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  • 1
    Publication Date: 2011-02-12
    Description: Splicing of mammalian precursor transfer RNA (tRNA) molecules involves two enzymatic steps. First, intron removal by the tRNA splicing endonuclease generates separate 5' and 3' exons. In animals, the second step predominantly entails direct exon ligation by an elusive RNA ligase. Using activity-guided purification of tRNA ligase from HeLa cell extracts, we identified HSPC117, a member of the UPF0027 (RtcB) family, as the essential subunit of a tRNA ligase complex. RNA interference-mediated depletion of HSPC117 inhibited maturation of intron-containing pre-tRNA both in vitro and in living cells. The high sequence conservation of HSPC117/RtcB proteins is suggestive of RNA ligase roles of this protein family in various organisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Popow, Johannes -- Englert, Markus -- Weitzer, Stefan -- Schleiffer, Alexander -- Mierzwa, Beata -- Mechtler, Karl -- Trowitzsch, Simon -- Will, Cindy L -- Luhrmann, Reinhard -- Soll, Dieter -- Martinez, Javier -- New York, N.Y. -- Science. 2011 Feb 11;331(6018):760-4. doi: 10.1126/science.1197847.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), A-1030 Vienna, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21311021" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Exons ; HeLa Cells ; Humans ; Introns ; Molecular Sequence Data ; Proteins/*chemistry/isolation & purification/*metabolism ; RNA Interference ; RNA Ligase (ATP)/*chemistry/isolation & purification/*metabolism ; RNA Precursors/*metabolism ; *RNA Splicing ; RNA, Transfer/*metabolism ; Spliceosomes/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2014-06-21
    Description: Seventeen Middle Pleistocene crania from the Sima de los Huesos site (Atapuerca, Spain) are analyzed, including seven new specimens. This sample makes it possible to thoroughly characterize a Middle Pleistocene hominin paleodeme and to address hypotheses about the origin and evolution of the Neandertals. Using a variety of techniques, the hominin-bearing layer could be reassigned to a period around 430,000 years ago. The sample shows a consistent morphological pattern with derived Neandertal features present in the face and anterior vault, many of which are related to the masticatory apparatus. This suggests that facial modification was the first step in the evolution of the Neandertal lineage, pointing to a mosaic pattern of evolution, with different anatomical and functional modules evolving at different rates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arsuaga, J L -- Martinez, I -- Arnold, L J -- Aranburu, A -- Gracia-Tellez, A -- Sharp, W D -- Quam, R M -- Falgueres, C -- Pantoja-Perez, A -- Bischoff, J -- Poza-Rey, E -- Pares, J M -- Carretero, J M -- Demuro, M -- Lorenzo, C -- Sala, N -- Martinon-Torres, M -- Garcia, N -- Alcazar de Velasco, A -- Cuenca-Bescos, G -- Gomez-Olivencia, A -- Moreno, D -- Pablos, A -- Shen, C-C -- Rodriguez, L -- Ortega, A I -- Garcia, R -- Bonmati, A -- Bermudez de Castro, J M -- Carbonell, E -- New York, N.Y. -- Science. 2014 Jun 20;344(6190):1358-63. doi: 10.1126/science.1253958.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centro Mixto UCM-ISCIII de Evolucion y Comportamiento Humanos, Madrid, Spain. Departamento de Paleontologia, Facultad Ciencias Geologicas, Universidad Complutense de Madrid, Spain. jlarsuaga@isciii.es. ; Area de Paleontologia, Departamento de Geologia, Geografia y Medio Ambiente, Universidad de Alcala, Spain.Centro Mixto UCM-ISCIII de Evolucion y Comportamiento Humanos, Madrid, Spain. ; Centro Nacional de Investigacion sobre la Evolucion Humana Burgos, Spain. School of Earth and Environmental Sciences, the Environment Institute, and the Institute for Photonics and Advanced Sensing (IPAS), University of Adelaide, Australia. ; Departamento Mineralogia y Petrologia, Facultad de Ciencia y Tecnologia, Universidad del Pais Vasco, Spain. ; Berkeley Geochronology Center, Berkeley, CA, USA. ; Department of Anthropology, Binghamton University (State University of New York), Binghamton, NY, USA. Division of Anthropology, American Museum