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  • 1
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    Control of pancreas and liver gene expression by HNF transcription factors (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-02-28
    Description: The transcriptional regulatory networks that specify and maintain human tissue diversity are largely uncharted. To gain insight into this circuitry, we used chromatin immunoprecipitation combined with promoter microarrays to identify systematically the genes occupied by the transcriptional regulators HNF1alpha, HNF4alpha, and HNF6, together with RNA polymerase II, in human liver and pancreatic islets. We identified tissue-specific regulatory circuits formed by HNF1alpha, HNF4alpha, and HNF6 with other transcription factors, revealing how these factors function as master regulators of hepatocyte and islet transcription. Our results suggest how misregulation of HNF4alpha can contribute to type 2 diabetes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012624/" 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/PMC3012624/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Odom, Duncan T -- Zizlsperger, Nora -- Gordon, D Benjamin -- Bell, George W -- Rinaldi, Nicola J -- Murray, Heather L -- Volkert, Tom L -- Schreiber, Jorg -- Rolfe, P Alexander -- Gifford, David K -- Fraenkel, Ernest -- Bell, Graeme I -- Young, Richard A -- N01-DK-9-2310/DK/NIDDK NIH HHS/ -- R01 HG002668/HG/NHGRI NIH HHS/ -- R01 HG002668-01/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2004 Feb 27;303(5662):1378-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14988562" target="_blank"〉PubMed〈/a〉
    Keywords: Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; Carbohydrate Metabolism ; *DNA-Binding Proteins ; Diabetes Mellitus, Type 2/etiology/genetics ; Gene Expression Profiling ; *Gene Expression Regulation ; Genome, Human ; Gluconeogenesis ; Hepatocyte Nuclear Factor 1 ; Hepatocyte Nuclear Factor 1-alpha ; Hepatocyte Nuclear Factor 1-beta ; Hepatocyte Nuclear Factor 4 ; Hepatocyte Nuclear Factor 6 ; Hepatocytes/*metabolism ; Homeodomain Proteins/*metabolism ; Humans ; Islets of Langerhans/*metabolism ; Lipid Metabolism ; *Nuclear Proteins ; Oligonucleotide Array Sequence Analysis ; Phosphoproteins/*metabolism ; Precipitin Tests ; Promoter Regions, Genetic ; RNA Polymerase II/metabolism ; Trans-Activators/*metabolism ; Transcription Factors/*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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  • 2
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    Publication rights for sequence data producers (2001)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2001-02-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bell, E -- New York, N.Y. -- Science. 2000 Dec 1;290(5497):1696-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11186390" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Base Sequence ; Databases, Factual ; *Genome ; Guidelines as Topic ; Humans ; Major Histocompatibility Complex/*genetics ; Mice ; Peer Review, Research ; *Publishing
    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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    Insulators and boundaries: versatile regulatory elements in the eukaryotic genome (2001)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2001-03-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bell, A C -- West, A G -- Felsenfeld, G -- New York, N.Y. -- Science. 2001 Jan 19;291(5503):447-50.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892-0540, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11228144" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chromatin/chemistry/*genetics ; Drosophila/genetics ; Enhancer Elements, Genetic ; *Gene Expression Regulation ; Gene Silencing ; *Genome ; Genomic Imprinting ; Humans ; Models, Genetic ; Promoter Regions, Genetic ; Protein Structure, Tertiary ; *Regulatory Sequences, Nucleic Acid ; Saccharomyces cerevisiae/genetics ; Vertebrates/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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  • 4
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    Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-01-05
