Browsing by Subject "Genetics"
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Item Assessing the Effects of Inorganic Arsenic on IL-1β and TNFα Secretion, Gene Expression, and DNA Methylation in Murine Macrophages to Gauge Immunotoxic Effects(2019) DeLong, Lauren; Biological SciencesI plan to investigate whether or not genes for the NLRP3 inflammasome or TACE (Adam 17) are indeed differentially regulated in M1 macrophages exposed to arsenite. If these genes are differentially expressed, I will have insight to future steps of analysis that may reveal the mechanism by which the toxicants influence this process. This study hypothesizes that treatment of murine macrophages in vitro at nanomolar concentrations of arsenite will create cytotoxic or sub-cytotoxic conditions that induce increased secretion of inflammatory cytokine IL-1B and TNFa. Furthermore, an increase in IL-1B secretion will be coupled with an upregulation of genes involved in the formation of the NLRP3 inflammasome, and an increase in TNFa secretion will be coupled with an upregulation of genes involved with TACE (Adam17). Results that reveal the mechanism by which arsenite poisoning or public health measures related to low dose arsenite-induced immune dysfunction.Item EVALUATION OF THE EFFECTS OF TWO EARLY CHILDHOOD INTERVENTIONS ON ADULTHOOD INCOME: EXAMINING THE ASSOCIATION OF PROXIMAL AND DISTAL INTERVENTION EFFECTS WITH SUBJECT-LEVEL HETEROGENEITY(2019-01-01) Johnston, Stephen S.; Salkever, David S; School of Public Policy; Public PolicyThe long-term evaluation and subsequent replication of early childhood interventions can be costly. Thus, approaches that maximize the efficiency of these tasks are critical to the economic feasibility of such interventions. I use longitudinal data from the Johns Hopkins University (JHU) Prevention Research Center (PRC) intervention trials to: (a) evaluate the impact of two randomized classroom-based early childhood interventions - the Good Behavior Game (GBG) and Mastery Learning (ML) - on adulthood income, and (b) explore the role of various forms of subject-level heterogeneity in the impact of these interventions on adulthood income. My dissertations centers around three core empirical analyses: (#1) Empirical evaluation of the effects of the GBG and ML interventions on adulthood income: testing a recursive model of proximal and distal effects vs. a reduced-form model of distal effects; (#2) Empirical evaluation of subject-level heterogeneity in sociodemographic and behavioral characteristics and their influence on the effects of the ML and GBG interventions on adulthood income; (#3) Empirical evaluation of subject-level heterogeneity in polygenic propensity for educational attainment and its influence on the effects of the ML and GBG interventions on adulthood income. In each analysis, I use multivariable generalized linear models to test my statistical hypotheses. In sensitivity analyses, I apply inverse probability of attrition weights to address longitudinal loss to follow-up. I find that universally, the ML and GBG interventions do not appear to have a significant impact on adulthood income. However, the ML intervention increased the probability of adulthood employment. The impact of these interventions, particularly the ML, varied by sociodemographic and behavioral heterogeneity and by polygenic propensity for educational attainment. Proximal measures of young adulthood educational attainment were strongly predictive of adulthood income and employment and therefore may serve as a proximal marker of distal intervention success. Aside from the interventions, participants' grade 1 global Teacher Observation of Classroom Adaptation - Revised (TOCA-R rating), grade 1 free lunch status, and EduYears GPS (a score summarizing the polygenic propensity for educational attainment) for the were remarkably predictive of adulthood income and employment outcomes, and these factors may be ideal for targeting at-risk populations for interventions.Item Identification of Genetic Variants Influencing Efficacy of Lisinopril Treatment on Age-specific Physical Performance: A Genome-wide Analysis in Drosophila melanogaster(2018-01-01) Gabrawy, Mariann; Leips, Jeff; Abadir, Peter; Biological Sciences; Biological SciencesAge-related decline in physical performance is a general phenomenon in most organisms and in humans confers high risk for disability and mortality. Despite the near ubiquity of senescence and extensive variation among individuals in age-related decline in physical performance, we know little about the genes responsible for this variation. In humans, alterations in the Renin-Angiotensin System (RAS) have been implicated in the pathogenesis of late life physical decline. Pharmacological blockade of RAS, such as that by angiotensin-converting enzyme inhibitor Lisinopril, has been proposed as a treatment to attenuate such age-related declines. Some studies have shown effectiveness of these drugs for treatment of late-age declines while others have failed to show any effect. Conflicting results between studies can potentially be explained by genetic differences among individuals. The primary goal of this research was to develop methods to measure physical performance with age and identify, via genome-wide association (GWA) and follow-up functional genetic studies, genes associated with physical ability at late age and those that contribute to differences among genotypes in the phenotypic response (climbing speed and endurance) to Lisinopril. I used Drosophila melanogaster as a model system and the Drosophila Genetic Reference Panel (DGRP) for GWA mapping. The second goal was to map climbing speed and endurance in untreated and Lisinopril-treated flies. This revealed genetic pathways that are acted on by this drug and polymorphisms that altered individual responses to the drug. My results have contributed to our understanding of the genetic bases of natural variation in physical performance at older ages. Many of the genes identified this study have human orthologs. As a result, my findings have laid the groundwork for designing personalized medical applications to treat age-related declines in physical performance and provide novel genetic targets for pharmaceutical development to extend health span in older adults.Item Investigating interactions between climate, host life history and viral diversity across a trans-hemispheric range of marine ecosystems(2022-01-01) Zhao, Mingli; Schott, Eric; Schreier, Harold; Marine-Estuarine Environmental Sciences; Marine-Estuarine-Environmental SciencesMarine infectious diseases and pathogens substantially impact the structure and function of marine communities by causing mortalities and altering host behaviors. The interactions between host and pathogen, determining the epidemiologicaloutcomes are affected by many factors including climate, host life history, and human activities. Studies on marine disease epidemiology and ecology, including both natural and anthropogenic transmission pathways, are necessary for better understanding how these factors potentially influence the host-pathogen interactions. A significant proportion of marine pathogens are viruses; they cause severe infectious diseases and mortalities in many marine organisms, including crustaceans. Virus-related diseases and mortalities have been identified and reported in the Atlantic blue crab, Callinectes sapidus, for more than half a century. With a wide geographic distribution across both hemispheres and a temperature-dependent variable life history, blue crab and its pathogenic viruses constitute a well-suited pathosystem for investigating the potential influences of climate, seasonality, and host life history on viral disease emergence and spread in marine ecosystems. This dissertations applied the "blue crab-virus” pathosystem, to investigate factors that potentially influence the interactions between blue crab and its viral symbionts. The studies mainly focused on three objectives: 1) Investigate the influences of climate, seasonality, and host life history on the prevalence and disease ecology of a virus that is pathogenic to blue crab. 2) Assess the influences of climate, seasonality, and host life history on viral genetic diversity and genetic structures across a wide spatial and temporal range. 3) Characterize genome sequences and biological characteristics of newly identified viruses in blue crabs. The studies encompassed in this dissertations demonstrate, in a single host species, that climate, temperature, and host life history traits drive patterns of virus species diversity and genetic variation across the entire range of the host. One significant revelation was the evidence of long-distance movement of virus pathogen genotypes by human transport of infected blue crabs between states in the United States. The dissertations concludes with a discussion of the potential for next-generation sequencing to discover and study the movement of known and newly discovered viruses in marine hosts.Item The identification and characterization of novel basic helix-loop-helix proteins in Caenorhabditis elegans.(2004-09-23) McMiller, Tracee Lynn; Johnson, Casonya M.; Master of Science