| 1. |
- Zillikens, M. C., et al.
(författare)
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Large meta-analysis of genome-wide association studies identifies five loci for lean body mass
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 x 10(-8)) or suggestively genome wide (p < 2.3 x 10(-6)). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/ near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/ near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.
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| 2. |
- Wood, A. R., et al.
(författare)
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A Genome-Wide Association Study of IVGTT-Based Measures of First-Phase Insulin Secretion Refines the Underlying Physiology of Type 2 Diabetes Variants
- 2017
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 66:8, s. 2296-2309
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the physiological mechanisms by which common variants predispose to type 2 diabetes requires large studies with detailed measures of insulin secretion and sensitivity. Here we performed the largest genome-wide association study of first-phase insulin secretion, as measured by intravenous glucose tolerance tests, using up to 5,567 individuals without diabetes from 10 studies. We aimed to refine the mechanisms of 178 known associations between common variants and glycemic traits and identify new loci. Thirty type 2 diabetes or fasting glucose-raising alleles were associated with a measure of first-phase insulin secretion at P < 0.05 and provided new evidence, or the strongest evidence yet, that insulin secretion, intrinsic to the islet cells, is a key mechanism underlying the associations at the HNF1A, IGF2BP2, KCNQ1, HNF1B, VPS13C/C2CD4A, FAF1, PTPRD, AP3S2, KCNK16, MAEA, LPP, WFS1, and TMPRSS6 loci. The fasting glucose-raising allele near PDX1, a known key insulin transcription factor, was strongly associated with lower first-phase insulin secretion but has no evidence for an effect on type 2 diabetes risk. The diabetes risk allele at TCF7L2 was associated with a stronger effect on peak insulin response than on C-peptide-based insulin secretion rate, suggesting a possible additional role in hepatic insulin clearance or insulin processing. In summary, our study provides further insight into the mechanisms by which common genetic variation influences type 2 diabetes risk and glycemic traits.
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| 3. |
- Arguedas Cuendis, S., et al.
(författare)
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First results on the search for chameleons with the KWISP detector at CAST
- 2019
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Ingår i: Physics of the Dark Universe. - : Elsevier. - 2212-6864. ; 26
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Tidskriftsartikel (refereegranskat)abstract
- We report on a first measurement with a sensitive opto-mechanical force sensor designed for the direct detection of coupling of real chameleons to matter. These dark energy candidates could be produced in the Sun and stream unimpeded to Earth. The KWISP detector installed on the CAST axion search experiment at CERN looks for tiny displacements of a thin membrane caused by the mechanical effect of solar chameleons. The displacements are detected by a Michelson interferometer with a homodyne readout scheme. The sensor benefits from the focusing action of the ABRIXAS X-ray telescope installed at CAST, which increases the chameleon flux on the membrane. A mechanical chopper placed between the telescope output and the detector modulates the incoming chameleon stream. We present the results of the solar chameleon measurements taken at CAST in July 2017, setting an upper bound on the force acting on the membrane of 80pN at 95% confidence level. The detector is sensitive for direct coupling to matter 104≤βm≤108, where the coupling to photons is locally bound to βγ≤1011.
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| 4. |
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| 5. |
- Baier, Florian, et al.
(författare)
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Cryptic genetic variation shapes the adaptive evolutionary potential of enzymes
- 2019
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Ingår i: eLIFE. - : ELIFE SCIENCES PUBLICATIONS LTD. - 2050-084X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variation among orthologous proteins can cause cryptic phenotypic properties that only manifest in changing environments. Such variation may impact the evolvability of proteins, but the underlying molecular basis remains unclear. Here, we performed comparative directed evolution of four orthologous metallo-beta-lactamases toward a new function and found that different starting genotypes evolved to distinct evolutionary outcomes. Despite a low initial fitness, one ortholog reached a significantly higher fitness plateau than its counterparts, via increasing catalytic activity. By contrast, the ortholog with the highest initial activity evolved to a less-optimal and phenotypically distinct outcome through changes in expression, oligomerization and activity. We show how cryptic molecular properties and conformational variation of active site residues in the initial genotypes cause epistasis, that could lead to distinct evolutionary outcomes. Our work highlights the importance of understanding the molecular details that connect genetic variation to protein function to improve the prediction of protein evolution.
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| 10. |
- Malko, A., et al.
(författare)
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Optimization of the efficiency of single-photon sources based on quantum dots under optical excitation
- 2006
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 88, s. 081905-
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate efficient, regulated single-photon operation from site-controlled InGaAs quantum dots (QDs) grown on a prepatterned substrate. Under nonresonant optical excitation, carriers trapped at structural or compositional defects of the adjacent nanostructures led to a degradation of the single-photon statistics from a QD. When the QD was excited quasiresonantly, single photons were emitted and a nearly complete suppression of multiphoton emission was achieved, making these QDs promising candidates for effective solid-state single-photon sources
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