Genomic clones for the human CD95 (Fas/APO-1) and CD40 genes have been isolated and 2.3 kb of the CD95 and 0.8 kb of the CD40 gene 5'-flanking regions sequenced. Comparisons of the human CD95 gene with the human CD40 and the murine CD40 and TNFR-II genes showed a low degree of sequence similarity. However, dot matrix analyses revealed conservation of two stretches between human CD95 (-387 to -362 and -288 to 261 in CD95) and murine TNFR-II genes. Additionally, TCCTCC motifs are present within 400 bp up-stream of the ATG of all genes examined. Repeated interferon-beta (IFN-beta) silencer B motifs and a lysozyme silencer 1 motif have been found in the CD95 gene at approximately -1,600 and -1,100, respectively. Sequence comparison of the 5'-flanking regions of the murine and human CD40 genes revealed the presence of a conserved AP-4 site and two SP-1 sites. CD95, CD40, and TNFR-II genes all lack classical TATA and CAAT boxes. However, a strongly increased frequency of CpG dinucleotides was found. Primer extension analysis revealed multiple transcriptional start sites in the CD95 gene, where the usage of individual start sites appeared to be cell type-specific. Functional analysis, using reporter constructs and transient transfections, identified a silencer activity residing between nucleotide positions -1,781 and -1007 and a strong enhancer region between -1,007 and -425 in the human CD95 gene. The region between -425 and -1 retained a basal promoter activity.(ABSTRACT TRUNCATED AT 250 WORDS)

The prevalence of MS has increased in the overall area, most markedly in Orkney, then Shetland, over the past 30 years. This increase could be due to a number of factors, but rising incidence as reflected by a rising sex ratio, influenced by gene-environment interaction, is the most likely. Orkney has the highest prevalence rate recorded worldwide.

Multiple sclerosis (MS) is an inflammatory autoimmune disorder affecting the central nervous system (CNS), with unresolved aetiology. Previous studies have implicated N-glycosylation, a highly regulated enzymatic attachment of complex sugars to targeted proteins, in MS pathogenesis. We investigated individual variation in N-glycosylation of the total plasma proteome and of IgG in MS. Both plasma protein and IgG N-glycans were chromatographically profiled and quantified in 83 MS cases and 88 age- and sex-matched controls. Comparing levels of glycosylation features between MS cases and controls revealed that core fucosylation (p = 6.96 × 10−3) and abundance of high-mannose structures (p = 1.48 × 10−2) were the most prominently altered IgG glycosylation traits. Significant changes in plasma protein N-glycome composition were observed for antennary fucosylated, tri- and tetrasialylated, tri- and tetragalactosylated, high-branched N-glycans (p-value range 1.66 × 10−2–4.28 × 10−2). Classification performance of N-glycans was examined by ROC curve analysis, resulting in an AUC of 0.852 for the total plasma N-glycome and 0.798 for IgG N-glycome prediction models. Our results indicate that multiple aspects of protein glycosylation are altered in MS, showing increased proinflammatory potential. N-glycan alterations showed substantial value in classification of the disease status, nonetheless, additional studies are warranted to explore their exact role in MS development and utility as biomarkers.

This qualitative research focused on identifying those store image attributes perceived as important by a selected group of female apparel consumers. In addition, their perception of Lindquist’s proposed dimensions of store image attributes was examined. Data were collected by means of eight focus groups. The non-verbal quali-quantive Schutte Visual Scale was employed to quantify responses. Results indicated that Merchandise and Clientele were perceived as the most important dimensions, followed by Service. The dimension Physical facilities was perceived as the least important. Differences between age and population groups were investigated. The store image attribute dimensions generated by the respondents differed slightly from those proposed by Lindquist. Implications for retailers and for further research were formulated.

There is strong evidence for both genetic and environmental risk factors comprising the aetiology of multiple sclerosis (MS). While much progress has been made in recent years in identifying common genetic variants using genome-wide association studies, alternative approaches have remained relatively neglected. The prevalence of MS in Orkney and Shetland is among the highest in the world. Previous studies have suggested that a higher degree of parental relatedness in these isolated communities may contribute to the high rates of MS, indicating that recessive effects have an important role in MS aetiology. The Northern Isles Multiple Sclerosis (NIMS) study investigated the potential role of genome-wide homozygosity in MS risk by genotyping 88 MS patients, 89 controls matched by age, sex and ancestry, and a further 89 controls matched for sex and ancestry, but passed the majority of lifetime risk of developing MS (470 years of age). Three participants were removed on the basis of pedigreegenomic anomalies (n¼263). Three measures of genome-wide homozygosity were generated for each individual, and association with MS was assessed using logistic regression models. No effect of genome-wide homozygosity was detected, indicating that inbreeding and consanguinity are not risk factors for MS in this population.