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  • History, 20th Century  (570)
  • Reproducibility of Results  (484)
  • Mice, Inbred C57BL  (470)
  • Molecular Sequence Data  (463)
  • Nature Publishing Group (NPG)  (1,948)
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  • 1
    Publication Date: 2010-04-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Check Hayden, Erika -- England -- Nature. 2010 Apr 1;464(7289):664-7. doi: 10.1038/464664a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360709" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Data Mining ; Gene Expression Regulation ; Genes/genetics ; Genome, Human/*genetics ; Genomics/history/trends ; History, 20th Century ; History, 21st Century ; Human Genome Project/history ; Humans ; *Models, Biological ; Molecular Biology/*history ; Neoplasms/genetics/therapy ; RNA, Untranslated/genetics/metabolism ; Sea Urchins/embryology/genetics ; Systems Biology/*trends ; Tumor Suppressor Protein p53/chemistry/genetics/metabolism ; *Uncertainty
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
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    Nature Publishing Group (NPG)
    Publication Date: 2010-02-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schiermeier, Quirin -- England -- Nature. 2010 Feb 4;463(7281):596-7. doi: 10.1038/463596a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20130621" target="_blank"〉PubMed〈/a〉
    Keywords: *Conflict of Interest ; Ecology/ethics/organization & administration/*standards ; Ethics, Professional ; *Global Warming/statistics & numerical data ; Ice Cover ; Reproducibility of Results ; Research Design ; Risk Assessment ; United Nations/ethics/*organization & administration/standards
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  • 3
    Publication Date: 2010-02-09
    Description: Although the notion of an early origin and diversification of life on Earth during the Archaean eon has received increasing support in geochemical, sedimentological and palaeontological evidence, ambiguities and controversies persist regarding the biogenicity and syngeneity of the record older than Late Archaean. Non-biological processes are known to produce morphologies similar to some microfossils, and hydrothermal fluids have the potential to produce abiotic organic compounds with depleted carbon isotope values, making it difficult to establish unambiguous traces of life. Here we report the discovery of a population of large (up to about 300 mum in diameter) carbonaceous spheroidal microstructures in Mesoarchaean shales and siltstones of the Moodies Group, South Africa, the Earth's oldest siliciclastic alluvial to tidal-estuarine deposits. These microstructures are interpreted as organic-walled microfossils on the basis of petrographic and geochemical evidence for their endogenicity and syngeneity, their carbonaceous composition, cellular morphology and ultrastructure, occurrence in populations, taphonomic features of soft wall deformation, and the geological context plausible for life, as well as a lack of abiotic explanation falsifying a biological origin. These are the oldest and largest Archaean organic-walled spheroidal microfossils reported so far. Our observations suggest that relatively large microorganisms cohabited with earlier reported benthic microbial mats in the photic zone of marginal marine siliciclastic environments 3.2 billion years ago.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Javaux, Emmanuelle J -- Marshall, Craig P -- Bekker, Andrey -- England -- Nature. 2010 Feb 18;463(7283):934-8. doi: 10.1038/nature08793. Epub 2010 Feb 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Geology, University of Liege, 17 allee du 6 Aout B18, Liege 4000, Belgium. ej.javaux@ulg.ac.be〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20139963" target="_blank"〉PubMed〈/a〉
    Keywords: Acids ; Bacteria/chemistry/cytology/isolation & purification/metabolism ; Carbon/analysis/chemistry ; Carbon Isotopes ; *Ecosystem ; Eukaryotic Cells/chemistry/cytology ; *Fossils ; Geologic Sediments/*microbiology ; History, Ancient ; Oceans and Seas ; Organic Chemicals/*analysis/chemistry ; *Phylogeny ; Reproducibility of Results ; Seawater/*microbiology ; South Africa ; Spectrum Analysis, Raman ; Sunlight
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  • 4
    Publication Date: 2010-08-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Javitt, Gail -- England -- Nature. 2010 Aug 12;466(7308):817-8. doi: 10.1038/466817a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Berman Institute of Bioethics, Johns Hopkins University, USA. gjavitt1@jhu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20703288" target="_blank"〉PubMed〈/a〉
    Keywords: *Consumer Advocacy ; Genetic Counseling/*legislation & jurisprudence/standards ; Genetic Predisposition to Disease/*genetics ; Genetic Testing/*legislation & jurisprudence/*standards ; *Government Regulation ; Humans ; Marketing ; Reproducibility of Results ; United States ; United States Food and Drug Administration/legislation & jurisprudence
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  • 5
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    Nature Publishing Group (NPG)
    Publication Date: 2010-11-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Olby, Robert -- England -- Nature. 2010 Nov 4;468(7320):37. doi: 10.1038/468037e.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21048750" target="_blank"〉PubMed〈/a〉
    Keywords: *Correspondence as Topic ; History, 20th Century
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  • 6
    Publication Date: 2010-03-09
    Description: In the ovules of most sexual flowering plants female gametogenesis is initiated from a single surviving gametic cell, the functional megaspore, formed after meiosis of the somatically derived megaspore mother cell (MMC). Because some mutants and certain sexual species exhibit more than one MMC, and many others are able to form gametes without meiosis (by apomixis), it has been suggested that somatic cells in the ovule are competent to respond to a local signal likely to have an important function in determination. Here we show that the Arabidopsis protein ARGONAUTE 9 (AGO9) controls female gamete formation by restricting the specification of gametophyte precursors in a dosage-dependent, non-cell-autonomous manner. Mutations in AGO9 lead to the differentiation of multiple gametic cells that are able to initiate gametogenesis. The AGO9 protein is not expressed in the gamete lineage; instead, it is expressed in cytoplasmic foci of somatic companion cells. Mutations in SUPPRESSOR OF GENE SILENCING 3 and RNA-DEPENDENT RNA POLYMERASE 6 exhibit an identical defect to ago9 mutants, indicating that the movement of small RNA (sRNAs) silencing out of somatic companion cells is necessary for controlling the specification of gametic cells. AGO9 preferentially interacts with 24-nucleotide sRNAs derived from transposable elements (TEs), and its activity is necessary to silence TEs in female gametes and their accessory cells. Our results show that AGO9-dependent sRNA silencing is crucial to specify cell fate in the Arabidopsis ovule, and that epigenetic reprogramming in companion cells is necessary for sRNA-dependent silencing in plant gametes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613780/" 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/PMC4613780/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Olmedo-Monfil, Vianey -- Duran-Figueroa, Noe -- Arteaga-Vazquez, Mario -- Demesa-Arevalo, Edgar -- Autran, Daphne -- Grimanelli, Daniel -- Slotkin, R Keith -- Martienssen, Robert A -- Vielle-Calzada, Jean-Philippe -- R01 GM067014/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Mar 25;464(7288):628-32. doi: 10.1038/nature08828. Epub 2010 Mar 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Grupo de Desarrollo Reproductivo y Apomixis, Laboratorio Nacional de Genomica para la Biodiversidad y Departamento de Ingenieria Genetica de Plantas, Cinvestav Irapuato CP36500 Guanajuato, Mexico.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20208518" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/genetics/growth & development/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Argonaute Proteins ; DNA Transposable Elements/genetics ; Gametogenesis, Plant/*physiology ; Gene Expression Regulation, Plant ; Gene Silencing ; Meiosis ; Molecular Sequence Data ; Mutagenesis, Insertional/genetics ; Ovule/growth & development/*metabolism ; Phenotype ; RNA, Plant/*metabolism ; RNA-Binding Proteins/genetics/*metabolism
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  • 7
    Publication Date: 2010-02-19
    Description: E1 enzymes activate ubiquitin (Ub) and ubiquitin-like (Ubl) proteins in two steps by carboxy-terminal adenylation and thioester bond formation to a conserved catalytic cysteine in the E1 Cys domain. The structural basis for these intermediates remains unknown. Here we report crystal structures for human SUMO E1 in complex with SUMO adenylate and tetrahedral intermediate analogues at 2.45 and 2.6 A, respectively. These structures show that side chain contacts to ATP.Mg are released after adenylation to facilitate a 130 degree rotation of the Cys domain during thioester bond formation that is accompanied by remodelling of key structural elements including the helix that contains the E1 catalytic cysteine, the crossover and re-entry loops, and refolding of two helices that are required for adenylation. These changes displace side chains required for adenylation with side chains required for thioester bond formation. Mutational and biochemical analyses indicate these mechanisms are conserved in other E1s.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866016/" 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/PMC2866016/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Olsen, Shaun K -- Capili, Allan D -- Lu, Xuequan -- Tan, Derek S -- Lima, Christopher D -- F32 GM075695/GM/NIGMS NIH HHS/ -- F32 GM075695-03/GM/NIGMS NIH HHS/ -- R01 AI068038/AI/NIAID NIH HHS/ -- R01 AI068038-02/AI/NIAID NIH HHS/ -- R01 AI068038-03/AI/NIAID NIH HHS/ -- R01 GM065872/GM/NIGMS NIH HHS/ -- R01 GM065872-09/GM/NIGMS NIH HHS/ -- RR-15301/RR/NCRR NIH HHS/ -- England -- Nature. 2010 Feb 18;463(7283):906-12. doi: 10.1038/nature08765.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Biology, Sloan-Kettering Institute, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20164921" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Amino Acid Sequence ; *Biocatalysis ; Catalytic Domain/*physiology ; Conserved Sequence ; Crystallography, X-Ray ; Cysteine/chemistry/metabolism ; Humans ; Magnesium/metabolism ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; SUMO-1 Protein/*chemistry/*metabolism ; Saccharomyces cerevisiae ; Saccharomyces cerevisiae Proteins/metabolism ; Small Ubiquitin-Related Modifier Proteins/metabolism ; Sulfides/*metabolism ; Ubiquitin/metabolism ; Ubiquitin-Activating Enzymes/*chemistry/*metabolism ; Ubiquitins/metabolism
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  • 8
    Publication Date: 2010-07-20
    Description: Chronic myelogenous leukaemia (CML) can progress from a slow growing chronic phase to an aggressive blast crisis phase, but the molecular basis of this transition remains poorly understood. Here we have used mouse models of CML to show that disease progression is regulated by the Musashi-Numb signalling axis. Specifically, we find that the chronic phase is marked by high levels of Numb expression whereas the blast crisis phase has low levels of Numb expression, and that ectopic expression of Numb promotes differentiation and impairs advanced-phase disease in vivo. As a possible explanation for the decreased levels of Numb in the blast crisis phase, we show that NUP98-HOXA9, an oncogene associated with blast crisis CML, can trigger expression of the RNA-binding protein Musashi2 (Msi2), which in turn represses Numb. Notably, loss of Msi2 restores Numb expression and significantly impairs the development and propagation of blast crisis CML in vitro and in vivo. Finally we show that Msi2 expression is not only highly upregulated during human CML progression but is also an early indicator of poorer prognosis. These data show that the Musashi-Numb pathway can control the differentiation of CML cells, and raise the possibility that targeting this pathway may provide a new strategy for the therapy of aggressive leukaemias.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918284/" 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/PMC2918284/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ito, Takahiro -- Kwon, Hyog Young -- Zimdahl, Bryan -- Congdon, Kendra L -- Blum, Jordan -- Lento, William E -- Zhao, Chen -- Lagoo, Anand -- Gerrard, Gareth -- Foroni, Letizia -- Goldman, John -- Goh, Harriet -- Kim, Soo-Hyun -- Kim, Dong-Wook -- Chuah, Charles -- Oehler, Vivian G -- Radich, Jerald P -- Jordan, Craig T -- Reya, Tannishtha -- AI067798/AI/NIAID NIH HHS/ -- CA122206/CA/NCI NIH HHS/ -- CA140371/CA/NCI NIH HHS/ -- CA18029/CA/NCI NIH HHS/ -- DK072234/DK/NIDDK NIH HHS/ -- DK63031/DK/NIDDK NIH HHS/ -- DP1 CA174422/CA/NCI NIH HHS/ -- DP1 OD006430/OD/NIH HHS/ -- DP1 OD006430-01/OD/NIH HHS/ -- DP1 OD006430-02/OD/NIH HHS/ -- DP1OD006430/OD/NIH HHS/ -- HL097767/HL/NHLBI NIH HHS/ -- P01 CA018029/CA/NCI NIH HHS/ -- R01 CA140371/CA/NCI 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/ -- R01 HL097767/HL/NHLBI NIH HHS/ -- R01 HL097767-01/HL/NHLBI NIH HHS/ -- R01 HL097767-02/HL/NHLBI NIH HHS/ -- T32 GM007184-33/GM/NIGMS 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. 2010 Aug 5;466(7307):765-8. doi: 10.1038/nature09171. Epub 2010 Jul 18.〈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/20639863" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blast Crisis/genetics/metabolism/pathology ; *Cell Differentiation/genetics ; Disease Progression ; Fusion Proteins, bcr-abl/genetics/metabolism ; Gene Expression Regulation, Neoplastic ; Homeodomain Proteins/genetics/metabolism ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics/*metabolism/*pathology ; Membrane Proteins/biosynthesis/genetics/metabolism ; Mice ; Mice, Inbred C57BL ; Nerve Tissue Proteins/biosynthesis/genetics/metabolism ; Nuclear Pore Complex Proteins/genetics/metabolism ; Oncogene Proteins, Fusion/genetics/metabolism ; Prognosis ; RNA-Binding Proteins/biosynthesis/genetics/*metabolism ; Receptor, Notch1/metabolism ; Signal Transduction ; Tumor Suppressor Protein p53/metabolism ; Up-Regulation
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  • 9
    Publication Date: 2010-05-14
    Description: The main reason why tumours are not controlled by the immune system is that, unlike pathogens, they do not express potent tumour rejection antigens (TRAs). Tumour vaccination aims at stimulating a systemic immune response targeted to, mostly weak, antigens expressed in the disseminated tumour lesions. Main challenges in developing effective vaccination protocols are the identification of potent and broadly expressed TRAs and effective adjuvants to stimulate a robust and durable immune response. Here we describe an alternative approach in which the expression of new, and thereby potent, antigens are induced in tumour cells by inhibiting nonsense-mediated messenger RNA decay (NMD). Small interfering RNA (siRNA)-mediated inhibition of NMD in tumour cells led to the expression of new antigenic determinants and their immune-mediated rejection. In subcutaneous and metastatic tumour models, tumour-targeted delivery of NMD factor-specific siRNAs conjugated to oligonucleotide aptamer ligands led to significant inhibition of tumour growth that was superior to that of vaccination with granulocyte-macrophage colony-stimulating factor (GM-CSF)-expressing irradiated tumour cells, and could be further enhanced by co-stimulation. Tumour-targeted NMD inhibition forms the basis of a simple, broadly useful, and clinically feasible approach to enhance the antigenicity of disseminated tumours leading to their immune recognition and rejection. The cell-free chemically synthesized oligonucleotide backbone of aptamer-siRNAs reduces the risk of immunogenicity and enhances the feasibility of generating reagents suitable for clinical use.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107067/" 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/PMC3107067/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pastor, Fernando -- Kolonias, Despina -- Giangrande, Paloma H -- Gilboa, Eli -- R01 CA138503/CA/NCI NIH HHS/ -- R01 CA151857-02/CA/NCI NIH HHS/ -- England -- Nature. 2010 May 13;465(7295):227-30. doi: 10.1038/nature08999.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology & Immunology, Dodson Interdisciplinary Immunotherapy Institute, University of Miami Miller School of Medicine Miami, Florida 33134, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20463739" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Neoplasm/*genetics/*immunology ; Aptamers, Nucleotide/genetics ; Cancer Vaccines/genetics/immunology/metabolism ; Carrier Proteins/genetics ; Cell Line, Tumor ; Chickens/genetics ; Colonic Neoplasms/*genetics/*immunology/pathology ; Gene Expression Regulation, Neoplastic ; Granulocyte-Macrophage Colony-Stimulating Factor/genetics/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Nude ; Neoplasm Transplantation ; RNA Interference ; RNA Stability/*genetics ; RNA, Small Interfering/*genetics/therapeutic use ; Xenograft Model Antitumor Assays
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  • 10
    Publication Date: 2010-12-03
    Description: The capacity to fine-tune cellular bioenergetics with the demands of stem-cell maintenance and regeneration is central to normal development and ageing, and to organismal survival during periods of acute stress. How energy metabolism and stem-cell homeostatic processes are coordinated is not well understood. Lkb1 acts as an evolutionarily conserved regulator of cellular energy metabolism in eukaryotic cells and functions as the major upstream kinase to phosphorylate AMP-activated protein kinase (AMPK) and 12 other AMPK-related kinases. Whether Lkb1 regulates stem-cell maintenance remains unknown. Here we show that Lkb1 has an essential role in haematopoietic stem cell (HSC) homeostasis. We demonstrate that ablation of Lkb1 in adult mice results in severe pancytopenia and subsequent lethality. Loss of Lkb1 leads to impaired survival and escape from quiescence of HSCs, resulting in exhaustion of the HSC pool and a marked reduction of HSC repopulating potential in vivo. Lkb1 deletion has an impact on cell proliferation in HSCs, but not on more committed compartments, pointing to context-specific functions for Lkb1 in haematopoiesis. The adverse impact of Lkb1 deletion on haematopoiesis was predominantly cell-autonomous and mTOR complex 1 (mTORC1)-independent, and involves multiple mechanisms converging on mitochondrial apoptosis and possibly downregulation of PGC-1 coactivators and their transcriptional network, which have critical roles in mitochondrial biogenesis and function. Thus, Lkb1 serves as an essential regulator of HSCs and haematopoiesis, and more generally, points to the critical importance of coupling energy metabolism and stem-cell homeostasis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058342/" 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/PMC3058342/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gan, Boyi -- Hu, Jian -- Jiang, Shan -- Liu, Yingchun -- Sahin, Ergun -- Zhuang, Li -- Fletcher-Sananikone, Eliot -- Colla, Simona -- Wang, Y Alan -- Chin, Lynda -- Depinho, Ronald A -- 01CA141508/CA/NCI NIH HHS/ -- R21 CA135057/CA/NCI NIH HHS/ -- R21 CA135057-01/CA/NCI NIH HHS/ -- R21CA135057/CA/NCI NIH HHS/ -- U01 CA141508/CA/NCI NIH HHS/ -- U01 CA141508-01/CA/NCI NIH HHS/ -- England -- Nature. 2010 Dec 2;468(7324):701-4. doi: 10.1038/nature09595.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21124456" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Cell Cycle/*physiology ; Cell Proliferation ; Cell Survival ; *Energy Metabolism ; Female ; Gene Deletion ; Hematopoiesis ; Hematopoietic Stem Cells/*cytology/*metabolism/pathology ; *Homeostasis ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria/metabolism/pathology ; Multiprotein Complexes ; Pancytopenia/genetics ; Phenotype ; Protein-Serine-Threonine Kinases/deficiency/genetics/*metabolism ; Proteins/metabolism ; Survival Analysis ; TOR Serine-Threonine Kinases ; Transcription Factors/metabolism
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  • 11
    Publication Date: 2010-05-21
    Description: Type II topoisomerases are required for the management of DNA tangles and supercoils, and are targets of clinical antibiotics and anti-cancer agents. These enzymes catalyse the ATP-dependent passage of one DNA duplex (the transport or T-segment) through a transient, double-stranded break in another (the gate or G-segment), navigating DNA through the protein using a set of dissociable internal interfaces, or 'gates'. For more than 20 years, it has been established that a pair of dimer-related tyrosines, together with divalent cations, catalyse G-segment cleavage. Recent efforts have proposed that strand scission relies on a 'two-metal mechanism', a ubiquitous biochemical strategy that supports vital cellular processes ranging from DNA synthesis to RNA self-splicing. Here we present the structure of the DNA-binding and cleavage core of Saccharomyces cerevisiae topoisomerase II covalently linked to DNA through its active-site tyrosine at 2.5A resolution, revealing for the first time the organization of a cleavage-competent type II topoisomerase configuration. Unexpectedly, metal-soaking experiments indicate that cleavage is catalysed by a novel variation of the classic two-metal approach. Comparative analyses extend this scheme to explain how distantly-related type IA topoisomerases cleave single-stranded DNA, unifying the cleavage mechanisms for these two essential enzyme families. The structure also highlights a hitherto undiscovered allosteric relay that actuates a molecular 'trapdoor' to prevent subunit dissociation during cleavage. This connection illustrates how an indispensable chromosome-disentangling machine auto-regulates DNA breakage to prevent the aberrant formation of mutagenic and cytotoxic genomic lesions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882514/" 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/PMC2882514/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schmidt, Bryan H -- Burgin, Alex B -- Deweese, Joseph E -- Osheroff, Neil -- Berger, James M -- CA077373/CA/NCI NIH HHS/ -- GM033944/GM/NIGMS NIH HHS/ -- GM053960/GM/NIGMS NIH HHS/ -- GM08295/GM/NIGMS NIH HHS/ -- R01 CA077373/CA/NCI NIH HHS/ -- R01 CA077373-11S1/CA/NCI NIH HHS/ -- R01 CA077373-12/CA/NCI NIH HHS/ -- R01 GM033944/GM/NIGMS NIH HHS/ -- T32 CA009592/CA/NCI NIH HHS/ -- T32CA09592/CA/NCI NIH HHS/ -- England -- Nature. 2010 Jun 3;465(7298):641-4. doi: 10.1038/nature08974.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20485342" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Base Sequence ; Catalytic Domain ; Crystallography, X-Ray ; DNA/*chemistry/genetics/*metabolism ; DNA Topoisomerases, Type I/*chemistry/*metabolism ; DNA Topoisomerases, Type II/*chemistry/*metabolism ; Kinetics ; Models, Molecular ; Molecular Sequence Data ; Saccharomyces cerevisiae/*enzymology ; Tyrosine
