Digital Commons Network^™

Impact Of Tumor Cell Expressed Cd38 On Metastasis And Immune Evasion In Breast Cancer, Tanvi Visal

Dissertations and Theses (Open Access)

Triple-negative breast cancer (TNBC) is a highly metastatic breast cancer subtype. The epithelial-to-mesenchymal transition (EMT) of cancer cells is a key feature of the metastatic cascade and is not a binary process but often generates malignant cells with both epithelial (E) and mesenchymal (M) traits known as hybrid EM cells. Recent studies highlight the enhanced metastatic potential of the hybrid EM cells. However, molecular insights and targetable vulnerabilities within hybrid EM remain elusive. We discovered that hybrid EM murine tumors are enriched in CD38, an immunesuppressive molecule associated with worse clinical outcomes in liquid malignancies but relatively understudied in solid …

Rod Photoreceptor Regeneration In A Zebrafish Model With Retinitis Pigmentosa, Eyad Shihabeddin

Dissertations and Theses (Open Access)

A cellular hallmark of inherited retinal degenerative diseases is progressive loss of photoreceptors until one is completely blind. Unlike mammalian models, Zebrafish have the ability to naturally regenerate their neurons after injury or disease is detected. We have generated a zebrafish model with the most common autosomal dominant form of the inherited retinal degenerative disease known as Retinitis Pigmentosa. We utilize immunohistochemistry, single-cell RNA sequencing, several analysis tools, behavioral assays and oligonucleotides to characterize our zebrafish model and identify the transcription factors necessary for rod photoreceptor regeneration. We show that our zebrafish model has continuous degeneration and regeneration of rod …

Exploring Veto Activity: Dnam-1-Cd155 Axis In Overcoming Nk Cell-Mediated Allo-Rejection And Applications For Car-T Cell Therapy, Wei-Hsin Liu

Dissertations and Theses (Open Access)

As Miller et al. defined veto activity, it enables cells to target host cytotoxic T lymphocyte (CTL) precursors specific to veto cells' antigens, selectively eliminating anti- donor T cell clones without inducing rejection. By leveraging this unique immune property, two key research aims were proposed: “Exploration of the Impact of Veto Activity on Natural Killer (NK) Cell-Mediated Allo-rejection” and “Development of Off-the- shelf Chimeric Antigen Receptor (CAR)-T Therapy: Engineering Anti-Viral Veto CD8+ T Cells”. As demonstrated in our previous research, in a murine model with mild conditioning, anti-third-party central memory CD8+ veto T cells (veto Tcm) can prevent T cell- …

The Gut Microbiome As A Novel Approach For Reversing Long-Term Inflammation And Accelerated Aging Across The Lifespan, Janelle M. Korf

Dissertations and Theses (Open Access)

Introduction: Neonatal hypoxic-ischemic encephalopathy (HIE) arises from disrupted perinatal cerebral oxygenation and perfusion. It is a leading global cause of infant death and disability which disproportionally affects males. Like adult stroke, HIE initiates a rapid influx of inflammatory cells across the blood brain barrier and a loss of microglial homeostasis. Persistent peripheral inflammation in children with a history of HIE is recognized but its ramifications, including accelerated aging, are poorly understood. As this coincides with critical stages of brain development, interventions started months or years post-injury may still improve survivors’ quality of life. One promising intervention is to manipulate the …

Overcoming Resistance To Cdk4/6-Targeted Therapy Using Jak2/Stat3 Inhibitor In Triple-Negative Breast Cancer, Chuling Zhuang

Dissertations and Theses (Open Access)

Breast cancer is the most common type of cancer diagnosed in women, with nearly 30% of cases becoming metastatic accounting for over 90% of breast cancer-related deaths. Among different breast cancer subtypes, triple-negative breast cancer (TNBC) has the worst prognosis and the highest propensity to metastasize. However, TNBC patients have limited treatment options due to their lack of actionable drug targets while therapeutic resistances result in high rates of recurrence and metastasis. Cyclin-dependent kinase 4 and 6 (CDK4/6) are major cell cycle regulators that control G1 to S phase transition and aberrant hyperactivation of the CDK4/6 pathway results in uncontrolled …

