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- Sliz, E., et al.
(författare)
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Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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| 2. |
- 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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| 5. |
- Irace, AL, et al.
(författare)
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Additive Manufacturing of Resected Oral and Oropharyngeal Tissue: A Pilot Study
- 2021
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Ingår i: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 18:3
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Tidskriftsartikel (refereegranskat)abstract
- Better visualization of tumor structure and orientation are needed in the postoperative setting. We aimed to assess the feasibility of a system in which oral and oropharyngeal tumors are resected, photographed, 3D modeled, and printed using additive manufacturing techniques. Three patients diagnosed with oral/oropharyngeal cancer were included. All patients underwent preoperative magnetic resonance imaging followed by resection. In the operating room (OR), the resected tissue block was photographed using a smartphone. Digital photos were imported into Agisoft Photoscan to produce a digital 3D model of the resected tissue. Physical models were then printed using binder jetting techniques. The aforementioned process was applied in pilot cases including carcinomas of the tongue and larynx. The number of photographs taken for each case ranged from 63 to 195. The printing time for the physical models ranged from 2 to 9 h, costs ranging from 25 to 141 EUR (28 to 161 USD). Digital photography may be used to additively manufacture models of resected oral/oropharyngeal tumors in an easy, accessible and efficient fashion. The model may be used in interdisciplinary discussion regarding postoperative care to improve understanding and collaboration, but further investigation in prospective studies is required.
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| 8. |
- Vihervaara, Anniina, et al.
(författare)
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Stress-induced transcriptional memory accelerates promoter-proximal pause release and decelerates termination over mitotic divisions
- 2021
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Ingår i: Molecular Cell. - : Elsevier BV. - 1097-2765 .- 1097-4164. ; 81:8, s. 1715-
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Tidskriftsartikel (refereegranskat)abstract
- Heat shock instantly reprograms transcription. Whether gene and enhancer transcription fully recover from stress and whether stress establishes a memory by provoking transcription regulation that persists through mitosis remained unknown. Here, we measured nascent transcription and chromatin accessibility in unconditioned cells and in the daughters of stress-exposed cells. Tracking transcription genome-wide at nucleotide-resolution revealed that cells precisely restored RNA polymerase II (Pol II) distribution at gene bodies and enhancers upon recovery from stress. However, a single heat exposure in embryonic fibroblasts primed a faster gene induction in their daughter cells by increasing promoter-proximal Pol II pausing and by accelerating the pause release. In K562 erythroleukemia cells, repeated stress refined basal and heat-induced transcription over mitotic division and decelerated termination-coupled pre-mRNA processing. The slower termination retained transcripts on the chromatin and reduced recycling of Pol II. These results demonstrate that heat-induced transcriptional memory acts through promoter-proximal pause release and pre-mRNA processing at transcription termination.
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