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  • 12
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2010-10-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Sep 30;467(7315):499-500. doi: 10.1038/467499b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20881967" target="_blank"〉PubMed〈/a〉
    Keywords: European Union ; Financing, Organized/economics ; Germany ; History, 20th Century ; History, 21st Century ; Internationality ; Politics ; Research Support as Topic/economics/history ; Science/economics/history/*standards/*trends
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  • 13
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2010-09-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Sep 23;467(7314):368. doi: 10.1038/467368a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20864950" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/*methods ; Animals ; Cattle ; Disease Reservoirs/microbiology/*statistics & numerical data/*veterinary ; *Federal Government ; Great Britain/epidemiology ; *Mustelidae/microbiology ; Reproducibility of Results ; Tuberculosis Vaccines ; Tuberculosis, Bovine/epidemiology/*prevention & control/transmission ; Vaccination/veterinary
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  • 14
    Publication Date: 2010-02-26
    Description: The Red Queen hypothesis proposes that coevolution of interacting species (such as hosts and parasites) should drive molecular evolution through continual natural selection for adaptation and counter-adaptation. Although the divergence observed at some host-resistance and parasite-infectivity genes is consistent with this, the long time periods typically required to study coevolution have so far prevented any direct empirical test. Here we show, using experimental populations of the bacterium Pseudomonas fluorescens SBW25 and its viral parasite, phage Phi2 (refs 10, 11), that the rate of molecular evolution in the phage was far higher when both bacterium and phage coevolved with each other than when phage evolved against a constant host genotype. Coevolution also resulted in far greater genetic divergence between replicate populations, which was correlated with the range of hosts that coevolved phage were able to infect. Consistent with this, the most rapidly evolving phage genes under coevolution were those involved in host infection. These results demonstrate, at both the genomic and phenotypic level, that antagonistic coevolution is a cause of rapid and divergent evolution, and is likely to be a major driver of evolutionary change within species.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717453/" 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/PMC3717453/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Paterson, Steve -- Vogwill, Tom -- Buckling, Angus -- Benmayor, Rebecca -- Spiers, Andrew J -- Thomson, Nicholas R -- Quail, Mike -- Smith, Frances -- Walker, Danielle -- Libberton, Ben -- Fenton, Andrew -- Hall, Neil -- Brockhurst, Michael A -- 079643/Wellcome Trust/United Kingdom -- 098051/Wellcome Trust/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Mar 11;464(7286):275-8. doi: 10.1038/nature08798. Epub 2010 Feb 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Biological Sciences, Biosciences Building, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20182425" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteriophages/genetics/*physiology ; *Biological Evolution ; *Evolution, Molecular ; Genetic Variation ; Molecular Sequence Data ; Phenotype ; Pseudomonas fluorescens/*genetics/*virology ; Selection, Genetic/genetics
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  • 15
    Publication Date: 2010-01-19
    Description: Influenza A virus, being responsible for seasonal epidemics and reoccurring pandemics, represents a worldwide threat to public health. High mutation rates facilitate the generation of viral escape mutants, rendering vaccines and drugs directed against virus-encoded targets potentially ineffective. In contrast, targeting host cell determinants temporarily dispensable for the host but crucial for virus replication could prevent viral escape. Here we report the discovery of 287 human host cell genes influencing influenza A virus replication in a genome-wide RNA interference (RNAi) screen. Using an independent assay we confirmed 168 hits (59%) inhibiting either the endemic H1N1 (119 hits) or the current pandemic swine-origin (121 hits) influenza A virus strains, with an overlap of 60%. Notably, a subset of these common hits was also essential for replication of a highly pathogenic avian H5N1 strain. In-depth analyses of several factors provided insights into their infection stage relevance. Notably, SON DNA binding protein (SON) was found to be important for normal trafficking of influenza virions to late endosomes early in infection. We also show that a small molecule inhibitor of CDC-like kinase 1 (CLK1) reduces influenza virus replication by more than two orders of magnitude, an effect connected with impaired splicing of the viral M2 messenger RNA. Furthermore, influenza-virus-infected p27(-/-) (cyclin-dependent kinase inhibitor 1B; Cdkn1b) mice accumulated significantly lower viral titres in the lung, providing in vivo evidence for the importance of this gene. Thus, our results highlight the potency of genome-wide RNAi screening for the dissection of virus-host interactions and the identification of drug targets for a broad range of influenza viruses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Karlas, Alexander -- Machuy, Nikolaus -- Shin, Yujin -- Pleissner, Klaus-Peter -- Artarini, Anita -- Heuer, Dagmar -- Becker, Daniel -- Khalil, Hany -- Ogilvie, Lesley A -- Hess, Simone -- Maurer, Andre P -- Muller, Elke -- Wolff, Thorsten -- Rudel, Thomas -- Meyer, Thomas F -- England -- Nature. 2010 Feb 11;463(7282):818-22. doi: 10.1038/nature08760. Epub 2010 Jan 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biology Department, Max Planck Institute for Infection Biology, Chariteplatz 1, 10117 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20081832" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Factors/genetics/metabolism ; Cell Line ; Cells, Cultured ; Chick Embryo ; Cyclin-Dependent Kinase Inhibitor p27/deficiency/genetics/metabolism ; Epithelial Cells/virology ; Genome, Human/genetics ; *Host-Pathogen Interactions/genetics/physiology ; Humans ; Influenza A Virus, H1N1 Subtype/classification/*growth & development ; Influenza, Human/*genetics/*virology ; Lung/cytology ; Mice ; Mice, Inbred C57BL ; Protein-Serine-Threonine Kinases/genetics ; Protein-Tyrosine Kinases/genetics ; *RNA Interference ; Virus Replication/*physiology
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  • 16
    Publication Date: 2010-09-25
    Description: Plasmodium falciparum is the most prevalent and lethal of the malaria parasites infecting humans, yet the origin and evolutionary history of this important pathogen remain controversial. Here we develop a single-genome amplification strategy to identify and characterize Plasmodium spp. DNA sequences in faecal samples from wild-living apes. Among nearly 3,000 specimens collected from field sites throughout central Africa, we found Plasmodium infection in chimpanzees (Pan troglodytes) and western gorillas (Gorilla gorilla), but not in eastern gorillas (Gorilla beringei) or bonobos (Pan paniscus). Ape plasmodial infections were highly prevalent, widely distributed and almost always made up of mixed parasite species. Analysis of more than 1,100 mitochondrial, apicoplast and nuclear gene sequences from chimpanzees and gorillas revealed that 99% grouped within one of six host-specific lineages representing distinct Plasmodium species within the subgenus Laverania. One of these from western gorillas comprised parasites that were nearly identical to P. falciparum. In phylogenetic analyses of full-length mitochondrial sequences, human P. falciparum formed a monophyletic lineage within the gorilla parasite radiation. These findings indicate that P. falciparum is of gorilla origin and not of chimpanzee, bonobo or ancient human origin.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997044/" 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/PMC2997044/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Weimin -- Li, Yingying -- Learn, Gerald H -- Rudicell, Rebecca S -- Robertson, Joel D -- Keele, Brandon F -- Ndjango, Jean-Bosco N -- Sanz, Crickette M -- Morgan, David B -- Locatelli, Sabrina -- Gonder, Mary K -- Kranzusch, Philip J -- Walsh, Peter D -- Delaporte, Eric -- Mpoudi-Ngole, Eitel -- Georgiev, Alexander V -- Muller, Martin N -- Shaw, George M -- Peeters, Martine -- Sharp, Paul M -- Rayner, Julian C -- Hahn, Beatrice H -- P30 AI 7767/AI/NIAID NIH HHS/ -- P30 AI027767/AI/NIAID NIH HHS/ -- P30 AI027767-21A1/AI/NIAID NIH HHS/ -- R01 AI058715/AI/NIAID NIH HHS/ -- R01 AI058715-06A1/AI/NIAID NIH HHS/ -- R01 AI058715-07/AI/NIAID NIH HHS/ -- R01 AI50529/AI/NIAID NIH HHS/ -- R01 I58715/PHS HHS/ -- R03 AI074778/AI/NIAID NIH HHS/ -- R03 AI074778-02/AI/NIAID NIH HHS/ -- R37 AI050529/AI/NIAID NIH HHS/ -- R37 AI050529-07/AI/NIAID NIH HHS/ -- R37 AI050529-08/AI/NIAID NIH HHS/ -- T32 AI007245/AI/NIAID NIH HHS/ -- T32 AI007245-26/AI/NIAID NIH HHS/ -- T32 GM008111/GM/NIGMS NIH HHS/ -- T32 GM008111-13/GM/NIGMS NIH HHS/ -- U19 AI 067854/AI/NIAID NIH HHS/ -- U19 AI067854/AI/NIAID NIH HHS/ -- U19 AI067854-06/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Sep 23;467(7314):420-5. doi: 10.1038/nature09442.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20864995" target="_blank"〉PubMed〈/a〉
    Keywords: Africa/epidemiology ; Animals ; Animals, Wild/classification/parasitology ; Ape Diseases/epidemiology/*parasitology/transmission ; DNA, Mitochondrial/analysis/genetics ; Evolution, Molecular ; Feces/parasitology ; Genes, Mitochondrial/genetics ; Genetic Variation/genetics ; Genome, Protozoan/genetics ; Gorilla gorilla/classification/*parasitology ; Humans ; Malaria, Falciparum/epidemiology/*parasitology/transmission/*veterinary ; Molecular Sequence Data ; Pan paniscus/parasitology ; Pan troglodytes/parasitology ; Phylogeny ; Plasmodium/classification/genetics/isolation & purification ; Plasmodium falciparum/genetics/*isolation & purification ; Prevalence ; Zoonoses/parasitology/transmission
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  • 17
    Publication Date: 2010-01-16
    Description: Soybean (Glycine max) is one of the most important crop plants for seed protein and oil content, and for its capacity to fix atmospheric nitrogen through symbioses with soil-borne microorganisms. We sequenced the 1.1-gigabase genome by a whole-genome shotgun approach and integrated it with physical and high-density genetic maps to create a chromosome-scale draft sequence assembly. We predict 46,430 protein-coding genes, 70% more than Arabidopsis and similar to the poplar genome which, like soybean, is an ancient polyploid (palaeopolyploid). About 78% of the predicted genes occur in chromosome ends, which comprise less than one-half of the genome but account for nearly all of the genetic recombination. Genome duplications occurred at approximately 59 and 13 million years ago, resulting in a highly duplicated genome with nearly 75% of the genes present in multiple copies. The two duplication events were followed by gene diversification and loss, and numerous chromosome rearrangements. An accurate soybean genome sequence will facilitate the identification of the genetic basis of many soybean traits, and accelerate the creation of improved soybean varieties.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schmutz, Jeremy -- Cannon, Steven B -- Schlueter, Jessica -- Ma, Jianxin -- Mitros, Therese -- Nelson, William -- Hyten, David L -- Song, Qijian -- Thelen, Jay J -- Cheng, Jianlin -- Xu, Dong -- Hellsten, Uffe -- May, Gregory D -- Yu, Yeisoo -- Sakurai, Tetsuya -- Umezawa, Taishi -- Bhattacharyya, Madan K -- Sandhu, Devinder -- Valliyodan, Babu -- Lindquist, Erika -- Peto, Myron -- Grant, David -- Shu, Shengqiang -- Goodstein, David -- Barry, Kerrie -- Futrell-Griggs, Montona -- Abernathy, Brian -- Du, Jianchang -- Tian, Zhixi -- Zhu, Liucun -- Gill, Navdeep -- Joshi, Trupti -- Libault, Marc -- Sethuraman, Anand -- Zhang, Xue-Cheng -- Shinozaki, Kazuo -- Nguyen, Henry T -- Wing, Rod A -- Cregan, Perry -- Specht, James -- Grimwood, Jane -- Rokhsar, Dan -- Stacey, Gary -- Shoemaker, Randy C -- Jackson, Scott A -- England -- Nature. 2010 Jan 14;463(7278):178-83. doi: 10.1038/nature08670.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉HudsonAlpha Genome Sequencing Center, 601 Genome Way, Huntsville, Alabama 35806, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20075913" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/genetics ; Breeding ; Chromosomes, Plant/genetics ; Evolution, Molecular ; Gene Duplication ; Genes, Duplicate/genetics ; Genes, Plant/genetics ; Genome, Plant/*genetics ; *Genomics ; Molecular Sequence Data ; Multigene Family/genetics ; Phylogeny ; Plant Root Nodulation/genetics ; *Polyploidy ; Quantitative Trait Loci/genetics ; Recombination, Genetic ; Repetitive Sequences, Nucleic Acid/genetics ; Soybean Oil/biosynthesis ; Soybeans/*genetics ; Synteny/genetics ; Transcription Factors/genetics
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  • 18
    Publication Date: 2010-01-30
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4456675/" 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/PMC4456675/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Berman, Helen M -- Kleywegt, Gerard J -- Nakamura, Haruki -- Markley, John L -- Burley, Stephen K -- P41 LM005799/LM/NLM NIH HHS/ -- England -- Nature. 2010 Jan 28;463(7280):425. doi: 10.1038/463425c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20110969" target="_blank"〉PubMed〈/a〉
    Keywords: Databases, Protein/*ethics/*standards ; Ethics, Research ; Reproducibility of Results ; Scientific Misconduct
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  • 19
    Publication Date: 2010-10-12
    Description: Jasmonates are a family of plant hormones that regulate plant growth, development and responses to stress. The F-box protein CORONATINE INSENSITIVE 1 (COI1) mediates jasmonate signalling by promoting hormone-dependent ubiquitylation and degradation of transcriptional repressor JAZ proteins. Despite its importance, the mechanism of jasmonate perception remains unclear. Here we present structural and pharmacological data to show that the true Arabidopsis jasmonate receptor is a complex of both COI1 and JAZ. COI1 contains an open pocket that recognizes the bioactive hormone (3R,7S)-jasmonoyl-l-isoleucine (JA-Ile) with high specificity. High-affinity hormone binding requires a bipartite JAZ degron sequence consisting of a conserved alpha-helix for COI1 docking and a loop region to trap the hormone in its binding pocket. In addition, we identify a third critical component of the jasmonate co-receptor complex, inositol pentakisphosphate, which interacts with both COI1 and JAZ adjacent to the ligand. Our results unravel the mechanism of jasmonate perception and highlight the ability of F-box proteins to evolve as multi-component signalling hubs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988090/" 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/PMC2988090/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sheard, Laura B -- Tan, Xu -- Mao, Haibin -- Withers, John -- Ben-Nissan, Gili -- Hinds, Thomas R -- Kobayashi, Yuichi -- Hsu, Fong-Fu -- Sharon, Michal -- Browse, John -- He, Sheng Yang -- Rizo, Josep -- Howe, Gregg A -- Zheng, Ning -- P30 DK056341/DK/NIDDK NIH HHS/ -- P30 DK056341-10/DK/NIDDK NIH HHS/ -- R01 AI068718/AI/NIAID NIH HHS/ -- R01 AI068718-04/AI/NIAID NIH HHS/ -- R01 CA107134/CA/NCI NIH HHS/ -- R01 CA107134-07/CA/NCI NIH HHS/ -- R01 GM057795/GM/NIGMS NIH HHS/ -- R01 GM057795-12/GM/NIGMS NIH HHS/ -- R01AI068718/AI/NIAID NIH HHS/ -- R01GM57795/GM/NIGMS NIH HHS/ -- T32 GM07270/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Nov 18;468(7322):400-5. doi: 10.1038/nature09430. Epub 2010 Oct 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Box 357280, University of Washington, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20927106" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acids/chemistry/metabolism ; Arabidopsis/chemistry/metabolism ; Arabidopsis Proteins/*chemistry/*metabolism ; Binding Sites ; Crystallography, X-Ray ; Cyclopentanes/chemistry/*metabolism ; F-Box Proteins/chemistry/metabolism ; Indenes/chemistry/metabolism ; Inositol Phosphates/*metabolism ; Isoleucine/analogs & derivatives/chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Oxylipins/chemistry/*metabolism ; Peptide Fragments/chemistry/metabolism ; Plant Growth Regulators/chemistry/*metabolism ; Protein Binding ; Protein Structure, Tertiary ; Repressor Proteins/*chemistry/*metabolism ; Signal Transduction
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  • 20
    Publication Date: 2010-07-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Deborah -- Carter, Philip -- England -- Nature. 2010 Jul 15;466(7304):315. doi: 10.1038/466315a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20631779" target="_blank"〉PubMed〈/a〉
    Keywords: *Conflict of Interest ; *Drug Industry ; Humans ; *Influenza A Virus, H1N1 Subtype ; Influenza Vaccines/*supply & distribution ; Influenza, Human/*epidemiology/prevention & control/virology ; Reproducibility of Results ; Time Factors ; *Vaccination ; *World Health Organization
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  • 21
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2010-12-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Katsnelson, Alla -- England -- Nature. 2010 Dec 9;468(7325):741. doi: 10.1038/468741a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21150963" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological ; Arsenic/*metabolism ; Bacteria/cytology/growth & development/*metabolism ; California ; DNA, Bacterial/chemistry/metabolism ; Exobiology ; Life ; Phosphates/metabolism ; Phosphorus/metabolism ; RNA, Bacterial/chemistry/metabolism ; Reproducibility of Results
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  • 22
    Publication Date: 2010-01-08
    Description: The ability to silence the activity of genetically specified neurons in a temporally precise fashion would provide the opportunity to investigate the causal role of specific cell classes in neural computations, behaviours and pathologies. Here we show that members of the class of light-driven outward proton pumps can mediate powerful, safe, multiple-colour silencing of neural activity. The gene archaerhodopsin-3 (Arch) from Halorubrum sodomense enables near-100% silencing of neurons in the awake brain when virally expressed in the mouse cortex and illuminated with yellow light. Arch mediates currents of several hundred picoamps at low light powers, and supports neural silencing currents approaching 900 pA at light powers easily achievable in vivo. Furthermore, Arch spontaneously recovers from light-dependent inactivation, unlike light-driven chloride pumps that enter long-lasting inactive states in response to light. These properties of Arch are appropriate to mediate the optical silencing of significant brain volumes over behaviourally relevant timescales. Arch function in neurons is well tolerated because pH excursions created by Arch illumination are minimized by self-limiting mechanisms to levels comparable to those mediated by channelrhodopsins or natural spike firing. To highlight how proton pump ecological and genomic diversity may support new innovation, we show that the blue-green light-drivable proton pump from the fungus Leptosphaeria maculans (Mac) can, when expressed in neurons, enable neural silencing by blue light, thus enabling alongside other developed reagents the potential for independent silencing of two neural populations by blue versus red light. Light-driven proton pumps thus represent a high-performance and extremely versatile class of 'optogenetic' voltage and ion modulator, which will broadly enable new neuroscientific, biological, neurological and psychiatric investigations.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939492/" 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/PMC2939492/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chow, Brian Y -- Han, Xue -- Dobry, Allison S -- Qian, Xiaofeng -- Chuong, Amy S -- Li, Mingjie -- Henninger, Michael A -- Belfort, Gabriel M -- Lin, Yingxi -- Monahan, Patrick E -- Boyden, Edward S -- 1K99MH085944/MH/NIMH NIH HHS/ -- DP2 OD002002/OD/NIH HHS/ -- DP2 OD002002-01/OD/NIH HHS/ -- K99 MH085944/MH/NIMH NIH HHS/ -- K99 MH085944-01/MH/NIMH NIH HHS/ -- England -- Nature. 2010 Jan 7;463(7277):98-102. doi: 10.1038/nature08652.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The MIT Media Laboratory, Synthetic Neurobiology Group, and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20054397" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials/radiation effects ; Animals ; Ascomycota/metabolism/radiation effects ; Color ; Electric Conductivity ; Euryarchaeota/metabolism/radiation effects ; Genetic Engineering/*methods ; Hydrogen-Ion Concentration ; Mice ; Molecular Sequence Data ; Neocortex/cytology/physiology/radiation effects ; Neurons/*metabolism/*radiation effects ; Proton Pumps/classification/genetics/*metabolism/*radiation effects ; Rhodopsins, Microbial/antagonists & inhibitors/genetics/metabolism/radiation ; effects ; Wakefulness
