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  • Humans  (1,447)
  • Nature Publishing Group (NPG)  (1,447)
  • Krefeld : Geologischer Dienst Nordhein-Westfalen
  • Irkutsk : Ross. Akad. Nauk, Sibirskoe Otd., Inst. Zemnoj Kory
  • 2005-2009  (1,447)
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Year
  • 101
    Publication Date: 2009-01-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burnap, Don -- England -- Nature. 2009 Jan 29;457(7229):533. doi: 10.1038/457533b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19177110" target="_blank"〉PubMed〈/a〉
    Keywords: *Biomedical Enhancement/history ; Cannabinoids/*history ; *Cognition ; Creativity ; Hallucinogens/*history ; Health ; History, 20th Century ; History, 21st Century ; Humans ; Lysergic Acid Diethylamide/*history
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 102
    Publication Date: 2009-04-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ross, Christopher A -- Margolis, Russell L -- England -- Nature. 2009 Apr 23;458(7241):976-7. doi: 10.1038/458976a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19396131" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Glycogen Synthase Kinase 3/metabolism ; Humans ; Mice ; Nerve Tissue Proteins/genetics/*metabolism ; Schizophrenia/drug therapy/*metabolism/pathology ; *Signal Transduction ; Wnt1 Protein/metabolism ; beta Catenin/metabolism
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 103
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    Nature Publishing Group (NPG)
    Publication Date: 2009-04-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burton, Dennis R -- Poignard, Pascal -- England -- Nature. 2009 Apr 2;458(7238):584-5. doi: 10.1038/458584a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19340071" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/immunology ; B-Lymphocytes/*immunology ; HIV Antibodies/*immunology ; HIV Infections/*immunology ; Humans ; Immunologic Memory/*immunology ; Neutralization Tests
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 104
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    Nature Publishing Group (NPG)
    Publication Date: 2009-12-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mitchinson, Andrew -- England -- Nature. 2009 Dec 24;462(7276):992. doi: 10.1038/462992a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20033032" target="_blank"〉PubMed〈/a〉
    Keywords: Alcohol Drinking/*metabolism ; Alcoholic Beverages/adverse effects/*analysis ; Humans
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 105
    Publication Date: 2009-02-27
    Description: Lung disease is the major cause of morbidity and mortality in cystic fibrosis, an autosomal recessive disease caused by mutations in CFTR. In cystic fibrosis, chronic infection and dysregulated neutrophilic inflammation lead to progressive airway destruction. The severity of cystic fibrosis lung disease has considerable heritability, independent of CFTR genotype. To identify genetic modifiers, here we performed a genome-wide single nucleotide polymorphism scan in one cohort of cystic fibrosis patients, replicating top candidates in an independent cohort. This approach identified IFRD1 as a modifier of cystic fibrosis lung disease severity. IFRD1 is a histone-deacetylase-dependent transcriptional co-regulator expressed during terminal neutrophil differentiation. Neutrophils, but not macrophages, from Ifrd1-deficient mice showed blunted effector function, associated with decreased NF-kappaB p65 transactivation. In vivo, IFRD1 deficiency caused delayed bacterial clearance from the airway, but also less inflammation and disease-a phenotype primarily dependent on haematopoietic cell expression, or lack of expression, of IFRD1. In humans, IFRD1 polymorphisms were significantly associated with variation in neutrophil effector function. These data indicate that IFRD1 modulates the pathogenesis of cystic fibrosis lung disease through the regulation of neutrophil effector function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2841516/" 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/PMC2841516/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gu, YuanYuan -- Harley, Isaac T W -- Henderson, Lindsay B -- Aronow, Bruce J -- Vietor, Ilja -- Huber, Lukas A -- Harley, John B -- Kilpatrick, Jeffrey R -- Langefeld, Carl D -- Williams, Adrienne H -- Jegga, Anil G -- Chen, Jing -- Wills-Karp, Marsha -- Arshad, S Hasan -- Ewart, Susan L -- Thio, Chloe L -- Flick, Leah M -- Filippi, Marie-Dominique -- Grimes, H Leighton -- Drumm, Mitchell L -- Cutting, Garry R -- Knowles, Michael R -- Karp, Christopher L -- R01 AI024717/AI/NIAID NIH HHS/ -- R01 HL068890/HL/NHLBI NIH HHS/ -- R01 HL068890-01/HL/NHLBI NIH HHS/ -- R01 HL068927/HL/NHLBI NIH HHS/ -- R01 HL068927-01/HL/NHLBI NIH HHS/ -- R01 HL079312/HL/NHLBI NIH HHS/ -- R01 HL079312-01A1/HL/NHLBI NIH HHS/ -- R37 AI024717/AI/NIAID NIH HHS/ -- England -- Nature. 2009 Apr 23;458(7241):1039-42. doi: 10.1038/nature07811. Epub 2009 Feb 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Molecular Immunology, Cincinnati Children's Hospital Research Foundation and the University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19242412" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Cohort Studies ; Cystic Fibrosis/*genetics/*pathology ; Disease Models, Animal ; Genotype ; Humans ; Immediate-Early Proteins/deficiency/*genetics ; Inflammation/genetics/pathology ; Mice ; Mice, Inbred C57BL ; Neutrophils/immunology/metabolism ; Polymorphism, Single Nucleotide/genetics ; Pseudomonas aeruginosa/immunology/pathogenicity ; Transcription Factor RelA/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 106
    Publication Date: 2009-07-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thomas Scott, Christopher -- Owen-Smith, Jason -- McCormick, Jennifer -- England -- Nature. 2009 Jul 2;460(7251):33. doi: 10.1038/460033b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19571864" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; *Federal Government ; *Guidelines as Topic ; Humans ; *National Institutes of Health (U.S.) ; *Stem Cells ; United States
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 107
    Publication Date: 2009-03-31
    Description: Typically developing human infants preferentially attend to biological motion within the first days of life. This ability is highly conserved across species and is believed to be critical for filial attachment and for detection of predators. The neural underpinnings of biological motion perception are overlapping with brain regions involved in perception of basic social signals such as facial expression and gaze direction, and preferential attention to biological motion is seen as a precursor to the capacity for attributing intentions to others. However, in a serendipitous observation, we recently found that an infant with autism failed to recognize point-light displays of biological motion, but was instead highly sensitive to the presence of a non-social, physical contingency that occurred within the stimuli by chance. This observation raised the possibility that perception of biological motion may be altered in children with autism from a very early age, with cascading consequences for both social development and the lifelong impairments in social interaction that are a hallmark of autism spectrum disorders. Here we show that two-year-olds with autism fail to orient towards point-light displays of biological motion, and their viewing behaviour when watching these point-light displays can be explained instead as a response to non-social, physical contingencies--physical contingencies that are disregarded by control children. This observation has far-reaching implications for understanding the altered neurodevelopmental trajectory of brain specialization in autism.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2758571/" 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/PMC2758571/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Klin, Ami -- Lin, David J -- Gorrindo, Phillip -- Ramsay, Gordon -- Jones, Warren -- U54 MH066494/MH/NIMH NIH HHS/ -- U54 MH066494-010001/MH/NIMH NIH HHS/ -- U54 MH066494-019001/MH/NIMH NIH HHS/ -- U54-MH66494/MH/NIMH NIH HHS/ -- England -- Nature. 2009 May 14;459(7244):257-61. doi: 10.1038/nature07868.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Yale Child Study Center, Yale University School of Medicine, New Haven, Connecticut 06519-1124, USA. ami.klin@yale.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19329996" target="_blank"〉PubMed〈/a〉
    Keywords: Acoustic Stimulation ; Attention/*physiology ; Autistic Disorder/*physiopathology ; Calibration ; Child, Preschool ; Computers ; Fixation, Ocular/physiology ; Humans ; Light ; Motion ; Motion Pictures as Topic ; Movement/*physiology ; Photic Stimulation ; *Social Behavior ; Video Recording
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 108
    Publication Date: 2009-03-06
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4440453/" 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/PMC4440453/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burz, David S -- Shekhtman, Alexander -- R01 GM085006/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Mar 5;458(7234):37-8. doi: 10.1038/458037a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19262658" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Proteins/chemistry/genetics ; Drug Evaluation, Preclinical/methods ; Escherichia coli/*cytology/genetics/*metabolism ; Humans ; Intracellular Space/*metabolism ; Nuclear Magnetic Resonance, Biomolecular/*methods ; Oocytes/metabolism ; Protein Binding ; Thermus thermophilus/genetics ; Xenopus laevis
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 109
    Publication Date: 2009-01-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2009 Jan 29;457(7229):533. doi: 10.1038/457533c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19177108" target="_blank"〉PubMed〈/a〉
    Keywords: *Biomedical Enhancement ; *Cognition ; Conflict of Interest ; Drug Industry ; *Health ; Humans ; Research Personnel/*ethics/*standards
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 110
    Publication Date: 2009-09-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dempsey, Patrick -- England -- Nature. 2009 Sep 17;461(7262):341. doi: 10.1038/461341a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19759599" target="_blank"〉PubMed〈/a〉
    Keywords: Africa, Eastern ; Alligators and Crocodiles/*physiology ; Animals ; Archaeology/methods ; *Hominidae ; Humans ; Paleontology/*methods ; Reproducibility of Results ; Stomach/*physiology ; *Technology
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  • 111
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    Nature Publishing Group (NPG)
    Publication Date: 2009-01-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thomson, David J -- England -- Nature. 2009 Jan 22;457(7228):391-2. doi: 10.1038/457391a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19158781" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Migration ; Animals ; Carbon Dioxide/analysis ; *Greenhouse Effect ; Human Activities ; Humans ; Models, Theoretical ; *Seasons ; *Temperature ; Time Factors
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 112
    Publication Date: 2009-10-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kloor, Harry -- England -- Nature. 2009 Oct 15;461(7266):885. doi: 10.1038/461885a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19829358" target="_blank"〉PubMed〈/a〉
    Keywords: Astronauts/trends ; Awards and Prizes ; Humans ; *Motion Pictures as Topic ; *Science/economics/education ; Space Flight/economics/trends ; Spacecraft ; United States ; United States National Aeronautics and Space Administration
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 113
    Publication Date: 2009-03-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thompson, Scott M -- Mattison, Hayley A -- R01 MH065488/MH/NIMH NIH HHS/ -- England -- Nature. 2009 Mar 19;458(7236):296-7. doi: 10.1038/458296a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19295601" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/metabolism ; Calcium Channels, L-Type/metabolism ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics/*metabolism ; Dendritic Spines/*enzymology/*physiology ; Enzyme Activation ; Fluorescence ; Fluorescence Resonance Energy Transfer ; Glutamic Acid/metabolism ; Humans ; Long-Term Potentiation/*physiology ; Receptors, N-Methyl-D-Aspartate/metabolism ; Synapses/metabolism ; Synaptic Potentials/physiology ; Time Factors
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 114
    Publication Date: 2009-09-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Denker, Hans-Werner -- England -- Nature. 2009 Sep 17;461(7262):341. doi: 10.1038/461341b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19759600" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Dedifferentiation ; Cloning, Organism/*ethics/legislation & jurisprudence/methods/*trends ; Embryo Research/ethics/legislation & jurisprudence ; Fibroblasts/cytology ; Humans ; Mice ; Pluripotent Stem Cells/cytology
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 115
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    Nature Publishing Group (NPG)
    Publication Date: 2009-01-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2009 Jan 29;457(7229):511. doi: 10.1038/457511a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19177074" target="_blank"〉PubMed〈/a〉
    Keywords: *Acquired Immunodeficiency Syndrome/epidemiology/prevention & control ; *Federal Government ; Humans ; International Cooperation ; Iran/epidemiology ; Physicians/*legislation & jurisprudence ; United States
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 116
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    Nature Publishing Group (NPG)
    Publication Date: 2009-11-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2009 Nov 26;462(7272):398-9. doi: 10.1038/462398a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19940888" target="_blank"〉PubMed〈/a〉
    Keywords: France/epidemiology ; Great Britain/epidemiology ; Humans ; Influenza A Virus, H1N1 Subtype/immunology/*isolation & purification ; Influenza, Human/*epidemiology/immunology/*virology ; *Population Surveillance/methods ; Prevalence ; Vietnam/epidemiology
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 117
