2,042 research outputs found

    Mechanism of Sugar Transport by a Phosphoenolpyruvate-Dependent Phosphotransferase

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    X-Ray Structure of a Mammalian Stearoyl-Coa Desaturase-1

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    Black hole mergers: the first light

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    The coalescence of supermassive black hole binaries occurs via the emission of gravitational waves, that can impart a substantial recoil to the merged black hole. We consider the energy dissipation, that results if the recoiling black hole is surrounded by a thin circumbinary disc. Our results differ significantly from those of previous investigations. We show analytically that the dominant source of energy is often potential energy, released as gas in the outer disc attempts to circularize at smaller radii. Thus, dimensional estimates, that include only the kinetic energy gained by the disc gas, underestimate the real energy loss. This underestimate can exceed an order of magnitude, if the recoil is directed close to the disc plane. We use three dimensional Smooth Particle Hydrodynamics (SPH) simulations and two dimensional finite difference simulations to verify our analytic estimates. We also compute the bolometric light curve, which is found to vary strongly depending upon the kick angle. A prompt emission signature due to this mechanism may be observable for low mass (10^6 Solar mass) black holes whose recoil velocities exceed about 1000 km/s. Emission at earlier times can mainly result from the response of the disc to the loss of mass, as the black holes merge. We derive analytically the condition for this to happen.Comment: 16 pages, accepted by MNRAS. Animations of the simulations are available at http://jilawww.colorado.edu/~pja/recoil.htm

    X-ray structure of a soluble Rieske-type ferredoxin from Mus musculus

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    The X-ray crystal structure of a soluble Rieske ferredoxin from M. musculus was solved at 2.07 Å resolution, revealing an iron–sulfur cluster-binding domain with similar architecture to the Rieske-type domains of bacterial aromatic dioxygenases. The ferredoxin was also shown to be capable of accepting electrons from both eukaryotic and prokaryotic oxidoreductases

    Structure of a Membrane-Embedded Prenyltransferase Homologous to UBIAD1

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    Membrane-embedded prenyltransferases from the UbiA family catalyze the Mg2+-dependent transfer of a hydrophobic polyprenyl chain onto a variety of acceptor molecules and are involved in the synthesis of molecules that mediate electron transport, including Vitamin K and Coenzyme Q. In humans, missense mutations to the protein UbiA prenyltransferase domain-containing 1 (UBIAD1) are responsible for Schnyder crystalline corneal dystrophy, which is a genetic disease that causes blindness. Mechanistic understanding of this family of enzymes has been hampered by a lack of three-dimensional structures. We have solved structures of a UBIAD1 homolog from Archaeoglobus fulgidus, AfUbiA, in an unliganded form and bound to Mg2+ and two different isoprenyl diphosphates. Functional assays on MenA, a UbiA family member from E. coli, verified the importance of residues involved in Mg2+ and substrate binding. The structural and functional studies led us to propose a mechanism for the prenyl transfer reaction. Disease-causing mutations in UBIAD1 are clustered around the active site in AfUbiA, suggesting the mechanism of catalysis is conserved between the two homologs

    Differences in Accumulation and Virulence Determine the Outcome of Competition during Tobacco etch virus Coinfection

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    Understanding the evolution of virulence for RNA viruses is essential for developing appropriate control strategies. Although it has been usually assumed that virulence is a consequence of within-host replication of the parasite, viral strains may be highly virulent without experiencing large accumulation as a consequence of immunopathological host responses. Using two strains of Tobacco etch potyvirus (TEV) that show a negative relationship between virulence and accumulation rate, we first explored the evolution of virulence and fitness traits during simple and mixed infections. Short-term evolution experiments initiated with each strain independently confirmed the genetic and evolutionary stability of virulence and viral load, although infectivity significantly increased for both strains. Second, competition experiments between hypo- and hypervirulent TEV strains have shown that the outcome of competition is driven by differences in replication rate. A simple mathematical model has been developed to analyze the dynamics of these two strains during coinfection. The model qualitatively reproduced the experimental results using biologically meaningful parameters. Further analyses of the model also revealed a wide parametric region in which a low-fitness but hypovirulent virus can still outcompete a high-fitness but hypervirulent one. These results provide additional support to the observation that virulence and within-host replication may not necessarily be strongly tied in plant RNA viruses

    Prevalence and trends of markers of hepatitis B virus, hepatitis C virus and human Immunodeficiency virus in Argentine blood donors