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  • 23
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    Nature Publishing Group (NPG)
    Publication Date: 2010-10-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Simmons, John Galbraith -- England -- Nature. 2010 Oct 14;467(7317):S14-5. doi: 10.1038/467S14a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20944614" target="_blank"〉PubMed〈/a〉
    Keywords: Age Factors ; Blogging ; Congresses as Topic/*history/*trends ; Conservation of Natural Resources/trends ; Germany ; History, 20th Century ; History, 21st Century ; *Nobel Prize ; Nuclear Warfare ; *Research Personnel/history/trends ; Science/*history/*trends
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  • 24
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2010-03-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Mar 18;464(7287):325. doi: 10.1038/464325a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20237517" target="_blank"〉PubMed〈/a〉
    Keywords: Education, Graduate/trends ; Forensic Sciences/economics/education/organization & administration/*trends ; Reproducibility of Results ; Research/economics/organization & administration/trends ; United States ; United States Government Agencies/economics/organization & administration/trends
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  • 25
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2010-08-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wadman, Meredith -- England -- Nature. 2010 Aug 12;466(7308):808-10. doi: 10.1038/466808a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20703281" target="_blank"〉PubMed〈/a〉
    Keywords: American Recovery and Reinvestment Act/economics ; Biomedical Research/economics/organization & administration/trends ; Budgets/trends ; Comparative Effectiveness Research ; History, 20th Century ; History, 21st Century ; Human Genome Project/history ; Humans ; National Institutes of Health (U.S.)/*economics/*organization & ; administration/trends ; Religion and Science ; Translational Medical Research ; United States
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  • 26
    Publication Date: 2010-08-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mastrandrea, Michael D -- England -- Nature. 2010 Aug 19;466(7309):933. doi: 10.1038/466933a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Intergovernmental Panel on Climate Change Working Group II, Stanford University, Stanford, California 94305, USA. mikemas@stanford.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20725032" target="_blank"〉PubMed〈/a〉
    Keywords: Aerosols ; Climate Change/*history ; History, 20th Century ; History, 21st Century ; Policy Making ; United States
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  • 27
    Publication Date: 2010-10-01
    Description: RANK ligand (RANKL), a TNF-related molecule, is essential for osteoclast formation, function and survival through interaction with its receptor RANK. Mammary glands of RANK- and RANKL-deficient mice develop normally during sexual maturation, but fail to form lobuloalveolar structures during pregnancy because of defective proliferation and increased apoptosis of mammary epithelium. It has been shown that RANKL is responsible for the major proliferative response of mouse mammary epithelium to progesterone during mammary lactational morphogenesis, and in mouse models, manipulated to induce activation of the RANK/RANKL pathway in the absence of strict hormonal control, inappropriate mammary proliferation is observed. However, there is no evidence so far of a functional contribution of RANKL to tumorigenesis. Here we show that RANK and RANKL are expressed within normal, pre-malignant and neoplastic mammary epithelium, and using complementary gain-of-function (mouse mammary tumour virus (MMTV)-RANK transgenic mice) and loss-of function (pharmacological inhibition of RANKL) approaches, define a direct contribution of this pathway in mammary tumorigenesis. Accelerated pre-neoplasias and increased mammary tumour formation were observed in MMTV-RANK transgenic mice after multiparity or treatment with carcinogen and hormone (progesterone). Reciprocally, selective pharmacological inhibition of RANKL attenuated mammary tumour development not only in hormone- and carcinogen-treated MMTV-RANK and wild-type mice, but also in the MMTV-neu transgenic spontaneous tumour model. The reduction in tumorigenesis upon RANKL inhibition was preceded by a reduction in pre-neoplasias as well as rapid and sustained reductions in hormone- and carcinogen-induced mammary epithelial proliferation and cyclin D1 levels. Collectively, our results indicate that RANKL inhibition is acting directly on hormone-induced mammary epithelium at early stages in tumorigenesis, and the permissive contribution of progesterone to increased mammary cancer incidence is due to RANKL-dependent proliferative changes in the mammary epithelium. The current study highlights a potential role for RANKL inhibition in the management of proliferative breast disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gonzalez-Suarez, Eva -- Jacob, Allison P -- Jones, Jon -- Miller, Robert -- Roudier-Meyer, Martine P -- Erwert, Ryan -- Pinkas, Jan -- Branstetter, Dan -- Dougall, William C -- England -- Nature. 2010 Nov 4;468(7320):103-7. doi: 10.1038/nature09495. Epub 2010 Sep 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Hematology/Oncology Research, Amgen Inc, Seattle, Washington 98119, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20881963" target="_blank"〉PubMed〈/a〉
    Keywords: 9,10-Dimethyl-1,2-benzanthracene/administration & dosage/adverse effects ; Animals ; Breast Neoplasms/metabolism/pathology ; Cell Proliferation/drug effects ; Cell Transformation, Neoplastic/*chemically induced/*drug effects/pathology ; Disease Models, Animal ; Epithelial Cells/drug effects/metabolism/pathology ; Female ; Humans ; Lung Neoplasms/secondary ; Mammary Neoplasms, Experimental/*chemically ; induced/genetics/metabolism/*pathology ; Mammary Tumor Virus, Mouse/genetics/physiology ; Medroxyprogesterone Acetate/administration & dosage/adverse effects ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neoplasm Invasiveness ; Precancerous Conditions/pathology/prevention & control ; Progesterone/administration & dosage/adverse effects ; Progestins/administration & dosage/*adverse effects ; RANK Ligand/antagonists & inhibitors/genetics/*metabolism ; Receptor Activator of Nuclear Factor-kappa B/genetics/metabolism
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  • 28
    Publication Date: 2010-01-22
    Description: In the lowermost layer of the atmosphere-the troposphere-ozone is an important source of the hydroxyl radical, an oxidant that breaks down most pollutants and some greenhouse gases. High concentrations of tropospheric ozone are toxic, however, and have a detrimental effect on human health and ecosystem productivity. Moreover, tropospheric ozone itself acts as an effective greenhouse gas. Much of the present tropospheric ozone burden is a consequence of anthropogenic emissions of ozone precursors resulting in widespread increases in ozone concentrations since the late 1800s. At present, east Asia has the fastest-growing ozone precursor emissions. Much of the springtime east Asian pollution is exported eastwards towards western North America. Despite evidence that the exported Asian pollution produces ozone, no previous study has found a significant increase in free tropospheric ozone concentrations above the western USA since measurements began in the late 1970s. Here we compile springtime ozone measurements from many different platforms across western North America. We show a strong increase in springtime ozone mixing ratios during 1995-2008 and we have some additional evidence that a similar rate of increase in ozone mixing ratio has occurred since 1984. We find that the rate of increase in ozone mixing ratio is greatest when measurements are more heavily influenced by direct transport from Asia. Our result agrees with previous modelling studies, which indicate that global ozone concentrations should be increasing during the early part of the twenty-first century as a result of increasing precursor emissions, especially at northern mid-latitudes, with western North America being particularly sensitive to rising Asian emissions. We suggest that the observed increase in springtime background ozone mixing ratio may hinder the USA's compliance with its ozone air quality standard.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cooper, O R -- Parrish, D D -- Stohl, A -- Trainer, M -- Nedelec, P -- Thouret, V -- Cammas, J P -- Oltmans, S J -- Johnson, B J -- Tarasick, D -- Leblanc, T -- McDermid, I S -- Jaffe, D -- Gao, R -- Stith, J -- Ryerson, T -- Aikin, K -- Campos, T -- Weinheimer, A -- Avery, M A -- England -- Nature. 2010 Jan 21;463(7279):344-8. doi: 10.1038/nature08708.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cooperative Institute for Research in Environmental Sciences, University of Colorado, Boulder, Colorado 80309, USA. owen.r.cooper@noaa.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20090751" target="_blank"〉PubMed〈/a〉
    Keywords: Air Pollutants/analysis/chemistry ; Asia ; Atmosphere/*chemistry ; Ecosystem ; Greenhouse Effect ; History, 20th Century ; History, 21st Century ; North America ; Ozone/*analysis/chemical synthesis/chemistry ; Sample Size ; Seasons
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  • 29
    Publication Date: 2009-10-09
    Description: Structural variations of DNA greater than 1 kilobase in size account for most bases that vary among human genomes, but are still relatively under-ascertained. Here we use tiling oligonucleotide microarrays, comprising 42 million probes, to generate a comprehensive map of 11,700 copy number variations (CNVs) greater than 443 base pairs, of which most (8,599) have been validated independently. For 4,978 of these CNVs, we generated reference genotypes from 450 individuals of European, African or East Asian ancestry. The predominant mutational mechanisms differ among CNV size classes. Retrotransposition has duplicated and inserted some coding and non-coding DNA segments randomly around the genome. Furthermore, by correlation with known trait-associated single nucleotide polymorphisms (SNPs), we identified 30 loci with CNVs that are candidates for influencing disease susceptibility. Despite this, having assessed the completeness of our map and the patterns of linkage disequilibrium between CNVs and SNPs, we conclude that, for complex traits, the heritability void left by genome-wide association studies will not be accounted for by common CNVs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3330748/" 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/PMC3330748/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Conrad, Donald F -- Pinto, Dalila -- Redon, Richard -- Feuk, Lars -- Gokcumen, Omer -- Zhang, Yujun -- Aerts, Jan -- Andrews, T Daniel -- Barnes, Chris -- Campbell, Peter -- Fitzgerald, Tomas -- Hu, Min -- Ihm, Chun Hwa -- Kristiansson, Kati -- Macarthur, Daniel G -- Macdonald, Jeffrey R -- Onyiah, Ifejinelo -- Pang, Andy Wing Chun -- Robson, Sam -- Stirrups, Kathy -- Valsesia, Armand -- Walter, Klaudia -- Wei, John -- Wellcome Trust Case Control Consortium -- Tyler-Smith, Chris -- Carter, Nigel P -- Lee, Charles -- Scherer, Stephen W -- Hurles, Matthew E -- 077006/Z/05/Z/Wellcome Trust/United Kingdom -- 077008/Wellcome Trust/United Kingdom -- 077009/Wellcome Trust/United Kingdom -- 077014/Wellcome Trust/United Kingdom -- 088340/Wellcome Trust/United Kingdom -- GM081533/GM/NIGMS NIH HHS/ -- HG004221/HG/NHGRI NIH HHS/ -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2010 Apr 1;464(7289):704-12. doi: 10.1038/nature08516. Epub 2009 Oct 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19812545" target="_blank"〉PubMed〈/a〉
    Keywords: Continental Population Groups/genetics ; DNA Copy Number Variations/*genetics ; Gene Duplication ; Genetic Predisposition to Disease/*genetics ; Genome, Human/*genetics ; Genome-Wide Association Study ; Genotype ; Haplotypes/genetics ; Humans ; Mutagenesis/*genetics ; Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide/genetics ; Reproducibility of Results
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  • 30
    Publication Date: 2010-10-12
    Description: Reciprocity of inflammation, oxidative stress and neovascularization is emerging as an important mechanism underlying numerous processes from tissue healing and remodelling to cancer progression. Whereas the mechanism of hypoxia-driven angiogenesis is well understood, the link between inflammation-induced oxidation and de novo blood vessel growth remains obscure. Here we show that the end products of lipid oxidation, omega-(2-carboxyethyl)pyrrole (CEP) and other related pyrroles, are generated during inflammation and wound healing and accumulate at high levels in ageing tissues in mice and in highly vascularized tumours in both murine and human melanoma. The molecular patterns of carboxyalkylpyrroles are recognized by Toll-like receptor 2 (TLR2), but not TLR4 or scavenger receptors on endothelial cells, leading to an angiogenic response that is independent of vascular endothelial growth factor. CEP promoted angiogenesis in hindlimb ischaemia and wound healing models through MyD88-dependent TLR2 signalling. Neutralization of endogenous carboxyalkylpyrroles impaired wound healing and tissue revascularization and diminished tumour angiogenesis. Both TLR2 and MyD88 are required for CEP-induced stimulation of Rac1 and endothelial migration. Taken together, these findings establish a new function of TLR2 as a sensor of oxidation-associated molecular patterns, providing a key link connecting inflammation, oxidative stress, innate immunity and angiogenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990914/" 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/PMC2990914/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉West, Xiaoxia Z -- Malinin, Nikolay L -- Merkulova, Alona A -- Tischenko, Mira -- Kerr, Bethany A -- Borden, Ernest C -- Podrez, Eugene A -- Salomon, Robert G -- Byzova, Tatiana V -- CA126847/CA/NCI NIH HHS/ -- GM021249/GM/NIGMS NIH HHS/ -- HL071625/HL/NHLBI NIH HHS/ -- HL073311/HL/NHLBI NIH HHS/ -- HL077213/HL/NHLBI NIH HHS/ -- R01 HL071625/HL/NHLBI NIH HHS/ -- R01 HL071625-07/HL/NHLBI NIH HHS/ -- R01 HL071625-08/HL/NHLBI NIH HHS/ -- R01 HL077213/HL/NHLBI NIH HHS/ -- England -- Nature. 2010 Oct 21;467(7318):972-6. doi: 10.1038/nature09421. Epub 2010 Oct 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Cardiology, J. J. Jacobs Center for Thrombosis and Vascular Biology, NB50, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20927103" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/metabolism ; Animals ; Antigens, CD31/metabolism ; Aorta/cytology/drug effects ; Cell Line ; Cell Movement ; Endothelial Cells/metabolism ; Hindlimb/metabolism ; Humans ; Immunity, Innate/immunology ; Inflammation/metabolism ; Ischemia/metabolism ; Ligands ; Melanoma/blood supply/metabolism ; Mice ; Mice, Inbred C57BL ; Myeloid Differentiation Factor 88/metabolism ; Neovascularization, Pathologic/*metabolism ; *Neovascularization, Physiologic/drug effects ; Oxidation-Reduction ; Oxidative Stress/*physiology ; Propionates ; Pyrroles/chemistry/*metabolism/pharmacology ; Receptors, Scavenger/metabolism ; Signal Transduction/drug effects ; Toll-Like Receptor 2/agonists/*metabolism ; Toll-Like Receptor 4/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Wound Healing/drug effects/physiology ; rac1 GTP-Binding Protein/metabolism
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  • 31
    Publication Date: 2010-01-08
    Description: Archaea, one of three major evolutionary lineages of life, encode proteasomes highly related to those of eukaryotes. In contrast, archaeal ubiquitin-like proteins are less conserved and not known to function in protein conjugation. This has complicated our understanding of the origins of ubiquitination and its connection to proteasomes. Here we report two small archaeal modifier proteins, SAMP1 and SAMP2, with a beta-grasp fold and carboxy-terminal diglycine motif similar to ubiquitin, that form protein conjugates in the archaeon Haloferax volcanii. The levels of SAMP-conjugates were altered by nitrogen-limitation and proteasomal gene knockout and spanned various functions including components of the Urm1 pathway. LC-MS/MS-based collision-induced dissociation demonstrated isopeptide bonds between the C-terminal glycine of SAMP2 and the epsilon-amino group of lysines from a number of protein targets and Lys 58 of SAMP2 itself, revealing poly-SAMP chains. The widespread distribution and diversity of pathways modified by SAMPylation suggest that this type of protein conjugation is central to the archaeal lineage.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2872088/" 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/PMC2872088/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Humbard, Matthew A -- Miranda, Hugo V -- Lim, Jae-Min -- Krause, David J -- Pritz, Jonathan R -- Zhou, Guangyin -- Chen, Sixue -- Wells, Lance -- Maupin-Furlow, Julie A -- 1S10 RR025418-01/RR/NCRR NIH HHS/ -- P41 RR018502/RR/NCRR NIH HHS/ -- P41 RR018502-07/RR/NCRR NIH HHS/ -- R01 GM057498/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Jan 7;463(7277):54-60. doi: 10.1038/nature08659.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Cell Science, University of Florida, Gainesville, Florida 32611, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20054389" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Archaeal Proteins/chemistry/*metabolism ; Gene Deletion ; Glycylglycine/metabolism ; Haloferax volcanii/genetics/metabolism ; Immunoprecipitation ; Mass Spectrometry ; Molecular Sequence Data ; Nitrogen/metabolism ; Proteasome Endopeptidase Complex/genetics/metabolism ; Sequence Alignment ; Sulfur/metabolism ; Ubiquitination ; Ubiquitins/chemistry/*metabolism
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  • 32
    Publication Date: 2010-10-12
    Description: Blood pressure is critically controlled by angiotensins, which are vasopressor peptides specifically released by the enzyme renin from the tail of angiotensinogen-a non-inhibitory member of the serpin family of protease inhibitors. Although angiotensinogen has long been regarded as a passive substrate, the crystal structures solved here to 2.1 A resolution show that the angiotensin cleavage site is inaccessibly buried in its amino-terminal tail. The conformational rearrangement that makes this site accessible for proteolysis is revealed in our 4.4 A structure of the complex of human angiotensinogen with renin. The co-ordinated changes involved are seen to be critically linked by a conserved but labile disulphide bridge. Here we show that the reduced unbridged form of angiotensinogen is present in the circulation in a near 40:60 ratio with the oxidized sulphydryl-bridged form, which preferentially interacts with receptor-bound renin. We propose that this redox-responsive transition of angiotensinogen to a form that will more effectively release angiotensin at a cellular level contributes to the modulation of blood pressure. Specifically, we demonstrate the oxidative switch of angiotensinogen to its more active sulphydryl-bridged form in the maternal circulation in pre-eclampsia-the hypertensive crisis of pregnancy that threatens the health and survival of both mother and child.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024006/" 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/PMC3024006/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Aiwu -- Carrell, Robin W -- Murphy, Michael P -- Wei, Zhenquan -- Yan, Yahui -- Stanley, Peter L D -- Stein, Penelope E -- Broughton Pipkin, Fiona -- Read, Randy J -- 082961/Wellcome Trust/United Kingdom -- BS/05/002/18361/British Heart Foundation/United Kingdom -- MC_U105663142/Medical Research Council/United Kingdom -- PG/08/041/24818/British Heart Foundation/United Kingdom -- PG/09/072/27945/British Heart Foundation/United Kingdom -- British Heart Foundation/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Nov 4;468(7320):108-11. doi: 10.1038/nature09505. Epub 2010 Oct 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK. awz20@cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20927107" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Angiotensinogen/blood/*chemistry/*metabolism ; Angiotensins/chemistry/*metabolism/secretion ; Blood Pressure ; Crystallography, X-Ray ; Disulfides/chemistry/metabolism ; Female ; Humans ; Kinetics ; Models, Molecular ; Molecular Sequence Data ; Oxidation-Reduction ; Oxidative Stress ; Pre-Eclampsia/blood/metabolism ; Pregnancy ; Protein Conformation ; *Protein Processing, Post-Translational ; Renin/chemistry/metabolism
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  • 33
    Publication Date: 2010-04-29
    Description: The nucleolytic activity of animal Argonaute proteins is deeply conserved, despite its having no obvious role in microRNA-directed gene regulation. In mice, Ago2 (also known as Eif2c2) is uniquely required for viability, and only this family member retains catalytic competence. To investigate the evolutionary pressure to conserve Argonaute enzymatic activity, we engineered a mouse with catalytically inactive Ago2 alleles. Homozygous mutants died shortly after birth with an obvious anaemia. Examination of microRNAs and their potential targets revealed a loss of miR-451, a small RNA important for erythropoiesis. Though this microRNA is processed by Drosha (also known as Rnasen), its maturation does not require Dicer. Instead, the pre-miRNA becomes loaded into Ago and is cleaved by the Ago catalytic centre to generate an intermediate 3' end, which is then further trimmed. Our findings link the conservation of Argonaute catalysis to a conserved mechanism of microRNA biogenesis that is important for vertebrate development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995450/" 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/PMC2995450/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cheloufi, Sihem -- Dos Santos, Camila O -- Chong, Mark M W -- Hannon, Gregory J -- P01 CA013106/CA/NCI NIH HHS/ -- P01 CA013106-38/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Jun 3;465(7298):584-9. doi: 10.1038/nature09092.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cold Spring Harbor Laboratory, Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor, New York 11724, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20424607" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Anemia/genetics/metabolism ; Animals ; Argonaute Proteins ; Base Sequence ; *Biocatalysis ; Embryo, Mammalian/embryology/metabolism ; Eukaryotic Initiation Factor-2/genetics/*metabolism ; Homozygote ; MicroRNAs/*biosynthesis ; Molecular Sequence Data ; Ribonuclease III/metabolism
