58 research outputs found

    APOA5 Q97X Mutation Identified through homozygosity mapping causes severe hypertriglyceridemia in a Chilean consanguineous family

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    BACKGROUND: Severe hypertriglyceridemia (HTG) has been linked to defects in LPL, APOC2, APOA5, LMF1 and GBIHBP1 genes. However, a number of severe HTG cases are probably caused by as yet unidentified mutations. Very high triglyceride plasma levels (>112 mmol/L at diagnosis) were found in two sisters of a Chilean consanguineous family, which is strongly suggestive of a recessive highly penetrant mutation. The aim of this study was to determine the genetic locus responsible for the severe HTG in this family. METHODS: We carried out a genome-wide linkage study with nearly 300,000 biallelic markers (Illumina Human CytoSNP-12 panel). Using the homozygosity mapping strategy, we searched for chromosome regions with excess of homozygous genotypes in the affected cases compared to non-affected relatives. RESULTS: A large homozygous segment was found in the long arm of chromosome 11, with more than 2,500 consecutive homozygous SNP shared by the proband with her affected sister, and containing the APOA5/A4/C3/A1 cluster. Direct sequencing of the APOA5 gene revealed a known homozygous nonsense Q97X mutation (p.Gln97Ter) found in both affected sisters but not in non-affected relatives nor in a sample of unrelated controls. CONCLUSION: The Q97X mutation of the APOA5 gene in homozygous status is responsible for the severe hypertriglyceridemia in this family. We have shown that homozygosity mapping correctly pinpointed the genomic region containing the gene responsible for severe hypertriglyceridemia in this consanguineous Chilean famil

    Consumo e gĂȘnero: uma revisĂŁo da produção historiogrĂĄfica recente sobre a AmĂ©rica Latina no sĂ©culo XX

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    A partir de una revisiĂłn de la producciĂłn historiogrĂĄfica reciente que estudia el siglo XX, este artĂ­culo muestra la relevancia del gĂ©nero para la construcciĂłn de una historia del consumo en AmĂ©rica Latina. Con este objetivo, se enfoca el anĂĄlisis en tres lĂ­neas de investigaciĂłn que, desde una aproximaciĂłn interseccional, aportan nuevas miradas y preguntas: la primera destaca la dimensiĂłn polĂ­tica del consumo, centrĂĄndose en la relaciĂłn entre gĂ©nero y clase; la segunda aborda consumo y trabajo domĂ©stico, señalando el vĂ­nculo entre gĂ©nero y naciĂłn; y la tercera analiza cultura material y corporalidades, destacando la articulaciĂłn entre gĂ©nero y edad.Starting from a recent historiographical production’s revision studying the 20th Century, this article depicts the relevance of gender for the history of consumption-building in Latin America. Bearing that in mind, the analysis is geared to three researching lines, contributing with new perspectives and questions, as from an inter sectorial approach: the first one highlights the political dimension of consumption based upon the interaction between gender and class; the second addresses consumption and domestic work, displaying a link between gender and nation, and the third one analyses material culture and corporality emphasizing upon the articulation between gender and age.A partir de uma revisĂŁo da produção historiogrĂĄfica recente que estuda o sĂ©culo XX, este artigo mostra a relevĂąncia do gĂȘnero para a construção de uma histĂłria do consumo na AmĂ©rica Latina. Com esse objetivo, a anĂĄlise estĂĄ focada em trĂȘs linhas de pesquisa que, sob uma aproximação interseccional, contribuem com novos olhares e perguntas: a primeira destaca a dimensĂŁo polĂ­tica do consumo e foca-se na relação gĂȘnero e classe; a segunda aborda consumo e trabalho domĂ©stico, e sinaliza o vĂ­nculo entre gĂȘnero e nação; a terceira analisa cultura material e corporalidade, e destaca a articulação entre gĂȘnero e idade.Fil: PĂ©rez, InĂ©s. Universidad Nacional de Mar del Plata. Facultad de Humanidades. Departamento de Sociologia; Argentina. Universidad Nacional de Mar del Plata. Facultad de Humanidades. Departamento de Historia. Centro de Estudios HistĂłricos; Argentina. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - Mar del Plata; Argentin

