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  • American Association for the Advancement of Science (AAAS)  (20)
  • American Chemical Society
  • Springer
  • 2010-2014  (20)
  • 1980-1984
  • 2010  (20)
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  • 2010-2014  (20)
  • 1980-1984
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  • 1
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    The genetic landscape of the childhood cancer medulloblastoma (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-12-18
    Description: Medulloblastoma (MB) is the most common malignant brain tumor of children. To identify the genetic alterations in this tumor type, we searched for copy number alterations using high-density microarrays and sequenced all known protein-coding genes and microRNA genes using Sanger sequencing in a set of 22 MBs. We found that, on average, each tumor had 11 gene alterations, fewer by a factor of 5 to 10 than in the adult solid tumors that have been sequenced to date. In addition to alterations in the Hedgehog and Wnt pathways, our analysis led to the discovery of genes not previously known to be altered in MBs. Most notably, inactivating mutations of the histone-lysine N-methyltransferase genes MLL2 or MLL3 were identified in 16% of MB patients. These results demonstrate key differences between the genetic landscapes of adult and childhood cancers, highlight dysregulation of developmental pathways as an important mechanism underlying MBs, and identify a role for a specific type of histone methylation in human tumorigenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110744/" 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/PMC3110744/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Parsons, D Williams -- Li, Meng -- Zhang, Xiaosong -- Jones, Sian -- Leary, Rebecca J -- Lin, Jimmy Cheng-Ho -- Boca, Simina M -- Carter, Hannah -- Samayoa, Josue -- Bettegowda, Chetan -- Gallia, Gary L -- Jallo, George I -- Binder, Zev A -- Nikolsky, Yuri -- Hartigan, James -- Smith, Doug R -- Gerhard, Daniela S -- Fults, Daniel W -- VandenBerg, Scott -- Berger, Mitchel S -- Marie, Suely Kazue Nagahashi -- Shinjo, Sueli Mieko Oba -- Clara, Carlos -- Phillips, Peter C -- Minturn, Jane E -- Biegel, Jaclyn A -- Judkins, Alexander R -- Resnick, Adam C -- Storm, Phillip B -- Curran, Tom -- He, Yiping -- Rasheed, B Ahmed -- Friedman, Henry S -- Keir, Stephen T -- McLendon, Roger -- Northcott, Paul A -- Taylor, Michael D -- Burger, Peter C -- Riggins, Gregory J -- Karchin, Rachel -- Parmigiani, Giovanni -- Bigner, Darell D -- Yan, Hai -- Papadopoulos, Nick -- Vogelstein, Bert -- Kinzler, Kenneth W -- Velculescu, Victor E -- CA057345/CA/NCI NIH HHS/ -- CA096832/CA/NCI NIH HHS/ -- CA118822/CA/NCI NIH HHS/ -- CA121113/CA/NCI NIH HHS/ -- CA135877/CA/NCI NIH HHS/ -- GM074906-01A1/GM/NIGMS NIH HHS/ -- HHSN261200800001E/PHS HHS/ -- P01 CA096832/CA/NCI NIH HHS/ -- P01 CA096832-03/CA/NCI NIH HHS/ -- R01 CA108622/CA/NCI NIH HHS/ -- R01 CA121113/CA/NCI NIH HHS/ -- R01 CA121113-05/CA/NCI NIH HHS/ -- R37 CA057345/CA/NCI NIH HHS/ -- R37 CA057345-20/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Jan 28;331(6016):435-9. doi: 10.1126/science.1198056. Epub 2010 Dec 16.〈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/21163964" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Cerebellar Neoplasms/*genetics/metabolism ; Child ; DNA Copy Number Variations ; DNA-Binding Proteins/genetics/metabolism ; *Genes, Neoplasm ; Genes, Tumor Suppressor ; Histone-Lysine N-Methyltransferase/genetics/metabolism ; Histones/metabolism ; Humans ; Medulloblastoma/*genetics/metabolism ; Methylation ; MicroRNAs/genetics ; *Mutation ; Neoplasm Proteins/genetics/metabolism ; Oligonucleotide Array Sequence Analysis ; Point Mutation ; Sequence Analysis, DNA ; Signal Transduction
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
