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- Tabassum, R, et al.
(författare)
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Genetic architecture of human plasma lipidome and its link to cardiovascular disease
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4329-
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Tidskriftsartikel (refereegranskat)abstract
- Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD.
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| 2. |
- Pärn, J., et al.
(författare)
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Nitrogen-rich organic soils under warm well-drained conditions are global nitrous oxide emission hotspots
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Nitrous oxide (N2O) is a powerful greenhouse gas and the main driver of stratospheric ozone depletion. Since soils are the largest source of N2O, predicting soil response to changes in climate or land use is central to understanding and managing N2O. Here we find that N2O flux can be predicted by models incorporating soil nitrate concentration (NO3 -), water content and temperature using a global field survey of N2O emissions and potential driving factors across a wide range of organic soils. N2O emissions increase with NO3 - and follow a bell-shaped distribution with water content. Combining the two functions explains 72% of N2O emission from all organic soils. Above 5 mg NO3 --N kg-1, either draining wet soils or irrigating well-drained soils increases N2O emission by orders of magnitude. As soil temperature together with NO3 - explains 69% of N2O emission, tropical wetlands should be a priority for N2O management.
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| 3. |
- Ruuth, M., et al.
(författare)
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Susceptibility of low-density lipoprotein particles to aggregate depends on particle lipidome, ismodifiable, and associates with future cardiovascular deaths
- 2018
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 39:27
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Tidskriftsartikel (refereegranskat)abstract
- Aims Low-density lipoprotein (LDL) particles cause atherosclerotic cardiovascular disease (ASCVD) through their retention, modification, and accumulation within the arterial intima. High plasma concentrations of LDL drive this disease, but LDL quality may also contribute. Here, we focused on the intrinsic propensity of LDL to aggregate upon modification. We examined whether inter-individual differences in this quality are linked with LDL lipid composition and coronary artery disease (CAD) death, and basic mechanisms for plaque growth and destabilization. Methods and results We developed a novel, reproducible method to assess the susceptibility of LDL particles to aggregate during lipolysis induced ex vivo by human recombinant secretory sphingomyelinase. Among patients with an established CAD, we found that the presence of aggregation-prone LDL was predictive of future cardiovascular deaths, independently of conventional risk factors. Aggregation-prone LDL contained more sphingolipids and less phosphatidylcholines than did aggregation-resistant LDL. Three interventions in animal models to rationally alter LDL composition lowered its susceptibility to aggregate and slowed atherosclerosis. Similar compositional changes induced in humans by PCSK9 inhibition or healthy diet also lowered LDL aggregation susceptibility. Aggregated LDL in vitro activated macrophages and T cells, two key cell types involved in plaque progression and rupture. Conclusion Our results identify the susceptibility of LDL to aggregate as a novel measurable and modifiable factor in the progression of human ASCVD.
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| 6. |
- Liukkonen, J, et al.
(författare)
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Salivary biomarkers in association with periodontal parameters and the periodontitis risk haplotype
- 2018
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Ingår i: Innate immunity. - : SAGE Publications. - 1753-4267 .- 1753-4259. ; 24:7, s. 439-447
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Tidskriftsartikel (refereegranskat)abstract
- Genetic factors play a role in periodontitis. Here we examined whether the risk haplotype of MHC class III region BAT1-NFKBIL1-LTA and lymphotoxin-α polymorphisms associate with salivary biomarkers of periodontal disease. A total of 455 individuals with detailed clinical and radiographic periodontal health data were included in the study. A 610 K genotyping chip and a Sequenom platform were used in genotyping analyses. Phospholipid transfer protein activity, concentrations of lymphotoxin-α, IL-8 and myeloperoxidase, and a cumulative risk score (combining Porphyromonas gingivalis, IL-1β and matrix metalloproteinase-8) were examined in saliva samples. Elevated IL-8 and myeloperoxidase concentrations and cumulative risk scores associated with advanced tooth loss, deepened periodontal pockets and signs of periodontal inflammation. In multiple logistic regression models adjusted for periodontal parameters and risk factors, myeloperoxidase concentration (odds ratio (OR); 1.37, P = 0.007) associated with increased odds for having the risk haplotype and lymphotoxin-α concentration with its genetic variants rs2857708, rs2009658 and rs2844482. In conclusion, salivary levels of IL-8, myeloperoxidase and cumulative risk scores associate with periodontal inflammation and tissue destruction, while those of myeloperoxidase and lymphotoxin-α associate with genetic factors as well.