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  • 34
    Publication Date: 2010-02-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ferry, Georgina -- England -- Nature. 2010 Feb 25;463(7284):1025. doi: 10.1038/4631025a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20182497" target="_blank"〉PubMed〈/a〉
    Keywords: Archives ; *Biography as Topic ; Electronic Mail ; History, 20th Century ; Nobel Prize ; Research Personnel/history ; Science/history ; *Writing
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  • 35
    Publication Date: 2010-09-30
    Description: Cell-cell signalling of semaphorin ligands through interaction with plexin receptors is important for the homeostasis and morphogenesis of many tissues and is widely studied for its role in neural connectivity, cancer, cell migration and immune responses. SEMA4D and Sema6A exemplify two diverse vertebrate, membrane-spanning semaphorin classes (4 and 6) that are capable of direct signalling through members of the two largest plexin classes, B and A, respectively. In the absence of any structural information on the plexin ectodomain or its interaction with semaphorins the extracellular specificity and mechanism controlling plexin signalling has remained unresolved. Here we present crystal structures of cognate complexes of the semaphorin-binding regions of plexins B1 and A2 with semaphorin ectodomains (human PLXNB1(1-2)-SEMA4D(ecto) and murine PlxnA2(1-4)-Sema6A(ecto)), plus unliganded structures of PlxnA2(1-4) and Sema6A(ecto). These structures, together with biophysical and cellular assays of wild-type and mutant proteins, reveal that semaphorin dimers independently bind two plexin molecules and that signalling is critically dependent on the avidity of the resulting bivalent 2:2 complex (monomeric semaphorin binds plexin but fails to trigger signalling). In combination, our data favour a cell-cell signalling mechanism involving semaphorin-stabilized plexin dimerization, possibly followed by clustering, which is consistent with previous functional data. Furthermore, the shared generic architecture of the complexes, formed through conserved contacts of the amino-terminal seven-bladed beta-propeller (sema) domains of both semaphorin and plexin, suggests that a common mode of interaction triggers all semaphorin-plexin based signalling, while distinct insertions within or between blades of the sema domains determine binding specificity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587840/" 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/PMC3587840/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Janssen, Bert J C -- Robinson, Ross A -- Perez-Branguli, Francesc -- Bell, Christian H -- Mitchell, Kevin J -- Siebold, Christian -- Jones, E Yvonne -- 082301/Wellcome Trust/United Kingdom -- 083111/Wellcome Trust/United Kingdom -- 10976/Cancer Research UK/United Kingdom -- A10976/Cancer Research UK/United Kingdom -- A3964/Cancer Research UK/United Kingdom -- A5261/Cancer Research UK/United Kingdom -- G0700232/Medical Research Council/United Kingdom -- G0700232(82098)/Medical Research Council/United Kingdom -- G0900084/Medical Research Council/United Kingdom -- G9900061/Medical Research Council/United Kingdom -- G9900061(69203)/Medical Research Council/United Kingdom -- Cancer Research UK/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Oct 28;467(7319):1118-22. doi: 10.1038/nature09468. Epub 2010 Sep 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20877282" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/chemistry/genetics/metabolism ; Binding Sites ; Cell Adhesion Molecules/*chemistry/genetics/*metabolism ; Cell Communication ; Crystallography, X-Ray ; Humans ; Ligands ; Mice ; Mice, Inbred C57BL ; Models, Molecular ; NIH 3T3 Cells ; Nerve Tissue Proteins/*chemistry/genetics/*metabolism ; Protein Binding ; Protein Structure, Tertiary ; Receptors, Cell Surface/chemistry/genetics/metabolism ; Semaphorins/*chemistry/genetics/*metabolism ; *Signal Transduction ; Structure-Activity Relationship
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  • 36
    Publication Date: 2010-06-26
    Description: Lymph nodes (LNs) capture microorganisms that breach the body's external barriers and enter draining lymphatics, limiting the systemic spread of pathogens. Recent work has shown that CD11b(+)CD169(+) macrophages, which populate the subcapsular sinus (SCS) of LNs, are critical for the clearance of viruses from the lymph and for initiating antiviral humoral immune responses. Here we show, using vesicular stomatitis virus (VSV), a relative of rabies virus transmitted by insect bites, that SCS macrophages perform a third vital function: they prevent lymph-borne neurotropic viruses from infecting the central nervous system (CNS). On local depletion of LN macrophages, about 60% of mice developed ascending paralysis and died 7-10 days after subcutaneous infection with a small dose of VSV, whereas macrophage-sufficient animals remained asymptomatic and cleared the virus. VSV gained access to the nervous system through peripheral nerves in macrophage-depleted LNs. In contrast, within macrophage-sufficient LNs VSV replicated preferentially in SCS macrophages but not in adjacent nerves. Removal of SCS macrophages did not compromise adaptive immune responses against VSV, but decreased type I interferon (IFN-I) production within infected LNs. VSV-infected macrophages recruited IFN-I-producing plasmacytoid dendritic cells to the SCS and in addition were a major source of IFN-I themselves. Experiments in bone marrow chimaeric mice revealed that IFN-I must act on both haematopoietic and stromal compartments, including the intranodal nerves, to prevent lethal infection with VSV. These results identify SCS macrophages as crucial gatekeepers to the CNS that prevent fatal viral invasion of the nervous system on peripheral infection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892812/" 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/PMC2892812/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Iannacone, Matteo -- Moseman, E Ashley -- Tonti, Elena -- Bosurgi, Lidia -- Junt, Tobias -- Henrickson, Sarah E -- Whelan, Sean P -- Guidotti, Luca G -- von Andrian, Ulrich H -- AI069259/AI/NIAID NIH HHS/ -- AI072252/AI/NIAID NIH HHS/ -- AI078897/AI/NIAID NIH HHS/ -- AR42689/AR/NIAMS NIH HHS/ -- P01 AI078897/AI/NIAID NIH HHS/ -- P01 AI078897-01/AI/NIAID NIH HHS/ -- P01 CA071932/CA/NCI NIH HHS/ -- P01 CA071932-12S29003/CA/NCI NIH HHS/ -- R01 AI069259/AI/NIAID NIH HHS/ -- R01 AI069259-06/AI/NIAID NIH HHS/ -- R01 AI072252/AI/NIAID NIH HHS/ -- R01 AI072252-04/AI/NIAID NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Jun 24;465(7301):1079-83. doi: 10.1038/nature09118.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immune Disease Institute and Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA. Matteo_Iannacone@hms.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20577213" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Central Nervous System/cytology/*immunology/*virology ; Dendritic Cells/immunology ; Injections ; Interferon Type I/immunology ; Lymph Nodes/cytology/*immunology/innervation/*virology ; Macrophages/*immunology/virology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Paralysis/complications/virology ; Peripheral Nerves/virology ; Receptor, Interferon alpha-beta/deficiency ; Rhabdoviridae Infections/complications/*immunology/virology ; Survival Rate ; Vesicular stomatitis Indiana virus/immunology/pathogenicity/physiology ; Vesicular stomatitis New Jersey virus/immunology/pathogenicity/physiology ; Vesiculovirus/*immunology/pathogenicity/physiology
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  • 37
    Publication Date: 2010-04-20
    Description: Ever since Darwin's pioneering research, the evolution of self-fertilisation (selfing) has been regarded as one of the most prevalent evolutionary transitions in flowering plants. A major mechanism to prevent selfing is the self-incompatibility (SI) recognition system, which consists of male and female specificity genes at the S-locus and SI modifier genes. Under conditions that favour selfing, mutations disabling the male recognition component are predicted to enjoy a relative advantage over those disabling the female component, because male mutations would increase through both pollen and seeds whereas female mutations would increase only through seeds. Despite many studies on the genetic basis of loss of SI in the predominantly selfing plant Arabidopsis thaliana, it remains unknown whether selfing arose through mutations in the female specificity gene (S-receptor kinase, SRK), male specificity gene (S-locus cysteine-rich protein, SCR; also known as S-locus protein 11, SP11) or modifier genes, and whether any of them rose to high frequency across large geographic regions. Here we report that a disruptive 213-base-pair (bp) inversion in the SCR gene (or its derivative haplotypes with deletions encompassing the entire SCR-A and a large portion of SRK-A) is found in 95% of European accessions, which contrasts with the genome-wide pattern of polymorphism in European A. thaliana. Importantly, interspecific crossings using Arabidopsis halleri as a pollen donor reveal that some A. thaliana accessions, including Wei-1, retain the female SI reaction, suggesting that all female components including SRK are still functional. Moreover, when the 213-bp inversion in SCR was inverted and expressed in transgenic Wei-1 plants, the functional SCR restored the SI reaction. The inversion within SCR is the first mutation disrupting SI shown to be nearly fixed in geographically wide samples, and its prevalence is consistent with theoretical predictions regarding the evolutionary advantage of mutations in male components.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tsuchimatsu, Takashi -- Suwabe, Keita -- Shimizu-Inatsugi, Rie -- Isokawa, Sachiyo -- Pavlidis, Pavlos -- Stadler, Thomas -- Suzuki, Go -- Takayama, Seiji -- Watanabe, Masao -- Shimizu, Kentaro K -- England -- Nature. 2010 Apr 29;464(7293):1342-6. doi: 10.1038/nature08927. Epub 2010 Apr 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Plant Biology, University Research Priority Program in Systems Biology/Functional Genomics & Zurich-Basel Plant Science Center, University of Zurich, Zollikerstrasse 107, CH-8008 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20400945" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis/chemistry/classification/*genetics/*physiology ; *Biological Evolution ; Crosses, Genetic ; Genes, Plant/*genetics ; Haplotypes/genetics ; Hybridization, Genetic/genetics ; Molecular Sequence Data ; Mutation/*genetics ; Pollen/physiology ; Pollination ; Reproduction/genetics/physiology
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  • 38
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    Nature Publishing Group (NPG)
    Publication Date: 2010-06-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clayton, Julie -- England -- Nature. 2010 Jun 24;465(7301):S4-5. doi: 10.1038/nature09220.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20571553" target="_blank"〉PubMed〈/a〉
    Keywords: Acute Disease ; Animals ; Carrier State/epidemiology/immunology/parasitology ; *Chagas Disease/drug therapy/epidemiology/parasitology/transmission ; Chronic Disease/drug therapy/epidemiology ; Clinical Trials as Topic ; History, 16th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; Humans ; Insect Vectors/parasitology ; Latin America/epidemiology/ethnology ; Neglected Diseases/economics ; Nitroimidazoles/pharmacology/therapeutic use ; Trypanocidal Agents/pharmacology/therapeutic use ; Trypanosoma cruzi/immunology/pathogenicity/physiology
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  • 39
    Publication Date: 2010-04-30
    Description: In sensory cortex regions, neurons are tuned to specific stimulus features. For example, in the visual cortex, many neurons fire predominantly in response to moving objects of a preferred orientation. However, the characteristics of the synaptic input that cortical neurons receive to generate their output firing pattern remain unclear. Here we report a novel approach for the visualization and functional mapping of sensory inputs to the dendrites of cortical neurons in vivo. By combining high-speed two-photon imaging with electrophysiological recordings, we identify local subthreshold calcium signals that correspond to orientation-specific synaptic inputs. We find that even inputs that share the same orientation preference are widely distributed throughout the dendritic tree. At the same time, inputs of different orientation preference are interspersed, so that adjacent dendritic segments are tuned to distinct orientations. Thus, orientation-tuned neurons can compute their characteristic firing pattern by integrating spatially distributed synaptic inputs coding for multiple stimulus orientations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jia, Hongbo -- Rochefort, Nathalie L -- Chen, Xiaowei -- Konnerth, Arthur -- England -- Nature. 2010 Apr 29;464(7293):1307-12. doi: 10.1038/nature08947.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Neuroscience and Center for Integrated Protein Science, Technical University Munich, Biedersteinerstrasse 29, 80802 Munich, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20428163" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Calcium Signaling ; Dendrites/*physiology ; Mice ; Mice, Inbred C57BL ; Models, Neurological ; Sensory Receptor Cells/cytology/*physiology ; Synapses/metabolism ; Visual Cortex/*cytology
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  • 40
    Publication Date: 2010-08-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Oreskes, Naomi -- Conway, Erik M -- England -- Nature. 2010 Aug 12;466(7308):815. doi: 10.1038/466815d.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20703283" target="_blank"〉PubMed〈/a〉
    Keywords: Acid Rain/*statistics & numerical data ; Federal Government ; History, 20th Century ; Peer Review ; United States
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  • 41
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    Nature Publishing Group (NPG)
    Publication Date: 2010-04-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Venter, J Craig -- England -- Nature. 2010 Apr 1;464(7289):676-7. doi: 10.1038/464676a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉J. Craig Venter Institute, La Jolla, California 92121, USA. jcventer@jcvi.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360717" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Continental Population Groups/genetics ; Diploidy ; Female ; Genetic Predisposition to Disease/genetics ; Genetic Variation/genetics ; Genetics, Medical/*trends ; Genome, Human/*genetics ; Genomics/economics/history/*trends ; Haploidy ; Haplotypes/genetics ; History, 20th Century ; History, 21st Century ; Human Genome Project/economics/history ; Humans ; Male ; Phenotype ; Precision Medicine/*trends ; Sequence Analysis, DNA/economics/history/instrumentation/methods
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  • 42
    Publication Date: 2010-07-24
    Description: Learning new action sequences subserves a plethora of different abilities such as escaping a predator, playing the piano, or producing fluent speech. Proper initiation and termination of each action sequence is critical for the organization of behaviour, and is compromised in nigrostriatal disorders like Parkinson's and Huntington's diseases. Using a self-paced operant task in which mice learn to perform a particular sequence of actions to obtain an outcome, we found neural activity in nigrostriatal circuits specifically signalling the initiation or the termination of each action sequence. This start/stop activity emerged during sequence learning, was specific for particular actions, and did not reflect interval timing, movement speed or action value. Furthermore, genetically altering the function of striatal circuits disrupted the development of start/stop activity and selectively impaired sequence learning. These results have important implications for understanding the functional organization of actions and the sequence initiation and termination impairments observed in basal ganglia disorders.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477867/" 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/PMC3477867/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jin, Xin -- Costa, Rui M -- 243393/European Research Council/International -- Z01 AA000416-02/Intramural NIH HHS/ -- England -- Nature. 2010 Jul 22;466(7305):457-62. doi: 10.1038/nature09263.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Bethesda, Maryland 20892-9412, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20651684" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Behavior, Animal/physiology ; Dopamine/metabolism ; Glutamic Acid/metabolism ; Learning/*physiology ; Male ; Mice ; Mice, Inbred C57BL ; Models, Neurological ; Neostriatum/*physiology ; Neural Pathways/*physiology ; Receptors, N-Methyl-D-Aspartate/deficiency/genetics/metabolism ; Substantia Nigra/*physiology
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  • 43
    Publication Date: 2010-06-04
    Description: Brown algae (Phaeophyceae) are complex photosynthetic organisms with a very different evolutionary history to green plants, to which they are only distantly related. These seaweeds are the dominant species in rocky coastal ecosystems and they exhibit many interesting adaptations to these, often harsh, environments. Brown algae are also one of only a small number of eukaryotic lineages that have evolved complex multicellularity (Fig. 1). We report the 214 million base pair (Mbp) genome sequence of the filamentous seaweed Ectocarpus siliculosus (Dillwyn) Lyngbye, a model organism for brown algae, closely related to the kelps (Fig. 1). Genome features such as the presence of an extended set of light-harvesting and pigment biosynthesis genes and new metabolic processes such as halide metabolism help explain the ability of this organism to cope with the highly variable tidal environment. The evolution of multicellularity in this lineage is correlated with the presence of a rich array of signal transduction genes. Of particular interest is the presence of a family of receptor kinases, as the independent evolution of related molecules has been linked with the emergence of multicellularity in both the animal and green plant lineages. The Ectocarpus genome sequence represents an important step towards developing this organism as a model species, providing the possibility to combine genomic and genetic approaches to explore these and other aspects of brown algal biology further.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cock, J Mark -- Sterck, Lieven -- Rouze, Pierre -- Scornet, Delphine -- Allen, Andrew E -- Amoutzias, Grigoris -- Anthouard, Veronique -- Artiguenave, Francois -- Aury, Jean-Marc -- Badger, Jonathan H -- Beszteri, Bank -- Billiau, Kenny -- Bonnet, Eric -- Bothwell, John H -- Bowler, Chris -- Boyen, Catherine -- Brownlee, Colin -- Carrano, Carl J -- Charrier, Benedicte -- Cho, Ga Youn -- Coelho, Susana M -- Collen, Jonas -- Corre, Erwan -- Da Silva, Corinne -- Delage, Ludovic -- Delaroque, Nicolas -- Dittami, Simon M -- Doulbeau, Sylvie -- Elias, Marek -- Farnham, Garry -- Gachon, Claire M M -- Gschloessl, Bernhard -- Heesch, Svenja -- Jabbari, Kamel -- Jubin, Claire -- Kawai, Hiroshi -- Kimura, Kei -- Kloareg, Bernard -- Kupper, Frithjof C -- Lang, Daniel -- Le Bail, Aude -- Leblanc, Catherine -- Lerouge, Patrice -- Lohr, Martin -- Lopez, Pascal J -- Martens, Cindy -- Maumus, Florian -- Michel, Gurvan -- Miranda-Saavedra, Diego -- Morales, Julia -- Moreau, Herve -- Motomura, Taizo -- Nagasato, Chikako -- Napoli, Carolyn A -- Nelson, David R -- Nyvall-Collen, Pi -- Peters, Akira F -- Pommier, Cyril -- Potin, Philippe -- Poulain, Julie -- Quesneville, Hadi -- Read, Betsy -- Rensing, Stefan A -- Ritter, Andres -- Rousvoal, Sylvie -- Samanta, Manoj -- Samson, Gaelle -- Schroeder, Declan C -- Segurens, Beatrice -- Strittmatter, Martina -- Tonon, Thierry -- Tregear, James W -- Valentin, Klaus -- von Dassow, Peter -- Yamagishi, Takahiro -- Van de Peer, Yves -- Wincker, Patrick -- England -- Nature. 2010 Jun 3;465(7298):617-21. doi: 10.1038/nature09016.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉UPMC Universite Paris 6, The Marine Plants and Biomolecules Laboratory, UMR 7139, Station Biologique de Roscoff, Place Georges Teissier, BP74, 29682 Roscoff Cedex, France. cock@sb-roscoff.fr〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20520714" target="_blank"〉PubMed〈/a〉
    Keywords: Algal Proteins/*genetics ; Animals ; *Biological Evolution ; Eukaryota ; Evolution, Molecular ; Genome/*genetics ; Molecular Sequence Data ; Phaeophyta/*cytology/*genetics/metabolism ; Phylogeny ; Pigments, Biological/biosynthesis ; Signal Transduction/genetics
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  • 44
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    Nature Publishing Group (NPG)
    Publication Date: 2010-10-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Oct 28;467(7319):1136. doi: 10.1038/4671136a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20981104" target="_blank"〉PubMed〈/a〉
    Keywords: DNA Copy Number Variations/*genetics ; Genome, Human/*genetics ; Genomics/*methods ; Humans ; Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide/genetics ; Reproducibility of Results
