24 research outputs found

    Deformation microstructures of Barre granite: An optical, Sem and Tem study

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    New scanning electron microscope techniques have been developed for characterizing ductile deformation microstructures in felsic rocks. In addition, the thermomechanical history of the macroscopically undeformed Barre granite (Vermont, U.S.A.) has been reconstructed based on examination of deformation microstructures using optical microscopy, scanning electron microscopy, and transmission electron microscopy. The microstructures reveal three distinct events: 1. (1) a low-stress, high-temperature event that produced subgrains in feldspars, and subgrains and recrystallized grains in quartz;2. (2) a high-stress, low-temperature event that produced a high dislocation density in quartz and feldspars; and3. (3) a lowest-temperature event that produced cracks, oriented primarily along cleavage planes in feldspars, and parallel to the macroscopic rift in quartz. The first two events are believed to reflect various stages in the intrusion and cooling history of the pluton, and the last may be related to the last stages of cooling, or to later tectonism.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26275/1/0000360.pd

    Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits : A Multi-Ethnic Meta-Analysis of 45,891 Individuals

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    J. Kaprio, S. Ripatti ja M.-L. Lokki työryhmien jäseniä.Peer reviewe

    Blood and islet phenotypes indicate immunological heterogeneity in type 1 diabetes

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    Studies in type 1 diabetes indicate potential disease heterogeneity, notably in the rate of β-cell loss, responsiveness to immunotherapies, and, in limited studies, islet pathology. We sought evidence for different immunological phenotypes using two approaches. First, we defined blood autoimmune response phenotypes by combinatorial, multiparameter analysis of autoantibodies and autoreactive T-cell responses in 33 children/adolescents with newly diagnosed diabetes. Multidimensional cluster analysis showed two equal-sized patient agglomerations characterized by proinflammatory (interferon-γ–positive, multiautoantibody-positive) and partially regulated (interleukin-10–positive, pauci-autoantibody–positive) responses. Multiautoantibody-positive nondiabetic siblings at high risk of disease progression showed similar clustering. Additionally, pancreas samples obtained post mortem from a separate cohort of 21 children/adolescents with recently diagnosed type 1 diabetes were examined immunohistologically. This revealed two distinct types of insulitic lesions distinguishable by the degree of cellular infiltrate and presence of B cells that we termed “hyper-immune CD20Hi” and “pauci-immune CD20Lo.” Of note, subjects had only one infiltration phenotype and were partitioned by this into two equal-sized groups that differed significantly by age at diagnosis, with hyper-immune CD20Hi subjects being 5 years younger. These data indicate potentially related islet and blood autoimmune response phenotypes that coincide with and precede disease. We conclude that different immunopathological processes (endotypes) may underlie type 1 diabetes, carrying important implications for treatment and prevention strategies

    DNA methylation of lipid-related genes affects blood lipid levels: A genome-wide screen.

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    Background: Epigenetic mechanisms might be involved in the regulation of interindividual lipid level variability and thus may contribute to the cardiovascular risk profile. Aim of this study was to systematically investigate the association between genome-wide DNA methylation in whole blood and serum lipid levels of HDL-C, LDL-C, triglycerides (TG) and total cholesterol (TC).    Results: Genome-wide DNA methylation patterns were determined in blood samples of 1776 subjects of the KORA F4 cohort using the Infinium HumanMethylation450 BeadChip (Illumina). Associations between DNA methylation and lipid levels were analyzed using linear mixed-effects models with lipid levels as response. To correct for multiple comparisons, a genome-wide significance level of 1.1E-07 was used according to the Bonferroni procedure. We identified eleven lipid-related CpGs annotated to several genes including ABCG1. One CpG site located in ABCG1 was associated in opposite directions with both HDL-C ( coefficient=0.049, p=8.26E-17) and TG levels (=0.070, p=1.21E-27). Nine of the associations were confirmed by replication in KORA F3 (N=499) and InCHIANTI (N=472). Associations between TG levels and CpGs of two genes were also found in adipose but not in skin tissue of the MuTHER cohort, indicating tissue specificity. Expression analysis revealed that the association between ABCG1 methylation and lipid levels is partly mediated by the expression of ABCG1. The identified association between ABCG1 methylation and ABCG1 mRNA levels is possibly based on methylation-dependent transcription factor binding as observed in electrophoretic mobility shift assays. DNA methylation of ABCG1 was also associated with previous myocardial infarction in KORA F4 (odds ratio 1.15, 95%CI=1.06-1.25).     Conclusion: We found associations between DNA methylation and lipid levels for genes contributing to the modulation of cholesterol and fatty acid metabolism. The results indicate an epigenetic impact on metabolic regulation in humans and give new insights into the complex picture of lipid-related complex diseases
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