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| 2. |
- Postmus, Iris, et al.
(författare)
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Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.
- 2014
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.
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| 3. |
- Cappellini, Enrico, et al.
(författare)
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Early Pleistocene enamel proteome from Dmanisi resolves Stephanorhinus phylogeny
- 2019
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 574:7776, s. 103-
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Tidskriftsartikel (refereegranskat)abstract
- The sequencing of ancient DNA has enabled the reconstruction of speciation, migration and admixture events for extinct taxa(1). However, the irreversible post-mortem degradation(2) of ancient DNA has so far limited its recovery-outside permafrost areasto specimens that are not older than approximately 0.5 million years (Myr)(3). By contrast, tandem mass spectrometry has enabled the sequencing of approximately 1.5-Myr-old collagen type I-4. and suggested the presence of protein residues in fossils of the Cretaceous period(5)-although with limited phylogenetic use(6). In the absence of molecular evidence, the speciation of several extinct species of the Early and Middle Pleistocene epoch remains contentious. Here we address the phylogenetic relationships of the Eurasian Rhinocerotidae of the Pleistocene epoch(7-9), using the proteome of dental enamel from a Stephanorhinus tooth that is approximately 1.77-Myr old, recovered from the archaeological site of Dmanisi (South Caucasus, Georgia)(10). Molecular phylogenetic analyses place this Stephanorhinus as a sister group to the Glade formed by the woolly rhinoceros (Coelodonta antiquitatis) and Merck's rhinoceros (Stephanorhinus kirchbergensis). We show that Coelodonta evolved from an early Stephanorhinus lineage, and that this latter genus includes at least two distinct evolutionary lines. The genus Stephanorhinus is therefore currently paraphyletic, and its systematic revision is needed. We demonstrate that sequencing the proteome of Early Pleistocene dental enamel overcomes the limitations of phylogenetic inference based on ancient collagen or DNA. Our approach also provides additional information about the sex and taxonomic assignment of other specimens from Dmanisi. Our findings reveal that proteomic investigation of ancient dental enamel-which is the hardest tissue in vertebrates(11), and is highly abundant in the fossil record-can push the reconstruction of molecular evolution further back into the Early Pleistocene epoch, beyond the currently known limits of ancient DNA preservation.
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| 4. |
- Pattaro, Cristian, et al.
(författare)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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| 5. |
- Peloso, Gina M, et al.
(författare)
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Association of low-frequency and rare coding-sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks.
- 2014
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 94:2, s. 223-232
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Tidskriftsartikel (refereegranskat)abstract
- Low-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. It is uncertain whether the PCSK9 example represents a paradigm or an isolated exception. We used the "Exome Array" to genotype >200,000 low-frequency and rare coding sequence variants across the genome in 56,538 individuals (42,208 European ancestry [EA] and 14,330 African ancestry [AA]) and tested these variants for association with LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. Although we did not identify new genes associated with LDL-C, we did identify four low-frequency (frequencies between 0.1% and 2%) variants (ANGPTL8 rs145464906 [c.361C>T; p.Gln121(∗)], PAFAH1B2 rs186808413 [c.482C>T; p.Ser161Leu], COL18A1 rs114139997 [c.331G>A; p.Gly111Arg], and PCSK7 rs142953140 [c.1511G>A; p.Arg504His]) with large effects on HDL-C and/or triglycerides. None of these four variants was associated with risk for CHD, suggesting that examples of low-frequency coding variants with robust effects on both lipids and CHD will be limited.
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| 6. |
- Stafford, Joshua D., et al.
