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- Sandholm, Niina, et al.
(författare)
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New susceptibility loci associated with kidney disease in type 1 diabetes
- 2012
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Ingår i: PLOS Genetics. - San Francisco, USA : Public Library of Science, PLOS. - 1553-7390 .- 1553-7404. ; 8:9, s. e1002921-
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Tidskriftsartikel (refereegranskat)abstract
- Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genomewide association studies (GWAS) of T1D DN comprising similar to 2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2 x 10(-8)) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0 x 10(-9)). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-beta 1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1 x 10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.
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- Hietala, H., et al.
(författare)
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Supermagnetosonic subsolar magnetosheath jets and their effects : from the solar wind to the ionospheric convection
- 2012
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Ingår i: Annales Geophysicae. - : Copernicus GmbH. - 0992-7689 .- 1432-0576. ; 30:1, s. 33-48
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Tidskriftsartikel (refereegranskat)abstract
- It has recently been proposed that ripples inherent to the bow shock during radial interplanetary magnetic field (IMF) may produce local high speed flows in the magnetosheath. These jets can have a dynamic pressure much larger than the dynamic pressure of the solar wind. On 17 March 2007, several jets of this type were observed by the Cluster spacecraft. We study in detail these jets and their effects on the magnetopause, the magnetosphere, and the ionospheric convection. We find that (1) the jets could have a scale size of up to a few RE but less than similar to 6 R-E transverse to the XGSE axis; (2) the jets caused significant local magnetopause perturbations due to their high dynamic pressure; (3) during the period when the jets were observed, irregular pulsations at the geostationary orbit and localised flow enhancements in the ionosphere were detected. We suggest that these inner magnetospheric phenomena were caused by the magnetosheath jets.
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