism ; Serine/metabolism ; Signal Transduction
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  • 19
    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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  • 20
    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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  • 21
    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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  • 22
    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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  • 23
    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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  • 24
    Publication Date: 2009-03-03
    Description: Although senile plaques focally disrupt neuronal health, the functional response of astrocytes to Alzheimer's disease pathology is unknown. Using multiphoton fluorescence lifetime imaging microscopy in vivo, we quantitatively imaged astrocytic calcium homeostasis in a mouse model of Alzheimer's disease. Resting calcium was globally elevated in the astrocytic network, but was independent of proximity to individual plaques. Time-lapse imaging revealed that calcium transients in astrocytes were more frequent, synchronously coordinated across long distances, and uncoupled from neuronal activity. Furthermore, rare intercellular calcium waves were observed, but only in mice with amyloid-beta plaques, originating near plaques and spreading radially at least 200 micrometers. Thus, although neurotoxicity is observed near amyloid-beta deposits, there exists a more general astrocyte-based network response to focal pathology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2884172/" 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/PMC2884172/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kuchibhotla, Kishore V -- Lattarulo, Carli R -- Hyman, Bradley T -- Bacskai, Brian J -- EB000768/EB/NIBIB NIH HHS/ -- F31 NS058075-02/NS/NINDS NIH HHS/ -- NS580752/NS/NINDS NIH HHS/ -- R01 AG008487/AG/NIA NIH HHS/ -- R01 AG008487-19/AG/NIA NIH HHS/ -- R01 EB000768/EB/NIBIB NIH HHS/ -- R01 EB000768-08/EB/NIBIB NIH HHS/ -- S10 RR025645/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2009 Feb 27;323(5918):1211-5. doi: 10.1126/science.1169096.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts General Hospital, Department of Neurology/Alzheimer's Disease Research Laboratory, 114 16th Street, Charlestown, MA 02129, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19251629" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/pathology/*physiopathology ; Amyloid beta-Peptides/analysis ; Animals ; Astrocytes/metabolism/pathology/*physiology ; Calcium/*metabolism ; *Calcium Signaling ; Disease Models, Animal ; Homeostasis ; Humans ; Mice ; Mice, Transgenic ; Microscopy, Fluorescence, Multiphoton ; Neurons/pathology/physiology ; Plaque, Amyloid/pathology
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  • 25
    Publication Date: 2009-08-01
    Description: Commensal bacteria in the lower intestine of mammals are 10 times as numerous as the body's cells. We investigated the relative importance of different immune mechanisms in limiting the spread of the intestinal microbiota. Here, we reveal a flexible continuum between innate and adaptive immune function in containing commensal microbes. Mice deficient in critical innate immune functions such as Toll-like receptor signaling or oxidative burst production spontaneously produce high-titer serum antibodies against their commensal microbiota. These antibody responses are functionally essential to maintain host-commensal mutualism in vivo in the face of innate immune deficiency. Spontaneous hyper-activation of adaptive immunity against the intestinal microbiota, secondary to innate immune deficiency, may clarify the underlying mechanisms of inflammatory diseases where immune dysfunction is implicated.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3730530/" 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/PMC3730530/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Slack, Emma -- Hapfelmeier, Siegfried -- Stecher, Barbel -- Velykoredko, Yuliya -- Stoel, Maaike -- Lawson, Melissa A E -- Geuking, Markus B -- Beutler, Bruce -- Tedder, Thomas F -- Hardt, Wolf-Dietrich -- Bercik, Premysl -- Verdu, Elena F -- McCoy, Kathy D -- Macpherson, Andrew J -- AI56363/AI/NIAID NIH HHS/ -- CA105001/CA/NCI NIH HHS/ -- R01 CA105001/CA/NCI NIH HHS/ -- U19 AI056363/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2009 Jul 31;325(5940):617-20. doi: 10.1126/science.1172747.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON L8S 4L8, Canada. andrew.macpherson@insel.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19644121" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Bacterial/biosynthesis/blood/*immunology ; Bacteremia/immunology/microbiology ; Bacteria/growth & development/*immunology/isolation & purification ; Bacterial Infections/immunology/microbiology ; CD4-Positive T-Lymphocytes/immunology ; Colony Count, Microbial ; Enterococcus faecalis/growth & development/immunology/isolation & purification ; Escherichia coli K12/growth & development/immunology/isolation & purification ; Germ-Free Life ; Immunity ; *Immunity, Innate ; Intestinal Mucosa/immunology/*microbiology ; Intestines/immunology/*microbiology ; Lymphoid Tissue/microbiology ; Mice ; Mice, Inbred C57BL ; Permeability ; Respiratory Burst ; Signal Transduction ; Specific Pathogen-Free Organisms ; Spleen/microbiology ; Toll-Like Receptors/genetics/*metabolism
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  • 26
    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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  • 27
    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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  • 28
    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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  • 29
    Publication Date: 2009-05-16
    Description: Sequence preferences of DNA binding proteins are a primary mechanism by which cells interpret the genome. Despite the central importance of these proteins in physiology, development, and evolution, comprehensive DNA binding specificities have been determined experimentally for only a few proteins. Here, we used microarrays containing all 10-base pair sequences to examine the binding specificities of 104 distinct mouse DNA binding proteins representing 22 structural classes. Our results reveal a complex landscape of binding, with virtually every protein analyzed possessing unique preferences. Roughly half of the proteins each recognized multiple distinctly different sequence motifs, challenging our molecular understanding of how proteins interact with their DNA binding sites. This complexity in DNA recognition may be important in gene regulation and in the evolution of transcriptional regulatory networks.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2905877/" 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/PMC2905877/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Badis, Gwenael -- Berger, Michael F -- Philippakis, Anthony A -- Talukder, Shaheynoor -- Gehrke, Andrew R -- Jaeger, Savina A -- Chan, Esther T -- Metzler, Genita -- Vedenko, Anastasia -- Chen, Xiaoyu -- Kuznetsov, Hanna -- Wang, Chi-Fong -- Coburn, David -- Newburger, Daniel E -- Morris, Quaid -- Hughes, Timothy R -- Bulyk, Martha L -- R01 HG003985/HG/NHGRI NIH HHS/ -- R01 HG003985-01/HG/NHGRI NIH HHS/ -- R01 HG003985-02/HG/NHGRI NIH HHS/ -- R01 HG003985-03/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2009 Jun 26;324(5935):1720-3. doi: 10.1126/science.1162327. Epub 2009 May 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19443739" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Base Sequence ; Binding Sites ; DNA/chemistry/*metabolism ; Electrophoretic Mobility Shift Assay ; Gene Expression Regulation ; Gene Regulatory Networks ; Humans ; Mice ; Protein Array Analysis ; Protein Binding ; Protein Structure, Tertiary ; Recombinant Fusion Proteins/chemistry/metabolism ; Transcription Factors/*chemistry/*metabolism
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  • 30
    Publication Date: 2009-05-30
