12 research outputs found

    INSIG1 influences obesity-related hypertriglyceridemia in humans

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    In our analysis of a quantitative trait locus (QTL) for plasma triglyceride (TG) levels [logarithm of odds (LOD) = 3.7] on human chromosome 7q36, we examined 29 single nucleotide polymorphisms (SNPs) across INSIG1, a biological candidate gene in the region. Insulin-induced genes (INSIGs) are feedback mediators of cholesterol and fatty acid synthesis in animals, but their role in human lipid regulation is unclear. In our cohort, the INSIG1 promoter SNP rs2721 was associated with TG levels (P = 2 × 10−3 in 1,560 individuals of the original linkage cohort, P = 8 × 10−4 in 920 unrelated individuals of the replication cohort, combined P = 9.9 × 10−6). Individuals homozygous for the T allele had 9% higher TG levels and 2-fold lower expression of INSIG1 in surgical liver biopsy samples when compared with individuals homozygous for the G allele. Also, the T allele showed additional binding of nuclear proteins from HepG2 liver cells in gel shift assays. Finally, the variant rs7566605 in INSIG2, the only homolog of INSIG1, enhances the effect of rs2721 (P = 0.00117). The variant rs2721 alone explains 5.4% of the observed linkage in our cohort, suggesting that additional, yet-undiscovered genes and sequence variants in the QTL interval also contribute to alterations in TG levels in humans

    Epigenetic Age Acceleration Assessed with Human White-Matter Images

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    Item does not contain fulltextThe accurate estimation of age using methylation data has proved a useful and heritable biomarker, with acceleration in epigenetic age predicting a number of age-related phenotypes. Measures of white matter integrity in the brain are also heritable and highly sensitive to both normal and pathological aging processes across adulthood. We consider the phenotypic and genetic interrelationships between epigenetic age acceleration and white matter integrity in humans. Our goal was to investigate processes that underlie interindividual variability in age-related changes in the brain. Using blood taken from a Mexican-American extended pedigree sample (n = 628; age = 23.28-93.11 years), epigenetic age was estimated using the method developed by Horvath (2013). For n = 376 individuals, diffusion tensor imaging scans were also available. The interrelationship between epigenetic age acceleration and global white matter integrity was investigated with variance decomposition methods. To test for neuroanatomical specificity, 16 specific tracts were additionally considered. We observed negative phenotypic correlations between epigenetic age acceleration and global white matter tract integrity (rhopheno = -0.119, p = 0.028), with evidence of shared genetic (rhogene = -0.463, p = 0.013) but not environmental influences. Negative phenotypic and genetic correlations with age acceleration were also seen for a number of specific white matter tracts, along with additional negative phenotypic correlations between granulocyte abundance and white matter integrity. These findings (i.e., increased acceleration in epigenetic age in peripheral blood correlates with reduced white matter integrity in the brain and shares common genetic influences) provide a window into the neurobiology of aging processes within the brain and a potential biomarker of normal and pathological brain aging.SIGNIFICANCE STATEMENT Epigenetic measures can be used to predict age with a high degree of accuracy and so capture acceleration in biological age, relative to chronological age. The white matter tracts within the brain are also highly sensitive to aging processes. We show that increased biological aging (measured using epigenetic data from blood samples) is correlated with reduced integrity of white matter tracts within the human brain (measured using diffusion tensor imaging) with data from a large sample of Mexican-American families. Given the family design of the sample, we are also able to demonstrate that epigenetic aging and white matter tract integrity also share common genetic influences. Therefore, epigenetic age may be a potential, and accessible, biomarker of brain aging

    Thermometry in Normal Liquid He-3 Using a Quartz Tuning Fork Viscometer

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    We have developed the use of quartz tuning forks for thermometry in normal liquid He-3. We have used a standard 32 kHz tuning fork to measure the viscosity of liquid He-3 over a wide temperature range, 6 mK <T <1.8 K, at SVP. For thermometry above 40 mK we used a calibrated ruthenium oxide resistor. At lower temperatures we used vibrating wire thermometry. Our data compare well with previous viscosity measurements, and we give a simple empirical formula which fits the viscosity data over the full temperature range. We discuss how tuning forks can be used as convenient thermometers in this range of temperatures with just a single parameter needed for calibration

    Emotional intelligence and its relationship to transformational leadership and key project manager competences

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    Key dimensions of project manager behaviors considered to be associated with successful project outcomes have included both appropriate collaborative behaviors and transformational leadership. More recently, emotional intelligence has been suggested as a unique area of individual differences that is likely to underpin sets of behaviors in this area. Based on a sample of 67 UK project managers, it was found that emotional intelligence ability measures and empathy explained additional variance in the project manager competences of teamwork, attentiveness, and managing conflict, and the transformational leadership behaviors of idealized influence and individualized consideration, after controlling for cognitive ability and personalit

    Surfactant adsorption layers at liquid—fluid interfaces.

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    Physico-chemical and formulation-induced veterinary drug-product bioinequivalencies

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