of Natural History, New York, NY, USA.Centro Mixto UCM-ISCIII de Evolucion y Comportamiento Humanos, Madrid, Spain. ; Departement de Prehistoire, Museum National d'Histoire Naturelle, Paris, France. ; Centro Mixto UCM-ISCIII de Evolucion y Comportamiento Humanos, Madrid, Spain. Departamento de Paleontologia, Facultad Ciencias Geologicas, Universidad Complutense de Madrid, Spain. ; U.S. Geological Survey, Menlo Park, CA,USA. ; Centro Nacional de Investigacion sobre la Evolucion Humana Burgos, Spain. ; Laboratorio de Evolucion Humana, Departamento de Ciencias Historicas y Geografia, Universidad de Burgos, Spain. ; Centro Nacional de Investigacion sobre la Evolucion Humana Burgos, Spain. Institute for Photonics and Advanced Sensing (IPAS), School of Chemistry and Physics, University of Adelaide, Australia. ; Area de Prehistoria, Departamento d'Historia i Historia de l'Art, Universitat Rovira i Virgili (URV), Tarragona, Spain. Institut Catala de Paleoecologia Humana i Evolucio Social, Tarragona, Spain.Centro Mixto UCM-ISCIII de Evolucion y Comportamiento Humanos, Madrid, Spain. ; Centro Mixto UCM-ISCIII de Evolucion y Comportamiento Humanos, Madrid, Spain. ; Paleontologia, Aragosaurus-IUCA and Facultad Ciencias, Universidad de Zaragoza, Spain. ; Centro Mixto UCM-ISCIII de Evolucion y Comportamiento Humanos, Madrid, Spain. Departement de Prehistoire, Museum National d'Histoire Naturelle, Paris, France. PAVE Research Group, Division of Biological Anthropology, Cambridge, UK. ; Departement de Prehistoire, Museum National d'Histoire Naturelle, Paris, France. Laboratorio de Evolucion Humana, Departamento de Ciencias Historicas y Geografia, Universidad de Burgos, Spain. ; Centro Mixto UCM-ISCIII de Evolucion y Comportamiento Humanos, Madrid, Spain. Centro Nacional de Investigacion sobre la Evolucion Humana Burgos, Spain. Laboratorio de Evolucion Humana, Departamento de Ciencias Historicas y Geografia, Universidad de Burgos, Spain. ; High-Precision Mass Spectrometry and Environment Change Laboratory (HISPEC), Department of Geosciences, National Taiwan University, Taiwan ROC. ; Institut Catala de Paleoecologia Humana i Evolucio Social, Tarragona, Spain. Area de Prehistoria, Departamento d'Historia i Historia de l'Art, Universitat Rovira i Virgili (URV), Tarragona, Spain. Institute of Vertebrate Paleontology and Paleoanthropology of Beijing (IVPP), China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24948730" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/anatomy & histology ; Extinction, Biological ; *Fossils ; Genetic Drift ; Humans ; Neanderthals/*anatomy & histology/*genetics ; Organ Size ; Reproductive Isolation ; Skull/*anatomy & histology ; Spain
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2014-10-04
    Description: The thermal stability of proteins can be used to assess ligand binding in living cells. We have generalized this concept by determining the thermal profiles of more than 7000 proteins in human cells by means of mass spectrometry. Monitoring the effects of small-molecule ligands on the profiles delineated more than 50 targets for the kinase inhibitor staurosporine. We identified the heme biosynthesis enzyme ferrochelatase as a target of kinase inhibitors and suggest that its inhibition causes the phototoxicity observed with vemurafenib and alectinib. Thermal shifts were also observed for downstream effectors of drug treatment. In live cells, dasatinib induced shifts in BCR-ABL pathway proteins, including CRK/CRKL. Thermal proteome profiling provides an unbiased measure of drug-target engagement and facilitates identification of markers for drug efficacy and toxicity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Savitski, Mikhail M -- Reinhard, Friedrich B M -- Franken, Holger -- Werner, Thilo -- Savitski, Maria Falth -- Eberhard, Dirk -- Martinez Molina, Daniel -- Jafari, Rozbeh -- Dovega, Rebecca Bakszt -- Klaeger, Susan -- Kuster, Bernhard -- Nordlund, Par -- Bantscheff, Marcus -- Drewes, Gerard -- New York, N.Y. -- Science. 