| 1. |
- Farnelid, Hanna, et al.
(författare)
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Putative N-2-fixing heterotrophic bacteria associated with dinoflagellate-Cyanobacteria consortia in the low-nitrogen Indian Ocean
- 2010
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Ingår i: Aquatic Microbial Ecology. - : Inter-Research Science Center. - 0948-3055 .- 1616-1564. ; 61:2, s. 105-117
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Tidskriftsartikel (refereegranskat)abstract
- Heterotrophic dinoflagellates bearing unicellular cyanobacterial symbionts are common within the order Dinophysiales. However, the ecological role of these symbionts is unclear. Due to the occurrence of such consortia in oceanic waters characterized by low nitrogen concentrations, we hypothesized that the symbionts fix gaseous nitrogen (N-2). Individual heterotrophic dinoflagellates containing cyanobacterial symbionts were isolated from the open Indian Ocean and off Western Australia, and characterized using light microscopy, transmission electron microscopy (TEM), and nitrogenase (nifH) gene amplification, cloning, and sequencing. Cyanobacteria, heterotrophic bacteria and eukaryotic algae were recognized as symbionts of the heterotrophic dinoflagellates. nifH gene sequences were obtained from 23 of 37 (62%) specimens of dinoflagellates (Ornithocercus spp. and Amphisolenia spp.). Interestingly, only 2 specimens contained cyanobacterial nifH sequences, while 21 specimens contained nifH genes related to heterotrophic bacteria. Of the 137 nifH sequences obtained 68% were most similar to Alpha-, Beta-, and Gammaproteobacteria, 8% clustered with anaerobic bacteria, and 5% were related to second alternative nitrogenases (anfH). Twelve sequences from 5 host cells formed a discrete cluster which may represent a not yet classified nifH cluster. Eight dinoflagellates contained only 1 type of nifH sequence (>99% sequence identity) but overall the putative N-2-fixing symbionts did not appear host specific and mixed assemblages were often found in single host cells. This study provides the first insights into the nifH diversity of dinoflagellate symbionts and suggests a symbiotic co-existence of non-diazotrophic cyanobacteria and N-2-fixing heterotrophic bacteria in heterotrophic dinoflagellates.
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| 2. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 3. |
- Annenkova, Nataliia, et al.
(författare)
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Recent radiation in a marine and freshwater dinoflagellate species flock.
- 2015
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Ingår i: The Isme Journal. - : Springer Science and Business Media LLC. - 1751-7362 .- 1751-7370. ; 9:8, s. 1821-1834
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Tidskriftsartikel (refereegranskat)abstract
- Processes of rapid radiation among unicellular eukaryotes are much less studied than among multicellular organisms. We have investigated a lineage of cold-water microeukaryotes (protists) that appear to have diverged recently. This lineage stands in stark contrast to known examples of phylogenetically closely related protists, in which genetic difference is typically larger than morphological differences. We found that the group not only consists of the marine-brackish dinoflagellate species Scrippsiella hangoei and the freshwater species Peridinium aciculiferum as discovered previously but also of a whole species flock. The additional species include Peridinium euryceps and Peridinium baicalense, which are restricted to a few lakes, in particular to the ancient Lake Baikal, Russia, and freshwater S. hangoei from Lake Baikal. These species are characterized by relatively large conspicuous morphological differences, which have given rise to the different species descriptions. However, our scanning electron microscopic studies indicate that they belong to a single genus according to traditional morphological characterization of dinoflagellates (thecal plate patterns). Moreover, we found that they have identical SSU (small subunit) rDNA fragments and distinct but very small differences in the DNA markers LSU (large subunit) rDNA, ITS2 (internal transcribed spacer 2) and COB (cytochrome b) gene, which are used to delineate dinoflagellates species. As some of the species co-occur, and all four have small but species-specific sequence differences, we suggest that these taxa are not a case of phenotypic plasticity but originated via recent adaptive radiation. We propose that this is the first clear example among free-living microeukaryotes of recent rapid diversification into several species followed by dispersion to environments with different ecological conditions.The ISME Journal advance online publication, 20 January 2015; doi:10.1038/ismej.2014.267.
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| 4. |
- Annenkova, Nataliia V., et al.
