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  • 1
    Publication Date: 2016-06-15
    Description: Opioid use for pain management has dramatically increased, with little assessment of potential pathophysiological consequences for the primary pain condition. Here, a short course of morphine, starting 10 d after injury in male rats, paradoxically and remarkably doubled the duration of chronic constriction injury (CCI)-allodynia, months after morphine ceased. No...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 2
    Publication Date: 2015-06-27
    Description: The Palos Verdes Fault (PVF) is one of few active faults in Southern California that crosses the shoreline and can be studied using both terrestrial and subaqueous methodologies. To characterize the near-seafloor fault morphology, tectonic influences on continental slope sedimentary processes and Late Pleistocene–Holocene slip rate, a grid of high-resolution multibeam bathymetric data and chirp sub-bottom profiles were acquired with an autonomous underwater vehicle (AUV) along the main trace of PVF in water depths between 250 and 600 m. Radiocarbon dates were obtained from vibracores collected using a remotely operated vehicle (ROV) and ship-based gravity cores. The PVF is expressed as a well-defined seafloor lineation marked by subtle along-strike bends. Right-stepping transtensional bends exert first-order control on sediment flow dynamics and the spatial distribution of Holocene depocenters; deformed strata within a small pull-apart basin record punctuated growth faulting associated with at least three Holocene surface ruptures. An upper (shallower) landslide scarp, a buried sedimentary mound, and a deeper scarp have been right-laterally offset across the PVF by 55±5, 52±4 m and 39±8, respectively. The ages of the upper scarp and buried mound are approximately 31 ka; the age of the deeper scarp is bracketed to 17–24 ka. These three piercing points yield an average Late Pleistocene–Present slip rate of 1.4–2.9 mm/yr and a best estimate of 1.6–1.9 mm/yr. The deformation observed along the PVF is characteristic of strike-slip faulting and accounts for 20–30% of the total right-lateral slip-budget accommodated offshore southern California.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 3
    Publication Date: 2016-01-23
    Description: Article A material weakly linking two superconductors may itself exhibit superconductivity whilst its material properties strongly influence the nature of the supercurrent. Here, the authors identify a supercurrent with p -wave symmetry in such a Josephson junction made of topologically non-trivial material. Nature Communications doi: 10.1038/ncomms10303 Authors: J. Wiedenmann, E. Bocquillon, R. S. Deacon, S. Hartinger, O. Herrmann, T. M. Klapwijk, L. Maier, C. Ames, C. Brüne, C. Gould, A. Oiwa, K. Ishibashi, S. Tarucha, H. Buhmann, L. W. Molenkamp
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 4
    Publication Date: 2011-03-02
    Description: A 6.9 million-feature oligonucleotide array of the human transcriptome [Glue Grant human transcriptome (GG-H array)] has been developed for high-throughput and cost-effective analyses in clinical studies. This array allows comprehensive examination of gene expression and genome-wide identification of alternative splicing as well as detection of coding SNPs and noncoding transcripts. The performance of the array was examined and compared with mRNA sequencing (RNA-Seq) results over multiple independent replicates of liver and muscle samples. Compared with RNA-Seq of 46 million uniquely mappable reads per replicate, the GG-H array is highly reproducible in estimating gene and exon abundance. Although both platforms detect similar expression changes at the gene level, the GG-H array is more sensitive at the exon level. Deeper sequencing is required to adequately cover low-abundance transcripts. The array has been implemented in a multicenter clinical program and has generated high-quality, reproducible data. Considering the clinical trial requirements of cost, sample availability, and throughput, the GG-H array has a wide range of applications. An emerging approach for large-scale clinical genomic studies is to first use RNA-Seq to the sufficient depth for the discovery of transcriptome elements relevant to the disease process followed by high-throughput and reliable screening of these elements on thousands of patient samples using custom-designed arrays.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 5
    Publication Date: 2011-08-18
