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Elucidating EXO1’s Key Interactions with MutS in DNA Mismatch Repair Via Atomic Force Microscopy
Get PDFDNA mismatch repair (MMR) is a highly conserved pathway that ensures genomic stability by correcting errors and excising mismatched base pairs in newly synthesized DNA. Even after proofreading by DNA polymerases, errors occur in DNA replication at a rate of 1 in 100,000 nucleotides. In a genome of six billion base pairs, this error rate leads to ~120,000 replication errors per cell division. Uncorrected replication errors can lead to harmful mutations that drive cancer and other genetic disorders. These errors are exemplified in Lynch Syndrome, a hereditary cancer predisposition caused by mutations in core MMR proteins. Two key proteins in the MMR pathway are MutS, which recognizes the site of the mismatch, and EXO1, an exonuclease that excises the erroneous base pair. This work will specifically characterize EXO1's interactions with MutS in the MMR pathway using atomic force microscopy (AFM), which will elucidate novel conformational information about EXO1-MutS complexes through quantitative analyses involving volumes and heights of complexes. These findings will contribute to a deeper understanding of EXOI's mechanistic role in MMR, which may have implications for therapeutic strategies targeting MMR-deficient cancers.Bachelor of Scienc
FROM RIFT TO RECONCILIATION: NAVIGATING FAMILY POLITICAL POLARIZATION
Get PDFFor families across the U.S., political polarization has increasingly affected family functioning and relations. While it is clear that this polarization is affecting families, the primary influences of polarization and how to mitigate its effects are less clear. This thematic analysis examines the influences of political identity and polarization on family systems, and how to manage these divides with support from Bowen’s Family Systems Theory, which describes the family as a unit or system with interconnected parts. This analysis utilized peer-reviewed sources, and was supplemented by surveys from Pew Research Center, episodes of television, a Ted Talk, and media articles. It was coded based on Braun and Clarke’s (2006) guidelines for thematic analysis. The results of this analysis indicated that Othering, Media Influence, Developmental Influence, and Politics in Identity Formation are the primary influences on political polarization, and Communication Styles, Consideration of Others, and Self-Reflection are mitigating factors in preventing family division. This thematic analysis offers recommendations for family-based practitioners and family life educators that work with politically divided populations, as well as families that are directly affected by political polarization.Bachelor of Art
Making vancomycin a potent broad-spectrum antimicrobial agent using polyaziridine-stabilized gold nanoparticles as a delivery vehicle
Get PDFThe rise of antimicrobial drug resistance among microorganisms presents a global challenge to clinicians. Therefore, it is essential to investigate drug delivery systems to combat resistant bacteria and fungi. This study examined the potential and mode of action of vancomycin-conjugated gold nanoparticles (PEI-AuNP@Van) to enhance vancomycin’s biocidal activity against C. tropicalis, C. albicans, E. coli, and P. aeruginosa. Drug conjugation and nanoparticle characterization were assessed using UV-Vis spectroscopy, X-ray diffraction, TEM, ATR-FTIR, and fluorescence spectroscopy. Effective vancomycin conjugation on polyethyleneimine-stabilized gold nanoparticles was achieved via electrostatic interactions or hydrogen bonding between the COO-/OH groups of vancomycin and the NH- groups of polyethyleneimine, yielding nanoparticles with a narrow size distribution and high zeta potential. The high luminescence of the nanoparticles facilitated their detection in microbial cells. PEI-AuNP@Van was internalized in C. albicans and C. tropicalis but showed surface adsorption in E. coli and P. aeruginosa. The in vitro results indicated that the nanodelivery system exhibited superior biocidal activity against the tested strains compared to free vancomycin and unconjugated AuNPs. The mode of action of PEI-AuNP@Van was cell-type-dependent, involving intracellular reactive oxygen species accumulation, cell membrane integrity loss, and apoptosis. The development of antimicrobial nanoformulations using AuNPs and efficient conjugation systems offers a promising approach to address antimicrobial drug resistance.Graphical Abstrac
Professional Pharmacology and Pharmacy Organization Responses to the Dobbs v. Jackson Supreme Court Ruling