    Description: Chronic viral infection is often associated with the dysfunction of virus-specific T cells. Our studies using Il21r-deficient (Il21r-/-) mice now suggest that interleukin-21 (IL-21) is critical for the long-term maintenance and functionality of CD8+ T cells and the control of chronic lymphocytic choriomeningitis virus infection in mice. Cell-autonomous IL-21 receptor (IL-21R)-dependent signaling by CD8+ T cells was required for sustained cell proliferation and cytokine production during chronic infection. Il21r-/- mice showed normal CD8+ T cell expansion, effector function, memory homeostasis, and recall responses during acute and after resolved infection with several other nonpersistent viruses. These data suggest that IL-21R signaling is required for the maintenance of polyfunctional T cells during chronic viral infections and have implications for understanding the immune response to other persisting antigens, such as tumors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Frohlich, Anja -- Kisielow, Jan -- Schmitz, Iwana -- Freigang, Stefan -- Shamshiev, Abdijapar T -- Weber, Jacqueline -- Marsland, Benjamin J -- Oxenius, Annette -- Kopf, Manfred -- New York, N.Y. -- Science. 2009 Jun 19;324(5934):1576-80. doi: 10.1126/science.1172815. Epub 2009 May 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biomedicine, Institute of Integrative Biology, ETH Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19478140" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CD8-Positive T-Lymphocytes/*immunology ; Chronic Disease ; Humans ; Immunologic Memory ; Interferon-gamma/biosynthesis ; Lymphocytic Choriomeningitis/*immunology ; Mice ; Mice, Inbred C57BL ; Peptide Fragments/biosynthesis ; Receptors, Interleukin-21/*immunology ; Signal Transduction
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  • 31
    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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  • 32
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-01-10
    Description: Histone deacetylase 4 (HDAC4) shuttles between the nucleus and cytoplasm and serves as a nuclear co-repressor that regulates bone and muscle development. We report that HDAC4 regulates the survival of retinal neurons in the mouse in normal and pathological conditions. Reduction in HDAC4 expression during normal retinal development led to apoptosis of rod photoreceptors and bipolar (BP) interneurons, whereas overexpression reduced naturally occurring cell death of the BP cells. HDAC4 overexpression in a mouse model of retinal degeneration prolonged photoreceptor survival. The survival effect was due to the activity of HDAC4 in the cytoplasm and relied at least partly on the activity of hypoxia-inducible factor 1alpha (HIF1alpha). These data provide evidence that HDAC4 plays an important role in promoting the survival of retinal neurons.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3339762/" 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/PMC3339762/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Bo -- Cepko, Constance L -- EYO 14466/PHS HHS/ -- R01 EY014466/EY/NEI NIH HHS/ -- R01 EY014466-05/EY/NEI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Jan 9;323(5911):256-9. doi: 10.1126/science.1166226.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. bochen@genetics.med.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19131628" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Animals ; Apoptosis ; Cell Nucleus/enzymology ; Cell Survival ; Cytoplasm/enzymology ; Electroporation ; Histone Deacetylases/genetics/*metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Mice ; Mutation ; Retina/cytology/*enzymology ; Retinal Degeneration/*enzymology/pathology ; Retinal Neurons/enzymology/*physiology ; Retinal Rod Photoreceptor Cells/enzymology/*physiology ; Rhodopsin/genetics/metabolism ; Transfection
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  • 33
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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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  • 34
    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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  • 35
    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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  • 36
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-10-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Greg -- New York, N.Y. -- Science. 2009 Oct 16;326(5951):349. doi: 10.1126/science.326_349a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19833928" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carbon Dioxide/*metabolism ; *Carbonated Beverages ; Carbonic Anhydrase IV/antagonists & inhibitors/genetics/*metabolism ; Carbonic Anhydrase Inhibitors/pharmacology ; Humans ; Mechanoreceptors/physiology ; Mice ; Protons ; Taste Buds/cytology/*enzymology/physiology ; *Taste Perception
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  • 37
    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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  • 38
    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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  • 39
    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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  • 40
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-05-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wijnen, Herman -- R01 GM078339/GM/NIGMS NIH HHS/ -- R01 GM078339-03/GM/NIGMS NIH HHS/ -- R01 GM78839/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 May 1;324(5927):598-9. doi: 10.1126/science.1174132.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of Virginia, Charlottesville, VA 22904, USA. hw9u@virginai.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19407188" target="_blank"〉PubMed〈/a〉
    Keywords: ARNTL Transcription Factors ; Acetylation ; Acrylamides/pharmacology ; Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism ; *Biological Clocks ; CLOCK Proteins ; *Circadian Rhythm ; Cytokines/antagonists & inhibitors/genetics/*metabolism ; *Feedback, Physiological ; Gene Expression Regulation ; Mice ; Mutation ; NAD/*metabolism ; Nicotinamide Phosphoribosyltransferase/antagonists & ; inhibitors/genetics/*metabolism ; Piperidines/pharmacology ; Sirtuin 1 ; Sirtuins/*metabolism ; Trans-Activators/genetics/metabolism ; Transcription Factors/genetics/metabolism ; Transcription, Genetic
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  • 41
    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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  • 42
    Publication Date: 2009-12-08
    Description: Two critical stages of mammalian oocyte regulation are prophase I arrest, which is important for sustaining the oocyte pool, and the progression through meiosis I (MI) to produce fertilizable eggs. We have found that the spindle assembly checkpoint protein BubR1 regulates both stages in mouse oocytes. We show that oocytes depleted of BubR1 cannot sustain prophase I arrest and readily undergo germinal vesicle breakdown, a marker for reentry into MI. BubR1-depleted oocytes then arrest before completing MI, marked by failure of polar body extrusion. Both meiotic defects in BubR1-depleted oocytes are due to reduced activity of the master regulator known as the anaphase-promoting complex (APC), brought about through diminished levels of the APC coactivator Cdh1.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3428834/" 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/PMC3428834/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Homer, Hayden -- Gui, Liming -- Carroll, John -- 082587/Wellcome Trust/United Kingdom -- 082587/Z/07/Z/Wellcome Trust/United Kingdom -- G0400530/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2009 Nov 13;326(5955):991-4. doi: 10.1126/science.1175326.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Oocyte and Embryo Research Laboratory, Department of Cell and Developmental Biology, Division of Biosciences and Institute for Women's Health, University College London, London, UK. h.homer@ucl.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965510" target="_blank"〉PubMed〈/a〉
    Keywords: Anaphase-Promoting Complex-Cyclosome ; Animals ; Carrier Proteins/metabolism ; Cdc20 Proteins ; Cdh1 Proteins ; Cell Cycle Proteins/metabolism ; Cyclin B1/metabolism ; Female ; Gene Silencing ; Meiosis/*physiology ; Meiotic Prophase I/*physiology ; Mice ; Oocytes/*physiology ; Prometaphase/*physiology/*radiation effects ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; Securin ; Ubiquitin-Protein Ligase Complexes/metabolism
