| 1. |
- 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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| 2. |
- Hunkeler, Priska A., et al.
(författare)
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A glimpse beneath Antarctic sea ice : Platelet layer volume from multifrequency electromagnetic induction sounding
- 2016
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 43:1, s. 222-231
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Tidskriftsartikel (refereegranskat)abstract
- In Antarctica, ice crystals emerge from ice-shelf cavities and accumulate in unconsolidated layers beneath nearby sea ice. Such sub-ice platelet layers form a unique habitat, and serve as an indicator for the state of an ice shelf. However, the lack of a suitable methodology impedes an efficient quantification of this phenomenon on scales beyond point measurements. In this study, we inverted multi-frequency electromagnetic (EM) induction soundings of > 100 km length, obtained on fast ice with an underlying platelet layer in the eastern Weddell Sea. EM-derived platelet-layer thickness and conductivity are consistent with other field observations. Our results further suggest that platelet-layer volume is higher than previously thought in this region, and that platelet-layer ice-volume fraction is proportional to its thickness. We conclude that multi-frequency EM is a suitable tool to determine platelet-layer volume, with the potential to obtain crucial knowledge of associated processes in otherwise inaccessible ice-shelf cavities.
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| 3. |
- Hunkeler, Priska A., et al.
(författare)
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Improved 1D inversions for sea ice thickness and conductivity from electromagnetic induction data : Inclusion of nonlinearities caused by passive bucking
- 2016
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Ingår i: Geophysics. - 0016-8033 .- 1942-2156. ; 81:1, s. WA45-WA58
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Tidskriftsartikel (refereegranskat)abstract
- The porosity of sea ice is a fundamental physical parameter that governs the mechanical strength of sea ice and the mobility of gases and nutrients for biological processes and biogeochemical cycles in the sea ice layer. However, little is known about the spatial distribution of the sea ice porosity and its variability between different sea ice types; an efficient and nondestructive method to measure this property is currently missing. Sea ice porosity is linked to the bulk electrical conductivity of sea ice, a parameter routinely used to discriminate between sea ice and seawater by electromagnetic (EM) induction sensors. Here, we have evaluated the prospect of porosity retrieval of sea ice by means of bulk conductivity estimates using 1D multi-frequency EM inversion schemes. We have focused on two inversion algorithms, a smoothness-constrained inversion and a Marquardt-Levenberg inversion, which we modified for the nonlinear signal bias caused by a passive bucking coil operated in such a highly conductive environment. Using synthetic modeling studies, 1D inversion algorithms and multiple frequencies, we found that we can resolve the sea ice conductivity within +/- 0.01 S/m. Using standard assumptions for the conductivity-porosity relation of sea ice, we were able to estimate porosity with an uncertainty of +/- 1.2%, which enables efficient and nondestructive surveys of the internal state of the sea ice cover.
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| 4. |
- Schafmayer, Clemens, et al.
(författare)
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Genome-wide association analysis of diverticular disease points towards neuromuscular, connective tissue and epithelial pathomechanisms
- 2019
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 68:5, s. 854-865
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Tidskriftsartikel (refereegranskat)abstract
- Objective Diverticular disease is a common complex disorder characterised by mucosal outpouchings of the colonic wall that manifests through complications such as diverticulitis, perforation and bleeding. We report the to date largest genome-wide association study (GWAS) to identify genetic risk factors for diverticular disease. Design Discovery GWAS analysis was performed on UK Biobank imputed genotypes using 31 964 cases and 419 135 controls of European descent. Associations were replicated in a European sample of 3893 cases and 2829 diverticula-free controls and evaluated for risk contribution to diverticulitis and uncomplicated diverticulosis. Transcripts at top 20 replicating loci were analysed by real-time quatitative PCR in preparations of the mucosal, submucosal and muscular layer of colon. The localisation of expressed protein at selected loci was investigated by immunohistochemistry. Results We discovered 48 risk loci, of which 12 are novel, with genome-wide significance and consistent OR in the replication sample. Nominal replication (p< 0.05) was observed for 27 loci, and additional 8 in meta-analysis with a population-based cohort. The most significant novel risk variant rs9960286 is located near CTAGE1 with a p value of 2.3x10-10 and 0.002 (OR allelic = 1.14 (95% CI 1.05 to 1.24)) in the replication analysis. Four loci showed stronger effects for diverticulitis, PHGR1 (OR 1.32, 95% CI 1.12 to 1.56), FAM155A-2 (OR 1.21, 95% CI 1.04 to 1.42), CALCB (OR 1.17, 95% CI 1.03 to 1.33) and S100A10 (OR 1.17, 95% CI 1.03 to 1.33). Conclusion I n silico analyses point to diverticulosis primarily as a disorder of intestinal neuromuscular function and of impaired connective fibre support, while an additional diverticulitis risk might be conferred by epithelial dysfunction.
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| 5. |
- Werner, Kirstin, et al.
(författare)
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Arctic in Rapid Transition : Priorities for the future of marine and coastal research in the Arctic
- 2016
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Ingår i: Polar Science. - : Elsevier BV. - 1873-9652 .- 1876-4428. ; 10:3, s. 364-373
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Tidskriftsartikel (refereegranskat)abstract
- Understanding and responding to the rapidly occurring environmental changes in the Arctic over the past few decades require new approaches in science. This includes improved collaborations within the scientific community but also enhanced dialogue between scientists and societal stakeholders, especially with Arctic communities. As a contribution to the Third International Conference on Arctic Research Planning (ICARPIII), the Arctic in Rapid Transition (ART) network held an international workshop in France, in October 2014, in order to discuss high-priority requirements for future Arctic marine and coastal research from an early-career scientists (ECS) perspective. The discussion encompassed a variety of research fields, including topics of oceanographic conditions, sea-ice monitoring, marine biodiversity, land-ocean interactions, and geological reconstructions, as well as law and governance issues. Participants of the workshop strongly agreed on the need to enhance interdisciplinarity in order to collect comprehensive knowledge about the modern and past Arctic Ocean's geo-ecological dynamics. Such knowledge enables improved predictions of Arctic developments and provides the basis for elaborate decision-making on future actions under plausible environmental and climate scenarios in the high northern latitudes. Priority research sheets resulting from the workshop's discussions were distributed during the ICARPIII meetings in April 2015 in Japan, and are publicly available online. (C) 2016 Elsevier B.V. and NIPR. All rights reserved.
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| 6. |
- Willatt, Rosemary, et al.
(författare)
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Retrieval of Snow Depth on Arctic Sea Ice From Surface-Based, Polarimetric, Dual-Frequency Radar Altimetry
- 2023
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 50:20
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Tidskriftsartikel (refereegranskat)abstract
- Snow depth on sea ice is an Essential Climate Variable and a major source of uncertainty in satellite altimetry-derived sea ice thickness. During winter of the MOSAiC Expedition, the “KuKa” dual-frequency, fully polarized Ku- and Ka-band radar was deployed in “stare” nadir-looking mode to investigate the possibility of combining these two frequencies to retrieve snow depth. Three approaches were investigated: dual-frequency, dual-polarization and waveform shape, and compared to independent snow depth measurements. Novel dual-polarization approaches yielded r2 values up to 0.77. Mean snow depths agreed within 1cm, even for data sub-banded to CryoSat-2 SIRAL and SARAL AltiKa bandwidths. Snow depths from co-polarized dual-frequency approaches were at least a factor of four too small and had a r2 0.15 or lower. r2 for waveform shape techniques reached 0.72 but depths were underestimated. Snow depth retrievals using polarimetric information or waveform shape may therefore be possible from airborne/satellite radar altimeters.
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