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- Sedimbi, S. K., et al.
(författare)
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SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients
- 2007
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Ingår i: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 518-21
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Tidskriftsartikel (refereegranskat)abstract
- SUMO4 M55V, located in IDDM5, has been a focus for debate because of its association to type I diabetes (TIDM) in Asians but not in Caucasians. The current study aims to test the significance of M55V association to TIDM in a large cohort of Swedish Caucasians, and to test whether M55V is associated in those carrying human leukocyte antigen (HLA) class II molecules. A total of 673 TIDM patients and 535 age- and sex-matched healthy controls were included in the study. PCR-RFLP was performed to identify the genotype and allele variations. Our data suggest that SUMO4 M55V is not associated with susceptibility to TIDM by itself. When we stratified our patients and controls based on heterozygosity for HLA-DR3/DR4 and SUMO4 genotypes, we found that presence of SUMO4 GG increased further the relative risk conferred by HLA-DR3/DR4 to TIDM, whereas SUMO4 AA decreased the risk. From the current study, we conclude that SUMO4 M55V is associated with TIDM in association with high-risk HLA-DR3 and DR4, but not by itself.
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| 3. |
- Johansson, R, et al.
(författare)
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Transiently binding antibody fragments against Lewis x and sialyl-Lewis x
- 2006
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Ingår i: Journal of Immunological Methods. - : Elsevier BV. - 1872-7905 .- 0022-1759. ; 312:1-2, s. 20-26
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Tidskriftsartikel (refereegranskat)abstract
- Biomolecular recognition is often characterised by low affinity where many weak interactions work either alone or in concert, resulting in an inherent dynamic situation. For example the well-studied weak binding of cell-cell interactions is predominantly based on a range of carbohydrates that interact with numerous (protein) ligands. Finding appropriate binders to these carbohydrate structures may pave the way for new analytical strategies based on low affinity, and recombinant antibody technology is a promising approach to the development of such reagents. We have in the present study characterised two low affinity human single chain antibody fragments (scFv) by surface plasmon resonance for use in such applications. The two clones, LeX1 and sLeX10, had been selected from a naive phage display library against Lewis x (Le(x)) and sialyl Le(x) (sLe(x)), respectively. Both LeX1 and sLeX10 showed low affinity, with K-D values of 3.5 +/- 0.7 x 10(-5) M for Le(x) and 2.6 +/- 0.7 x 10(-5) M for sLe(x), respectively. Kinetic studies revealed the scFvs to be associated with fast dissociation rates, with K-d values higher than 0.1 s(-1) for both LeX1 and sLeX10. Apart from the Lewis structures Le(x) and sLe(x), we investigated the conforinational isomers Lewis a and sialyl-Lewis a together with the monosaccharide units of the Lewis structures, and both scFvs showed high specificity for their respective carbohydrate. Taking these observations together we have demonstrated that scFv with fast reaction kinetics and low affinity have the necessary characteristics for further development as specific tools in analytical strategies, e.g. differentiation of cells based on the various configurations of carbohydrate epitopes. (c) 2006 Elsevier B.V. All rights reserved.
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| 6. |
- Nilsson, R. Anders, 1976-
(författare)
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Dangerous Liaisons : Why Ex-Combatants Return to Violence. Cases from the Republic of Congo and Sierra Leone
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- After disarming and demobilizing, why do some ex-combatants re-engage in organized vio-lence, while others do not? Even though former fighters have been identified as a major source of insecurity in post-civil war societies due to their military know-how, there have been few efforts to systematically examine this puzzle. This study fills this research gap by comparing the presence or absence of organized violence in different ex-combatant communi-ties – all the former fighters that used to belong to the same armed faction and who share a common, horizontal identity based on shared war-and peacetime experiences. It does so by analyzing six ex-combatant communities in two countries: ex-Cobra, Cocoye and Ninja in the Republic of Congo and ex-AFRC, CDF and RUF in Sierra Leone. More specifically, three concepts – remarginalization (former fighters’ lack of political influence, personal security or economic assistance), remobilizers (individuals who have the will, capacity and skills to coordinate organized violence in a post-conflict setting) and relationships (whether or not remobilizers share social or material bonds, conducive for war, with ex-combatant communi-ties and each other) – are applied to the six cases, in order to explain why relatively many former CDF, Cobra, Ninja and RUF fighters resorted to violence, while no or hardly any ex-AFRC and Cocoye combatants did the same. Contrary to assumptions found in previous research, this study finds that structural factors, relating to remarginalization, have little ex-planatory value in themselves. Being a rule, rather than an exception, remarginalization can best be understood as a background variable, creating conducive conditions for violence to take place. Instead, the main determinants of ex-combatant violence are whether former fight-ers have access to regional or domestic elites in the market for experienced fighters and to second-tier individuals – such as former mid-level commanders – who can act as intermediar-ies between the two. By utilizing relationships based on selective incentives and social net-works, these two kinds of remobilizers are able to generate the needed enticements and feel-ings of affinity, trust or fear, to convince ex-combatants to resort to arms. These findings demonstrate that the outbreak of ex-combatant violence can only be understood by more clearly incorporating an actor perspective, focusing on three levels of analysis: the elite, mid-level and grass-root.
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| 8. |
- Shin, J. H., et al.
(författare)
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IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5
- 2007
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Ingår i: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 503-12
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Tidskriftsartikel (refereegranskat)abstract
- In a large case-control study of Swedish incident type I diabetes patients and controls, 0-34 years of age, we tested the hypothesis that the GIMAP5 gene, a key genetic factor for lymphopenia in spontaneous BioBreeding rat diabetes, is associated with type I diabetes; with islet autoantibodies in incident type I diabetes patients or with age at clinical onset in incident type I diabetes patients. Initial scans of allelic association were followed by more detailed logistic regression modeling that adjusted for known type I diabetes risk factors and potential confounding variables. The single nucleotide polymorphism (SNP) rs6598, located in a polyadenylation signal of GIMAP5, was associated with the presence of significant levels of IA-2 autoantibodies in the type I diabetes patients. Patients with the minor allele A of rs6598 had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected P=0.003), after adjusting for age at clinical onset (P=8.0 x 10(-13)) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 x 10(-5)) and DQ A1*0301-B1*0302 haplotypes (P=0.002). GIMAP5 polymorphism was not associated with type I diabetes or with GAD65 or insulin autoantibodies, ICA, or age at clinical onset in patients. These data suggest that the GIMAP5 gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.
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