Life Sciences Commons^™

Informatics-Based Discovery Of New Natural Products, Their Biosynthesis, And Their Biological Roles, Ethan Older

Theses and Dissertations

In this work, genome mining and biosynthetic knowledge are applied for the discovery of new natural products, their biosynthetic pathways, and their promising biological activities and roles through the development of two unique new informatics-based approaches.

In chapter one, an overview of microbial natural product biological functions and biosynthesis is provided. The use of bioinformatics leveraging microbial natural product biosynthetic knowledge is also introduced. This chapter highlights the importance and need for developing innovative approaches to accessing microbial natural products, a vastly untapped source of new molecules with promising biological activities.

In chapter two, a correlational network linking the gene-encoded …

Diversification And Evolution Of Hawaiian Megalagrion Damselflies (Pinapinao, Odonata: Coenagrionidae), Robert K. Hadfield

Theses and Dissertations

The Megalagrion damselflies of HawaiÊ»i present a valuable study system for understanding the impacts of geology on evolutionary processes. Despite their significance, our understanding of the temporal, geographic, and phylogenetic origins of these damselflies remains incomplete. Prior phylogenetic studies have proposed adaptive ecological and morphological progressions, but evaluating these hypotheses relies on a sound understanding of phylogenetic relationships within the genus. Previous phylogenetic analyses have produced conflicting topologies. To resolve these uncertainties, we performed phylogenetic analyses including divergence time estimation with 90 nuclear loci (>50 kbp) and 2 mitochondrial loci (>1000 bp), sampling representatives from each genus within …

Illuminating The Twilight Zone: In-Situ Imaging Facilitates Discovery Of Mesopelagic Plankton Dynamics And Community Structure, Alexander Barth

Theses and Dissertations

Ocean ecosystems provide both food and regulation of climate. Much of ocean ecosystem functioning occurs through processes in the pelagic, where plankton are the dominant organisms. While plankton have been researched for several centuries, recent advances in technology are greatly improving the ability to better understand plankton and how their communities are structured. Specifically, in-situ imaging allows oceanographers and plankton ecologists to better sample fragile taxa and record organisms’ true traits at high frequencies. These tools can facilitate investigation into new topics in plankton ecology and better understand critically understudied habitats, like the mesopelagic of open-ocean systems. However, in-situ imaging …

A Comprehensive Review And Meta-Analysis Of Breast Cancer Gene Expression Data: Understanding The Molecular Complexity Of A Silent Epidemic, Ifeanyichukwu O. Nwosu

Theses and Dissertations

Breast cancer is the most frequently diagnosed cancer type and the leading cause of cancer death; it accounts for 23% of total cases and 14% of deaths, with over 2 million new cases diagnosed and 600,000 deaths in 2020. This is a huge public health burden. Traditionally, clinical subtypes of breast cancer are defined based on a patient's immunohistochemistry profile. These profiles are determined by the combined expression status of three receptors: estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. It has also been observed that women of African descent, more commonly present with ER, PR and …

Perspectives From Caregivers For Children With Retinoblastoma: Psychosocial Concerns And Genetic Counseling, Kayla Marie Lashinger

Theses and Dissertations

Caregivers play a vital role in the care of children affected with retinoblastoma as most cases are diagnosed before the age of five years old. While previous studies have explored the psychosocial needs of caregivers of children with pediatric cancer, these have not specifically focused on retinoblastoma in the United States (US). Prior research identified the profound emotional burden in terms of depression, anxiety, guilt, isolation, and loneliness experienced by caregivers. Given previous findings and the National Cancer Institute’s recommendation for genetic counseling and testing for all individuals affected with retinoblastoma, this study aimed to assess psychosocial concerns in relation …

Preimplantation Genetic Testing For Sickle Cell Disease; Exploring The Effect Health Disparities Have On Parental Awareness And Interest, Justine Frances Manigault

Theses and Dissertations

Sickle cell disease (SCD) is a group of disorders of the hemoglobin resulting in episodes of chronic pain, pulmonary hypertension, progressive multiorgan damage, risk for stroke, and increased mortality. It is caused by biallelic pathogenic variants in the HBB gene and 1 in 12 African Americans, 1 in 100 Hispanic individuals, and 1 in 30-50 Mediterranean people are reported to be carriers of the disease and have sickle cell trait (SCT). SCD is typically diagnosed through newborn screening; however, when prospective parents are aware of their carrier status, they can conceive via in vitro fertilization (IVF) and have genetic testing …

Modulation Of Neurodegenerative Disease Progression By Antioxidant Status, Elena Kelety

Theses and Dissertations

Neurodegenerative diseases, including Amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease, profoundly impact the brain and nervous system. In 2019, the United States reported the highest global prevalence of neurological disorders. This thesis approaches neurodegenerative diseases by emphasizing the critical role of a well-maintained antioxidant system, its intricate relationship with dietary patterns, and proposes an alternative fate of the antioxidant urate.

