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  • 1
    Publication Date: 2014-12-30
    Description: The skin represents the primary interface between the host and the environment. This organ is also home to trillions of microorganisms that play an important role in tissue homeostasis and local immunity. Skin microbial communities are highly diverse and can be remodelled over time or in response to environmental challenges. How, in the context of this complexity, individual commensal microorganisms may differentially modulate skin immunity and the consequences of these responses for tissue physiology remains unclear. Here we show that defined commensals dominantly affect skin immunity and identify the cellular mediators involved in this specification. In particular, colonization with Staphylococcus epidermidis induces IL-17A(+) CD8(+) T cells that home to the epidermis, enhance innate barrier immunity and limit pathogen invasion. Commensal-specific T-cell responses result from the coordinated action of skin-resident dendritic cell subsets and are not associated with inflammation, revealing that tissue-resident cells are poised to sense and respond to alterations in microbial communities. This interaction may represent an evolutionary means by which the skin immune system uses fluctuating commensal signals to calibrate barrier immunity and provide heterologous protection against invasive pathogens. These findings reveal that the skin immune landscape is a highly dynamic environment that can be rapidly and specifically remodelled by encounters with defined commensals, findings that have profound implications for our understanding of tissue-specific immunity and pathologies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667810/" 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/PMC4667810/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Naik, Shruti -- Bouladoux, Nicolas -- Linehan, Jonathan L -- Han, Seong-Ji -- Harrison, Oliver J -- Wilhelm, Christoph -- Conlan, Sean -- Himmelfarb, Sarah -- Byrd, Allyson L -- Deming, Clayton -- Quinones, Mariam -- Brenchley, Jason M -- Kong, Heidi H -- Tussiwand, Roxanne -- Murphy, Kenneth M -- Merad, Miriam -- Segre, Julia A -- Belkaid, Yasmine -- R01 CA173861/CA/NCI NIH HHS/ -- R01 CA190400/CA/NCI NIH HHS/ -- U01 AI095611/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- England -- Nature. 2015 Apr 2;520(7545):104-8. doi: 10.1038/nature14052. Epub 2015 Jan 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Immunity at Barrier Sites Initiative, National Institute of Allergy and Infectious Diseases, NIH, Bethesda 20892, USA [2] Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892, USA. ; Translational and Functional Genomics Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA. ; 1] Immunity at Barrier Sites Initiative, National Institute of Allergy and Infectious Diseases, NIH, Bethesda 20892, USA [2] Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892, USA [3] Translational and Functional Genomics Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA. ; Bioinformatics and Computational Bioscience Branch, National Institute of Allergy and Infectious Diseases, NIH Bethesda, Maryland 20892, USA. ; 1] Immunity at Barrier Sites Initiative, National Institute of Allergy and Infectious Diseases, NIH, Bethesda 20892, USA [2] Immunopathogenesis Section, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH Bethesda, Maryland 20892, USA. ; Dermatology Branch, National Cancer Institute, NIH Bethesda, Maryland 20892, USA. ; Howard Hughes Medical Institute, Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA. ; Department of Oncological Sciences, Tisch Cancer Institute and Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25539086" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Bacterial/immunology ; CD8-Positive T-Lymphocytes/cytology/*immunology ; Dendritic Cells/cytology/*immunology ; Humans ; Immunity, Innate/immunology ; Interleukin-17/immunology ; Langerhans Cells/cytology/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Primates ; Skin/cytology/*immunology/*microbiology ; Staphylococcus epidermidis/immunology ; Symbiosis/*immunology
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  • 2
    Publication Date: 2014-12-30