2014 Oct 3;346(6205):1255784. doi: 10.1126/science.1255784. Epub 2014 Oct 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cellzome GmbH, Molecular Discovery Research, GlaxoSmithKline, Meyerhofstrasse 1, Heidelberg, Germany. mikhail.m.savitski@gsk.com marcus.x.bantscheff@gsk.com gerard.c.drewes@gsk.com. ; Cellzome GmbH, Molecular Discovery Research, GlaxoSmithKline, Meyerhofstrasse 1, Heidelberg, Germany. ; Division of Biophysics, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. ; Department of Proteomics and Bioanalytics, Technische Universitat Munchen, Emil Erlenmeyer Forum 5, Freising, Germany. German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany. ; Division of Biophysics, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. Centre for Biomedical Structural Biology, Nanyang Technological University, Singapore.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25278616" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/metabolism ; Antineoplastic Agents/*pharmacology ; Hot Temperature ; Humans ; K562 Cells ; Ligands ; Protein Binding ; Protein Denaturation ; Protein Stability ; Proteome/*drug effects ; Proteomics/*methods
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2011-10-08
    Description: The exchange of the oocyte's genome with the genome of a somatic cell, followed by the derivation of pluripotent stem cells, could enable the generation of specific cells affected in degenerative human diseases. Such cells, carrying the patient's genome, might be useful for cell replacement. Here we report that the development of human oocytes after genome exchange arrests at late cleavage stages in association with transcriptional abnormalities. In contrast, if the oocyte genome is not removed and the somatic cell genome is merely added, the resultant triploid cells develop to the blastocyst stage. Stem cell lines derived from these blastocysts differentiate into cell types of all three germ layers, and a pluripotent gene expression program is established on the genome derived from the somatic cell. This result demonstrates the feasibility of reprogramming human cells using oocytes and identifies removal of the oocyte genome as the primary cause of developmental failure after genome exchange.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Noggle, Scott -- Fung, Ho-Lim -- Gore, Athurva -- Martinez, Hector -- Satriani, Kathleen Crumm -- Prosser, Robert -- Oum, Kiboong -- Paull, Daniel -- Druckenmiller, Sarah -- Freeby, Matthew -- Greenberg, Ellen -- Zhang, Kun -- Goland, Robin -- Sauer, Mark V -- Leibel, Rudolph L -- Egli, Dieter -- England -- Nature. 2011 Oct 5;478(7367):70-5. doi: 10.1038/nature10397.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The New York Stem Cell Foundation Laboratory, New York, New York, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21979046" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Blastocyst/cytology/metabolism ; Cell Differentiation ; *Cellular Reprogramming ; DNA Methylation ; Epigenesis, Genetic ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Genome, Human/genetics ; Germ Layers/cytology/embryology/metabolism ; Humans ; Induced Pluripotent Stem Cells/*cytology/*metabolism ; Oocyte Donation ; Oocytes/*cytology/growth & development/*physiology ; Primary Cell Culture ; Transcription, Genetic ; Triploidy ; Young Adult
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2014-08-01
    Description: Microorganisms evolve via a range of mechanisms that may include or involve sexual/parasexual reproduction, mutators, aneuploidy, Hsp90 and even prions. Mechanisms that may seem detrimental can be repurposed to generate diversity. Here we show that the human fungal pathogen Mucor circinelloides develops spontaneous resistance to the antifungal drug FK506 (tacrolimus) via two distinct mechanisms. One involves Mendelian mutations that confer stable drug resistance; the other occurs via an epigenetic RNA interference (RNAi)-mediated pathway resulting in unstable drug resistance. The peptidylprolyl isomerase FKBP12 interacts with FK506 forming a complex that inhibits the protein phosphatase calcineurin. Calcineurin inhibition by FK506 blocks M. circinelloides transition to hyphae and enforces yeast growth. Mutations in the fkbA gene encoding FKBP12 or the calcineurin cnbR or cnaA genes confer FK506 resistance and