    Natural disasters and indicators of social cohesion

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    Do adversarial environmental conditions create social cohesion? We provide new answers to this question by exploiting spatial and temporal variation in exposure to earthquakes across Chile. Using a variety of methods and controlling for a number of socio-economic variables, we find that exposure to earthquakes has a positive effect on several indicators of social cohesion. Social cohesion increases after a big earthquake and slowly erodes in periods where environmental conditions are less adverse. Our results contribute to the current debate on whether and how environmental conditions shape formal and informal institutions

    CARD15/NOD2 Is Required for Peyer's Patches Homeostasis in Mice

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    BACKGROUND: CARD15/NOD2 mutations are associated with susceptibility to Crohn's Disease (CD) and Graft Versus Host Disease (GVHD). CD and GVHD are suspected to be related with the dysfunction of Peyer's patches (PP) and isolated lymphoid follicles (LFs). Using a new mouse model invalidated for Card15/Nod2 (KO), we thus analysed the impact of the gene in these lymphoid formations together with the development of experimental colitis. METHODOLOGY/PRINCIPAL FINDINGS: At weeks 4, 12 and 52, the numbers of PPs and LFs were higher in KO mice while no difference was observed at birth. At weeks 4 and 12, the size and cellular composition of PPs were analysed by flow cytometry and immunohistochemistry. PPs of KO mice were larger with an increased proportion of M cells and CD4(+) T-cells. KO mice were also characterised by higher concentrations of TNFalpha, IFNgamma, IL12 and IL4 measured by ELISA. In contrast, little differences were found in the PP-free ileum and the spleen of KO mice. By using chamber experiments, we found that this PP phenotype is associated with an increased of both paracellular permeability and yeast/bacterial translocation. Finally, KO mice were more susceptible to the colitis induced by TNBS. CONCLUSIONS: Card15/Nod2 deficiency induces an abnormal development and function of the PPs characterised by an exaggerated immune response and an increased permeability. These observations provide a comprehensive link between the molecular defect and the Human CARD15/NOD2 associated disorders: CD and GVHD

    Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

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    Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

    Observing glacier elevation changes from spaceborne optical and radar sensors – an inter-comparison experiment using ASTER and TanDEM-X data

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    Observations of glacier mass changes are key to understanding the response of glaciers to climate change and related impacts, such as regional runoff, ecosystem changes, and global sea-level rise. Spaceborne optical and radar sensors make it possible to quantify glacier elevation changes, and thus multi-annual mass changes, on a regional and global scale. However, estimates from a growing number of studies show a wide range of results with differences often beyond uncertainty bounds. Here, we present the outcome of a community-based inter-comparison experiment using spaceborne optical stereo (ASTER) and synthetic aperture radar interferometry (TanDEM-X) data to estimate elevation changes for defined glaciers and target periods that pose different assessment challenges. Using provided or self-processed digital elevation models (DEMs) for five test sites, 12 research groups provided a total of 97 spaceborne elevation-change datasets using various processing strategies. Validation with airborne data showed that using an ensemble estimate is promising to reduce random errors from different instruments and processing methods, but still requires a more comprehensive investigation and correction of systematic errors. We found that scene selection, DEM processing, and co-registration have the biggest impact on the results. Other processing steps, such as treating spatial data voids, differences in survey periods, or radar penetration, can still be important for individual cases. Future research should focus on testing different implementations of individual processing steps (e.g. co-registration) and addressing issues related to temporal corrections, radar penetration, glacier area changes, and density conversion. Finally, there is a clear need for our community to develop best practices, use open, reproducible software, and assess overall uncertainty in order to enhance inter-comparison and empower physical process insights across glacier elevation-change studies
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