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  • Mice  (64)
  • Adult
  • Base Sequence
  • American Association for the Advancement of Science (AAAS)  (77)
  • American Chemical Society
  • Springer
  • 2010-2014  (77)
  • 1980-1984
  • 2011  (77)
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  • 2010-2014  (77)
  • 1980-1984
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  • 1
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    The ecoresponsive genome of Daphnia pulex (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-02-05
    Description: We describe the draft genome of the microcrustacean Daphnia pulex, which is only 200 megabases and contains at least 30,907 genes. The high gene count is a consequence of an elevated rate of gene duplication resulting in tandem gene clusters. More than a third of Daphnia's genes have no detectable homologs in any other available proteome, and the most amplified gene families are specific to the Daphnia lineage. The coexpansion of gene families interacting within metabolic pathways suggests that the maintenance of duplicated genes is not random, and the analysis of gene expression under different environmental conditions reveals that numerous paralogs acquire divergent expression patterns soon after duplication. Daphnia-specific genes, including many additional loci within sequenced regions that are otherwise devoid of annotations, are the most responsive genes to ecological challenges.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3529199/" 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/PMC3529199/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Colbourne, John K -- Pfrender, Michael E -- Gilbert, Donald -- Thomas, W Kelley -- Tucker, Abraham -- Oakley, Todd H -- Tokishita, Shinichi -- Aerts, Andrea -- Arnold, Georg J -- Basu, Malay Kumar -- Bauer, Darren J -- Caceres, Carla E -- Carmel, Liran -- Casola, Claudio -- Choi, Jeong-Hyeon -- Detter, John C -- Dong, Qunfeng -- Dusheyko, Serge -- Eads, Brian D -- Frohlich, Thomas -- Geiler-Samerotte, Kerry A -- Gerlach, Daniel -- Hatcher, Phil -- Jogdeo, Sanjuro -- Krijgsveld, Jeroen -- Kriventseva, Evgenia V -- Kultz, Dietmar -- Laforsch, Christian -- Lindquist, Erika -- Lopez, Jacqueline -- Manak, J Robert -- Muller, Jean -- Pangilinan, Jasmyn -- Patwardhan, Rupali P -- Pitluck, Samuel -- Pritham, Ellen J -- Rechtsteiner, Andreas -- Rho, Mina -- Rogozin, Igor B -- Sakarya, Onur -- Salamov, Asaf -- Schaack, Sarah -- Shapiro, Harris -- Shiga, Yasuhiro -- Skalitzky, Courtney -- Smith, Zachary -- Souvorov, Alexander -- Sung, Way -- Tang, Zuojian -- Tsuchiya, Dai -- Tu, Hank -- Vos, Harmjan -- Wang, Mei -- Wolf, Yuri I -- Yamagata, Hideo -- Yamada, Takuji -- Ye, Yuzhen -- Shaw, Joseph R -- Andrews, Justen -- Crease, Teresa J -- Tang, Haixu -- Lucas, Susan M -- Robertson, Hugh M -- Bork, Peer -- Koonin, Eugene V -- Zdobnov, Evgeny M -- Grigoriev, Igor V -- Lynch, Michael -- Boore, Jeffrey L -- P42 ES004699/ES/NIEHS NIH HHS/ -- P42 ES004699-25/ES/NIEHS NIH HHS/ -- P42ES004699/ES/NIEHS NIH HHS/ -- R01 ES019324/ES/NIEHS NIH HHS/ -- R24 GM078274/GM/NIGMS NIH HHS/ -- R24 GM078274-01A1/GM/NIGMS NIH HHS/ -- R24GM07827401/GM/NIGMS NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2011 Feb 4;331(6017):555-61. doi: 10.1126/science.1197761.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Genomics and Bioinformatics, Indiana University, 915 East Third Street, Bloomington, IN 47405, USA. jcolbour@indiana.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21292972" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological ; Amino Acid Sequence ; Animals ; Base Sequence ; Chromosome Mapping ; Daphnia/*genetics/physiology ; *Ecosystem ; Environment ; Evolution, Molecular ; Gene Conversion ; Gene Duplication ; Gene Expression ; Gene Expression Profiling ; Gene Expression Regulation ; Genes ; Genes, Duplicate ; *Genome ; Metabolic Networks and Pathways/genetics ; Molecular Sequence Annotation ; Molecular Sequence Data ; Multigene Family ; Phylogeny ; Sequence Analysis, DNA
    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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  • 2
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    Noncanonical TGFbeta signaling contributes to aortic aneurysm progression in Marfan syndrome mice (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-04-16