restore hyphal growth. In parallel, RNAi is spontaneously triggered to silence the fkbA gene, giving rise to drug-resistant epimutants. FK506-resistant epimutants readily reverted to the drug-sensitive wild-type phenotype when grown without exposure to the drug. The establishment of these epimutants is accompanied by generation of abundant fkbA small RNAs and requires the RNAi pathway as well as other factors that constrain or reverse the epimutant state. Silencing involves the generation of a double-stranded RNA trigger intermediate using the fkbA mature mRNA as a template to produce antisense fkbA RNA. This study uncovers a novel epigenetic RNAi-based epimutation mechanism controlling phenotypic plasticity, with possible implications for antimicrobial drug resistance and RNAi-regulatory mechanisms in fungi and other eukaryotes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4177005/" 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/PMC4177005/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Calo, Silvia -- Shertz-Wall, Cecelia -- Lee, Soo Chan -- Bastidas, Robert J -- Nicolas, Francisco E -- Granek, Joshua A -- Mieczkowski, Piotr -- Torres-Martinez, Santiago -- Ruiz-Vazquez, Rosa M -- Cardenas, Maria E -- Heitman, Joseph -- R01 AI039115/AI/NIAID NIH HHS/ -- R01 AI50438-10/AI/NIAID NIH HHS/ -- R01 CA154499/CA/NCI NIH HHS/ -- R01 CA154499-04/CA/NCI NIH HHS/ -- R37 AI039115/AI/NIAID NIH HHS/ -- R37 AI39115-17/AI/NIAID NIH HHS/ -- England -- Nature. 2014 Sep 25;513(7519):555-8. doi: 10.1038/nature13575. Epub 2014 Jul 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA. ; 1] Regional Campus of International Excellence "Campus Mare Nostrum", Murcia 30100, Spain [2] Department of Genetics and Microbiology, Faculty of Biology, University of Murcia, Murcia 30100, Spain. ; 1] Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA [2] Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina 27710, USA [3] Duke Center for the Genomics of Microbial Systems, Duke University Medical Center, Durham, North Carolina 27710, USA. ; High-Throughput Sequencing Facility, University of North Carolina, Chapel Hill, North Carolina 27599, USA. ; Department of Genetics and Microbiology, Faculty of Biology, University of Murcia, Murcia 30100, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25079329" target="_blank"〉PubMed〈/a〉
    Keywords: Calcineurin/genetics/metabolism ; Calcineurin Inhibitors ; Drug Resistance, Fungal/*genetics ; Epigenesis, Genetic/*genetics ; Humans ; Hyphae/drug effects/genetics/growth & development ; Molecular Sequence Data ; Mucor/*drug effects/*genetics/growth & development ; Mucormycosis/drug therapy/microbiology ; Mutation/*genetics ; Phenotype ; *RNA Interference ; Tacrolimus/metabolism/*pharmacology ; Tacrolimus Binding Protein 1A/deficiency/genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2014-01-28
    Description: Ancient genomic sequences have started to reveal the origin and the demographic impact of farmers from the Neolithic period spreading into Europe. The adoption of farming, stock breeding and sedentary societies during the Neolithic may have resulted in adaptive changes in genes associated with immunity and diet. However, the limited data available from earlier hunter-gatherers preclude an understanding of the selective processes associated with this crucial transition to agriculture in recent human evolution. Here we sequence an approximately 7,000-year-old Mesolithic skeleton discovered at the La Brana-Arintero site in Leon, Spain, to retrieve a complete pre-agricultural European human genome. Analysis of this genome in the context of other ancient samples suggests the existence of a common ancient genomic signature across western and central Eurasia from the Upper Paleolithic to the Mesolithic. The La Brana individual carries ancestral alleles in several skin pigmentation genes, suggesting that the light skin of modern Europeans was not yet ubiquitous in Mesolithic times. Moreover, we provide evidence that a significant number of derived, putatively adaptive variants associated with pathogen resistance in modern Europeans were already present in this