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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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- Aberg, J, et al.
(författare)
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Electrical properties of the TiSi2-Si transition region in contacts : The influence of an interposed layer of Nb
- 2001
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 90:5, s. 2380-2388
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Tidskriftsartikel (refereegranskat)abstract
- The influence of an interposed ultrathin Nb layer between Ti and Si on the silicide formation and the electrical contact between the silicide formed and the Si substrate is investigated. The presence of the Nb interlayer results in the formation of ternary alloy (Nb,Ti)Si-2 in the C40 crystallographic structure adjacent to the Si substrate. Depending on the nature of the Si substrates and/or the amount of the initial Nb, the interfacial C40 (Nb,Ti)Si-2 leads, in turn, to either epitaxial growth of a highly faulted metastable C40 TiSi2 or formation of the desired C54 TiSi2 at a lower temperature than needed for it to form in reference samples with Ti deposited directly on Si. On p-type substrates doped to various concentrations, the Nb also leads to a considerably lower specific contact resistivity than that obtained in the reference samples: a twofold to fourfold reduction in the contact resistivity is found using cross-bridge Kelvin structures in combination with two-dimensional numerical simulation. As C40 (Nb,Ti)Si-2 forms at the interface when an interfacial Nb is present, the interface characterized is likely to represent the one between (Nb,Ti)Si-2 and Si. For the reference samples, the interface studied is between TiSi2 and Si.
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- Aberg, V., et al.
(författare)
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Synthesis and absolute configuration of methyl(-)-(3R)-8-(4-bromophenyl)-7-(naphthalen-1-yl-methyl)-5-oxo-2,3-dihydro-5H-thiazolo 3,2-a pyridine-3-carboxylate
- 2002
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Ingår i: Acta Crystallographica Section E. - : International Union of Crystallography (IUCr). - 1600-5368. ; 58, s. o812-o814
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Tidskriftsartikel (refereegranskat)abstract
- The title molecule, C26H20BrNO3S, contains a ring-fused 2-pyridinone framework substituted with a 4-bromo-phenyl-, a naphthalen-1-ylmethyl and a methoxycarbonyl substituent. The main goal of this work was to confirm the stereochemistry for the methoxycarbonyl substituent, which proved to be 3R. Moreover, the 4-bromophenyl substituent was shown to be rotated out of the plane of the 2-pyridinone ring, with a torsion angle of 61.2 (5)degrees. To allow the best packing arrangement, the naphthalen-1-ylmethyl substituent is positioned to mediate an intermolecular pi-pi interaction.
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- Appelkvist, E L, et al.
(författare)
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Regulation of coenzyme Q biosynthesis
- 1994
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Ingår i: Molecular Aspects of Medicine. - 0098-2997 .- 1872-9452. ; 15:Suppl., s. 37-46
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Forskningsöversikt (refereegranskat)abstract
- The side-chain moiety of coenzyme Q is synthesized by a trans-prenyltransferase present in microsomes. Condensation of this moiety with the precursor ring takes place in the Golgi system. The enzymes involved, as well as the cytosolic geranylgeranyl-PP synthase, are regulated in an independent fashion. When the size of the farnesyl-PP pool is decreased or increased by employing appropriate inhibitors, the rate of CoQ synthesis is modified accordingly, indicating the dependence of trans-prenyltransferase activity on the level of intracellular substrate concentrations. Administration of peroxisome proliferators elevates CoQ concentrations not only in blood, but also in various tissues. Thus, it may be possible in the future to selectively increase CoQ concentrations in certain organs, without increasing the level of cholesterol.
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- Guintivano, Jerry, et al.
(författare)
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Meta-Analyses of Genome-Wide Association Studies for Postpartum Depression
- 2023
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Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 180:12, s. 884-895
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Postpartum depression (PPD) is a common subtype of major depressive disorder (MDD) that is more heritable, yet is understudied in psychiatric genetics. The authors conducted meta-analyses of genome-wide association studies (GWASs) to investigate the genetic architecture of PPD.METHOD: Meta-analyses were conducted on 18 cohorts of European ancestry (17,339 PPD cases and 53,426 controls), one cohort of East Asian ancestry (975 cases and 3,780 controls), and one cohort of African ancestry (456 cases and 1,255 controls), totaling 18,770 PPD cases and 58,461 controls. Post-GWAS analyses included 1) single-nucleotide polymorphism (SNP)-based heritability ([Formula: see text]), 2) genetic correlations between PPD and other phenotypes, and 3) enrichment of the PPD GWAS findings in 27 human tissues and 265 cell types from the mouse central and peripheral nervous system.RESULTS: No SNP achieved genome-wide significance in the European or the trans-ancestry meta-analyses. The [Formula: see text] of PPD was 0.14 (SE=0.02). Significant genetic correlations were estimated for PPD with MDD, bipolar disorder, anxiety disorders, posttraumatic stress disorder, insomnia, age at menarche, and polycystic ovary syndrome. Cell-type enrichment analyses implicate inhibitory neurons in the thalamus and cholinergic neurons within septal nuclei of the hypothalamus, a pattern that differs from MDD.CONCLUSIONS: While more samples are needed to reach genome-wide levels of significance, the results presented confirm PPD as a polygenic and heritable phenotype. There is also evidence that despite a high correlation with MDD, PPD may have unique genetic components. Cell enrichment results suggest GABAergic neurons, which converge on a common mechanism with the only medication approved by the U.S. Food and Drug Administration for PPD (brexanolone).
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- Hjern, A, et al.