    Description: The ages of the most common stars--low-mass (cool) stars like the Sun, and smaller--are difficult to derive because traditional dating methods use stellar properties that either change little as the stars age or are hard to measure. The rotation rates of all cool stars decrease substantially with time as the stars steadily lose their angular momenta. If properly calibrated, rotation therefore can act as a reliable determinant of their ages based on the method of gyrochronology. To calibrate gyrochronology, the relationship between rotation period and age must be determined for cool stars of different masses, which is best accomplished with rotation period measurements for stars in clusters with well-known ages. Hitherto, such measurements have been possible only in clusters with ages of less than about one billion years, and gyrochronology ages for older stars have been inferred from model predictions. Here we report rotation period measurements for 30 cool stars in the 2.5-billion-year-old cluster NGC 6819. The periods reveal a well-defined relationship between rotation period and stellar mass at the cluster age, suggesting that ages with a precision of order 10 per cent can be derived for large numbers of cool Galactic field stars.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meibom, Soren -- Barnes, Sydney A -- Platais, Imants -- Gilliland, Ronald L -- Latham, David W -- Mathieu, Robert D -- England -- Nature. 2015 Jan 29;517(7536):589-91. doi: 10.1038/nature14118. Epub 2015 Jan 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Harvard-Smithsonian Center for Astrophysics, Cambridge, Massachusetts 02138, USA. ; 1] Leibniz Institute for Astrophysics, An der Sternwarte 16, 14482 Potsdam, Germany [2] Space Science Institute, 4750 Walnut Street #205, Boulder, Colorado 80301, USA. ; Department of Physics and Astronomy, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA. ; Center for Exoplanets and Habitable Worlds, The Pennsylvania State University, University Park, Pennsylvania 16802, USA. ; Department of Astronomy, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25539085" target="_blank"〉PubMed〈/a〉
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2014-12-30
    Description: Hox genes regulate regionalization of the axial skeleton in vertebrates, and changes in their expression have been proposed to be a fundamental mechanism driving the evolution of new body forms. The origin of the snake-like body form, with its deregionalized pre-cloacal axial skeleton, has been explained as either homogenization of Hox gene expression domains, or retention of standard vertebrate Hox domains with alteration of downstream expression that suppresses development of distinct regions. Both models assume a highly regionalized ancestor, but the extent of deregionalization of the primaxial domain (vertebrae, dorsal ribs) of the skeleton in snake-like body forms has never been analysed. Here we combine geometric morphometrics and maximum-likelihood analysis to show that the pre-cloacal primaxial domain of elongate, limb-reduced lizards and snakes is not deregionalized compared with limbed taxa, and that the phylogenetic structure of primaxial morphology in reptiles does not support a loss of regionalization in the evolution of snakes. We demonstrate that morphometric regional boundaries correspond to mapped gene expression domains in snakes, suggesting that their primaxial domain is patterned by a normally functional Hox code. Comparison of primaxial osteology in fossil and modern amniotes with Hox gene distributions within Amniota indicates that a functional, sequentially expressed Hox code patterned a subtle morphological gradient along the anterior-posterior axis in stem members of amniote clades and extant lizards, including snakes. The highly regionalized skeletons of extant archosaurs and mammals result from independent evolution in the Hox code and do not represent ancestral conditions for clades with snake-like body forms. The developmental origin of snakes is best explained by decoupling of the primaxial and abaxial domains and by increases in somite number, not by changes in the function of primaxial Hox genes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Head, Jason J -- Polly, P David -- England -- Nature. 2015 Apr 2;520(7545):86-9. doi: 10.1038/nature14042. Epub 2015 Jan 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Earth and Atmospheric Sciences and Nebraska State Museum of Natural History, University of Nebraska-Lincoln, Lincoln, Nebraska 68588-0340, USA. ; Departments of Geological Sciences, Biology and Anthropology, Indiana University, Bloomington, Indiana 47405-1405, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25539083" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cloaca ; Developmental Biology ; Extremities/anatomy & histology ; *Fossils ; Genes, Homeobox/*genetics ; Lizards/anatomy & histology ; Models, Biological ; *Phylogeny ; Sacrum ; Snakes/*anatomy & histology/*genetics ; Spine/*anatomy & histology
