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- Pervjakova, Natalia, et al.
(författare)
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Multi-ancestry genome-wide association study of gestational diabetes mellitus highlights genetic links with type 2 diabetes
- 2022
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 31:19, s. 3377-3391
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Tidskriftsartikel (refereegranskat)abstract
- Gestational diabetes mellitus (GDM) is associated with increased risk of pregnancy complications and adverse perinatal outcomes. GDM often reoccurs and is associated with increased risk of subsequent diagnosis of type 2 diabetes (T2D). To improve our understanding of the aetiological factors and molecular processes driving the occurrence of GDM, including the extent to which these overlap with T2D pathophysiology, the GENetics of Diabetes In Pregnancy (GenDIP) Consortium assembled genome-wide association studies (GWAS) of diverse ancestry in a total of 5485 women with GDM and 347 856 without GDM. Through multi-ancestry meta-analysis, we identified five loci with genome-wide significant association (p < 5x10-8) with GDM, mapping to/near MTNR1B (p = 4.3x10-54), TCF7L2 (p = 4.0x10-16), CDKAL1 (p = 1.6 × 10-14), CDKN2A-CDKN2B (p = 4.1x10-9) and HKDC1 (p = 2.9x10-8). Multiple lines of evidence pointed to the shared pathophysiology of GDM and T2D: (i) four of the five GDM loci (not HKDC1) have been previously reported at genome-wide significance for T2D; (ii) significant enrichment for associations with GDM at previously reported T2D loci; (iii) strong genetic correlation between GDM and T2D; and (iv) enrichment of GDM associations mapping to genomic annotations in diabetes-relevant tissues and transcription factor binding sites. Mendelian randomisation analyses demonstrated significant causal association (5% false discovery rate) of higher body mass index on increased GDM risk. Our results provide support for the hypothesis that GDM and T2D are part of the same underlying pathology but that, as exemplified by the HKDC1 locus, there are genetic determinants of GDM that are specific to glucose regulation in pregnancy.
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- Sevastianova, K, et al.
(författare)
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Comparison of Dorsocervical With Abdominal Subcutaneous Adipose Tissue in Patients With and Without Antiretroviral Therapy-Associated Lipodystrophy
- 2011
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 60:7, s. 1894-1900
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Combination antiretroviral therapy (cART) is associated with lipodystrophy, i.e., loss of subcutaneous adipose tissue in the abdomen, limbs, and face and its accumulation intra-abdominally. No fat is lost dorsocervically and it can even accumulate in this region (buffalo hump). It is unknown how preserved dorsocervical fat differs from abdominal subcutaneous fat in HIV-1-infected cART-treated patients with (cART+LD+) and without (cART+LD-) lipodystrophy. RESEARCH DESIGN AND METHODS: We used histology, microarray, PCR, and magnetic resonance imaging to compare dorsocervical and abdominal subcutaneous adipose tissue in cART+LD+ (n=21) and cART+LD- (n=11). RESULTS: Albeit dorsocervical adipose tissue in cART+LD+ seems spared from lipoatrophy, its mitochondrial DNA (mtDNA; copies/cell) content was significantly lower (by 62%) than that of the corresponding tissue in cART+LD-. Expression of CD68 mRNA, a marker of macrophages, and numerous inflammatory genes in microarray were significantly lower in dorsocervical versus abdominal subcutaneous adipose tissue. Genes with the greatest difference in expression between the two depots were those involved in regulation of transcription and regionalization (homeobox genes), irrespective of lipodystrophy status. There was negligible mRNA expression of uncoupling protein 1, a gene characteristic of brown adipose tissue, in either depot. CONCLUSIONS: Because mtDNA is depleted even in the nonatrophic dorsocervical adipose tissue, it is unlikely that the cause of lipoatrophy is loss of mtDNA. Dorsocervical adipose tissue is less inflamed than lipoatrophic adipose tissue. It does not resemble brown adipose tissue. The greatest difference in gene expression between dorsocervical and abdominal subcutaneous adipose tissue is in expression of homeobox genes.
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| 60. |
- Van Dorsselaere, J. -P, et al.
(författare)
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Status of the SARNET network on severe accidents
- 2010
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Ingår i: International Congress on Advances in Nuclear Power Plants 2010, ICAPP 2010. - 9781617386435 ; , s. 1029-1043
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Konferensbidrag (refereegranskat)abstract
- After four and a half years of operation in the frame of the 6th Framework Programme (FP6) of the European Commission, SARNET (Severe Accidents Research NETwork of excellence) continues in the FP7 (project named SARNET2) from April 2009 for 4 years. Forty-one organisations from 21 countries network their capacities of research in order to resolve the most important remaining uncertainties and safety issues on severe accidents (SA) in existing and future water-cooled nuclear power plants (NPPs). It includes a large majority of the Europeanactors involved in SA research plus a few non-European important ones. The objective is to perform the common research programmes that have been defined in the network first phase and to continue to improve the common computer tools and methodologies for NPP safety assessment. It will consolidate the sustainable integration of the European SA research capacities. These research programmes concern essentially the six highest priority safety issues that were identified after ranking in the first phase of the network: in-vessel core coolability, molten-corium-concrete-interaction, fuel-coolant interaction, hydrogen mixing and combustion in containment, impact of oxidising conditions on source term, and iodine chemistry. The Joint Programme of Activities includes the following main tasks: Performing new experiments on the above mentioned issues andjointly analysing their results in order to elaborate a common understanding of the concerned physical phenomena; Continuing the development and assessment of the ASTEC integral computer code (jointly developed by IRSN and GRS to predict the NPP behaviour during a postulated SA), which capitalizes in terms of models the knowledge produced in the network. In particular efforts are being extended to its applicability to BWR and CANDU NPP types; Continuing the storage of the SA experimental results in a scientific database, based on the STRESA JRC tool; Promoting educational and training courses, ERMSAR (European Review Meeting on Severe Accident Research) international conferences (to be held once a year) and mobility of young researchers or students between the various European organisations. Some R&D results obtained in the first year of the project are presented, in particular: the VULCANO experiment done in CEA mid-2009 on molten-core-corium-interaction, and the release of the first version of the new ASTEC V2 series.
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