Neurodegenerative disease pathogenesis involves a complex interplay of neuroinflammation, mitochondrial dysfunction, misfolded proteins, and oxidative stress. Oxidative stress arises from an imbalance in the antioxidant defense system and the production of reactive oxygen species. Synergistic antioxidant interactions are vital …

The Autistic Adult's Perspective On Genetic Testing In The Prenatal And Cancer Settings, Robin Lisa Urban

Theses and Dissertations

Prenatal and cancer genetic tests are recommended by many professional medical organizations. Previous studies have shown that autistic adults have a negative opinion towards genetic testing for autism but have not explored if this sentiment is shared for other types of genetic testing. We used a descriptive, web-based survey of autistic adults to assess their attitudes towards prenatal and cancer genetic testing (n=36). Our data showed that overall attitudes towards prenatal and cancer genetic testing are positive. Notably, participants had slightly more positive attitudes towards prenatal genetic testing related to neurodevelopmental disorders when compared to testing for disorders primarily affecting …

Perspectives On Transition To Adult Healthcare For Adults With Williams Syndrome And Their Caregivers, Andrea Johnson

Theses and Dissertations

Transitioning to adult care services is a crucial time for young adults with a genetic condition. Many of these conditions are diagnosed early in childhood, with follow-up care fragmented and dependent on the specific needs of the individual. Williams syndrome (WS) is a complex genetic condition characterized by multisystemic features. The variation in the clinical presentation of adults with WS can influence the individual’s ability to transition from pediatric care because of its medical complications, variable and poorly characterized psychiatric needs, and intellectual disability that causes difficulty communicating health-related needs to providers. This study focused on understanding the needs of …

Effects Of Mmp14 Overexpression On Cardiac And Ovarian Connective Tissue And Myocyte Size In Pregnant And Post-Partum Mice, Emily Catherine Walliser

Theses and Dissertations

The main protein component of extracellular matrix is collagen, which fills spaces and supports cells. In the heart, collagen provides the scaffolding for cardiomyocytes and aids in contractile forces. In the ovary, collagen gives follicles their structural support. MMP14 or membrane type 1 matrix metalloproteinase is a membrane bound proteinase that cleaves extracellular matrix proteins, including collagen I and III. Recent studies have shown that overexpression of MMP14 influences collagen content in the heart, and elevated MMP14 has also been linked to ovarian cancer. In the current study, we investigate the effects of overexpression of a human MMP14 (hMMP14) transgene …

Design Of An Artificial Transcription Factor For Inducing Potent Interferon-Γ Signals, Ashley King

Theses and Dissertations

Cytokines are small immune signaling proteins responsible for cellular communication and their levels are tightly regulated throughout immune recognition and defense. Interferon gamma is a key cytokine responsible for upregulation of antigen presentation and supports the differentiation of pro-inflammatory effector cells. Due to its role in regulation, excess interferon gamma is cleared from the body limiting the success of interferon gamma immunotherapies. This study reports the design and validation of an artificial transcription factor (ATF) that induces endogenous interferon gamma expression. The transcription factor contains zinc finger proteins to recognize the interferon gamma gene and an activation domain to promote …

Quantification Of Immunometabolite Derived Protein Modifications During Mitochondrial Metabolic Stress, Justin Hunter Cox

Theses and Dissertations

The immunometabolite itaconate accumulates during lipopolysaccharide (LPS) stimulation of macrophages and microglia. Itaconate non-enzymatically reacts with cysteine residues to generate 2,3-dicarboxypropylcysteine (2,3-DCP), referred to as protein dicarboxypropylation. The tricarboxylic acid (TCA) cycle metabolite fumarate non-enzymatically reacts with the amino acid cysteine to form S-(2-succino)-cysteine (2SC), resulting in irreversible protein succination. Since fumarate and itaconate levels dynamically change in activated immune cells, the levels of both 2SC and 2,3-DCP reflect the abundance of these metabolites and their capacity to modify protein structure and function. I generated esters of 2SC and 2,3-DCP from protein hydrolysates and used stable isotope dilution liquid chromatography-tandem …

