6 research outputs found

    The role of T cell subsets and cytokines in the regulation of intracellular bacterial infection

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    Cellular immune responses are a critical part of the host's defense against intracellular bacterial infections. Immunity to Brucella abortus crucially depends on antigen-specific T cell-mediated activation of macrophages, which are the major effectors of cell-mediated killing of this organism. T lymphocytes that proliferate in response to B. abortus were characterized for phenotype and cytokine activity. Human, murine, and bovine T lymphocytes exhibited a type 1 cytokine profile, suggesting an analogous immune response in these different hosts. In vivo protection afforded by a particular cell type is dependent on the antigen presented and the mechanism of antigen presentation. Studies using MHC class I and class II knockout mice infected with B. abortus have demonstrated that protective immunity to brucellosis is especially dependent on CD8+ T cells. To target MHC class I presentation we transfected ex vivo a murine macrophage cell line with B. abortus genes and adoptively transferred them to BALB/c mice. These transgenic macrophage clones induced partial protection in mice against experimental brucellosis. Knowing the cells required for protection, vaccines can be designed to activate the protective T cell subset. Lastly, as a new strategy for priming a specific class I-restricted T cell response in vivo, we used genetic immunization by particle bombardment-mediated gene transfe

    Non-volant mammals of Carlos Botelho State Park, Paranapiacaba Forest Continuum

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    A Mata Atlântica é o bioma melhor conhecido em relação à mastofauna no Brasil, contudo ainda assim apresenta uma série de lacunas de conhecimento sobre a persistência e distribuição de espécies, o que representa um risco adicional à conservação de mamíferos. Neste trabalho, através da coleta de dados por diferentes métodos - armadilhas fotográficas, censos diurnos, registro de vestígios, armadilhas de queda e captura viva - ao longo de oito anos (2004-2012), foi realizado o inventário da mastofauna não voadora do Parque Estadual Carlos Botelho (SP). No total foram registradas 53 espécies, sendo 12 espécies ameaçadas regionalmente e uma exótica (Lepus europaeus), com a presença da maioria dos mamíferos esperados para o Continuum Florestal da Serra do Paranapiacaba. A comunidade de mamíferos não voadores quase completa, e a presença de espécies ameaçadas reforçam o papel desta área protegida para a conservação de mamíferos na Mata Atlântica. Embora, a extinção local de uma espécie, Tayassu pecari, alerte para a necessidade de medidas efetivas de proteção.The Atlantic Forest is one of the most studied Brazilian biomes in relation to its mammalian fauna. However, there is still a series of gaps of knowledge about the distribution and persistence of some of these species which prevents taking adequate conservation measures to better protect the mammals. In order to make the inventory of the non-volant mammalian fauna of the Carlos Botelho State Park (SP), we compiled data of camera trapping, diurnal census, track records, pitfall and live trapping collected over 8 years (2004-2012). We registered a total of 53 species, of which 12 are regionally threatened and one is an exotic species (Lepus europaeus), including the presence of most mammal species expected for the Paranapiacaba Forest Continuum. The high non-volant mammals species richness allied to the presence of threatened species, strengthen the role of this protected area for mammal conservation in the Atlantic Forest. Although, the local extinction of one species, Tayassu pecari, alert to the need for effective measures of protection

    A saturated map of common genetic variants associated with human height

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    Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries

    A saturated map of common genetic variants associated with human height.

    No full text
    Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes <sup>1</sup> . Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel <sup>2</sup> ) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries
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