hunter-gatherer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269527/" 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/PMC4269527/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Olalde, Inigo -- Allentoft, Morten E -- Sanchez-Quinto, Federico -- Santpere, Gabriel -- Chiang, Charleston W K -- DeGiorgio, Michael -- Prado-Martinez, Javier -- Rodriguez, Juan Antonio -- Rasmussen, Simon -- Quilez, Javier -- Ramirez, Oscar -- Marigorta, Urko M -- Fernandez-Callejo, Marcos -- Prada, Maria Encina -- Encinas, Julio Manuel Vidal -- Nielsen, Rasmus -- Netea, Mihai G -- Novembre, John -- Sturm, Richard A -- Sabeti, Pardis -- Marques-Bonet, Tomas -- Navarro, Arcadi -- Willerslev, Eske -- Lalueza-Fox, Carles -- F32 GM106656/GM/NIGMS NIH HHS/ -- F32GM106656/GM/NIGMS NIH HHS/ -- R01 HG007089/HG/NHGRI NIH HHS/ -- R01-HG007089/HG/NHGRI NIH HHS/ -- England -- Nature. 2014 Mar 13;507(7491):225-8. doi: 10.1038/nature12960. Epub 2014 Jan 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Institut de Biologia Evolutiva, CSIC-UPF, Barcelona 08003, Spain [2]. ; 1] Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, DK-1350 Copenhagen K, Denmark [2]. ; Institut de Biologia Evolutiva, CSIC-UPF, Barcelona 08003, Spain. ; Department of Ecology and Evolutionary Biology, University of California, Los Angeles, California 90095, USA. ; 1] Department of Integrative Biology, University of California, Berkeley, California 94720, USA [2] Department of Biology, Pennsylvania State University, 502 Wartik Laboratory, University Park, Pennsylvania 16802, USA. ; Center for Biological Sequence Analysis, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark. ; I.E.S.O. 'Los Salados', Junta de Castilla y Leon, E-49600 Benavente, Spain. ; Junta de Castilla y Leon, Servicio de Cultura de Leon, E-24071 Leon, Spain. ; Center for Theoretical Evolutionary Genomics, University of California, Berkeley, California 94720, USA. ; Department of Medicine and Nijmegen Institute for Infection, Inflammation and Immunity, Radboud University Nijmegen Medical Centre, 6500 Nijmegen, The Netherlands. ; Department of Human Genetics, University of Chicago, Illinois 60637, USA. ; Institute for Molecular Bioscience, Melanogenix Group, The University of Queensland, Brisbane, Queensland 4072, Australia. ; 1] Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138, USA [2] Broad Institute of the Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142, USA. ; 1] Institut de Biologia Evolutiva, CSIC-UPF, Barcelona 08003, Spain [2] Institucio Catalana de Recerca i Estudis Avancats (ICREA), 08010 Barcelona, Catalonia, Spain. ; 1] Institut de Biologia Evolutiva, CSIC-UPF, Barcelona 08003, Spain [2] Institucio Catalana de Recerca i Estudis Avancats (ICREA), 08010 Barcelona, Catalonia, Spain [3] Centre de Regulacio Genomica (CRG), Barcelona 08003, Catalonia, Spain [4] National Institute for Bioinformatics (INB), Barcelona 08003, Catalonia, Spain. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, DK-1350 Copenhagen K, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24463515" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/history ; *Alleles ; Biological Evolution ; Caves ; European Continental Ancestry Group/*genetics ; Eye Color/genetics ; *Fossils ; Genome, Human/genetics ; Genomics ; History, Ancient ; Humans ; Immunity/*genetics ; Lactose Intolerance/genetics ; Male ; Pigmentation/*genetics ; Polymorphism, Single Nucleotide/genetics ; Principal Component Analysis ; Skeleton ; Skin Pigmentation/genetics ; Spain/ethnology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2011-08-05