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  • 43
    Publication Date: 2009-03-07
    Description: Patten recognition receptors, which recognize pathogens or components of injured cells (danger), trigger activation of the innate immune system. Whether and how the host distinguishes between danger- versus pathogen-associated molecular patterns remains unresolved. We report that CD24-deficient mice exhibit increased susceptibility to danger- but not pathogen-associated molecular patterns. CD24 associates with high mobility group box 1, heat shock protein 70, and heat shock protein 90; negatively regulates their stimulatory activity; and inhibits nuclear factor kappaB (NF-kappaB) activation. This occurs at least in part through CD24 association with Siglec-10 in humans or Siglec-G in mice. Our results reveal that the CD24-Siglec G pathway protects the host against a lethal response to pathological cell death and discriminates danger- versus pathogen-associated molecular patterns.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2765686/" 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/PMC2765686/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Guo-Yun -- Tang, Jie -- Zheng, Pan -- Liu, Yang -- AI064350/AI/NIAID NIH HHS/ -- CA112001/CA/NCI NIH HHS/ -- CA58033/CA/NCI NIH HHS/ -- R01 AI064350/AI/NIAID NIH HHS/ -- R01 AI064350-04/AI/NIAID NIH HHS/ -- R01 CA058033/CA/NCI NIH HHS/ -- R01 CA058033-16A2/CA/NCI NIH HHS/ -- R01 CA112001/CA/NCI NIH HHS/ -- R01 CA112001-02/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Mar 27;323(5922):1722-5. doi: 10.1126/science.1168988. Epub 2009 Mar 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Immunotherapy, Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19264983" target="_blank"〉PubMed〈/a〉
    Keywords: Acetaminophen/toxicity ; Animals ; Antigens, CD24/genetics/*metabolism ; Cytokines/metabolism ; Dendritic Cells/immunology ; HMGB1 Protein/chemistry/immunology/*metabolism ; HSP70 Heat-Shock Proteins/metabolism ; HSP90 Heat-Shock Proteins/metabolism ; Humans ; *Immunity, Innate ; Immunoprecipitation ; Inflammation/*immunology ; Lectins/*metabolism ; Lipopolysaccharides/toxicity ; Liver/immunology/pathology ; Mice ; Mutant Proteins/chemistry/metabolism ; Necrosis/chemically induced/immunology ; Protein Structure, Tertiary ; Protein Tyrosine Phosphatase, Non-Receptor Type 6/metabolism ; Receptors, Antigen, B-Cell/*metabolism ; Receptors, Cell Surface/metabolism ; Receptors, Pattern Recognition/immunology/metabolism ; Signal Transduction ; Transcription Factor RelA/metabolism
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  • 44
    Publication Date: 2009-03-03
    Description: Amyotrophic lateral sclerosis (ALS) is a fatal degenerative motor neuron disorder. Ten percent of cases are inherited; most involve unidentified genes. We report here 13 mutations in the fused in sarcoma/translated in liposarcoma (FUS/TLS) gene on chromosome 16 that were specific for familial ALS. The FUS/TLS protein binds to RNA, functions in diverse processes, and is normally located predominantly in the nucleus. In contrast, the mutant forms of FUS/TLS accumulated in the cytoplasm of neurons, a pathology that is similar to that of the gene TAR DNA-binding protein 43 (TDP43), whose mutations also cause ALS. Neuronal cytoplasmic protein aggregation and defective RNA metabolism thus appear to be common pathogenic mechanisms involved in ALS and possibly in other neurodegenerative disorders.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kwiatkowski, T J Jr -- Bosco, D A -- Leclerc, A L -- Tamrazian, E -- Vanderburg, C R -- Russ, C -- Davis, A -- Gilchrist, J -- Kasarskis, E J -- Munsat, T -- Valdmanis, P -- Rouleau, G A -- Hosler, B A -- Cortelli, P -- de Jong, P J -- Yoshinaga, Y -- Haines, J L -- Pericak-Vance, M A -- Yan, J -- Ticozzi, N -- Siddique, T -- McKenna-Yasek, D -- Sapp, P C -- Horvitz, H R -- Landers, J E -- Brown, R H Jr -- New York, N.Y. -- Science. 2009 Feb 27;323(5918):1205-8. doi: 10.1126/science.1166066.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, USA. tkwiatkowski@partners.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19251627" target="_blank"〉PubMed〈/a〉
    Keywords: Age of Onset ; Amino Acid Substitution ; Amyotrophic Lateral Sclerosis/*genetics/metabolism/pathology ; Animals ; Brain/pathology ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Chromosomes, Human, Pair 16/*genetics ; Cytoplasm/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Exons ; Female ; Humans ; Male ; Mice ; Motor Neurons/chemistry/metabolism/ultrastructure ; Mutant Proteins/chemistry/genetics/metabolism ; *Mutation, Missense ; Neurons/metabolism/ultrastructure ; RNA/metabolism ; RNA-Binding Protein FUS/chemistry/*genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Sequence Analysis, DNA ; Spinal Cord/pathology
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  • 45
    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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  • 46
    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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  • 47
    Publication Date: 2009-05-16
    Description: Understanding the factors that regulate the induction, quality, and longevity of antiviral T cell responses is essential for devising rational strategies to prevent or combat infections. In this study, we show that interleukin-21 (IL-21), likely produced by CD4+ T cells, directly influences the generation of polyfunctional CD8+ T cells and that the number of CD4+ T cells that produce IL-21 differs markedly between acute and chronic infections. IL-21 regulates the development of CD8+ T cell exhaustion and the ability to contain chronic lymphocytic choriomeningitis virus infection. Thus, IL-21 serves as a critical helper factor that shapes the functional quality of antiviral CD8+ T cells and is required for viral control.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2736049/" 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/PMC2736049/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yi, John S -- Du, Ming -- Zajac, Allan J -- AI049360/AI/NIAID NIH HHS/ -- AI067993/AI/NIAID NIH HHS/ -- R01 AI049360/AI/NIAID NIH HHS/ -- R01 AI049360-08/AI/NIAID NIH HHS/ -- R01 AI067993/AI/NIAID NIH HHS/ -- R01 AI067993-03/AI/NIAID NIH HHS/ -- T32 AI007051/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2009 Jun 19;324(5934):1572-6. doi: 10.1126/science.1175194. Epub 2009 May 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294-2170, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19443735" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CD4-Positive T-Lymphocytes/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; Chronic Disease ; Interleukins/*immunology ; Lymphocytic Choriomeningitis/*immunology ; Lymphocytic choriomeningitis virus ; Mice ; Mice, Inbred C57BL ; Viral Load
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  • 48
    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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  • 49
    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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  • 50
    Publication Date: 2009-08-08