    Description: Transforming growth factor-beta (TGFbeta) signaling drives aneurysm progression in multiple disorders, including Marfan syndrome (MFS), and therapies that inhibit this signaling cascade are in clinical trials. TGFbeta can stimulate multiple intracellular signaling pathways, but it is unclear which of these pathways drives aortic disease and, when inhibited, which result in disease amelioration. Here we show that extracellular signal-regulated kinase (ERK) 1 and 2 and Smad2 are activated in a mouse model of MFS, and both are inhibited by therapies directed against TGFbeta. Whereas selective inhibition of ERK1/2 activation ameliorated aortic growth, Smad4 deficiency exacerbated aortic disease and caused premature death in MFS mice. Smad4-deficient MFS mice uniquely showed activation of Jun N-terminal kinase-1 (JNK1), and a JNK antagonist ameliorated aortic growth in MFS mice that lacked or retained full Smad4 expression. Thus, noncanonical (Smad-independent) TGFbeta signaling is a prominent driver of aortic disease in MFS mice, and inhibition of the ERK1/2 or JNK1 pathways is a potential therapeutic strategy for the disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3111087/" 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/PMC3111087/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holm, Tammy M -- Habashi, Jennifer P -- Doyle, Jefferson J -- Bedja, Djahida -- Chen, YiChun -- van Erp, Christel -- Lindsay, Mark E -- Kim, David -- Schoenhoff, Florian -- Cohn, Ronald D -- Loeys, Bart L -- Thomas, Craig J -- Patnaik, Samarjit -- Marugan, Juan J -- Judge, Daniel P -- Dietz, Harry C -- P01 AR049698/AR/NIAMS NIH HHS/ -- P01 AR049698-07/AR/NIAMS NIH HHS/ -- R01 AR041135/AR/NIAMS NIH HHS/ -- R01 AR041135-12/AR/NIAMS NIH HHS/ -- R01 AR041135-17/AR/NIAMS NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2011 Apr 15;332(6027):358-61. doi: 10.1126/science.1192149.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21493862" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anthracenes/pharmacology/therapeutic use ; Aorta/pathology ; Aortic Aneurysm/*metabolism/pathology/physiopathology/prevention & control ; Diphenylamine/analogs & derivatives/pharmacology/therapeutic use ; Disease Models, Animal ; Disease Progression ; Enzyme Activation ; Losartan/pharmacology/therapeutic use ; *MAP Kinase Signaling System ; Marfan Syndrome/drug therapy/*metabolism/pathology ; Mice ; Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/*metabolism ; Mitogen-Activated Protein Kinase 3/antagonists & inhibitors/*metabolism ; Mitogen-Activated Protein Kinase 8/antagonists & inhibitors/metabolism ; Protein Kinase Inhibitors/pharmacology/therapeutic use ; Smad2 Protein/metabolism ; Smad4 Protein/deficiency/genetics ; Sulfonamides/pharmacology/therapeutic use ; Transforming Growth Factor beta/antagonists & inhibitors/immunology/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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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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    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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  • 5
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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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  • 6
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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
    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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    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
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
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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
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Pretreatment mitochondrial priming correlates with clinical response to cytotoxic chemotherapy (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-10-29
    Description: Cytotoxic chemotherapy targets elements common to all nucleated human cells, such as DNA and microtubules, yet it selectively kills tumor cells. Here we show that clinical response to these drugs correlates with, and may be partially governed by, the pretreatment proximity of tumor cell mitochondria to the apoptotic threshold, a property called mitochondrial priming. We used BH3 profiling to measure priming in tumor cells from patients with multiple myeloma, acute myelogenous and lymphoblastic leukemia, and ovarian cancer. This assay measures mitochondrial response to peptides derived from proapoptotic BH3 domains of proteins critical for death signaling to mitochondria. Patients with highly primed cancers exhibited superior clinical response to chemotherapy. In contrast, chemoresistant cancers and normal tissues were poorly primed. Manipulation of mitochondrial priming might enhance the efficacy of cytotoxic agents.