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    Publication Date: 2009-03-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gunn, William -- England -- Nature. 2009 Mar 19;458(7236):281. doi: 10.1038/458281c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19295585" target="_blank"〉PubMed〈/a〉
    Keywords: Humans ; Peer Review, Research/*methods/*standards/trends
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 118
    Publication Date: 2009-12-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Knepper, Mark A -- Mindell, Joseph A -- England -- Nature. 2009 Dec 10;462(7274):733-4. doi: 10.1038/462733a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20010678" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography, X-Ray ; Desulfovibrio vulgaris/*chemistry ; Humans ; Kidney/metabolism ; Membrane Transport Proteins/*chemistry/*metabolism ; Protein Structure, Quaternary ; Structure-Activity Relationship ; Urea/chemistry/*metabolism
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  • 119
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    Nature Publishing Group (NPG)
    Publication Date: 2009-11-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2009 Nov 12;462(7270):146-7. doi: 10.1038/462146a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19907462" target="_blank"〉PubMed〈/a〉
    Keywords: Bioterrorism/*prevention & control ; *Containment of Biohazards ; European Union ; Humans ; Laboratories/economics/organization & administration/*supply & ; distribution/trends
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  • 120
    Publication Date: 2009-11-13
    Description: Direct inhibition of transcription factor complexes remains a central challenge in the discipline of ligand discovery. In general, these proteins lack surface involutions suitable for high-affinity binding by small molecules. Here we report the design of synthetic, cell-permeable, stabilized alpha-helical peptides that target a critical protein-protein interface in the NOTCH transactivation complex. We demonstrate that direct, high-affinity binding of the hydrocarbon-stapled peptide SAHM1 prevents assembly of the active transcriptional complex. Inappropriate NOTCH activation is directly implicated in the pathogenesis of several disease states, including T-cell acute lymphoblastic leukaemia (T-ALL). The treatment of leukaemic cells with SAHM1 results in genome-wide suppression of NOTCH-activated genes. Direct antagonism of the NOTCH transcriptional program causes potent, NOTCH-specific anti-proliferative effects in cultured cells and in a mouse model of NOTCH1-driven T-ALL.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2951323/" 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/PMC2951323/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moellering, Raymond E -- Cornejo, Melanie -- Davis, Tina N -- Del Bianco, Cristina -- Aster, Jon C -- Blacklow, Stephen C -- Kung, Andrew L -- Gilliland, D Gary -- Verdine, Gregory L -- Bradner, James E -- 5T32GM007598/GM/NIGMS NIH HHS/ -- N01-CO-12400/CO/NCI NIH HHS/ -- P01 CA119070/CA/NCI NIH HHS/ -- P01 CA119070-049001/CA/NCI NIH HHS/ -- R01 CA092433/CA/NCI NIH HHS/ -- R01 CA092433-06A2/CA/NCI NIH HHS/ -- R56 CA092433/CA/NCI NIH HHS/ -- R56 CA092433-06A1/CA/NCI NIH HHS/ -- T32 GM007598/GM/NIGMS NIH HHS/ -- T32 GM007598-30/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Nov 12;462(7270):182-8. doi: 10.1038/nature08543.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry & Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19907488" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding, Competitive ; Cell Line, Tumor ; Cell Membrane Permeability ; Cell Proliferation/drug effects ; DNA-Binding Proteins/chemistry/metabolism ; Disease Models, Animal ; Drosophila Proteins/chemistry ; Gene Expression Regulation, Neoplastic/drug effects ; Genome/drug effects/genetics ; Humans ; Immunoglobulin J Recombination Signal Sequence-Binding Protein/metabolism ; Mice ; Models, Molecular ; Nuclear Proteins/chemistry ; Peptides/chemical synthesis/chemistry/metabolism/*pharmacology ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/genetics/pathology ; Protein Binding/drug effects ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptor, Notch1/*antagonists & inhibitors/chemistry/metabolism ; Signal Transduction/drug effects ; Substrate Specificity ; Transcription Factors/chemistry/metabolism ; Transcriptional Activation/*drug effects
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  • 121
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    Nature Publishing Group (NPG)
    Publication Date: 2009-01-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2009 Jan 29;457(7229):533. doi: 10.1038/457533d.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19177107" target="_blank"〉PubMed〈/a〉
    Keywords: *Biomedical Enhancement ; *Cognition ; *Health ; Humans ; Neurology ; *Physician's Role ; Risk Assessment
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  • 122
    Publication Date: 2009-01-27
    Description: The transcriptomes of eukaryotic cells are incredibly complex. Individual non-coding RNAs dwarf the number of protein-coding genes, and include classes that are well understood as well as classes for which the nature, extent and functional roles are obscure. Deep sequencing of small RNAs (〈200 nucleotides) from human HeLa and HepG2 cells revealed a remarkable breadth of species. These arose both from within annotated genes and from unannotated intergenic regions. Overall, small RNAs tended to align with CAGE (cap-analysis of gene expression) tags, which mark the 5' ends of capped, long RNA transcripts. Many small RNAs, including the previously described promoter-associated small RNAs, appeared to possess cap structures. Members of an extensive class of both small RNAs and CAGE tags were distributed across internal exons of annotated protein coding and non-coding genes, sometimes crossing exon-exon junctions. Here we show that processing of mature mRNAs through an as yet unknown mechanism may generate complex populations of both long and short RNAs whose apparently capped 5' ends coincide. Supplying synthetic promoter-associated small RNAs corresponding to the c-MYC transcriptional start site reduced MYC messenger RNA abundance. The studies presented here expand the catalogue of cellular small RNAs and demonstrate a biological impact for at least one class of non-canonical small RNAs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2719882/" 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/PMC2719882/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Affymetrix ENCODE Transcriptome Project -- Cold Spring Harbor Laboratory ENCODE Transcriptome Project -- U54 HG004557/HG/NHGRI NIH HHS/ -- U54 HG004557-01/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Feb 19;457(7232):1028-32. doi: 10.1038/nature07759. Epub 2009 Jan 25.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19169241" target="_blank"〉PubMed〈/a〉
    Keywords: 5' Untranslated Regions/*genetics ; Cell Line, Tumor ; Exons/genetics ; Gene Expression Profiling ; Genes, myc/genetics ; Genome, Human/genetics ; HeLa Cells ; Humans ; Models, Genetic ; RNA/classification/*genetics/*metabolism ; RNA Caps/genetics/metabolism ; RNA Processing, Post-Transcriptional/*genetics ; RNA, Untranslated/genetics/metabolism ; Transcription Initiation Site
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  • 123
    Publication Date: 2009-04-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Deshaies, Raymond J -- England -- Nature. 2009 Apr 9;458(7239):709-10. doi: 10.1038/458709a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19360071" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/*therapeutic use ; *Drug Discovery ; Humans ; Neoplasms/*drug therapy ; Proteins/metabolism ; Ubiquitins/therapeutic use
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  • 124
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    Nature Publishing Group (NPG)
    Publication Date: 2009-11-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2009 Nov 5;462(7269):19. doi: 10.1038/462017a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19890296" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Clinical Trials as Topic ; Culicidae/immunology/parasitology ; Humans ; Malaria/*epidemiology/parasitology/*prevention & control/transmission ; Malaria Vaccines/immunology ; Plasmodium/immunology
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  • 125
    Publication Date: 2009-01-27
    Description: Although the role of Hedgehog (Hh) signalling in embryonic pattern formation is well established, its functions in adult tissue renewal and maintenance remain unclear, and the relationship of these functions to cancer development has not been determined. Here we show that the loss of Smoothened (Smo), an essential component of the Hh pathway, impairs haematopoietic stem cell renewal and decreases induction of chronic myelogenous leukaemia (CML) by the BCR-ABL1 oncoprotein. Loss of Smo causes depletion of CML stem cells--the cells that propagate the leukaemia--whereas constitutively active Smo augments CML stem cell number and accelerates disease. As a possible mechanism for Smo action, we show that the cell fate determinant Numb, which depletes CML stem cells, is increased in the absence of Smo activity. Furthermore, pharmacological inhibition of Hh signalling impairs not only the propagation of CML driven by wild-type BCR-ABL1, but also the growth of imatinib-resistant mouse and human CML. These data indicate that Hh pathway activity is required for maintenance of normal and neoplastic stem cells of the haematopoietic system and raise the possibility that the drug resistance and disease recurrence associated with imatinib treatment of CML might be avoided by targeting this essential stem cell maintenance pathway.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946231/" 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/PMC2946231/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhao, Chen -- Chen, Alan -- Jamieson, Catriona H -- Fereshteh, Mark -- Abrahamsson, Annelie -- Blum, Jordan -- Kwon, Hyog Young -- Kim, Jynho -- Chute, John P -- Rizzieri, David -- Munchhof, Michael -- VanArsdale, Todd -- Beachy, Philip A -- Reya, Tannishtha -- AI067798/AI/NIAID NIH HHS/ -- DK072234/DK/NIDDK NIH HHS/ -- DK63031/DK/NIDDK NIH HHS/ -- R01 DK063031/DK/NIDDK NIH HHS/ -- R01 DK063031-01/DK/NIDDK NIH HHS/ -- R01 DK063031-01S1/DK/NIDDK NIH HHS/ -- R01 DK063031-02/DK/NIDDK NIH HHS/ -- R01 DK063031-03/DK/NIDDK NIH HHS/ -- R01 DK063031-04/DK/NIDDK NIH HHS/ -- R01 DK063031-05/DK/NIDDK NIH HHS/ -- R01 DK063031-06/DK/NIDDK NIH HHS/ -- R01 DK063031-07/DK/NIDDK NIH HHS/ -- R01 DK063031-07S1/DK/NIDDK NIH HHS/ -- R01 DK063031-08/DK/NIDDK NIH HHS/ -- R01 DK072234/DK/NIDDK NIH HHS/ -- R01 DK072234-01A1/DK/NIDDK NIH HHS/ -- R01 DK072234-02/DK/NIDDK NIH HHS/ -- R01 DK072234-03/DK/NIDDK NIH HHS/ -- R01 DK072234-04/DK/NIDDK NIH HHS/ -- U19 AI067798/AI/NIAID NIH HHS/ -- U19 AI067798-010006/AI/NIAID NIH HHS/ -- U19 AI067798-020006/AI/NIAID NIH HHS/ -- U19 AI067798-030006/AI/NIAID NIH HHS/ -- U19 AI067798-040006/AI/NIAID NIH HHS/ -- U19 AI067798-050006/AI/NIAID NIH HHS/ -- England -- Nature. 2009 Apr 9;458(7239):776-9. doi: 10.1038/nature07737.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19169242" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/pharmacology ; Cells, Cultured ; Hedgehog Proteins/*physiology ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*physiopathology ; Membrane Proteins/metabolism ; Mice ; Neoplastic Stem Cells/*physiology ; Nerve Tissue Proteins/metabolism ; Proto-Oncogene Proteins c-abl/metabolism ; Receptors, G-Protein-Coupled/antagonists & inhibitors/genetics/metabolism ; *Signal Transduction ; Tomatine/analogs & derivatives/pharmacology ; Veratrum Alkaloids/pharmacology
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  • 126
    Publication Date: 2009-01-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Knoepfler, Paul -- England -- Nature. 2009 Jan 22;457(7228):361. doi: 10.1038/457361e.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of California, Davis, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19158746" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; Comparative Genomic Hybridization ; Embryonic Stem Cells/*cytology/*pathology ; Humans ; Neoplasms/*pathology ; Neoplastic Stem Cells/pathology ; Pluripotent Stem Cells/*cytology/*pathology
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  • 127
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    Nature Publishing Group (NPG)
    Publication Date: 2009-10-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2009 Oct 29;461(7268):1187. doi: 10.1038/4611187a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19865138" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/*immunology ; *Clinical Trials, Phase III as Topic ; HIV Infections/*prevention & control ; Humans ; Reproducibility of Results ; Thailand ; Viral Load
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  • 128
    Publication Date: 2009-11-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Timoshkina, Yulia -- England -- Nature. 2009 Nov 19;462(7271):276. doi: 10.1038/462276c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19924188" target="_blank"〉PubMed〈/a〉
    Keywords: Climate Change/economics ; *Conservation of Natural Resources ; Humans ; United Nations ; *Water ; Water Supply/standards
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  • 129
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    Nature Publishing Group (NPG)
    Publication Date: 2009-12-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Russo, Gene -- England -- Nature. 2009 Oct 29;461(7268):1308-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19998548" target="_blank"〉PubMed〈/a〉
    Keywords: Biological Science Disciplines/*economics/education/manpower/*trends ; Biotechnology/economics/manpower/organization & administration/trends ; Brazil ; Emigration and Immigration/statistics & numerical data ; Financing, Government ; Humans ; Research Personnel/economics/statistics & numerical data ; Research Support as Topic
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  • 130
    Publication Date: 2009-03-20