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  • 45
    Publication Date: 2010-12-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schofield, Paul N -- Tapio, Soile -- Grosche, Bernd -- England -- Nature. 2010 Dec 2;468(7324):634. doi: 10.1038/468634a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21124436" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Archives/*history ; Databases, Factual/history ; Europe ; History, 20th Century ; Information Storage and Retrieval ; Japan ; Radiobiology/*history ; Time Factors ; United States
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  • 46
    Publication Date: 2010-05-21
    Description: The need to maintain the structural and functional integrity of an evolving protein severely restricts the repertoire of acceptable amino-acid substitutions. However, it is not known whether these restrictions impose a global limit on how far homologous protein sequences can diverge from each other. Here we explore the limits of protein evolution using sequence divergence data. We formulate a computational approach to study the rate of divergence of distant protein sequences and measure this rate for ancient proteins, those that were present in the last universal common ancestor. We show that ancient proteins are still diverging from each other, indicating an ongoing expansion of the protein sequence universe. The slow rate of this divergence is imposed by the sparseness of functional protein sequences in sequence space and the ruggedness of the protein fitness landscape: approximately 98 per cent of sites cannot accept an amino-acid substitution at any given moment but a vast majority of all sites may eventually be permitted to evolve when other, compensatory, changes occur. Thus, approximately 3.5 x 10(9) yr has not been enough to reach the limit of divergent evolution of proteins, and for most proteins the limit of sequence similarity imposed by common function may not exceed that of random sequences.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Povolotskaya, Inna S -- Kondrashov, Fyodor A -- England -- Nature. 2010 Jun 17;465(7300):922-6. doi: 10.1038/nature09105. Epub 2010 May 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bioinformatics and Genomics Programme, Centre for Genomic Regulation, Calle Dr Aiguader 88, Barcelona Biomedical Research Park Building, 08003 Barcelona, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20485343" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Amino Acids/chemistry ; *Evolution, Molecular ; *Genetic Variation ; Molecular Sequence Data ; Mutation ; Prokaryotic Cells ; Protein Structure, Secondary ; Proteins/*chemistry ; Selection, Genetic/genetics ; Sequence Analysis, Protein ; Sequence Homology, Amino Acid
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  • 47
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    Nature Publishing Group (NPG)
    Publication Date: 2010-06-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Katsnelson, Alla -- England -- Nature. 2010 Jun 3;465(7298):537. doi: 10.1038/465537a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20520682" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Culture Techniques/*methods/*standards ; Cell Line/*classification ; Cell Lineage ; *DNA Fingerprinting/methods/standards ; HeLa Cells ; Humans ; Organ Specificity ; Reproducibility of Results
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  • 48
    Publication Date: 2010-01-15
    Description: All immune systems must distinguish self from non-self to repel invaders without inducing autoimmunity. Clustered, regularly interspaced, short palindromic repeat (CRISPR) loci protect bacteria and archaea from invasion by phage and plasmid DNA through a genetic interference pathway. CRISPR loci are present in approximately 40% and approximately 90% of sequenced bacterial and archaeal genomes, respectively, and evolve rapidly, acquiring new spacer sequences to adapt to highly dynamic viral populations. Immunity requires a sequence match between the invasive DNA and the spacers that lie between CRISPR repeats. Each cluster is genetically linked to a subset of the cas (CRISPR-associated) genes that collectively encode 〉40 families of proteins involved in adaptation and interference. CRISPR loci encode small CRISPR RNAs (crRNAs) that contain a full spacer flanked by partial repeat sequences. CrRNA spacers are thought to identify targets by direct Watson-Crick pairing with invasive 'protospacer' DNA, but how they avoid targeting the spacer DNA within the encoding CRISPR locus itself is unknown. Here we have defined the mechanism of CRISPR self/non-self discrimination. In Staphylococcus epidermidis, target/crRNA mismatches at specific positions outside of the spacer sequence license foreign DNA for interference, whereas extended pairing between crRNA and CRISPR DNA repeats prevents autoimmunity. Hence, this CRISPR system uses the base-pairing potential of crRNAs not only to specify a target, but also to spare the bacterial chromosome from interference. Differential complementarity outside of the spacer sequence is a built-in feature of all CRISPR systems, indicating that this mechanism is a broadly applicable solution to the self/non-self dilemma that confronts all immune pathways.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2813891/" 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/PMC2813891/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marraffini, Luciano A -- Sontheimer, Erik J -- R03 AI079722/AI/NIAID NIH HHS/ -- R03 AI079722-01A1/AI/NIAID NIH HHS/ -- England -- Nature. 2010 Jan 28;463(7280):568-71. doi: 10.1038/nature08703. Epub 2010 Jan 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, 2205 Tech Drive, Evanston, Illinois 60208, USA. marraffini@northwestern.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20072129" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/genetics ; Base Pairing/genetics ; Base Sequence ; Conserved Sequence ; DNA, Intergenic/genetics ; Molecular Sequence Data ; Mutation/genetics ; RNA, Bacterial/*genetics/metabolism ; Repetitive Sequences, Nucleic Acid/*genetics/*immunology ; Staphylococcus epidermidis/*genetics/*immunology
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  • 49
    Publication Date: 2010-11-05
    Description: Bacteria and Archaea have developed several defence strategies against foreign nucleic acids such as viral genomes and plasmids. Among them, clustered regularly interspaced short palindromic repeats (CRISPR) loci together with cas (CRISPR-associated) genes form the CRISPR/Cas immune system, which involves partially palindromic repeats separated by short stretches of DNA called spacers, acquired from extrachromosomal elements. It was recently demonstrated that these variable loci can incorporate spacers from infecting bacteriophages and then provide immunity against subsequent bacteriophage infections in a sequence-specific manner. Here we show that the Streptococcus thermophilus CRISPR1/Cas system can also naturally acquire spacers from a self-replicating plasmid containing an antibiotic-resistance gene, leading to plasmid loss. Acquired spacers that match antibiotic-resistance genes provide a novel means to naturally select bacteria that cannot uptake and disseminate such genes. We also provide in vivo evidence that the CRISPR1/Cas system specifically cleaves plasmid and bacteriophage double-stranded DNA within the proto-spacer, at specific sites. Our data show that the CRISPR/Cas immune system is remarkably adapted to cleave invading DNA rapidly and has the potential for exploitation to generate safer microbial strains.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Garneau, Josiane E -- Dupuis, Marie-Eve -- Villion, Manuela -- Romero, Dennis A -- Barrangou, Rodolphe -- Boyaval, Patrick -- Fremaux, Christophe -- Horvath, Philippe -- Magadan, Alfonso H -- Moineau, Sylvain -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2010 Nov 4;468(7320):67-71. doi: 10.1038/nature09523.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departement de biochimie, de microbiologie et de bio-informatique, Faculte des sciences et de genie, Groupe de recherche en ecologie buccale, Faculte de medecine dentaire, Felix d'Herelle Reference Center for Bacterial Viruses, Universite Laval, Quebec City, Quebec G1V 0A6, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21048762" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteriophages/*genetics/metabolism ; Base Sequence ; DNA, Intergenic/genetics/metabolism ; DNA, Viral/genetics/*metabolism ; Drug Resistance, Bacterial/genetics ; Genetic Loci/*genetics/*immunology ; Interspersed Repetitive Sequences/genetics ; Molecular Sequence Data ; Mutation ; Plasmids/genetics/*metabolism ; RNA, Bacterial/genetics/immunology ; Streptococcus thermophilus/genetics/*immunology/*virology
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  • 50
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    Nature Publishing Group (NPG)
    Publication Date: 2010-04-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Collins, Francis -- England -- Nature. 2010 Apr 1;464(7289):674-5. doi: 10.1038/464674a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Institutes of Health, Bethesda, Maryland 20892, USA. francis.collins@nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360716" target="_blank"〉PubMed〈/a〉
    Keywords: Access to Information ; Genetic Predisposition to Disease/genetics ; Genetics, Medical/*trends ; Genome, Human/*genetics ; Genome-Wide Association Study ; Genomics/economics/history/*trends ; Haplotypes/genetics ; History, 20th Century ; History, 21st Century ; Humans ; Precision Medicine/*trends ; Sequence Analysis, DNA/economics/history/trends
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  • 51
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    Nature Publishing Group (NPG)
    Publication Date: 2010-08-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schrope, Mark -- England -- Nature. 2010 Aug 12;466(7308):802. doi: 10.1038/466802a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20703275" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Disasters/*statistics & numerical data ; Ecology ; *Ecosystem ; Marine Biology ; Oceanography ; Oceans and Seas ; Petroleum/adverse effects/*analysis ; Reproducibility of Results ; Seawater/*chemistry ; *Uncertainty ; Volatilization
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  • 52
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    Nature Publishing Group (NPG)
    Publication Date: 2010-07-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schrope, Mark -- England -- Nature. 2010 Jul 15;466(7304):304-5. doi: 10.1038/466304a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20631769" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Disasters/history ; *Ecosystem ; Fisheries/history/statistics & numerical data ; History, 20th Century ; History, 21st Century ; Marine Biology/history/trends ; Mexico ; Oceans and Seas ; Ostreidae ; Petroleum/*analysis/*toxicity ; Population Dynamics ; Research/history/*statistics & numerical data/trends ; Seawater/*chemistry
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  • 53
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    Nature Publishing Group (NPG)
    Publication Date: 2010-08-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Aug 12;466(7308):797. doi: 10.1038/466797a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20703263" target="_blank"〉PubMed〈/a〉
    Keywords: *Consumer Advocacy ; Genetic Testing/*legislation & jurisprudence/*standards ; Government Regulation ; Humans ; Marketing/standards ; Oligonucleotide Array Sequence Analysis ; Reproducibility of Results ; United States ; United States Food and Drug Administration/legislation & jurisprudence
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  • 54
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    Nature Publishing Group (NPG)
    Publication Date: 2010-02-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Borrell, Brendan -- England -- Nature. 2010 Feb 18;463(7283):858. doi: 10.1038/463858a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20164888" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line, Tumor/*metabolism ; Genetics, Medical/*methods/*trends ; Genomics/*methods/*trends ; Humans ; Neoplasms/*genetics/*pathology ; Reproducibility of Results ; Sequence Analysis, DNA/trends
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  • 55
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    Nature Publishing Group (NPG)
    Publication Date: 2010-04-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Apr 22;464(7292):1103-4. doi: 10.1038/4641103b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20414265" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Benzhydryl Compounds ; Chemical Industry/*legislation & jurisprudence/*standards ; *Evaluation Studies as Topic ; *Federal Government ; Guidelines as Topic ; Humans ; Phenols/adverse effects/toxicity ; Reproducibility of Results ; Safety/*legislation & jurisprudence/*standards ; *Toxicity Tests/methods/standards ; United States
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  • 56
    Publication Date: 2010-02-26
    Description: Despite the essential roles of sphingolipids both as structural components of membranes and critical signalling molecules, we have a limited understanding of how cells sense and regulate their levels. Here we reveal the function in sphingolipid metabolism of the ORM genes (known as ORMDL genes in humans)-a conserved gene family that includes ORMDL3, which has recently been identified as a potential risk factor for childhood asthma. Starting from an unbiased functional genomic approach in Saccharomyces cerevisiae, we identify Orm proteins as negative regulators of sphingolipid synthesis that form a conserved complex with serine palmitoyltransferase, the first and rate-limiting enzyme in sphingolipid production. We also define a regulatory pathway in which phosphorylation of Orm proteins relieves their inhibitory activity when sphingolipid production is disrupted. Changes in ORM gene expression or mutations to their phosphorylation sites cause dysregulation of sphingolipid metabolism. Our work identifies the Orm proteins as critical mediators of sphingolipid homeostasis and raises the possibility that sphingolipid misregulation contributes to the development of childhood asthma.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2877384/" 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/PMC2877384/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Breslow, David K -- Collins, Sean R -- Bodenmiller, Bernd -- Aebersold, Ruedi -- Simons, Kai -- Shevchenko, Andrej -- Ejsing, Christer S -- Weissman, Jonathan S -- N01-HV-28179/HV/NHLBI NIH HHS/ -- P50 GM073210/GM/NIGMS NIH HHS/ -- P50 GM073210-06/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Feb 25;463(7284):1048-53. doi: 10.1038/nature08787.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology, University of California, San Francisco, 1700 4th Street, San Francisco, California 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20182505" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Asthma/metabolism ; Cell Line ; Conserved Sequence ; Fatty Acids, Monounsaturated/pharmacology ; HeLa Cells ; *Homeostasis ; Humans ; Molecular Sequence Data ; *Multigene Family ; Multiprotein Complexes/chemistry/metabolism ; Phosphoric Monoester Hydrolases/genetics/metabolism ; Phosphorylation ; Protein Binding ; Saccharomyces cerevisiae/drug effects/enzymology/genetics/*metabolism ; Saccharomyces cerevisiae Proteins/classification/genetics/*metabolism ; Serine C-Palmitoyltransferase/genetics/metabolism ; Sphingolipids/biosynthesis/*metabolism
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  • 57
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    Nature Publishing Group (NPG)
    Publication Date: 2010-08-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Briggs, Derek E G -- England -- Nature. 2010 Aug 5;466(7307):706. doi: 10.1038/466706a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Geology and Geophysics, and the Peabody Museum of Natural History, Yale University, New Haven, Connecticut 06520, USA. derek.briggs@yale.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20686564" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; British Columbia ; *Fossils ; Geologic Sediments/analysis/chemistry ; Great Britain ; History, 20th Century ; History, 21st Century ; Paleontology/*history ; United States
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  • 58
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    Nature Publishing Group (NPG)
    Publication Date: 2010-01-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dalton, Rex -- England -- Nature. 2010 Jan 7;463(7277):16. doi: 10.1038/463016a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20054370" target="_blank"〉PubMed〈/a〉
    Keywords: California ; Disasters/prevention & control/statistics & numerical data ; Earthquakes/history/*statistics & numerical data ; Floods/history/*statistics & numerical data ; Fresh Water ; History, 15th Century ; History, 18th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; *Risk Management ; Rivers ; Water Movements
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  • 59
    Publication Date: 2010-01-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉von Storch, Hans -- Allen, Myles -- England -- Nature. 2010 Jan 7;463(7277):25. doi: 10.1038/463025a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20054378" target="_blank"〉PubMed〈/a〉
    Keywords: *Electronic Mail ; *Global Warming/statistics & numerical data ; Great Britain ; *Human Activities/statistics & numerical data ; Reproducibility of Results ; Research Personnel/ethics ; *Temperature
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  • 60
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    Nature Publishing Group (NPG)
    Publication Date: 2010-04-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉White, Craig R -- England -- Nature. 2010 Apr 1;464(7289):691-3. doi: 10.1038/464691a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360729" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basal Metabolism/*physiology ; Body Size/*physiology ; Body Temperature/physiology ; Fractals ; History, 19th Century ; History, 20th Century ; Hot Temperature ; Mammals/*anatomy & histology/*physiology ; *Models, Biological
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  • 61
    Publication Date: 2010-01-15
    Description: Immune homeostasis is dependent on tight control over the size of a population of regulatory T (T(reg)) cells capable of suppressing over-exuberant immune responses. The T(reg) cell subset is comprised of cells that commit to the T(reg) lineage by upregulating the transcription factor Foxp3 either in the thymus (tT(reg)) or in the periphery (iT(reg)). Considering a central role for Foxp3 in T(reg) cell differentiation and function, we proposed that conserved non-coding DNA sequence (CNS) elements at the Foxp3 locus encode information defining the size, composition and stability of the T(reg) cell population. Here we describe the function of three Foxp3 CNS elements (CNS1-3) in T(reg) cell fate determination in mice. The pioneer element CNS3, which acts to potently increase the frequency of T(reg) cells generated in the thymus and the periphery, binds c-Rel in in vitro assays. In contrast, CNS1, which contains a TGF-beta-NFAT response element, is superfluous for tT(reg) cell differentiation, but has a prominent role in iT(reg) cell generation in gut-associated lymphoid tissues. CNS2, although dispensable for Foxp3 induction, is required for Foxp3 expression in the progeny of dividing T(reg) cells. Foxp3 binds to CNS2 in a Cbf-beta-Runx1 and CpG DNA demethylation-dependent manner, suggesting that Foxp3 recruitment to this 'cellular memory module' facilitates the heritable maintenance of the active state of the Foxp3 locus and, therefore, T(reg) lineage stability. Together, our studies demonstrate that the composition, size and maintenance of the T(reg) cell population are controlled by Foxp3 CNS elements engaged in response to distinct cell-extrinsic or -intrinsic cues.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2884187/" 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/PMC2884187/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zheng, Ye -- Josefowicz, Steven -- Chaudhry, Ashutosh -- Peng, Xiao P -- Forbush, Katherine -- Rudensky, Alexander Y -- R37 AI034206/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Feb 11;463(7282):808-12. doi: 10.1038/nature08750. Epub 2010 Jan 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Immunology, University of Washington, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20072126" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation ; Cell Lineage/*genetics ; Chromatin Assembly and Disassembly ; Conserved Sequence/*genetics ; CpG Islands/genetics ; DNA Methylation ; Female ; Forkhead Transcription Factors/*genetics/metabolism ; Gene Expression Regulation ; Lymphocyte Count ; Male ; Mice ; Mice, Inbred C57BL ; Proto-Oncogene Proteins c-rel/metabolism ; Regulatory Sequences, Nucleic Acid/*genetics ; Response Elements/genetics ; T-Lymphocytes, Regulatory/*cytology/immunology/*metabolism ; Thymus Gland/cytology/immunology/metabolism
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    Nature Publishing Group (NPG)
    Publication Date: 2010-03-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hughes, Virginia -- England -- Nature. 2010 Mar 18;464(7287):340-2. doi: 10.1038/464340a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20237536" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Antisocial Personality Disorder/physiopathology/psychology ; Child ; Female ; Forensic Sciences/ethics/*methods/trends ; Homicide/*legislation & jurisprudence/*psychology ; Humans ; Insanity Defense ; Magnetic Resonance Imaging/standards/*utilization ; Male ; *Neurosciences ; Positron-Emission Tomography/utilization ; Rape/legislation & jurisprudence/psychology ; Reproducibility of Results
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  • 63
    Publication Date: 2010-03-09