    Description: Tumor progression is driven by genetic mutations, but little is known about the environmental conditions that select for these mutations. Studying the transcriptomes of paired colorectal cancer cell lines that differed only in the mutational status of their KRAS or BRAF genes, we found that GLUT1, encoding glucose transporter-1, was one of three genes consistently up-regulated in cells with KRAS or BRAF mutations. The mutant cells exhibited enhanced glucose uptake and glycolysis and survived in low-glucose conditions, phenotypes that all required GLUT1 expression. In contrast, when cells with wild-type KRAS alleles were subjected to a low-glucose environment, very few cells survived. Most surviving cells expressed high levels of GLUT1, and 4% of these survivors had acquired KRAS mutations not present in their parents. The glycolysis inhibitor 3-bromopyruvate preferentially suppressed the growth of cells with KRAS or BRAF mutations. Together, these data suggest that glucose deprivation can drive the acquisition of KRAS pathway mutations in human tumors.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2820374/" 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/PMC2820374/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yun, Jihye -- Rago, Carlo -- Cheong, Ian -- Pagliarini, Ray -- Angenendt, Philipp -- Rajagopalan, Harith -- Schmidt, Kerstin -- Willson, James K V -- Markowitz, Sandy -- Zhou, Shibin -- Diaz, Luis A Jr -- Velculescu, Victor E -- Lengauer, Christoph -- Kinzler, Kenneth W -- Vogelstein, Bert -- Papadopoulos, Nickolas -- CA43460/CA/NCI NIH HHS/ -- CA62924/CA/NCI NIH HHS/ -- R37 CA043460/CA/NCI NIH HHS/ -- R37 CA043460-27/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Sep 18;325(5947):1555-9. doi: 10.1126/science.1174229. Epub 2009 Aug 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19661383" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line, Tumor ; Cell Proliferation ; Colorectal Neoplasms/*genetics/metabolism ; Gene Expression Regulation, Neoplastic ; Gene Targeting ; *Genes, ras ; Glucose/*metabolism ; Glucose Transporter Type 1/genetics/metabolism ; Glycolysis/drug effects ; Humans ; Lactic Acid/metabolism ; Mice ; Mice, Nude ; *Mutation ; Neoplasm Transplantation ; Oligonucleotide Array Sequence Analysis ; Proto-Oncogene Proteins B-raf/*genetics ; Pyruvates/pharmacology ; Transplantation, Heterologous
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  • 51
    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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  • 52
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-06-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johnson, Lisa D S -- Jameson, Stephen C -- New York, N.Y. -- Science. 2009 Jun 19;324(5934):1525-6. doi: 10.1126/science.1176487.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19541985" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CD4-Positive T-Lymphocytes/*immunology ; Chronic Disease ; Interleukins/*immunology ; Mice ; Virus Diseases/*immunology
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  • 53
    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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  • 54
    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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  • 55
    Publication Date: 2009-11-07
    Description: Virtually all of the 560 human proteases are stored as inactive proenyzmes and are strictly regulated. We report the identification and characterization of the first small molecules that directly activate proenzymes, the apoptotic procaspases-3 and -6. It is surprising that these compounds induce autoproteolytic activation by stabilizing a conformation that is both more active and more susceptible to intermolecular proteolysis. These procaspase activators bypass the normal upstream proapoptotic signaling cascades and induce rapid apoptosis in a variety of cell lines. Systematic biochemical and biophysical analyses identified a cluster of mutations in procaspase-3 that resist small-molecule activation both in vitro and in cells. Compounds that induce gain of function are rare, and the activators reported here will enable direct control of the executioner caspases in apoptosis and in cellular differentiation. More generally, these studies presage the discovery of other proenzyme activators to explore fundamental processes of proenzyme activation and their fate-determining roles in biology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2886848/" 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/PMC2886848/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wolan, Dennis W -- Zorn, Julie A -- Gray, Daniel C -- Wells, James A -- F32 CA119641/CA/NCI NIH HHS/ -- F32 CA119641-03/CA/NCI NIH HHS/ -- R01 CA136779/CA/NCI NIH HHS/ -- R21 N5057022/PHS HHS/ -- New York, N.Y. -- Science. 2009 Nov 6;326(5954):853-8. doi: 10.1126/science.1177585.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmaceutical Chemistry, University of California, San Francisco, Byers Hall, 1700 4th Street, San Francisco, CA 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19892984" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Benzopyrans/chemistry/*metabolism/pharmacology ; Biocatalysis ; Caspase 3/chemistry/genetics/*metabolism ; Caspase 6/chemistry/genetics/*metabolism ; Caspase Inhibitors ; Catalytic Domain ; Cell Line, Transformed ; Cell Line, Tumor ; Cells, Cultured ; Enzyme Activation ; Enzyme Activators/chemistry/*metabolism/pharmacology ; Enzyme Inhibitors/metabolism/pharmacology ; Enzyme Precursors/antagonists & inhibitors/chemistry/genetics/*metabolism ; Granzymes/metabolism ; Humans ; Imidazoles/chemistry/*metabolism/pharmacology ; Kinetics ; Mice ; Molecular Structure ; Mutagenesis ; Pyridines/chemistry/*metabolism/pharmacology ; Signal Transduction ; Small Molecule Libraries/chemistry/metabolism
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  • 56
    Publication Date: 2009-07-18
    Description: Effective B cell-mediated immunity and antibody responses often require help from CD4+ T cells. It is thought that a distinct CD4+ effector T cell subset, called T follicular helper cells (T(FH)), provides this help; however, the molecular requirements for T(FH) differentiation are unknown. We found that expression of the transcription factor Bcl6 in CD4+ T cells is both necessary and sufficient for in vivo T(FH) differentiation and T cell help to B cells in mice. In contrast, the transcription factor Blimp-1, an antagonist of Bcl6, inhibits T(FH) differentiation and help, thereby preventing B cell germinal center and antibody responses. These findings demonstrate that T(FH) cells are required for proper B cell responses in vivo and that Bcl6 and Blimp-1 play central but opposing roles in T(FH) differentiation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2766560/" 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/PMC2766560/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johnston, Robert J -- Poholek, Amanda C -- DiToro, Daniel -- Yusuf, Isharat -- Eto, Danelle -- Barnett, Burton -- Dent, Alexander L -- Craft, Joe -- Crotty, Shane -- AR40072/AR/NIAMS NIH HHS/ -- AR44076/AR/NIAMS NIH HHS/ -- P30 AR053495/AR/NIAMS NIH HHS/ -- R01 063107/PHS HHS/ -- R01 072543/PHS HHS/ -- R01 AI063107/AI/NIAID NIH HHS/ -- R01 AI063107-01A1/AI/NIAID NIH HHS/ -- R01 AI072543/AI/NIAID NIH HHS/ -- R01 AI072543-01A1/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2009 Aug 21;325(5943):1006-10. doi: 10.1126/science.1175870. Epub 2009 Jul 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology (LIAI), 9420 Athena Circle, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19608860" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibody Formation ; Arenaviridae Infections/immunology ; B-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/cytology/immunology ; Cell Differentiation ; Cell Lineage ; Cytokines/metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Gene Expression Regulation ; Germinal Center/cytology/immunology ; Lymphocyte Activation ; Lymphocytic choriomeningitis virus/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; RNA, Messenger/genetics/metabolism ; Signal Transduction ; T-Lymphocyte Subsets/cytology/*immunology ; T-Lymphocytes, Helper-Inducer/cytology/*immunology ; Transcription Factors/genetics/*metabolism
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  • 57
    Publication Date: 2009-07-11
    Description: The dentate gyrus (DG) of the mammalian hippocampus is hypothesized to mediate pattern separation-the formation of distinct and orthogonal representations of mnemonic information-and also undergoes neurogenesis throughout life. How neurogenesis contributes to hippocampal function is largely unknown. Using adult mice in which hippocampal neurogenesis was ablated, we found specific impairments in spatial discrimination with two behavioral assays: (i) a spatial navigation radial arm maze task and (ii) a spatial, but non-navigable, task in the mouse touch screen. Mice with ablated neurogenesis were impaired when stimuli were presented with little spatial separation, but not when stimuli were more widely separated in space. Thus, newborn neurons may be necessary for normal pattern separation function in the DG of adult mice.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997634/" 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/PMC2997634/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clelland, C D -- Choi, M -- Romberg, C -- Clemenson, G D Jr -- Fragniere, A -- Tyers, P -- Jessberger, S -- Saksida, L M -- Barker, R A -- Gage, F H -- Bussey, T J -- NS-050217/NS/NINDS NIH HHS/ -- R01 NS050217/NS/NINDS NIH HHS/ -- R01 NS050217-05/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2009 Jul 10;325(5937):210-3. doi: 10.1126/science.1173215.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19590004" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cues ; Dentate Gyrus/cytology/*physiology ; Discrimination Learning/*physiology ; Female ; Hippocampus/cytology/*physiology ; Maze Learning ; Memory/*physiology ; Mice ; Mice, Inbred C57BL ; *Neurogenesis ; Neurons/*physiology ; Psychomotor Performance ; *Space Perception