Assessing Obgyn Residents’ Knowledge, Attitudes, And Current Practices For Carrier Screening, Aubrey Morgan Surian

Theses and Dissertations

Obstetricians and gynecologists (OBGYNs) are the main providers that order carrier screening on a regular basis, so it is important to understand their knowledge, attitudes, and current practices regarding this screening. There are two primary professional organizations that have established practice guidelines for carrier screening, the American College of Obstetrics and Gynecology (ACOG) and American College of Medical Genetics (ACMG). With the growth of pan-ethnic carrier screening, these guidelines have become remarkably different. This study aimed to assess resident OBGYN’s utilization of pan-ethnic carrier screening, discern any discrepancies between knowledge, attitudes, and current practices, identify possible practice resources that may …

Investigation Of The Environmental Factors Regulating The Biomass And Toxin Production Of The Benthic Cyanobacterium Microseira Wollei In Lake Wateree, South Carolina, Kara Clyburn

Theses and Dissertations

Impacts from anthropogenic activities and climate change are significantly altering nitrogen (N) cycling processes and biological productivity along the freshwater to marine continuum, and the acceleration rate of excessive N and phosphorus (P) concentrations entering aquatic environments is unprecedented. As a result, nutrient pollution is contributing to the increasing magnitude and duration of cyanobacterial harmful algal blooms (cHABs), oxygen (O2) depletion, loss of biodiversity, and impacts to human and ecosystem health. Lake Wateree, South Carolina (SC) is a freshwater drinking and contact recreational water resource with elevated symptoms of eutrophication, including the increasing prevalence of the N2 fixing benthic cyanobacterium …

Perception Of Alzheimer’S Actionability Among End Users Of Direct-To-Consumer Genetic Tests, Emily Mason

Theses and Dissertations

The APOE ε4 allele is the best-known genetic risk factor for developing late-onset Alzheimer’s disease. Although new evidence is emerging, the extent to which lifestyle improvements can reduce Alzheimer’s risk needs further investigation. Research suggests that individuals with a higher genetic risk may be more likely to engage in risk-reducing health behavior changes following results disclosure. This study aimed to better understand these findings by assessing the health behavior and perceptions of Alzheimer’s actionability among consumers of DTC genetic tests. Our study revealed that individuals with 2 copies of the APOE ε4 allele were less likely to make lifestyle modifications …

Estuarine Microbial Community Composition And Efficiency Changes In Response To Vibrio Parahaemolyticus Exposure, Sarah Mulligan

Theses and Dissertations

Vibrio parahaemolyticus is a pathogenic bacterium whose full impact on natural estuarine phytoplankton communities has not been fully resolved. The primary goal of this research was to test how the addition of V. parahaemolyticus to a natural estuarine microbial community would impact the other microbes present. We hypothesized V. parahaemolyticus exposure would reduce phytoplankton biomass and alter the composition of phytoplankton and bacterial communities. Experimental bioassays (60h) were used to assess the effects of the presence of V. parahaemolyticus . Samples for measurements of chemotaxonomic photopigment concentrations, 16S sequencing-based community composition, photosynthetic efficiency, cell density, and V. parahaemolyticus abundance were …

Understanding The Role Of Host Derived Interleukin 1 Alpha In Breast Cancer Progression, Manikanda Raja Keerthi Raja

Theses and Dissertations

In breast cancer research, Interleukin-1 alpha (IL1α) remains a lesser-explored frontier, while its counterpart, Interleukin-1 beta, has garnered extensive scrutiny and understanding. To address this knowledge gap, our investigation leveraged the MMTVdriven HER2+ orthotopic model in Wildtype (WT) and IL1α-/- mice. Our approach demonstrated tumor regression in IL1α-/- mice at the 2-week timepoint, while WT tumors grew exponentially. At 2 weeks, IL1α-/- mice exhibited an immune "hot" microenvironment with increased CD45+ immune cells, particularly CD11b+ myeloid, and CD8+ T cells. CD8+ cells in IL1α-/- mice showed enhanced anti-tumor cytokine production and proliferative capability, with …

Histories Of Stress: A Life Course Approach To Population Health In Late Medieval And Early Modern Berlin, Emily Brennan

Theses and Dissertations

Given our current climate crisis and urban population increases, researchers are increasingly interested in the health outcomes at the intersection of climate change and urbanization. Since climate change and urbanization affects human health in a variety of ways, more work is needed in diverse cultural contexts to understand temporal and geographic variations of such phenomena more fully. Using skeletal individuals from 13^th – 18^th century Berlin (n = 387), this project analyses demographic and health trends from the founding of the city in the late medieval period (c. 1200 – 1500) to the early modern period, when the …