(författare)
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Spring migration of waterfowl in the northern hemisphere : a conservation perspective
- 2014
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Ingår i: Wildfowl. - 0954-6324 .- 2052-6458. ; :Special Issue 4, s. 70-85
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Tidskriftsartikel (refereegranskat)abstract
- Spring migration is a key part of the annual cycle for waterfowl populations in the northern hemisphere, due to its temporal proximity to the breeding season and because resources may be limited at one or more staging sites. Research based on field observations during spring lags behind other periods of the year, despite the potential for fitness consequences through diminished survival or cross-seasonal effects of conditions experienced during migration. Consequently, conservation strategies for waterfowl on spring migration are often only refined versions of practices used during autumn and winter. Here we discuss the current state of knowledge of habitat requirements for waterfowl at their spring migratory sites and the intrinsic and extrinsic factors that lead to variability in those requirements. The provision of plant foods has become the main conservation strategy during spring because of the birds’ energy requirements at this time, not only to fuel migration but to facilitate early clutch formation on arrival at the breeding grounds. Although energy sources are important to migrants, there is little evidence on the extent to which the availability of carbohydrate-based food is limiting for many migratory waterfowl populations. Such limitation is relatively unlikely among populations that exploit agricultural grain during migration (e.g. arctic-nesting geese), suggesting that conservation strategies for these populations may be misplaced. In general, however, we found few cases in which an ecological understanding of spring-migrating waterfowl was sufficient to indicate true resource limitation during migration, and still fewer cases where conservation efforts ameliorated these limitations. We propose a framework that aims to address knowledge gaps and apply empirical research results to conservation strategies based on documented limitations and associated fitness impacts on migrating waterfowl. Such a strategy would improve allocation of scarce conservation resources during spring migration and greatly improve ecological understanding of migratory waterfowl and their habitats in the northern hemisphere.
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| 7. |
- Stafford, Joshua D., et al.
(författare)
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Spring migration of waterfowl in the northern hemisphere : a conservation perspective
- 2014
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Ingår i: Wildfowl. - : Wildfowl and Wetlands Trust. - 0954-6324. ; :Special Issue 4, s. 70-85
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Tidskriftsartikel (refereegranskat)abstract
- Spring migration is a key part of the annual cycle for waterfowl populations in the northern hemisphere, due to its temporal proximity to the breeding season and because resources may be limited at one or more staging sites. Research based on field observations during spring lags behind other periods of the year, despite the potential for fitness consequences through diminished survival or cross-seasonal effects of conditions experienced during migration. Consequently, conservation strategies for waterfowl on spring migration are often only refined versions of practices used during autumn and winter. Here we discuss the current state of knowledge of habitat requirements for waterfowl at their spring migratory sites and the intrinsic and extrinsic factors that lead to variability in those requirements. The provision of plant foods has become the main conservation strategy during spring because of the birds’ energy requirements at this time, not only to fuel migration but to facilitate early clutch formation on arrival at the breeding grounds. Although energy sources are important to migrants, there is little evidence on the extent to which the availability of carbohydrate-based food is limiting for many migratory waterfowl populations. Such limitation is relatively unlikely among populations that exploit agricultural grain during migration (e.g. arctic-nesting geese), suggesting that conservation strategies for these populations may be misplaced. In general, however, we found few cases in which an ecological understanding of spring-migrating waterfowl was sufficient to indicate true resource limitation during migration, and still fewer cases where conservation efforts ameliorated these limitations. We propose a framework that aims to address knowledge gaps and apply empirical research results to conservation strategies based on documented limitations and associated fitness impacts on migrating waterfowl. Such a strategy would improve allocation of scarce conservation resources during spring migration and greatly improve ecological understanding of migratory waterfowl and their habitats in the northern hemisphere.
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| 8. |
- Ardo, Shane, et al.
(författare)
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Pathways to electrochemical solar-hydrogen technologies
- 2018
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Ingår i: Energy & Environmental Science. - : Royal Society of Chemistry. - 1754-5692 .- 1754-5706. ; 11:10, s. 2768-2783
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Forskningsöversikt (refereegranskat)abstract
- Solar-powered electrochemical production of hydrogen through water electrolysis is an active and important research endeavor. However, technologies and roadmaps for implementation of this process do not exist. In this perspective paper, we describe potential pathways for solar-hydrogen technologies into the marketplace in the form of photoelectrochemical or photovoltaic-driven electrolysis devices and systems. We detail technical approaches for device and system architectures, economic drivers, societal perceptions, political impacts, technological challenges, and research opportunities. Implementation scenarios are broken down into short-term and long-term markets, and a specific technology roadmap is defined. In the short term, the only plausible economical option will be photovoltaic-driven electrolysis systems for niche applications. In the long term, electrochemical solar-hydrogen technologies could be deployed more broadly in energy markets but will require advances in the technology, significant cost reductions, and/ or policy changes. Ultimately, a transition to a society that significantly relies on solar-hydrogen technologies will benefit from continued creativity and influence from the scientific community.
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