Get PDFThe US Supreme Court's decision in Dobbs v. Jackson Women’s Health Organization has sparked significant changes in reproductive healthcare laws, allowing individual states to regulate abortion rights. This study focuses on the responses of professional pharmacy organizations in the US to this landmark decision, recognizing its potential to influence healthcare education and training. The research aims to broadly establish the impact of the Dobbs decision on pharmacy organizations through analyzing public statements. An online search of responses to the Dobbs decision was conducted on organizations’ official websites and social media pages. Search strings used included terms pertaining to abortion, Dobbs v. Jackson, or Roe v. Wade. This study only included U.S.-based professional organizations within the field of pharmacy practice/pharmacology/pharmaceutical sciences. Statements were analyzed using the Pillars of Reproductive Wellbeing by Power To Decide, a non-profit organization committed to ensuring that young people have the power to decide if, when, and under what circumstances to have babies.Doctor of Pharmac
Basal Ganglia Tissue Iron Development and Associations with Depressive Symptoms Across Adolescence
Get PDFAdolescence is a critical developmental period marked by the maturation of brain regions, including the basal ganglia, and is often when mental disorders first emerge in predisposed individuals. Basal ganglia tissue iron concentrations can be used as an indicator of dopaminergic functioning and have been implicated in reward processing, motivated behavior, and depression severity. However, developmental relationships between tissue iron and depressive symptoms have not been characterized. Utilizing longitudinal neuroimaging and survey data collected from 167 adolescents (ages 11.9-18.6) over five years, the current study aimed to delineate the relationship between developing tissue iron and depressive symptom severity across adolescence. We anticipated that adolescents with diminished age-related increases in tissue iron would exhibit increasing depressive symptom severity across adolescence. In agreement with prior work, basal ganglia tissue iron significantly increased with age. Further, a significant age x sex interaction on caudate tissue iron was observed, with girls showing relatively higher age-related increases. While we did not observe significant relationships between within-person changes in tissue iron and depressive symptoms, exploratory analyses demonstrated a significant relationship between average depressive symptoms and caudate tissue iron development, such that adolescents with higher average depressive symptoms displayed relatively greater age-related increases in caudate tissue iron when controlling for sex. These findings suggest that while age effects on the developmental trajectory of basal ganglia tissue iron are empirically supported, interactions with depression may be more complicated than initially expected. Further research is necessary to explore how biological sex and external forces, including early life stress, influence the relationship between tissue iron and depression development to inform adolescent mental health interventions.Bachelor of Scienc
Modulating Mitochondrial Calcium Dynamics in the Mesolimbic Pathway as a Pharmacological Tool for Cocaine Use Disorder
Get PDFCocaine use disorder (CUD) is a major public health problem. Despite existing behavioral interventions, there is no current FDA approved pharmacological treatment for CUD. Current treatment approaches may be ineffective due to their inability to address mitochondrial dysfunction within neural circuits involved in drug reward. Cocaine disrupts mitochondrial calcium homeostasis, impairs ATP synthesis, and increases oxidative stress within neurons. Our studies aim to characterize the contribution of a key regulator of calcium (Ca2+) influx into mitochondria, the mitochondrial calcium uniporter complex subunit MICU1, to behavior and drug reward learning. We hypothesize that cocaine exposure increases mitochondrial calcium influx through the MCU complex in dopamine axon terminals in the nucleus accumbens to modulate reward-related learning. We first validated the use of a MICU1-targeting compound (MCU-i4) by measuring calcium dynamics in HeLA cells. Our overall project uses pharmacological approaches, CRISPR-Cas9-mediated gene editing, and mitochondrially-targeted fluorescent sensors to assess mitochondrial function in dopamine neurons of mice in vivo. Cocaine conditioned place preference, cocaine locomotor sensitization, and elevated plus maze (EPM) were tested in the present studies to evaluate behavioral effects of pharmacologically targeting MICU1. We predict that blocking Ca2+ transporter function in mitochondria during cocaine exposure will block cocaine-mediated changes in behavior and neural activity. We then assessed interactions between cocaine and MCU-i4 on dopamine release in the nucleus accumbens in vivo using the fluorescent dopamine receptor-based sensor dLight. Overall, the findings from this research will contribute to the development of treatments for cocaine use disorder.Bachelor of Scienc
Behavioral Determinants of Flood Insurance Purchasing