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    A draft sequence of the Neandertal genome (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-05-08
    Description: Neandertals, the closest evolutionary relatives of present-day humans, lived in large parts of Europe and western Asia before disappearing 30,000 years ago. We present a draft sequence of the Neandertal genome composed of more than 4 billion nucleotides from three individuals. Comparisons of the Neandertal genome to the genomes of five present-day humans from different parts of the world identify a number of genomic regions that may have been affected by positive selection in ancestral modern humans, including genes involved in metabolism and in cognitive and skeletal development. We show that Neandertals shared more genetic variants with present-day humans in Eurasia than with present-day humans in sub-Saharan Africa, suggesting that gene flow from Neandertals into the ancestors of non-Africans occurred before the divergence of Eurasian groups from each other.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Green, Richard E -- Krause, Johannes -- Briggs, Adrian W -- Maricic, Tomislav -- Stenzel, Udo -- Kircher, Martin -- Patterson, Nick -- Li, Heng -- Zhai, Weiwei -- Fritz, Markus Hsi-Yang -- Hansen, Nancy F -- Durand, Eric Y -- Malaspinas, Anna-Sapfo -- Jensen, Jeffrey D -- Marques-Bonet, Tomas -- Alkan, Can -- Prufer, Kay -- Meyer, Matthias -- Burbano, Hernan A -- Good, Jeffrey M -- Schultz, Rigo -- Aximu-Petri, Ayinuer -- Butthof, Anne -- Hober, Barbara -- Hoffner, Barbara -- Siegemund, Madlen -- Weihmann, Antje -- Nusbaum, Chad -- Lander, Eric S -- Russ, Carsten -- Novod, Nathaniel -- Affourtit, Jason -- Egholm, Michael -- Verna, Christine -- Rudan, Pavao -- Brajkovic, Dejana -- Kucan, Zeljko -- Gusic, Ivan -- Doronichev, Vladimir B -- Golovanova, Liubov V -- Lalueza-Fox, Carles -- de la Rasilla, Marco -- Fortea, Javier -- Rosas, Antonio -- Schmitz, Ralf W -- Johnson, Philip L F -- Eichler, Evan E -- Falush, Daniel -- Birney, Ewan -- Mullikin, James C -- Slatkin, Montgomery -- Nielsen, Rasmus -- Kelso, Janet -- Lachmann, Michael -- Reich, David -- Paabo, Svante -- GM40282/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2010 May 7;328(5979):710-22. doi: 10.1126/science.1188021.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Evolutionary Genetics, Max-Planck Institute for Evolutionary Anthropology, D-04103 Leipzig, Germany. green@eva.mpg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20448178" target="_blank"〉PubMed〈/a〉
    Keywords: African Continental Ancestry Group/genetics ; Animals ; Asian Continental Ancestry Group/genetics ; Base Sequence ; Bone and Bones ; DNA, Mitochondrial/genetics ; European Continental Ancestry Group/genetics ; Evolution, Molecular ; Extinction, Biological ; Female ; *Fossils ; Gene Dosage ; Gene Flow ; Genetic Variation ; *Genome ; *Genome, Human ; Haplotypes ; Hominidae/*genetics ; Humans ; Pan troglodytes/genetics ; Polymorphism, Single Nucleotide ; Selection, Genetic ; Sequence Alignment ; *Sequence Analysis, DNA ; Time
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    Five-vertebrate ChIP-seq reveals the evolutionary dynamics of transcription factor binding (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-04-10
    Description: Transcription factors (TFs) direct gene expression by binding to DNA regulatory regions. To explore the evolution of gene regulation, we used chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) to determine experimentally the genome-wide occupancy of two TFs, CCAAT/enhancer-binding protein alpha and hepatocyte nuclear factor 4 alpha, in the livers of five vertebrates. Although each TF displays highly conserved DNA binding preferences, most binding is species-specific, and aligned binding events present in all five species are rare. Regions near genes with expression levels that are dependent on a TF are often bound by the TF in multiple species yet show no enhanced DNA sequence constraint. Binding divergence between species can be largely explained by sequence changes to the bound motifs. Among the binding events lost in one lineage, only half are recovered by another binding event within 10 kilobases. Our results reveal large interspecies differences in transcriptional regulation and provide insight into regulatory evolution.