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  • 4
    Publication Date: 2014-12-30
    Description: Meiotic recombination is a critical step in gametogenesis for many organisms, enabling the creation of genetically diverse haploid gametes. In each meiotic cell, recombination is initiated by numerous DNA double-strand breaks (DSBs) created by Spo11, the evolutionarily conserved topoisomerase-like protein, but how these DSBs are distributed relatively uniformly across the four chromatids that make up each chromosome pair is poorly understood. Here we employ Saccharomyces cerevisiae to demonstrate distance-dependent DSB interference in cis (in which the occurrence of a DSB suppresses adjacent DSB formation)--a process that is mediated by the conserved DNA damage response kinase, Tel1(ATM). The inhibitory function of Tel1 acts on a relatively local scale, while over large distances DSBs have a tendency to form independently of one another even in the presence of Tel1. Notably, over very short distances, loss of Tel1 activity causes DSBs to cluster within discrete zones of concerted DSB activity. Our observations support a hierarchical view of recombination initiation where Tel1(ATM) prevents clusters of DSBs, and further suppresses DSBs within the surrounding chromosomal region. Such collective negative regulation will help to ensure that recombination events are dispersed evenly and arranged optimally for genetic exchange and efficient chromosome segregation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Garcia, Valerie -- Gray, Stephen -- Allison, Rachal M -- Cooper, Tim J -- Neale, Matthew J -- Medical Research Council/United Kingdom -- England -- Nature. 2015 Apr 2;520(7545):114-8. doi: 10.1038/nature13993. Epub 2015 Jan 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genome Damage and Stability Centre, University of Sussex, Brighton BN1 9RQ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25539084" target="_blank"〉PubMed〈/a〉
    Keywords: 3-Isopropylmalate Dehydrogenase/genetics ; Alcohol Oxidoreductases/genetics ; Aminohydrolases/genetics ; Chromatin/chemistry/genetics/metabolism ; Chromosomes, Fungal/genetics ; *DNA Breaks, Double-Stranded ; Endodeoxyribonucleases/antagonists & inhibitors/metabolism ; Genes, Fungal/genetics ; Homologous Recombination/genetics ; Intracellular Signaling Peptides and Proteins/deficiency/genetics/*metabolism ; Meiosis/*genetics ; Protein-Serine-Threonine Kinases/deficiency/genetics/*metabolism ; Pyrophosphatases/genetics ; Saccharomyces cerevisiae/cytology/*enzymology/*genetics ; Saccharomyces cerevisiae Proteins/antagonists & inhibitors/genetics/*metabolism
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  • 5
    Publication Date: 2014-12-24
    Description: The kinetochore is the crucial apparatus regulating chromosome segregation in mitosis and meiosis. Particularly in meiosis I, unlike in mitosis, sister kinetochores are captured by microtubules emanating from the same spindle pole (mono-orientation) and centromeric cohesion mediated by cohesin is protected in the following anaphase. Although meiotic kinetochore factors have been identified only in budding and fission yeasts, these molecules and their functions are thought to have diverged earlier. Therefore, a conserved mechanism for meiotic kinetochore regulation remains elusive. Here we have identified in mouse a meiosis-specific kinetochore factor that we termed MEIKIN, which functions in meiosis I but not in meiosis II or mitosis. MEIKIN plays a crucial role in both mono-orientation and centromeric cohesion protection, partly by stabilizing the localization of the cohesin protector shugoshin. These functions are mediated mainly by the activity of Polo-like kinase PLK1, which is enriched to kinetochores in a MEIKIN-dependent manner. Our integrative analysis indicates that the long-awaited key regulator of meiotic kinetochore function is Meikin, which is conserved from yeasts to humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Jihye -- Ishiguro, Kei-ichiro -- Nambu, Aya -- Akiyoshi, Bungo -- Yokobayashi, Shihori -- Kagami, Ayano -- Ishiguro, Tadashi -- Pendas, Alberto M -- Takeda, Naoki -- Sakakibara, Yogo -- Kitajima, Tomoya S -- Tanno, Yuji -- Sakuno, Takeshi -- Watanabe, Yoshinori -- England -- Nature. 2015 Jan 22;517(7535):466-71. doi: 10.1038/nature14097. Epub 2014 Dec 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1Yayoi, Tokyo 113-0032, Japan. ; Instituto de Biologia Molecular y Celular del Cancer (CSIC-USAL), 37007 Salamanca, Spain. ; Center for Animal Resources and Development, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811 Japan. ; Laboratory for Chromosome Segregation, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25533956" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Cycle Proteins/metabolism ; Centromere/metabolism ; Chromosomal Proteins, Non-Histone/deficiency/genetics/*metabolism ; *Conserved Sequence ; Female ; Humans ; Infertility/genetics/metabolism ; Kinetochores/*metabolism ; Male ; *Meiosis ; Mice ; Molecular Sequence Data ; Protein-Serine-Threonine Kinases/metabolism ; Proto-Oncogene Proteins/metabolism ; Saccharomyces cerevisiae Proteins/metabolism ; Schizosaccharomyces pombe Proteins/metabolism
