| 1. |
- Justice, Anne E., et al.
(författare)
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Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
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Tidskriftsartikel (refereegranskat)abstract
- Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
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| 2. |
- Moilanen, Carolina, et al.
(författare)
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Influence of strain rate, temperature and fatigue on the radial compression behaviour of Norway spruce
- 2017
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Ingår i: Holzforschung. - : Walter de Gruyter GmbH. - 0018-3830 .- 1437-434X. ; 71:6, s. 505-514
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Tidskriftsartikel (refereegranskat)abstract
- A dynamic elastoplastic compression model of Norway spruce for virtual computer optimization of mechanical pulping processes was developed. The empirical wood behaviour was fitted to a Voigt-Kelvin material model, which is based on quasi static compression and high strain rate compression tests (QSCT and HSRT, respectively) of wood at room temperature and at high temperature (80-100 degrees C). The effect of wood fatigue was also included in the model. Wood compression stress-strain curves have an initial linear elastic region, a plateau region and a densification region. The latter was not reached in the HSRT. Earlywood (EW) and latewood (LW) contributions were considered separately. In the radial direction, the wood structure is layered and can well be modelled by serially loaded layers. The EW model was a two part linear model and the LW was modelled by a linear model, both with a strain rate dependent term. The model corresponds well to the measured values and this is the first compression model for EW and LW that is based on experiments under conditions close to those used in mechanical pulping.
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| 3. |
- Moilanen, Carolina S., et al.
(författare)
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High strain rate radial compression of Norway spruce earlywood and latewood
- 2016
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Ingår i: Cellulose. - : Springer Science and Business Media LLC. - 0969-0239 .- 1572-882X. ; 23:1, s. 873-889
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Tidskriftsartikel (refereegranskat)abstract
- The mechanical properties of Norway spruce were studied and a compression model for mechanical pulping was developed. The split-Hopkinson pressure bar technique was combined with high-speed photography to analyse local radial compression. Data analysis focussed on the differences between mechanical properties of earlywood and latewood. Measurements were conducted at both room temperature and 135 C. The effect of prefatigue treatment was also studied. A simple material model was defined linearly in parts and fitted to the measurement data to quantify the differences. New results were found on the differences in inelastic behaviour of earlywood and latewood at large deformations. In addition, other results were in line with previously published results.
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| 4. |
- Turcot, Valerie, et al.
(författare)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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