| 1. |
- Gorski, Mathias, et al.
(författare)
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Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline
- 2021
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Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 99:4, s. 926-939
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Tidskriftsartikel (refereegranskat)abstract
- Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
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| 2. |
- Kjær, Kurt H., et al.
(författare)
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A 2-million-year-old ecosystem in Greenland uncovered by environmental DNA
- 2022
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 612:7939, s. 283-291
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Tidskriftsartikel (refereegranskat)abstract
- Late Pliocene and Early Pleistocene epochs 3.6 to 0.8 million years ago1 had climates resembling those forecasted under future warming2. Palaeoclimatic records show strong polar amplification with mean annual temperatures of 11–19 °C above contemporary values3,4. The biological communities inhabiting the Arctic during this time remain poorly known because fossils are rare5. Here we report an ancient environmental DNA6 (eDNA) record describing the rich plant and animal assemblages of the Kap København Formation in North Greenland, dated to around two million years ago. The record shows an open boreal forest ecosystem with mixed vegetation of poplar, birch and thuja trees, as well as a variety of Arctic and boreal shrubs and herbs, many of which had not previously been detected at the site from macrofossil and pollen records. The DNA record confirms the presence of hare and mitochondrial DNA from animals including mastodons, reindeer, rodents and geese, all ancestral to their present-day and late Pleistocene relatives. The presence of marine species including horseshoe crab and green algae support a warmer climate than today. The reconstructed ecosystem has no modern analogue. The survival of such ancient eDNA probably relates to its binding to mineral surfaces. Our findings open new areas of genetic research, demonstrating that it is possible to track the ecology and evolution of biological communities from two million years ago using ancient eDNA.
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| 3. |
- Taal, H. Rob, et al.
(författare)
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Common variants at 12q15 and 12q24 are associated with infant head circumference
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:5, s. 532-538
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Tidskriftsartikel (refereegranskat)abstract
- To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
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| 4. |
- Wuttke, Matthias, et al.
(författare)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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| 5. |
- Algaba, Juan-Carlos, et al.
(författare)
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Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign
- 2021
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 911:1
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Forskningsöversikt (refereegranskat)abstract
- In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M o˙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87's spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded.
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| 6. |
- Becher, Paul, et al.
(författare)
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Yeast, not fruit volatiles mediate Drosophila melanogaster attraction, oviposition and development
- 2012
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Ingår i: Functional Ecology. - : Wiley. - 1365-2435 .- 0269-8463. ; 26:4, s. 822-828
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Tidskriftsartikel (refereegranskat)abstract
- 1.In nature, the fruit fly Drosophila melanogaster is attracted to fermenting fruit. Micro-organisms like Saccharomyces yeasts growing on fruit occupy a commonly overlooked trophic level between fruit and insects. Although the dietary quality of yeast is well established for D.melanogaster, the individual contribution of fruit and yeast on host finding and reproductive success has not been established. 2.Here, we show that baker's yeast Saccharomyces cerevisiae on its own is sufficient for fruit fly attraction, oviposition and larval development. In contrast, attraction and oviposition were significantly lower if non-fermented grape juice or growth media were used, and yeast-free grapes did not support larval development either. 3.Despite a strong preference for fermented substrates, moderate attraction to and oviposition on unfermented fruit might be adaptive in view of the fly's capacity to vector yeast. 4.Signals emitted by fruit were only of secondary importance because fermenting yeast without fruit induced the same fly behaviour as yeast fermenting on fruit. We identified a synthetic mimic of yeast odour, comprising ethanol, acetic acid, acetoin, 2-phenyl ethanol and 3-methyl-1-butanol, which was as attractive for the fly as fermenting grape juice or fermenting yeast minimal medium. 5.Yeast odours represent the critical signal to establish the flyfruityeast relationship. The traditional plantherbivore niche concept needs to be updated, to accommodate for the role of micro-organisms in insectplant interactions.
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| 7. |
- Bergmann, Peter, et al.
(författare)
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Review on geophysical monitoring of CO2 injection at Ketzin, Germany
- 2016
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Ingår i: Journal of Petroleum Science and Engineering. - : Elsevier BV. - 0920-4105. ; 139, s. 112-136
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Tidskriftsartikel (refereegranskat)abstract
- Geophysical monitoring activities were an important component of the CO2 injection program at the Ketzin site, Germany. Here we report on the seismic and electrical resistivity tomography (ERT) measurements performed during the period of the site development and CO2 injection. Details on the site geology, the history of the CO2 injection operation, and petrophysical models relevant for the interpretation of the geophysical data are presented. The seismic measurements comprise 2D and 3D surface seismic surveys, vertical seismic profilings, and crosshole measurements. Apart from the measurements, results from advanced processing methods, such as impedance inversion and full-waveform inversion are also presented. In addition, results from crosshole ERT and surface-downhole ERT are presented. If operational efforts are taken into consideration we conclude that a combination of several geophysical methods is preferable given the demands of a spatiotemporally comprehensive monitoring program. We base this conclusion on that the different imaging characteristics and petrophysical sensitivities of different methods can complement each other. An important finding is, based on signal quality and reduced operational costs, that the use of permanent installations is promising. Generally, specific monitoring layouts will depend on site-specific characteristics, such as reservoir depth, availability of wells, petrophysical characteristics, and accessibility of surface locations. Given the comprehensive range of methods applied, the reported results are not only relevant to the operation of CO2 storage sites, but are also of interest to other monitoring projects dealing with fluid injection or production.