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    BACKGROUND: Transfusion-transmitted infections are a major problem associated with blood transfusion. The aim of this study was to determine prevalence and trends of HBV, HCV and HIV in blood donors in Argentina. METHODS: A retrospective study was carried out in blood donors of 27 transfusion centers covering the whole country over a period of eight years (2004-2011). Serologic screening assays for HBsAg, anti-HBc, anti-HCV, and anti-HIV were performed in all centers and nucleic acid amplification testing (NAT) was performed in 2 out of the 27 centers. RESULTS: The 2,595,852 samples tested nationwide from 2004 to 2011 showed that the prevalence of HBsAg decreased from 0.336% to 0.198% (p < 0.0001), that of anti-HBc from 2.391% to 2.007% (p < 0.0001), that of anti-HCV from 0.721% to 0.460%, (p < 0.0001) and that of anti-HIV from 0.208% to 0.200 (p = 0.075). The prevalence of HBV, HCV and HIV was unevenly distributed among the different regions of the country. Two out of 74,838 screening- negative samples were positive in NAT assays (1 HIV-RNA and 1 HCV-RNA); moreover, HBV-DNA, HCV-RNA and HIV-RNA were detected in 60.29, 24.54 and 66.67% of screening-positive samples of the corresponding assays. As regards donors age, positive HBV-DNA and HCV-RNA donors were significantly older than healthy donors (46.6, 50.5 and 39.5 y respectively, p < 0.001). CONCLUSIONS: Argentina has a low prevalence of HBsAg, anti-HCV and anti-HIV in blood donors, with a decreasing trend for HBsAg, anti-HBc and anti-HCV but not for anti-HIV over the last 8 years. The uneven distribution of transfusion-transmitted infections prevalence among the different regions of the country highlights the need to implement regional awareness campaigns and prevention. The discrepancy between samples testing positive for screening assays and negative for NAT assays highlights the problem of blood donors who test repeatedly reactive in screening assays but are not confirmed as positive upon further testing. The uneven distribution of age between healthy donors and NAT-positive donors could be related to changes in risks of these pathogens in the general population and might be attributed to a longer exposure to transmission risk factors in elderly people.Fil: Flichman, Diego Martin. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Blejer, Jorgelina L.. Fundación Hemocentro; ArgentinaFil: Livellara, Beatriz I.. Hospital Italiano; ArgentinaFil: Ré, Viviana Elizabeth. Universidad Nacional de Cordoba. Facultad de Medicina. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bartoli, Sonia. Centro regional de Hemoterapia Jujuy; ArgentinaFil: Bustos, Juan A.. Banco de sangre San Jorge; ArgentinaFil: Ansola, Claudia P.. Provincia de Mendoza. Servicio de Hemoterapia; ArgentinaFil: Hidalgo, Susana. Hospital Dr. Enrique Vera Barros; ArgentinaFil: Cerda, Martín E.. Hospital Dr. Lucio Molas; ArgentinaFil: Levin, Alicia E.. Provincia de Mendoza. Servicio de Hemoterapia; ArgentinaFil: Huenul, Adriana. Hospital Artémides Zatti; ArgentinaFil: Riboldi, Victoria. Hospital Regional Río Gallegos; ArgentinaFil: Treviño, Elena M. C.. Universidad Nacional de Córdoba; ArgentinaFil: Salamone, Horacio J.. Fundación Favaloro; ArgentinaFil: Nuñez, Felix A.. Hospital Italiano; ArgentinaFil: Fernández, Robert J.. Fundación Hemocentro; ArgentinaFil: Reybaud, Juan F.. Fundación Favaloro; ArgentinaFil: Campos, Rodolfo Hector. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

    Duodenal Anaerobutyricum soehngenii infusion stimulates GLP-1 production, ameliorates glycaemic control and beneficially shapes the duodenal transcriptome in metabolic syndrome subjects : a randomised double-blind placebo-controlled cross-over study