    Description: The majority of outer membrane proteins (OMPs) from Gram-negative bacteria and many of mitochondria and chloroplasts are β-barrels. Insertion and assembly of these proteins are catalyzed by the Omp85 protein family in a seemingly conserved process. All members of this family exhibit a characteristic N-terminal polypeptide-transport–associated (POTRA) and a C-terminal 16-stranded β-barrel domain. In plants, two phylogenetically distinct and essential Omp85's exist in the chloroplast outer membrane, namely Toc75-III and Toc75-V. Whereas Toc75-V, similar to the mitochondrial Sam50, is thought to possess the original bacterial function, its homolog, Toc75-III, evolved to the pore-forming unit of the TOC translocon for preprotein import. In all current models of OMP biogenesis and preprotein translocation, a topology of Omp85 with the POTRA domain in the periplasm or intermembrane space is assumed. Using self-assembly GFP-based in vivo experiments and in situ topology studies by electron cryotomography, we show that the POTRA domains of both Toc75-III and Toc75-V are exposed to the cytoplasm. This unexpected finding explains many experimental observations and requires a reevaluation of current models of OMP biogenesis and TOC complex function.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 6
    Publication Date: 2013-02-22
    Description: Pathogens often infect hosts through collective actions: they secrete growth-promoting compounds or virulence factors, or evoke host reactions that fuel the colonization of the host. Such behaviours are vulnerable to the rise of mutants that benefit from the collective action without contributing to it; how these behaviours can be evolutionarily stable is not well understood. We address this question using the intestinal pathogen Salmonella enterica serovar Typhimurium (hereafter termed S. typhimurium), which manipulates its host to induce inflammation, and thereby outcompetes the commensal microbiota. Notably, the virulence factors needed for host manipulation are expressed in a bistable fashion, leading to a slow-growing subpopulation that expresses virulence genes, and a fast-growing subpopulation that is phenotypically avirulent. Here we show that the expression of the genetically identical but phenotypically avirulent subpopulation is essential for the evolutionary stability of virulence in this pathogen. Using a combination of mathematical modelling, experimental evolution and competition experiments we found that within-host evolution leads to the emergence of mutants that are genetically avirulent and fast-growing. These mutants are defectors that exploit inflammation without contributing to it. In infection experiments initiated with wild-type S. typhimurium, defectors increase only slowly in frequency. In a genetically modified S. typhimurium strain in which the phenotypically avirulent subpopulation is reduced in size, defectors rise more rapidly, inflammation ceases prematurely, and S. typhimurium is quickly cleared from the gut. Our results establish that host manipulation by S. typhimurium is a cooperative trait that is vulnerable to the rise of avirulent defectors; the expression of a phenotypically avirulent subpopulation that grows as fast as defectors slows down this process, and thereby promotes the evolutionary stability of virulence. This points to a key role of bistable virulence gene expression in stabilizing cooperative virulence and may lead the way to new approaches for controlling pathogens.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Diard, Mederic -- Garcia, Victor -- Maier, Lisa -- Remus-Emsermann, Mitja N P -- Regoes, Roland R -- Ackermann, Martin -- Hardt, Wolf-Dietrich -- England -- Nature. 2013 Feb 21;494(7437):353-6. doi: 10.1038/nature11913.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Microbiology, ETH Zurich, Wolfgang-Pauli-Str. 10, 8093 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23426324" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Host-Pathogen Interactions ; Inflammation/microbiology/pathology ; Intestines/microbiology ; Mice ; Mice, Inbred C57BL ; Mutation ; *Phenotype ; Salmonella Infections/microbiology/prevention & control/transmission ; Salmonella typhimurium/genetics/growth & development/*pathogenicity ; Virulence/genetics/physiology ; Virulence Factors/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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  • 7
    Publication Date: 2012-06-23