(författare)
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Migration and atopic disorder in Swedish conscripts
- 1999
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Ingår i: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. - : Wiley. - 0905-6157. ; 10:3, s. 209-215
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Tidskriftsartikel (refereegranskat)
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- Norén, Åsa, et al.
(författare)
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Perioperative kidney injury in liver transplantation: a prospective study with renal histology and measured glomerular filtration rates
- 2022
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 57:5, s. 595-602
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Tidskriftsartikel (refereegranskat)abstract
- Background Acute kidney injury (AKI) is frequent after liver transplantation (LT), with impact on graft function, morbidity and mortality. Although multifactorial, the pathophysiology of perioperative kidney injury remains unclear. Our aims were to analyze the frequency, evolution and risk factors for kidney impairment during the peri- and early post-operative period. Methods In a prospective, single-center study of 27 adult patients undergoing first single-organ LT, we analyzed measured glomerular filtration rate (mGFR) pre-transplant, at post-operative day (POD) 10, and at 1, 3, 12 and 36 months. Kidney and liver graft biopsies were performed during LT. Results A median mGFR decline of 45% was detected from pre-transplant to POD 10, correlating strongly with the mGFR evolution from baseline to 12 months (rs = 0.80, p<.001) and baseline to 36 months (rs = 0.82, p<.001). AKI occurred in 59% of recipients within 48 h of LT, notably before the introduction of calcineurin inhibitors on POD 3. AKI was strongly associated with mGFR at 12 and 36 months. Kidney and liver graft biopsies showed only minor histological changes. Donor and recipient body mass index, recipient age, model of end-stage liver disease score, diagnosis of hepatitis C, donor cause of death, as well as bleeding, transfusions and duration of the anhepatic phase correlated with early kidney dysfunction. Conclusion The greatest decline in mGFR was evident within 10 days and AKI within hours of LT, irrespective of baseline mGFR and before introduction of calcineurin inhibitors. Very early post-LT kidney injury has substantial consequences for long-term kidney function.
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| 31. |
- Norrman, AE, et al.
(författare)
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Salivary Biomarkers and Oral Health in Liver Transplant Recipients, with an Emphasis on Diabetes
- 2021
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Ingår i: Diagnostics (Basel, Switzerland). - : MDPI AG. - 2075-4418. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- Salivary biomarkers have been linked to various systemic diseases. We examined the association between salivary biomarkers, periodontal health, and microbial burden in liver transplant (LT) recipients with and without diabetes, after transplantation. We hypothesized that diabetic recipients would exhibit impaired parameters. This study included 84 adults who received an LT between 2000 and 2006 in Finland. Dental treatment preceded transplantation. The recipients were re-examined, on average, six years later. We evaluated a battery of salivary biomarkers, microbiota, and subjective oral symptoms. Periodontal health was assessed, and immunosuppressive treatments were recorded. Recipients with impaired periodontal health showed higher matrix metalloproteinase-8 (MMP-8) levels (p < 0.05) and MMP-8/tissue inhibitor of matrix metalloproteinase 1 (TIMP1) ratios (p < 0.001) than recipients with good periodontal health. Diabetes post-LT was associated with impaired periodontal health (p < 0.05). No difference between groups was found in the microbial counts. Salivary biomarker levels did not seem to be affected by diabetes. However, the advanced pro-inflammatory state induced by and associated with periodontal inflammation was reflected in the salivary biomarker levels, especially MMP-8 and the MMP-8/TIMP-1 molar ratio. Thus, these salivary biomarkers may be useful for monitoring the oral inflammatory state and the course of LT recipients.
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- Schmitz, Birger, et al.
(författare)
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Basaltic explosive volcanism, but no comet impact, at the Paleocene-Eocene boundary: high-resolution chemical and isotopic records from Egypt, Spain and Denmark
- 2004
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Ingår i: Earth and Planetary Science Letters. - : Elsevier BV. - 1385-013X .- 0012-821X. ; 225:1-2, s. 1-17
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Tidskriftsartikel (refereegranskat)abstract
- In the search for a triggering mechanism for the Paleocene-Eocene (P-E) boundary event, 55 Ma, centimeter-resolution chemical (e.g., Ir, Os, Pt) and isotope (e.g., (OS)-O-187/Os-188, He-3/He-4, Sr-87/Sr-86) records across this boundary have been established for six uplifted marine sections in Egypt, Spain and Denmark. The sections studied represent some of the stratigraphically most complete records across the onset of the carbon isotopic excursion (CIE) and associated benthic foraminifera extinctions that mark the Paleocene-Eocene boundary. High-sensitivity analyses failed to uncover evidence of extraterrestrial element or isotope enrichments in the six sections, refuting the hypothesis of a major comet impact at the boundary. Preliminary searches for other impact-indicative features, such as spherules or shocked quartz, also gave negative results. In the Danish section studied, three basaltic Ir-rich ash layers occur at the Paleocene-Eocene boundary, but no similar ashes were found in Egypt or Spain. The three ashes represent the earliest known manifestation of an unusual I to 2 million year long phase of explosive basaltic volcanism in the Faero-Greenland region. This volcanism is synchronous with major flood basalt effusions in East Greenland and is associated with prominent paleogeographic changes in the high-latitude North Atlantic region. Discharge of mantle-derived Os to seawater during this volcanism may explain a small decrease in (OS)-O-187/(OS)-O-188 ratio at the Paleocene-Eocene boundary in the Zumaya section in Spain. The environmental perturbations at the Paleocene-Eocene boundary appear to have been triggered by basaltic volcanism, but any model for the detailed causal relation remains speculative. (C) 2004 Elsevier B.V. All rights reserved.
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