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- Saliba-Gustafsson, P., et al.
(författare)
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Subclinical atherosclerosis and its progression are modulated by PLIN2 through a feed-forward loop between LXR and autophagy
- 2019
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 660-675
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Tidskriftsartikel (refereegranskat)abstract
- Background Hyperlipidaemia is a major risk factor for cardiovascular disease, and atherosclerosis is the underlying cause of both myocardial infarction and stroke. We have previously shown that the Pro251 variant of perilipin-2 reduces plasma triglycerides and may therefore be beneficial to reduce atherosclerosis development. Objective We sought to delineate putative beneficial effects of the Pro251 variant of perlipin-2 on subclinical atherosclerosis and the mechanism by which it acts. Methods A pan-European cohort of high-risk individuals where carotid intima-media thickness has been assessed was adopted. Human primary monocyte-derived macrophages were prepared from whole blood from individuals recruited by perilipin-2 genotype or from buffy coats from the Karolinska University hospital blood central. Results The Pro251 variant of perilipin-2 is associated with decreased intima-media thickness at baseline and over 30 months of follow-up. Using human primary monocyte-derived macrophages from carriers of the beneficial Pro251 variant, we show that this variant increases autophagy activity, cholesterol efflux and a controlled inflammatory response. Through extensive mechanistic studies, we demonstrate that increase in autophagy activity is accompanied with an increase in liver-X-receptor (LXR) activity and that LXR and autophagy reciprocally activate each other in a feed-forward loop, regulated by CYP27A1 and 27OH-cholesterol. Conclusions For the first time, we show that perilipin-2 affects susceptibility to human atherosclerosis through activation of autophagy and stimulation of cholesterol efflux. We demonstrate that perilipin-2 modulates levels of the LXR ligand 27OH-cholesterol and initiates a feed-forward loop where LXR and autophagy reciprocally activate each other; the mechanism by which perilipin-2 exerts its beneficial effects on subclinical atherosclerosis.
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- Merlone, A., et al.
(författare)
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The MeteoMet project - metrology for meteorology: challenges and results
- 2015
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Ingår i: Meteorological Applications. - : Wiley. - 1350-4827 .- 1469-8080. ; 22, s. 820-829
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Tidskriftsartikel (refereegranskat)abstract
- The study describes significant outcomes of the Metrology for Meteorology' project, MeteoMet, which is an attempt to bridge the meteorological and metrological communities. The concept of traceability, an idea used in both fields but with a subtle difference in meaning, is at the heart of the project. For meteorology, a traceable measurement is the one that can be traced back to a particular instrument, time and location. From a metrological perspective, traceability further implies that the measurement can be traced back to a primary realization of the quantity being measured in terms of the base units of the International System of Units, the SI. These two perspectives reflect long-standing differences in culture and practice and this project - and this study - represents only the first step towards better communication between the two communities. The 3 year MeteoMet project was funded by the European Metrology Research Program (EMRP) and involved 18 European National Metrological Institutes, 3 universities and 35 collaborating stakeholders including national meteorology organizations, research institutes, universities, associations and instrument companies. The project brought a metrological perspective to several long-standing measurement problems in meteorology and climatology, varying from conventional ground-based measurements to those made in the upper atmosphere. It included development and testing of novel instrumentation as well as improved calibration procedures and facilities, instrument intercomparison under realistic conditions and best practice dissemination. Additionally, the validation of historical temperature data series with respect to measurement uncertainties and a methodology for recalculation of the values were included.
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- Steinthorsdottir, V, et al.
(författare)
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Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 5976-
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Tidskriftsartikel (refereegranskat)abstract
- Preeclampsia is a serious complication of pregnancy, affecting both maternal and fetal health. In genome-wide association meta-analysis of European and Central Asian mothers, we identify sequence variants that associate with preeclampsia in the maternal genome at ZNF831/20q13 and FTO/16q12. These are previously established variants for blood pressure (BP) and the FTO variant has also been associated with body mass index (BMI). Further analysis of BP variants establishes that variants at MECOM/3q26, FGF5/4q21 and SH2B3/12q24 also associate with preeclampsia through the maternal genome. We further show that a polygenic risk score for hypertension associates with preeclampsia. However, comparison with gestational hypertension indicates that additional factors modify the risk of preeclampsia.