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  • 6
    Publication Date: 2014-12-24
    Description: Broadly, tissue regeneration is achieved in two ways: by proliferation of common differentiated cells and/or by deployment of specialized stem/progenitor cells. Which of these pathways applies is both organ- and injury-specific. Current models in the lung posit that epithelial repair can be attributed to cells expressing mature lineage markers. By contrast, here we define the regenerative role of previously uncharacterized, rare lineage-negative epithelial stem/progenitor (LNEP) cells present within normal distal lung. Quiescent LNEPs activate a DeltaNp63 (a p63 splice variant) and cytokeratin 5 remodelling program after influenza or bleomycin injury in mice. Activated cells proliferate and migrate widely to occupy heavily injured areas depleted of mature lineages, at which point they differentiate towards mature epithelium. Lineage tracing revealed scant contribution of pre-existing mature epithelial cells in such repair, whereas orthotopic transplantation of LNEPs, isolated by a definitive surface profile identified through single-cell sequencing, directly demonstrated the proliferative capacity and multipotency of this population. LNEPs require Notch signalling to activate the DeltaNp63 and cytokeratin 5 program, and subsequent Notch blockade promotes an alveolar cell fate. Persistent Notch signalling after injury led to parenchymal 'micro-honeycombing' (alveolar cysts), indicative of failed regeneration. Lungs from patients with fibrosis show analogous honeycomb cysts with evidence of hyperactive Notch signalling. Our findings indicate that distinct stem/progenitor cell pools repopulate injured tissue depending on the extent of the injury, and the outcomes of regeneration or fibrosis may depend in part on the dynamics of LNEP Notch signalling.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312207/" 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/PMC4312207/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vaughan, Andrew E -- Brumwell, Alexis N -- Xi, Ying -- Gotts, Jeffrey E -- Brownfield, Doug G -- Treutlein, Barbara -- Tan, Kevin -- Tan, Victor -- Liu, Feng Chun -- Looney, Mark R -- Matthay, Michael A -- Rock, Jason R -- Chapman, Harold A -- F32 HL117600-01/HL/NHLBI NIH HHS/ -- R01 HL44712/HL/NHLBI NIH HHS/ -- U01 HL099995/HL/NHLBI NIH HHS/ -- U01 HL099999/HL/NHLBI NIH HHS/ -- U01 HL111054/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Jan 29;517(7536):621-5. doi: 10.1038/nature14112. Epub 2014 Dec 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco (UCSF), San Francisco, California 94143, USA. ; Department of Biochemistry, Stanford University School of Medicine and Howard Hughes Medical Institute, Stanford, California 94305, USA. ; Max Planck Institute for Evolutionary Anthropology, Department of Evolutionary Genetics, Deutscher Platz 6, 04103 Leipzig, Germany. ; Department of Anatomy, School of Medicine, University of California, San Francisco (UCSF), San Francisco, California 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25533958" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bleomycin ; Cell Lineage ; Cell Proliferation ; Cell Separation ; Cysts/metabolism/pathology ; Epithelial Cells/*cytology/metabolism/*pathology ; Female ; Humans ; Keratin-5/metabolism ; Lung/*cytology/*pathology/physiology ; Lung Injury/chemically induced/*pathology/virology ; Male ; Mice ; Orthomyxoviridae Infections/pathology/virology ; Phosphoproteins/genetics/metabolism ; *Re-Epithelialization ; Receptors, Notch/metabolism ; Signal Transduction ; Stem Cell Transplantation ; Stem Cells/*cytology/metabolism ; Trans-Activators/genetics/metabolism
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  • 7
    Publication Date: 2014-12-24