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3008766/" 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/PMC3008766/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schmidt, Dominic -- Wilson, Michael D -- Ballester, Benoit -- Schwalie, Petra C -- Brown, Gordon D -- Marshall, Aileen -- Kutter, Claudia -- Watt, Stephen -- Martinez-Jimenez, Celia P -- Mackay, Sarah -- Talianidis, Iannis -- Flicek, Paul -- Odom, Duncan T -- 062023/Wellcome Trust/United Kingdom -- 079643/Wellcome Trust/United Kingdom -- 15603/Cancer Research UK/United Kingdom -- 202218/European Research Council/International -- A15603/Cancer Research UK/United Kingdom -- WT062023/Wellcome Trust/United Kingdom -- WT079643/Wellcome Trust/United Kingdom -- Cancer Research UK/United Kingdom -- New York, N.Y. -- Science. 2010 May 21;328(5981):1036-40. doi: 10.1126/science.1186176. Epub 2010 Apr 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20378774" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Animals ; Base Sequence ; Binding Sites ; Biological Evolution ; CCAAT-Enhancer-Binding Protein-alpha/*metabolism ; Chickens/genetics ; Chromatin Immunoprecipitation ; DNA/genetics/metabolism ; Dogs ; *Evolution, Molecular ; *Gene Expression Regulation ; *Genome ; Genome, Human ; Hepatocyte Nuclear Factor 4/*metabolism ; Humans ; Liver/*metabolism ; Mice ; Opossums/genetics ; Protein Binding ; Regulatory Sequences, Nucleic Acid ; Sequence Analysis, DNA ; Species Specificity ; Vertebrates/*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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  • 4
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    Prediction of individual brain maturity using fMRI (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-09-11
    Description: Group functional connectivity magnetic resonance imaging (fcMRI) studies have documented reliable changes in human functional brain maturity over development. Here we show that support vector machine-based multivariate pattern analysis extracts sufficient information from fcMRI data to make accurate predictions about individuals' brain maturity across development. The use of only 5 minutes of resting-state fcMRI data from 238 scans of typically developing volunteers (ages 7 to 30 years) allowed prediction of individual brain maturity as a functional connectivity maturation index. The resultant functional maturation curve accounted for 55% of the sample variance and followed a nonlinear asymptotic growth curve shape. The greatest relative contribution to predicting individual brain maturity was made by the weakening of short-range functional connections between the adult brain's major functional networks.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135376/" 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/PMC3135376/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dosenbach, Nico U F -- Nardos, Binyam -- Cohen, Alexander L -- Fair, Damien A -- Power, Jonathan D -- Church, Jessica A -- Nelson, Steven M -- Wig, Gagan S -- Vogel, Alecia C -- Lessov-Schlaggar, Christina N -- Barnes, Kelly Anne -- Dubis, Joseph W -- Feczko, Eric -- Coalson, Rebecca S -- Pruett, John R Jr -- Barch, Deanna M -- Petersen, Steven E -- Schlaggar, Bradley L -- DA027046/DA/NIDA NIH HHS/ -- EY16336/EY/NEI NIH HHS/ -- HD057076/HD/NICHD NIH HHS/ -- MH62130/MH/NIMH NIH HHS/ -- NS00169011/NS/NINDS NIH HHS/ -- NS053425/NS/NINDS NIH HHS/ -- NS32979/NS/NINDS NIH HHS/ -- NS41255/NS/NINDS NIH HHS/ -- NS46424/NS/NINDS NIH HHS/ -- NS51281/NS/NINDS NIH HHS/ -- NS55582/NS/NINDS NIH HHS/ -- R01 HD057076/HD/NICHD NIH HHS/ -- R01 HD057076-04/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2010 Sep 10;329(5997):1358-61. doi: 10.1126/science.1194144.