    Description: The shell structure of atomic nuclei is associated with 'magic numbers' and originates in the nearly independent motion of neutrons and protons in a mean potential generated by all nucleons. During beta(+)-decay, a proton transforms into a neutron in a previously not fully occupied orbital, emitting a positron-neutrino pair with either parallel or antiparallel spins, in a Gamow-Teller or Fermi transition, respectively. The transition probability, or strength, of a Gamow-Teller transition depends sensitively on the underlying shell structure and is usually distributed among many states in the neighbouring nucleus. Here we report measurements of the half-life and decay energy for the decay of (100)Sn, the heaviest doubly magic nucleus with equal numbers of protons and neutrons. In the beta-decay of (100)Sn, a large fraction of the strength is observable because of the large decay energy. We determine the largest Gamow-Teller strength so far measured in allowed nuclear beta-decay, establishing the 'superallowed' nature of this Gamow-Teller transition. The large strength and the low-energy states in the daughter nucleus, (100)In, are well reproduced by modern, large-scale shell model calculations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hinke, C B -- Bohmer, M -- Boutachkov, P -- Faestermann, T -- Geissel, H -- Gerl, J -- Gernhauser, R -- Gorska, M -- Gottardo, A -- Grawe, H -- Grebosz, J L -- Krucken, R -- Kurz, N -- Liu, Z -- Maier, L -- Nowacki, F -- Pietri, S -- Podolyak, Zs -- Sieja, K -- Steiger, K -- Straub, K -- Weick, H -- Wollersheim, H-J -- Woods, P J -- Al-Dahan, N -- Alkhomashi, N -- Atac, A -- Blazhev, A -- Braun, N F -- Celikovic, I T -- Davinson, T -- Dillmann, I -- Domingo-Pardo, C -- Doornenbal, P C -- de France, G -- Farrelly, G F -- Farinon, F -- Goel, N -- Habermann, T C -- Hoischen, R -- Janik, R -- Karny, M -- Kaskas, A -- Kojouharov, I M -- Kroll, Th -- Litvinov, Y -- Myalski, S -- Nebel, F -- Nishimura, S -- Nociforo, C -- Nyberg, J -- Parikh, A R -- Prochazka, A -- Regan, P H -- Rigollet, C -- Schaffner, H -- Scheidenberger, C -- Schwertel, S -- Soderstrom, P-A -- Steer, S J -- Stolz, A -- Strmen, P -- England -- Nature. 2012 Jun 20;486(7403):341-5. doi: 10.1038/nature11116.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Physik Department E12, Technische Universitat Munchen, D-85748 Garching, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22722192" target="_blank"〉PubMed〈/a〉
    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: 2013-03-01
    Description: Circular RNAs (circRNAs) in animals are an enigmatic class of RNA with unknown function. To explore circRNAs systematically, we sequenced and computationally analysed human, mouse and nematode RNA. We detected thousands of well-expressed, stable circRNAs, often showing tissue/developmental-stage-specific expression. Sequence analysis indicated important regulatory functions for circRNAs. We found that a human circRNA, antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as), is densely bound by microRNA (miRNA) effector complexes and harbours 63 conserved binding sites for the ancient miRNA miR-7. Further analyses indicated that CDR1as functions to bind miR-7 in neuronal tissues. Human CDR1as expression in zebrafish impaired midbrain development, similar to knocking down miR-7, suggesting that CDR1as is a miRNA antagonist with a miRNA-binding capacity ten times higher than any other known transcript. Together, our data provide evidence that circRNAs form a large class of post-transcriptional regulators. Numerous circRNAs form by head-to-tail splicing of exons, suggesting previously unrecognized regulatory potential of coding sequences.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Memczak, Sebastian -- Jens, Marvin -- Elefsinioti, Antigoni -- Torti, Francesca -- Krueger, Janna -- Rybak, Agnieszka -- Maier, Luisa -- Mackowiak, Sebastian D -- Gregersen, Lea H -- Munschauer, Mathias -- Loewer, Alexander -- Ziebold, Ulrike -- Landthaler, Markus -- Kocks, Christine -- le Noble, Ferdinand -- Rajewsky, Nikolaus -- England -- Nature. 2013 Mar 21;495(7441):333-8. doi: 10.1038/nature11928. Epub 2013 Feb 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Systems Biology of Gene Regulatory Elements, Max-Delbruck-Center for Molecular Medicine, Robert-Rossle-Strasse 10, 13125 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23446348" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autoantigens/genetics/metabolism ; Binding Sites ; Brain/metabolism ; Caenorhabditis elegans/genetics/metabolism ; Cell Line ; Conserved Sequence ; Female ; *Gene Expression Regulation ; HEK293 Cells ; Humans ; Male ; Mice ; MicroRNAs/genetics/metabolism ; Nerve Tissue Proteins/genetics/metabolism ; RNA/genetics/*metabolism ; Zebrafish/embryology/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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  • 9
    Publication Date: 2015-03-15