Characterizing The Role Of The Escherchia Coli Monothiol Glutaredoxin, Grxd, As An Iron-Sulfur Cluster Carrier Protein, Claire Elizabeth Fisher

Theses and Dissertations

Iron-sulfur (Fe-S) clusters are important cofactors with a primary role of electron transport that are required by proteins involved in wide range of biological pathways such as respiration, photosynthesis, and DNA repair. In Escherichia coli (E. coli), the assembly and transfer of these clusters to their target apo-protein is a highly coordinated process encoded by the multiprotein systems iscRSUAhscBAfdx and sufABCDSE operons. These clusters are assembled on a scaffold protein, where they are then transferred to a carrier protein that will deliver the cluster to the target apo-protein. The Isc and Suf systems contain their own carrier proteins IscA …

Patients’ Experience Of Care Following Perinatal Case Conference, Mary Elise Nolen

Theses and Dissertations

The Perinatal Case Conference (PCC) at Prisma Health-Midlands Maternal-Fetal Medicine (MFM) is a biweekly multidisciplinary meeting to discuss pregnancies with prenatally identified congenital anomalies. Patients are primarily cared for by MFM and may have appointments with various subspecialists during their pregnancy. The goals of the PCC are multidisciplinary collaboration in planning for the management of each pregnancy and familiarizing each practitioner with the pending cases, so if or when intervention is needed, the clinicians are familiar with the case.

Researchers performed a chart review and surveyed patients whose pregnancies were discussed in the PCC to learn the patient’s perspective of …

The Utility Of Referrals From A State Early Intervention System To A Pediatric Genetics Clinic To Increase Access To Genetic Services, Mikayla Jennings

Theses and Dissertations

Infants or toddlers enrolled in state early intervention programs have developmental delays or are diagnosed with conditions that may result in developmental delays. These infants receive a wide range of services from early intervention. In the state of South Carolina, children in the early intervention program are offered genetic evaluations at no cost to the family. Exploring the relationship between state early intervention systems and genetic clinics and the impact on this particular patient population can provide support for new and continued use of this service delivery model.

The purpose of this study was to evaluate the service delivery model …

Cancer Screening For Patients With Intellectual Disability: Exploring Parent And Caregiver Perspectives, Jennifer Ryan

Theses and Dissertations

Intellectual disability (ID) is defined as a combination of deficits in cognitive and adaptive function, both of which must be present early in life. Adults with ID frequently have unique healthcare needs; however, they also require care that is routine for all adults. This includes cancer screening. The goal of this study was to evaluate whether or not adults with ID are undergoing cancer screening, understand the barriers they have faced in obtaining screening, and collect recommendations from parents and caregivers on ways to improve access to and facilitate screening for this population. We surveyed parents and caregivers of adults …

The Effects Of High Fat Diet On Lipid Deposition In Skeletal Muscle, Alexander Huss

Theses and Dissertations

By the year 2030, almost 50% of adults in the United States are expected to be obese. Obesity has been shown to increase the risk of several chronic metabolic diseases, several cancers, and is associated with impaired skeletal muscle function and metabolism. Despite this, little it is known about the role of altered muscle lipid homeostasis, lipid droplet dynamics, and lipid droplet-mitochondrial interactions in contributing to muscle dysfunction in obesity. Therefore, we sought to investigate the impact of high-fat diet induced obesity on overall skeletal muscle lipid deposition, intramyocellular lipid droplet content and morphology, and lipid droplet-mitochondrial contact. Male C57/BL6 …

Optimal Limb Regeneration Strategies In Hemigrapsus Sanguineus, Laura S. Fletcher

Theses and Dissertations

Diet quality and energy allocation influence an individual’s life-history traits by determining how much energy is available for processes such as growth and reproduction. One common method of assessing diet quality involves measuring gut length or size, which is typically inversely related to diet quality. However, this often requires animal sacrifice and time- consuming dissections. Similarly, many traditional bioenergetics models fail to capture the context-dependence of energy allocation, as these models rely on fixed energy allocation rules. One such rule is the κ-rule of dynamic energy budget theory, which assumes a fixed proportion (κ) of assimilated energy is always allocated …

Microbial Hydrolysis Process To Improve Anaerobic Digestion For Biofuel Generation, Caleb Michael Jensen