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA. ndosenbach@wustl.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20829489" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Aging ; Algorithms ; Artificial Intelligence ; Brain/*growth & development/*physiology ; Brain Mapping ; Cerebellum/growth & development/physiology ; Child ; Female ; Frontal Lobe/growth & development/physiology ; Humans ; *Magnetic Resonance Imaging ; Male ; Multivariate Analysis ; Neural Pathways ; Occipital Lobe/growth & development/physiology ; Young Adult
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
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    A genetic variant BDNF polymorphism alters extinction learning in both mouse and human (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-01-16
    Description: Mouse models are useful for studying genes involved in behavior, but whether they are relevant to human behavior is unclear. Here, we identified parallel phenotypes in mice and humans resulting from a common single-nucleotide polymorphism in the brain-derived neurotrophic factor (BDNF) gene, which is involved in anxiety-related behavior. An inbred genetic knock-in mouse strain expressing the variant BDNF recapitulated the phenotypic effects of the human polymorphism. Both were impaired in extinguishing a conditioned fear response, which was paralleled by atypical frontoamygdala activity in humans. Thus, this variant BDNF allele may play a role in anxiety disorders showing impaired learning of cues that signal safety versus threat and in the efficacy of treatments that rely on extinction mechanisms, such as exposure therapy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829261/" 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/PMC2829261/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Soliman, Fatima -- Glatt, Charles E -- Bath, Kevin G -- Levita, Liat -- Jones, Rebecca M -- Pattwell, Siobhan S -- Jing, Deqiang -- Tottenham, Nim -- Amso, Dima -- Somerville, Leah H -- Voss, Henning U -- Glover, Gary -- Ballon, Douglas J -- Liston, Conor -- Teslovich, Theresa -- Van Kempen, Tracey -- Lee, Francis S -- Casey, B J -- GM07739/GM/NIGMS NIH HHS/ -- HD055177/HD/NICHD NIH HHS/ -- MH060478/MH/NIMH NIH HHS/ -- MH079513/MH/NIMH NIH HHS/ -- NS052819/NS/NINDS NIH HHS/ -- P50 MH079513/MH/NIMH NIH HHS/ -- P50 MH079513-01A1/MH/NIMH NIH HHS/ -- P50 MH079513-01A10001/MH/NIMH NIH HHS/ -- P50 MH079513-02/MH/NIMH NIH HHS/ -- P50 MH079513-020001/MH/NIMH NIH HHS/ -- R01 MH091864/MH/NIMH NIH HHS/ -- R01 NS052819/NS/NINDS NIH HHS/ -- R01 NS052819-05/NS/NINDS NIH HHS/ -- R25 MH060478/MH/NIMH NIH HHS/ -- R25 MH060478-10/MH/NIMH NIH HHS/ -- T32 GM007739/GM/NIGMS NIH HHS/ -- T32 GM007739-30/GM/NIGMS NIH HHS/ -- T32 HD055177/HD/NICHD NIH HHS/ -- T32 HD055177-01A2/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2010 Feb 12;327(5967):863-6. doi: 10.1126/science.1181886. Epub 2010 Jan 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Sackler Institute for Developmental Psychobiology, Weill Cornell Medical College, New York, NY 10065, USA. fas2002@med.cornell.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20075215" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Alleles ; Amygdala/physiology ; Animals ; Brain Mapping ; Brain-Derived Neurotrophic Factor/*genetics/*physiology ; *Conditioning, Classical ; Cues ; Ethnic Groups/genetics ; *Extinction, Psychological ; *Fear ; Female ; Gene Knock-In Techniques ; Genotype ; Humans ; Magnetic Resonance Imaging ; Male ; Mice ; *Polymorphism, Single Nucleotide ; Prefrontal Cortex/physiology ; Young Adult
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    Dopaminergic network differences in human impulsivity (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-07-31
