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  • Humans  (147)
  • American Association for the Advancement of Science (AAAS)  (147)
  • Springer Nature
  • 2010-2014  (147)
  • 1990-1994
  • 2011  (147)
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  • 2010-2014  (147)
  • 1990-1994
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  • 1
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    Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-07-19
    Description: Passive transfer of broadly neutralizing HIV antibodies can prevent infection, which suggests that vaccines that elicit such antibodies would be protective. Thus far, however, few broadly neutralizing HIV antibodies that occur naturally have been characterized. To determine whether these antibodies are part of a larger group of related molecules, we cloned 576 new HIV antibodies from four unrelated individuals. All four individuals produced expanded clones of potent broadly neutralizing CD4-binding-site antibodies that mimic binding to CD4. Despite extensive hypermutation, the new antibodies shared a consensus sequence of 68 immunoglobulin H (IgH) chain amino acids and arise independently from two related IgH genes. Comparison of the crystal structure of one of the antibodies to the broadly neutralizing antibody VRC01 revealed conservation of the contacts to the HIV spike.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3351836/" 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/PMC3351836/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scheid, Johannes F -- Mouquet, Hugo -- Ueberheide, Beatrix -- Diskin, Ron -- Klein, Florian -- Oliveira, Thiago Y K -- Pietzsch, John -- Fenyo, David -- Abadir, Alexander -- Velinzon, Klara -- Hurley, Arlene -- Myung, Sunnie -- Boulad, Farid -- Poignard, Pascal -- Burton, Dennis R -- Pereyra, Florencia -- Ho, David D -- Walker, Bruce D -- Seaman, Michael S -- Bjorkman, Pamela J -- Chait, Brian T -- Nussenzweig, Michel C -- P01 AI081677/AI/NIAID NIH HHS/ -- P30 AI060354/AI/NIAID NIH HHS/ -- R01 AI033292/AI/NIAID NIH HHS/ -- RR00862/RR/NCRR NIH HHS/ -- RR022220/RR/NCRR NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Sep 16;333(6049):1633-7. doi: 10.1126/science.1207227. Epub 2011 Jul 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21764753" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Antibodies, Neutralizing/*chemistry/*immunology/metabolism ; Antibody Affinity ; Antibody Specificity ; Antigens, CD4/immunology/*metabolism ; Binding Sites ; Binding Sites, Antibody ; Cloning, Molecular ; Consensus Sequence ; Crystallography, X-Ray ; Genes, Immunoglobulin Heavy Chain ; HIV Antibodies/*chemistry/*immunology/metabolism ; HIV Envelope Protein gp120/chemistry/*immunology/metabolism ; HIV Infections/immunology ; Humans ; Immunoglobulin Fab Fragments/chemistry ; Immunoglobulin Heavy Chains/chemistry ; Immunoglobulin Light Chains/chemistry ; Molecular Mimicry ; Molecular Sequence Data ; Mutation ; Protein Conformation
    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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    Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1 (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-07-30
    Description: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. To explore the genetic origins of this cancer, we used whole-exome sequencing and gene copy number analyses to study 32 primary tumors. Tumors from patients with a history of tobacco use had more mutations than did tumors from patients who did not use tobacco, and tumors that were negative for human papillomavirus (HPV) had more mutations than did HPV-positive tumors. Six of the genes that were mutated in multiple tumors were assessed in up to 88 additional HNSCCs. In addition to previously described mutations in TP53, CDKN2A, PIK3CA, and HRAS, we identified mutations in FBXW7 and NOTCH1. Nearly 40% of the 28 mutations identified in NOTCH1 were predicted to truncate the gene product, suggesting that NOTCH1 may function as a tumor suppressor gene rather than an oncogene in this tumor type.