Theses and Dissertations

Human development results in billions of tons of waste per year, which contributes to major issues such as pollution, climate change, and habitat destruction. In this study, we explored the impact of bacterial inoculation on volatile fatty acid (VFA) production, volatile solids (VS), and gas output in anaerobic digesters under different substrate treatments. Our results reveal that bacterial inoculation significantly boosts VFA levels, especially acetic acid, with both Caldicellulosiruptor bescii and mixed Caldicellulosiruptor, cultures showing notable differences compared to controls, especially in untreated manure and WAS treatments. Acetic acid and VS/TS increased in untreated WAS when inoculated with C. bescii …

Corneal Epithelial Tissue Engineering Approaches To Treat Limbal Stem Cell Deficiency, Sasirekha K

Theses and Dissertations

A clear healthy cornea is essential for visual acuity. As a self-renewing and regenerating tissue, the corneal epithelium has a stem cell pool, the limbus that acts as its proliferative reservoir. When limbal epithelial stem cells are destroyed or become dysfunctional, a pathological state known as limbal stem cell deficiency (LSCD) manifests. Damaged corneas have been successfully reconstructed by transplanting the cultured limbal epithelial stem cells. Limbal stem cell transplantation (LSCT) is one of the applicable and most challenging procedures in clinical ophthalmology for the reconstruction of the stratified ocular surface epithelium in patients with LSCD. Given the above challenge, …

The Effects Of Combining Β-Lactam Antibiotics And Mefloquine In Multi-Drug Resistant Pseudomonas Aeruginosa, Kayla C. Maas

Theses and Dissertations

Pseudomonas aeruginosa, a notorious opportunistic pathogen, is a leading cause of hospital-acquired infections. The newest generation of β-lactam antibiotics, the carbapenems, are often used to treat multi-drug resistant (MDR) P. aeruginosa infections. Treatment of P. aeruginosa has become increasingly difficult due to its remarkable ability to resist antibiotics through various intrinsic and acquired mechanisms. Physicians rely on a limited group of antibiotics to treat these infections, but many P. aeruginosa isolates are evolving to become resistant to all available antibiotics, including carbapenems. The multifaceted mechanisms underlying P. aeruginosa antibiotic resistance include β -lactamases, efflux pumps, altered membrane porins, and antibiotic …

Exploring The Role Of Rb1 In Cellular Differentiation Using Patient-Derived Stem Cells, Ambily Vincent

Theses and Dissertations

The Retinoblastoma (RB1) gene, predominantly recognized as a tumour suppressor, plays a crucial role in early growth and development. Mice lacking the retinoblastoma gene do not survive and exhibit defects in the differentiation of various tissues, underscoring its involvement in cellular differentiation. This suggests that the functions of the RB1 gene extend beyond its role as a tumour suppressor, encompassing cell cycle regulation, maintenance of genomic stability, cellular senescence, and cellular differentiation.

While the tumour suppressor function of the RB1 has been extensively studied, its role in cellular differentiation remains incompletely understood. Existing literature, primarily based on animal models, has …

Quantifying The Influence Of Air Resistance And Drafting On The Metabolic, Kinematic And Kinetic Demands Of Running, Jared Robert Deandreis Steele

Theses and Dissertations

Purpose: This study aimed to quantify the effects of air resistance on metabolic, kinetic, and kinematic parameters during treadmill running and to investigate how drafting influences these parameters. Methods: Thirty-three well-trained distance runners participated in biomechanical assessments, and seventeen of these also participated in metabolic assessments. The protocol involved running at 80-85% of critical speed on a force-instrumented treadmill facing a wind tunnel. Five wind conditions were tested: no fan (NF), headwind (HW), headwind with drafting (HWD), no wind (NW), and no wind with drafting (NWD). Ground reaction forces (GRF) and kinematic data were collected and analyzed using linear mixed-effects …

Rna Sequencing Reveals Chemotherapy-Induced Changes In Genes Associated With Neurogenesis And Neuronal Function, Bailey Cronin

Theses and Dissertations

Over 310,000 new cases of breast cancer will be diagnosed in 2024, making it the most commonly diagnosed cancer in United States women. Advancements in treatment options such as chemotherapy and radiation have resulted in a 5-year survival rate of 91%. With nearly 4.1 million breast cancer survivors living in the United States today, there is a need for a better understanding of the long-term side effects of these treatments and the impact these may have on the quality of life for these survivors. Reported in up to 78% of cancer patients who received chemotherapy, chemotherapy induced cognitive impairment (CICI), …