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- Hov, J. R., et al.
(författare)
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Electrostatic Modifications of the Human Leukocyte Antigen-DR P9 Peptide-Binding Pocket and Susceptibility to Primary Sclerosing Cholangitis
- 2011
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Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 53:6, s. 1967-1976
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Tidskriftsartikel (refereegranskat)abstract
- The strongest genetic risk factors for primary sclerosing cholangitis (PSC) are found in the human leukocyte antigen (HLA) complex at chromosome 6p21. Genes in the HLA class II region encode molecules that present antigen to T lymphocytes. Polymorphisms in these genes are associated with most autoimmune diseases, most likely because they contribute to the specificity of immune responses. The aim of this study was to analyze the structure and electrostatic properties of the peptide-binding groove of HLA-DR in relation to PSC. Thus, four-digit resolution HLA-DRB1 genotyping was performed in 356 PSC patients and 366 healthy controls. Sequence information was used to assign which amino acids were encoded at all polymorphic positions. In stepwise logistic regressions, variations at residues 37 and 86 were independently associated with PSC (P = 1.2 x 10(-32) and P = 1.8 x 10(-22) in single-residue models, respectively). Three-dimensional modeling was performed to explore the effect of these key residues on the HLA-DR molecule. This analysis indicated that residue 37 was a major determinant of the electrostatic properties of pocket P9 of the peptide-binding groove. Asparagine at residue 37, which was associated with PSC, induced a positive charge in pocket P9. Tyrosine, which protected against PSC, induced a negative charge in this pocket. Consistent with the statistical observations, variation at residue 86 also indirectly influenced the electrostatic properties of this pocket. DRB1*13:01, which was PSC-associated, had a positive P9 pocket and DRB1*13:02, protective against PSC, had a negative P9 pocket. Conclusion: The results suggest that in patients with PSC, residues 37 and 86 of the HLA-DR beta chain critically influence the electrostatic properties of pocket P9 and thereby the range of peptides presented. (HEPATOLOGY 2011;53:1967-1976)
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- Kjellström, Erik, et al.
(författare)
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Emerging regional climate change signals for Europe under varying large-scale circulation conditions
- 2013
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Ingår i: Climate Research (CR). - : Inter-Research Science Center. - 0936-577X .- 1616-1572. ; 56:2, s. 103-119
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Tidskriftsartikel (refereegranskat)abstract
- A large ensemble of regional climate model projections was investigated regarding if and when they show an emergence of significant climate change signals in seasonal temperature and precipitation within Europe. The influence of the North Atlantic Oscillation (NAO), as simulated in the projections, was investigated. In most parts of Europe, the projections indicate robust emergence of temperature change in the first 2 decades of the 21st century, typically earlier for summer than for winter. For precipitation changes, signals generally emerge much later than for temperature. For Europe as a whole, the precipitation signals tend to emerge some 40 to 60 yr later than the temperature signals. In some sub-regions, robust signals for precipitation are not found within the studied period, i.e. until 2100. Some sub-regions, notably the Mediterranean area and Scandinavia, show different behaviour in some aspects compared to the ensemble-based results as a whole. NAO has some influence on the temperature change signals, which emerge earlier in winter for some models and regions if NAO is accounted for. For summer temperatures, the influence of NAO is less evident. Similarly, for precipitation, accounting for NAO leads to an earlier emergence in some regions and models. Here, we find an impact for both summer and winter.
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