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3162986/" 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/PMC3162986/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Agrawal, Nishant -- Frederick, Mitchell J -- Pickering, Curtis R -- Bettegowda, Chetan -- Chang, Kyle -- Li, Ryan J -- Fakhry, Carole -- Xie, Tong-Xin -- Zhang, Jiexin -- Wang, Jing -- Zhang, Nianxiang -- El-Naggar, Adel K -- Jasser, Samar A -- Weinstein, John N -- Trevino, Lisa -- Drummond, Jennifer A -- Muzny, Donna M -- Wu, Yuanqing -- Wood, Laura D -- Hruban, Ralph H -- Westra, William H -- Koch, Wayne M -- Califano, Joseph A -- Gibbs, Richard A -- Sidransky, David -- Vogelstein, Bert -- Velculescu, Victor E -- Papadopoulos, Nickolas -- Wheeler, David A -- Kinzler, Kenneth W -- Myers, Jeffrey N -- 5P50CA09700708/CA/NCI NIH HHS/ -- CA121113/CA/NCI NIH HHS/ -- CA16672/CA/NCI NIH HHS/ -- CA43460/CA/NCI NIH HHS/ -- CA57345/CA/NCI NIH HHS/ -- CN43302/CN/NCI NIH HHS/ -- N01 CN043302/CN/NCI NIH HHS/ -- P50 CA097007/CA/NCI NIH HHS/ -- P50 CA097007-05/CA/NCI NIH HHS/ -- P50 DE019032/DE/NIDCR NIH HHS/ -- P50 DE019032-07/DE/NIDCR NIH HHS/ -- P50 DE019032-10/DE/NIDCR NIH HHS/ -- P50DE019032/DE/NIDCR NIH HHS/ -- R01 CA121113/CA/NCI NIH HHS/ -- R01 CA121113-01/CA/NCI NIH HHS/ -- R37 CA043460/CA/NCI NIH HHS/ -- R37 CA043460-16/CA/NCI NIH HHS/ -- R37 CA057345/CA/NCI NIH HHS/ -- R37 CA057345-20/CA/NCI NIH HHS/ -- R37 DE012588/DE/NIDCR NIH HHS/ -- R37 DE012588-14/DE/NIDCR NIH HHS/ -- RC2 DE020957/DE/NIDCR NIH HHS/ -- RC2 DE020957-01/DE/NIDCR NIH HHS/ -- RC2 DE020957-02/DE/NIDCR NIH HHS/ -- RC2 DE020958/DE/NIDCR NIH HHS/ -- RC2 DE020958-02/DE/NIDCR NIH HHS/ -- RC2DE020957/DE/NIDCR NIH HHS/ -- RC2DE020958/DE/NIDCR NIH HHS/ -- T32 CA009574/CA/NCI NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Aug 26;333(6046):1154-7. doi: 10.1126/science.1206923. Epub 2011 Jul 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA. nagrawal@jhmi.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21798897" target="_blank"〉PubMed〈/a〉
    Keywords: Carcinoma/drug therapy/*genetics/virology ; Carcinoma, Squamous Cell ; Cell Cycle Proteins/*genetics ; Codon, Nonsense ; Exons ; F-Box Proteins/*genetics ; Gene Dosage ; *Genes, Tumor Suppressor ; Genes, p53 ; Head and Neck Neoplasms/drug therapy/*genetics/virology ; Humans ; INDEL Mutation ; *Mutation ; Mutation, Missense ; Neoplasms, Squamous Cell/drug therapy/*genetics/virology ; Oligonucleotide Array Sequence Analysis ; Oncogenes ; Papillomaviridae/isolation & purification ; Papillomavirus Infections/virology ; Receptor, Notch1/chemistry/*genetics ; Sequence Analysis, DNA ; Smoking ; Tobacco ; Ubiquitin-Protein Ligases/*genetics
    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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    Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-01-06
    Description: Adenosine monophosphate-activated protein kinase (AMPK) is a conserved sensor of intracellular energy activated in response to low nutrient availability and environmental stress. In a screen for conserved substrates of AMPK, we identified ULK1 and ULK2, mammalian orthologs of the yeast protein kinase Atg1, which is required for autophagy. Genetic analysis of AMPK or ULK1 in mammalian liver and Caenorhabditis elegans revealed a requirement for these kinases in autophagy. In mammals, loss of AMPK or ULK1 resulted in aberrant accumulation of the autophagy adaptor p62 and defective mitophagy. Reconstitution of ULK1-deficient cells with a mutant ULK1 that cannot be phosphorylated by AMPK revealed that such phosphorylation is required for mitochondrial homeostasis and cell survival during starvation. These findings uncover a conserved biochemical mechanism coupling nutrient status with autophagy and cell survival.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3030664/" 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/PMC3030664/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Egan, Daniel F -- Shackelford, David B -- Mihaylova, Maria M -- Gelino, Sara -- Kohnz, Rebecca A -- Mair, William -- Vasquez, Debbie S -- Joshi, Aashish -- Gwinn, Dana M -- Taylor, Rebecca -- Asara, John M -- Fitzpatrick, James -- Dillin, Andrew -- Viollet, Benoit -- Kundu, Mondira -- Hansen, Malene -- Shaw, Reuben J -- 1P01CA120964/CA/NCI NIH HHS/ -- 1P01CA120964-01A/CA/NCI NIH HHS/ -- 5P30CA006516-43/CA/NCI NIH HHS/ -- P01 CA120964/CA/NCI NIH HHS/ -- P01 CA120964-05/CA/NCI NIH HHS/ -- P30 CA006516/CA/NCI NIH HHS/ -- P30 CA006516-43/CA/NCI NIH HHS/ -- P30CA014195/CA/NCI NIH HHS/ -- R01 DK080425/DK/NIDDK NIH HHS/ -- R01 DK080425-04/DK/NIDDK NIH HHS/ -- R01 DK080425-05/DK/NIDDK NIH HHS/ -- T32 CA009370/CA/NCI NIH HHS/ -- T32 CA009370-29/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Jan 28;331(6016):456-61. doi: 10.1126/science.1196371. Epub 2010 Dec 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular and Cell Biology Laboratory, Dulbecco Center for Cancer Research, 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/21205641" target="_blank"〉PubMed〈/a〉