    Description: The hCHK2 gene encodes the human homolog of the yeast Cds1 and Rad53 G2 checkpoint kinases, whose activation in response to DNA damage prevents cellular entry into mitosis. Here, it is shown that heterozygous germ line mutations in hCHK2 occur in Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in the TP53 gene. These observations suggest that hCHK2 is a tumor suppressor gene conferring predisposition to sarcoma, breast cancer, and brain tumors, and they also provide a link between the central role of p53 inactivation in human cancer and the well-defined G2 checkpoint in yeast.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bell, D W -- Varley, J M -- Szydlo, T E -- Kang, D H -- Wahrer, D C -- Shannon, K E -- Lubratovich, M -- Verselis, S J -- Isselbacher, K J -- Fraumeni, J F -- Birch, J M -- Li, F P -- Garber, J E -- Haber, D A -- New York, N.Y. -- Science. 1999 Dec 24;286(5449):2528-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts General Hospital Center for Cancer Risk Analysis and Harvard Medical School, Building 149, Charlestown, MA 02129, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10617473" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Apoptosis ; Brain Neoplasms/genetics ; Breast Neoplasms/genetics ; Checkpoint Kinase 2 ; Female ; G1 Phase ; *G2 Phase ; *Genes, Tumor Suppressor ; Genes, p53 ; Genetic Predisposition to Disease ; *Germ-Line Mutation ; Heterozygote ; Humans ; Li-Fraumeni Syndrome/enzymology/*genetics/pathology ; Male ; Pedigree ; Polymorphism, Genetic ; Protein Kinases/genetics ; Protein-Serine-Threonine Kinases/*genetics/metabolism ; Sarcoma/genetics ; Signal Transduction ; Tumor Cells, Cultured
    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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    Genetic analysis of complex disease (1997)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1997-02-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bell, D A -- Taylor, J A -- New York, N.Y. -- Science. 1997 Feb 28;275(5304):1327-8; author reply 1329-30.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9064789" target="_blank"〉PubMed〈/a〉
    Keywords: Case-Control Studies ; Cohort Studies ; Environmental Exposure ; Family Health ; Genetic Diseases, Inborn/*genetics ; *Genetic Predisposition to Disease ; *Genetic Techniques ; Genetics, Population ; Humans
    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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    Results from the Mars Pathfinder camera (1997)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1997
    Description: Images of the martian surface returned by the Imager for Mars Pathfinder (IMP) show a complex surface of ridges and troughs covered by rocks that have been transported and modified by fluvial, aeolian, and impact processes. Analysis of the spectral signatures in the scene (at 440- to 1000-nanometer wavelength) reveal three types of rock and four classes of soil. Upward-looking IMP images of the predawn sky show thin, bluish clouds that probably represent water ice forming on local atmospheric haze (opacity approximately 0.5). Haze particles are about 1 micrometer in radius and the water vapor column abundance is about 10 precipitable micrometers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smith, P H -- Bell, J F 3rd -- Bridges, N T -- Britt, D T -- Gaddis, L -- Greeley, R -- Keller, H U -- Herkenhoff, K E -- Jaumann, R -- Johnson, J R -- Kirk, R L -- Lemmon, M -- Maki, J N -- Malin, M C -- Murchie, S L -- Oberst, J -- Parker, T J -- Reid, R J -- Sablotny, R -- Soderblom, L A -- Stoker, C -- Sullivan, R -- Thomas, N -- Tomasko, M G -- Wegryn, E -- New York, N.Y. -- Science. 1997 Dec 5;278(5344):1758-65.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lunar and Planetary Laboratory, University of Arizona, Tucson, AZ 85721, USA. psmith@lpl.arizona.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9388170" target="_blank"〉PubMed〈/a〉
    Keywords: Atmosphere ; *Extraterrestrial Environment ; Ice ; *Mars ; Minerals ; *Water ; Wind
    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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    In situ evidence for an ancient aqueous environment at Meridiani Planum, Mars (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-12-04