    Description: Despite three decades of successful, predominantly phenotype-driven discovery of the genetic causes of monogenic disorders, up to half of children with severe developmental disorders of probable genetic origin remain without a genetic diagnosis. Particularly challenging are those disorders rare enough to have eluded recognition as a discrete clinical entity, those with highly variable clinical manifestations, and those that are difficult to distinguish from other, very similar, disorders. Here we demonstrate the power of using an unbiased genotype-driven approach to identify subsets of patients with similar disorders. By studying 1,133 children with severe, undiagnosed developmental disorders, and their parents, using a combination of exome sequencing and array-based detection of chromosomal rearrangements, we discovered 12 novel genes associated with developmental disorders. These newly implicated genes increase by 10% (from 28% to 31%) the proportion of children that could be diagnosed. Clustering of missense mutations in six of these newly implicated genes suggests that normal development is being perturbed by an activating or dominant-negative mechanism. Our findings demonstrate the value of adopting a comprehensive strategy, both genome-wide and nationwide, to elucidate the underlying causes of rare genetic disorders.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Deciphering Developmental Disorders Study -- 098395/Wellcome Trust/United Kingdom -- 100140/Wellcome Trust/United Kingdom -- CZD/16/6/Chief Scientist Office/United Kingdom -- WT098051/Wellcome Trust/United Kingdom -- Department of Health/United Kingdom -- England -- Nature. 2015 Mar 12;519(7542):223-8. doi: 10.1038/nature14135. Epub 2014 Dec 24.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25533962" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Animals ; Carrier Proteins/genetics ; Child ; Child, Preschool ; Chromosomal Proteins, Non-Histone/genetics ; Chromosome Aberrations ; DEAD-box RNA Helicases/genetics ; DNA-Binding Proteins/genetics ; Developmental Disabilities/*diagnosis/*genetics ; Dynamin I/genetics ; Exome/genetics ; Female ; Gene Expression Regulation, Developmental ; Genes, Dominant/genetics ; Genome, Human/genetics ; Great Britain ; Guanine Nucleotide Exchange Factors/genetics ; Homeodomain Proteins/genetics ; Humans ; Infant ; Infant, Newborn ; Male ; Mutation, Missense/genetics ; Nerve Tissue Proteins/genetics ; Nuclear Proteins/genetics ; Parents ; Phosphoproteins/genetics ; Polycomb Repressive Complex 1/genetics ; Protein Phosphatase 2/genetics ; Protein-Serine-Threonine Kinases/genetics ; Rare Diseases/genetics ; Transcription Factors/genetics ; Transposases/genetics ; Zebrafish/genetics
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  • 8
    Publication Date: 2014-12-24
    Description: A distinctive feature of prokaryotic gene expression is the absence of 5'-capped RNA. In eukaryotes, 5',5'-triphosphate-linked 7-methylguanosine protects messenger RNA from degradation and modulates maturation, localization and translation. Recently, the cofactor nicotinamide adenine dinucleotide (NAD) was reported as a covalent modification of bacterial RNA. Given the central role of NAD in redox biochemistry, posttranslational protein modification and signalling, its attachment to RNA indicates that there are unknown functions of RNA in these processes and undiscovered pathways in RNA metabolism and regulation. The unknown identity of NAD-modified RNAs has so far precluded functional analyses. Here we identify NAD-linked RNAs from bacteria by chemo-enzymatic capture and next-generation sequencing (NAD captureSeq). Among those identified, specific regulatory small RNAs (sRNAs) and sRNA-like 5'-terminal fragments of certain mRNAs are particularly abundant. Analogous to a eukaryotic cap, 5'-NAD modification is shown in vitro to stabilize RNA against 5'-processing by the RNA-pyrophosphohydrolase RppH and against endonucleolytic cleavage by ribonuclease (RNase) E. The nudix phosphohydrolase NudC decaps NAD-RNA and thereby triggers RNase-E-mediated RNA decay, while being inactive against triphosphate-RNA. In vivo, approximately 13% of the abundant sRNA RNAI is NAD-capped in the presence, and approximately 26% in the absence, of functional NudC. To our knowledge, this is the first description of a cap-like structure and a decapping machinery in bacteria.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cahova, Hana -- Winz, Marie-Luise -- Hofer, Katharina -- Nubel, Gabriele -- Jaschke, Andres -- England -- Nature. 2015 Mar 19;519(7543):374-7. doi: 10.1038/nature14020. Epub 2014 Dec 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Pharmacy and Molecular Biotechnology (IPMB), Heidelberg University, 69120 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25533955" target="_blank"〉PubMed〈/a〉