    Description: The principles of natural protein engineering are obscured by overlapping functions and complexity accumulated through natural selection and evolution. Completely artificial proteins offer a clean slate on which to define and test these protein engineering principles, while recreating and extending natural functions. Here we introduce this method with the design of an oxygen transport protein, akin to human neuroglobin. Beginning with a simple and unnatural helix-forming sequence with just three different amino acids, we assembled a four-helix bundle, positioned histidines to bis-histidine ligate haems, and exploited helical rotation and glutamate burial on haem binding to introduce distal histidine strain and facilitate O(2) binding. For stable oxygen binding without haem oxidation, water is excluded by simple packing of the protein interior and loops that reduce helical-interface mobility. O(2) affinities and exchange timescales match natural globins with distal histidines, with the remarkable exception that O(2) binds tighter than CO.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3539743/" 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/PMC3539743/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Koder, Ronald L -- Anderson, J L Ross -- Solomon, Lee A -- Reddy, Konda S -- Moser, Christopher C -- Dutton, P Leslie -- R01 GM041048/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Mar 19;458(7236):305-9. doi: 10.1038/nature07841.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19295603" target="_blank"〉PubMed〈/a〉
    Keywords: Biological Transport ; Carbon Monoxide/metabolism ; Carrier Proteins/*chemical synthesis/chemistry/*metabolism ; Drug Design ; Globins/chemistry ; Glutamic Acid/metabolism ; Heme/metabolism ; Histidine/metabolism ; Humans ; Kinetics ; Ligands ; Nerve Tissue Proteins/chemistry ; Oxidation-Reduction ; Oxygen/*metabolism ; *Protein Engineering ; Protein Structure, Secondary ; Rotation ; Spectroscopy, Fourier Transform Infrared ; Substrate Specificity ; Water/analysis/metabolism
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  • 131
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    Nature Publishing Group (NPG)
    Publication Date: 2009-09-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2009 Sep 17;461(7262):323. doi: 10.1038/461323a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19759588" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*economics/*organization & administration/trends ; Charities/economics ; *Developing Countries ; Drug Industry/economics ; Global Health ; Humans ; India ; Organizations, Nonprofit/economics/organization & administration ; Vaccines/biosynthesis/*economics/*supply & distribution
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  • 132
    Publication Date: 2009-02-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dholakia, Kishan -- England -- Nature. 2009 Feb 26;457(7233):1061. doi: 10.1038/4571061e.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of St Andrews, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19242433" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Fatty Acids, Omega-3/metabolism ; Fluorescent Dyes ; Humans ; *Lasers ; Lung Neoplasms/metabolism ; Mice ; Pharmaceutical Preparations/metabolism ; Pharmacokinetics ; Sensitivity and Specificity ; Skin/metabolism ; Spectrum Analysis, Raman/*instrumentation/*methods
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  • 133
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    Nature Publishing Group (NPG)
    Publication Date: 2009-01-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2009 Jan 15;457(7227):258-61. doi: 10.1038/457258a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19148081" target="_blank"〉PubMed〈/a〉
    Keywords: Bioterrorism/*prevention & control ; Embryo Research/legislation & jurisprudence ; Environmental Pollution/*prevention & control ; *Federal Government ; Greenhouse Effect ; Humans ; *International Cooperation ; Leadership ; National Institutes of Health (U.S.)/legislation & jurisprudence/*organization & ; administration ; Public Policy ; Security Measures/economics/organization & administration ; United States ; United States Environmental Protection Agency/*organization & administration ; United States Food and Drug Administration/*organization & ; administration/standards
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  • 134
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    Nature Publishing Group (NPG)
    Publication Date: 2009-08-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2009 Aug 13;460(7257):786-7. doi: 10.1038/460786b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19675613" target="_blank"〉PubMed〈/a〉
    Keywords: *Databases, Factual/trends ; Humans ; Influenza A Virus, H1N1 Subtype ; Influenza, Human/*epidemiology/*virology ; International Cooperation ; Orthomyxoviridae/*genetics/*isolation & purification/physiology
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  • 135
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    Nature Publishing Group (NPG)
    Publication Date: 2009-01-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ruth, Thomas -- England -- Nature. 2009 Jan 29;457(7229):536-7. doi: 10.1038/457536a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉TRIUMF, Vancouver, Canada. truth@triumf.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19177112" target="_blank"〉PubMed〈/a〉
    Keywords: Humans ; Internationality ; Netherlands ; Nuclear Medicine/*instrumentation/*methods ; Nuclear Reactors/supply & distribution ; Ontario ; Organotechnetium Compounds/chemical synthesis/supply & distribution ; Positron-Emission Tomography/instrumentation/methods ; Radioisotopes/chemistry/*supply & distribution ; *Radionuclide Imaging ; Time Factors
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  • 136
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    Publication Date: 2009-01-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2009 Jan 15;457(7227):236. doi: 10.1038/457236a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19148049" target="_blank"〉PubMed〈/a〉
    Keywords: *Acquired Immunodeficiency Syndrome/drug ; therapy/economics/epidemiology/prevention & control ; *Federal Government ; Female ; Humans ; International Cooperation ; *Leadership ; Male ; Sexual Abstinence ; United States/epidemiology
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  • 137
    Publication Date: 2009-04-17
    Description: Biosynthesis of the DNA base thymine depends on activity of the enzyme thymidylate synthase to catalyse the methylation of the uracil moiety of 2'-deoxyuridine-5'-monophosphate. All known thymidylate synthases rely on an active site residue of the enzyme to activate 2'-deoxyuridine-5'-monophosphate. This functionality has been demonstrated for classical thymidylate synthases, including human thymidylate synthase, and is instrumental in mechanism-based inhibition of these enzymes. Here we report an example of thymidylate biosynthesis that occurs without an enzymatic nucleophile. This unusual biosynthetic pathway occurs in organisms containing the thyX gene, which codes for a flavin-dependent thymidylate synthase (FDTS), and is present in several human pathogens. Our findings indicate that the putative active site nucleophile is not required for FDTS catalysis, and no alternative nucleophilic residues capable of serving this function can be identified. Instead, our findings suggest that a hydride equivalent (that is, a proton and two electrons) is transferred from the reduced flavin cofactor directly to the uracil ring, followed by an isomerization of the intermediate to form the product, 2'-deoxythymidine-5'-monophosphate. These observations indicate a very different chemical cascade than that of classical thymidylate synthases or any other known biological methylation. The findings and chemical mechanism proposed here, together with available structural data, suggest that selective inhibition of FDTSs, with little effect on human thymine biosynthesis, should be feasible. Because several human pathogens depend on FDTS for DNA biosynthesis, its unique mechanism makes it an attractive target for antibiotic drugs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759699/" 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/PMC2759699/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Koehn, Eric M -- Fleischmann, Todd -- Conrad, John A -- Palfey, Bruce A -- Lesley, Scott A -- Mathews, Irimpan I -- Kohen, Amnon -- GM08270/GM/NIGMS NIH HHS/ -- R01 GM065368/GM/NIGMS NIH HHS/ -- R01 GM065368-05/GM/NIGMS NIH HHS/ -- R01 GM61087/GM/NIGMS NIH HHS/ -- U54GM074898/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Apr 16;458(7240):919-23. doi: 10.1038/nature07973.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of Iowa, Iowa City, Iowa 52242, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19370033" target="_blank"〉PubMed〈/a〉
    Keywords: Biocatalysis ; Catalytic Domain ; Crystallography, X-Ray ; Deoxyuracil Nucleotides/chemistry/metabolism ; Deuterium/metabolism ; Electrons ; Flavin-Adenine Dinucleotide/chemistry/metabolism ; Flavins/chemistry/*metabolism ; Helicobacter pylori/enzymology ; Humans ; Magnetic Resonance Spectroscopy ; Methylation ; Models, Molecular ; Mycobacterium tuberculosis/enzymology ; Protons ; Thermotoga maritima/*enzymology/*metabolism ; Thymidine/analogs & derivatives/metabolism ; Thymidine Monophosphate/*biosynthesis ; Thymidylate Synthase/antagonists & inhibitors/*genetics/*metabolism ; Uracil/metabolism
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  • 138
    Publication Date: 2009-06-06
    Description: Most protein mutations, and mutations that alter protein functions in particular, undermine stability and are therefore deleterious. Chaperones, or heat-shock proteins, are often implicated in buffering mutations, and could thus facilitate the acquisition of neutral genetic diversity and the rate of adaptation. We examined the ability of the Escherichia coli GroEL/GroES chaperonins to buffer destabilizing and adaptive mutations. Here we show that mutational drifts performed in vitro with four different enzymes indicated that GroEL/GroES overexpression doubled the number of accumulating mutations, and promoted the folding of enzyme variants carrying mutations in the protein core and/or mutations with higher destabilizing effects (destabilization energies of 〉3.5 kcal mol(-)(1), on average, versus approximately 1 kcal mol(-)(1) in the absence of GroEL/GroES). The divergence of modified enzymatic specificity occurred much faster under GroEL/GroES overexpression, in terms of the number of adapted variants (〉or=2-fold) and their improved specificity and activity (〉or=10-fold). These results indicate that protein stability is a major constraint in protein evolution, and buffering mechanisms such as chaperonins are key in alleviating this constraint.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tokuriki, Nobuhiko -- Tawfik, Dan S -- W81XWH-07-2-0020/PHS HHS/ -- England -- Nature. 2009 Jun 4;459(7247):668-73. doi: 10.1038/nature08009.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19494908" target="_blank"〉PubMed〈/a〉
    Keywords: Chaperonin 10/genetics/metabolism ; Chaperonin 60/genetics/metabolism ; Chaperonins/*metabolism ; Escherichia coli/*genetics/*metabolism ; Esterases/metabolism ; *Evolution, Molecular ; *Gene Expression ; *Genetic Variation ; Glyceraldehyde-3-Phosphate Dehydrogenases/metabolism ; Humans ; Mutation ; Protein Stability ; Pseudomonas/enzymology ; Substrate Specificity
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  • 139
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    Nature Publishing Group (NPG)
    Publication Date: 2009-11-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Todes, Daniel -- England -- Nature. 2009 Nov 5;462(7269):36-7. doi: 10.1038/462036a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of the History of Medicine at Johns Hopkins University, 1900 East Monument Street, Baltimore, Maryland 21205, USA. dtodes@jhmi.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19890312" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Biological Science Disciplines/*history ; *Competitive Behavior ; Cooperative Behavior ; *Cultural Diversity ; Food Supply ; Great Britain ; History, 19th Century ; History, 20th Century ; Humans ; Literature, Modern/history ; Metaphor ; Models, Biological ; Population Density ; Russia ; Selection, Genetic
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  • 140
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    Nature Publishing Group (NPG)
    Publication Date: 2009-07-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Toledo, Franck -- Bardot, Boris -- England -- Nature. 2009 Jul 23;460(7254):466-7. doi: 10.1038/460466a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19626103" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Gene Expression Regulation, Neoplastic ; Genes, p53/genetics/*physiology ; Humans ; Mice ; MicroRNAs/*metabolism ; Mutation ; Neoplasms/*metabolism
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  • 141
    Publication Date: 2009-02-06
    Description: The influenza virus polymerase, a heterotrimer composed of three subunits, PA, PB1 and PB2, is responsible for replication and transcription of the eight separate segments of the viral RNA genome in the nuclei of infected cells. The polymerase synthesizes viral messenger RNAs using short capped primers derived from cellular transcripts by a unique 'cap-snatching' mechanism. The PB2 subunit binds the 5' cap of host pre-mRNAs, which are subsequently cleaved after 10-13 nucleotides by the viral endonuclease, hitherto thought to reside in the PB2 (ref. 5) or PB1 (ref. 2) subunits. Here we describe biochemical and structural studies showing that the amino-terminal 209 residues of the PA subunit contain the endonuclease active site. We show that this domain has intrinsic RNA and DNA endonuclease activity that is strongly activated by manganese ions, matching observations reported for the endonuclease activity of the intact trimeric polymerase. Furthermore, this activity is inhibited by 2,4-dioxo-4-phenylbutanoic acid, a known inhibitor of the influenza endonuclease. The crystal structure of the domain reveals a structural core closely resembling resolvases and type II restriction endonucleases. The active site comprises a histidine and a cluster of three acidic residues, conserved in all influenza viruses, which bind two manganese ions in a configuration similar to other two-metal-dependent endonucleases. Two active site residues have previously been shown to specifically eliminate the polymerase endonuclease activity when mutated. These results will facilitate the optimisation of endonuclease inhibitors as potential new anti-influenza drugs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dias, Alexandre -- Bouvier, Denis -- Crepin, Thibaut -- McCarthy, Andrew A -- Hart, Darren J -- Baudin, Florence -- Cusack, Stephen -- Ruigrok, Rob W H -- England -- Nature. 2009 Apr 16;458(7240):914-8. doi: 10.1038/nature07745. Epub 2009 Feb 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Unit of Virus Host-Cell Interactions, UJF-EMBL-CNRS, UMR 5233, 6 rue Jules Horowitz, BP181, 38042 Grenoble Cedex 9, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19194459" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Catalytic Domain ; Endonucleases/chemistry/*metabolism ; Enzyme Stability ; Histidine/metabolism ; Humans ; Influenza A Virus, H3N2 Subtype/*enzymology ; Influenza A Virus, H5N1 Subtype/enzymology ; Influenzavirus C/enzymology ; Manganese/metabolism/pharmacology ; Models, Molecular ; Molecular Sequence Data ; Protein Subunits/*chemistry/*metabolism ; RNA Caps/*metabolism ; RNA Replicase/*chemistry/*metabolism ; Viral Proteins/*chemistry/*metabolism