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  • 58
    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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  • 59
    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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  • 60
    Publication Date: 2009-01-24
    Description: Models of the differentiation of memory CD8+ T cells that replicate during secondary infections differ over whether such cells had acquired effector function during primary infections. We created a transgenic mouse line that permits mapping of the fate of granzyme B (gzmB)-expressing CD8+ T cells and their progeny by indelibly marking them with enhanced yellow fluorescent protein (EYFP). Virus-specific CD8+ T cells express gzmB within the first 2 days of a primary response to infection with influenza, without impairment of continued primary clonal expansion. On secondary infection, virus-specific CD8+ T cells that became EYFP+ during a primary infection clonally expand as well as all virus-specific CD8+ T cells. Thus, CD8+ T cells that have acquired an effector phenotype during primary infection may function as memory cells with replicative function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653633/" 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/PMC2653633/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bannard, Oliver -- Kraman, Matthew -- Fearon, Douglas T -- 075289/Wellcome Trust/United Kingdom -- 082259/Wellcome Trust/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2009 Jan 23;323(5913):505-9. doi: 10.1126/science.1166831.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Immunology Unit, Department of Medicine, University of Cambridge, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19164749" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CD8-Positive T-Lymphocytes/*cytology/*immunology ; Cell Differentiation ; Cell Division ; Granzymes/genetics/metabolism ; *Immunologic Memory ; Influenza A Virus, H1N1 Subtype/immunology ; Influenza A Virus, H3N2 Subtype/immunology ; Luminescent Proteins/genetics/metabolism ; Lung/immunology ; Mice ; Mice, Transgenic ; Orthomyxoviridae Infections/*immunology ; Phenotype ; Spleen/immunology ; T-Lymphocyte Subsets/cytology/immunology
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  • 61
    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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  • 62
    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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  • 63
    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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  • 64
    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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  • 65
    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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  • 66
    Publication Date: 2009-07-11
    Description: Sensory information detected by the peripheral nervous system is represented as a topographic map in the brain. It has long been thought that the topography of the map is determined by graded positional cues that are expressed by the target. Here, we analyzed the pre-target axon sorting for olfactory map formation in mice. In olfactory sensory neurons, an axon guidance receptor, Neuropilin-1, and its repulsive ligand, Semaphorin-3A, are expressed in a complementary manner. We found that expression levels of Neuropilin-1 determined both pre-target sorting and projection sites of axons. Olfactory sensory neuron-specific knockout of Semaphorin-3A perturbed axon sorting and altered the olfactory map topography. Thus, pre-target axon sorting plays an important role in establishing the topographic order based on the relative levels of guidance molecules expressed by axons.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Imai, Takeshi -- Yamazaki, Takahiro -- Kobayakawa, Reiko -- Kobayakawa, Ko -- Abe, Takaya -- Suzuki, Misao -- Sakano, Hitoshi -- New York, N.Y. -- Science. 2009 Jul 31;325(5940):585-90. doi: 10.1126/science.1173596. Epub 2009 Jul 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Tokyo 113-0032, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19589963" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/*physiology ; Brain Mapping ; Cell Communication ; Cues ; Cyclic AMP/metabolism ; Ligands ; Mice ; Mice, Knockout ; Mice, Transgenic ; Neuroglia/physiology ; Neuropilin-1/*metabolism ; Olfactory Bulb/cytology/*physiology ; Olfactory Mucosa/cytology/physiology ; Olfactory Pathways/cytology/*physiology ; Olfactory Receptor Neurons/cytology/*physiology ; Receptors, Odorant/metabolism ; Semaphorin-3A/metabolism ; Signal Transduction
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  • 67
    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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  • 68
    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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  • 69
    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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  • 70
    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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  • 71
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-10-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaeberlein, Matt -- Kapahi, Pankaj -- R01 AG031108/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2009 Oct 2;326(5949):55-6. doi: 10.1126/science.1181034.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, University of Washington, Seattle, WA 98195, USA. kaeber@u.washington.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19797648" target="_blank"〉PubMed〈/a〉
    Keywords: AMP-Activated Protein Kinases/genetics/metabolism ; Aging/*physiology ; Animals ; Caloric Restriction ; Enzyme Activation ; Female ; Gene Expression ; Longevity/*physiology ; Male ; Mice ; Mice, Knockout ; Oligonucleotide Array Sequence Analysis ; Phosphorylation ; Protein Biosynthesis ; Protein Kinases/metabolism ; Protein Subunits ; Ribosomal Protein S6/*metabolism ; Ribosomal Protein S6 Kinases, 90-kDa/genetics/*metabolism ; *Signal Transduction ; Sirolimus/pharmacology ; TOR Serine-Threonine Kinases
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  • 72
    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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  • 73
    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
    Print ISSN: 0036-8075
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  • 74
    Publication Date: 2009-10-10
    Description: Neurons in the central nervous system (CNS) lose their ability to regenerate early in development, but the underlying mechanisms are unknown. By screening genes developmentally regulated in retinal ganglion cells (RGCs), we identified Kruppel-like factor-4 (KLF4) as a transcriptional repressor of axon growth in RGCs and other CNS neurons. RGCs lacking KLF4 showed increased axon growth both in vitro and after optic nerve injury in vivo. Related KLF family members suppressed or enhanced axon growth to differing extents, and several growth-suppressive KLFs were up-regulated postnatally, whereas growth-enhancing KLFs were down-regulated. Thus, coordinated activities of different KLFs regulate the regenerative capacity of CNS neurons.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882032/" 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/PMC2882032/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moore, Darcie L -- Blackmore, Murray G -- Hu, Ying -- Kaestner, Klaus H -- Bixby, John L -- Lemmon, Vance P -- Goldberg, Jeffrey L -- P30 EY014801/EY/NEI NIH HHS/ -- R01 NS059866/NS/NINDS NIH HHS/ -- R01 NS059866-01A2/NS/NINDS NIH HHS/ -- R01 NS061348/NS/NINDS NIH HHS/ -- R01 NS061348-01A2/NS/NINDS NIH HHS/ -- R01 NS061348-02/NS/NINDS NIH HHS/ -- R01 NS061348-03/NS/NINDS NIH HHS/ -- R01 NS061348-04/NS/NINDS NIH HHS/ -- R03 EY016790/EY/NEI NIH HHS/ -- R03 EY016790-01/EY/NEI NIH HHS/ -- R03 EY016790-02/EY/NEI NIH HHS/ -- R03 EY016790-03/EY/NEI NIH HHS/ -- T32 NS007459/NS/NINDS NIH HHS/ -- T32 NS07492/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2009 Oct 9;326(5950):298-301. doi: 10.1126/science.1175737.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19815778" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/*physiology/ultrastructure ; Cell Count ; Cell Survival ; Cells, Cultured ; Down-Regulation ; Gene Knockout Techniques ; Growth Cones/physiology ; Hippocampus/cytology/physiology ; Kruppel-Like Transcription Factors/genetics/*physiology ; Mice ; Nerve Crush ; Nerve Regeneration ; Neurites/physiology ; Neurons/*physiology ; Optic Nerve Injuries/physiopathology ; Rats ; Retinal Ganglion Cells/cytology/*physiology ; Transcription, Genetic ; Transfection ; Up-Regulation