    Keywords: AMP-Activated Protein Kinases/*metabolism ; Adaptor Proteins, Signal Transducing/metabolism ; Animals ; *Autophagy ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans Proteins/genetics/metabolism ; Cell Line ; Cell Line, Tumor ; Cell Survival ; Energy Metabolism ; Hepatocytes/metabolism ; Humans ; Insulin/metabolism ; Intracellular Signaling Peptides and Proteins/chemistry/genetics/*metabolism ; Liver/metabolism ; Metformin/pharmacology ; Mice ; Mitochondria, Liver/metabolism/ultrastructure ; Phenformin/pharmacology ; Phosphorylation ; Protein-Serine-Threonine Kinases/chemistry/genetics/*metabolism ; Signal Transduction ; Transcription Factors/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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    The mutational landscape of head and neck squamous cell carcinoma (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-07-30
    Description: Head and neck squamous cell carcinoma (HNSCC) is a common, morbid, and frequently lethal malignancy. To uncover its mutational spectrum, we analyzed whole-exome sequencing data from 74 tumor-normal pairs. The majority exhibited a mutational profile consistent with tobacco exposure; human papillomavirus was detectable by sequencing DNA from infected tumors. In addition to identifying previously known HNSCC genes (TP53, CDKN2A, PTEN, PIK3CA, and HRAS), our analysis revealed many genes not previously implicated in this malignancy. At least 30% of cases harbored mutations in genes that regulate squamous differentiation (for example, NOTCH1, IRF6, and TP63), implicating its dysregulation as a major driver of HNSCC carcinogenesis. More generally, the results indicate the ability of large-scale sequencing to reveal fundamental tumorigenic mechanisms.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3415217/" 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/PMC3415217/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stransky, Nicolas -- Egloff, Ann Marie -- Tward, Aaron D -- Kostic, Aleksandar D -- Cibulskis, Kristian -- Sivachenko, Andrey -- Kryukov, Gregory V -- Lawrence, Michael S -- Sougnez, Carrie -- McKenna, Aaron -- Shefler, Erica -- Ramos, Alex H -- Stojanov, Petar -- Carter, Scott L -- Voet, Douglas -- Cortes, Maria L -- Auclair, Daniel -- Berger, Michael F -- Saksena, Gordon -- Guiducci, Candace -- Onofrio, Robert C -- Parkin, Melissa -- Romkes, Marjorie -- Weissfeld, Joel L -- Seethala, Raja R -- Wang, Lin -- Rangel-Escareno, Claudia -- Fernandez-Lopez, Juan Carlos -- Hidalgo-Miranda, Alfredo -- Melendez-Zajgla, Jorge -- Winckler, Wendy -- Ardlie, Kristin -- Gabriel, Stacey B -- Meyerson, Matthew -- Lander, Eric S -- Getz, Gad -- Golub, Todd R -- Garraway, Levi A -- Grandis, Jennifer R -- P50 CA097190/CA/NCI NIH HHS/ -- R01 CA077308/CA/NCI NIH HHS/ -- R01 CA098372/CA/NCI NIH HHS/ -- UL1 TR000005/TR/NCATS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Aug 26;333(6046):1157-60. doi: 10.1126/science.1208130. Epub 2011 Jul 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21798893" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Apoptosis ; Carcinoma/*genetics/metabolism/virology ; Carcinoma, Squamous Cell ; Cell Differentiation ; Exons ; Head and Neck Neoplasms/*genetics/metabolism/virology ; Humans ; *Mutation ; Neoplasms, Squamous Cell/*genetics/metabolism/virology ; Papillomaviridae/isolation & purification ; Papillomavirus Infections/virology ; Point Mutation ; Receptor, Notch1/*genetics/metabolism ; *Sequence Analysis, DNA ; Sequence Deletion ; Signal Transduction ; Smoking ; Tobacco
    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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    Linking long-term dietary patterns with gut microbial enterotypes (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-09-03