(författare)
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Closely related dinoflagellate species in vastly different habitats–an example of a marine–freshwater transition
- 2020
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Ingår i: European Journal of Phycology. - : Informa UK Limited. - 0967-0262 .- 1469-4433. ; 55:4, s. 478-489
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Tidskriftsartikel (refereegranskat)abstract
- Phytoplankton are present in a large variety of aquatic environments, ranging from small freshwater ponds to the oceans. Typically, freshwater and marine species are not closely related, indicating an ancient divergence and that salinity poses a strong dispersal barrier. Here we reveal a common recent origin of two dinoflagellates that are well adapted to different habitats. Gymnodinium baicalense inhabits the geologically old freshwater Lake Baikal, which is located in the middle of the Eurasian continent. Gymnodinium corollarium, on the other hand, is a brackish water species from the Baltic Sea. Both species form blooms under ice during the spring. We generated 10 DNA sequences from these species. The partial 28S rRNA gene from G. baicalense and the partial 18S rRNA gene and internal transcribed spacer-2 (ITS2) from G. corollarium were sequenced for the first time. A more detailed description of G. baicalense, which was previously known only from light microscopy observations, is also provided. In the laboratory we demonstrated that G. baicalense is strictly adapted to fresh water, while G. corollarium had a wide salinity tolerance. However, the two species have almost identical morphology, identical SSU rRNA gene sequences, and only small differences in the LSU rRNA gene and ITS2. We infer a common ancestor, which was a species from the Arctic region with a tolerance to a range of salinities. Our data support the scenario that the under-ice phytoplankton community in Lake Baikal has been formed recently, even though the lake is the oldest in the world.
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| 5. |
- Dalbøge, Annett, et al.
(författare)
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Upper arm elevation and repetitive shoulder movements : A general population job exposure matrix based on expert ratings and technical measurements
- 2016
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Ingår i: Occupational and Environmental Medicine. - : BMJ. - 1351-0711 .- 1470-7926. ; 73:8, s. 553-560
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Tidskriftsartikel (refereegranskat)abstract
- Objectives We recently constructed a general population job exposure matrix (JEM), The Shoulder JEM, based on expert ratings. The overall aim of this study was to convert expert-rated job exposures for upper arm elevation and repetitive shoulder movements to measurement scales. Methods The Shoulder JEM covers all Danish occupational titles, divided into 172 job groups. For 36 of these job groups, we obtained technical measurements (inclinometry) of upper arm elevation and repetitive shoulder movements. To validate the expert-rated job exposures against the measured job exposures, we used Spearman rank correlations and the explained variance according to linear regression analyses (36 job groups). We used the linear regression equations to convert the expert-rated job exposures for all 172 job groups into predicted measured job exposures. Bland-Altman analyses were used to assess the agreement between the predicted and measured job exposures. Results The Spearman rank correlations were 0.63 for upper arm elevation and 0.64 for repetitive shoulder movements. The expert-rated job exposures explained 64% and 41% of the variance of the measured job exposures, respectively. The corresponding calibration equations were y=0.5%time+0.16×expert rating and y=27°/s+0.47×expert rating. The mean differences between predicted and measured job exposures were zero due to calibration; the 95% limits of agreement were ±2.9% time for upper arm elevation >90° and ±33°/s for repetitive shoulder movements. Conclusions The updated Shoulder JEM can be used to present exposure-response relationships on measurement scales.
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| 6. |
- de Jong, Roelof S., et al.
(författare)
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4MOST-4-metre Multi-Object Spectroscopic Telescope
- 2014
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Ingår i: Ground-based and Airborne Instrumentation for Astronomy V. - : SPIE. - 0277-786X .- 1996-756X. ; 9147
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Konferensbidrag (refereegranskat)abstract
- 4MOST is a wide-field, high-multiplex spectroscopic survey facility under development for the VISTA telescope of the European Southern Observatory (ESO). Its main science drivers are in the fields of galactic archeology, high-energy physics, galaxy evolution and cosmology. 4MOST will in particular provide the spectroscopic complements to the large area surveys coming from space missions like Gaia, eROSITA, Euclid, and PLATO and from ground-based facilities like VISTA, VST, DES, LSST and SKA. The 4MOST baseline concept features a 2.5 degree diameter field-of-view with similar to 2400 fibres in the focal surface that are configured by a fibre positioner based on the tilting spine principle. The fibres feed two types of spectrographs; similar to 1600 fibres go to two spectrographs with resolution R> 5000 (lambda similar to 390-930 nm) and similar to 800 fibres to a spectrograph with R> 18,000 (lambda similar to 392-437 nm & 515-572 nm & 605-675 nm). Both types of spectrographs are fixed-configuration, three-channel spectrographs. 4MOST will have an unique operations concept in which 5 year public surveys from both the consortium and the ESO community will be combined and observed in parallel during each exposure, resulting in more than 25 million spectra of targets spread over a large fraction of the southern sky. The 4MOST Facility Simulator (4FS) was developed to demonstrate the feasibility of this observing concept. 4MOST has been accepted for implementation by ESO with operations expected to start by the end of 2020. This paper provides a top-level overview of the 4MOST facility, while other papers in these proceedings provide more detailed descriptions of the instrument concept[1], the instrument requirements development[2], the systems engineering implementation[3], the instrument model[4], the fibre positioner concepts[5], the fibre feed[6], and the spectrographs[7].
