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- Vimaleswaran, Karani S, et al.
(författare)
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Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study.
- 2014
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Ingår i: The lancet. Diabetes & endocrinology. - 2213-8595 .- 2213-8587. ; 2:9, s. 719-29
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Tidskriftsartikel (refereegranskat)abstract
- Background Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. Methods In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. Findings In phenotypic analyses (up to n=49363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, −0·12 mm Hg, 95% CI −0·20 to −0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97–0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, −0·02 mm Hg, −0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of −0·10 mm Hg in systolic blood pressure (−0·21 to −0·0001; p=0·0498) and a change of −0·08 mm Hg in diastolic blood pressure (−0·15 to −0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96–0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of −0·29 mm Hg in diastolic blood pressure (−0·52 to −0·07; p=0·01), a change of −0·37 mm Hg in systolic blood pressure (−0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87–0·97; p=0·002). Interpretation Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.
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| 3. |
- Dupont, Chris L., et al.
(författare)
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Functional Tradeoffs Underpin Salinity-Driven Divergence in Microbial Community Composition
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2, s. e89549-
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial community composition and functional potential change subtly across gradients in the surface ocean. In contrast, while there are significant phylogenetic divergences between communities from freshwater and marine habitats, the underlying mechanisms to this phylogenetic structuring yet remain unknown. We hypothesized that the functional potential of natural bacterial communities is linked to this striking divide between microbiomes. To test this hypothesis, metagenomic sequencing of microbial communities along a 1,800 km transect in the Baltic Sea area, encompassing a continuous natural salinity gradient from limnic to fully marine conditions, was explored. Multivariate statistical analyses showed that salinity is the main determinant of dramatic changes in microbial community composition, but also of large scale changes in core metabolic functions of bacteria. Strikingly, genetically and metabolically different pathways for key metabolic processes, such as respiration, biosynthesis of quinones and isoprenoids, glycolysis and osmolyte transport, were differentially abundant at high and low salinities. These shifts in functional capacities were observed at multiple taxonomic levels and within dominant bacterial phyla, while bacteria, such as SAR11, were able to adapt to the entire salinity gradient. We propose that the large differences in central metabolism required at high and low salinities dictate the striking divide between freshwater and marine microbiomes, and that the ability to inhabit different salinity regimes evolved early during bacterial phylogenetic differentiation. These findings significantly advance our understanding of microbial distributions and stress the need to incorporate salinity in future climate change models that predict increased levels of precipitation and a reduction in salinity.
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| 4. |
- Hamrin, Kerstin, et al.
(författare)
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Prolonged Exercise-Induced Stimulation of Skeletal Muscle Glucose Uptake Is due to Sustained Increases in Tissue Perfusion and Fractional Glucose Extraction
- 2011
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 96:4, s. 1085-1092
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Tidskriftsartikel (refereegranskat)abstract
- Context: The mechanisms behind the positive effects of physical activity on glucose metabolism in skeletal muscle and the time course of the effects need to be more elucidated. Objective: The aim was to examine the prolonged effects of an acute bout of one-legged exercise on local skeletal muscle glucose utilization and tissue perfusion. Design and Setting: Interstitial glucose concentration, local tissue perfusion, glucose uptake, and effects of insulin infusion were studied 12 h after an acute bout of exercise and without prior exercise. Participants: Ten healthy subjects, five women and five men, participated in the study. Intervention: Microdialysis measurements, (133)Xe clearance, and a 2-h hyperinsulinemic euglycemic clamp were performed on two occasions. Main Outcome Measures: We measured interstitial glucose concentration and tissue perfusion in the quadriceps femoris muscle of both legs. Results: Tissue perfusion (3.3 +/- 0.6 ml x 100 g(-1) x min(-1) vs. 1.4 +/- 0.2 ml x 100 g(-1) x min(-1); P = 0.007) and basal glucose uptake (2.3 +/- 0.5 mu mol x 100 g(-1) x min(-1) vs. 0.9 +/- 0.2 mu mol x 100 g(-1) x min(-1); P = 0.006) were increased in the leg that had exercised compared to the resting leg; the findings in the resting leg were comparable to those in the control experiment without prior exercise. The relative effect of insulin on fractional skeletal muscle glucose uptake was the same in all experimental settings, and insulin did not affect tissue perfusion. Conclusions: The prolonged stimulatory effect of physical exercise on skeletal muscle glucose uptake was mediated via vascular effects combined with an increase in basal glucose transport independent of enhancement of insulin responses.
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| 5. |
- Holmström, Stefan, et al.
(författare)
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The talent development environments in two Scandinavian soccer academies’
- 2012
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Ingår i: 3rd World Conference on Science and Soccer, 14-16 May 2012, Ghent, Belgium.
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Konferensbidrag (refereegranskat)abstract
- Current research on psychological aspects of talent development has tended to focus on individual athletes and their micro-environments. In this study the talent development environments of a Swedish and a Danish soccer academy were examined, each club with a history of successfully producing top-level senior athletes from among its juniors. The aim was to explore and compare the clubs work on individual development within specifically defined areas (managing competition, career transitions, introduction of new players, injuries, challenges and support in life, school and family). Method: A qualitative methodology was used and semi-structured interviews were conducted with a total of 17 participants: four players and three leaders of the Swedish Club, and three players and seven leaders from the Danish club. Results and Conclusion: In both the Swedish and Danish club have a specified goal that the youth academy should prioritize individual development before the outcome of the game. Work on the development of the players individual skills are organized in different ways in the Swedish and Danish club. The Danish club has a much clearer structure on how to work with individual development, they use development plans in greater degree, plans which is anchored with the players and a more individualized training plans for the player's position and needs. Both clubs stresses the importance of developing the whole individual, not just play soccer characteristics, but also school work and the wellbeing of the individual player. The combination of soccer practice and school work was one thing that players from both clubs highlighted as challenging and stressful.