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  • 75
    Publication Date: 2009-03-03
    Description: Mammals have single-rowed dentitions, whereas many nonmammalian vertebrates have teeth in multiple rows. Neither the molecular mechanism regulating iterative tooth initiation nor that restricting mammalian tooth development in one row is known. We found that mice lacking the transcription factor odd-skipped related-2 (Osr2) develop supernumerary teeth lingual to their molars because of expansion of the odontogenic field. Osr2 was expressed in a lingual-to-buccal gradient and restricted expression of bone morphogenetic protein 4 (Bmp4), an essential odontogenic signal, in the developing tooth mesenchyme. Expansion of odontogenic field in Osr2-deficient mice required Msx1, a feedback activator of Bmp4 expression. These findings suggest that the Bmp4-Msx1 pathway propagates mesenchymal activation for sequential tooth induction and that spatial modulation of this pathway provides a mechanism for patterning vertebrate dentition.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2650836/" 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/PMC2650836/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Zunyi -- Lan, Yu -- Chai, Yang -- Jiang, Rulang -- R01 DE013681/DE/NIDCR NIH HHS/ -- R01 DE013681-06/DE/NIDCR NIH HHS/ -- R01 DE013681-07/DE/NIDCR NIH HHS/ -- R01 DE013681-08/DE/NIDCR NIH HHS/ -- R01 DE013681-09/DE/NIDCR NIH HHS/ -- R01DE013681/DE/NIDCR NIH HHS/ -- T32DE007202/DE/NIDCR NIH HHS/ -- New York, N.Y. -- Science. 2009 Feb 27;323(5918):1232-4. doi: 10.1126/science.1167418.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Oral Biology and Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY 14642, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19251632" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Morphogenetic Protein 4/metabolism ; Dentition ; Epithelium/embryology/metabolism ; Gene Expression ; Gene Expression Profiling ; MSX1 Transcription Factor/genetics/*metabolism ; Mesoderm/embryology/metabolism ; Mice ; Molar/embryology ; Morphogenesis ; Mutation ; *Odontogenesis ; Tooth Germ/embryology/metabolism ; Tooth, Supernumerary/*embryology ; Transcription Factors/genetics/*metabolism
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  • 76
    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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  • 77
    Publication Date: 2009-08-08
    Description: Itch and pain are two distinct sensations. Although our previous study suggested that gastrin-releasing peptide receptor (GRPR) is an itch-specific gene in the spinal cord, a long-standing question of whether there are separate neuronal pathways for itch and pain remains unsettled. We selectively ablated lamina I neurons expressing GRPR in the spinal cord of mice. These mice showed profound scratching deficits in response to all of the itching (pruritogenic) stimuli tested, irrespective of their histamine dependence. In contrast, pain behaviors were unaffected. Our data also suggest that GRPR+ neurons are different from the spinothalamic tract neurons that have been the focus of the debate. Together, the present study suggests that GRPR+ neurons constitute a long-sought labeled line for itch sensation in the spinal cord.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2786498/" 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/PMC2786498/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sun, Yan-Gang -- Zhao, Zhong-Qiu -- Meng, Xiu-Li -- Yin, Jun -- Liu, Xian-Yu -- Chen, Zhou-Feng -- P01 NS049048-23/NS/NINDS NIH HHS/ -- P30 NS057105/NS/NINDS NIH HHS/ -- P30 NS057105-04/NS/NINDS NIH HHS/ -- R01 AR056318/AR/NIAMS NIH HHS/ -- R01 AR056318-01A1/AR/NIAMS NIH HHS/ -- R01 NS046036/NS/NINDS NIH HHS/ -- R01 NS046036-05/NS/NINDS NIH HHS/ -- UL1 RR024992/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2009 Sep 18;325(5947):1531-4. doi: 10.1126/science.1174868. Epub 2009 Aug 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Anesthesiology, Psychiatry, and Developmental Biology, Washington University School of Medicine Pain Center, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19661382" target="_blank"〉PubMed〈/a〉
    Keywords: Afferent Pathways/physiology ; Animals ; Behavior, Animal ; Bombesin/pharmacology ; Chronic Disease ; Histamine ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Neurons/*physiology ; Pain/physiopathology ; Pruritus/*physiopathology ; Receptors, Bombesin/genetics/*metabolism ; Ribosome Inactivating Proteins, Type 1/pharmacology ; Sensation/physiology ; Spinal Cord/*cytology ; Spinothalamic Tracts/cytology/physiology
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  • 78
    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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  • 79
    Publication Date: 2009-08-01
    Description: A current paradigm states that monocytes circulate freely and patrol blood vessels but differentiate irreversibly into dendritic cells (DCs) or macrophages upon tissue entry. Here we show that bona fide undifferentiated monocytes reside in the spleen and outnumber their equivalents in circulation. The reservoir monocytes assemble in clusters in the cords of the subcapsular red pulp and are distinct from macrophages and DCs. In response to ischemic myocardial injury, splenic monocytes increase their motility, exit the spleen en masse, accumulate in injured tissue, and participate in wound healing. These observations uncover a role for the spleen as a site for storage and rapid deployment of monocytes and identify splenic monocytes as a resource that the body exploits to regulate inflammation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2803111/" 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/PMC2803111/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Swirski, Filip K -- Nahrendorf, Matthias -- Etzrodt, Martin -- Wildgruber, Moritz -- Cortez-Retamozo, Virna -- Panizzi, Peter -- Figueiredo, Jose-Luiz -- Kohler, Rainer H -- Chudnovskiy, Aleksey -- Waterman, Peter -- Aikawa, Elena -- Mempel, Thorsten R -- Libby, Peter -- Weissleder, Ralph -- Pittet, Mikael J -- 1R01HL095612/HL/NHLBI NIH HHS/ -- P01 A154904/PHS HHS/ -- P01 AI054904/AI/NIAID NIH HHS/ -- P01 AI054904-010001/AI/NIAID NIH HHS/ -- P50 CA086355/CA/NCI NIH HHS/ -- P50 CA086355-07/CA/NCI NIH HHS/ -- P50 CA86355/CA/NCI NIH HHS/ -- R00 HL094533/HL/NHLBI NIH HHS/ -- R01 HL095629/HL/NHLBI NIH HHS/ -- R01 HL096576/HL/NHLBI NIH HHS/ -- R24 CA69246/CA/NCI NIH HHS/ -- U01 HL080731/HL/NHLBI NIH HHS/ -- U01 HL080731-05/HL/NHLBI NIH HHS/ -- U54 CA126515/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Jul 31;325(5940):612-6. doi: 10.1126/science.1175202.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. fswirski@mgh.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19644120" target="_blank"〉PubMed〈/a〉
    Keywords: Angiotensin II/blood/pharmacology ; Animals ; Antigens, Ly/metabolism ; Bone Marrow Cells/physiology ; Cell Differentiation ; Cell Movement ; Cell Size ; Female ; Inflammation/*pathology ; Mice ; Mice, Inbred C57BL ; Monocytes/cytology/*physiology ; Myocardial Infarction/immunology/*pathology/*physiopathology ; Myocardium/*immunology/*pathology ; Rats ; Rats, Wistar ; Receptors, Angiotensin/metabolism ; Spleen/cytology/*immunology ; Splenectomy
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  • 80
