Development of gene expression-based biomarkers of exposure to metals and pesticides in the freshwater amphipod Hyalella azteca

Ecological risk assessment (ERA) is a framework for monitoring risks of exposure and adverse effects of environmental stressors to populations or communities of interest. One tool of ERA is the biomarker, which is a characteristic of an organism that reliably indicates exposure to or effects of a stressor like chemical pollution. Traditional biomarkers which rely on characteristics at the tissue level and higher often detect only acute exposures to stressors. Sensitive molecular biomarkers may detect lower stressor levels than traditional biomarkers, which helps inform risk mitigation and restoration efforts before populations and communities are irreversibly affected. In this study I developed gene expression-based molecular biomarkers of exposure to metals and insecticides in the model toxicological freshwater amphipod Hyalella azteca. My goals were to not only create sensitive molecular biomarkers for these chemicals, but also to show the utility and versatility of H. azteca in molecular studies for toxicology and risk assessment. I sequenced and assembled the H. azteca transcriptome to identify reference and stress-response gene transcripts suitable for expression monitoring. I exposed H. azteca to sub-lethal concentrations of metals (cadmium and copper) and insecticides (DDT, permethrin, and imidacloprid). Reference genes used to create normalization factors were determined for each exposure using the programs BestKeeper, GeNorm, and NormFinder. Both metals increased expression of a nuclear transcription factor (Cnc), an ABC transporter (Mrp4), and a heat shock protein (Hsp90), giving evidence of general metal exposure signature. Cadmium uniquely increased expression of a DNA repair protein (Rad51) and increased Mrp4 expression more than copper (7-fold increase compared to 2-fold increase). Together these may be unique biomarkers distinguishing cadmium and copper exposures. DDT increased expression of Hsp90, Mrp4, and the immune response gene Lgbp. Permethrin increased expression of a cytochrome P450 (Cyp2j2) and decreased expression of the immune response gene Lectin-1. Imidacloprid did not affect gene expression. Unique biomarkers were seen for DDT and permethrin, but the genes studied were not sensitive enough to detect imidacloprid at the levels used here. I demonstrated that gene expression in H. azteca detects specific chemical exposures at sub-lethal concentrations, making expression monitoring using this amphipod a useful and sensitive biomarker for risk assessment of chemical exposure.

THE HEALTH OF YOUNG ADULTS WITH DISABILITIES IN THE UNITED STATES: THE COLLECTIVE ROLES OF RISK FACTORS IN SOCIAL ECOLOGIC FRAMEWORK

Background: Over the last few decades, the prevalence of young adults with disabilities (YAD) has steadily risen as a result of advances in medicine, clinical treatment, and biomedical technologythat enhanced their survival into adulthood. Despite investments in services, family supports, and insurance, they experience poor health status and barriers to successful transition into adulthood. Objectives: We investigated the collective roles of multi-faceted factors at intrapersonal, interpersonal and community levels within the social ecological framework on health related outcome including self-rated health (SRH) of YAD. The three specific aims are: 1) to examine sociodemographic differences and health insurance coverage in adolescence; 2) to investigate the role of social skills in relationships with family and peers developed in adolescence; and 3) to collectively explore the association of sociodemographic characteristics, social skills, and community participation in adolescence on SRH. Methods: Using longitudinal data (N=5,020) from the National Longitudinal Transition Study (NLTS2), we conducted multivariate logistic regression analyses to understand the association between insurance status as well as social skills in adolescence and YAD’s health related outcomes. Structural equation modeling (SEM) assessed the confluence of multi-faceted factors from the social ecological model that link to health in early adulthood. Results: Compared with YAD who had private insurance, YAD who had public health insurance in adolescence are at higher odds of experiencing poorer health related outcomes in self-rated health [adjusted odds ratio (aOR=2.89, 95% confidence interval (CI): 1.16, 7.23), problems with health (aOR=2.60, 95%CI: 1.26, 5.35), and missing social activities due to health problems (aOR=2.86, 95%CI: 1.39, 5.85). At the interpersonal level, overall social skills developed through relationship with family and peers in adolescence do not appear to have association with health related outcomes in early adulthood. Finally, at the community level, community participation in adolescence does not have an association with SRH in early adulthood. Conclusions: Having public health insurance coverage does not equate to good health. YAD need additional supports to achieve positive health outcomes. The findings in social skills and community participation suggest other potential factors may be at play for health related outcomes for YAD and the need for further investigation.