The Combined Deficiency of Immunoproteasome Subunits Affects Both the Magnitude and Quality of Pathogen- and Genetic Vaccination-Induced CD8+ T Cell Responses to the Human Protozoan Parasite Trypanosoma cruzi

The beta1i, beta2i and beta5i immunoproteasome subunits have an important role in defining the repertoire of MHC class I-restricted epitopes. However, the impact of combined deficiency of the three immunoproteasome subunits in the development of protective immunity to intracellular pathogens has not been investigated. Here, we demonstrate that immunoproteasomes play a key role in host resistance and genetic vaccination-induced protection against the human pathogen Trypanosoma cruzi (the causative agent of Chagas disease), immunity to which is dependent on CD8+ T cells and IFN-gamma (the classical immunoproteasome inducer). We observed that infection with T. cruzi triggers the transcription of immunoproteasome genes, both in mice and humans. Importantly, genetically vaccinated or T. cruzi-infected beta1i, beta2i and beta5i triple knockout (TKO) mice presented significantly lower frequencies and numbers of splenic CD8+ effector T cells (CD8+CD44highCD62Llow) specific for the previously characterized immunodominant (VNHRFTLV) H-2Kb-restricted T. cruzi epitope. Not only the quantity, but also the quality of parasite-specific CD8+ T cell responses was altered in TKO mice. Hence, the frequency of double-positive (IFN-gamma+/TNF+) or single-positive (IFN-gamma+) cells specific for the H-2Kb-restricted immunodominant as well as subdominant T. cruzi epitopes were higher in WT mice, whereas TNF single-positive cells prevailed among CD8+ T cells from TKO mice. Contrasting with their WT counterparts, TKO animals were also lethally susceptible to T. cruzi challenge, even after an otherwise protective vaccination with DNA and adenoviral vectors. We conclude that the immunoproteasome subunits are key determinants in host resistance to T. cruzi infection by influencing both the magnitude and quality of CD8+ T cell responses

Mediators of the Link Between Autistic Traits and Relationship Satisfaction in a Non-Clinical Sample

People with ASD have deficits in their social skills and may therefore experience lower relationship satisfaction. This study investigated possible mechanisms to explain whether and how autistic traits, measured with the AQ, influence relationship satisfaction in a non-clinical sample of 195 married couples. More autistic traits were associated with lower relationship satisfaction for husbands but not for wives. Multiple mediation analyses revealed that husbands’ responsiveness towards their wives, trust, and intimacy mediated this link between autistic traits and relationship satisfaction. These findings suggest that autistic traits may hamper men’s relationship satisfaction because they impede relationship-specific feelings and behavior. There was no partner-effect of autistic traits, indicating that more autistic traits do not necessarily influence the partner’s perceptions of relationship satisfaction

Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis

In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci

Mapping Robots to Therapy and Educational Objectives for Children with Autism Spectrum Disorder

The aim of this study was to increase knowledge on therapy and educational objectives professionals work on with children with autism spectrum disorder (ASD) and to identify corresponding state of the art robots. Focus group sessions (n = 9) with ASD professionals (n = 53) from nine organisations were carried out to create an objectives overview, followed by a systematic literature study to identify state of the art robots matching these objectives. Professionals identified many ASD objectives (n = 74) in 9 different domains. State of the art robots addressed 24 of these objectives in 8 domains. Robots can potentially be applied to a large scope of objectives for children with ASD. This objectives overview functions as a base to guide development of robot interventions for these children

Validation of the Body Concealment Scale for Scleroderma (BCSS): Replication in the Scleroderma Patient-centered Intervention Network (SPIN) Cohort

© 2016 Elsevier Ltd Body concealment is an important component of appearance distress for individuals with disfiguring conditions, including scleroderma. The objective was to replicate the validation study of the Body Concealment Scale for Scleroderma (BCSS) among 897 scleroderma patients. The factor structure of the BCSS was evaluated using confirmatory factor analysis and the Multiple-Indicator Multiple-Cause model examined differential item functioning of SWAP items for sex and age. Internal consistency reliability was assessed via Cronbach's alpha. Construct validity was assessed by comparing the BCSS with a measure of body image distress and measures of mental health and pain intensity. Results replicated the original validation study, where a bifactor model provided the best fit. The BCSS demonstrated strong internal consistency reliability and construct validity. Findings further support the BCSS as a valid measure of body concealment in scleroderma and provide new evidence that scores can be compared and combined across sexes and ages