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  • 142
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    Nature Publishing Group (NPG)
    Publication Date: 2009-07-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2009 Jul 16;460(7253):310-1. doi: 10.1038/460310b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19606108" target="_blank"〉PubMed〈/a〉
    Keywords: Antimalarials/*administration & dosage/*therapeutic use ; Artemisinins/*administration & dosage/*therapeutic use ; Drug Combinations ; Drug Industry/*legislation & jurisprudence ; Drug Resistance ; Humans ; Malaria/*drug therapy/parasitology ; *World Health Organization
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  • 143
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    Nature Publishing Group (NPG)
    Publication Date: 2009-07-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2009 Jul 23;460(7254):446. doi: 10.1038/460446a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19626079" target="_blank"〉PubMed〈/a〉
    Keywords: Adjuvants, Immunologic ; Antigens, Viral/immunology ; Disease Outbreaks/*prevention & control ; Europe ; Humans ; Influenza A Virus, H1N1 Subtype/*immunology ; Influenza Vaccines/economics/*immunology/standards/supply & distribution ; Influenza, Human/*prevention & control ; United States ; World Health Organization
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  • 144
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    Nature Publishing Group (NPG)
    Publication Date: 2009-06-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2009 Jun 18;459(7249):894-5. doi: 10.1038/459894b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19544601" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Humans ; Influenza A Virus, H1N1 Subtype/immunology/isolation & purification ; Influenza, Human/*epidemiology/immunology/transmission/*virology ; Internationality ; Orthomyxoviridae Infections/epidemiology/*veterinary/virology ; Population Surveillance ; Swine/*virology ; Swine Diseases/*epidemiology/transmission/virology ; Zoonoses/*epidemiology/transmission/*virology
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  • 145
    Publication Date: 2009-02-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Monastersky, Richard -- England -- Nature. 2009 Feb 26;457(7233):1077-8. doi: 10.1038/4571077a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19242449" target="_blank"〉PubMed〈/a〉
    Keywords: Alaska/ethnology ; Animals ; Arctic Regions ; Canada/ethnology ; *Ethnic Groups ; Greenhouse Effect ; Humans ; Reindeer ; Research/*manpower ; Ursidae/physiology ; *Weather
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  • 146
    Publication Date: 2009-12-18
    Description: Effects of susceptibility variants may depend on from which parent they are inherited. Although many associations between sequence variants and human traits have been discovered through genome-wide associations, the impact of parental origin has largely been ignored. Here we show that for 38,167 Icelanders genotyped using single nucleotide polymorphism (SNP) chips, the parental origin of most alleles can be determined. For this we used a combination of genealogy and long-range phasing. We then focused on SNPs that associate with diseases and are within 500 kilobases of known imprinted genes. Seven independent SNP associations were examined. Five-one with breast cancer, one with basal-cell carcinoma and three with type 2 diabetes-have parental-origin-specific associations. These variants are located in two genomic regions, 11p15 and 7q32, each harbouring a cluster of imprinted genes. Furthermore, we observed a novel association between the SNP rs2334499 at 11p15 and type 2 diabetes. Here the allele that confers risk when paternally inherited is protective when maternally transmitted. We identified a differentially methylated CTCF-binding site at 11p15 and demonstrated correlation of rs2334499 with decreased methylation of that site.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3746295/" 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/PMC3746295/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kong, Augustine -- Steinthorsdottir, Valgerdur -- Masson, Gisli -- Thorleifsson, Gudmar -- Sulem, Patrick -- Besenbacher, Soren -- Jonasdottir, Aslaug -- Sigurdsson, Asgeir -- Kristinsson, Kari Th -- Jonasdottir, Adalbjorg -- Frigge, Michael L -- Gylfason, Arnaldur -- Olason, Pall I -- Gudjonsson, Sigurjon A -- Sverrisson, Sverrir -- Stacey, Simon N -- Sigurgeirsson, Bardur -- Benediktsdottir, Kristrun R -- Sigurdsson, Helgi -- Jonsson, Thorvaldur -- Benediktsson, Rafn -- Olafsson, Jon H -- Johannsson, Oskar Th -- Hreidarsson, Astradur B -- Sigurdsson, Gunnar -- DIAGRAM Consortium -- Ferguson-Smith, Anne C -- Gudbjartsson, Daniel F -- Thorsteinsdottir, Unnur -- Stefansson, Kari -- 077016/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- G9723500/Medical Research Council/United Kingdom -- K08 AR055688/AR/NIAMS NIH HHS/ -- MC_U106179471/Medical Research Council/United Kingdom -- MC_U106179474/Medical Research Council/United Kingdom -- MC_U127592696/Medical Research Council/United Kingdom -- R01 DK029867/DK/NIDDK NIH HHS/ -- England -- Nature. 2009 Dec 17;462(7275):868-74. doi: 10.1038/nature08625.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland. kong@decode.is〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20016592" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Binding Sites ; Breast Neoplasms/genetics ; Carcinoma, Basal Cell/genetics ; Chromosomes, Human, Pair 11/genetics ; Chromosomes, Human, Pair 7/genetics ; DNA Methylation/genetics ; Diabetes Mellitus, Type 2/genetics ; *Fathers ; Female ; Genetic Predisposition to Disease/*genetics ; Genome, Human/genetics ; Genomic Imprinting/genetics ; Haplotypes ; Humans ; Iceland ; Male ; *Mothers ; Pedigree ; Polymorphism, Single Nucleotide/*genetics ; Repressor Proteins/metabolism
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  • 147
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    Nature Publishing Group (NPG)
    Publication Date: 2009-05-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2009 May 28;459(7246):490-1. doi: 10.1038/459490a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19478748" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Birds/virology ; Developing Countries ; *Geography ; Humans ; Influenza A Virus, H1N1 Subtype/genetics/*isolation & purification/*pathogenicity ; Influenza, Human/economics/*epidemiology/prevention & control/*virology ; Population Surveillance ; Reassortant Viruses/genetics/pathogenicity ; Swine/virology ; Time Factors ; *Tropical Climate
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  • 148
    Publication Date: 2009-09-11
    Description: Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement. To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population. Current annual worldwide potato crop losses due to late blight are conservatively estimated at $6.7 billion. Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars. Here we report the sequence of the P. infestans genome, which at approximately 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for approximately 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haas, Brian J -- Kamoun, Sophien -- Zody, Michael C -- Jiang, Rays H Y -- Handsaker, Robert E -- Cano, Liliana M -- Grabherr, Manfred -- Kodira, Chinnappa D -- Raffaele, Sylvain -- Torto-Alalibo, Trudy -- Bozkurt, Tolga O -- Ah-Fong, Audrey M V -- Alvarado, Lucia -- Anderson, Vicky L -- Armstrong, Miles R -- Avrova, Anna -- Baxter, Laura -- Beynon, Jim -- Boevink, Petra C -- Bollmann, Stephanie R -- Bos, Jorunn I B -- Bulone, Vincent -- Cai, Guohong -- Cakir, Cahid -- Carrington, James C -- Chawner, Megan -- Conti, Lucio -- Costanzo, Stefano -- Ewan, Richard -- Fahlgren, Noah -- Fischbach, Michael A -- Fugelstad, Johanna -- Gilroy, Eleanor M -- Gnerre, Sante -- Green, Pamela J -- Grenville-Briggs, Laura J -- Griffith, John -- Grunwald, Niklaus J -- Horn, Karolyn -- Horner, Neil R -- Hu, Chia-Hui -- Huitema, Edgar -- Jeong, Dong-Hoon -- Jones, Alexandra M E -- Jones, Jonathan D G -- Jones, Richard W -- Karlsson, Elinor K -- Kunjeti, Sridhara G -- Lamour, Kurt -- Liu, Zhenyu -- Ma, Lijun -- Maclean, Daniel -- Chibucos, Marcus C -- McDonald, Hayes -- McWalters, Jessica -- Meijer, Harold J G -- Morgan, William -- Morris, Paul F -- Munro, Carol A -- O'Neill, Keith -- Ospina-Giraldo, Manuel -- Pinzon, Andres -- Pritchard, Leighton -- Ramsahoye, Bernard -- Ren, Qinghu -- Restrepo, Silvia -- Roy, Sourav -- Sadanandom, Ari -- Savidor, Alon -- Schornack, Sebastian -- Schwartz, David C -- Schumann, Ulrike D -- Schwessinger, Ben -- Seyer, Lauren -- Sharpe, Ted -- Silvar, Cristina -- Song, Jing -- Studholme, David J -- Sykes, Sean -- Thines, Marco -- van de Vondervoort, Peter J I -- Phuntumart, Vipaporn -- Wawra, Stephan -- Weide, Rob -- Win, Joe -- Young, Carolyn -- Zhou, Shiguo -- Fry, William -- Meyers, Blake C -- van West, Pieter -- Ristaino, Jean -- Govers, Francine -- Birch, Paul R J -- Whisson, Stephen C -- Judelson, Howard S -- Nusbaum, Chad -- BB/E007120/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/G015244/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- G0400284/Medical Research Council/United Kingdom -- England -- Nature. 2009 Sep 17;461(7262):393-8. doi: 10.1038/nature08358. Epub 2009 Sep 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02141, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19741609" target="_blank"〉PubMed〈/a〉
    Keywords: Algal Proteins/genetics ; DNA Transposable Elements/genetics ; DNA, Intergenic/genetics ; Evolution, Molecular ; Genome/*genetics ; Host-Pathogen Interactions/genetics ; Humans ; Ireland ; Molecular Sequence Data ; Necrosis ; Phenotype ; Phytophthora infestans/*genetics/pathogenicity ; Plant Diseases/immunology/*microbiology ; Solanum tuberosum/immunology/*microbiology ; Starvation
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  • 149
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    Nature Publishing Group (NPG)
    Publication Date: 2009-01-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2009 Jan 8;457(7226):130. doi: 10.1038/457130a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19129802" target="_blank"〉PubMed〈/a〉
    Keywords: Biotechnology/*economics/*trends ; Cuba ; Humans
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  • 150
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    Nature Publishing Group (NPG)
    Publication Date: 2009-05-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2009 May 14;459(7244):144-5. doi: 10.1038/459144a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19444174" target="_blank"〉PubMed〈/a〉
    Keywords: Age Factors ; Aging/immunology ; Disease Outbreaks/prevention & control ; Humans ; Influenza A Virus, H1N1 Subtype/growth & development/*immunology ; Influenza Vaccines/administration & dosage/immunology/standards/*supply & ; distribution ; Influenza, Human/immunology/*prevention & control/*virology ; International Cooperation ; Time Factors ; Vaccines, Attenuated/adverse effects/immunology/*supply & distribution ; Vaccines, Inactivated/administration & dosage/immunology/supply & distribution ; *World Health Organization
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  • 151
    Publication Date: 2009-02-06
    Description: The metabolism of oxygen, although central to life, produces reactive oxygen species (ROS) that have been implicated in processes as diverse as cancer, cardiovascular disease and ageing. It has recently been shown that central nervous system stem cells and haematopoietic stem cells and early progenitors contain lower levels of ROS than their more mature progeny, and that these differences are critical for maintaining stem cell function. We proposed that epithelial tissue stem cells and their cancer stem cell (CSC) counterparts may also share this property. Here we show that normal mammary epithelial stem cells contain lower concentrations of ROS than their more mature progeny cells. Notably, subsets of CSCs in some human and murine breast tumours contain lower ROS levels than corresponding non-tumorigenic cells (NTCs). Consistent with ROS being critical mediators of ionizing-radiation-induced cell killing, CSCs in these tumours develop less DNA damage and are preferentially spared after irradiation compared to NTCs. Lower ROS levels in CSCs are associated with increased expression of free radical scavenging systems. Pharmacological depletion of ROS scavengers in CSCs markedly decreases their clonogenicity and results in radiosensitization. These results indicate that, similar to normal tissue stem cells, subsets of CSCs in some tumours contain lower ROS levels and enhanced ROS defences compared to their non-tumorigenic progeny, which may contribute to tumour radioresistance.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2778612/" 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/PMC2778612/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Diehn, Maximilian -- Cho, Robert W -- Lobo, Neethan A -- Kalisky, Tomer -- Dorie, Mary Jo -- Kulp, Angela N -- Qian, Dalong -- Lam, Jessica S -- Ailles, Laurie E -- Wong, Manzhi -- Joshua, Benzion -- Kaplan, Michael J -- Wapnir, Irene -- Dirbas, Frederick M -- Somlo, George -- Garberoglio, Carlos -- Paz, Benjamin -- Shen, Jeannie -- Lau, Sean K -- Quake, Stephen R -- Brown, J Martin -- Weissman, Irving L -- Clarke, Michael F -- R01 CA100225/CA/NCI NIH HHS/ -- R01 CA100225-05/CA/NCI NIH HHS/ -- U54 CA126524/CA/NCI NIH HHS/ -- U54 CA126524-04/CA/NCI NIH HHS/ -- England -- Nature. 2009 Apr 9;458(7239):780-3. doi: 10.1038/nature07733.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19194462" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breast Neoplasms/physiopathology ; Cells, Cultured ; DNA Damage/genetics/radiation effects ; Female ; Gene Expression ; Humans ; Mammary Glands, Human/cytology/metabolism ; Mice ; Mice, Inbred C57BL ; Neoplastic Stem Cells/*metabolism/*radiation effects ; Radiation Tolerance/*physiology ; Reactive Oxygen Species/*metabolism