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| 7. |
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| 8. |
- Elberling, Bo, et al.
(författare)
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Arctic vegetation damage by winter-generated coal mining pollution released upon thawing
- 2007
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 41:7, s. 2407-2413
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Tidskriftsartikel (refereegranskat)abstract
- Acid mine drainage (known as AMD) is a well-known environmental problem resulting from the oxidation of sulfidic mine waste. In cold regions, AMD is often considered limited by low temperatures most of the year and observed environmental impact is related to pollution generated during the warm summer period. Here we show that heat generation within an oxidizing, sulfidic, coal-mining waste-rock pile in Svalbard (78 degrees N) is high enough to keep the pile warm (roughly 5 degrees C throughout the year) despite mean annual air temperatures below -5 degrees C. Consequently, weathering processes continue year-round within the waste-rock pile. During the winter, weathering products accumulate within the pile because of a frozen outer layer on the pile and are released as a flush within 2 weeks of soil thawing in the spring. Consequently, spring runoff water contains elevated concentrations of metals. Several of these metals are taken up and accumulated in plants where they reach phytotoxic levels, including aluminum and manganese. Laboratory experiments document that uptake of Al and Mn in native plant species is highly correlated with dissolved concentrations. Therefore, future remedial actions to control the adverse environmental impacts of cold region coal-mining need to pay more attention to winter processes including AMD generation and accumulation of weathering products.
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| 9. |
- Engert, Andreas, et al.
(författare)
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The European Hematology Association Roadmap for European Hematology Research : a consensus document
- 2016
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Ingår i: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
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Tidskriftsartikel (refereegranskat)abstract
- The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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| 10. |
- Epishin, Alexander, et al.
(författare)
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Synchrotron Sub-μ X-ray Tomography of Kirkendall Porosity in a Diffusion Couple of Nickel-Base Superalloy and Nickel after Annealing at 1250 °C
- 2021
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Ingår i: Advanced Engineering Materials. - : Wiley. - 1527-2648 .- 1438-1656. ; 23:4
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Tidskriftsartikel (refereegranskat)abstract
- Kirkendall porosity that forms during interdiffusion in a diffusion couple of nickel-base superalloy CMSX-10 with pure nickel is investigated. The diffusion experiments are conducted at a temperature of 1250 °C, where the strengthening γ′-phase is partially dissolved. The porosity is studied by X-ray sub-μ tomography with a spatial resolution of about 0.353 μm3 at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. It is found that depending on the distance from the interface the Kirkendall pores take different shapes: octahedral, rounded pyramidal, drop shaped, dendritic, pear shaped, and joint shapes. Such a variety of pore morphologies indicates a complex multistage process of porosity nucleation and growth under vacancy supersaturation of different degrees. The experimental findings are interpreted on the basis of the results of diffusion modeling. It is shown that the kinetics of porosity growth is essentially influenced by the dissolution of the γ′-phase.
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| 11. |
- Frazier-Wood, Alexis C., et al.
(författare)
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Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
- 2016
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Ingår i: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
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Tidskriftsartikel (refereegranskat)abstract
- Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
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| 12. |
- Heid, Iris M, et al.
(författare)
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Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
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Tidskriftsartikel (refereegranskat)abstract
- Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
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| 13. |
- Heilskov-Hansen, Thomas, et al.
(författare)
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Exposure-response relationships between movements and postures of the wrist and carpal tunnel syndrome among male and female house painters : a retrospective cohort study
- 2016
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Ingår i: Occupational and Environmental Medicine. - : BMJ. - 1470-7926 .- 1351-0711. ; 73:6, s. 401-408
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To investigate exposure-response relationships between measured movements and postures of the wrist and the incidence of carpal tunnel syndrome (CTS), and any modifications by sex.METHODS: In 2011, we established a historical cohort of 9364 members of the Painters' Union in Denmark. Self-reported task distributions were obtained by questionnaire (53% responded) and combined with sex-specific task exposure matrices to get individual estimates of exposure intensity, that is, velocity of wrist flexion/extension, mean power frequency (MPF) and non-neutral wrist postures. Exposure duration was assessed from yearly working proportions. Registered first-time hospital discharge CTS diagnoses and CTS surgery were collected as outcomes. The cohort was followed from 1994 to 2010. Log-linear Poisson regression was used.RESULTS: For CTS diagnoses, the adjusted incidence rate ratios (IRRs) increased with increasing wrist velocity (IRR=1.37 (95% CI 1.10 to 1.71) per °/s) and MPF (IRR=1.53 (95% CI 1.21 to 1.91) per 0.01 Hz). For CTS surgery, the results were similar. The outcomes were not related to non-neutral postures or exposure duration. The adjusted IRRs for women were higher than those for men. There were no multiplicative interaction effects between exposure intensity, exposure duration and sex. However, the absolute incidence rates (IRs) increased at a steeper rate for women than for men, indicating an additive interaction.CONCLUSIONS: The incidence of CTS increased with increasing velocity of wrist flexion/extension and MPF of wrist movements. The relative increase in incidence rates was the same for women and men, but the absolute incidence rates increased at a steeper rate for women than for men.
