Andrea Chan

Admixture in Mexico City: implications for admixture mapping of Type 2 diabetes genetic risk factors

Admixture mapping is a recently developed method for identifying genetic risk factors involved in complex traits or diseases showing prevalence differences between major continental groups. Type 2 diabetes (T2D) is at least twice as prevalent in Native American populations as in populations of European ancestry, so admixture mapping is well suited to study the genetic basis of this complex disease. We have characterized the admixture proportions in a sample of 286 unrelated T2D patients and 275 controls from Mexico City and we discuss the implications of the results for admixture mapping studies. Admixture proportions were estimated using 69 autosomal ancestry-informative markers (AIMs). Maternal and paternal contributions were estimated from geographically informative mtDNA and Y-specific polymorphisms. The average proportions of Native American, European and, West African admixture were estimated as 65, 30, and 5%, respectively. The contributions of Native American ancestors to maternal and paternal lineages were estimated as 90 and 40%, respectively. In a logistic model with higher educational status as dependent variable, the odds ratio for higher educational status associated with an increase from 0 to 1 in European admixture proportions was 9.4 (95%, credible interval 3.8–22.6). This association of socioeconomic status with individual admixture proportion shows that genetic stratification in this population is paralleled, and possibly maintained, by socioeconomic stratification. The effective number of generations back to unadmixed ancestors was 6.7 (95% CI 5.7–8.0), from which we can estimate that genome-wide admixture mapping will require typing about 1,400 evenly distributed AIMs to localize genes underlying disease risk between populations of European and Native American ancestry. Sample sizes of about 2,000 cases will be required to detect any locus that contributes an ancestry risk ratio of at least 1.5.

Social support for improved work integration

Purpose – This paper aims to explore the ways in which social supports can promote enduring attachments to work and improve overall well-being of disadvantaged workers, within the context of social purpose enterprises. Design/methodology/approach – With coordinators, managers and directors as informants, this mixed-methods study uses a survey and interviews to establish the availability and importance of different social supports found in social purpose enterprises across Canada, and to explore the reasons for such support mobilization and the influences that determine whether social supports are sought or accepted. Findings – Findings substantiate the prevalence and importance of work-centred social supports. Social supports can promote more sustainable attachment to work by addressing work process challenges, ameliorating workplace conflict, attending to non-vocational work barriers and building workers’ self-confidence and self-belief. The source of a support, as well as the relationship between suppor...

Supported Social Enterprise A Modified Social Welfare Organization

This article presents a study of supported social enterprise, a hybrid organization that not only either employs or trains members of marginalized social groups, often on disability pensions and social assistance, but also has social welfare characteristics. These organizations sell services and goods, like other forms of social enterprise, but rely heavily on external support from government programs, foundations, and a parenting nonprofit. The article presents an empirical study using a survey and interviews of participants in these organizations from Ontario, Canada, and notes that even though they earn minimally from work in these organizations, they view the experience positively. The final discussion centers on the concept of supported social enterprise and raises the question as to whether such organizations should be viewed primarily as a form of social enterprise or as a modified form of social welfare organization.

A two phase regulation of bone regeneration: IL-17F mediates osteoblastogenesis via C/EBP-β in vitro

T lymphocytes and pro-inflammatory cytokines, specifically interleukin-17F (IL-17F) have been identified as important regulators in bone regeneration during fracture repair. To better understand the molecular mechanisms of IL-17F-mediated osteoblastogenesis, a mouse pre-osteoblast cell line (MC3T3-E1) was utilized to characterize the intracellular signal transduction of IL-17F. Comparisons to the established canonical Wnt signaling pathway were made using Wnt3a ligand. Our results demonstrated greater bone marker gene expression in IL-17F-treated cells, compared to cells treated with Wnt3a. Western blot analysis confirmed degradation of β-catenin and up-regulation of two key proteins in osteoblast differentiation, Runx2 and C/EBP-β, in response to IL-17F treatment. RNA silencing of IL-17F receptors, IL-17Ra and IL-17Rc via siRNA transfection resulted in decreased expression of Act2, Runx2, and C/EBP-β, demonstrating the direct ligand-receptor interaction between IL-17F and IL-17Ra/c as an activator of osteoblastogenesis. Our findings suggest that IL-17F promotes osteoblast differentiation independent of the canonical Wnt pathway and β-catenin signaling, presenting new insights on modulating the adaptive immune response in the inflammatory phase, temporally distinct from the reparative and remodeling phases of fracture healing.