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- Vehmas, A. P., et al.
(författare)
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Ovarian Endometriosis Signatures Established through Discovery and Directed Mass Spectrometry Analysis
- 2014
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 13:11, s. 4983-4994
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Tidskriftsartikel (refereegranskat)abstract
- New molecular information on potential therapeutic targets or tools for noninvasive diagnosis for endometriosis are important for patient care and treatment. However, surprisingly few efforts have described endometriosis at the protein level. In this work we enumerate the proteins in patient endometrium and ovarian endometrioma by extensive and comprehensive analysis of minute amounts of cryosectioned tissues in a three-tiered mass spectrometric approach. Quantitative comparison of the tissues revealed 214 differentially expressed proteins in ovarian endometrioma and endometrium. These proteins are reported here as a resource of SRM (selected reaction monitoring) assays that are unique, standardized, and openly available. Pathway analysis of the proteome measurements revealed a potential role for Transforming growth factor beta-1 in ovarian endometriosis development. Subsequent mRNA microarray analysis further revealed clear ovarian endometrioma specificity for a subset of these proteins, which was also supported by further in silico studies. In this process two important proteins emerged, Calponin-1 and EMILIN-1, that were additionally confirmed in ovarian endometrioma tissues by immunohistochemistry and Western blotting. This study provides the most comprehensive molecular description of ovarian endometriosis to date and researchers with new molecular methods and tools for high throughput patient screening using the SRM assays.
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- Bell, S., et al.
(författare)
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METefnet : Developments in metrology for moisture in materials
- 2015
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Ingår i: 17th International Congress of Metrology, CIM 2015. - Les Ulis, France : EDP Sciences.
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Konferensbidrag (refereegranskat)abstract
- Bien que les mesures de teneur en eau soient largement utilisées dans l'industrie, les considérations métrologiques quant à cette mesure ne sont pas complètement abouties de sorte à fournir des mesures fiables et traçables au SI. Afin de remédier à ceci, le projet de recherche conjoint, Joint Research Project SIB64 “METefnet – Metrology for moisture in materials”, est actuellement en cours, et contribue au programme européen de recherche en métrologie European Metrology Research Programme. Le projet METefnet a pour objectifs de développer et d'améliorer l'approche métrologique de ce sujet. Ceci inclus notamment: le travail sur de nouvelles méthodes de référence pour évaluer la fraction massique en eau, l'amélioration des mesures mettant en œuvre la méthode primaire de type titration Karl Fischer, le développement de nouveaux matériaux de référence certifiés présentant une très bonne stabilité et permettant une traçabilité au SI, le développement de nouveaux étalons de transfert, la réalisation d'études visant à quantifier et réduire les effets liés à la prise d'échantillon, son transport et sa manipulation, le développement d'une nouvelle méthode pour étalonner les instruments mesurant l'humidité de surface, et l'amélioration des méthodes d'estimation d'incertitudes de ces mesures. Ce travail, réalisé dans le domaine de la métrologie de l'humidité au sein des matériaux, couvre à la fois le mesurande décrit comme étant spécifiquement la teneur en eau, seule, dans les matériaux, mais également un mesurande plus large pouvant inclure l'eau ainsi que d'autres liquides ou composés organiques volatiles; ceci afin de bien mettre en exergue la différence qui peut être observée entre ces deux mesurandes. Le projet global a pour objectif de soutenir une action de dissémination et de traçabilité au système SI des mesures de teneur en eau dans les matériaux avec une exactitude optimale et de développer une infrastructure métrologique cohérente pour ce type de mesures. Le travail technique ainsi que les dernières avancées vous sont ainsi présentées.
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