    Description: Diet strongly affects human health, partly by modulating gut microbiome composition. We used diet inventories and 16S rDNA sequencing to characterize fecal samples from 98 individuals. Fecal communities clustered into enterotypes distinguished primarily by levels of Bacteroides and Prevotella. Enterotypes were strongly associated with long-term diets, particularly protein and animal fat (Bacteroides) versus carbohydrates (Prevotella). A controlled-feeding study of 10 subjects showed that microbiome composition changed detectably within 24 hours of initiating a high-fat/low-fiber or low-fat/high-fiber diet, but that enterotype identity remained stable during the 10-day study. Thus, alternative enterotype states are associated with long-term diet.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3368382/" 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/PMC3368382/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, Gary D -- Chen, Jun -- Hoffmann, Christian -- Bittinger, Kyle -- Chen, Ying-Yu -- Keilbaugh, Sue A -- Bewtra, Meenakshi -- Knights, Dan -- Walters, William A -- Knight, Rob -- Sinha, Rohini -- Gilroy, Erin -- Gupta, Kernika -- Baldassano, Robert -- Nessel, Lisa -- Li, Hongzhe -- Bushman, Frederic D -- Lewis, James D -- K24 DK078228/DK/NIDDK NIH HHS/ -- K24-DK078228/DK/NIDDK NIH HHS/ -- P30 DK050306/DK/NIDDK NIH HHS/ -- R01 AI39368/AI/NIAID NIH HHS/ -- S10RR024525/RR/NCRR NIH HHS/ -- UH2 DK083981/DK/NIDDK NIH HHS/ -- UL1RR024134/RR/NCRR NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Oct 7;334(6052):105-8. doi: 10.1126/science.1208344. Epub 2011 Sep 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. gdwu@mail.med.upenn.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21885731" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Bacteria/classification/*isolation & purification ; Bacteroides/classification/isolation & purification ; Child ; Child, Preschool ; Cross-Sectional Studies ; *Diet ; Dietary Carbohydrates/administration & dosage ; Dietary Fats/administration & dosage ; Dietary Fiber/administration & dosage ; Feces/*microbiology ; Gastrointestinal Tract/*microbiology ; Humans ; *Metagenome ; Middle Aged ; Prevotella/classification/isolation & purification ; Ruminococcus/classification/isolation & purification ; Time Factors ; Young Adult
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    Aberrant overexpression of satellite repeats in pancreatic and other epithelial cancers (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-01-15
    Description: Satellite repeats in heterochromatin are transcribed into noncoding RNAs that have been linked to gene silencing and maintenance of chromosomal integrity. Using digital gene expression analysis, we showed that these transcripts are greatly overexpressed in mouse and human epithelial cancers. In 8 of 10 mouse pancreatic ductal adenocarcinomas (PDACs), pericentromeric satellites accounted for a mean 12% (range 1 to 50%) of all cellular transcripts, a mean 40-fold increase over that in normal tissue. In 15 of 15 human PDACs, alpha satellite transcripts were most abundant and HSATII transcripts were highly specific for cancer. Similar patterns were observed in cancers of the lung, kidney, ovary, colon, and prostate. Derepression of satellite transcripts correlated with overexpression of the long interspersed nuclear element 1 (LINE-1) retrotransposon and with aberrant expression of neuroendocrine-associated genes proximal to LINE-1 insertions. The overexpression of satellite transcripts in cancer may reflect global alterations in heterochromatin silencing and could potentially be useful as a biomarker for cancer detection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3701432/" 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/PMC3701432/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ting, David T -- Lipson, Doron -- Paul, Suchismita -- Brannigan, Brian W -- Akhavanfard, Sara -- Coffman, Erik J -- Contino, Gianmarco -- Deshpande, Vikram -- Iafrate, A John -- Letovsky, Stan -- Rivera, Miguel N -- Bardeesy, Nabeel -- Maheswaran, Shyamala -- Haber, Daniel A -- CA129933/CA/NCI NIH HHS/ -- L30 CA142210/CA/NCI NIH HHS/ -- P01 CA117969/CA/NCI NIH HHS/ -- R01 CA129933/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Feb 4;331(6017):593-6. doi: 10.1126/science.1200801. Epub 