Medicine and Health Sciences Commons^™

The Role Of Tumor Suppressor Dear1 In The Acquisition Of Mammary Stem/Progenitor Cell Properties, Uyen Le

Dissertations & Theses (Open Access)

Breast cancer is the most commonly diagnosed cancer in women in America. Ductal carcinoma in situ (DCIS), one of the earliest pre-invasive forms of invasive ductal carcinoma (IDC), has a 30-50% risk of progressing to IDC. Understanding the mechanisms regulating progression from DCIS to IDC would help identify biomarkers to stratify patients at higher risk of progression or metastasis. Cumulative literature suggests the earliest phase of dissemination from the primary tumor is driven by the epithelial-mesenchymal transition (EMT) program. DEAR1 is a tumor suppressor gene which is mutated, undergoes loss of heterozygosity in breast cancer, and is downregulated in DCIS …

Molecular Survey For The Honey Bee Trypanosome Parasites Crithidia Mellificae And Lotmaria Passim, Mary-Kate Williams

Graduate Theses and Dissertations

Honey bee populations have been fluctuating within recent years. No one cause has been attributed to colony fluctuations due to the theory that multiple stressors interact with one another to impact colony health. Consequently, microorganisms such as internal parasites of honey bees have been understudied as a contributor to colony health decline.

Molecular diagnostics were utilized to detect the presence of two honey bee trypanosome parasites, Crithidia mellificae and Lotmaria passim, in managed and feral honey bee populations from eight states in the United States (USA). Because studies on trypanosome infections are lacking in the USA, it is important to …

Genetic Testing Practices Of Genetic Counselors, Geneticists, And Pediatric Neurologists With Regard To Childhood-Onset Neurogenetic Conditions, Sara Wofford

Dissertations & Theses (Open Access)

Identifying genetic diagnoses for neurological conditions with a considerable hereditary component, such as autism spectrum disorder (ASD), intellectual disability, and epilepsy, is critical to providing proper medical management for these patients and their families. However, many patients with these conditions are not tested appropriately or receive no genetic testing at all. The current study was designed to characterize the genetic testing practices of the providers most likely to evaluate or order genetic testing for these patients: pediatric neurologists, geneticists, and genetic counselors. The study noted significant variance between the testing strategies selected by pediatric neurologists compared to those of geneticists …

Epigenome-Wide Association Study Of Metabolic Syndrome In African-American Adults, Tomi Akinyemiju, Anh N. Do, Amit Patki, Stella Aslibekyan, Degui Zhi, Bertha Hidalgo, Hemant K. Tiwari, Devin Absher, Xin Geng, Donna K. Arnett, Marguerite R. Irvin

Epidemiology and Environmental Health Faculty Publications

Background: The high prevalence of obesity among US adults has resulted in significant increases in associated metabolic disorders such as diabetes, dyslipidemia, and high blood pressure. Together, these disorders constitute metabolic syndrome, a clinically defined condition highly prevalent among African-Americans. Identifying epigenetic alterations associated with metabolic syndrome may provide additional information regarding etiology beyond current evidence from genome-wide association studies.

Methods: Data on metabolic syndrome and DNA methylation was assessed on 614 African-Americans from the Hypertension Genetic Epidemiology Network (HyperGEN) study. Metabolic syndrome was defined using the joint harmonized criteria, and DNA methylation was assessed using the Illumina HumanMethylation450K Bead …

Obesity And Obesogenic Growth Are Both Highly Heritable And Modified By Diet In A Nonhuman Primate Model, The African Green Monkey (Chlorocebus Aethiops Sabaeus), C. A. Schmitt, S. K. Service, A. J. Jasinska, Thomas D. Dyer, M. J. Jorgensen, R. M. Cantor, G. M. Weinstock, John Blangero, J. R. Kaplan, N. B. Freimer

School of Medicine Publications and Presentations

OBJECTIVE: In humans, the ontogeny of obesity throughout the life course and the genetics underlying it has been historically difficult to study. We compared, in a non-human primate model, the lifelong growth trajectories of obese and non-obese adults to assess the heritability of and map potential genomic regions implicated in growth and obesity.

