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- Petkevicius, K., et al.
(författare)
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TLCD1 and TLCD2 regulate cellular phosphatidylethanolamine composition and promote the progression of non-alcoholic steatohepatitis
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- The regulation of cellular phosphatidylethanolamine (PE) acyl chain composition is poorly understood. Here, the authors show that TLCD1 and TLCD2 proteins mediate the formation of monounsaturated fatty acid-containing PE species and promote the progression of non-alcoholic steatohepatitis. The fatty acid composition of phosphatidylethanolamine (PE) determines cellular metabolism, oxidative stress, and inflammation. However, our understanding of how cells regulate PE composition is limited. Here, we identify a genetic locus on mouse chromosome 11, containing two poorly characterized genes Tlcd1 and Tlcd2, that strongly influences PE composition. We generated Tlcd1/2 double-knockout (DKO) mice and found that they have reduced levels of hepatic monounsaturated fatty acid (MUFA)-containing PE species. Mechanistically, TLCD1/2 proteins act cell intrinsically to promote the incorporation of MUFAs into PEs. Furthermore, TLCD1/2 interact with the mitochondria in an evolutionarily conserved manner and regulate mitochondrial PE composition. Lastly, we demonstrate the biological relevance of our findings in dietary models of metabolic disease, where Tlcd1/2 DKO mice display attenuated development of non-alcoholic steatohepatitis compared to controls. Overall, we identify TLCD1/2 proteins as key regulators of cellular PE composition, with our findings having broad implications in understanding and treating disease.
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| 2. |
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| 3. |
- Forsstrom, S., et al.
(författare)
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Elemental carbon distribution in Svalbard snow
- 2009
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 114
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Tidskriftsartikel (refereegranskat)abstract
- The concentration of apparent elemental carbon (ECa, based on a thermal-optical method) in the snow was investigated in Svalbard (European Arctic) during spring 2007. The median ECa concentration of 81 samples was 4.1 mu g l(-1) and the values ranged from 0 to 80.8 mu g l(-1) of melt water. The median concentration is nearly an order of magnitude lower than the previously published data of equivalent black carbon (BCe, based on an optical method), obtained from Svalbard snow in the 1980s. A systematic regional difference was evident: ECa concentrations were higher in east Svalbard compared to west Svalbard. The observations of snow ECa cover spatial scales up to several hundred kilometers, which is comparable to the resolution of many climate models. Measurements of atmospheric carbonaceous aerosol (2002-2008) at Zeppelin station in Ny-Alesund, Svalbard, were divided to air mass sectors based on calculated back trajectories. The results show that air originating from the eastern sector contains more than two and half times higher levels of soot than air arriving from south to west. The observed east-west gradient of ECa concentrations in snow may be because of a combination of the atmospheric concentration gradient, the orographic effect of the archipelago, and the efficient scavenging of the carbonaceous particles through precipitation
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| 4. |
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| 5. |
- Cajuso, T, et al.
(författare)
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Retrotransposon insertions can initiate colorectal cancer and are associated with poor survival
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4022-
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Tidskriftsartikel (refereegranskat)abstract
- Genomic instability pathways in colorectal cancer (CRC) have been extensively studied, but the role of retrotransposition in colorectal carcinogenesis remains poorly understood. Although retrotransposons are usually repressed, they become active in several human cancers, in particular those of the gastrointestinal tract. Here we characterize retrotransposon insertions in 202 colorectal tumor whole genomes and investigate their associations with molecular and clinical characteristics. We find highly variable retrotransposon activity among tumors and identify recurrent insertions in 15 known cancer genes. In approximately 1% of the cases we identify insertions in APC, likely to be tumor-initiating events. Insertions are positively associated with the CpG island methylator phenotype and the genomic fraction of allelic imbalance. Clinically, high number of insertions is independently associated with poor disease-specific survival.
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