2011 Jan 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts General Hospital Cancer Center and Department of Medicine, Harvard Medical School, Boston, MA 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21233348" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carcinoma in Situ/genetics/pathology ; Carcinoma, Pancreatic Ductal/genetics/pathology ; Colonic Neoplasms/genetics/pathology ; DNA Methylation ; DNA, Neoplasm/genetics ; DNA, Satellite/*genetics ; Female ; Gene Expression ; Gene Expression Profiling ; Heterochromatin/chemistry/genetics ; Humans ; Long Interspersed Nucleotide Elements ; Lung Neoplasms/genetics/pathology ; Male ; Mice ; Mice, Nude ; Neoplasms/*genetics/pathology ; Neurosecretory Systems/metabolism ; Ovarian Neoplasms/genetics/pathology ; Pancreatic Neoplasms/*genetics/pathology ; Prostatic Neoplasms/genetics/pathology ; RNA, Neoplasm/*genetics/metabolism ; RNA, Untranslated/*genetics/metabolism ; Transcription, Genetic
    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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    Rapid pneumococcal evolution in response to clinical interventions (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-01-29
    Description: Epidemiological studies of the naturally transformable bacterial pathogen Streptococcus pneumoniae have previously been confounded by high rates of recombination. Sequencing 240 isolates of the PMEN1 (Spain(23F)-1) multidrug-resistant lineage enabled base substitutions to be distinguished from polymorphisms arising through horizontal sequence transfer. More than 700 recombinations were detected, with genes encoding major antigens frequently affected. Among these were 10 capsule-switching events, one of which accompanied a population shift as vaccine-escape serotype 19A isolates emerged in the USA after the introduction of the conjugate polysaccharide vaccine. The evolution of resistance to fluoroquinolones, rifampicin, and macrolides was observed to occur on multiple occasions. This study details how genomic plasticity within lineages of recombinogenic bacteria can permit adaptation to clinical interventions over remarkably short time scales.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648787/" 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/PMC3648787/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Croucher, Nicholas J -- Harris, Simon R -- Fraser, Christophe -- Quail, Michael A -- Burton, John -- van der Linden, Mark -- McGee, Lesley -- von Gottberg, Anne -- Song, Jae Hoon -- Ko, Kwan Soo -- Pichon, Bruno -- Baker, Stephen -- Parry, Christopher M -- Lambertsen, Lotte M -- Shahinas, Dea -- Pillai, Dylan R -- Mitchell, Timothy J -- Dougan, Gordon -- Tomasz, Alexander -- Klugman, Keith P -- Parkhill, Julian -- Hanage, William P -- Bentley, Stephen D -- 076962/Wellcome Trust/United Kingdom -- 076964/Wellcome Trust/United Kingdom -- G0800596/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2011 Jan 28;331(6016):430-4. doi: 10.1126/science.1198545.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21273480" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological ; Anti-Bacterial Agents/pharmacology ; Antigenic Variation ; DNA Transposable Elements ; Drug Resistance, Multiple, Bacterial ; *Evolution, Molecular ; Genome, Bacterial ; Humans ; Molecular Epidemiology ; Phylogeny ; Phylogeography ; Pneumococcal Infections/drug therapy/*microbiology ; Pneumococcal Vaccines/immunology ; Polymorphism, Single Nucleotide ; Prophages/genetics ; *Recombination, Genetic ; Selection, Genetic ; Serotyping ; Streptococcus Phages/genetics ; Streptococcus pneumoniae/classification/drug effects/*genetics/immunology
    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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    Imaging of Plasmodium liver stages to drive next-generation antimalarial drug discovery (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-11-19