STUDY POPULATION: A total of 905 African green monkeys, or vervets (Chlorocebus aethiops sabaeus) (472 females, 433 males) from a pedigreed captive colony. METHODS: We measured fasted body weight (BW), crown-to-rump length (CRL), body-mass index (BMI) and waist circumference (WC) from 2000 to 2015. We used a …

An Exome-Wide Sequencing Study Of Lipid Response To High-Fat Meal And Fenofibrate In Caucasians From The Goldn Cohort, Xin Geng, Marguerite R. Irvin, Bertha Hidalgo, Stella Aslibekyan, Vinodh Srinivasasainagendra, Ping An, Alexis C. Frazier-Wood, Hemant K. Tiwari, Tushar Dave, Kathleen Ryan, Jose M. Ordovas, Robert J. Straka, Mary F. Feitosa, Paul N. Hopkins, Ingrid Borecki, Michael A. Province, Braxton D. Mitchell, Donna K. Arnett, Degui Zhi

Epidemiology and Environmental Health Faculty Publications

Our understanding of genetic influences on the response of lipids to specific interventions is limited. In this study, we sought to elucidate effects of rare genetic variants on lipid response to a high-fat meal challenge and fenofibrate (FFB) therapy in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) cohort using an exome-wide sequencing-based association study. Our results showed that the rare coding variants in ITGA7, SIPA1L2, and CEP72 are significantly associated with fasting LDL cholesterol response to FFB (P = 1.24E-07), triglyceride postprandial area under the increase (AUI) (P = 2.31E-06), and triglyceride postprandial …

Qatar: Diabetes, Diangelo Gonzalez

Global Public Health

The State of Qatar is a developed nation that is located in the Middle East and borders the Persian Gulf and Saudi Arabia. The nation is a constitutional monarchy and is currently led by Amir Tamim bin Hamad Al Thani. The 2,300,000+ people of Qatar face many major challenges. Although it is one of the wealthiest nations in the Middle East, Qatar faces issues of human trafficking, migrants willing to work in poor conditions, and Middle Eastern Respiratory Syndrome (MERS). The most critical issue that plagues this county is diabetes, both I and II. Diabetes is a disease that is …

Molecular Brain Adaptations To Ethanol: Role Of Glycogen Synthase Kinase-3 Beta In The Transition To Excessive Consumption, Andrew D. Van Der Vaart

Theses and Dissertations

Alcoholism is a complex neuropsychiatric disease that is characterized by compulsive alcohol use and intensifying cravings and withdrawals, often culminating in physiologic dependency. Fundamental alterations in brain chemistry underlie the transition from initial ethanol exposure to repetitive excessive use. Key mediators of this adaptation include changes in gene expression and signal transduction. Here we investigated gene expression pathways in prefrontal cortex and nucleus accumbens following acute or chronic ethanol treatment, to identify genes with potentially conserved involvement in the long-term response of the corticolimbic system to repeated ethanol exposure. We investigated Gsk3b, which encodes glycogen synthase kinase 3-beta, as a …

Gain-Of-Function Experiments With Bacteriophage Lambda Uncover Residues Under Diversifying Selection In Nature, Rohan Maddamsetti, Daniel T. Johnson, Stephanie J. Spielman, Katherine L. Petrie, Debora S. Marks, Justin R. Meyer

Biological Sciences Faculty Publications

Viral gain-of-function mutations frequently evolve during laboratory experiments. Whether the specific mutations that evolve in the lab also evolve in nature and whether they have the same impact on evolution in the real world is unknown. We studied a model virus, bacteriophage λ, that repeatedly evolves to exploit a new host receptor under typical laboratory conditions. Here, we demonstrate that two residues of λ’s J protein are required for the new function. In natural λ variants, these amino acid sites are highly diverse and evolve at high rates. Insertions and deletions at these locations are associated with phylogenetic patterns indicative …

Crispr Genetic Editing: Paths For Christian Acceptance And Analysis Of In Vivo And In Vitro Efficiency, Mandeep Sandhu

Scripps Senior Theses

With advancements in CRISPR-cas9 broadening the potential paths for clinical usage of genetic editing, conversations about genetic editing have grown to outside simply scientific communities and into mainstream conversations. This study focuses specifically on Christian discourse of genetic editing and locates four major tensions for many Christians when they think about genetic editing: beginning of life, Creator-human relationship, imago Dei, and stewardship. With these major concerns in mind, I identify epigenetics, somatic cell genetic editing, and in vivo genetic editing research as important research paths to pursue as they can potentially produce techniques that more Christian individuals would feel comfortable …