    Description: Dust has the potential to modify global climate by influencing the radiative balance of the atmosphere and by supplying iron and other essential limiting micronutrients to the ocean. Indeed, dust supply to the Southern Ocean increases during ice ages, and 'iron fertilization' of the subantarctic zone may have contributed up to 40 parts per million by volume (p.p.m.v.) of the decrease (80-100 p.p.m.v.) in atmospheric carbon dioxide observed during late Pleistocene glacial cycles. So far, however, the magnitude of Southern Ocean dust deposition in earlier times and its role in the development and evolution of Pleistocene glacial cycles have remained unclear. Here we report a high-resolution record of dust and iron supply to the Southern Ocean over the past four million years, derived from the analysis of marine sediments from ODP Site 1090, located in the Atlantic sector of the subantarctic zone. The close correspondence of our dust and iron deposition records with Antarctic ice core reconstructions of dust flux covering the past 800,000 years (refs 8, 9) indicates that both of these archives record large-scale deposition changes that should apply to most of the Southern Ocean, validating previous interpretations of the ice core data. The extension of the record beyond the interval covered by the Antarctic ice cores reveals that, in contrast to the relatively gradual intensification of glacial cycles over the past three million years, Southern Ocean dust and iron flux rose sharply at the Mid-Pleistocene climatic transition around 1.25 million years ago. This finding complements previous observations over late Pleistocene glacial cycles, providing new evidence of a tight connection between high dust input to the Southern Ocean and the emergence of the deep glaciations that characterize the past one million years of Earth history.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Martinez-Garcia, Alfredo -- Rosell-Mele, Antoni -- Jaccard, Samuel L -- Geibert, Walter -- Sigman, Daniel M -- Haug, Gerald H -- England -- Nature. 2011 Aug 3;476(7360):312-5. doi: 10.1038/nature10310.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Geological Institute, ETH Zurich, Zurich 8092, Switzerland. alfredo.martinez-garcia@erdw.ethz.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21814203" target="_blank"〉PubMed〈/a〉
    Keywords: Alkanes/analysis ; Atlantic Ocean ; Atmosphere/chemistry ; Carbon Cycle ; Carbon Dioxide/analysis ; *Climate ; Diatoms/metabolism ; Dust/*analysis ; Ecosystem ; Geologic Sediments/chemistry ; History, Ancient ; Ice/analysis ; Iron/analysis ; Nitrates/analysis ; Oceans and Seas ; Reproducibility of Results ; Seawater/*chemistry ; Uncertainty ; Wind
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2011-02-25
    Description: Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal human premature ageing disease, characterized by premature arteriosclerosis and degeneration of vascular smooth muscle cells (SMCs). HGPS is caused by a single point mutation in the lamin A (LMNA) gene, resulting in the generation of progerin, a truncated splicing mutant of lamin A. Accumulation of progerin leads to various ageing-associated nuclear defects including disorganization of nuclear lamina and loss of heterochromatin. Here we report the generation of induced pluripotent stem cells (iPSCs) from fibroblasts obtained from patients with HGPS. HGPS-iPSCs show absence of progerin, and more importantly, lack the nuclear envelope and epigenetic alterations normally associated with premature ageing. Upon differentiation of HGPS-iPSCs, progerin and its ageing-associated phenotypic consequences are restored. Specifically, directed differentiation of HGPS-iPSCs to SMCs leads to the appearance of premature senescence phenotypes associated with vascular ageing. Additionally, our studies identify DNA-dependent protein kinase catalytic subunit (DNAPKcs, also known as PRKDC) as a downstream target of progerin. The absence of nuclear DNAPK holoenzyme correlates with premature as well as physiological ageing. Because progerin also accumulates during physiological ageing, our results provide an in vitro iPSC-based model to study the pathogenesis of human premature and physiological vascular ageing.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3088088/" 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/PMC3088088/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Guang-Hui -- Barkho, Basam Z -- Ruiz, Sergio -- Diep, Dinh -- Qu, Jing -- Yang, Sheng-Lian -- Panopoulos, Athanasia D -- Suzuki, Keiichiro -- Kurian, Leo -- Walsh, Christopher -- Thompson, James -- Boue, Stephanie -- Fung, Ho Lim -- Sancho-Martinez, Ignacio -- Zhang, Kun -- Yates, John 3rd -- Izpisua Belmonte, Juan Carlos -- P41 RR011823/RR/NCRR NIH HHS/ -- R01 DA025779/DA/NIDA NIH HHS/ -- R01 DA025779-01/DA/NIDA NIH HHS/ -- R01-DA025779/DA/NIDA NIH HHS/ -- T32 CA009370/CA/NCI NIH HHS/ -- T32 CA009370-25A1/CA/NCI NIH HHS/ -- England -- Nature. 