    Description: Most malaria drug development focuses on parasite stages detected in red blood cells, even though, to achieve eradication, next-generation drugs active against both erythrocytic and exo-erythrocytic forms would be preferable. We applied a multifactorial approach to a set of 〉4000 commercially available compounds with previously demonstrated blood-stage activity (median inhibitory concentration 〈 1 micromolar) and identified chemical scaffolds with potent activity against both forms. From this screen, we identified an imidazolopiperazine scaffold series that was highly enriched among compounds active against Plasmodium liver stages. The orally bioavailable lead imidazolopiperazine confers complete causal prophylactic protection (15 milligrams/kilogram) in rodent models of malaria and shows potent in vivo blood-stage therapeutic activity. The open-source chemical tools resulting from our effort provide starting points for future drug discovery programs, as well as opportunities for researchers to investigate the biology of exo-erythrocytic forms.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3473092/" 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/PMC3473092/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meister, Stephan -- Plouffe, David M -- Kuhen, Kelli L -- Bonamy, Ghislain M C -- Wu, Tao -- Barnes, S Whitney -- Bopp, Selina E -- Borboa, Rachel -- Bright, A Taylor -- Che, Jianwei -- Cohen, Steve -- Dharia, Neekesh V -- Gagaring, Kerstin -- Gettayacamin, Montip -- Gordon, Perry -- Groessl, Todd -- Kato, Nobutaka -- Lee, Marcus C S -- McNamara, Case W -- Fidock, David A -- Nagle, Advait -- Nam, Tae-gyu -- Richmond, Wendy -- Roland, Jason -- Rottmann, Matthias -- Zhou, Bin -- Froissard, Patrick -- Glynne, Richard J -- Mazier, Dominique -- Sattabongkot, Jetsumon -- Schultz, Peter G -- Tuntland, Tove -- Walker, John R -- Zhou, Yingyao -- Chatterjee, Arnab -- Diagana, Thierry T -- Winzeler, Elizabeth A -- R01 AI079709/AI/NIAID NIH HHS/ -- R01 AI079709-04/AI/NIAID NIH HHS/ -- R01 AI090141/AI/NIAID NIH HHS/ -- R01 AI090141-02/AI/NIAID NIH HHS/ -- R01AI090141/AI/NIAID NIH HHS/ -- WT078285/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2011 Dec 9;334(6061):1372-7. doi: 10.1126/science.1211936. Epub 2011 Nov 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, The Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22096101" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antimalarials/chemistry/pharmacokinetics/*pharmacology/therapeutic use ; Cell Line, Tumor ; *Drug Discovery ; Drug Evaluation, Preclinical ; Drug Resistance ; Erythrocytes/parasitology ; Humans ; Imidazoles/chemistry/pharmacokinetics/*pharmacology/therapeutic use ; Liver/*parasitology ; Malaria/*drug therapy/parasitology/prevention & control ; Mice ; Mice, Inbred BALB C ; Molecular Structure ; Piperazines/chemistry/pharmacokinetics/*pharmacology/therapeutic use ; Plasmodium/cytology/*drug effects/growth & development/physiology ; Plasmodium berghei/cytology/drug effects/growth & development/physiology ; Plasmodium falciparum/cytology/drug effects/growth & development/physiology ; Plasmodium yoelii/cytology/drug effects/growth & development/physiology ; Polymorphism, Single Nucleotide ; Protozoan Proteins/chemistry/genetics/metabolism ; Random Allocation ; Small Molecule Libraries ; Sporozoites/drug effects/growth & development
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    The C-terminal domain of RNA polymerase II is modified by site-specific methylation (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-04-02
    Description: The carboxy-terminal domain (CTD) of RNA polymerase II (RNAPII) in mammals undergoes extensive posttranslational modification, which is essential for transcriptional initiation and elongation. Here, we show that the CTD of RNAPII is methylated at a single arginine (R1810) by the coactivator-associated arginine methyltransferase 1 (CARM1). Although methylation at R1810 is present on the hyperphosphorylated form of RNAPII in vivo, Ser2 or Ser5 phosphorylation inhibits CARM1 activity toward this site in vitro, suggesting that methylation occurs before transcription initiation. Mutation of R1810 results in the misexpression of a variety of small nuclear RNAs and small nucleolar RNAs, an effect that is also observed in Carm1(-/-) mouse embryo fibroblasts. These results demonstrate that CTD methylation facilitates the expression of select RNAs, perhaps serving to discriminate the RNAPII-associated machinery recruited to distinct gene types.