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  • 152
    Publication Date: 2009-04-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moorman, David E -- Aston-Jones, Gary -- England -- Nature. 2009 Apr 23;458(7241):980-1. doi: 10.1038/458980a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19396134" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cyclic AMP Response Element-Binding Protein/metabolism ; *Genetic Engineering ; Humans ; Intracellular Space/metabolism/radiation effects ; Nucleus Accumbens/cytology/metabolism/radiation effects ; Receptors, Adrenergic/genetics/metabolism ; Receptors, G-Protein-Coupled/genetics/*metabolism ; Recombinant Fusion Proteins/genetics/metabolism ; Reward ; Rhodopsin/genetics/*metabolism ; Signal Transduction/*radiation effects ; Structure-Activity Relationship
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  • 153
    Publication Date: 2009-05-22
    Description: Cohesin-mediated sister chromatid cohesion is essential for chromosome segregation and post-replicative DNA repair. In addition, evidence from model organisms and from human genetics suggests that cohesin is involved in the control of gene expression. This non-canonical role has recently been rationalized by the findings that mammalian cohesin complexes are recruited to a subset of DNase I hypersensitive sites and to conserved noncoding sequences by the DNA-binding protein CTCF. CTCF functions at insulators (which control interactions between enhancers and promoters) and at boundary elements (which demarcate regions of distinct chromatin structure), and cohesin contributes to its enhancer-blocking activity. The underlying mechanisms remain unknown, and the full spectrum of cohesin functions remains to be determined. Here we show that cohesin forms the topological and mechanistic basis for cell-type-specific long-range chromosomal interactions in cis at the developmentally regulated cytokine locus IFNG. Hence, the ability of cohesin to constrain chromosome topology is used not only for the purpose of sister chromatid cohesion, but also to dynamically define the spatial conformation of specific loci. This new aspect of cohesin function is probably important for normal development and disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2869028/" 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/PMC2869028/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hadjur, Suzana -- Williams, Luke M -- Ryan, Natalie K -- Cobb, Bradley S -- Sexton, Tom -- Fraser, Peter -- Fisher, Amanda G -- Merkenschlager, Matthias -- G0900491/Medical Research Council/United Kingdom -- G117/530/Medical Research Council/United Kingdom -- MC_U120027516/Medical Research Council/United Kingdom -- U.1200(U.1200)/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- England -- Nature. 2009 Jul 16;460(7253):410-3. doi: 10.1038/nature08079. Epub 2009 May 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London W12 0NN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19458616" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CD4-Positive T-Lymphocytes/metabolism ; Cell Cycle Proteins/*metabolism ; Cell Line ; Chromosomal Proteins, Non-Histone/*metabolism ; Chromosomes/*genetics/*metabolism ; *Gene Expression Regulation, Developmental ; Histones/metabolism ; Humans ; Interferon-gamma/*genetics ; Mice ; Nuclear Proteins/genetics/metabolism ; Organ Specificity ; Phosphoproteins/genetics/metabolism ; Repressor Proteins/metabolism
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  • 154
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    Publication Date: 2009-02-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sachs, Jeffrey -- England -- Nature. 2009 Feb 19;457(7232):958. doi: 10.1038/457958a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Earth Institute at Columbia University, New York, USA. sachs@columbia.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19225500" target="_blank"〉PubMed〈/a〉
    Keywords: Africa ; Conservation of Natural Resources/economics/trends ; Developing Countries/*economics ; Humans ; *International Cooperation ; Investments/*economics/trends
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  • 155
    Publication Date: 2009-11-13
    Description: The signalling pathways controlling both the evolution and development of language in the human brain remain unknown. So far, the transcription factor FOXP2 (forkhead box P2) is the only gene implicated in Mendelian forms of human speech and language dysfunction. It has been proposed that the amino acid composition in the human variant of FOXP2 has undergone accelerated evolution, and this two-amino-acid change occurred around the time of language emergence in humans. However, this remains controversial, and whether the acquisition of these amino acids in human FOXP2 has any functional consequence in human neurons remains untested. Here we demonstrate that these two human-specific amino acids alter FOXP2 function by conferring differential transcriptional regulation in vitro. We extend these observations in vivo to human and chimpanzee brain, and use network analysis to identify novel relationships among the differentially expressed genes. These data provide experimental support for the functional relevance of changes in FOXP2 that occur on the human lineage, highlighting specific pathways with direct consequences for human brain development and disease in the central nervous system (CNS). Because FOXP2 has an important role in speech and language in humans, the identified targets may have a critical function in the development and evolution of language circuitry in humans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2778075/" 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/PMC2778075/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Konopka, Genevieve -- Bomar, Jamee M -- Winden, Kellen -- Coppola, Giovanni -- Jonsson, Zophonias O -- Gao, Fuying -- Peng, Sophia -- Preuss, Todd M -- Wohlschlegel, James A -- Geschwind, Daniel H -- N01-HD-4-3368/HD/NICHD NIH HHS/ -- N01-HD-4-3383/HD/NICHD NIH HHS/ -- R21 MH075028/MH/NIMH NIH HHS/ -- R21 MH075028-02/MH/NIMH NIH HHS/ -- R21MH075028/MH/NIMH NIH HHS/ -- R37 MH060233/MH/NIMH NIH HHS/ -- R37 MH060233-06A1/MH/NIMH NIH HHS/ -- R37MH60233-06A1/MH/NIMH NIH HHS/ -- RR00165/RR/NCRR NIH HHS/ -- T32HD007032/HD/NICHD NIH HHS/ -- T32MH073526/MH/NIMH NIH HHS/ -- England -- Nature. 2009 Nov 12;462(7270):213-7. doi: 10.1038/nature08549.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Neurogenetics, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA. gena@alum.mit.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19907493" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/cytology/*embryology/*metabolism ; Cell Line ; Evolution, Molecular ; Forkhead Transcription Factors/chemistry/genetics/*metabolism ; *Gene Expression Regulation, Developmental ; Humans ; Language ; Pan troglodytes/embryology/genetics/metabolism ; Promoter Regions, Genetic/genetics ; Species Specificity ; Speech/physiology ; *Transcription, Genetic ; Transcriptional Activation
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  • 156
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    Nature Publishing Group (NPG)
    Publication Date: 2009-05-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2009 Apr 30;458(7242):1082-3. doi: 10.1038/4581082a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19407756" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Birds/virology ; Centers for Disease Control and Prevention (U.S.) ; Disease Outbreaks/*statistics & numerical data ; Humans ; Influenza A Virus, H1N1 Subtype/genetics/*isolation & purification/pathogenicity ; Influenza A Virus, H5N1 Subtype/pathogenicity ; Influenza, Human/*epidemiology/mortality/transmission/virology ; *Internationality ; Mexico/epidemiology ; Swine/*virology ; United States ; World Health Organization
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  • 157
    Publication Date: 2009-01-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moriguchi, Hisashi -- Sato, Chifumi -- England -- Nature. 2009 Jan 15;457(7227):257. doi: 10.1038/457257c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19148077" target="_blank"〉PubMed〈/a〉
    Keywords: Embryo Research/*legislation & jurisprudence ; *Embryonic Stem Cells/cytology ; Humans ; Japan ; Patents as Topic ; Pluripotent Stem Cells/cytology
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  • 158
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    Publication Date: 2009-12-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kool, Richard -- England -- Nature. 2009 Dec 24;462(7276):984. doi: 10.1038/462984a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20033021" target="_blank"〉PubMed〈/a〉
    Keywords: History, 19th Century ; Humans ; *Periodicals as Topic ; Science/*history ; Selection, Genetic
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  • 159
    Publication Date: 2009-06-19
    Description: Common copy number variations (CNVs) represent a significant source of genetic diversity, yet their influence on phenotypic variability, including disease susceptibility, remains poorly understood. To address this problem in human cancer, we performed a genome-wide association study of CNVs in the childhood cancer neuroblastoma, a disease in which single nucleotide polymorphism variations are known to influence susceptibility. We first genotyped 846 Caucasian neuroblastoma patients and 803 healthy Caucasian controls at approximately 550,000 single nucleotide polymorphisms, and performed a CNV-based test for association. We then replicated significant observations in two independent sample sets comprised of a total of 595 cases and 3,357 controls. Here we describe the identification of a common CNV at chromosome 1q21.1 associated with neuroblastoma in the discovery set, which was confirmed in both replication sets. This CNV was validated by quantitative polymerase chain reaction, fluorescent in situ hybridization and analysis of matched tumour specimens, and was shown to be heritable in an independent set of 713 cancer-free parent-offspring trios. We identified a previously unknown transcript within the CNV that showed high sequence similarity to several neuroblastoma breakpoint family (NBPF) genes and represents a new member of this gene family (NBPF23). This transcript was preferentially expressed in fetal brain and fetal sympathetic nervous tissues, and the expression level was strictly correlated with CNV state in neuroblastoma cells. These data demonstrate that inherited copy number variation at 1q21.1 is associated with neuroblastoma and implicate a previously unknown neuroblastoma breakpoint family gene in early tumorigenesis of this childhood cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755253/" 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/PMC2755253/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Diskin, Sharon J -- Hou, Cuiping -- Glessner, Joseph T -- Attiyeh, Edward F -- Laudenslager, Marci -- Bosse, Kristopher -- Cole, Kristina -- Mosse, Yael P -- Wood, Andrew -- Lynch, Jill E -- Pecor, Katlyn -- Diamond, Maura -- Winter, Cynthia -- Wang, Kai -- Kim, Cecilia -- Geiger, Elizabeth A -- McGrady, Patrick W -- Blakemore, Alexandra I F -- London, Wendy B -- Shaikh, Tamim H -- Bradfield, Jonathan -- Grant, Struan F A -- Li, Hongzhe -- Devoto, Marcella -- Rappaport, Eric R -- Hakonarson, Hakon -- Maris, John M -- GM081519/GM/NIGMS NIH HHS/ -- R00 CA151869/CA/NCI NIH HHS/ -- R01 CA087847/CA/NCI NIH HHS/ -- R01 CA087847-05/CA/NCI NIH HHS/ -- R01 CA124709/CA/NCI NIH HHS/ -- R01 CA124709-02/CA/NCI NIH HHS/ -- R01-CA124709/CA/NCI NIH HHS/ -- R01-CA87847/CA/NCI NIH HHS/ -- T32-HG000046/HG/NHGRI NIH HHS/ -- U10 CA098543/CA/NCI NIH HHS/ -- U10 CA098543-07/CA/NCI NIH HHS/ -- U10-CA98543/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Jun 18;459(7249):987-91. doi: 10.1038/nature08035.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19536264" target="_blank"〉PubMed〈/a〉
    Keywords: Child ; Chromosome Breakage ; Chromosomes, Human, Pair 1/*genetics ; European Continental Ancestry Group/genetics ; Fetus/metabolism ; Gene Dosage/*genetics ; Genetic Predisposition to Disease/genetics ; Genetic Variation/*genetics ; Genome-Wide Association Study ; Genotype ; Humans ; In Situ Hybridization, Fluorescence ; Neuroblastoma/*genetics ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide/genetics ; RNA, Messenger/genetics ; Reproducibility of Results
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  • 160
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    Nature Publishing Group (NPG)
    Publication Date: 2009-05-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2009 May 7;459(7243):14-5. doi: 10.1038/459014a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19424121" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antiviral Agents/therapeutic use ; Disease Outbreaks/prevention & control/*statistics & numerical data ; Humans ; Influenza A Virus, H1N1 Subtype/*physiology ; Influenza Vaccines ; Influenza, Human/drug therapy/*epidemiology/mortality/prevention & control ; Oseltamivir/therapeutic use ; Time Factors ; Zanamivir/therapeutic use
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  • 161
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    Nature Publishing Group (NPG)
    Publication Date: 2009-04-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dobson, Jerome E -- England -- Nature. 2009 Apr 23;458(7241):968. doi: 10.1038/458968a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Geography at the University of Kansas, Lawrence, Kansas 66045, USA. dobson@ku.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19396123" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Phones/utilization ; Geographic Information Systems/*utilization ; Human Rights ; Humans ; Informed Consent ; *Locomotion ; Monitoring, Physiologic/instrumentation ; Privacy ; Social Behavior
