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- Efe, C., et al.
(författare)
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Extrahepatic autoimmune diseases in primary biliary cholangitis: Prevalence and significance for clinical presentation and disease outcome
- 2021
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Ingår i: Journal of Gastroenterology and Hepatology. - : Wiley. - 0815-9319 .- 1440-1746. ; 36:4, s. 936-942
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aim The prevalence and clinical significance of extrahepatic autoimmune diseases (EHAIDs) have not been evaluated in a large cohort of primary biliary cholangitis (PBC). Methods The medical records of 1554 patients with PBC from 20 international centers were retrospectively reviewed. Development of decompensated cirrhosis (ascites, variceal bleeding, and/or hepatic encephalopathy) and hepatocellular carcinoma were considered clinical endpoints. Results A total of 35 different EHAIDs were diagnosed in 440 (28.3%) patients with PBC. Patients with EHAIDs were more often female (92.5%vs86.1%,P < 0.001) and seropositive for anti-mitochondrial antibodies (88%vs84%,P = 0.05) and antinuclear antibodies and/or smooth muscle antibodies (53.8%vs43.6%,P = 0.005). At presentation, patients with EHAIDs had significantly lower levels of alkaline phosphatase (1.76vs1.98 x upper limit of normal [ULN],P = 0.006), aspartate aminotransferase (1.29vs1.50 x ULN,P < 0.001), and total bilirubin (0.53vs0.58 x ULN,P = 0.002). Patients with EHAIDs and without EHAIDs had similar rates of GLOBE high-risk status (12.3%vs16.1%,P = 0.07) and Paris II response (71.4%vs69.4%,P = 0.59). Overall, event-free survival was not different in patients with and without EHAIDs (90.8%vs90.7%,P = 0.53, log rank). Coexistence of each autoimmune thyroid diseases (10.6%), Sjogren disease (8.3%), systemic sclerosis (2.9%), rheumatoid arthritis (2.7%), systemic lupus erythematosus (1.7%), celiac disease (1.7%), psoriasis (1.5%), and inflammatory bowel diseases (1.3%) did not influence the outcome. Conclusions Our study confirms that EHAIDs are frequently diagnosed in patients with PBC. The presence of EHAIDs may influence the clinical phenotype of PBC at presentation but has no impact on PBC outcome.
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- Johansson, Pia A, et al.
(författare)
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A cis-acting structural variation at the ZNF558 locus controls a gene regulatory network in human brain development
- 2022
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Ingår i: Cell Stem Cell. - : Elsevier BV. - 1934-5909 .- 1875-9777. ; 29:1, s. 8-69
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Tidskriftsartikel (refereegranskat)abstract
- The human forebrain has expanded in size and complexity compared to chimpanzees despite limited changes in protein-coding genes, suggesting that gene expression regulation is an important driver of brain evolution. Here, we identify a KRAB-ZFP transcription factor, ZNF558, that is expressed in human but not chimpanzee forebrain neural progenitor cells. ZNF558 evolved as a suppressor of LINE-1 transposons but has been co-opted to regulate a single target, the mitophagy gene SPATA18. ZNF558 plays a role in mitochondrial homeostasis, and loss-of-function experiments in cerebral organoids suggests that ZNF558 influences developmental timing during early human brain development. Expression of ZNF558 is controlled by the size of a variable number tandem repeat that is longer in chimpanzees compared to humans, and variable in the human population. Thus, this work provides mechanistic insight into how a cis-acting structural variation establishes a regulatory network that affects human brain evolution.
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- Delmont, T. O., et al.
(författare)
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Heterotrophic bacterial diazotrophs are more abundant than their cyanobacterial counterparts in metagenomes covering most of the sunlit ocean
- 2022
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Ingår i: The ISME Journal. - : Springer Science and Business Media LLC. - 1751-7362 .- 1751-7370. ; 16:4, s. 927-936
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Tidskriftsartikel (refereegranskat)abstract
- Biological nitrogen fixation contributes significantly to marine primary productivity. The current view depicts few cyanobacterial diazotrophs as the main marine nitrogen fixers. Here, we used 891 Tara Oceans metagenomes derived from surface waters of five oceans and two seas to generate a manually curated genomic database corresponding to free-living, filamentous, colony-forming, particle-attached, and symbiotic bacterial and archaeal populations. The database provides the genomic content of eight cyanobacterial diazotrophs including a newly discovered population related to known heterocystous symbionts of diatoms, as well as 40 heterotrophic bacterial diazotrophs that considerably expand the known diversity of abundant marine nitrogen fixers. These 48 populations encapsulate 92% of metagenomic signal for known nifH genes in the sunlit ocean, suggesting that the genomic characterization of the most abundant marine diazotrophs may be nearing completion. Newly identified heterotrophic bacterial diazotrophs are widespread, express their nifH genes in situ, and also occur in large planktonic size fractions where they might form aggregates that provide the low-oxygen microenvironments required for nitrogen fixation. Critically, we found heterotrophic bacterial diazotrophs to be more abundant than cyanobacterial diazotrophs in most metagenomes from the open oceans and seas, emphasizing the importance of a wide range of heterotrophic populations in the marine nitrogen balance.
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