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| 7. |
- Purhonen, J, et al.
(författare)
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Ketogenic diet attenuates hepatopathy in mouse model of respiratory chain complex III deficiency caused by a Bcs1l mutation
- 2017
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1, s. 957-
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial disorders are among the most prevalent inborn errors of metabolism but largely lack treatments and have poor outcomes. High-fat, low-carbohydrate ketogenic diets (KDs) have shown beneficial effects in mouse models of mitochondrial myopathies, with induction of mitochondrial biogenesis as the suggested main mechanism. We fed KD to mice with respiratory chain complex III (CIII) deficiency and progressive hepatopathy due to mutated BCS1L, a CIII assembly factor. The mutant mice became persistently ketotic and tolerated the KD for up to 11 weeks. Liver disease progression was attenuated by KD as shown by delayed fibrosis, reduced cell death, inhibition of hepatic progenitor cell response and stellate cell activation, and normalization of liver enzyme activities. Despite no clear signs of increased mitochondrial biogenesis in the liver, CIII assembly and activity were improved and mitochondrial morphology in hepatocytes normalized. Induction of hepatic glutathione transferase genes and elevated total glutathione level were normalized by KD. Histological findings and transcriptome changes indicated modulation of liver macrophage populations by the mutation and the diet. These results reveal a striking beneficial hepatic response to KD in mice with mitochondrial hepatopathy and warrant further investigations of dietary modification in the management of these conditions in patients.
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| 9. |
- O'Dwyer, J, et al.
(författare)
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Methanesulfonic acid in a Svalbard ice core as an indicator of ocean climate
- 2000
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Ingår i: GEOPHYSICAL RESEARCH LETTERS. - 0094-8276. ; 27:8, s. 1159-1162
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Tidskriftsartikel (refereegranskat)abstract
- Methanesulfonic acid (MSA) is an atmospheric oxidation product of dimethyl sulfide, produced by marine biota. MSA preserved in a Svalbard glacier between 1920 and 1996 is compared with the sea surface temperature (SST) and sea-ice extent of the surrounding ocean over the same period. On decadal timescales high MSA concentrations are found to be associated with warm SST and reduced sea-ice extent. MSA appears to be influenced by climatic changes related to variations in the import of warm Atlantic Water to the Barents Sea. Atlantic Water plays an important role in the Arctic climate system, therefore MSA concentrations may indirectly reflect larger-scale changes in the region and may be useful as a proxy for past climate.
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| 10. |
- Pohjola, V, et al.
(författare)
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Effect of periodic melting on geochemical and isotopic signals in an ice core from Lomonosovfonna, Svalbard
- 2002
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Ingår i: J.Geophys.Res.. ; 107:D4, s. ACL 1-14
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Tidskriftsartikel (refereegranskat)abstract
- In this work we examine the quality of the atmospherically deposited signals in an ice core taken from a periodically melting ice field, Lomonosovfonna on central Spitsbergen, Svalbard. The aim is to investigate how much the atmospheric deposited signals in the stratigraphy of ice pack are changed by periodic melting of the ice. To determine the impact of this melting on the stratigraphy found in the ice core, we use three diagnostics: 1) Association between peak values in the ice chemical and isotopic record and ice facies type; 2) Number of “annual” cycles in these records compared with independently-determined number of years represented in the ice core; 3) Statistical comparison between the isotopic record in the ice core and the isotope records from coastal stations from the same region. We find that during warm summers as much as 50% of the annual accumulation may melt and percolate into the firn, and in a median year this decreases to ca. 25 %. As a consequence of percolation the most mobile acids show upto 50 % higher concentrations in bubble poor ice facies compared with facies that are less affected by melt. Most of the other chemical species are less affected than the strong acids, and the stable water isotopes show little evidence of mobility Annual, or bi-annual cycles are detected in most parameters, and the water isotope record has a comparable statistical distribution to isotopic records from coastal stations. We conclude that ice cores from sites like Lomonosovfonna preserve an useful environmental record despite melt events and percolation, where most parameters displays an annual, or in poor cases a bi-annual atmospheric signal.
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