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  • 162
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    Nature Publishing Group (NPG)
    Publication Date: 2009-04-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2009 Apr 23;458(7241):950-1. doi: 10.1038/458950b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19396104" target="_blank"〉PubMed〈/a〉
    Keywords: Anti-HIV Agents/*economics ; Drug Combinations ; Drug Industry/*economics/*organization & administration ; HIV Infections/drug therapy ; Humans ; London ; New York
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  • 163
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    Nature Publishing Group (NPG)
    Publication Date: 2009-01-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2009 Jan 1;457(7225):7-8. doi: 10.1038/457007b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19122601" target="_blank"〉PubMed〈/a〉
    Keywords: *Bibliometrics ; Evaluation Studies as Topic ; Great Britain ; Humans ; *Peer Review, Research/methods/standards
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  • 164
    Publication Date: 2009-11-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dolan, Paul -- England -- Nature. 2009 Nov 5;462(7269):35. doi: 10.1038/462035a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19890311" target="_blank"〉PubMed〈/a〉
    Keywords: Evidence-Based Medicine/*methods/*standards ; Great Britain ; Health Care Rationing/*methods/standards ; Humans ; *Public Opinion ; *Quality of Life ; Quality-Adjusted Life Years
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  • 165
    Publication Date: 2009-12-18
    Description: Mutations in BRCA1 are associated with a high risk of breast and ovarian cancer. BRCA1 participates in the DNA damage response and acts as a ubiquitin ligase. However, its regulation remains poorly understood. Here we report that BRCA1 is modified by small ubiquitin-like modifier (SUMO) in response to genotoxic stress, and co-localizes at sites of DNA damage with SUMO1, SUMO2/3 and the SUMO-conjugating enzyme Ubc9. PIAS SUMO E3 ligases co-localize with and modulate SUMO modification of BRCA1, and are required for BRCA1 ubiquitin ligase activity in cells. In vitro SUMO modification of the BRCA1/BARD1 heterodimer greatly increases its ligase activity, identifying it as a SUMO-regulated ubiquitin ligase (SRUbL). Further, PIAS SUMO ligases are required for complete accumulation of double-stranded DNA (dsDNA) damage-repair proteins subsequent to RNF8 accrual, and for proficient double-strand break repair. These data demonstrate that the SUMOylation pathway plays a significant role in mammalian DNA damage response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morris, Joanna R -- Boutell, Chris -- Keppler, Melanie -- Densham, Ruth -- Weekes, Daniel -- Alamshah, Amin -- Butler, Laura -- Galanty, Yaron -- Pangon, Laurent -- Kiuchi, Tai -- Ng, Tony -- Solomon, Ellen -- 10331/Cancer Research UK/United Kingdom -- 6900577/Medical Research Council/United Kingdom -- C8820/A9494/Cancer Research UK/United Kingdom -- G0100152 #56891/Medical Research Council/United Kingdom -- G9600577/Medical Research Council/United Kingdom -- MC_UP_A550_1030/Medical Research Council/United Kingdom -- England -- Nature. 2009 Dec 17;462(7275):886-90. doi: 10.1038/nature08593.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical and Molecular Genetics, King's College London, Guy's Medical School Campus, London SE1 9RT, UK. jo.morris@genetics.kcl.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20016594" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; BRCA1 Protein/*metabolism ; COS Cells ; Cell Line ; Cercopithecus aethiops ; DNA Breaks, Double-Stranded ; *DNA Damage ; DNA Repair ; HeLa Cells ; Histones/metabolism ; Humans ; Protein Inhibitors of Activated STAT/metabolism ; Small Ubiquitin-Related Modifier Proteins/*metabolism ; Ubiquitin-Conjugating Enzymes/metabolism ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination
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  • 166
    Publication Date: 2009-02-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abate-Shen, Cory -- Shen, Michael M -- England -- Nature. 2009 Feb 12;457(7231):799-800. doi: 10.1038/457799a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19212391" target="_blank"〉PubMed〈/a〉
    Keywords: Biomarkers/metabolism ; Humans ; Male ; *Metabolome ; Prostatic Neoplasms/*diagnosis ; Sarcosine/metabolism
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  • 167
    Publication Date: 2009-03-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zlitni, Soumaya -- Brown, Eric D -- England -- Nature. 2009 Mar 5;458(7234):39-40. doi: 10.1038/458039a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19262660" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Bacterial Agents/*pharmacology ; Drug Evaluation, Preclinical ; *Drug Resistance, Bacterial ; Fatty Acids/analysis/*biosynthesis/chemistry/pharmacology ; Gram-Positive Bacteria/*drug effects/enzymology/genetics/pathogenicity ; Humans ; Reproducibility of Results ; Serum/chemistry/microbiology ; Substrate Specificity
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  • 168
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    Publication Date: 2009-12-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dolgin, Elie -- England -- Nature. 2009 Dec 17;462(7275):843-5. doi: 10.1038/462843a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20016572" target="_blank"〉PubMed〈/a〉
    Keywords: Female ; Genome, Human/*genetics ; History, 20th Century ; History, 21st Century ; *Human Genome Project/history ; Humans ; Male ; Reproducibility of Results ; Research Design ; *Research Personnel ; Research Subjects
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  • 169
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    Publication Date: 2009-10-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dolgin, Elie -- England -- Nature. 2009 Oct 15;461(7266):854-5. doi: 10.1038/461854b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19829337" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Disease Models, Animal ; Homeodomain Proteins/metabolism ; Humans ; Mice ; Microfluidic Analytical Techniques ; Neoplasm Metastasis/diagnosis/drug therapy/*pathology/prevention & control ; Neoplasms/drug therapy/metabolism/mortality/*pathology ; Neoplastic Stem Cells/pathology ; Transcription Factors/metabolism ; rho-Associated Kinases/antagonists & inhibitors/metabolism
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  • 170
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    Publication Date: 2009-11-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abbott, Alison -- England -- Nature. 2009 Nov 19;462(7271):265. doi: 10.1038/462265a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19924182" target="_blank"〉PubMed〈/a〉
    Keywords: *Embryonic Stem Cells ; Germany ; Humans ; Patents as Topic/ethics/*legislation & jurisprudence
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  • 171
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    Nature Publishing Group (NPG)
    Publication Date: 2009-08-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dolgin, Elie -- England -- Nature. 2009 Aug 27;460(7259):1069. doi: 10.1038/4601069a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19713906" target="_blank"〉PubMed〈/a〉
    Keywords: Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal, Humanized ; Cetuximab ; Colorectal Neoplasms/diagnosis/drug therapy/genetics ; Drug Labeling/*legislation & jurisprudence ; Genes, ras/genetics ; Genetic Markers/genetics ; Genetic Testing ; Humans ; Pharmacogenetics ; Randomized Controlled Trials as Topic ; United States ; United States Food and Drug Administration/*legislation & jurisprudence
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  • 172
    Publication Date: 2009-07-22
    Description: Acquired uniparental disomy (aUPD) is a common feature of cancer genomes, leading to loss of heterozygosity. aUPD is associated not only with loss-of-function mutations of tumour suppressor genes, but also with gain-of-function mutations of proto-oncogenes. Here we show unique gain-of-function mutations of the C-CBL (also known as CBL) tumour suppressor that are tightly associated with aUPD of the 11q arm in myeloid neoplasms showing myeloproliferative features. The C-CBL proto-oncogene, a cellular homologue of v-Cbl, encodes an E3 ubiquitin ligase and negatively regulates signal transduction of tyrosine kinases. Homozygous C-CBL mutations were found in most 11q-aUPD-positive myeloid malignancies. Although the C-CBL mutations were oncogenic in NIH3T3 cells, c-Cbl was shown to functionally and genetically act as a tumour suppressor. C-CBL mutants did not have E3 ubiquitin ligase activity, but inhibited that of wild-type C-CBL and CBL-B (also known as CBLB), leading to prolonged activation of tyrosine kinases after cytokine stimulation. c-Cbl(-/-) haematopoietic stem/progenitor cells (HSPCs) showed enhanced sensitivity to a variety of cytokines compared to c-Cbl(+/+) HSPCs, and transduction of C-CBL mutants into c-Cbl(-/-) HSPCs further augmented their sensitivities to a broader spectrum of cytokines, including stem-cell factor (SCF, also known as KITLG), thrombopoietin (TPO, also known as THPO), IL3 and FLT3 ligand (FLT3LG), indicating the presence of a gain-of-function that could not be attributed to a simple loss-of-function. The gain-of-function effects of C-CBL mutants on cytokine sensitivity of HSPCs largely disappeared in a c-Cbl(+/+) background or by co-transduction of wild-type C-CBL, which suggests the pathogenic importance of loss of wild-type C-CBL alleles found in most cases of C-CBL-mutated myeloid neoplasms. Our findings provide a new insight into a role of gain-of-function mutations of a tumour suppressor associated with aUPD in the pathogenesis of some myeloid cancer subsets.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sanada, Masashi -- Suzuki, Takahiro -- Shih, Lee-Yung -- Otsu, Makoto -- Kato, Motohiro -- Yamazaki, Satoshi -- Tamura, Azusa -- Honda, Hiroaki -- Sakata-Yanagimoto, Mamiko -- Kumano, Keiki -- Oda, Hideaki -- Yamagata, Tetsuya -- Takita, Junko -- Gotoh, Noriko -- Nakazaki, Kumi -- Kawamata, Norihiko -- Onodera, Masafumi -- Nobuyoshi, Masaharu -- Hayashi, Yasuhide -- Harada, Hiroshi -- Kurokawa, Mineo -- Chiba, Shigeru -- Mori, Hiraku -- Ozawa, Keiya -- Omine, Mitsuhiro -- Hirai, Hisamaru -- Nakauchi, Hiromitsu -- Koeffler, H Phillip -- Ogawa, Seishi -- 2R01CA026038-30/CA/NCI NIH HHS/ -- England -- Nature. 2009 Aug 13;460(7257):904-8. doi: 10.1038/nature08240. Epub 2009 Jul 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Genomics Project, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19620960" target="_blank"〉PubMed〈/a〉
    Keywords: Allelic Imbalance ; Amino Acid Sequence ; Animals ; Base Sequence ; Chromosomes, Human, Pair 11/genetics ; Female ; *Genes, Tumor Suppressor ; Humans ; Leukemia, Myeloid/*genetics/metabolism/pathology ; Male ; Mice ; Mice, Knockout ; Mice, Nude ; Models, Molecular ; Molecular Sequence Data ; Mutant Proteins/chemistry/genetics/*metabolism ; Mutation ; NIH 3T3 Cells ; Neoplasm Transplantation ; Oncogenes/genetics ; Phosphorylation ; Protein Conformation ; Proto-Oncogene Proteins c-cbl/antagonists & ; inhibitors/chemistry/deficiency/*genetics/*metabolism ; Ubiquitination ; Uniparental Disomy/genetics ; ras Proteins/genetics/metabolism
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  • 173
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    Nature Publishing Group (NPG)
    Publication Date: 2009-02-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2009 Feb 12;457(7231):772-3. doi: 10.1038/457772a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19212370" target="_blank"〉PubMed〈/a〉
    Keywords: Anti-Infective Agents/administration & dosage/economics ; Foundations/economics ; *Global Health ; Humans ; Parasitic Diseases/prevention & control ; Preventive Health Services/*economics/organization & administration ; Trachoma/prevention & control ; Tropical Medicine/economics/organization & administration
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  • 174
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    Nature Publishing Group (NPG)
    Publication Date: 2009-08-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dolgin, Elie -- England -- Nature. 2009 Aug 20;460(7258):939. doi: 10.1038/460939a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19693051" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/trends ; Budgets ; Clinical Medicine/trends ; Developing Countries ; Genetic Predisposition to Disease ; Health Care Costs ; Humans ; National Institutes of Health (U.S.)/economics/*organization & ; administration/*trends ; Rare Diseases ; Religion and Science ; United States
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  • 175
    Publication Date: 2009-10-13
    Description: To initiate gene transcription, RNA polymerase II (Pol II) requires the transcription factor IIB (B). Here we present the crystal structure of the complete Pol II-B complex at 4.3 A resolution, and complementary functional data. The results indicate the mechanism of transcription initiation, including the transition to RNA elongation. Promoter DNA is positioned over the Pol II active centre cleft with the 'B-core' domain that binds the wall at the end of the cleft. DNA is then opened with the help of the 'B-linker' that binds the Pol II rudder and clamp coiled-coil at the edge of the cleft. The DNA template strand slips into the cleft and is scanned for the transcription start site with the help of the 'B-reader' that approaches the active site. Synthesis of the RNA chain and rewinding of upstream DNA displace the B-reader and B-linker, respectively, to trigger B release and elongation complex formation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kostrewa, Dirk -- Zeller, Mirijam E -- Armache, Karim-Jean -- Seizl, Martin -- Leike, Kristin -- Thomm, Michael -- Cramer, Patrick -- England -- Nature. 2009 Nov 19;462(7271):323-30. doi: 10.1038/nature08548.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gene Center Munich and Center for Integrated Protein Science Munich (CIPSM), Department of Chemistry and Biochemistry, Ludwig-Maximilians-Universitat Munchen, Feodor-Lynen-Strasse 25, 81377 Munich, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19820686" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Proteins/chemistry ; DNA Polymerase II/*chemistry/*metabolism ; Humans ; *Models, Molecular ; Molecular Sequence Data ; Protein Structure, Quaternary ; Saccharomyces cerevisiae/*genetics/*metabolism ; Sequence Alignment ; TATA-Box Binding Protein/chemistry/metabolism ; Transcription Factor TFIIB/*chemistry/*metabolism
