Insights into the molecular genetics of celiac disease : Applying family- and population-based strategies

Celiac disease, or gluten intolerance, is triggered by dietary glutens in genetically susceptible individuals and it affects approximately 1% of the Caucasian population. The best known genetic risk factors for celiac disease are HLA DQ2 and DQ8 heterodimers, which are necessary for the development of the disease. However, they alone are not sufficient for disease induction, other risk factors are required. This thesis investigated genetic factors for celiac disease, concentrating on susceptibility loci on chromosomes 5q31-q33, 19p13 and 2q12 previously reported in genome-wide linkage and association studies. In addition, a novel genotyping method for the detection of HLA DQ2 and DQ8 coding haplotypes was validated. This study was conducted using Finnish and Hungarian family materials, and Finnish, Hungarian and Italian case-control materials. Genetic linkage and association were analysed in these materials using candidate gene and fine-mapping approaches. The results confirmed linkage to celiac disease on the chromosomal regions 5q31-q33 and 19p13. Fine-mapping on chromosome 5q31-q33 revealed several modest associations in the region, and highlighted the need for further investigations to locate the causal risk variants. The MYO9B gene on chromosome 19p13 showed evidence for linkage and association particularly with dermatitis herpetiformis, the skin manifestation of celiac disease. This implies a potential difference in the genetic background of the intestinal and skin forms of the disease, although studies on larger samplesets are required. The IL18RAP locus on chromosome 2q12, shown to be associated with celiac disease in a previous genome-wide association study and a subsequent follow-up, showed association in the Hungarian population in this study. The expression of IL18RAP was further investigated in small intestinal tissue and in peripheral blood mononuclear cells. The results showed that IL18RAP is expressed in the relevant tissues. Two putative isoforms of IL18RAP were detected by Western blot analysis, and the results suggested that the ratios and total levels of these isoforms may contribute to the aetiology of celiac disease. A novel genotyping method for celiac disease-associated HLA haplotypes was also validated in this thesis. The method utilises single-nucleotide polymorphisms tagging these HLA haplotypes with high sensitivity and specificity. Our results suggest that this method is transferable between populations, and it is suitable for large-scale analysis. In conclusion, this doctorate study provides an insight into the roles of the 5q31-q33, MYO9B, IL18RAP and HLA loci in the susceptibility to celiac disease in the Finnish, Hungarian and Italian populations, highlighting the need for further studies at these genetic loci and examination of the function of the candidate genes.

Physical characterization of plastic surfaces in wearing and cleanability research

Plastic surfaces are a group of materials used for many purposes. The present study was focused on methods for investigation of surface topography, wearing and cleanability of polyvinyl chloride (PVC) model surfaces and industrial plastic surfaces. Contact profilometry, scanning electron microscopy (SEM) and atomic force microscopy (AFM) are powerful methods for studying the topography of plastic surfaces. Although they have their own limitations, they are together an effective tool providing useful information on surface topography, especially when studying laboratory-made PVC model surfaces with known chemical compositions and structures. All examined laboratory-made PVC plastic surfaces examined in this work could be considered as smooth according to both AFM and profilometer measurements because height differences are in the nanoscale on every surface. Industrial plastic surfaces are a complex group of materials because of their chemical and topographical heterogeneity, but they are nevertheless important reference materials when developing cleaning and wearing methods. According to the results of this study the Soiling and Wearing Drum and the Frick-Taber methods are very useful when simulating three-body wearing of plastic surfaces. Both the investigated wearing methods can be used to compare the wearing of different plastic materials using appropriate evaluation methods of wearing and industrial use. In this study, physical methods were developed and adapted from other fields of material research to cleanability studies. The thesis focuses on the methodology for investigating the cleanability of plastic surfaces under realistic conditions, where surface topography and the effect of wear cleanability were among the major topics. A colorimetric method proved to be suitable for examining the cleanability of the industrial plastic surfaces. The results were utilized to evaluate the relationship between cleanability and the surface properties of plastic surfaces. The devices and methods used in the work can be utilized both in material research and product development.

Henkilöstöjohtamisen tehostaminen valtionhallinnossa henkilöstötilinpäätös-informaation avulla. Empiirinen tutkimus Suomen valtionhallinnossa tuotettavan henkilöstötilinpäätösinformaation arvosta johtamisessa

Tutkimuksessa selvitetään, edistääkö Suomen valtionhallinnossa tuotettava henkilöstötilinpäätösinformaatio henkilöstöprosesseihin perustuvan henkilöstöstrategian tehokasta toteuttamista. Tutkimuksen uutuusarvo alan kansainvälisen tutkimuksen kentässä perustuu laaja-alaiseen tarkastelunäkökulmaan. Tämän mahdollisti tutkimuskohteena olevasta ilmiöstä käytössä oleva monipuolinen, yhtenäisiin käsitteisiin perustuva ja useita vuosia koskeva henkilöstötilinpäätöksen tunnuslukuaineisto. Aikaisempien tutkimusten usein yksittäisiin tekijöihin perustuvasta analyysistä poiketen, tutkimuksella selvitettiin henkilöstön johtamiseen ja tuloksellisuuteen sidoksissa olevien tekijöiden vaikutuksia laajoina kokonaisuuksina, koskien kaikkia henkilöstön johtamisprosesseja. Tutkimus avaa uusia näköaloja henkilöstöinformaation hyväksikäytölle henkilöstön eri johtamisprosesseissa, jotka liittyvät saumattomasti organisaation toimintaan ja kokonaisjohtamiseen. Käytetty henkilöstön johtamisprosessikeskeinen tarkastelukulma auttaa ymmärtämään henkilöstön osaamisen, motivaation, työhyvinvoinnin, johtamisen ja palkinnan yhteyksiä sekä toisiinsa että organisaation pitkäjänteiseen toimintaan ja tuloksellisuuteen. Tutkimuksen keskeinen tavoite on motivoida johtoa, esimiehiä ja HR -ammattilaisia entistä enemmän hyväksikäyttämään henkilöstöön liittyvää analysoitua tietoa henkilöstöstrategioiden teon ja käytäntöön viennin, johtamisen ja henkilöstösuunnittelun apuvälineenä.