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280949/" 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/PMC3280949/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ni Chonghaile, Triona -- Sarosiek, Kristopher A -- Vo, Thanh-Trang -- Ryan, Jeremy A -- Tammareddi, Anupama -- Moore, Victoria Del Gaizo -- Deng, Jing -- Anderson, Kenneth C -- Richardson, Paul -- Tai, Yu-Tzu -- Mitsiades, Constantine S -- Matulonis, Ursula A -- Drapkin, Ronny -- Stone, Richard -- Deangelo, Daniel J -- McConkey, David J -- Sallan, Stephen E -- Silverman, Lewis -- Hirsch, Michelle S -- Carrasco, Daniel Ruben -- Letai, Anthony -- P01CA068484/CA/NCI NIH HHS/ -- P01CA139980/CA/NCI NIH HHS/ -- R01 CA129974/CA/NCI NIH HHS/ -- R01 CA129974-05/CA/NCI NIH HHS/ -- R01CA129974/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2011 Nov 25;334(6059):1129-33. doi: 10.1126/science.1206727. Epub 2011 Oct 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22033517" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Aged ; Animals ; Antineoplastic Agents/*therapeutic use ; *Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Child ; Disease-Free Survival ; Drug Resistance, Neoplasm ; Female ; Humans ; Leukemia, Myeloid, Acute/drug therapy/physiopathology ; Male ; Membrane Potential, Mitochondrial ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Mitochondria/*physiology ; Multiple Myeloma/drug therapy/physiopathology ; Neoplasms/*drug therapy/*physiopathology ; Ovarian Neoplasms/drug therapy/physiopathology ; Peptide Fragments/metabolism ; Permeability ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/physiopathology ; Proto-Oncogene Proteins c-bcl-2/chemistry/metabolism ; Remission Induction ; 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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    CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-03-26
    Description: Immunosuppressive tumor microenvironments can restrain antitumor immunity, particularly in pancreatic ductal adenocarcinoma (PDA). Because CD40 activation can reverse immune suppression and drive antitumor T cell responses, we tested the combination of an agonist CD40 antibody with gemcitabine chemotherapy in a small cohort of patients with surgically incurable PDA and observed tumor regressions in some patients. We reproduced this treatment effect in a genetically engineered mouse model of PDA and found unexpectedly that tumor regression required macrophages but not T cells or gemcitabine. CD40-activated macrophages rapidly infiltrated tumors, became tumoricidal, and facilitated the depletion of tumor stroma. Thus, cancer immune surveillance does not necessarily depend on therapy-induced T cells; rather, our findings demonstrate a CD40-dependent mechanism for targeting tumor stroma in the treatment of cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3406187/" 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/PMC3406187/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Beatty, Gregory L -- Chiorean, Elena G -- Fishman, Matthew P -- Saboury, Babak -- Teitelbaum, Ursina R -- Sun, Weijing -- Huhn, Richard D -- Song, Wenru -- Li, Dongguang -- Sharp, Leslie L -- Torigian, Drew A -- O'Dwyer, Peter J -- Vonderheide, Robert H -- K08 CA138907/CA/NCI NIH HHS/ -- K12 CA076931/CA/NCI NIH HHS/ -- P30 CA016520/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2011 Mar 25;331(6024):1612-6. doi: 10.1126/science.1198443.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21436454" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Aged ; Animals ; Antibodies, Monoclonal/administration & dosage/adverse ; effects/metabolism/*therapeutic use ; Antigens, CD40/*agonists/*immunology ; Antineoplastic Agents/administration & dosage/adverse effects/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Carcinoma, Pancreatic Ductal/*drug therapy/immunology/pathology/secondary ; Deoxycytidine/analogs & derivatives/therapeutic use ; Disease Models, Animal ; Disease-Free Survival ; Female ; Humans ; Immunologic Surveillance ; Macrophage Activation ; Macrophages/immunology ; Male ; Mice ; Middle Aged ; Pancreatic Neoplasms/*drug therapy/immunology/pathology ; T-Lymphocytes/immunology ; Tumor Microenvironment ; 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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