    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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  • 81
    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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  • 82
    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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  • 83
    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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  • 84
    Publication Date: 2009-03-28
    Description: In the early stages of viral infection, outcomes depend on a race between expansion of infection and the immune response generated to contain it. We combined in situ tetramer staining with in situ hybridization to visualize, map, and quantify relationships between immune effector cells and their targets in tissues. In simian immunodeficiency virus infections in macaques and lymphocytic choriomeningitis virus infections in mice, the magnitude and timing of the establishment of an excess of effector cells versus targets were found to correlate with the extent of control and the infection outcome (i.e., control and clearance versus partial or poor control and persistent infection). This method highlights the importance of the location, timing, and magnitude of the immune response needed for a vaccine to be effective against agents of persistent infection, such as HIV-1.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2753492/" 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/PMC2753492/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Qingsheng -- Skinner, Pamela J -- Ha, Sang-Jun -- Duan, Lijie -- Mattila, Teresa L -- Hage, Aaron -- White, Cara -- Barber, Daniel L -- O'Mara, Leigh -- Southern, Peter J -- Reilly, Cavan S -- Carlis, John V -- Miller, Christopher J -- Ahmed, Rafi -- Haase, Ashley T -- AI066314/AI/NIAID NIH HHS/ -- AI20048/AI/NIAID NIH HHS/ -- AI48484/AI/NIAID NIH HHS/ -- P01 AI066314/AI/NIAID NIH HHS/ -- P01 AI066314-010003/AI/NIAID NIH HHS/ -- P01 AI066314-020003/AI/NIAID NIH HHS/ -- P01 AI066314-030003/AI/NIAID NIH HHS/ -- P01 AI066314-040003/AI/NIAID NIH HHS/ -- P51 RR000169/RR/NCRR NIH HHS/ -- P51 RR000169-430198/RR/NCRR NIH HHS/ -- R01 AI048484/AI/NIAID NIH HHS/ -- R01 AI048484-01/AI/NIAID NIH HHS/ -- R01 AI048484-02/AI/NIAID NIH HHS/ -- R01 AI048484-03/AI/NIAID NIH HHS/ -- R01 AI048484-04/AI/NIAID NIH HHS/ -- RR00169/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2009 Mar 27;323(5922):1726-9. doi: 10.1126/science.1168676.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, Medical School, University of Minnesota, Minneapolis, MN 55455, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19325114" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arenaviridae Infections/*immunology/virology ; Cell Count ; Cervix Uteri/immunology/virology ; Female ; In Situ Hybridization ; Lymph Nodes/immunology/virology ; Lymphocytic choriomeningitis virus/*immunology ; Lymphoid Tissue/immunology/virology ; Macaca mulatta ; Mice ; RNA, Viral/analysis ; Simian Acquired Immunodeficiency Syndrome/*immunology/virology ; Simian Immunodeficiency Virus/*immunology/physiology ; Spleen/immunology/virology ; Staining and Labeling ; T-Lymphocytes, Cytotoxic/*immunology ; Time Factors ; Vagina/immunology/virology ; Virus Replication
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  • 85
    Publication Date: 2009-01-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lipton, Stuart A -- Li, Hao -- Zaremba, Jeffrey D -- McKercher, Scott R -- Cui, Jiankun -- Kang, Yeon-Joo -- Nie, Zhiguo -- Soussou, Walid -- Talantova, Maria -- Okamoto, Shu-Ichi -- Nakanishi, Nobuki -- New York, N.Y. -- Science. 2009 Jan 9;323(5911):208. doi: 10.1126/science.323.5911.208b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19131610" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autistic Disorder/*genetics/*physiopathology ; Embryonic Stem Cells/physiology ; Gene Knockout Techniques ; MEF2 Transcription Factors ; Mice ; Mice, Knockout ; Myogenic Regulatory Factors/*genetics/*physiology ; *Neurogenesis ; Neurons/cytology/*physiology ; Phenotype ; Rett Syndrome/genetics/physiopathology ; Synapses/physiology
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  • 86
    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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  • 87
    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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  • 88
    Publication Date: 2009-09-26
    Description: Amyloid-beta (Abeta) accumulation in the brain extracellular space is a hallmark of Alzheimer's disease. The factors regulating this process are only partly understood. Abeta aggregation is a concentration-dependent process that is likely responsive to changes in brain interstitial fluid (ISF) levels of Abeta. Using in vivo microdialysis in mice, we found that the amount of ISF Abeta correlated with wakefulness. The amount of ISF Abeta also significantly increased during acute sleep deprivation and during orexin infusion, but decreased with infusion of a dual orexin receptor antagonist. Chronic sleep restriction significantly increased, and a dual orexin receptor antagonist decreased, Abeta plaque formation in amyloid precursor protein transgenic mice. Thus, the sleep-wake cycle and orexin may play a role in the pathogenesis of Alzheimer's disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2789838/" 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/PMC2789838/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kang, Jae-Eun -- Lim, Miranda M -- Bateman, Randall J -- Lee, James J -- Smyth, Liam P -- Cirrito, John R -- Fujiki, Nobuhiro -- Nishino, Seiji -- Holtzman, David M -- AG025824/AG/NIA NIH HHS/ -- AG029524/AG/NIA NIH HHS/ -- AG030946/AG/NIA NIH HHS/ -- K01 AG029524/AG/NIA NIH HHS/ -- K01 AG029524-03/AG/NIA NIH HHS/ -- K23 AG030946/AG/NIA NIH HHS/ -- K23 AG030946-03/AG/NIA NIH HHS/ -- MH072525/MH/NIMH NIH HHS/ -- NS065667/NS/NINDS NIH HHS/ -- P30 DK056341/DK/NIDDK NIH HHS/ -- P30 DK056341-09/DK/NIDDK NIH HHS/ -- P30 NS057105/NS/NINDS NIH HHS/ -- P30 NS057105-04/NS/NINDS NIH HHS/ -- P50 AG005681/AG/NIA NIH HHS/ -- R01 AG025824/AG/NIA NIH HHS/ -- R01 AG025824-03/AG/NIA NIH HHS/ -- R01 MH072525/MH/NIMH NIH HHS/ -- R01 MH072525-04/MH/NIMH NIH HHS/ -- R01 NS065667/NS/NINDS NIH HHS/ -- R01 NS065667-02/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2009 Nov 13;326(5955):1005-7. doi: 10.1126/science.1180962. Epub 2009 Sep 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, Washington University, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19779148" target="_blank"〉PubMed〈/a〉
    Keywords: Acetamides/pharmacology ; Alzheimer Disease/metabolism/*physiopathology ; Amyloid beta-Peptides/cerebrospinal fluid/*metabolism ; Animals ; Antigens, Surface/metabolism ; Circadian Rhythm ; Disease Models, Animal ; Extracellular Fluid/*metabolism ; Female ; Hippocampus/*metabolism ; Humans ; Intracellular Signaling Peptides and Proteins/administration & dosage/*metabolism ; Isoquinolines/pharmacology ; Light ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neuropeptides/administration & dosage/*metabolism ; Orexin Receptors ; Orexins ; Receptors, Cell Surface/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Receptors, Neuropeptide/metabolism ; Signal Transduction ; *Sleep ; Sleep Deprivation ; *Wakefulness
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  • 89
    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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  • 90
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-03-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bianchi, Marco E -- Manfredi, Angelo A -- New York, N.Y. -- Science. 2009 Mar 27;323(5922):1683-4. doi: 10.1126/science.1172794.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉San Raffaele University, Faculty of Medicine, and San Raffaele Scientific Institute, via Olgettina 58, 20132 Milano, Italy. bianchi.marco@hsr.it〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19325105" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD24/immunology/metabolism ; Autoimmunity ; HMGB1 Protein/metabolism ; Immunity ; *Immunity, Innate ; Infection/*immunology ; Inflammation/*immunology ; Lectins/immunology/metabolism ; Liver/*immunology/pathology ; Mice ; Necrosis/chemically induced/immunology ; Receptors, Antigen, B-Cell/immunology/metabolism ; Receptors, Pattern Recognition/immunology/metabolism ; Signal Transduction ; Wounds and Injuries/*immunology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 91