    Description: Sepsis is a frequently fatal condition characterized by an uncontrolled and harmful host reaction to microbial infection. Despite the prevalence and severity of sepsis, we lack a fundamental grasp of its pathophysiology. Here we report that the cytokine interleukin-3 (IL-3) potentiates inflammation in sepsis. Using a mouse model of abdominal sepsis, we showed that innate response activator B cells produce IL-3, which induces myelopoiesis of Ly-6C(high) monocytes and neutrophils and fuels a cytokine storm. IL-3 deficiency protects mice against sepsis. In humans with sepsis, high plasma IL-3 levels are associated with high mortality even after adjusting for prognostic indicators. This study deepens our understanding of immune activation, identifies IL-3 as an orchestrator of emergency myelopoiesis, and reveals a new therapeutic target for treating sepsis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376966/" 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/PMC4376966/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weber, Georg F -- Chousterman, Benjamin G -- He, Shun -- Fenn, Ashley M -- Nairz, Manfred -- Anzai, Atsushi -- Brenner, Thorsten -- Uhle, Florian -- Iwamoto, Yoshiko -- Robbins, Clinton S -- Noiret, Lorette -- Maier, Sarah L -- Zonnchen, Tina -- Rahbari, Nuh N -- Scholch, Sebastian -- Klotzsche-von Ameln, Anne -- Chavakis, Triantafyllos -- Weitz, Jurgen -- Hofer, Stefan -- Weigand, Markus A -- Nahrendorf, Matthias -- Weissleder, Ralph -- Swirski, Filip K -- 5R01HL095612/HL/NHLBI NIH HHS/ -- R01 HL095612/HL/NHLBI NIH HHS/ -- R56 AI104695/AI/NIAID NIH HHS/ -- R56-AI104695/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2015 Mar 13;347(6227):1260-5. doi: 10.1126/science.aaa4268.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Department of Visceral, Thoracic and Vascular Surgery, Technische Universitat Dresden, Dresden, Germany. fswirski@mgh.harvard.edu georg.weber@uniklinikum-dresden.de. ; Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. ; Department of Anesthesiology, University of Heidelberg, Heidelberg, Germany. ; Department of Visceral, Thoracic and Vascular Surgery, Technische Universitat Dresden, Dresden, Germany. ; Department of Clinical Pathobiochemistry and Institute for Clinical Chemistry and Laboratory Medicine, Technische Universitat Dresden, Dresden, Germany. ; Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. ; Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. fswirski@mgh.harvard.edu georg.weber@uniklinikum-dresden.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25766237" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocyte Subsets/immunology ; Cytokines/immunology/metabolism ; Disease Models, Animal ; Humans ; Inflammation ; Interleukin-3/blood/*immunology/metabolism ; Lipopolysaccharides/immunology ; Lymphoid Tissue/immunology ; Mice ; Mice, Inbred BALB C ; Monocytes/immunology ; Myelopoiesis ; Neutrophils/immunology ; Peritonitis/immunology/pathology ; Prognosis ; Sepsis/*immunology/mortality/pathology/therapy
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2012-12-25
    Description: The Lucia Chica channel system is an avulsion belt with four adjacent channels that progressively avulsed to the north-east from a single, upslope feeder channel. Avulsion occurred from underfilled channels, leaving open channels that were reactivated by flows stripped from younger, adjacent channels. Differences in relief (height from channel thalweg to levée crest), sinuosity and levée stratigraphy between adjacent channels correspond to relative channel age, and indicate a change in channel morphology and architecture with time. Potential triggers for the change over time include differences in gradient, flow behaviour and characteristics, and channel evolution. Gradient does not appear to be a major control on channel formation and avulsion because adjacent channels formed on the same gradient. Based on available ultra-high-resolution remote imaging obtained with an Autonomous Underwater Vehicle, differences in adjacent channel morphology are interpreted to be primarily a result of differences in channel maturity. The interpreted sequence of channel maturity involves erosional channel inception through scouring and incipient channels (defined by linear trains of scours) prior to development of continuous thalwegs. Channel narrowing, formation and growth of levées, increasing channel relief and development of sinuosity occurred as channels evolved. The evolutionary sequence interpreted from the high-resolution Lucia Chica dataset provides a unique perspective on intrinsic controls of architecture for single channel elements. In addition to helping bridge the gap between outcrop and industry-standard reflection-seismic data resolutions and scopes, interpretations in this study also expose potential problems with hierarchical classifications in three-dimensional imaging of distributary systems, and provide potentially important analogues for evolutionary morphologies not resolved in other deep-water channel systems.
    Print ISSN: 0037-0746
    Electronic ISSN: 1365-3091
    Topics: Geosciences
    Published by Wiley
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