    Description: Dopamine (DA) has long been implicated in impulsivity, but the precise mechanisms linking human variability in DA signaling to differences in impulsive traits remain largely unknown. By using a dual-scan positron emission tomography approach in healthy human volunteers with amphetamine and the D2/D3 ligand [18F]fallypride, we found that higher levels of trait impulsivity were predicted by diminished midbrain D2/D3 autoreceptor binding and greater amphetamine-induced DA release in the striatum, which was in turn associated with stimulant craving. Path analysis confirmed that the impact of decreased midbrain D2/D3 autoreceptor availability on trait impulsivity is mediated in part through its effect on stimulated striatal DA release.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3161413/" 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/PMC3161413/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buckholtz, Joshua W -- Treadway, Michael T -- Cowan, Ronald L -- Woodward, Neil D -- Li, Rui -- Ansari, M Sib -- Baldwin, Ronald M -- Schwartzman, Ashley N -- Shelby, Evan S -- Smith, Clarence E -- Kessler, Robert M -- Zald, David H -- R01 DA019670/DA/NIDA NIH HHS/ -- R01 DA019670-04/DA/NIDA NIH HHS/ -- R01DA019670-04/DA/NIDA NIH HHS/ -- T32 MH018921/MH/NIMH NIH HHS/ -- T32 MH018921-22/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2010 Jul 30;329(5991):532. doi: 10.1126/science.1185778.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychology, Vanderbilt University, Nashville, TN 37240, USA. joshua.buckholtz@vanderbilt.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20671181" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Amphetamine-Related Disorders/etiology/metabolism ; Autoreceptors/metabolism ; Benzamides/metabolism ; Corpus Striatum/*metabolism ; Dextroamphetamine/*administration & dosage ; Dopamine/*metabolism ; Female ; Humans ; Impulsive Behavior/*metabolism ; Ligands ; Male ; Positron-Emission Tomography ; Pyrrolidines/metabolism ; Receptors, Dopamine D2/metabolism ; Receptors, Dopamine D3/*metabolism ; Signal Transduction ; Substantia Nigra/metabolism ; Tegmentum Mesencephali/*metabolism ; Ventral Tegmental Area/metabolism ; Young Adult
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
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    Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01 (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-07-10
    Description: During HIV-1 infection, antibodies are generated against the region of the viral gp120 envelope glycoprotein that binds CD4, the primary receptor for HIV-1. Among these antibodies, VRC01 achieves broad neutralization of diverse viral strains. We determined the crystal structure of VRC01 in complex with a human immunodeficiency virus HIV-1 gp120 core. VRC01 partially mimics CD4 interaction with gp120. A shift from the CD4-defined orientation, however, focuses VRC01 onto the vulnerable site of initial CD4 attachment, allowing it to overcome the glycan and conformational masking that diminishes the neutralization potency of most CD4-binding-site antibodies. To achieve this recognition, VRC01 contacts gp120 mainly through immunoglobulin V-gene regions substantially altered from their genomic precursors. Partial receptor mimicry and extensive affinity maturation thus facilitate neutralization of HIV-1 by natural human antibodies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981354/" 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/PMC2981354/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Tongqing -- Georgiev, Ivelin -- Wu, Xueling -- Yang, Zhi-Yong -- Dai, Kaifan -- Finzi, Andres -- Kwon, Young Do -- Scheid, Johannes F -- Shi, Wei -- Xu, Ling -- Yang, Yongping -- Zhu, Jiang -- Nussenzweig, Michel C -- Sodroski, Joseph -- Shapiro, Lawrence -- Nabel, Gary J -- Mascola, John R -- Kwong, Peter D -- P30 AI060354/AI/NIAID NIH HHS/ -- Z99 AI999999/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2010 Aug 13;329(5993):811-7. doi: 10.1126/science.1192819. Epub 2010 Jul 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20616231" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines ; Amino Acid Sequence ; Antibodies, Neutralizing/*chemistry/*immunology ; Antibody Affinity ; Antigenic Variation ; Antigens, CD4/chemistry/immunology/metabolism ; Base Sequence ; Binding Sites, Antibody ; Crystallography, X-Ray ; Epitopes/immunology ; HIV Antibodies/*chemistry/*immunology ; HIV Envelope Protein gp120/chemistry/genetics/*immunology ; HIV-1/*immunology ; Humans ; Immunoglobulin Fab Fragments/chemistry/immunology/metabolism ; Models, Molecular ; Molecular Mimicry ; Molecular Sequence Data ; Neutralization Tests ; Protein Conformation ; Protein Structure, Tertiary
    Print ISSN: 0036-8075
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  • 8
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    Gamma-secretase gene mutations in familial acne inversa (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-10-12
    Description: Acne inversa (AI), also known as hidradenitis suppurativa, is a chronic, recurrent, inflammatory disease of hair follicles that often runs in families. We studied six Chinese families with features of AI as well as additional skin lesions on back, face, nape, and waist and found independent loss-of-function mutations in PSENEN, PSEN1, or NCSTN, the genes encoding essential components of the gamma-secretase multiprotein complex. Our results identify the gamma-secretase component genes as the culprits for a subset of familial AI, implicate the gamma-secretase-Notch pathway in the molecular pathogenesis of AI, and demonstrate that familial AI can be an allelic disorder of early-onset familial Alzheimer's disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Baoxi -- Yang, Wei -- Wen, Wen -- Sun, Jing -- Su, Bin -- Liu, Bo -- Ma, Donglai -- Lv, Dan -- Wen, Yaran -- Qu, Tao -- Chen, Min -- Sun, Miao -- Shen, Yan -- Zhang, Xue -- New York, N.Y. -- Science. 2010 Nov 19;330(6007):1065. doi: 10.1126/science.1196284. Epub 2010 Oct 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Peking Union Medical College Hospital, Chinese Academy of Medical Sciences-Peking Union Medical College (CAMS-PUMC), Beijing, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20929727" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alleles ; Alzheimer Disease/genetics ; Amyloid Precursor Protein Secretases/*genetics ; Asian Continental Ancestry Group/genetics ; Chromosomes, Human, Pair 19 ; DNA Mutational Analysis ; Female ; Hidradenitis Suppurativa/*enzymology/*genetics ; Humans ; Male ; Membrane Glycoproteins/genetics ; Membrane Proteins/genetics ; Middle Aged ; *Mutation ; Presenilin-1/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Young Adult
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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    Food safety. Genetically modified salmon and full impact assessment (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-11-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smith, Martin D -- Asche, Frank -- Guttormsen, Atle G -- Wiener, Jonathan B -- New York, N.Y. -- Science. 2010 Nov 19;330(6007):1052-3. doi: 10.1126/science.1197769.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Nicholas School of the Environment, Duke University, Durham, NC 27708, USA. marsmith@duke.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21097923" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; *Animals, Genetically Modified ; Animals, Wild ; Dietary Proteins ; Environment ; Fisheries/economics ; *Food, Genetically Modified/economics ; Humans ; Legislation, Food ; Marketing ; Perciformes/genetics ; Public Health ; *Risk Assessment/methods/standards ; Salmo salar/*genetics ; Salmon/genetics ; United States ; United States Food and Drug Administration