2011 Apr 14;472(7342):221-5. doi: 10.1038/nature09879. Epub 2011 Feb 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21346760" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/metabolism/pathology/physiology ; Aging, Premature/genetics/pathology/physiopathology ; Calcium-Binding Proteins/analysis ; Cell Aging ; Cell Differentiation ; Cell Line ; Cellular Reprogramming ; DNA-Activated Protein Kinase/metabolism ; Epigenesis, Genetic ; Fibroblasts/pathology ; Holoenzymes/metabolism ; Humans ; Induced Pluripotent Stem Cells/metabolism/*pathology ; Lamin Type A ; Microfilament Proteins/analysis ; Models, Biological ; Muscle, Smooth, Vascular/pathology ; Nuclear Envelope/pathology ; Nuclear Proteins/analysis/genetics/metabolism ; Phenotype ; Progeria/genetics/pathology/physiopathology ; Protein Precursors/analysis/genetics/metabolism ; Substrate Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2014-05-30
    Description: RNA ligases have essential roles in many cellular processes in eukaryotes, archaea and bacteria, including in RNA repair and stress-induced splicing of messenger RNA. In archaea and eukaryotes, RNA ligases also have a role in transfer RNA splicing to generate functional tRNAs required for protein synthesis. We recently identified the human tRNA splicing ligase, a multimeric protein complex with RTCB (also known as HSPC117, C22orf28, FAAP and D10Wsu52e) as the essential subunit. The functions of the additional complex components ASW (also known as C2orf49), CGI-99 (also known as C14orf166), FAM98B and the DEAD-box helicase DDX1 in the context of RNA ligation have remained unclear. Taking advantage of clusters of eukaryotic orthologous groups, here we find that archease (ARCH; also known as ZBTB8OS), a protein of unknown function, is required for full activity of the human tRNA ligase complex and, in cooperation with DDX1, facilitates the formation of an RTCB-guanylate intermediate central to mammalian RNA ligation. Our findings define a role for DDX1 in the context of the human tRNA ligase complex and suggest that the widespread co-occurrence of archease and RtcB proteins implies evolutionary conservation of their functional interplay.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4417724/" 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/PMC4417724/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Popow, Johannes -- Jurkin, Jennifer -- Schleiffer, Alexander -- Martinez, Javier -- P 24687/Austrian Science Fund FWF/Austria -- England -- Nature. 2014 Jul 3;511(7507):104-7. doi: 10.1038/nature13284. Epub 2014 May 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), A-1030 Vienna, Austria [2] European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany. ; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), A-1030 Vienna, Austria. ; IMP/IMBA Bioinformatics Core Facility, Research Institute of Molecular Pathology (IMP), A-1030 Vienna, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24870230" target="_blank"〉PubMed〈/a〉
    Keywords: Carrier Proteins/*metabolism ; Catalytic Domain ; Cell Survival ; Conserved Sequence ; DEAD-box RNA Helicases/*metabolism ; Evolution, Molecular ; Humans ; Multienzyme Complexes/chemistry/isolation & purification/*metabolism ; Proteins ; RNA Ligase (ATP)/*chemistry/isolation & purification/*metabolism ; *RNA Splicing ; RNA, Transfer/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2011-10-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carrero-Martinez, Franklin A -- New York, N.Y. -- Science. 2011 Oct 21;334(6054):313. doi: 10.1126/science.1209555.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of Puerto Rico, Mayaguez, Mayaguez, PR 00681. franklin.carrero@upr.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22021843" target="_blank"〉PubMed〈/a〉
    Keywords: Faculty ; Humans ; Mentors ; Minority Groups/*education ; *Research ; *Universities
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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