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| 14. |
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| 15. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 16. |
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| 17. |
- Meyland, Jacob, et al.
(författare)
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Sex differences in muscular load among house painters performing identical work tasks
- 2014
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Ingår i: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6327 .- 1439-6319. ; 114:9, s. 1901-1911
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Tidskriftsartikel (refereegranskat)abstract
- The present study aimed to estimate possible differences in upper body muscular load between male and female house painters performing identical work tasks. Sex-related differences in muscular load may help explain why women, in general, have more musculoskeletal complaints than men. In a laboratory setting, 16 male and 16 female house painters performed nine standardised work tasks common to house painters. Unilateral electromyography (EMG) recordings were obtained from the supraspinatus muscle by intramuscular electrodes and from the trapezius, extensor and flexor carpi radialis muscles by surface electrodes. Relative muscular loads in %EMG(max) as well as exerted force in Newton, based on ramp calibrations, were assessed. Sex differences were tested using a mixed model approach. Women worked at about 50 % higher relative muscular loads than men in the supraspinatus and forearm muscles at all percentiles and in all tasks. Women exerted about 30 % less force in the trapezius muscle at the 50th percentile. Female house painters had a higher relative muscular load than their male colleagues without exerting more force. The effects of a higher relative muscular load accumulated over years of work may in part explain why musculoskeletal complaints in the upper body occur more frequently among women than men.
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| 18. |
- Rengefors, Karin, et al.
(författare)
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Marine-derived dinoflagellates in Antarctic saline lakes: annual dynamics and community composition
- 2008
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Ingår i: Journal of Phycology. - : Wiley. - 0022-3646 .- 1529-8817. ; 44:3, s. 592-604
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Tidskriftsartikel (refereegranskat)abstract
- The saline lakes of the Vestfold Hills in Antarctica offer a remarkable natural laboratory where the adaptation of planktonic protists to a range of evolving physiochemical conditions can be investigated. This study illustrates how an ancestral marine community has undergone radical simplification leaving a small number of well-adapted species. Our objective was to investigate the species composition and annual dynamics of dinoflagellate communities in three saline Antarctic lakes. We observed that dinoflagellates occur year-round despite extremely low PAR during the southern winter, which suggests significant mixotrophic or heterotrophic activity. Only a small number of dominant dinoflagellate species were found in each lake, in contrast to the species-rich Southern Ocean from which the lake communities are believed to be derived. We verified that the lake species were representatives of the marine polar dinoflagellate community, and not freshwater species. Polarella glacialis Montresor, Procaccini et Stoecker, a bipolar marine species, was for the first time described in a lake habitat and was an important phototrophic component in the higher salinity lakes. In the brackish lakes, we found a new sibling species to the brackish-water species Scrippsiella hangoei (J. Schiller) J. Larsen, previously observed only in the Baltic Sea.
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| 19. |
- Speliotes, Elizabeth K., et al.
(författare)
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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| 20. |
- Zhang, Yao, et al.
(författare)
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Crucial role of alkaline sphingomyelinase in sphingomyelin digestion: A study on the enzyme knockout mice.
- 2010
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Ingår i: Journal of Lipid Research. - 1539-7262. ; 52:4, s. 771-781
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Tidskriftsartikel (refereegranskat)abstract
- Alkaline sphingomyelinase (alk-SMase) hydrolyses sphingomyelin (SM) to ceramide in the gut. To evaluate physiological importance of the enzyme, we generated alk-SMase knockout (KO) mice by Cre-LoxP system and studied SM digestion. Both wild type (WT) and the KO mice were fed 3H-palmitic acid labeled SM together with milk SM by gavage. The lipids in intestinal content, intestinal tissues, serum and liver were analysed by TLC. In KO mice, non-digested 3H-SM in the intestinal content increased by 6 fold and the formation of 3H-ceramide decreased markedly, resulting in 98% reduction of 3H-ceramide/3H-SM ratio 1 h after gavage. The absorbed 3H-palmitic acid portion was decreased by 95%. After three hours, a small increase in 3H-ceramide was identified in distal intestine in KO mice. In feces 3H-SM was increased by 243% and ceramide decreased by 74% in the KO mice. The KO mice also showed significantly decreased radioactivity in liver and serum. Furthermore alkaline phosphatase activity in the mucosa was reduced by 50%, and histological comparison of two female littermates preliminarily suggested mucosal hypertrophy in KO mice. The study provides definite proofs for crucial roles of alk-SMase in SM digestion and points to possible roles in regulating mucosal growth and alkaline phosphatase function.
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