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 10
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    Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-07-21
    Description: The Centre for the AIDS Program of Research in South Africa (CAPRISA) 004 trial assessed the effectiveness and safety of a 1% vaginal gel formulation of tenofovir, a nucleotide reverse transcriptase inhibitor, for the prevention of HIV acquisition in women. A double-blind, randomized controlled trial was conducted comparing tenofovir gel (n = 445 women) with placebo gel (n = 444 women) in sexually active, HIV-uninfected 18- to 40-year-old women in urban and rural KwaZulu-Natal, South Africa. HIV serostatus, safety, sexual behavior, and gel and condom use were assessed at monthly follow-up visits for 30 months. HIV incidence in the tenofovir gel arm was 5.6 per 100 women-years (person time of study observation) (38 out of 680.6 women-years) compared with 9.1 per 100 women-years (60 out of 660.7 women-years) in the placebo gel arm (incidence rate ratio = 0.61; P = 0.017). In high adherers (gel adherence 〉 80%), HIV incidence was 54% lower (P = 0.025) in the tenofovir gel arm. In intermediate adherers (gel adherence 50 to 80%) and low adherers (gel adherence 〈 50%), the HIV incidence reduction was 38 and 28%, respectively. Tenofovir gel reduced HIV acquisition by an estimated 39% overall, and by 54% in women with high gel adherence. No increase in the overall adverse event rates was observed. There were no changes in viral load and no tenofovir resistance in HIV seroconverters. Tenofovir gel could potentially fill an important HIV prevention gap, especially for women unable to successfully negotiate mutual monogamy or condom use.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001187/" 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/PMC3001187/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abdool Karim, Quarraisha -- Abdool Karim, Salim S -- Frohlich, Janet A -- Grobler, Anneke C -- Baxter, Cheryl -- Mansoor, Leila E -- Kharsany, Ayesha B M -- Sibeko, Sengeziwe -- Mlisana, Koleka P -- Omar, Zaheen -- Gengiah, Tanuja N -- Maarschalk, Silvia -- Arulappan, Natasha -- Mlotshwa, Mukelisiwe -- Morris, Lynn -- Taylor, Douglas -- CAPRISA 004 Trial Group -- AI51794/AI/NIAID NIH HHS/ -- D43 TW000231/TW/FIC NIH HHS/ -- D43 TW000231-17/TW/FIC NIH HHS/ -- D43TW00231/TW/FIC NIH HHS/ -- U01 AI068619/AI/NIAID NIH HHS/ -- U01AI068633/AI/NIAID NIH HHS/ -- U01AI46749/AI/NIAID NIH HHS/ -- U19 AI051794/AI/NIAID NIH HHS/ -- U19 AI051794-05/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2010 Sep 3;329(5996):1168-74. doi: 10.1126/science.1193748. Epub 2010 Jul 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for the AIDS Program of Research in South Africa (CAPRISA), Durban 4013, South Africa. caprisa@ukzn.ac.za〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20643915" target="_blank"〉PubMed〈/a〉
    Keywords: Adenine/administration & dosage/adverse effects/*analogs & ; derivatives/therapeutic use ; Administration, Intravaginal ; Adolescent ; Adult ; Anti-HIV Agents/*administration & dosage/adverse effects/therapeutic use ; Anti-Infective Agents, Local/administration & dosage/adverse effects/therapeutic ; use ; Double-Blind Method ; Drug Resistance, Viral ; Female ; HIV Infections/epidemiology/*prevention & control ; HIV-1/*drug effects/physiology ; Humans ; Incidence ; Organophosphonates/*administration & dosage/adverse effects/therapeutic use ; Patient Compliance ; Pregnancy ; Pregnancy Outcome ; Rural Population/statistics & numerical data ; Sexual Behavior ; South Africa/epidemiology ; Tenofovir ; Urban Population/statistics & numerical data ; Vaginal Creams, Foams, and Jellies ; Viral Load ; Young Adult
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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