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  • 176
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    Nature Publishing Group (NPG)
    Publication Date: 2009-11-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abbott, Alison -- England -- Nature. 2009 Nov 5;462(7269):24. doi: 10.1038/462024a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19890301" target="_blank"〉PubMed〈/a〉
    Keywords: Budgets ; *Financing, Government ; Germany ; Humans ; Political Systems ; *Research Support as Topic ; Science/*economics
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  • 177
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    Nature Publishing Group (NPG)
    Publication Date: 2009-03-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2009 Feb 26;457(7233):1064. doi: 10.1038/4571064a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19256077" target="_blank"〉PubMed〈/a〉
    Keywords: Child ; Drug Industry/*economics/*trends ; Humans ; *Patents as Topic ; Pharmaceutical Preparations/*economics/*supply & distribution ; Poverty/statistics & numerical data ; Public-Private Sector Partnerships/trends ; Rare Diseases/drug therapy/*economics/epidemiology
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  • 178
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    Nature Publishing Group (NPG)
    Publication Date: 2009-10-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mucke, Lennart -- England -- Nature. 2009 Oct 15;461(7266):895-7. doi: 10.1038/461895a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19829367" target="_blank"〉PubMed〈/a〉
    Keywords: Age of Onset ; Aging ; *Alzheimer Disease/diagnosis/epidemiology/etiology/physiopathology/therapy ; Amyloid beta-Peptides/metabolism ; Animals ; Controlled Clinical Trials as Topic ; Genetic Testing ; Humans ; Mice ; Stem Cell Transplantation ; Treatment Failure ; United States/epidemiology
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  • 179
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    Nature Publishing Group (NPG)
    Publication Date: 2009-02-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moses, Melanie -- England -- Nature. 2009 Feb 5;457(7230):660-1. doi: 10.1038/457660a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Computer Science, University of New Mexico, Albuquerque, NM 87131, USA. melaniem@unm.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19194432" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Birth Rate/trends ; *Conservation of Energy Resources/statistics & numerical data ; Developed Countries/*economics/*statistics & numerical data ; Educational Status ; Greenhouse Effect ; *Human Characteristics ; Humans ; Reproductive Behavior/*physiology ; Resource Allocation/*statistics & numerical data/trends ; Social Behavior ; Social Sciences/*trends ; Transportation ; Urbanization/trends
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  • 180
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    Nature Publishing Group (NPG)
    Publication Date: 2009-10-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abbott, Alison -- England -- Nature. 2009 Oct 15;461(7266):866-8. doi: 10.1038/461866a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19829345" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/*physiology/*surgery ; Brain Mapping/*methods ; Brain Neoplasms/surgery ; Decision Making/physiology ; Electrodes/utilization ; Epilepsy/surgery ; Gambling ; Hippocampus/physiology/surgery ; Humans ; Nucleus Accumbens/physiology/surgery ; Pattern Recognition, Visual/physiology ; Reward ; Writing
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  • 181
    Publication Date: 2009-06-16
    Description: Because nucleosomes are widely replaced by protamine in mature human sperm, the epigenetic contributions of sperm chromatin to embryo development have been considered highly limited. Here we show that the retained nucleosomes are significantly enriched at loci of developmental importance, including imprinted gene clusters, microRNA clusters, HOX gene clusters, and the promoters of stand-alone developmental transcription and signalling factors. Notably, histone modifications localize to particular developmental loci. Dimethylated lysine 4 on histone H3 (H3K4me2) is enriched at certain developmental promoters, whereas large blocks of H3K4me3 localize to a subset of developmental promoters, regions in HOX clusters, certain noncoding RNAs, and generally to paternally expressed imprinted loci, but not paternally repressed loci. Notably, trimethylated H3K27 (H3K27me3) is significantly enriched at developmental promoters that are repressed in early embryos, including many bivalent (H3K4me3/H3K27me3) promoters in embryonic stem cells. Furthermore, developmental promoters are generally DNA hypomethylated in sperm, but acquire methylation during differentiation. Taken together, epigenetic marking in sperm is extensive, and correlated with developmental regulators.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858064/" 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/PMC2858064/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hammoud, Saher Sue -- Nix, David A -- Zhang, Haiying -- Purwar, Jahnvi -- Carrell, Douglas T -- Cairns, Bradley R -- CA16056/CA/NCI NIH HHS/ -- CA24014/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Jul 23;460(7254):473-8. doi: 10.1038/nature08162. Epub 2009 Jun 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Oncological Sciences, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19525931" target="_blank"〉PubMed〈/a〉
    Keywords: Chromatin/*metabolism ; DNA Methylation ; Embryo, Mammalian/embryology ; Gene Expression Regulation, Developmental ; Genes/*genetics ; Genes, Homeobox/genetics ; Genomic Imprinting ; Genomics ; Humans ; Male ; MicroRNAs/genetics ; Multigene Family/genetics ; Nucleosomes/*metabolism ; Promoter Regions, Genetic ; Protamines/metabolism ; Spermatozoa/*metabolism
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  • 182
    Publication Date: 2009-11-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dominguez, Martin H -- Rakic, Pasko -- England -- Nature. 2009 Nov 12;462(7270):169-70. doi: 10.1038/462169a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19907485" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/embryology/metabolism ; Evolution, Molecular ; Forkhead Transcription Factors/chemistry/genetics/*metabolism ; Humans ; Language ; Motor Skills/physiology ; Pan troglodytes/genetics/metabolism ; Species Specificity ; Speech/*physiology
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  • 183
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    Publication Date: 2009-03-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sanchez, Pedro A -- England -- Nature. 2009 Mar 12;458(7235):148. doi: 10.1038/458148a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Earth Institute at Columbia University, 61 Route 9W, Palisades, New York 10964, USA. psanchez@ei.columbia.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19279615" target="_blank"〉PubMed〈/a〉
    Keywords: *Agriculture/economics/methods ; Food/economics ; Humans ; *Hunger ; *International Cooperation ; *Public Policy ; United Nations
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  • 184
    Publication Date: 2009-04-03
    Description: CRM1 (also known as XPO1 and exportin 1) mediates nuclear export of hundreds of proteins through the recognition of the leucine-rich nuclear export signal (LR-NES). Here we present the 2.9 A structure of CRM1 bound to snurportin 1 (SNUPN). Snurportin 1 binds CRM1 in a bipartite manner by means of an amino-terminal LR-NES and its nucleotide-binding domain. The LR-NES is a combined alpha-helical-extended structure that occupies a hydrophobic groove between two CRM1 outer helices. The LR-NES interface explains the consensus hydrophobic pattern, preference for intervening electronegative residues and inhibition by leptomycin B. The second nuclear export signal epitope is a basic surface on the snurportin 1 nucleotide-binding domain, which binds an acidic patch on CRM1 adjacent to the LR-NES site. Multipartite recognition of individually weak nuclear export signal epitopes may be common to CRM1 substrates, enhancing CRM1 binding beyond the generally low affinity LR-NES. Similar energetic construction is also used in multipartite nuclear localization signals to provide broad substrate specificity and rapid evolution in nuclear transport.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437623/" 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/PMC3437623/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dong, Xiuhua -- Biswas, Anindita -- Suel, Katherine E -- Jackson, Laurie K -- Martinez, Rita -- Gu, Hongmei -- Chook, Yuh Min -- 5-T32-GM008297/GM/NIGMS NIH HHS/ -- R01 GM069909/GM/NIGMS NIH HHS/ -- R01GM069909/GM/NIGMS NIH HHS/ -- R01GM069909-03S1/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Apr 30;458(7242):1136-41. doi: 10.1038/nature07975. Epub 2009 Apr 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park, Dallas, Texas 75390-9041, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19339969" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Crystallography, X-Ray ; Epitopes ; Fatty Acids, Unsaturated/pharmacology ; Humans ; Hydrophobic and Hydrophilic Interactions ; Karyopherins/*chemistry/*metabolism ; Leucine/*metabolism ; Models, Molecular ; Nuclear Export Signals/*physiology ; Protein Binding/drug effects ; Protein Conformation ; Receptors, Cytoplasmic and Nuclear/*chemistry/*metabolism ; Structure-Activity Relationship ; Substrate Specificity ; snRNP Core Proteins/chemistry/metabolism
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  • 185
    Publication Date: 2009-11-27
    Description: Receptor-activator of NF-kappaB ligand (TNFSF11, also known as RANKL, OPGL, TRANCE and ODF) and its tumour necrosis factor (TNF)-family receptor RANK are essential regulators of bone remodelling, lymph node organogenesis and formation of a lactating mammary gland. RANKL and RANK are also expressed in the central nervous system. However, the functional relevance of RANKL/RANK in the brain was entirely unknown. Here we report that RANKL and RANK have an essential role in the brain. In both mice and rats, central RANKL injections trigger severe fever. Using tissue-specific Nestin-Cre and GFAP-Cre rank(floxed) deleter mice, the function of RANK in the fever response was genetically mapped to astrocytes. Importantly, Nestin-Cre and GFAP-Cre rank(floxed) deleter mice are resistant to lipopolysaccharide-induced fever as well as fever in response to the key inflammatory cytokines IL-1beta and TNFalpha. Mechanistically, RANKL activates brain regions involved in thermoregulation and induces fever via the COX2-PGE(2)/EP3R pathway. Moreover, female Nestin-Cre and GFAP-Cre rank(floxed) mice exhibit increased basal body temperatures, suggesting that RANKL and RANK control thermoregulation during normal female physiology. We also show that two children with RANK mutations exhibit impaired fever during pneumonia. These data identify an entirely novel and unexpected function for the key osteoclast differentiation factors RANKL/RANK in female thermoregulation and the central fever response in inflammation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hanada, Reiko -- Leibbrandt, Andreas -- Hanada, Toshikatsu -- Kitaoka, Shiho -- Furuyashiki, Tomoyuki -- Fujihara, Hiroaki -- Trichereau, Jean -- Paolino, Magdalena -- Qadri, Fatimunnisa -- Plehm, Ralph -- Klaere, Steffen -- Komnenovic, Vukoslav -- Mimata, Hiromitsu -- Yoshimatsu, Hironobu -- Takahashi, Naoyuki -- von Haeseler, Arndt -- Bader, Michael -- Kilic, Sara Sebnem -- Ueta, Yoichi -- Pifl, Christian -- Narumiya, Shuh -- Penninger, Josef M -- England -- Nature. 2009 Nov 26;462(7272):505-9. doi: 10.1038/nature08596.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19940926" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Astrocytes/drug effects/metabolism ; Body Temperature Regulation/*drug effects/*physiology ; Child ; Dinoprostone/metabolism ; Female ; Fever/*chemically induced/complications/*metabolism ; Gene Expression Profiling ; Humans ; Injections, Intraventricular ; Male ; Mice ; Mice, Inbred C57BL ; Pneumonia/complications/metabolism ; RANK Ligand/administration & dosage/antagonists & ; inhibitors/metabolism/*pharmacology ; Rats ; Rats, Wistar ; Receptor Activator of Nuclear Factor-kappa B/genetics/*metabolism ; Receptors, Prostaglandin E/metabolism ; Receptors, Prostaglandin E, EP3 Subtype ; *Sex Characteristics
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  • 186
    Publication Date: 2009-02-17
    Description: Injury or impaired clearance of apoptotic cells leads to the pathological accumulation of necrotic corpses, which induce an inflammatory response that initiates tissue repair. In addition, antigens present in necrotic cells can sometimes provoke a specific immune response and it has been argued that necrosis could explain adaptive immunity in seemingly infection-free situations, such as after allograft transplantation or in spontaneous and therapy-induced tumour rejection. In the mouse, the CD8alpha+ subset of dendritic cells phagocytoses dead cell remnants and cross-primes CD8+ T cells against cell-associated antigens. Here we show that CD8alpha+ dendritic cells use CLEC9A (also known as DNGR-1), a recently-characterized C-type lectin, to recognize a preformed signal that is exposed on necrotic cells. Loss or blockade of CLEC9A does not impair the uptake of necrotic cell material by CD8+ dendritic cells, but specifically reduces cross-presentation of dead-cell-associated antigens in vitro and decreases the immunogenicity of necrotic cells in vivo. The function of CLEC9A requires a key tyrosine residue in its intracellular tail that allows the recruitment and activation of the tyrosine kinase SYK, which is also essential for cross-presentation of dead-cell-associated antigens. Thus, CLEC9A functions as a SYK-coupled C-type lectin receptor to mediate sensing of necrosis by the principal dendritic-cell subset involved in regulating cross-priming to cell-associated antigens.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671489/" 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/PMC2671489/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sancho, David -- Joffre, Olivier P -- Keller, Anna M -- Rogers, Neil C -- Martinez, Dolores -- Hernanz-Falcon, Patricia -- Rosewell, Ian -- Reis e Sousa, Caetano -- A3598/Cancer Research UK/United Kingdom -- Cancer Research UK/United Kingdom -- England -- Nature. 2009 Apr 16;458(7240):899-903. doi: 10.1038/nature07750.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immunobiology Laboratory, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19219027" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD8/metabolism ; CD8-Positive T-Lymphocytes/immunology ; Cells, Cultured ; Cross-Priming/immunology ; Dendritic Cells/*immunology/*metabolism ; Humans ; Lectins, C-Type/deficiency/genetics/*metabolism ; Ligands ; Mice ; Necrosis/*immunology/*metabolism ; Phagocytosis ; Receptors, Immunologic/deficiency/genetics/*metabolism ; Receptors, Mitogen/genetics/*metabolism ; Signal Transduction
