Зависимость свойств толстопленочных терморезисторов от состава базовой шпинели

Изменением соотношения компонентов шпинели Cu1-x-yCo2yMn2-yO4 получены толстопленочные терморезисторы с удельным объемным электросопротивлением 1,5-33 Омм и тепловой константой В25/85 2980-3690 К

HLA-A Confers an HLA-DRB1 Independent Influence on the Risk of Multiple Sclerosis

A recent high-density linkage screen confirmed that the HLA complex contains the strongest genetic factor for the risk of multiple sclerosis (MS). In parallel, a linkage disequilibrium analysis using 650 single nucleotide polymorphisms (SNP) markers of the HLA complex mapped the entire genetic effect to the HLA-DR-DQ subregion, reflected by the well-established risk haplotype HLA-DRB1*15,DQB1*06. Contrary to this, in a cohort of 1,084 MS patients and 1,347 controls, we show that the HLA-A gene confers an HLA-DRB1 independent influence on the risk of MS (P = 8.4×10−10). This supports the opposing view, that genes in the HLA class I region indeed exert an additional influence on the risk of MS, and confirms that the class I allele HLA-A*02 is negatively associated with the risk of MS (OR = 0.63, P = 7×10−12) not explained by linkage disequilibrium with class II. The combination of HLA-A and HLA-DRB1 alleles, as represented by HLA-A*02 and HLA-DRB1*15, was found to influence the risk of MS 23-fold. These findings imply complex autoimmune mechanisms involving both the regulatory and the effector arms of the immune system in the triggering of MS

Importance of Human Leukocyte Antigen (HLA) Class I and II Alleles on the Risk of Multiple Sclerosis

Multiple sclerosis (MS) is a complex disease of the central nervous system of unknown etiology. The human leukocyte antigen (HLA) locus on chromosome 6 confers a considerable part of the susceptibility to MS, and the most important factor is the class II allele HLA-DRB1*15:01. In addition, we and others have previously established a protective effect of HLA-A*02. Here, we genotyped 1,784 patients and 1,660 healthy controls from Scandinavia for the HLA-A, HLA-B, HLA-C and HLA-DRB1 genes and investigated their effects on MS risk by logistic regression. Several allele groups were found to exert effects independently of DRB1*15 and A*02, in particular DRB1*01 (OR = 0.82, p = 0.034) and B*12 (including B*44/45, OR = 0.76, p = 0.0028), confirming previous reports. Furthermore, we observed interaction between allele groups: DRB1*15 and DRB1*01 (multiplicative: OR = 0.54, p = 0.0041; additive: AP = 0.47, p = 4×10−06), DRB1*15 and C*12 (multiplicative: OR = 0.37, p = 0.00035; additive: AP = 0.58, p = 2.6×10−05), indicating that the effect size of these allele groups varies when taking DRB1*15 into account. Analysis of inferred haplotypes showed that almost all DRB1*15 bearing haplotypes were risk haplotypes, and that all A*02 bearing haplotypes were protective as long as they did not carry DRB1*15. In contrast, we found one class I haplotype, carrying A*02-C*05-B*12, which abolished the risk of DRB1*15. In conclusion, these results confirms a complex role of HLA class I and II genes that goes beyond DRB1*15 and A*02, in particular by including all three classical HLA class I genes as well as functional interactions between DRB1*15 and several alleles of DRB1 and class I genes

On genetics and transcriptomics of multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, where both genetic and environmental factors influence one individual s risk of developing the disease. This thesis is focused on genetic and transcriptomic aspects of MS. Twelve genes have been investigated genetically for their possible independent and interaction mediated effects on MS susceptibility and clinical phenotypes, of which five genes were assessed more thoroughly: HLAA, HLA-DRB1, CD58, HDGFRP3 and RPL5. The MS association with HLA-A was investigated in Study I using a cohort consisting of 1,084 MS patients and 1,347 controls. Logistic regression modelling firmly established an association suggesting a protective effect of the HLA-A*02 allele (OR: 0.63, p-value: 7x10-12). In Study IV CD58, HDGFRP3 and RPL5 were investigated genetically due to previously suggested association in a genome wide association study, and because they had shown differential expression in the CSF of MS patients (Study III). CD58 and RPL5 were confirmed to be associated with MS susceptibility in 1,077 MS patients and 1,217 controls. SNPs in CD58 conferred a multiplicative effect (ORs: 1.4-1.2, p-values: 8x10-5 3x10-2), whereas the effect of RPL5 variants on MS susceptibility was conferred by the heterozygotes (OR: 1.2, p-value: 2x10-2). These genes were suggested to affect MS independently of each other as well as other known risk factors: sex, HLA-DRB1, IL7R, IL2Rα, CLEC16A, CD226, SH2B3 and KIF1B. The interplay between these factors was elucidated, and possible epistatic effects were discovered that warrant further investigation. Furthermore, we confirmed the association between HLA-DRB1*15 and lower age at onset, but alleles of neither HLA-A, CD58, HDGFRP3 nor RPL5 were found to affect severity or course of disease in Study II & IV. In Study III gene expression profiling was performed for the first time in CSF cells from MS patients and over 4,000 transcripts were found to be differentially expressed. Simultaneously gene expression was also investigated in peripheral blood lymphocytes (PBL), and patients in an active phase of disease (relapse) were compared to those sampled in remission. These four comparisons revealed that in contrary to cells of the CSF, PBL samples did not show differential expression between MS patients and controls. Intriguingly, when comparing MS patients in relapse to those in remission, PBL samples showed more than 1,000 differentially expressed transcripts whereas in CSF cells no transcripts were differently expressed. Our results imply that MS is accompanied by active and proliferating cells in the CSF, distinguished by the regulation of genes belonging to immune related pathways. The differential expression in blood lymphocytes was characterized by a generally higher expression in relapse but with lower metabolism of several amino acids. The regulation in PBL, but not in CSF cells, implies the importance of peripheral events in driving a disease bout in MS

Migration background, eating disorder symptoms and healthcare service utilisation : findings from the Stockholm Public Health Cohort

Background: From a global perspective, eating disorders are increasingly common, probably because of societal transformation and improved detection. However, research on the impact of migration on the development of eating disorders is scarce, and previously reported results are conflicting. Aims: To explore if eating disorder symptom prevalence varies according to birth region, parents' birth region and neighbourhood characteristics, and analyse if the observed patterns match the likelihood of being in specialist treatment. Method: This study uses data from a large population-based health survey (N = 47 662) among adults in Stockholm, Sweden. A general linear model for complex samples, including adjustment for gender and age, was used to explore self-reported eating disorder symptoms. Odds ratios were calculated for individual symptoms. Results: Eating disorder symptoms are substantially more common in individuals born abroad, especially for migrants from a non-European country. This holds true for all surveyed symptoms, including restrictive eating (odds ratio 5.5, 95% CI 4.5-6.7), compensatory vomiting (odds ratio 6.1, 95% CI 4.6-8.0), loss-of-control eating (odds ratio 2.6, 95% CI 2.3-3.1) and preoccupation with food (odds ratio 2.3, 95% CI 1.9-2.8). Likewise, symptoms are more common in individuals with both parents born abroad and individuals living in districts with a high percentage of migrant residents. A gap exists between district-level symptom scores and the likelihood of being in specialist eating disorder treatment. Conclusions: These findings call for oversight of current outreach strategies, and highlight the need for efforts to reduce stigma and increase eating disorder symptom recognition in broader groups