    Description: The tumour suppressor ARF is specifically required for p53 activation under oncogenic stress. Recent studies showed that p53 activation mediated by ARF, but not that induced by DNA damage, acts as a major protection against tumorigenesis in vivo under certain biological settings, suggesting that the ARF-p53 axis has more fundamental functions in tumour suppression than originally thought. Because ARF is a very stable protein in most human cell lines, it has been widely assumed that ARF induction is mediated mainly at the transcriptional level and that activation of the ARF-p53 pathway by oncogenes is a much slower and largely irreversible process by comparison with p53 activation after DNA damage. Here we report that ARF is very unstable in normal human cells but that its degradation is inhibited in cancerous cells. Through biochemical purification, we identified a specific ubiquitin ligase for ARF and named it ULF. ULF interacts with ARF both in vitro and in vivo and promotes the lysine-independent ubiquitylation and degradation of ARF. ULF knockdown stabilizes ARF in normal human cells, triggering ARF-dependent, p53-mediated growth arrest. Moreover, nucleophosmin (NPM) and c-Myc, both of which are commonly overexpressed in cancer cells, are capable of abrogating ULF-mediated ARF ubiquitylation through distinct mechanisms, and thereby promote ARF stabilization in cancer cells. These findings reveal the dynamic feature of the ARF-p53 pathway and suggest that transcription-independent mechanisms are critically involved in ARF regulation during responses to oncogenic stress.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737736/" 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/PMC3737736/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Delin -- Shan, Jing -- Zhu, Wei-Guo -- Qin, Jun -- Gu, Wei -- P01 CA080058/CA/NCI NIH HHS/ -- P01 CA097403/CA/NCI NIH HHS/ -- R01 CA085533/CA/NCI NIH HHS/ -- R01 CA118561/CA/NCI NIH HHS/ -- R01 CA129627/CA/NCI NIH HHS/ -- R01 CA131439/CA/NCI NIH HHS/ -- England -- Nature. 2010 Mar 25;464(7288):624-7. doi: 10.1038/nature08820. Epub 2010 Mar 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Cancer Genetics, and Department of Pathology and Cell Biology College of Physicians & Surgeons, Columbia University, 1130 St Nicholas Avenue, New York, New York 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20208519" target="_blank"〉PubMed〈/a〉
    Keywords: ADP-Ribosylation Factors/*metabolism ; Cell Line ; Fibroblasts/metabolism ; *Gene Expression Regulation ; Humans ; Molecular Sequence Data ; Nuclear Proteins/metabolism ; Proto-Oncogene Proteins c-myc/metabolism ; Stress, Physiological/*physiology ; Tumor Suppressor Protein p53/*metabolism ; U937 Cells ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination
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  • 64
    Publication Date: 2010-02-02
    Description: The spectacular escalation in complexity in early bilaterian evolution correlates with a strong increase in the number of microRNAs. To explore the link between the birth of ancient microRNAs and body plan evolution, we set out to determine the ancient sites of activity of conserved bilaterian microRNA families in a comparative approach. We reason that any specific localization shared between protostomes and deuterostomes (the two major superphyla of bilaterian animals) should probably reflect an ancient specificity of that microRNA in their last common ancestor. Here, we investigate the expression of conserved bilaterian microRNAs in Platynereis dumerilii, a protostome retaining ancestral bilaterian features, in Capitella, another marine annelid, in the sea urchin Strongylocentrotus, a deuterostome, and in sea anemone Nematostella, representing an outgroup to the bilaterians. Our comparative data indicate that the oldest known animal microRNA, miR-100, and the related miR-125 and let-7 were initially active in neurosecretory cells located around the mouth. Other sets of ancient microRNAs were first present in locomotor ciliated cells, specific brain centres, or, more broadly, one of four major organ systems: central nervous system, sensory tissue, musculature and gut. These findings reveal that microRNA evolution and the establishment of tissue identities were closely coupled in bilaterian evolution. Also, they outline a minimum set of cell types and tissues that existed in the protostome-deuterostome ancestor.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981144/" 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/PMC2981144/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Christodoulou, Foteini -- Raible, Florian -- Tomer, Raju -- Simakov, Oleg -- Trachana, Kalliopi -- Klaus, Sebastian -- Snyman, Heidi -- Hannon, Gregory J -- Bork, Peer -- Arendt, Detlev -- P01 CA013106/CA/NCI NIH HHS/ -- P01 CA013106-38/CA/NCI NIH HHS/ -- P01 CA013106-39/CA/NCI NIH HHS/ -- England -- Nature. 2010 Feb 25;463(7284):1084-8. doi: 10.1038/nature08744. Epub 2010 Jan 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Developmental Biology Unit, European Molecular Biology Laboratory, D-69117 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20118916" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Annelida/anatomy & histology/cytology/genetics ; *Biological Evolution ; Brain/metabolism ; Cilia/physiology ; Conserved Sequence/genetics ; Digestive System/cytology/metabolism ; In Situ Hybridization ; MicroRNAs/*analysis/*genetics ; Molecular Sequence Data ; *Organ Specificity ; Phylogeny ; Polychaeta/*anatomy & histology/cytology/*genetics ; Sea Anemones/anatomy & histology/cytology/genetics ; Sea Urchins/anatomy & histology/cytology/genetics
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  • 65
    Publication Date: 2010-09-28
    Description: Epigenetic proteins are intently pursued targets in ligand discovery. So far, successful efforts have been limited to chromatin modifying enzymes, or so-called epigenetic 'writers' and 'erasers'. Potent inhibitors of histone binding modules have not yet been described. Here we report a cell-permeable small molecule (JQ1) that binds competitively to acetyl-lysine recognition motifs, or bromodomains. High potency and specificity towards a subset of human bromodomains is explained by co-crystal structures with bromodomain and extra-terminal (BET) family member BRD4, revealing excellent shape complementarity with the acetyl-lysine binding cavity. Recurrent translocation of BRD4 is observed in a genetically-defined, incurable subtype of human squamous carcinoma. Competitive binding by JQ1 displaces the BRD4 fusion oncoprotein from chromatin, prompting squamous differentiation and specific antiproliferative effects in BRD4-dependent cell lines and patient-derived xenograft models. These data establish proof-of-concept for targeting protein-protein interactions of epigenetic 'readers', and provide a versatile chemical scaffold for the development of chemical probes more broadly throughout the bromodomain family.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010259/" 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/PMC3010259/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Filippakopoulos, Panagis -- Qi, Jun -- Picaud, Sarah -- Shen, Yao -- Smith, William B -- Fedorov, Oleg -- Morse, Elizabeth M -- Keates, Tracey -- Hickman, Tyler T -- Felletar, Ildiko -- Philpott, Martin -- Munro, Shonagh -- McKeown, Michael R -- Wang, Yuchuan -- Christie, Amanda L -- West, Nathan -- Cameron, Michael J -- Schwartz, Brian -- Heightman, Tom D -- La Thangue, Nicholas -- French, Christopher A -- Wiest, Olaf -- Kung, Andrew L -- Knapp, Stefan -- Bradner, James E -- 13058/Cancer Research UK/United Kingdom -- G0500905/Medical Research Council/United Kingdom -- G1000807/Medical Research Council/United Kingdom -- G9400953/Medical Research Council/United Kingdom -- K08 CA128972/CA/NCI NIH HHS/ -- K08 CA128972-03/CA/NCI NIH HHS/ -- T32-075762/PHS HHS/ -- Canadian Institutes of Health Research/Canada -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Dec 23;468(7327):1067-73. doi: 10.1038/nature09504. Epub 2010 Sep 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20871596" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Azirines/chemical synthesis/chemistry/*pharmacology ; Binding Sites ; Carcinoma, Squamous Cell/physiopathology ; Cell Differentiation/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Chromatin/metabolism ; Dihydropyridines/chemical synthesis/chemistry/*pharmacology ; Female ; Humans ; Mice ; Mice, Nude ; *Models, Molecular ; Molecular Sequence Data ; Nuclear Proteins/*antagonists & inhibitors/*metabolism ; Protein Binding/drug effects ; Protein Structure, Tertiary ; Recombinant Proteins/metabolism ; Sequence Alignment ; Skin Neoplasms/physiopathology ; Stereoisomerism ; Transcription Factors/*antagonists & inhibitors/*metabolism
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  • 66
    Publication Date: 2010-06-22
    Description: Autophagy, the process by which proteins and organelles are sequestered in autophagosomal vesicles and delivered to the lysosome/vacuole for degradation, provides a primary route for turnover of stable and defective cellular proteins. Defects in this system are linked with numerous human diseases. Although conserved protein kinase, lipid kinase and ubiquitin-like protein conjugation subnetworks controlling autophagosome formation and cargo recruitment have been defined, our understanding of the global organization of this system is limited. Here we report a proteomic analysis of the autophagy interaction network in human cells under conditions of ongoing (basal) autophagy, revealing a network of 751 interactions among 409 candidate interacting proteins with extensive connectivity among subnetworks. Many new autophagy interaction network components have roles in vesicle trafficking, protein or lipid phosphorylation and protein ubiquitination, and affect autophagosome number or flux when depleted by RNA interference. The six ATG8 orthologues in humans (MAP1LC3/GABARAP proteins) interact with a cohort of 67 proteins, with extensive binding partner overlap between family members, and frequent involvement of a conserved surface on ATG8 proteins known to interact with LC3-interacting regions in partner proteins. These studies provide a global view of the mammalian autophagy interaction landscape and a resource for mechanistic analysis of this critical protein homeostasis pathway.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2901998/" 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/PMC2901998/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Behrends, Christian -- Sowa, Mathew E -- Gygi, Steven P -- Harper, J Wade -- R01 AG011085/AG/NIA NIH HHS/ -- R01 AG011085-18/AG/NIA NIH HHS/ -- R01 GM054137/GM/NIGMS NIH HHS/ -- R01 GM054137-14/GM/NIGMS NIH HHS/ -- R01 GM054137-14S1/GM/NIGMS NIH HHS/ -- R01 GM054137-15/GM/NIGMS NIH HHS/ -- R01 GM070565/GM/NIGMS NIH HHS/ -- R01 GM070565-05S1/GM/NIGMS NIH HHS/ -- R01 GM095567/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Jul 1;466(7302):68-76. doi: 10.1038/nature09204. Epub 2010 Jun 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20562859" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/genetics/metabolism ; Autophagy/genetics/*physiology ; Homeostasis ; Humans ; Microfilament Proteins/genetics/metabolism ; Phagosomes ; Phosphorylation ; Protein Binding ; *Protein Interaction Mapping ; Proteomics ; RNA Interference ; Reproducibility of Results ; Ubiquitination
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  • 67
    Publication Date: 2010-11-12
    Description: The central amygdala (CEA), a nucleus predominantly composed of GABAergic inhibitory neurons, is essential for fear conditioning. How the acquisition and expression of conditioned fear are encoded within CEA inhibitory circuits is not understood. Using in vivo electrophysiological, optogenetic and pharmacological approaches in mice, we show that neuronal activity in the lateral subdivision of the central amygdala (CEl) is required for fear acquisition, whereas conditioned fear responses are driven by output neurons in the medial subdivision (CEm). Functional circuit analysis revealed that inhibitory CEA microcircuits are highly organized and that cell-type-specific plasticity of phasic and tonic activity in the CEl to CEm pathway may gate fear expression and regulate fear generalization. Our results define the functional architecture of CEA microcircuits and their role in the acquisition and regulation of conditioned fear behaviour.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ciocchi, Stephane -- Herry, Cyril -- Grenier, Francois -- Wolff, Steffen B E -- Letzkus, Johannes J -- Vlachos, Ioannis -- Ehrlich, Ingrid -- Sprengel, Rolf -- Deisseroth, Karl -- Stadler, Michael B -- Muller, Christian -- Luthi, Andreas -- England -- Nature. 2010 Nov 11;468(7321):277-82. doi: 10.1038/nature09559.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21068837" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Amygdala/anatomy & histology/cytology/*physiology ; Animals ; Conditioning, Classical/*physiology ; Fear/*physiology ; Freezing Reaction, Cataleptic ; Male ; Mice ; Mice, Inbred C57BL ; Neural Inhibition/*physiology ; Neural Pathways/cytology/*physiology ; Neuronal Plasticity/physiology ; Neurons/physiology ; gamma-Aminobutyric Acid/metabolism
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  • 68
    Publication Date: 2010-12-24
    Description: The multi-component mechanistic target of rapamycin complex 1 (mTORC1) kinase is the central node of a mammalian pathway that coordinates cell growth with the availability of nutrients, energy and growth factors. Progress has been made in the identification of mTORC1 pathway components and in understanding their functions in cells, but there is relatively little known about the role of the pathway in vivo. Specifically, we have little knowledge regarding the role mTOCR1 has in liver physiology. In fasted animals, the liver performs numerous functions that maintain whole-body homeostasis, including the production of ketone bodies for peripheral tissues to use as energy sources. Here we show that mTORC1 controls ketogenesis in mice in response to fasting. We find that liver-specific loss of TSC1 (tuberous sclerosis 1), an mTORC1 inhibitor, leads to a fasting-resistant increase in liver size, and to a pronounced defect in ketone body production and ketogenic gene expression on fasting. The loss of raptor (regulatory associated protein of mTOR, complex 1) an essential mTORC1 component, has the opposite effects. In addition, we find that the inhibition of mTORC1 is required for the fasting-induced activation of PPARalpha (peroxisome proliferator activated receptor alpha), the master transcriptional activator of ketogenic genes, and that suppression of NCoR1 (nuclear receptor co-repressor 1), a co-repressor of PPARalpha, reactivates ketogenesis in cells and livers with hyperactive mTORC1 signalling. Like livers with activated mTORC1, livers from aged mice have a defect in ketogenesis, which correlates with an increase in mTORC1 signalling. Moreover, we show that the suppressive effects of mTORC1 activation and ageing on PPARalpha activity and ketone production are not additive, and that mTORC1 inhibition is sufficient to prevent the ageing-induced defect in ketogenesis. Thus, our findings reveal that mTORC1 is a key regulator of PPARalpha function and hepatic ketogenesis and suggest a role for mTORC1 activity in promoting the ageing of the liver.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sengupta, Shomit -- Peterson, Timothy R -- Laplante, Mathieu -- Oh, Stephanie -- Sabatini, David M -- CA103866/CA/NCI NIH HHS/ -- CA129105/CA/NCI NIH HHS/ -- R01 CA129105/CA/NCI NIH HHS/ -- R01 CA129105-04/CA/NCI NIH HHS/ -- Canadian Institutes of Health Research/Canada -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Dec 23;468(7327):1100-4. doi: 10.1038/nature09584.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21179166" target="_blank"〉PubMed〈/a〉
    Keywords: *Aging ; Animals ; Cell Line ; Fasting/*metabolism ; *Gene Expression Regulation ; Humans ; Ketone Bodies/*biosynthesis/metabolism ; Liver/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Multiprotein Complexes ; Nuclear Receptor Co-Repressor 1/metabolism ; PPAR alpha/antagonists & inhibitors/metabolism ; Proteins/genetics/*metabolism ; TOR Serine-Threonine Kinases
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  • 69
    Publication Date: 2010-11-05
    Description: Stroke is a leading cause of disability, but no pharmacological therapy is currently available for promoting recovery. The brain region adjacent to stroke damage-the peri-infarct zone-is critical for rehabilitation, as it shows heightened neuroplasticity, allowing sensorimotor functions to re-map from damaged areas. Thus, understanding the neuronal properties constraining this plasticity is important for the development of new treatments. Here we show that after a stroke in mice, tonic neuronal inhibition is increased in the peri-infarct zone. This increased tonic inhibition is mediated by extrasynaptic GABA(A) receptors and is caused by an impairment in GABA (gamma-aminobutyric acid) transporter (GAT-3/GAT-4) function. To counteract the heightened inhibition, we administered in vivo a benzodiazepine inverse agonist specific for alpha5-subunit-containing extrasynaptic GABA(A) receptors at a delay after stroke. This treatment produced an early and sustained recovery of motor function. Genetically lowering the number of alpha5- or delta-subunit-containing GABA(A) receptors responsible for tonic inhibition also proved beneficial for recovery after stroke, consistent with the therapeutic potential of diminishing extrasynaptic GABA(A) receptor function. Together, our results identify new pharmacological targets and provide the rationale for a novel strategy to promote recovery after stroke and possibly other brain injuries.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058798/" 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/PMC3058798/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clarkson, Andrew N -- Huang, Ben S -- Macisaac, Sarah E -- Mody, Istvan -- Carmichael, S Thomas -- NS30549/NS/NINDS NIH HHS/ -- R01 NS030549/NS/NINDS NIH HHS/ -- R01 NS030549-18/NS/NINDS NIH HHS/ -- England -- Nature. 2010 Nov 11;468(7321):305-9. doi: 10.1038/nature09511. Epub 2010 Nov 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, The David Geffen School of Medicine at UCLA, 635 Charles Young Drive South, Los Angeles, California 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21048709" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Benzodiazepines/pharmacology ; Cerebral Infarction/metabolism/pathology/physiopathology ; Disease Models, Animal ; Drug Inverse Agonism ; GABA Antagonists/pharmacology ; GABA Plasma Membrane Transport Proteins/metabolism ; Imidazoles/pharmacology ; Male ; Membrane Potentials/drug effects ; Mice ; Mice, Inbred C57BL ; Motor Cortex/metabolism/pathology/*physiology/*physiopathology ; Neuronal Plasticity/physiology ; Receptors, GABA/deficiency/genetics/metabolism ; Recovery of Function/*physiology ; Stroke/drug therapy/*metabolism/pathology ; Synapses/metabolism ; Time Factors ; gamma-Aminobutyric Acid/*metabolism
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  • 70
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    Nature Publishing Group (NPG)
    Publication Date: 2010-04-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ganellin, Robin -- Duncan, William -- England -- Nature. 2010 Apr 29;464(7293):1292. doi: 10.1038/4641292a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20428161" target="_blank"〉PubMed〈/a〉
    Keywords: Drug Industry/history ; History, 20th Century ; Nobel Prize ; Pharmacology/*history ; Scotland
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  • 71
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    Nature Publishing Group (NPG)
    Publication Date: 2010-11-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Nov 4;468(7320):6. doi: 10.1038/468006b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21048718" target="_blank"〉PubMed〈/a〉
    Keywords: Periodicals as Topic/*standards/statistics & numerical data ; Reproducibility of Results ; Research Personnel/ethics/statistics & numerical data ; *Retraction of Publication as Topic ; Scientific Misconduct/statistics & numerical data
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  • 72
    Publication Date: 2010-08-13
    Description: The use of homologous recombination to modify genes in embryonic stem (ES) cells provides a powerful means to elucidate gene function and create disease models. Application of this technology to engineer genes in rats has not previously been possible because of the absence of germline-competent ES cells in this species. We have recently established authentic rat ES cells. Here we report the generation of gene knockout rats using the ES-cell-based gene targeting technology. We designed a targeting vector to disrupt the tumour suppressor gene p53 (also known as Tp53) in rat ES cells by means of homologous recombination. p53 gene-targeted rat ES cells can be routinely generated. Furthermore, the p53 gene-targeted mutation in the rat ES-cell genome can transmit through the germ line via ES-cell rat chimaeras to create p53 gene knockout rats. The rat is the most widely used animal model in biological research. The establishment of gene targeting technology in rat ES cells, in combination with advances in genomics and the vast amount of research data on physiology and pharmacology in this species, now provide a powerful new platform for the study of human disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2937076/" 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/PMC2937076/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tong, Chang -- Li, Ping -- Wu, Nancy L -- Yan, Youzhen -- Ying, Qi-Long -- 1R01 RR025881/RR/NCRR NIH HHS/ -- R01 OD010926/OD/NIH HHS/ -- R01 RR025881/RR/NCRR NIH HHS/ -- R01 RR025881-01A2/RR/NCRR NIH HHS/ -- England -- Nature. 2010 Sep 9;467(7312):211-3. doi: 10.1038/nature09368. Epub 2010 Aug 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20703227" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Culture Techniques ; Embryo, Mammalian/cytology ; Embryonic Stem Cells/*cytology ; Female ; Gene Knockout Techniques/*methods ; *Genes, p53 ; Germ-Line Mutation ; Male ; Mice ; Molecular Sequence Data ; Rats/*genetics ; Rats, Inbred F344 ; Rats, Sprague-Dawley ; Recombination, Genetic