    Description: Sedimentary rocks at Eagle crater in Meridiani Planum are composed of fine-grained siliciclastic materials derived from weathering of basaltic rocks, sulfate minerals (including magnesium sulfate and jarosite) that constitute several tens of percent of the rock by weight, and hematite. Cross-stratification observed in rock outcrops indicates eolian and aqueous transport. Diagenetic features include hematite-rich concretions and crystal-mold vugs. We interpret the rocks to be a mixture of chemical and siliciclastic sediments with a complex diagenetic history. The environmental conditions that they record include episodic inundation by shallow surface water, evaporation, and desiccation. The geologic record at Meridiani Planum suggests that conditions were suitable for biological activity for a period of time in martian history.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Squyres, S W -- Grotzinger, J P -- Arvidson, R E -- Bell, J F 3rd -- Calvin, W -- Christensen, P R -- Clark, B C -- Crisp, J A -- Farrand, W H -- Herkenhoff, K E -- Johnson, J R -- Klingelhofer, G -- Knoll, A H -- McLennan, S M -- McSween, H Y Jr -- Morris, R V -- Rice, J W Jr -- Rieder, R -- Soderblom, L A -- New York, N.Y. -- Science. 2004 Dec 3;306(5702):1709-14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Astronomy, Cornell University, Ithaca, NY 14853, USA. squyres@astrosun.tn.cornell.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15576604" target="_blank"〉PubMed〈/a〉
    Keywords: Exobiology ; Extraterrestrial Environment ; Ferric Compounds ; Geologic Sediments ; Life ; *Mars ; Minerals ; Silicates ; Spacecraft ; Spectrum Analysis ; Sulfates ; Sulfur ; *Water
    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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    Surficial deposits at Gusev Crater along Spirit Rover traverses (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-08-07
    Description: The Mars Exploration Rover Spirit has traversed a fairly flat, rock-strewn terrain whose surface is shaped primarily by impact events, although some of the landscape has been altered by eolian processes. Impacts ejected basaltic rocks that probably were part of locally formed lava flows from at least 10 meters depth. Some rocks have been textured and/or partially buried by windblown sediments less than 2 millimeters in diameter that concentrate within shallow, partially filled, circular impact depressions referred to as hollows. The terrain traversed during the 90-sol (martian solar day) nominal mission shows no evidence for an ancient lake in Gusev crater.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grant, J A -- Arvidson, R -- Bell, J F 3rd -- Cabrol, N A -- Carr, M H -- Christensen, P -- Crumpler, L -- Des Marais, D J -- Ehlmann, B L -- Farmer, J -- Golombek, M -- Grant, F D -- Greeley, R -- Herkenhoff, K -- Li, R -- McSween, H Y -- Ming, D W -- Moersch, J -- Rice, J W Jr -- Ruff, S -- Richter, L -- Squyres, S -- Sullivan, R -- Weitz, C -- New York, N.Y. -- Science. 2004 Aug 6;305(5685):807-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Earth and Planetary Studies, National Air and Space Museum, Smithsonian Institution, Washington, DC 20560, USA. grantj@nasm.si.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15297659" target="_blank"〉PubMed〈/a〉
    Keywords: Extraterrestrial Environment ; Geologic Sediments ; *Mars ; Minerals ; Silicates ; Volcanic Eruptions ; Water
    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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  • 9
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    Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-07-31
    Description: Gefitinib (Iressa, Astra Zeneca Pharmaceuticals) is a tyrosine kinase inhibitor that targets the epidermal growth factor receptor (EGFR) and induces dramatic clinical responses in nonsmall cell lung cancers (NSCLCs) with activating mutations within the EGFR kinase domain. We report that these mutant EGFRs selectively activate Akt and signal transduction and activator of transcription (STAT) signaling pathways, which promote cell survival, but have no effect on extracellular signal-regulated kinase signaling, which induces proliferation. NSCLC cells expressing mutant EGFRs underwent extensive apoptosis after small interfering RNA-mediated knockdown of the mutant EGFR or treatment with pharmacological inhibitors of Akt and STAT signaling and were relatively resistant to apoptosis induced by conventional chemotherapeutic drugs. Thus, mutant EGFRs selectively transduce survival signals on which NSCLCs become dependent; inhibition of those signals by gefitinib may contribute to the drug's efficacy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sordella, Raffaella -- Bell, Daphne W -- Haber, Daniel A -- Settleman, Jeffrey -- P01 95281/PHS HHS/ -- New York, N.Y. -- Science. 