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| 8. |
- Hedström, Peter, et al.
(författare)
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On the Three-Dimensional Microstructure of Martensite in Carbon Steels
- 2012
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Ingår i: Proceedings Of The 1st International Conference On 3D Materials Science. - Hoboken, NJ, USA : John Wiley & Sons. - 9781118470398 - 9781627489331 ; , s. 19-24
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Konferensbidrag (refereegranskat)abstract
- The mechanical properties of high-performance steels are often reliant on the hard martensitic structure. It can either be the sole constituent e. g. in tool steels, or it can be part of a multi-phase structure as e. g. in dual-phase steels. It is well-known that the morphology of martensite changes from lath to plate martensite with increasing carbon content. The transition from lath to plate is however less known and in particular the three-dimensional (3D) aspects in the mixed lath and plate region require more work. Here the current view of the 3D microstructure of martensite in carbon steels is briefly reviewed and complemented by serial sectioning experiments using a focused ion beam scanning electron microscope (FIB-SEM). The large martensite units in the Fe-1.2 mass% C steel investigated here are found to have one dominant growth direction, less transverse growth and very limited thickening. There is also evident transformation twinning parallel to the transverse direction. It is concluded that more 3D analysis is required to understand the 3D microstructure of martensite in the mixed lath and plate region and to verify the recently proposed 3D phase field models of martensite in steels.
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| 9. |
- Levin, G. P., et al.
(författare)
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Genetic variants and associations of 25-hydroxyvitamin D concentrations with major clinical outcomes
- 2012
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 308:18, s. 1898-1905
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Tidskriftsartikel (refereegranskat)abstract
- Context Lower serum 25-hydroxyvitamin D concentrations are associated with greater risks of many chronic diseases across large, prospective community-based studies. Substrate 25-hydroxyvitamin D must be converted to 1,25-dihydroxyvitamin D for full biological activity, and complex metabolic pathways suggest that interindividual variability in vitamin D metabolism may alter the clinical consequences of measured serum 25-hydroxyvitamin D.Objective To investigate whether common variation within genes encoding the vitamin D–binding protein, megalin, cubilin, CYP27B1, CYP24A1, and the vitamin D receptor (VDR) modify associations of low 25-hydroxyvitamin D with major clinical outcomes.Design, Setting, and Participants Examination of 141 single-nucleotide polymorphisms in a discovery cohort of 1514 white participants (who were recruited from 4 US regions) from the community-based Cardiovascular Health Study. Participants had serum 25-hydroxyvitamin D measurements in 1992-1993 and were followed up for a median of 11 years (through 2006). Replication meta-analyses were conducted across the independent, community-based US Health, Aging, and Body Composition (n = 922; follow-up: 1998-1999 through 2005), Italian Invecchiare in Chianti (n = 835; follow-up: 1998-2000 through 2006), and Swedish Uppsala Longitudinal Study of Adult Men (n = 970; follow-up: 1991-1995 through 2008) cohort studies.Main Outcome Measure Composite outcome of incident hip facture, myocardial infarction, cancer, and mortality over long-term follow-up.Results Interactions between 5 single-nucleotide polymorphisms and low 25-hydroxyvitamin D concentration were identified in the discovery phase and 1 involving a variant in the VDR gene replicated in independent meta-analysis. Among Cardiovascular Health Study participants, low 25-hydroxyvitamin D concentration was associated with hazard ratios for risk of the composite outcome of 1.40 (95% CI, 1.12-1.74) for those who had 1 minor allele at rs7968585 and 1.82 (95% CI, 1.31-2.54) for those with 2 minor alleles at rs7968585. In contrast, there was no evidence of an association (estimated hazard ratio, 0.93 [95% CI, 0.70-1.24]) among participants who had 0 minor alleles at this single-nucleotide polymorphism.Conclusion Known associations of low 25-hydroxyvitamin D with major health outcomes may vary according to common genetic differences in the vitamin D receptor.
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| 10. |
- Niskanen, A. K., et al.
(författare)
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MHC variability supports dog domestication from a large number of wolves : high diversity in Asia
- 2013
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Ingår i: Heredity. - : Springer Science and Business Media LLC. - 0018-067X .- 1365-2540. ; 110:1, s. 80-85
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Tidskriftsartikel (refereegranskat)abstract
- The process of dog domestication is still somewhat unresolved. Earlier studies indicate that domestic dogs from all over the world have a common origin in Asia. So far, major histocompatibility complex (MHC) diversity has not been studied in detail in Asian dogs, although high levels of genetic diversity are expected at the domestication locality. We sequenced the second exon of the canine MHC gene DLA-DRB1 from 128 Asian dogs and compared our data with a previously published large data set of MHC alleles, mostly from European dogs. Our results show that Asian dogs have a higher MHC diversity than European dogs. We also estimated that there is only a small probability that new alleles have arisen by mutation since domestication. Based on the assumption that all of the currently known 102 DLA-DRB1 alleles come from the founding wolf population, we simulated the number of founding wolf individuals. Our simulations indicate an effective population size of at least 500 founding wolves, suggesting that the founding wolf population was large or that backcrossing has taken place.
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