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773223/" 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/PMC3773223/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sims, Robert J 3rd -- Rojas, Luis Alejandro -- Beck, David -- Bonasio, Roberto -- Schuller, Roland -- Drury, William J 3rd -- Eick, Dirk -- Reinberg, Danny -- F32 GM071166/GM/NIGMS NIH HHS/ -- GM-37120/GM/NIGMS NIH HHS/ -- GM-71166/GM/NIGMS NIH HHS/ -- R01 GM037120/GM/NIGMS NIH HHS/ -- R37 GM037120/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Apr 1;332(6025):99-103. doi: 10.1126/science.1202663.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute (HHMI), Department of Biochemistry, New York University School of Medicine, 522 First Avenue, Smilow 211, New York, NY 10016, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21454787" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arginine/metabolism ; Cell Line ; HeLa Cells ; Humans ; Methylation ; Mice ; Mutation ; Protein Interaction Domains and Motifs ; Protein Structure, Tertiary ; Protein-Arginine N-Methyltransferases/metabolism ; RNA Polymerase II/genetics/*metabolism ; RNA, Small Nuclear/metabolism ; RNA, Small Nucleolar/metabolism ; Recombinant Proteins
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-08-13
    Description: Antibody VRC01 is a human immunoglobulin that neutralizes about 90% of HIV-1 isolates. To understand how such broadly neutralizing antibodies develop, we used x-ray crystallography and 454 pyrosequencing to characterize additional VRC01-like antibodies from HIV-1-infected individuals. Crystal structures revealed a convergent mode of binding for diverse antibodies to the same CD4-binding-site epitope. A functional genomics analysis of expressed heavy and light chains revealed common pathways of antibody-heavy chain maturation, confined to the IGHV1-2*02 lineage, involving dozens of somatic changes, and capable of pairing with different light chains. Broadly neutralizing HIV-1 immunity associated with VRC01-like antibodies thus involves the evolution of antibodies to a highly affinity-matured state required to recognize an invariant viral structure, with lineages defined from thousands of sequences providing a genetic roadmap of their development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3516815/" 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/PMC3516815/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, Xueling -- Zhou, Tongqing -- Zhu, Jiang -- Zhang, Baoshan -- Georgiev, Ivelin -- Wang, Charlene -- Chen, Xuejun -- Longo, Nancy S -- Louder, Mark -- McKee, Krisha -- O'Dell, Sijy -- Perfetto, Stephen -- Schmidt, Stephen D -- Shi, Wei -- Wu, Lan -- Yang, Yongping -- Yang, Zhi-Yong -- Yang, Zhongjia -- Zhang, Zhenhai -- Bonsignori, Mattia -- Crump, John A -- Kapiga, Saidi H -- Sam, Noel E -- Haynes, Barton F -- Simek, Melissa -- Burton, Dennis R -- Koff, Wayne C -- Doria-Rose, Nicole A -- Connors, Mark -- NISC Comparative Sequencing Program -- Mullikin, James C -- Nabel, Gary J -- Roederer, Mario -- Shapiro, Lawrence -- Kwong, Peter D -- Mascola, John R -- 5U19 AI 067854-06/AI/NIAID NIH HHS/ -- R01 AI033292/AI/NIAID NIH HHS/ -- U19 AI067854/AI/NIAID NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2011 Sep 16;333(6049):1593-602. doi: 10.1126/science.1207532. Epub 2011 Aug 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine Research Center, 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/21835983" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines ; Amino Acid Sequence ; Antibodies, Neutralizing/*chemistry/genetics/*immunology/isolation & purification ; Antibody Affinity ; Antibody Specificity ; Antigens, CD4/metabolism ; Base Sequence ; Binding Sites ; Binding Sites, Antibody ; Complementarity Determining Regions/genetics ; Crystallography, X-Ray ; Epitopes ; *Evolution, Molecular ; Genes, Immunoglobulin Heavy Chain ; HIV Antibodies/*chemistry/genetics/*immunology/isolation & purification ; HIV Envelope Protein gp120/chemistry/*immunology/metabolism ; HIV Infections/immunology ; HIV-1/chemistry/*immunology ; High-Throughput Nucleotide Sequencing ; Humans ; Immunoglobulin Fab Fragments/chemistry/immunology ; Immunoglobulin Heavy Chains/chemistry/immunology ; Immunoglobulin J-Chains/genetics ; Immunoglobulin Light Chains/chemistry/immunology ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Sequence Analysis, DNA
    Print ISSN: 0036-8075
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