2004 Aug 20;305(5687):1163-7. Epub 2004 Jul 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Molecular Therapeutics, Massachusetts General Hospital Cancer Center and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15284455" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/pharmacology ; *Apoptosis ; Carcinoma, Non-Small-Cell Lung/drug therapy/*genetics/pathology ; Catalytic Domain ; Cell Line ; Cell Line, Tumor ; Cell Survival ; DNA-Binding Proteins/antagonists & inhibitors/metabolism ; Enzyme Activation ; Humans ; Lung Neoplasms/drug therapy/*genetics/pathology ; Mice ; *Milk Proteins ; Mitogen-Activated Protein Kinases/metabolism ; Mutation ; Mutation, Missense ; Phosphorylation ; Protein-Serine-Threonine Kinases/antagonists & inhibitors/metabolism ; Proto-Oncogene Proteins/antagonists & inhibitors/metabolism ; Proto-Oncogene Proteins c-akt ; Quinazolines/*pharmacology ; RNA, Small Interfering ; Receptor, Epidermal Growth Factor/*genetics/*metabolism ; STAT5 Transcription Factor ; Sequence Deletion ; Signal Transduction ; Trans-Activators/antagonists & inhibitors/metabolism ; Transfection ; Tyrosine/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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  • 10
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    The Opportunity Rover's Athena science investigation at Meridiani Planum, Mars (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-12-04
    Description: The Mars Exploration Rover Opportunity has investigated the landing site in Eagle crater and the nearby plains within Meridiani Planum. The soils consist of fine-grained basaltic sand and a surface lag of hematite-rich spherules, spherule fragments, and other granules. Wind ripples are common. Underlying the thin soil layer, and exposed within small impact craters and troughs, are flat-lying sedimentary rocks. These rocks are finely laminated, are rich in sulfur, and contain abundant sulfate salts. Small-scale cross-lamination in some locations provides evidence for deposition in flowing liquid water. We interpret the rocks to be a mixture of chemical and siliciclastic sediments formed by episodic inundation by shallow surface water, followed by evaporation, exposure, and desiccation. Hematite-rich spherules are embedded in the rock and eroding from them. We interpret these spherules to be concretions formed by postdepositional diagenesis, again involving liquid water.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Squyres, S W -- Arvidson, R E -- Bell, J F 3rd -- Bruckner, J -- Cabrol, N A -- Calvin, W -- Carr, M H -- Christensen, P R -- Clark, B C -- Crumpler, L -- Marais, D J Des -- d'Uston, C -- Economou, T -- Farmer, J -- Farrand, W -- Folkner, W -- Golombek, M -- Gorevan, S -- Grant, J A -- Greeley, R -- Grotzinger, J -- Haskin, L -- Herkenhoff, K E -- Hviid, S -- Johnson, J -- Klingelhofer, G -- Knoll, A H -- Landis, G -- Lemmon, M -- Li, R -- Madsen, M B -- Malin, M C -- McLennan, S M -- McSween, H Y -- Ming, D W -- Moersch, J -- Morris, R V -- Parker, T -- Rice, J W Jr -- Richter, L -- Rieder, R -- Sims, M -- Smith, M -- Smith, P -- Soderblom, L A -- Sullivan, R -- Wanke, H -- Wdowiak, T -- Wolff, M -- Yen, A -- New York, N.Y. -- Science. 2004 Dec 3;306(5702):1698-703.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Astronomy, Space Sciences Building, Cornell University, Ithaca, NY 14853, USA. squyres@astro.cornell.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15576602" target="_blank"〉PubMed〈/a〉
    Keywords: Atmosphere ; Evolution, Planetary ; Extraterrestrial Environment ; Ferric Compounds ; Geologic Sediments ; *Mars ; Minerals ; Silicates ; Spacecraft ; Water ; Wind
    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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