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Sökning: WFRF:(Scheele C.) > (2010-2014)

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  • Nilsson, E., et al. (författare)
  • Altered DNA Methylation and Differential Expression of Genes Influencing Metabolism and Inflammation in Adipose Tissue From Subjects With Type 2 Diabetes
  • 2014
  • Ingår i: Diabetes. - : American Diabetes Association Inc.. - 0012-1797 .- 1939-327X. ; 63:9, s. 2962-2976
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetics, epigenetics, and environment may together affect the susceptibility for type 2 diabetes (T2D). Our aim was to dissect molecular mechanisms underlying T2D using genome-wide expression and DNA methylation data in adipose tissue from monozygotic twin pairs discordant for T2D and independent case-control cohorts. In adipose tissue from diabetic twins, we found decreased expression of genes involved in oxidative phosphorylation; carbohydrate, amino acid, and lipid metabolism; and increased expression of genes involved in inflammation and glycan degradation. The most differentially expressed genes included ELOVL6, GYS2, FADS1, SPP1 (OPN), CCL18, and IL1RN. We replicated these results in adipose tissue from an independent case-control cohort. Several candidate genes for obesity and T2D (e.g., IRS1 and VEGFA) were differentially expressed in discordant twins. We found a heritable contribution to the genome-wide DNA methylation variability in twins. Differences in methylation between monozygotic twin pairs discordant for T2D were subsequently modest. However, 15,627 sites, representing 7,046 genes including PPARG, KCNQ1, TCF7L2, and IRS1, showed differential DNA methylation in adipose tissue from unrelated subjects with T2D compared with control subjects. A total of 1,410 of these sites also showed differential DNA methylation in the twins discordant for T2D. For the differentially methylated sites, the heritability estimate was 0.28. We also identified copy number variants (CNVs) in monozygotic twin pairs discordant for T2D. Taken together, subjects with T2D exhibit multiple transcriptional and epigenetic changes in adipose tissue relevant to the development of the disease.
  • Timmons, James A., et al. (författare)
  • Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans
  • 2010
  • Ingår i: Journal of applied physiology. - 8750-7587 .- 1522-1601. ; 108:6, s. 1487-1496
  • Tidskriftsartikel (refereegranskat)abstract
    • Timmons JA, Knudsen S, Rankinen T, Koch LG, Sarzynski M, Jensen T, Keller P, Scheele C, Vollaard NB, Nielsen S, Akerstrom T, MacDougald OA, Jansson E, Greenhaff PL, Tarnopolsky MA, van Loon LJ, Pedersen BK, Sundberg CJ, Wahlestedt C, Britton SL, Bouchard C. Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans. J Appl Physiol 108: 1487-1496, 2010. First published February 4, 2010; doi:10.1152/japplphysiol.01295.2009.-A low maximal oxygen consumption ((V) over dotO(2max)) is a strong risk factor for premature mortality. Supervised endurance exercise training increases (V) over dotO(2max) with a very wide range of effectiveness in humans. Discovering the DNA variants that contribute to this heterogeneity typically requires substantial sample sizes. In the present study, we first use RNA expression profiling to produce a molecular classifier that predicts (V) over dotO(2max) training response. We then hypothesized that the classifier genes would harbor DNA variants that contributed to the heterogeneous (V) over dotO(2max) response. Two independent preintervention RNA expression data sets were generated (n = 41 gene chips) from subjects that underwent supervised endurance training: one identified and the second blindly validated an RNA expression signature that predicted change in (V) over dotO(2max) (""predictor"" genes). The HERITAGE Family Study (n = 473) was used for genotyping. We discovered a 29-RNA signature that predicted (V) over dotO(2max) training response on a continuous scale; these genes contained similar to 6 new single-nucleotide polymorphisms associated with gains in (V) over dotO(2max) in the HERITAGE Family Study. Three of four novel candidate genes from the HERITAGE Family Study were confirmed as RNA predictor genes (i.e., ""reciprocal"" RNA validation of a quantitative trait locus genotype), enhancing the performance of the 29-RNA-based predictor. Notably, RNA abundance for the predictor genes was unchanged by exercise training, supporting the idea that expression was preset by genetic variation. Regression analysis yielded a model where 11 single-nucleotide polymorphisms explained 23% of the variance in gains in (V) over dotO(2max), corresponding to similar to 50% of the estimated genetic variance for (V) over dotO(2max). In conclusion, combining RNA profiling with single-gene DNA marker association analysis yields a strongly validated molecular predictor with meaningful explanatory power. (V) over dotO(2max) responses to endurance training can be predicted by measuring a similar to 30-gene RNA expression signature in muscle prior to training. The general approach taken could accelerate the discovery of genetic biomarkers, sufficiently discrete for diagnostic purposes, for a range of physiological and pharmacological phenotypes in humans.