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 73
    Publication Date: 2010-02-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Penders, Bart -- Vermeulen, Niki -- Parker, John N -- England -- Nature. 2010 Jan 14;463(7278):157. doi: 10.1038/463157d.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20075896" target="_blank"〉PubMed〈/a〉
    Keywords: Government ; History, 20th Century ; History, 21st Century ; *Learning ; Private Sector ; Public Policy ; Science/*history/*methods/trends ; *Search Engine ; Universities
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  • 74
    Publication Date: 2010-09-03
    Description: The structures of RNA molecules are often important for their function and regulation, yet there are no experimental techniques for genome-scale measurement of RNA structure. Here we describe a novel strategy termed parallel analysis of RNA structure (PARS), which is based on deep sequencing fragments of RNAs that were treated with structure-specific enzymes, thus providing simultaneous in vitro profiling of the secondary structure of thousands of RNA species at single nucleotide resolution. We apply PARS to profile the secondary structure of the messenger RNAs (mRNAs) of the budding yeast Saccharomyces cerevisiae and obtain structural profiles for over 3,000 distinct transcripts. Analysis of these profiles reveals several RNA structural properties of yeast transcripts, including the existence of more secondary structure over coding regions compared with untranslated regions, a three-nucleotide periodicity of secondary structure across coding regions and an anti-correlation between the efficiency with which an mRNA is translated and the structure over its translation start site. PARS is readily applicable to other organisms and to profiling RNA structure in diverse conditions, thus enabling studies of the dynamics of secondary structure at a genomic scale.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3847670/" 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/PMC3847670/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kertesz, Michael -- Wan, Yue -- Mazor, Elad -- Rinn, John L -- Nutter, Robert C -- Chang, Howard Y -- Segal, Eran -- R01 HG004361/HG/NHGRI NIH HHS/ -- R01HG004361/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Sep 2;467(7311):103-7. doi: 10.1038/nature09322.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20811459" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; *Genetic Techniques ; Genome-Wide Association Study ; Molecular Sequence Data ; *Nucleic Acid Conformation ; RNA, Fungal/*chemistry ; RNA, Messenger/*chemistry ; Saccharomyces cerevisiae/*chemistry/*genetics ; Transcription, Genetic
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  • 75
    Publication Date: 2010-08-13
    Description: Increased levels of brain amyloid-beta, a secreted peptide cleavage product of amyloid precursor protein (APP), is believed to be critical in the aetiology of Alzheimer's disease. Increased amyloid-beta can cause synaptic depression, reduce the number of spine protrusions (that is, sites of synaptic contacts) and block long-term synaptic potentiation (LTP), a form of synaptic plasticity; however, the receptor through which amyloid-beta produces these synaptic perturbations has remained elusive. Lauren et al. suggested that binding between oligomeric amyloid-beta (a form of amyloid-beta thought to be most active) and the cellular prion protein (PrP(C)) is necessary for synaptic perturbations. Here we show that PrP(C) is not required for amyloid-beta-induced synaptic depression, reduction in spine density, or blockade of LTP; our results indicate that amyloid-beta-mediated synaptic defects do not require PrP(c).〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057871/" 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/PMC3057871/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kessels, Helmut W -- Nguyen, Louis N -- Nabavi, Sadegh -- Malinow, Roberto -- R01 AG032132/AG/NIA NIH HHS/ -- R01 AG032132-14/AG/NIA NIH HHS/ -- R01 AG032132-15/AG/NIA NIH HHS/ -- R01 AG032132-17/AG/NIA NIH HHS/ -- R01 AG032132-18/AG/NIA NIH HHS/ -- R01 MH049159/MH/NIMH NIH HHS/ -- R01 MH049159-09/MH/NIMH NIH HHS/ -- R01 MH049159-21/MH/NIMH NIH HHS/ -- R01 MH049159-22/MH/NIMH NIH HHS/ -- England -- Nature. 2010 Aug 12;466(7308):E3-4; discussion E4-5. doi: 10.1038/nature09217.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Neural Circuits and Behavior, 9500 Gilman Drive 0634, University of California at San Diego, La Jolla, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20703260" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/metabolism/pathology ; Amyloid beta-Peptides/chemistry/genetics/*metabolism ; Animals ; Learning/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; PrPC Proteins/deficiency/genetics/*metabolism ; Reproducibility of Results ; Serotonin/metabolism ; Synapses/*metabolism/*pathology ; Synaptic Transmission
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  • 76
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    Nature Publishing Group (NPG)
    Publication Date: 2010-04-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Apr 1;464(7289):649-50. doi: 10.1038/464649a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360688" target="_blank"〉PubMed〈/a〉
    Keywords: Data Collection ; Genetic Testing/trends ; Genetics, Medical/*trends ; Genome, Human/*genetics ; Genomics/economics/*history/trends ; Haplotypes/genetics ; History, 20th Century ; History, 21st Century ; Human Genome Project/*history ; Humans ; Time Factors
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  • 77
    Publication Date: 2010-08-21
    Description: Laryngeal echolocation, used by most living bats to form images of their surroundings and to detect and capture flying prey, is considered to be a key innovation for the evolutionary success of bats, and palaeontologists have long sought osteological correlates of echolocation that can be used to infer the behaviour of fossil bats. Veselka et al. argued that the most reliable trait indicating echolocation capabilities in bats is an articulation between the stylohyal bone (part of the hyoid apparatus that supports the throat and larynx) and the tympanic bone, which forms the floor of the middle ear. They examined the oldest and most primitive known bat, Onychonycteris finneyi (early Eocene, USA), and argued that it showed evidence of this stylohyal-tympanic articulation, from which they concluded that O. finneyi may have been capable of echolocation. We disagree with their interpretation of key fossil data and instead argue that O. finneyi was probably not an echolocating bat.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Simmons, Nancy B -- Seymour, Kevin L -- Habersetzer, Jorg -- Gunnell, Gregg F -- England -- Nature. 2010 Aug 19;466(7309):E8; discussion E9. doi: 10.1038/nature09219.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉American Museum of Natural History, Central Park West at 79th Street, New York, New York 10024, USA. simmons@amnh.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20724993" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Structures/physiology ; Animals ; Bone and Bones/physiology ; Chiroptera/anatomy & histology/*physiology ; Echolocation/*physiology ; *Fossils ; Models, Biological ; Reproducibility of Results
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  • 78
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    Nature Publishing Group (NPG)
    Publication Date: 2010-11-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gomory, Ralph -- England -- Nature. 2010 Nov 18;468(7322):378. doi: 10.1038/468378a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21085164" target="_blank"〉PubMed〈/a〉
    Keywords: Fractals/*history ; France ; History, 20th Century ; History, 21st Century ; Mathematics/history ; Nature ; Poland ; United States
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  • 79
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    Nature Publishing Group (NPG)
    Publication Date: 2010-02-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dalton, Rex -- England -- Nature. 2010 Feb 11;463(7282):724-5. doi: 10.1038/463724a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20148008" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arctic Regions ; Cryopreservation ; DNA/genetics/isolation & purification ; DNA, Mitochondrial/analysis/genetics ; Denmark ; Emigration and Immigration/*history ; Feces ; Fossils ; Genetics, Medical/history ; Genome, Human/*genetics ; Greenland/ethnology ; History, 20th Century ; History, 21st Century ; History, Ancient ; Humans ; Inuits/*ethnology/*history ; Male ; Paleontology/*history ; Phylogeny ; Reproducibility of Results ; Sequence Analysis, DNA ; Siberia/ethnology
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  • 80
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    Nature Publishing Group (NPG)
    Publication Date: 2010-02-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dalton, Rex -- England -- Nature. 2010 Feb 11;463(7282):718-9. doi: 10.1038/463718a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20148004" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Birds ; Conservation of Natural Resources/economics/*trends ; *Extinction, Biological ; Reproducibility of Results
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  • 81
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    Nature Publishing Group (NPG)
    Publication Date: 2008-05-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ball, Philip -- England -- Nature. 2008 May 8;453(7192):160-2. doi: 10.1038/453160a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18464725" target="_blank"〉PubMed〈/a〉
    Keywords: Auditory Perception/physiology ; Brain/physiology ; History, 18th Century ; History, 20th Century ; History, Ancient ; History, Medieval ; Humans ; Mathematics ; *Music/history/psychology ; *Science/history
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  • 82
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    Nature Publishing Group (NPG)
    Publication Date: 2008-02-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Perry, Joseph W -- England -- Nature. 2008 Feb 7;451(7179):636-7. doi: 10.1038/451636a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18256651" target="_blank"〉PubMed〈/a〉
    Keywords: History, 20th Century ; Holography/history/*instrumentation/methods
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  • 83
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    Nature Publishing Group (NPG)
    Publication Date: 2008-10-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sharp, Paul M -- Hahn, Beatrice H -- England -- Nature. 2008 Oct 2;455(7213):605-6. doi: 10.1038/455605a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18833267" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Democratic Republic of the Congo/epidemiology ; *Evolution, Molecular ; Genetic Variation/*genetics ; HIV Infections/*epidemiology/*virology ; HIV-1/classification/*genetics/*isolation & purification ; History, 20th Century ; Humans ; Phylogeny
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  • 84
    Publication Date: 2008-02-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ball, Philip -- England -- Nature. 2008 Feb 28;451(7182):1065-6. doi: 10.1038/4511065a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18305535" target="_blank"〉PubMed〈/a〉
    Keywords: History, 20th Century ; Quinine/*chemical synthesis/chemistry/*history ; Reproducibility of Results
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  • 85
    Publication Date: 2008-08-15
    Description: Furin is one of seven proprotein convertase family members that promote proteolytic maturation of proproteins. It is induced in activated T cells and is reported to process a variety of substrates including the anti-inflammatory cytokine transforming growth factor (TGF)-beta1 (refs 2-4), but the non-redundant functions of furin versus other proprotein convertases in T cells are unclear. Here we show that conditional deletion of furin in T cells allowed for normal T-cell development but impaired the function of regulatory and effector T cells, which produced less TGF-beta1. Furin-deficient T regulatory (Treg) cells were less protective in a T-cell transfer colitis model and failed to induce Foxp3 in normal T cells. Additionally, furin-deficient effector cells were inherently over-active and were resistant to suppressive activity of wild-type Treg cells. Thus, our results indicate that furin is indispensable in maintaining peripheral tolerance, which is due, at least in part, to its non-redundant, essential function in regulating TGF-beta1 production. Targeting furin has emerged as a strategy in malignant and infectious disease. Our results suggest that inhibiting furin might activate immune responses, but may result in a breakdown in peripheral tolerance.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2758057/" 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/PMC2758057/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pesu, Marko -- Watford, Wendy T -- Wei, Lai -- Xu, Lili -- Fuss, Ivan -- Strober, Warren -- Andersson, John -- Shevach, Ethan M -- Quezado, Martha -- Bouladoux, Nicolas -- Roebroek, Anton -- Belkaid, Yasmine -- Creemers, John -- O'Shea, John J -- Z99 EY999999/Intramural NIH HHS/ -- England -- Nature. 2008 Sep 11;455(7210):246-50. doi: 10.1038/nature07210.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Immunology and Inflammation Branch, National Institute for Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. pesum@mail.nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18701887" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/immunology ; Antigens, CD4/immunology/metabolism ; Autoimmunity/immunology ; Colitis/immunology ; Furin/deficiency/genetics/*metabolism ; Gene Expression Profiling ; Immune Tolerance/*immunology ; Immunologic Memory/immunology ; Integrin alpha Chains/immunology ; Lymphocyte Activation/immunology ; Mice ; Mice, Inbred C57BL ; T-Lymphocytes/cytology/*enzymology/*immunology ; Thymus Gland/cytology/immunology ; Transforming Growth Factor beta1/biosynthesis/genetics/immunology
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  • 86
    Publication Date: 2008-03-14
    Description: Genetic data from two or more species provide information about the process of speciation. In their analysis of DNA from humans, chimpanzees, gorillas, orangutans and macaques (HCGOM), Patterson et al. suggest that the apparently short divergence time between humans and chimpanzees on the X chromosome is explained by a massive interspecific hybridization event in the ancestry of these two species. However, Patterson et al. do not statistically test their own null model of simple speciation before concluding that speciation was complex, and--even if the null model could be rejected--they do not consider other explanations of a short divergence time on the X chromosome. These include natural selection on the X chromosome in the common ancestor of humans and chimpanzees, changes in the ratio of male-to-female mutation rates over time, and less extreme versions of divergence with gene flow (see ref. 2, for example). I therefore believe that their claim of hybridization is unwarranted.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wakeley, John -- England -- Nature. 2008 Mar 13;452(7184):E3-4; discussion E4. doi: 10.1038/nature06805.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Organismic and Evolutionary Biology, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts 02138, USA. wakeley@fas.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18337768" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chromosomes, Mammalian/genetics ; Female ; *Genetic Speciation ; Humans ; Male ; *Models, Genetic ; Mutagenesis/genetics ; Pan troglodytes/*genetics ; Phylogeny ; Reproducibility of Results ; Selection, Genetic ; Sex Characteristics ; Time Factors ; X Chromosome/genetics
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  • 87
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    Publication Date: 2008-05-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huron, David -- England -- Nature. 2008 May 22;453(7194):456-7. doi: 10.1038/453456a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Music & Center for Cognitive Science, Ohio State University, Columbus, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18497806" target="_blank"〉PubMed〈/a〉
    Keywords: *Cultural Diversity ; *Cultural Evolution ; History, 17th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; Humans ; *Music/history ; *Neurosciences
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  • 88
    Publication Date: 2008-02-19
    Description: Cytosine DNA methylation is important in regulating gene expression and in silencing transposons and other repetitive sequences. Recent genomic studies in Arabidopsis thaliana have revealed that many endogenous genes are methylated either within their promoters or within their transcribed regions, and that gene methylation is highly correlated with transcription levels. However, plants have different types of methylation controlled by different genetic pathways, and detailed information on the methylation status of each cytosine in any given genome is lacking. To this end, we generated a map at single-base-pair resolution of methylated cytosines for Arabidopsis, by combining bisulphite treatment of genomic DNA with ultra-high-throughput sequencing using the Illumina 1G Genome Analyser and Solexa sequencing technology. This approach, termed BS-Seq, unlike previous microarray-based methods, allows one to sensitively measure cytosine methylation on a genome-wide scale within specific sequence contexts. Here we describe methylation on previously inaccessible components of the genome and analyse the DNA methylation sequence composition and distribution. We also describe the effect of various DNA methylation mutants on genome-wide methylation patterns, and demonstrate that our newly developed library construction and computational methods can be applied to large genomes such as that of mouse.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2377394/" 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/PMC2377394/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cokus, Shawn J -- Feng, Suhua -- Zhang, Xiaoyu -- Chen, Zugen -- Merriman, Barry -- Haudenschild, Christian D -- Pradhan, Sriharsa -- Nelson, Stanley F -- Pellegrini, Matteo -- Jacobsen, Steven E -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Mar 13;452(7184):215-9. doi: 10.1038/nature06745. Epub 2008 Feb 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cell, and Developmental Biology, University of California at Los Angeles, Los Angeles, California 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18278030" target="_blank"〉PubMed〈/a〉
    Keywords: 5-Methylcytosine/metabolism ; Animals ; Arabidopsis/*genetics ; Base Sequence ; Computational Biology ; Cytosine/metabolism ; *DNA Methylation ; Gene Expression Regulation, Plant/genetics ; Gene Library ; Genome, Plant/*genetics ; Mice ; Mutation/genetics ; Promoter Regions, Genetic/genetics ; Reproducibility of Results ; Sequence Analysis, DNA/*methods ; Sulfites/*metabolism ; Uracil/metabolism
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  • 89
    Publication Date: 2008-05-24
    Description: Proteasomal receptors that recognize ubiquitin chains attached to substrates are key mediators of selective protein degradation in eukaryotes. Here we report the identification of a new ubiquitin receptor, Rpn13/ARM1, a known component of the proteasome. Rpn13 binds ubiquitin through a conserved amino-terminal region termed the pleckstrin-like receptor for ubiquitin (Pru) domain, which binds K48-linked diubiquitin with an affinity of approximately 90 nM. Like proteasomal ubiquitin receptor Rpn10/S5a, Rpn13 also binds ubiquitin-like (UBL) domains of UBL-ubiquitin-associated (UBA) proteins. In yeast, a synthetic phenotype results when specific mutations of the ubiquitin binding sites of Rpn10 and Rpn13 are combined, indicating functional linkage between these ubiquitin receptors. Because Rpn13 is also the proteasomal receptor for Uch37, a deubiquitinating enzyme, our findings suggest a coupling of chain recognition and disassembly at the proteasome.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2839886/" 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/PMC2839886/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Husnjak, Koraljka -- Elsasser, Suzanne -- Zhang, Naixia -- Chen, Xiang -- Randles, Leah -- Shi, Yuan -- Hofmann, Kay -- Walters, Kylie J -- Finley, Daniel -- Dikic, Ivan -- CA097004/CA/NCI NIH HHS/ -- GM008700/GM/NIGMS NIH HHS/ -- GM043601/GM/NIGMS NIH HHS/ -- R01 CA097004/CA/NCI NIH HHS/ -- R01 CA097004-05/CA/NCI NIH HHS/ -- R01 CA097004-06A1/CA/NCI NIH HHS/ -- R37 GM043601/GM/NIGMS NIH HHS/ -- R37 GM043601-17/GM/NIGMS NIH HHS/ -- T32 GM008700/GM/NIGMS NIH HHS/ -- T32 GM008700-09/GM/NIGMS NIH HHS/ -- England -- Nature. 2008 May 22;453(7194):481-8. doi: 10.1038/nature06926.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Biochemistry II and Cluster of Excellence Macromolecular Complexes, Goethe University, Theodor-Stern-Kai 7, D-60590 Frankfurt (Main), Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18497817" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites/genetics ; Cell Adhesion Molecules/chemistry/genetics/metabolism ; Humans ; Membrane Glycoproteins/chemistry/genetics/metabolism ; Mice ; Molecular Sequence Data ; Mutation/genetics ; Phenotype ; Proteasome Endopeptidase Complex/*chemistry/genetics/*metabolism ; Protein Subunits/chemistry/genetics/metabolism ; Saccharomyces cerevisiae Proteins/chemistry/genetics/metabolism ; Ubiquitin/*metabolism
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  • 90
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2008-11-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Nov 20;456(7220):281. doi: 10.1038/456281a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19020564" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anniversaries and Special Events ; *Biological Evolution ; Biological Science Disciplines/history ; Genetic Speciation ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; Selection, Genetic
