| 2. |
- Agrawal, Mridul, et al.
(författare)
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TET2-mutant clonal hematopoiesis and risk of gout
- 2022
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 140:10, s. 1094-1103
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Tidskriftsartikel (refereegranskat)abstract
- Gout is a common inflammatory arthritis caused by precipitation of monosodium urate (MSU) crystals in individuals with hyperuricemia. Acute flares are accompanied by secretion of proinflammatory cytokines, including interleukin-1β (IL-1β). Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition predisposing to hematologic cancers and cardiovascular disease. CHIP is associated with elevated IL-1β, thus we investigated CHIP as a risk factor for gout. To test the clinical association between CHIP and gout, we analyzed whole exome sequencing data from 177 824 individuals in the MGB Biobank (MGBB) and UK Biobank (UKB). In both cohorts, the frequency of gout was higher among individuals with CHIP than without CHIP (MGBB, CHIP with variant allele fraction [VAF] ≥2%: odds ratio [OR], 1.69; 95% CI, 1.09-2.61; P = .0189; UKB, CHIP with VAF ≥10%: OR, 1.25; 95% CI, 1.05-1.50; P = .0133). Moreover, individuals with CHIP and a VAF ≥10% had an increased risk of incident gout (UKB: hazard ratio [HR], 1.28; 95% CI, 1.06-1.55; P = .0107). In murine models of gout pathogenesis, animals with Tet2 knockout hematopoietic cells had exaggerated IL-1β secretion and paw edema upon administration of MSU crystals. Tet2 knockout macrophages elaborated higher levels of IL-1β in response to MSU crystals in vitro, which was ameliorated through genetic and pharmacologic Nlrp3 inflammasome inhibition. These studies show that TET2-mutant CHIP is associated with an increased risk of gout in humans and that MSU crystals lead to elevated IL-1β levels in Tet2 knockout murine models. We identify CHIP as an amplifier of NLRP3-dependent inflammatory responses to MSU crystals in patients with gout.
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| 3. |
- Fossati, L., et al.
(författare)
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A detailed spectropolarimetric analysis of the planet-hosting star WASP-12
- 2010
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 720:1, s. 872-886
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Tidskriftsartikel (refereegranskat)abstract
- The knowledge of accurate stellar parameters is paramount in several fields of stellar astrophysics, particularly in the study of extrasolar planets, where often the star is the only visible component and therefore used to infer the planet's fundamental parameters. Another important aspect of the analysis of planetary systems is the stellar activity and the possible star planet interaction. Here, we present a self-consistent abundance analysis of the planet-hosting star WASP-12 and a high-precision search for a structured stellar magnetic field on the basis of spectropolarimetric observations obtained with the ESPaDOnS spectropolarimeter. Our results show that the star does not have a structured magnetic field, and that the obtained fundamental parameters are in good agreement with what was previously published. In addition, we derive improved constraints on the stellar age (1.0-2.65 Gyr), mass (1.23-1.49 M/M-circle dot), and distance (295-465 pc). WASP-12 is an ideal object in which to look for pollution signatures in the stellar atmosphere. We analyze the WASP-12 abundances as a function of the condensation temperature and compare them with those published by several other authors on planet-hosting and non-planet-hosting stars. We find hints of atmospheric pollution in WASP-12's photosphere but are unable to reach firm conclusions with our present data. We conclude that a differential analysis based on WASP-12 twins will probably clarify whether an atmospheric pollution is present as well as the nature of this pollution and its implications in planet formation and evolution. We also attempt the direct detection of the circumstellar disk through infrared excess, but without success.
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