Characterisation of the Immunophenotype of Dogs with Primary Immune-Mediated Haemolytic Anaemia

Immune-mediated haemolytic anaemia (IMHA) is reported to be the most common autoimmune disease of dogs, resulting in significant morbidity and mortality in affected animals. Haemolysis is caused by the action of autoantibodies, but the immunological changes that result in their production have not been elucidated.To investigate the frequency of regulatory T cells (Tregs) and other lymphocyte subsets and to measure serum concentrations of cytokines and peripheral blood mononuclear cell expression of cytokine genes in dogs with IMHA, healthy dogs and dogs with inflammatory diseases.19 dogs with primary IMHA, 22 dogs with inflammatory diseases and 32 healthy control dogs.Residual EDTA-anti-coagulated blood samples were stained with fluorophore-conjugated monoclonal antibodies and analysed by flow cytometry to identify Tregs and other lymphocyte subsets. Total RNA was also extracted from peripheral blood mononuclear cells to investigate cytokine gene expression, and concentrations of serum cytokines (interleukins 2, 6 10, CXCL-8 and tumour necrosis factor α) were measured using enhanced chemiluminescent assays. Principal component analysis was used to investigate latent variables that might explain variability in the entire dataset.There was no difference in the frequency or absolute numbers of Tregs among groups, nor in the proportions of other lymphocyte subsets. The concentrations of pro-inflammatory cytokines were greater in dogs with IMHA compared to healthy controls, but the concentration of IL-10 and the expression of cytokine genes did not differ between groups. Principal component analysis identified four components that explained the majority of the variability in the dataset, which seemed to correspond to different aspects of the immune response.The immunophenotype of dogs with IMHA differed from that of dogs with inflammatory diseases and from healthy control dogs; some of these changes could suggest abnormalities in peripheral tolerance that permit development of autoimmune disease. The frequency of Tregs did not differ between groups, suggesting that deficiency in the number of these cells is not responsible for development of IMHA

Phenotypic characterisation of regulatory T cells in dogs reveals signature transcripts conserved in humans and mice

Regulatory T cells (Tregs) are a double-edged regulator of the immune system. Aberrations of Tregs correlate with pathogenesis of inflammatory, autoimmune and neoplastic disorders. Phenotypically and functionally distinct subsets of Tregs have been identified in humans and mice on the basis of their extensive portfolios of monoclonal antibodies (mAb) against Treg surface antigens. As an important veterinary species, dogs are increasingly recognised as an excellent model for many human diseases. However, insightful study of canine Tregs has been restrained by the limited availability of mAb. We therefore set out to characterise CD4+CD25high T cells isolated ex vivo from healthy dogs and showed that they possess a regulatory phenotype, function, and transcriptomic signature that resembles those of human and murine Tregs. By launching a cross-species comparison, we unveiled a conserved transcriptomic signature of Tregs and identified that transcript hip1 may have implications in Treg function

Choreographies of Inhabitation: an investigation into visual, auditory and spatial relationships

This paper investigates the notion of occupation as dynamic physical and multisensory relationships within architectural environments. Our study specifically focuses on the construction of myriad relationships between physical, visual and auditory articulations of space, and how these shape human activities and interactions. By drawing on literature from the areas of visual and acoustic ecology (Gibson, Truax, Schafer) we seek to frame the notion of human occupation as temporal interrelations between acoustic arenas, soundmarks, and sonic events, as well as their visual equivalents. Additionally, we use Brian Massumi's discussion of synaesthetic fusion, movement and sensation as a philosophical tool for interrogating these interrelations. For the design project we have nominated a site within RMIT University's city campus in Melbourne, Australia. The applied research methods include the auditory and visual capture of environmental data via video, still photography and stereo recording techniques. We subsequently produce a series of sound and video compositions, constructing new spatiotemporal and sensory relations from the material captured within Bowen Street. This approach serves as a technique for initiating a qualitative design proposition for the site that shifts modes of occupation through visual and auditory interventions. The paper concludes with speculations about the significance of interrelations between visual and auditory spaces in designing environments for human occupation

Additional considerations to the use of single-step genomic predictions in a dominance setting

Recent publications indicate that single-step models are suitable to estimate breeding values, dominance deviations and total genetic values with acceptable quality. Additive single-step methods implicitly extend known number of allele information from genotyped to non-genotyped animals. This theory is well derived in an additive setting. It was recently shown, at least empirically, that this basic strategy can be extended to dominance with reasonable prediction quality. Our study addressed two additional issues. It illustrated the theoretical basis for extension and validated genomic predictions to dominance based on single-step genomic best linear unbiased prediction theory. This development was then extended to include inbreeding into dominance relationships, which is a currently not yet solved issue. Different parametrizations of dominance relationship matrices were proposed. Five dominance single-step inverse matrices were tested and described as C1, C2, C3, C4 and C5. Genotypes were simulated for a real pig population (n = 11,943 animals). In order to avoid any confounding issues with additive effects, pseudo-records including only dominance deviations and residuals were simulated. SNP effects of heterozygous genotypes were summed up to generate true dominance deviations. We added random noise to those values and used them as phenotypes. Accuracy was defined as correlation between true and predicted dominance deviations. We conducted five replicates and estimated accuracies in three sets: between all (S1), non-genotyped (S2) and inbred non-genotyped (S3) animals. Potential bias was assessed by regressing true dominance deviations on predicted values. Matrices accounting for inbreeding (C3, C4 and C5) best fit. Accuracies were on average 0.77, 0.40 and 0.46 in S1, S2 and S3, respectively. In addition, C3, C4 and C5 scenarios have shown better accuracies than C1 and C2, and dominance deviations were less biased. Better matrix compatibility (accuracy and bias) was observed by re-scaling diagonal elements to 1 minus the inbreeding coefficient (C5)

Ethnicity and child health in northern Tanzania: Maasai pastoralists are disadvantaged compared to neighbouring ethnic groups.

The Maasai of northern Tanzania, a semi-nomadic ethnic group predominantly reliant on pastoralism, face a number of challenges anticipated to have negative impacts on child health, including marginalisation, vulnerabilities to drought, substandard service provision and on-going land grabbing conflicts. Yet, stemming from a lack of appropriate national survey data, no large-scale comparative study of Maasai child health has been conducted. Savannas Forever Tanzania surveyed the health of over 3500 children from 56 villages in northern Tanzania between 2009 and 2011. The major ethnic groups sampled were the Maasai, Sukuma, Rangi, and the Meru. Using multilevel regression we compare each ethnic group on the basis of (i) measurements of child health, including anthropometric indicators of nutritional status and self-reported incidence of disease; and (ii) important proximate determinants of child health, including food insecurity, diet, breastfeeding behaviour and vaccination coverage. We then (iii) contrast households among the Maasai by the extent to which subsistence is reliant on livestock herding. Measures of both child nutritional status and disease confirm that the Maasai are substantially disadvantaged compared to neighbouring ethnic groups, Meru are relatively advantaged, and Rangi and Sukuma intermediate in most comparisons. However, Maasai children were less likely to report malaria and worm infections. Food insecurity was high throughout the study site, but particularly severe for the Maasai, and reflected in lower dietary intake of carbohydrate-rich staple foods, and fruits and vegetables. Breastfeeding was extended in the Maasai, despite higher reported consumption of cow's milk, a potential weaning food. Vaccination coverage was lowest in Maasai and Sukuma. Maasai who rely primarily on livestock herding showed signs of further disadvantage compared to Maasai relying primarily on agriculture. We discuss the potential ecological, socioeconomic, demographic and cultural factors responsible for these differences and the implications for population health research and policy