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  • 91
    Publication Date: 2008-11-18
    Description: The Myc oncogene regulates the expression of several components of the protein synthetic machinery, including ribosomal proteins, initiation factors of translation, RNA polymerase III and ribosomal DNA. Whether and how increasing the cellular protein synthesis capacity affects the multistep process leading to cancer remains to be addressed. Here we use ribosomal protein heterozygote mice as a genetic tool to restore increased protein synthesis in Emu-Myc/+ transgenic mice to normal levels, and show that the oncogenic potential of Myc in this context is suppressed. Our findings demonstrate that the ability of Myc to increase protein synthesis directly augments cell size and is sufficient to accelerate cell cycle progression independently of known cell cycle targets transcriptionally regulated by Myc. In addition, when protein synthesis is restored to normal levels, Myc-overexpressing precancerous cells are more efficiently eliminated by programmed cell death. Our findings reveal a new mechanism that links increases in general protein synthesis rates downstream of an oncogenic signal to a specific molecular impairment in the modality of translation initiation used to regulate the expression of selective messenger RNAs. We show that an aberrant increase in cap-dependent translation downstream of Myc hyperactivation specifically impairs the translational switch to internal ribosomal entry site (IRES)-dependent translation that is required for accurate mitotic progression. Failure of this translational switch results in reduced mitotic-specific expression of the endogenous IRES-dependent form of Cdk11 (also known as Cdc2l and PITSLRE), which leads to cytokinesis defects and is associated with increased centrosome numbers and genome instability in Emu-Myc/+ mice. When accurate translational control is re-established in Emu-Myc/+ mice, genome instability is suppressed. Our findings demonstrate how perturbations in translational control provide a highly specific outcome for gene expression, genome stability and cancer initiation that have important implications for understanding the molecular mechanism of cancer formation at the post-genomic level.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2880952/" 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/PMC2880952/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barna, Maria -- Pusic, Aya -- Zollo, Ornella -- Costa, Maria -- Kondrashov, Nadya -- Rego, Eduardo -- Rao, Pulivarthi H -- Ruggero, Davide -- R01 HL085572/HL/NHLBI NIH HHS/ -- R01 HL085572-03/HL/NHLBI NIH HHS/ -- England -- Nature. 2008 Dec 18;456(7224):971-5. doi: 10.1038/nature07449. Epub 2008 Nov 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry & Biophysics, University of California San Francisco, Rock Hall Room 384C, 1550 Fourth Street, San Francisco, California 94158-2517, USA. maria.barna@ucsf.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19011615" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; B-Lymphocytes/cytology/metabolism/pathology ; Cell Division ; Cell Size ; Cells, Cultured ; Cytokinesis ; Gene Expression Regulation, Neoplastic ; Genes, myc/*genetics ; Genomic Instability ; Heterozygote ; Lymphoma/genetics/pathology ; Mice ; Mice, Inbred C57BL ; Mitosis ; Oncogene Protein p55(v-myc)/*genetics/*metabolism ; Precancerous Conditions/metabolism/pathology ; *Protein Biosynthesis ; Protein-Serine-Threonine Kinases/metabolism ; Ribosomal Proteins/*deficiency/*genetics
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  • 92
    Publication Date: 2008-01-11
    Description: Sex determination in fungi is controlled by a small, specialized region of the genome in contrast to the large sex-specific chromosomes of animals and some plants. Different gene combinations reside at these mating-type (MAT) loci and confer sexual identity; invariably they encode homeodomain, alpha-box, or high mobility group (HMG)-domain transcription factors. So far, MAT loci have been characterized from a single monophyletic clade of fungi, the Dikarya (the ascomycetes and basidiomycetes), and the ancestral state and evolutionary history of these loci have remained a mystery. Mating in the basal members of the kingdom has been less well studied, and even their precise taxonomic inter-relationships are still obscure. Here we apply bioinformatic and genetic mapping to identify the sex-determining (sex) region in Phycomyces blakesleeanus (Zygomycota), which represents an early branch within the fungi. Each sex allele contains a single gene that encodes an HMG-domain protein, implicating the HMG-domain proteins as an earlier form of fungal MAT loci. Additionally, one allele also contains a copy of a unique, chromosome-specific repetitive element, suggesting a generalized mechanism for the earliest steps in the evolution of sex determination and sex chromosome structure in eukaryotes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Idnurm, Alexander -- Walton, Felicia J -- Floyd, Anna -- Heitman, Joseph -- England -- Nature. 2008 Jan 10;451(7175):193-6. doi: 10.1038/nature06453.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics and Microbiology, 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/18185588" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Sequence ; Chromosomes, Fungal/genetics ; Computational Biology ; Fertility/genetics ; Fungal Proteins/chemistry/genetics ; Fungi/classification/*genetics ; Genes, Fungal/*genetics ; Genes, Mating Type, Fungal/genetics ; HMG-Box Domains ; Heterozygote ; High Mobility Group Proteins/chemistry/genetics ; Molecular Sequence Data ; *Phylogeny ; Recombination, Genetic/genetics ; Repetitive Sequences, Nucleic Acid/genetics ; *Sex ; *Sex Determination Processes
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  • 93
    Publication Date: 2008-01-04
    Description: The carbon balance of terrestrial ecosystems is particularly sensitive to climatic changes in autumn and spring, with spring and autumn temperatures over northern latitudes having risen by about 1.1 degrees C and 0.8 degrees C, respectively, over the past two decades. A simultaneous greening trend has also been observed, characterized by a longer growing season and greater photosynthetic activity. These observations have led to speculation that spring and autumn warming could enhance carbon sequestration and extend the period of net carbon uptake in the future. Here we analyse interannual variations in atmospheric carbon dioxide concentration data and ecosystem carbon dioxide fluxes. We find that atmospheric records from the past 20 years show a trend towards an earlier autumn-to-winter carbon dioxide build-up, suggesting a shorter net carbon uptake period. This trend cannot be explained by changes in atmospheric transport alone and, together with the ecosystem flux data, suggest increasing carbon losses in autumn. We use a process-based terrestrial biosphere model and satellite vegetation greenness index observations to investigate further the observed seasonal response of northern ecosystems to autumnal warming. We find that both photosynthesis and respiration increase during autumn warming, but the increase in respiration is greater. In contrast, warming increases photosynthesis more than respiration in spring. Our simulations and observations indicate that northern terrestrial ecosystems may currently lose carbon dioxide in response to autumn warming, with a sensitivity of about 0.2 PgC degrees C(-1), offsetting 90% of the increased carbon dioxide uptake during spring. If future autumn warming occurs at a faster rate than in spring, the ability of northern ecosystems to sequester carbon may be diminished earlier than previously suggested.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Piao, Shilong -- Ciais, Philippe -- Friedlingstein, Pierre -- Peylin, Philippe -- Reichstein, Markus -- Luyssaert, Sebastiaan -- Margolis, Hank -- Fang, Jingyun -- Barr, Alan -- Chen, Anping -- Grelle, Achim -- Hollinger, David Y -- Laurila, Tuomas -- Lindroth, Anders -- Richardson, Andrew D -- Vesala, Timo -- England -- Nature. 2008 Jan 3;451(7174):49-52. doi: 10.1038/nature06444.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉LSCE, UMR CEA-CNRS, Batiment 709, CE, L'Orme des Merisiers, F-91191 Gif-sur-Yvette, France. slpiao@lsce.ipsl.fr〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18172494" target="_blank"〉PubMed〈/a〉
    Keywords: Atmosphere/chemistry ; Biomass ; Carbon Dioxide/analysis/*metabolism ; Cell Respiration ; *Ecosystem ; Fossil Fuels ; Geography ; Greenhouse Effect ; History, 20th Century ; History, 21st Century ; Oceans and Seas ; Photosynthesis ; Plant Transpiration ; Plants/metabolism ; Rain ; *Seasons ; Soil/analysis ; *Temperature ; Water/metabolism
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  • 94
    Publication Date: 2008-09-26
    Description: Listeria monocytogenes is a gram-positive, intracellular, food-borne pathogen that can cause severe illness in humans and animals. On infection, it is actively phagocytosed by macrophages; it then escapes from the phagosome, replicates in the cytosol, and subsequently spreads from cell to cell by a non-lytic mechanism driven by actin polymerization. Penetration of the phagosomal membrane is initiated by the secreted haemolysin listeriolysin O (LLO), which is essential for vacuolar escape in vitro and for virulence in animal models of infection. Reduction is required to activate the lytic activity of LLO in vitro, and we show here that reduction by the enzyme gamma-interferon-inducible lysosomal thiol reductase (GILT, also called Ifi30) is responsible for the activation of LLO in vivo. GILT is a soluble thiol reductase expressed constitutively within the lysosomes of antigen-presenting cells, and it accumulates in macrophage phagosomes as they mature into phagolysosomes. The enzyme is delivered by a mannose-6-phosphate receptor-dependent mechanism to the endocytic pathway, where amino- and carboxy-terminal pro-peptides are cleaved to generate a 30-kDa mature enzyme. The active site of GILT contains two cysteine residues in a CXXC motif that catalyses the reduction of disulphide bonds. Mice lacking GILT are deficient in generating major histocompatibility complex class-II-restricted CD4(+) T-cell responses to protein antigens that contain disulphide bonds. Here we show that these mice are resistant to L. monocytogenes infection. Replication of the organism in GILT-negative macrophages, or macrophages expressing an enzymatically inactive GILT mutant, is impaired because of delayed escape from the phagosome. GILT activates LLO within the phagosome by the thiol reductase mechanism shared by members of the thioredoxin family. In addition, purified GILT activates recombinant LLO, facilitating membrane permeabilization and red blood cell lysis. The data show that GILT is a critical host factor that facilitates L. monocytogenes infection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2775488/" 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/PMC2775488/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Singh, Reshma -- Jamieson, Amanda -- Cresswell, Peter -- AI023081/AI/NIAID NIH HHS/ -- R37 AI023081/AI/NIAID NIH HHS/ -- R37 AI023081-24/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Oct 30;455(7217):1244-7. doi: 10.1038/nature07344. Epub 2008 Sep 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunobiology, Yale University School of Medicine, 300 Cedar Street, New Haven, Connecticut 06250-8011, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18815593" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Toxins/metabolism ; Cell-Free System ; Heat-Shock Proteins/metabolism ; Hemolysin Proteins/metabolism ; Hemolysis ; Listeria monocytogenes/growth & development/*physiology ; Listeriosis/*metabolism/*microbiology ; Macrophages/cytology/metabolism/microbiology ; Mice ; Mice, Inbred C57BL ; Oxidation-Reduction ; Oxidoreductases/chemistry/deficiency/genetics/*metabolism ; Phagocytosis ; Phagosomes/microbiology ; Thioredoxins/metabolism ; Virulence Factors/metabolism
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  • 95
    Publication Date: 2008-09-12
    Description: Old-growth forests remove carbon dioxide from the atmosphere at rates that vary with climate and nitrogen deposition. The sequestered carbon dioxide is stored in live woody tissues and slowly decomposing organic matter in litter and soil. Old-growth forests therefore serve as a global carbon dioxide sink, but they are not protected by international treaties, because it is generally thought that ageing forests cease to accumulate carbon. Here we report a search of literature and databases for forest carbon-flux estimates. We find that in forests between 15 and 800 years of age, net ecosystem productivity (the net carbon balance of the forest including soils) is usually positive. Our results demonstrate that old-growth forests can continue to accumulate carbon, contrary to the long-standing view that they are carbon neutral. Over 30 per cent of the global forest area is unmanaged primary forest, and this area contains the remaining old-growth forests. Half of the primary forests (6 x 10(8) hectares) are located in the boreal and temperate regions of the Northern Hemisphere. On the basis of our analysis, these forests alone sequester about 1.3 +/- 0.5 gigatonnes of carbon per year. Thus, our findings suggest that 15 per cent of the global forest area, which is currently not considered when offsetting increasing atmospheric carbon dioxide concentrations, provides at least 10 per cent of the global net ecosystem productivity. Old-growth forests accumulate carbon for centuries and contain large quantities of it. We expect, however, that much of this carbon, even soil carbon, will move back to the atmosphere if these forests are disturbed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Luyssaert, Sebastiaan -- Schulze, E-Detlef -- Borner, Annett -- Knohl, Alexander -- Hessenmoller, Dominik -- Law, Beverly E -- Ciais, Philippe -- Grace, John -- England -- Nature. 2008 Sep 11;455(7210):213-5. doi: 10.1038/nature07276.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of Antwerp, 2610 Wilrijk, Belgium. sebastiaan.luyssaert@ua.ac.be〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18784722" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Atmosphere/chemistry ; Biomass ; Carbon/*metabolism ; Carbon Dioxide/metabolism ; Databases, Factual ; Disasters ; *Ecosystem ; History, 15th Century ; History, 16th Century ; History, 17th Century ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; History, Medieval ; Human Activities ; Time Factors ; Trees/*metabolism
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  • 96
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2008-06-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barron, Michael -- England -- Nature. 2008 Jun 12;453(7197):859-60. doi: 10.1038/453859a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Architecture and Civil Engineering, University of Bath, BA2 7AY, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18548056" target="_blank"〉PubMed〈/a〉
    Keywords: Absorption ; *Acoustics ; Auditory Perception ; *Facility Design and Construction/history ; Hearing/physiology ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Humans ; *Music/history
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  • 97
    Publication Date: 2008-03-26
    Description: The neuronal repressor REST (RE1-silencing transcription factor; also called NRSF) is expressed at high levels in mouse embryonic stem (ES) cells, but its role in these cells is unclear. Here we show that REST maintains self-renewal and pluripotency in mouse ES cells through suppression of the microRNA miR-21. We found that, as with known self-renewal markers, the level of REST expression is much higher in self-renewing mouse ES cells than in differentiating mouse ES (embryoid body, EB) cells. Heterozygous deletion of Rest (Rest+/-) and its short-interfering-RNA-mediated knockdown in mouse ES cells cause a loss of self-renewal-even when these cells are grown under self-renewal conditions-and lead to the expression of markers specific for multiple lineages. Conversely, exogenously added REST maintains self-renewal in mouse EB cells. Furthermore, Rest+/- mouse ES cells cultured under self-renewal conditions express substantially reduced levels of several self-renewal regulators, including Oct4 (also called Pou5f1), Nanog, Sox2 and c-Myc, and exogenously added REST in mouse EB cells maintains the self-renewal phenotypes and expression of these self-renewal regulators. We also show that in mouse ES cells, REST is bound to the gene chromatin of a set of miRNAs that potentially target self-renewal genes. Whereas mouse ES cells and mouse EB cells containing exogenously added REST express lower levels of these miRNAs, EB cells, Rest+/- ES cells and ES cells treated with short interfering RNA targeting Rest express higher levels of these miRNAs. At least one of these REST-regulated miRNAs, miR-21, specifically suppresses the self-renewal of mouse ES cells, corresponding to the decreased expression of Oct4, Nanog, Sox2 and c-Myc. Thus, REST is a newly discovered element of the interconnected regulatory network that maintains the self-renewal and pluripotency of mouse ES cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2830094/" 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/PMC2830094/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Singh, Sanjay K -- Kagalwala, Mohamedi N -- Parker-Thornburg, Jan -- Adams, Henry -- Majumder, Sadhan -- CA81255/CA/NCI NIH HHS/ -- CA97124/CA/NCI NIH HHS/ -- P30 CA016672/CA/NCI NIH HHS/ -- R01 CA081255/CA/NCI NIH HHS/ -- R01 CA081255-10/CA/NCI NIH HHS/ -- R01 CA097124/CA/NCI NIH HHS/ -- R01 CA097124-07/CA/NCI NIH HHS/ -- England -- Nature. 2008 May 8;453(7192):223-7. doi: 10.1038/nature06863. Epub 2008 Mar 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cancer Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18362916" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomarkers ; Cell Differentiation ; Cell Line ; Cell Lineage ; Cell Proliferation ; Chromatin/genetics/metabolism ; Embryonic Stem Cells/*cytology/*metabolism ; Mice ; Mice, Inbred C57BL ; Pluripotent Stem Cells/*cytology/*metabolism ; Repressor Proteins/genetics/*metabolism ; Transcription Factors/deficiency/genetics/*metabolism
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  • 98
    Publication Date: 2008-09-19
    Description: The use of small organic molecules as catalysts has been known for more than a century. But only in the past decade has organocatalysis become a thriving area of general concepts and widely applicable asymmetric reactions. Here I present my opinion on why the field of organocatalysis has blossomed so dramatically over the past decade.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉MacMillan, David W C -- R01 GM078201-01-01/GM/NIGMS NIH HHS/ -- England -- Nature. 2008 Sep 18;455(7211):304-8. doi: 10.1038/nature07367.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Merck Center for Catalysis at Princeton University, 116 Frick Laboratory, Princeton University, Princeton, New Jersey 08540, USA. dmacmill@princeton.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18800128" target="_blank"〉PubMed〈/a〉
    Keywords: Catalysis ; Chemistry, Organic/*history/*methods ; History, 20th Century ; History, 21st Century ; Hydrogen Bonding ; Ions/chemistry
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  • 99
    Publication Date: 2008-07-11
    Description: Polo-like kinase-1 (PLK1) is an essential mitotic kinase regulating multiple aspects of the cell division process. Activation of PLK1 requires phosphorylation of a conserved threonine residue (Thr 210) in the T-loop of the PLK1 kinase domain, but the kinase responsible for this has not yet been affirmatively identified. Here we show that in human cells PLK1 activation occurs several hours before entry into mitosis, and requires aurora A (AURKA, also known as STK6)-dependent phosphorylation of Thr 210. We find that aurora A can directly phosphorylate PLK1 on Thr 210, and that activity of aurora A towards PLK1 is greatly enhanced by Bora (also known as C13orf34 and FLJ22624), a known cofactor for aurora A (ref. 7). We show that Bora/aurora-A-dependent phosphorylation is a prerequisite for PLK1 to promote mitotic entry after a checkpoint-dependent arrest. Importantly, expression of a PLK1-T210D phospho-mimicking mutant partially overcomes the requirement for aurora A in checkpoint recovery. Taken together, these data demonstrate that the initial activation of PLK1 is a primary function of aurora A.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Macurek, Libor -- Lindqvist, Arne -- Lim, Dan -- Lampson, Michael A -- Klompmaker, Rob -- Freire, Raimundo -- Clouin, Christophe -- Taylor, Stephen S -- Yaffe, Michael B -- Medema, Rene H -- CA112967/CA/NCI NIH HHS/ -- GM-60594/GM/NIGMS NIH HHS/ -- England -- Nature. 2008 Sep 4;455(7209):119-23. doi: 10.1038/nature07185. Epub 2008 Jul 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Oncology, University Medical Center Utrecht, Utrecht 3584CG, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18615013" target="_blank"〉PubMed〈/a〉
    Keywords: Aurora Kinase A ; Aurora Kinases ; Cell Cycle/*physiology ; Cell Cycle Proteins/genetics/*metabolism ; Cell Line ; DNA Damage ; Enzyme Activation ; Humans ; Mitosis ; Molecular Sequence Data ; Phosphorylation ; Phosphothreonine/metabolism ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; Proto-Oncogene Proteins/genetics/*metabolism ; Time Factors
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  • 100
    Publication Date: 2008-02-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Beccaloni, George W -- Smith, Vincent S -- England -- Nature. 2008 Feb 28;451(7182):1050. doi: 10.1038/4511050d.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18305520" target="_blank"〉PubMed〈/a〉
    Keywords: Biology/*history ; History, 19th Century ; History, 20th Century ; History, 21st Century ; *Selection, Genetic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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