    Keywords: Acid Anhydride Hydrolases/metabolism ; Endoribonucleases/metabolism ; Escherichia coli/*genetics ; Escherichia coli Proteins/metabolism ; Gene Expression Regulation, Bacterial/genetics ; NAD/*metabolism ; Pyrophosphatases/metabolism ; RNA Caps/*chemistry/isolation & purification/*metabolism ; RNA Stability ; RNA, Bacterial/*chemistry/*isolation & purification/metabolism ; Sequence Analysis
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  • 9
    Publication Date: 2014-12-24
    Description: Models derived from human pluripotent stem cells that accurately recapitulate neural development in vitro and allow for the generation of specific neuronal subtypes are of major interest to the stem cell and biomedical community. Notch signalling, particularly through the Notch effector HES5, is a major pathway critical for the onset and maintenance of neural progenitor cells in the embryonic and adult nervous system. Here we report the transcriptional and epigenomic analysis of six consecutive neural progenitor cell stages derived from a HES5::eGFP reporter human embryonic stem cell line. Using this system, we aimed to model cell-fate decisions including specification, expansion and patterning during the ontogeny of cortical neural stem and progenitor cells. In order to dissect regulatory mechanisms that orchestrate the stage-specific differentiation process, we developed a computational framework to infer key regulators of each cell-state transition based on the progressive remodelling of the epigenetic landscape and then validated these through a pooled short hairpin RNA screen. We were also able to refine our previous observations on epigenetic priming at transcription factor binding sites and suggest here that they are mediated by combinations of core and stage-specific factors. Taken together, we demonstrate the utility of our system and outline a general framework, not limited to the context of the neural lineage, to dissect regulatory circuits of differentiation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4336237/" 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/PMC4336237/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ziller, Michael J -- Edri, Reuven -- Yaffe, Yakey -- Donaghey, Julie -- Pop, Ramona -- Mallard, William -- Issner, Robbyn -- Gifford, Casey A -- Goren, Alon -- Xing, Jeffrey -- Gu, Hongcang -- Cacchiarelli, Davide -- Tsankov, Alexander M -- Epstein, Charles -- Rinn, John L -- Mikkelsen, Tarjei S -- Kohlbacher, Oliver -- Gnirke, Andreas -- Bernstein, Bradley E -- Elkabetz, Yechiel -- Meissner, Alexander -- F32 DK095537/DK/NIDDK NIH HHS/ -- HG006911/HG/NHGRI NIH HHS/ -- P01 GM099117/GM/NIGMS NIH HHS/ -- P01GM099117/GM/NIGMS NIH HHS/ -- U01 ES017155/ES/NIEHS NIH HHS/ -- U01ES017155/ES/NIEHS NIH HHS/ -- U54 HG006991/HG/NHGRI NIH HHS/ -- England -- Nature. 2015 Feb 19;518(7539):355-9. doi: 10.1038/nature13990. Epub 2014 Dec 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA [3] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA. ; Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 6997801, Israel. ; 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA. ; Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA. ; 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA [3] Center for Systems Biology and Center for Cancer Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ; Applied Bioinformatics, Center for Bioinformatics and Quantitative Biology Center, University of Tubingen, Tubingen 72076, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25533951" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Cell Differentiation/*genetics ; Cell Lineage/genetics ; Embryonic Stem Cells/*cytology/metabolism ; Epigenesis, Genetic/*genetics ; Epigenomics/*methods ; Humans ; Neural Stem Cells/*cytology/*metabolism ; RNA, Small Interfering/analysis/genetics ; Reproducibility of Results ; Transcription Factors/metabolism ; Transcription, Genetic/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2014-12-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tachibana-Konwalski, Kikue -- England -- Nature. 2015 Jan 22;517(7535):441-2. doi: 10.1038/nature14087. Epub 2014 Dec 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), 1030 Vienna, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25533954" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chromosomal Proteins, Non-Histone/*metabolism ; *Conserved Sequence ; Female ; Humans ; Kinetochores/*metabolism ; Male ; *Meiosis
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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