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  • 187
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    Nature Publishing Group (NPG)
    Publication Date: 2009-09-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abbott, Alison -- England -- Nature. 2009 Sep 10;461(7261):158. doi: 10.1038/461158a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19741676" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Use Alternatives/economics/*methods/trends ; Animals ; Chemical Industry/economics/*methods ; Cosmetics/adverse effects/toxicity ; Europe ; Humans ; Mice ; Rats ; Toxicity Tests/economics/*methods/trends ; Toxicology/economics/*methods/trends ; United States
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  • 188
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    Nature Publishing Group (NPG)
    Publication Date: 2009-10-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abbott, Alison -- England -- Nature. 2009 Oct 8;461(7265):706-7. doi: 10.1038/461706a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19812642" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Aging ; DNA-Directed DNA Polymerase/metabolism ; History, 20th Century ; History, 21st Century ; Humans ; *Nobel Prize ; Saccharomyces cerevisiae/genetics ; Telomerase/genetics/*metabolism ; Telomere/genetics/*metabolism ; Tetrahymena thermophila/genetics ; United States
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  • 189
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    Nature Publishing Group (NPG)
    Publication Date: 2009-08-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abbott, Alison -- England -- Nature. 2009 Aug 20;460(7258):947-8. doi: 10.1038/460947a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19693060" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Laboratory ; Collagen Type I/genetics/metabolism ; Diagnostic Tests, Routine/*methods ; *Disease Models, Animal ; Forkhead Transcription Factors/genetics/metabolism ; Germany ; Humans ; Mice ; Mice, Mutant Strains ; Mice, Transgenic ; *Phenotype
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  • 190
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    Nature Publishing Group (NPG)
    Publication Date: 2009-08-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abbott, Alison -- England -- Nature. 2009 Aug 13;460(7257):788. doi: 10.1038/460788a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19675616" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Laboratory ; Biomedical Research/methods/trends ; Databases, Factual ; European Union ; Gene Knockout Techniques/trends ; Genomics/*trends ; Humans ; International Cooperation ; Mice ; *Models, Animal ; National Institutes of Health (U.S.) ; *Rats/genetics/physiology ; Systems Biology/methods/*trends ; United States
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  • 191
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    Nature Publishing Group (NPG)
    Publication Date: 2009-11-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Downward, Julian -- England -- Nature. 2009 Nov 5;462(7269):44-5. doi: 10.1038/462044a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19890318" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Humans ; Lung Neoplasms/genetics/*metabolism/*pathology ; Mice ; NF-kappa B/antagonists & inhibitors/*metabolism ; Oncogene Protein p21(ras)/genetics/*metabolism ; Protein-Serine-Threonine Kinases/antagonists & inhibitors/*metabolism ; *Signal Transduction
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  • 192
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    Nature Publishing Group (NPG)
    Publication Date: 2009-11-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hand, Eric -- England -- Nature. 2009 Nov 12;462(7270):147. doi: 10.1038/462147a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19907463" target="_blank"〉PubMed〈/a〉
    Keywords: Budgets ; *Facility Design and Construction/economics ; Humans ; Isotopes/economics/*supply & distribution ; Security Measures ; United States
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  • 193
    Publication Date: 2009-05-22
    Description: Transmembrane sodium-ion gradients provide energy that can be harnessed by 'secondary transporters' to drive the translocation of solute molecules into a cell. Decades of study have shown that such sodium-coupled transporters are involved in many physiological processes, making them targets for the treatment of numerous diseases. Within the past year, crystal structures of several sodium-coupled transporters from different families have been reported, showing a remarkable structural conservation between functionally unrelated transporters. These atomic-resolution structures are revealing the mechanism of the sodium-coupled transport of solutes across cellular membranes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Krishnamurthy, Harini -- Piscitelli, Chayne L -- Gouaux, Eric -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 May 21;459(7245):347-55. doi: 10.1038/nature08143.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Oregon 97239, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19458710" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Humans ; Membrane Transport Proteins/*chemistry/*metabolism ; Models, Molecular ; Protein Conformation ; Sodium/*metabolism
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  • 194
    Publication Date: 2009-06-19
    Description: Pluripotency of embryonic stem (ES) cells is controlled by defined transcription factors. During differentiation, mouse ES cells undergo global epigenetic reprogramming, as exemplified by X-chromosome inactivation (XCI) in which one female X chromosome is silenced to achieve gene dosage parity between the sexes. Somatic XCI is regulated by homologous X-chromosome pairing and counting, and by the random choice of future active and inactive X chromosomes. XCI and cell differentiation are tightly coupled, as blocking one process compromises the other and dedifferentiation of somatic cells to induced pluripotent stem cells is accompanied by X chromosome reactivation. Recent evidence suggests coupling of Xist expression to pluripotency factors occurs, but how the two are interconnected remains unknown. Here we show that Oct4 (also known as Pou5f1) lies at the top of the XCI hierarchy, and regulates XCI by triggering X-chromosome pairing and counting. Oct4 directly binds Tsix and Xite, two regulatory noncoding RNA genes of the X-inactivation centre, and also complexes with XCI trans-factors, Ctcf and Yy1 (ref. 17), through protein-protein interactions. Depletion of Oct4 blocks homologous X-chromosome pairing and results in the inactivation of both X chromosomes in female cells. Thus, we have identified the first trans-factor that regulates counting, and ascribed new functions to Oct4 during X-chromosome reprogramming.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057664/" 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/PMC3057664/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Donohoe, Mary E -- Silva, Susana S -- Pinter, Stefan F -- Xu, Na -- Lee, Jeannie T -- GM58839/GM/NIGMS NIH HHS/ -- R01 GM058839/GM/NIGMS NIH HHS/ -- R01 GM058839-10/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Jul 2;460(7251):128-32. doi: 10.1038/nature08098. Epub 2009 Jun 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19536159" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; *Chromosome Pairing ; Female ; Humans ; Male ; Mice ; Octamer Transcription Factor-3/deficiency/genetics/*metabolism ; Protein Binding ; RNA, Long Noncoding ; RNA, Untranslated/genetics ; Repressor Proteins/*metabolism ; SOXB1 Transcription Factors ; Transcriptional Activation ; X Chromosome/*genetics/*metabolism ; X Chromosome Inactivation/*genetics ; YY1 Transcription Factor/metabolism
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  • 195
    Publication Date: 2009-05-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mullard, Asher -- England -- Nature. 2009 May 14;459(7244):159-61. doi: 10.1038/459159a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19444186" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apolipoproteins B/genetics/metabolism ; Bacteria/drug effects/genetics/*metabolism/pathogenicity ; Eukaryotic Cells/drug effects/*metabolism/*microbiology ; Gene Transfer, Horizontal ; Host-Pathogen Interactions/drug effects/genetics/*physiology ; Humans ; Methicillin-Resistant Staphylococcus aureus/metabolism/pathogenicity ; Microbiology ; Quorum Sensing/drug effects/physiology
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  • 196
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    Nature Publishing Group (NPG)
    Publication Date: 2009-08-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abbott, Alison -- England -- Nature. 2009 Aug 6;460(7256):671. doi: 10.1038/460671a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19661876" target="_blank"〉PubMed〈/a〉
    Keywords: Greece ; Humans ; Research/*organization & administration ; *Research Personnel/psychology
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  • 197
    Publication Date: 2009-04-03
    Description: In the course of synaptic transmission in the brain and periphery, acetylcholine receptors (AChRs) rapidly transduce a chemical signal into an electrical impulse. The speed of transduction is facilitated by rapid ACh association and dissociation, suggesting a binding site relatively non-selective for small cations. Selective transduction has been thought to originate from the ability of ACh, over that of other organic cations, to trigger the subsequent channel-opening step. However, transitions to and from the open state were shown to be similar for agonists with widely different efficacies. By studying mutant AChRs, we show here that the ultimate closed-to-open transition is agonist-independent and preceded by two primed closed states; the first primed state elicits brief openings, whereas the second elicits long-lived openings. Long-lived openings and the associated primed state are detected in the absence and presence of an agonist, and exhibit the same kinetic signatures under both conditions. By covalently locking the agonist-binding sites in the bound conformation, we find that each site initiates a priming step. Thus, a change in binding-site conformation primes the AChR for channel opening in a process that enables selective activation by ACh while maximizing the speed and efficiency of the biological response.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2712348/" 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/PMC2712348/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mukhtasimova, Nuriya -- Lee, Won Yong -- Wang, Hai-Long -- Sine, Steven M -- NS031744/NS/NINDS NIH HHS/ -- R01 NS031744/NS/NINDS NIH HHS/ -- R01 NS031744-18/NS/NINDS NIH HHS/ -- England -- Nature. 2009 May 21;459(7245):451-4. doi: 10.1038/nature07923. Epub 2009 Apr 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Receptor Biology Laboratory, Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19339970" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Disulfides/metabolism ; Electric Conductivity ; Humans ; Kinetics ; Models, Molecular ; *Movement ; Nicotinic Agonists/pharmacology ; Patch-Clamp Techniques ; Protein Structure, Tertiary ; Receptors, Nicotinic/*chemistry/genetics/*metabolism ; Synaptic Transmission/physiology ; Torpedo
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  • 198
    Publication Date: 2009-06-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Doyle, Robert O -- England -- Nature. 2009 Jun 25;459(7250):1052. doi: 10.1038/4591052c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19553970" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Human Characteristics ; Humans ; *Personal Autonomy ; Philosophy
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  • 199
    Publication Date: 2009-08-29
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2974062/" 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/PMC2974062/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Krizhanovsky, Valery -- Lowe, Scott W -- P01 CA087497/CA/NCI NIH HHS/ -- P01 CA087497-090003/CA/NCI NIH HHS/ -- P30 CA008748/CA/NCI NIH HHS/ -- England -- Nature. 2009 Aug 27;460(7259):1085-6. doi: 10.1038/4601085a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19713919" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Aging ; Cell Division ; *Cellular Reprogramming ; Cyclin-Dependent Kinase Inhibitor p16/deficiency/genetics/metabolism ; Fibroblasts/cytology/metabolism ; Humans ; Mice ; Neoplasms/metabolism/pathology/therapy ; Pluripotent Stem Cells/*cytology/*metabolism ; Tumor Suppressor Protein p53/deficiency/genetics/*metabolism
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  • 200
    Publication Date: 2009-12-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Drew, Liam J -- MacDermott, Amy B -- England -- Nature. 2009 Dec 3;462(7273):580-1. doi: 10.1038/462580a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19956249" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Humans ; Mice ; Neuronal Plasticity/physiology ; Neurosciences ; Pain/*physiopathology ; Sensory Receptor Cells/*physiology ; Touch/*physiology ; Vesicular Glutamate Transport Proteins/physiology
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