Get PDFLarge populations across the United States are prone to flooding events, yet flood insurance uptake does not match objective risk exposure. Findings from previous literature about the effects of past flooding experiences and socio-demographic characteristics on flood insurance adoption, including the timing of such effects, are confirmed, but this research also considers more detailed mechanisms that may influence consumer perceptions of risk, including a subjective probability estimation process and a general risk aversion mechanism. Leveraging logistic regression, multinomial logit, and bivariate probit models, this research provides significant evidence to support the claim that background risks may affect flood insurance purchasing through multiple mechanisms, although there is insufficient evidence for drawing strong causal inferences. This paper also finds that coastal and riverine flooding risks are perceived differently by consumers, and that physical wealth effects dominate financial wealth effects, significantly impacting the ultimate decision to purchase flood insurance. Bachelor of Scienc
Nonlinear Climate Impacts on U.S. Crop Yields: Assessing the Moderating Role of Irrigation as an Adaptive Strategy
Get PDFThis research investigates nonlinear effects of climate variability—specificallytemperature and precipitation—on crop yields in the U.S., focusing on corn andsoybeans. It emphasizes the role of irrigation as a key adaptation strategy to miti-gate adverse weather impacts. Using county-level data from USDA NASS, the studyapplies fixed effects, instrumental variable and selection models, with groundwaterwell density as an instrument for irrigation. Findings underline irrigation’s impor-tance in climate adaptation while highlighting sustainability concerns under waterscarcity. Results provide insights for adaptive policy development in agricultureamid climate challenges.Bachelor of Scienc
Mandatory Civic Education in Public Colleges and Universities: The Case of the South Carolina REACH Act
Get PDFOver the past decade, state legislatures have become increasingly involved in decisions about the types of classes that are taught at public colleges and universities. One area of growing interest for legislators, particularly Republican legislators, are courses on the founding principles of the U.S. government. While “founding documents laws” have passed in several states, we know very little about how these laws emerged or the level of public support for this type of legislation. To better understand this phenomenon, this thesis focuses on one of the most comprehensive founding documents laws, South Carolina’s 2021 Reinforcing College Education on America's Constitutional Heritage (REACH) Act. Using a mixed-methods approach, this thesis analyzes a 2024 general population survey of South Carolinians from the Winthrop Poll that included questions about founding documents laws. This study also reports findings from interviews with university faculty to gain a better understanding of the creation and implementation of the South Carolina REACH Act. The results from the survey indicate that partisanship and racial resentment are important factors in support for the REACH Act among the general public. Interviews with faculty show a more nuanced view of the legislation and highlight the challenges of implementation. The findings from this thesis will be of interest to scholars of public policy, state policymaking, higher education policy, and public opinion. This research is also important because as more legislation like the REACH Act continues to be introduced across the country, taking key groups’ opinions into account will help inform policy decisions.Bachelor of Art
Understanding Quality of Life as Described by Adults with Intellectual and Developmental Disabilities
Get PDFConceptualizing and measuring Quality of Life (QoL) is complex, even more so when examining QoL among adults with Intellectual and Developmental Disabilities (IDD) who may have differences in communication and/or comprehension. This study addresses limitations noted in previous QoL literature which shows a variety of methodological flaws and ableist assumptions influencing how QoL is understood and measured. A mixed methods approach including a survey (n=20) and Photovoice/interview (n=9) was used to examine how adults with IDD describe their own QoL. Quantitative data showed that globally the participants rated their QoL quite high (1.84 mean score out of 2) with the highest score in the social inclusion domain (mean =1.94) , and the physical well-being domain with the lowest score (mean =1.76) Four QoL domains were represented in the qualitative data from the participants who also provided their perspectives on the study methodology and QoL itself. In addition to describing the QoL ratings among adults with IDD, this study highlights the importance of inclusive measures and the overlapping nature of QoL domains. Implications and future directions are discussed.Bachelor of Arts in Educatio