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| 8. |
- Bergström, Anders, et al.
(författare)
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Origins and genetic legacy of prehistoric dogs
- 2020
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 370:6516, s. 557-563
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Tidskriftsartikel (refereegranskat)abstract
- Dogs were the first domestic animal, but little is known about their population history and to what extent it was linked to humans. We sequenced 27 ancient dog genomes and found that all dogs share a common ancestry distinct from present-day wolves, with limited gene flow from wolves since domestication but substantial dog-to-wolf gene flow. By 11,000 years ago, at least five major ancestry lineages had diversified, demonstrating a deep genetic history of dogs during the Paleolithic. Coanalysis with human genomes reveals aspects of dog population history that mirror humans, including Levant-related ancestry in Africa and early agricultural Europe. Other aspects differ, including the impacts of steppe pastoralist expansions in West and East Eurasia and a near-complete turnover of Neolithic European dog ancestry.
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| 9. |
- Christiansen, Alexandra Golabek, et al.
(författare)
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Occupational exposure to epoxy components and risk of dermatitis : A registry-based follow-up study of the wind turbine industry
- 2024
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Ingår i: Contact Dermatitis. - 0105-1873. ; 90:1, s. 32-40
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Tidskriftsartikel (refereegranskat)abstract
- Background: Allergic contact allergy and dermatitis are frequently reported among epoxy-exposed workers. Objectives: To determine the risk of dermatitis associated with epoxy exposure. Methods: We followed 825 epoxy-exposed and 1091 non-exposed blue-collar workers, and 493 white-collar workers of a Danish wind turbine blade factory during 2017–2022 with linked data from national health registers on diagnoses, patch testing, or fillings of prescriptions for topical corticosteroids. Incidence rate ratios of dermatitis or a first-time topical corticosteroid prescription were estimated with Poisson regression using non-exposed blue-collar workers as reference. We similarly estimated incidence rate ratios for the duration of epoxy exposure and current epoxy exposure. Results: Epoxy-exposed blue-collar workers showed a dermatitis incidence rate of 2.1 per 100 000 person days, a two-fold increased risk of dermatitis and a 20% increased risk of filling a prescription for topical corticosteroids. Incidence rate ratios were higher during early exposure and declined with further exposure for both outcomes. White-collar workers had generally lower risks. Conclusion: We observed an increased risk of dermatitis following epoxy exposure confirming previous case reports and cross-sectional studies emphasizing the need for intensified focus on preventive efforts for this group of workers.
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| 10. |
- Christiansen, Alexandra G., et al.
(författare)
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Prevalence of skin sensitization and dermatitis among epoxy-exposed workers in the wind turbine industry
- 2022
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Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 187:6, s. 988-996
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Tidskriftsartikel (refereegranskat)abstract
- Background: A high prevalence of skin sensitization and dermatitis has been reported among workers exposed to epoxy components. Objectives: To estimate the risk of skin sensitization and dermatitis among workers exposed to epoxy components during production of wind turbine blades while using comprehensive safety measures. Methods: A cross-sectional study of 180 highly epoxy-exposed production workers and 41 nonexposed office workers was conducted at two wind turbine blade factories in Denmark. Participants underwent a skin examination, were tested with a tailored patch test panel including epoxy-containing products used at the factories, and answered a questionnaire. Results: Sixteen production workers (8·9%) were sensitized to an epoxy component compared with none of the office workers. Skin sensitization was more frequent within the first year of exposed employment. Strong selection bias by atopic status was indicated. Among nonatopic workers, the prevalence of dermatitis was higher among production workers (16·4%) than among office workers [6·5%, odds ratio (OR) 2·3, 95% confidence interval (CI) 0·6–9·1] and higher among the sensitized workers (43·8%) than the nonsensitized workers (14·6%, OR 4·5, 95% CI 1·6–12·7). Resins based on diglycidyl ether of bisphenol A and F were the most frequent sensitizers. One of the four workers sensitized to epoxy components used at the factories did not react to the epoxy resin of the TRUE test® panel. Conclusions: Despite comprehensive skin protection, sensitization and dermatitis are prevalent among highly epoxy-exposed workers in the wind turbine industry in Denmark. Our findings document the need for intensified preventive efforts and emphasize the importance of tailored patch testing. What is already known about this topic? Epoxy components are well-known sensitizers of the skin. A high prevalence of skin sensitization and dermatitis has been reported among workers exposed to epoxy components. Comprehensive protective equipment is recommended when working with epoxy components. What does this study add? Despite comprehensive skin protection, skin sensitization and dermatitis are prevalent among epoxy-exposed workers. We found that 40% of workers sensitized to epoxy products had dermatitis. Only 75% of the sensitized workers were detected by the epoxy resin of the TRUE test®, which emphasizes the importance of tailored testing.
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