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    Objective Although gut dysbiosis is increasingly recognised as a pathophysiological component of metabolic syndrome (MetS), the role and mode of action of specific gut microbes in metabolic health remain elusive. Previously, we identified the commensal butyrogenic Anaerobutyricum soehngenii to be associated with improved insulin sensitivity in subjects with MetS. In this proof-of-concept study, we investigated the potential therapeutic effects of A. soehngenii L2-7 on systemic metabolic responses and duodenal transcriptome profiles in individuals with MetS. Design In this randomised double-blind placebo-controlled cross-over study, 12 male subjects with MetS received duodenal infusions of A. soehngenii/ placebo and underwent duodenal biopsies, mixed meal tests (6 hours postinfusion) and 24-hour continuous glucose monitoring. Results A. soehngenii treatment provoked a markedly increased postprandial excursion of the insulinotropic hormone glucagon-like peptide 1 (GLP-1) and an elevation of plasma secondary bile acids, which were positively associated with GLP-1 levels. Moreover, A. soehngenii treatment robustly shaped the duodenal expression of 73 genes, with the highest fold induction in the expression of regenerating islet-protein 1B (REG1B)-encoding gene. Strikingly, duodenal REG1B expression positively correlated with GLP-1 levels and negatively correlated with peripheral glucose variability, which was significantly diminished in the 24 hours following A. soehngenii intake. Mechanistically, Reg1B expression is induced upon sensing butyrate or bacterial peptidoglycan. Importantly, A. soehngenii duodenal administration was safe and well tolerated. Conclusions A single dose of A. soehngenii improves peripheral glycaemic control within 24 hours; it specifically stimulates intestinal GLP-1 production and REG1B expression. Further studies are needed to delineate the specific pathways involved in REG1B induction and function in insulin sensitivity.Peer reviewe

    Microbial contributions to the persistence of coral reefs

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    On contemplating the adaptive capacity of reef organisms to a rapidly changing environment, the microbiome offers significant and greatly unrecognised potential. Microbial symbionts contribute to the physiology, development, immunity and behaviour of their hosts, and can respond very rapidly to changing environmental conditions, providing a powerful mechanism for acclimatisation and also possibly rapid evolution of coral reef holobionts. Environmentally acquired fluctuations in the microbiome can have significant functional consequences for the holobiont phenotype upon which selection can act. Environmentally induced changes in microbial abundance may be analogous to host gene duplication, symbiont switching / shuffling as a result of environmental change can either remove or introduce raw genetic material into the holobiont; and horizontal gene transfer can facilitate rapid evolution within microbial strains. Vertical transmission of symbionts is a key feature of many reef holobionts and this would enable environmentally acquired microbial traits to be faithfully passed to future generations, ultimately facilitating microbiome-mediated transgenerational acclimatisation (MMTA) and potentially even adaptation of reef species in a rapidly changing climate. In this commentary, we highlight the capacity and mechanisms for MMTA in reef species, propose a modified Price equation as a framework for assessing MMTA and recommend future areas of research to better understand how microorganisms contribute to the transgenerational acclimatisation of reef organisms, which is essential if we are to reliably predict the consequences of global change for reef ecosystems

    A shift from distal to proximal neoplasia in the colon: a decade of polyps and CRC in Italy

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    <p>Abstract</p> <p>Background</p> <p>In the last years a trend towards proximalization of colorectal carcinomas (CRC) has been reported. This study aims to evaluate the distribution of CRC and adenomatous polyps (ADP) to establish the presence of proximalization and to assess the potential predictors.</p> <p>Methods</p> <p>We retrieved histology reports of colonic specimens excised during colonoscopy, considering the exams performed between 1997 and 2006 at Cuneo Hospital, Italy. We compared the proportion of proximal lesions in the period 1997-2001 and in the period 2002-2006.</p> <p>Results</p> <p>Neoplastic lesions were detected in 3087 people. Proximal CRC moved from 25.9% (1997-2001) to 30.0% (2002-2006). Adjusting for sex and age, the difference was not significant (OR 1.23; 95% CI: 0,95-1,58). The proximal ADP proportion increased from 19.2% (1997-2001) to 26.0% (2002-2006) (OR: 1.43; 95% CI: 1.17-1.89). The corresponding figures for advanced proximal ADP were 6.6% and 9.5% (OR: 1.48; 95% CI: 1.02-2.17). Adjusting for gender, age, diagnostic period, symptoms and number of polyps the prevalence of proximal advanced ADP was increased among people ≥ 70 years compared to those aged 55-69 years (OR 1.49; 95% CI: 1.032.16). The main predictor of proximal advanced neoplasia was the number of polyps detected per exam (> 1 polyp versus 1 polyp: considering all ADP: OR 2.16; 95% CI: 1.59-2.93; considering advanced ADP OR 1.63; 95% CI: 1.08-2.46). Adjusting for these factors, the difference between the two periods was no longer significant.</p> <p>Conclusions</p> <p>CRC do not proximalize while a trend towards a proximal shift in adenomas was observed among people ≥ 70 years.</p
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