467 research outputs found

    Inferring stabilizing mutations from protein phylogenies : application to influenza hemagglutinin

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    One selection pressure shaping sequence evolution is the requirement that a protein fold with sufficient stability to perform its biological functions. We present a conceptual framework that explains how this requirement causes the probability that a particular amino acid mutation is fixed during evolution to depend on its effect on protein stability. We mathematically formalize this framework to develop a Bayesian approach for inferring the stability effects of individual mutations from homologous protein sequences of known phylogeny. This approach is able to predict published experimentally measured mutational stability effects (ΔΔG values) with an accuracy that exceeds both a state-of-the-art physicochemical modeling program and the sequence-based consensus approach. As a further test, we use our phylogenetic inference approach to predict stabilizing mutations to influenza hemagglutinin. We introduce these mutations into a temperature-sensitive influenza virus with a defect in its hemagglutinin gene and experimentally demonstrate that some of the mutations allow the virus to grow at higher temperatures. Our work therefore describes a powerful new approach for predicting stabilizing mutations that can be successfully applied even to large, complex proteins such as hemagglutinin. This approach also makes a mathematical link between phylogenetics and experimentally measurable protein properties, potentially paving the way for more accurate analyses of molecular evolution

    Factors Associated to Duration of Hepatitis A Outbreaks: Implications for Control

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    Even though hepatitis A mass vaccination effectiveness is high, outbreaks continue to occur. The aim of this study was to investigate the association between duration and characteristics of hepatitis A outbreaks. Hepatitis A (HA) outbreaks reported between 1991 and 2007 were studied. An outbreak was defined as ≥2 epidemiologically-linked cases with ≥1 case laboratory-confirmed by detection of HA immunoglobulin M (IgM) antibodies. Relationships between explanatory variables and outbreak duration were assessed by logistic regression. During the study period, 268 outbreaks (rate 2.45 per million persons-year) and 1396 cases (rate 1.28 per 105 persons-year) were reported. Factors associated with shorter duration were time to intervention (OR = 0.96; 95% CI: 0.94–0.98) and school setting (OR = 0.39; 95% CI: 0.16–0.92). In person-to-person transmission outbreaks only time to intervention was associated with shorter outbreak duration (OR = 0.96; 95% CI: 0.95–0.98). The only variables associated with shorter outbreak duration were early administration of IG or vaccine and a school setting. Timely reporting HA outbreaks was associated with outbreak duration. Making confirmed HA infections statutory reportable for clinical laboratories could diminish outbreak duration

    Macro-Climatic Distribution Limits Show Both Niche Expansion and Niche Specialization among C4 Panicoids

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    Grasses are ancestrally tropical understory species whose current dominance in warm open habitats is linked to the evolution of C4 photosynthesis. C4 grasses maintain high rates of photosynthesis in warm and water stressed environments, and the syndrome is considered to induce niche shifts into these habitats while adaptation to cold ones may be compromised. Global biogeographic analyses of C4 grasses have, however, concentrated on diversity patterns, while paying little attention to distributional limits. Using phylogenetic contrast analyses, we compared macro-climatic distribution limits among ~1300 grasses from the subfamily Panicoideae, which includes 4/5 of the known photosynthetic transitions in grasses. We explored whether evolution of C4 photosynthesis correlates with niche expansions, niche changes, or stasis at subfamily level and within the two tribes Paniceae and Paspaleae. We compared the climatic extremes of growing season temperatures, aridity, and mean temperatures of the coldest months. We found support for all the known biogeographic distribution patterns of C4 species, these patterns were, however, formed both by niche expansion and niche changes. The only ubiquitous response to a change in the photosynthetic pathway within Panicoideae was a niche expansion of the C4 species into regions with higher growing season temperatures, but without a withdrawal from the inherited climate niche. Other patterns varied among the tribes, as macro-climatic niche evolution in the American tribe Paspaleae differed from the pattern supported in the globally distributed tribe Paniceae and at family level.Fil: Aagesen, Lone. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Botánica Darwinion. Academia Nacional de Ciencias Exactas, Físicas y Naturales. Instituto de Botánica Darwinion; ArgentinaFil: Biganzoli, Fernando. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Métodos Cuantitativos y Sistemas de Información; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bena, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Botánica Darwinion. Academia Nacional de Ciencias Exactas, Físicas y Naturales. Instituto de Botánica Darwinion; ArgentinaFil: Godoy Bürki, Ana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Botánica Darwinion. Academia Nacional de Ciencias Exactas, Físicas y Naturales. Instituto de Botánica Darwinion; ArgentinaFil: Reinheimer, Renata. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; ArgentinaFil: Zuloaga, Fernando Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Botánica Darwinion. Academia Nacional de Ciencias Exactas, Físicas y Naturales. Instituto de Botánica Darwinion; Argentin

    Imprisonment and internment: Comparing penal facilities North and South

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    Recent references to the ‘warehouse prison’ in the United States and the prisión-depósito in Latin America seem to indicate that penal confinement in the western hemisphere has converged on a similar model. However, this article suggests otherwise. It contrasts penal facilities in North America and Latin America in terms of six interrelated aspects: regimentation; surveillance; isolation; supervision; accountability; and formalization. Quantitatively, control in North American penal facilities is assiduous (unceasing, persistent and intrusive), while in Latin America it is perfunctory (sporadic, indifferent and cursory). Qualitatively, North American penal facilities produce imprisonment (which enacts penal intervention through confinement), while in Latin America they produce internment (which enacts penal intervention through release). Closely entwined with this qualitative difference are distinct practices of judicial involvement in sentencing and penal supervision. Those practices, and the cultural and political factors that underpin them, represent an interesting starting point for the explanation of the contrasting nature of imprisonment and internment

    Intraspecific crosses resulting in the first occurrence of eight and nine B chromosomes in Prochilodus lineatus (Characiformes, Prochilodontidae)

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    B chromosomes are supernumerary elements present in about 15% of eukaryotic species and are most frequently heterochromatic, behave parasitically, show a transmission rate higher than standard (A) chromosomes, and can provoke harmful effects on carriers. In the current work, Prochilodus lineatus individuals carrying eight and nine B chromosomes were obtained by induced crossing performed involving breeders with different B chromosome numbers in their cells. The high B chromosome numbers found in the offspring were recorded for the first time in this species. The use of cytogenetic techniques applied in the present study revealed that regardless of the increase in number of B chromosomes in the genome of these individuals, those elements did not presented active genes, and showed their normal heterochromatic characteristic
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