    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
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  • 92
    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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  • 93
    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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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 94
    Publication Date: 2009-07-11
    Description: The turtle shell offers a fascinating case study of vertebrate evolution, based on the modification of a common body plan. The carapace is formed from ribs, which encapsulate the scapula; this stands in contrast to the typical amniote body plan and serves as a key to understanding turtle evolution. Comparative analyses of musculoskeletal development between the Chinese soft-shelled turtle and other amniotes revealed that initial turtle development conforms to the amniote pattern; however, during embryogenesis, lateral rib growth results in a shift of elements. In addition, some limb muscles establish new turtle-specific attachments associated with carapace formation. We propose that the evolutionary origin of the turtle body plan results from heterotopy based on folding and novel connectivities.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nagashima, Hiroshi -- Sugahara, Fumiaki -- Takechi, Masaki -- Ericsson, Rolf -- Kawashima-Ohya, Yoshie -- Narita, Yuichi -- Kuratani, Shigeru -- New York, N.Y. -- Science. 2009 Jul 10;325(5937):193-6. doi: 10.1126/science.1173826.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Evolutionary Morphology, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minami, Kobe 650-0047, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19590000" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Body Patterning ; Chick Embryo ; Embryo, Nonmammalian/anatomy & histology ; Embryonic Development ; Mice ; Muscle Development ; Muscle, Skeletal/anatomy & histology/*embryology ; Musculoskeletal Development ; Ribs/anatomy & histology/*embryology ; Scapula/anatomy & histology/*embryology ; Turtles/*anatomy & histology/*embryology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 95
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-06-27
    Description: The investigation and study of cancer stem cells (CSCs) have received enormous attention over the past 5 to 10 years but remain topics of considerable controversy. Opinions about the validity of the CSC hypothesis, the biological properties of CSCs, and the relevance of CSCs to cancer therapy differ widely. In the following commentary, we discuss the nature of the debate, the parameters by which CSCs can or cannot be defined, and the identification of new potential therapeutic targets elucidated by considering cancer as a problem in stem cell biology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2873047/" 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/PMC2873047/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rosen, Jeffrey M -- Jordan, Craig T -- R01 CA122206/CA/NCI NIH HHS/ -- R01 CA122206-02/CA/NCI NIH HHS/ -- R01-CA122206/CA/NCI NIH HHS/ -- R37 CA016303/CA/NCI NIH HHS/ -- R37 CA016303-36/CA/NCI NIH HHS/ -- R37-CA16303/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Jun 26;324(5935):1670-3. doi: 10.1126/science.1171837.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19556499" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Humans ; Mice ; Models, Biological ; Neoplasm Transplantation ; Neoplasms/genetics/metabolism/*pathology/therapy ; Neoplastic Stem Cells/cytology/*physiology ; Transcription, Genetic
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  • 96
    Publication Date: 2009-03-17
    Description: Dendritic cells (DCs) in lymphoid tissue arise from precursors that also produce monocytes and plasmacytoid DCs (pDCs). Where DC and monocyte lineage commitment occurs and the nature of the DC precursor that migrates from the bone marrow to peripheral lymphoid organs are unknown. We show that DC development progresses from the macrophage and DC precursor to common DC precursors that give rise to pDCs and classical spleen DCs (cDCs), but not monocytes, and finally to committed precursors of cDCs (pre-cDCs). Pre-cDCs enter lymph nodes through and migrate along high endothelial venules and later disperse and integrate into the DC network. Further cDC development involves cell division, which is controlled in part by regulatory T cells and fms-like tyrosine kinase receptor-3.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2803315/" 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/PMC2803315/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Kang -- Victora, Gabriel D -- Schwickert, Tanja A -- Guermonprez, Pierre -- Meredith, Matthew M -- Yao, Kaihui -- Chu, Fei-Fan -- Randolph, Gwendalyn J -- Rudensky, Alexander Y -- Nussenzweig, Michel -- P01 AI051573/AI/NIAID NIH HHS/ -- P01 AI051573-010004/AI/NIAID NIH HHS/ -- P01 AI051573-020004/AI/NIAID NIH HHS/ -- P01 AI051573-030004/AI/NIAID NIH HHS/ -- P01 AI051573-040004/AI/NIAID NIH HHS/ -- P01 AI051573-050004/AI/NIAID NIH HHS/ -- P01 AI051573-060004/AI/NIAID NIH HHS/ -- P01 AI051573-069005/AI/NIAID NIH HHS/ -- P01 AI051573-070004/AI/NIAID NIH HHS/ -- P01 AI051573-079005/AI/NIAID NIH HHS/ -- P01 AI051573-080004/AI/NIAID NIH HHS/ -- P01 AI051573-089005/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Apr 17;324(5925):392-7. doi: 10.1126/science.1170540. Epub 2009 Mar 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10065, USA. liuk@rockefeller.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19286519" target="_blank"〉PubMed〈/a〉
    Keywords: Adoptive Transfer ; Animals ; Blood Vessels/cytology ; Bone Marrow Cells/cytology ; Cell Differentiation ; Cell Division ; Cell Lineage ; Cell Movement ; Cell Shape ; Dendritic Cells/*cytology/immunology/physiology ; Homeostasis ; Lymph Nodes/blood supply/cytology/immunology ; Lymphoid Tissue/blood supply/*cytology/immunology ; Macrophages/cytology ; Mice ; Monocytes/*cytology ; Myeloid Progenitor Cells/*cytology/physiology ; Parabiosis ; Signal Transduction ; Spleen/cytology/immunology ; T-Lymphocytes, Regulatory/physiology ; Venules/cytology ; fms-Like Tyrosine Kinase 3/genetics/metabolism
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  • 97
    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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  • 98
    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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  • 99
    Publication Date: 2009-09-05
    Description: In adult animals, fear conditioning induces a permanent memory that is resilient to erasure by extinction. In contrast, during early postnatal development, extinction of conditioned fear leads to memory erasure, suggesting that fear memories are actively protected in adults. We show here that this protection is conferred by extracellular matrix chondroitin sulfate proteoglycans (CSPGs) in the amygdala. The organization of CSPGs into perineuronal nets (PNNs) coincided with the developmental switch in fear memory resilience. In adults, degradation of PNNs by chondroitinase ABC specifically rendered subsequently acquired fear memories susceptible to erasure. This result indicates that intact PNNs mediate the formation of erasure-resistant fear memories and identifies a molecular mechanism closing a postnatal critical period during which traumatic memories can be erased by extinction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gogolla, Nadine -- Caroni, Pico -- Luthi, Andreas -- Herry, Cyril -- New York, N.Y. -- Science. 2009 Sep 4;325(5945):1258-61. doi: 10.1126/science.1174146.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19729657" target="_blank"〉PubMed〈/a〉
    Keywords: Amygdala/cytology/growth & development/*physiology ; Animals ; Chondroitin ABC Lyase/metabolism ; Chondroitin Sulfate Proteoglycans/metabolism/*physiology ; Conditioning, Classical ; Cues ; *Extinction, Psychological ; Extracellular Matrix/physiology ; *Fear ; Learning ; Male ; Memory/*physiology ; Mice ; Mice, Inbred C57BL ; Neuronal Plasticity
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  • 100
    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
    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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