  • Sioris, C. E., et al. (författare)
  • The atmospheric limb sounding satellite (ALISS)
  • 2014
  • Ingår i: Proceedings of the International Astronautical Congress, IAC. - 0074-1795. ; 4, s. 2382-2392
  • Konferensbidrag (refereegranskat)abstract
    • The Atmospheric Limb Sounding Satellite (ALISS) is a joint Canadian-Swedish concept that is currently under study by agencies, industrial partners and academic institutions in both countries. Launch is not anticipated before late 2020. ALISS has significant heritage, resembling the current Odin mission in terms of some of the countries involved and the types of instruments. However, ALISS will have a focus on the upper troposphere in addition to Odin's primarily stratospheric focus. The ALISS mission has objectives relating to climate-chemistry coupling, UV radiation, dynamics, atmospheric composition in the upper troposphere and lower stratosphere, and in conjunction with nadir sensors, air quality, by virtue of the array of key atmospheric constituents that it will measure with an unprecedented combination of vertical and horizontal resolution for satellite-borne instruments. ALISS consists of four atmospheric limb remote sensing instruments. Three of these have space heritage and are: the Canadian-designed Atmospheric Tomography System (CATS) that is a derivative of the highly successful Optical Spectrograph and InfraRed Imaging System (OSIRIS) instrument, the Swedish-designed Stratosphere Troposphere Exchange And climate Monitoring Radiometer (STEAMR) that is a follow-on instrument to the sub-millimetre radiometer (SMR) that currently operates with OSIRIS on Odin, and a Global Positioning System Radio Occultation instrument. The fourth instrument, also Canadian, is the Spatial Heterodyne Observations of Water (SHOW). SHOW will measure profiles of water vapour using its near-infrared absorption. Among other things, the ALISS package will deliver atmospheric composition (O3, H2O, NO2, HNO3, BrO, CO, aerosol, and others) measurements within the extremely important upper troposphere and lower stratosphere region for chemistry and climate studies. One application of interest would be using these measurements in conjunction with total column measurements from nadir-viewing instruments as well as data assimilation systems in order to better monitor and forecast air quality. Also, the heritage of these instruments implies the ALISS measurements will be extremely valuable in the continuation of climate-quality time series of important constituents such as stratospheric aerosols, water vapour, and ozone. Continuity of these vertically resolved data records is currently threatened by a looming gap in satellite-based limb sounders. This talk will outline the ALISS concept and the utility of the measurements.
  • Gnad, T., et al. (författare)
  • Adenosine activates brown adipose tissue and recruits beige adipocytes via A(2A) receptors
  • 2014
  • Ingår i: Nature. - 0028-0836. ; 516:7531, s. 395-
  • Tidskriftsartikel (refereegranskat)abstract
    • Brown adipose tissue (BAT) is specialized in energy expenditure, making it a potential target for anti-obesity therapies(1-5). Following exposure to cold, BAT is activated by the sympathetic nervous system with concomitant release of catecholamines and activation of beta-adrenergic receptors(1-5). Because BAT therapies based on cold exposureor beta-adrenergic agonists are clinically not feasible, alternative strategies must be explored. Purinergic co-transmission might be involved in sympathetic control of BAT and previous studies reported inhibitory effects of the purinergic transmitter adenosine in BAT from hamster or rat(6-8). However, the role of adenosine in human BAT is unknown. Here we show that adenosine activates human and murine brown adipocytes at low nanomolar concentrations. Adenosine is released in BAT during stimulation of sympathetic nerves as well as from brown adipocytes. The adenosine A(2A) receptor is the most abundant adenosine receptor in human and murine BAT. Pharmacological blockade or genetic loss of A(2A) receptors in mice causes adecrease in BAT-dependent thermogenesis, whereas treatment with A(2A) agonists significantly increases energy expenditure. Moreover, pharmacological stimulation of A(2A) receptors or injection of lentiviral vectors expressing the A(2A) receptor into white fat induces brown-like cells-so-called beige adipocytes. Importantly, mice fed a high-fat diet and treated with an A(2A) agonist are leaner with improved glucose tolerance. Taken together, our results demonstrate that adenosine-A(2A) signalling plays an unexpected physiological role in sympathetic BAT activation and protects mice from diet-induced obesity. Those findings reveal new possibilities for developing novel obesity therapies.
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  • Resultat 1-5 av 5

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