Impact Of Personal And Family History Of Huntington's Disease On The Decision And Ability To Obtain Life, Long-Term Care, And Disability Insurance, Karli Livingston

Dissertations and Theses (Open Access)

Huntington’s disease (HD) is an inherited, neurodegenerative condition characterized by a clinical triad of motor, cognitive, and psychiatric symptoms. Individuals diagnosed with HD manifest characteristic symptoms of the disease including motor and cognitive changes, and they may or may not have undergone genetic testing to confirm the diagnosis. Individuals at-risk for HD are those who have not yet undergone genetic testing for HD, but have a first- or second- degree relative diagnosed with the disease. Genetic testing for HD is categorized into two forms: predictive and confirmatory. However, many individuals choose not to pursue testing due to a fear of …

Uncovering A Fundamental Mechanism Underlying Female Oocyte Quality And Rasopathies Using C. Elegans As A Model System, Han Bit Baek

Dissertations and Theses (Open Access)

Signaling pathways are molecular networks that allow cells to communicate between and within themselves. They are crucial for the coordination of diverse cellular processes and are the molecular mechanism in which cells sense and respond to their environment. RAS (Rat Sarcoma) is a small GTPase that transmits extracellular growth factor signals through a downstream kinase cascade and ERK (Extracellular-signal regulated kinase) is the terminal kinase, and it controls cellular processes such as proliferation, differentiation, and survival by phosphorylating its downstream effectors. This post translational modification regulates the effector by modulating its activity, levels, and/or interaction with other molecules. Given the …

Exploring The Immunologic Consequences Of Atrx Deficiency In Glioma, Benjamin Whitfield

Dissertations and Theses (Open Access)

ATRX is a key chromatin regulator that is frequently mutated across multiple cancer types. One of the most common ATRX-mutated tumor types is the adult-type glioma, IDH-mutant, Astrocytoma. It is known that ATRX mutation leads to increases in DNA damage, replication stress, and global epigenetic regulation at a cell level; however, less is known about the impact of ATRX mutation on immune signaling. Furthermore, little is known about the interaction of ATRX loss with gain-of-function mutations in IDH. In this paper we set out to explore the impact of ATRX loss on immune signaling in gliomas, both in the context …

Investigating Prefrontal Cortex Neuronal Signatures Of Opioid-Induced Risk-Taking Behavior, Cana Quave

Dissertations and Theses (Open Access)

Opioid use disorder occurs alongside impaired risk-related decision-making, but the underlying neural correlates are unclear. We developed an approach-avoidance conflict task using a modified conditioned place preference procedure to study neural signals of risky opioid seeking in the prefrontal cortex, a region implicated in executive decision-making. Following morphine conditioned place preference, rats underwent a conflict test in which fear-inducing cat odor was introduced in the previously drug-paired side of the apparatus. While the saline-exposed control group avoided cat odor, the morphine group included two subsets of rats that either maintained a preference for the paired side despite the presence of …

Mhc Class I Tyrosine Phosphorylation Site Y320 Augments Cd8+ T Cell Priming, Effector Function, And Memory Response, Yimo Sun, Gregory A Lizee, Yitao Tang, Priscilla Ortiz, R Eric Davis

Dissertations and Theses (Open Access)

The cytoplasmic domain of MHC class I (MHC-I) molecules contains a single, highly conserved tyrosine residue (Y320). In previous work, we found that mice expressing a Y320F-mutated form of H-2K^b had reduced capacity to generate K^b-restricted cytotoxic T lymphocyte (CTL) responses following viral infection, due (at least in part) to defects in endolysosomal trafficking of H-2K^b and antigen cross-presentation by dendritic cells (DCs). In this study, we investigated whether there are additional, post-presentation dependencies on Y320 for T-cell priming. We engineered both human- and mouse-derived antigen-presenting cells (APCs) to express either wild-type MHC-I or variants of …

Neural Activity Within And Between Visual And Executive Areas Is Modulated Post-Locomotion In Rhesus Macaques, Sergey Egranov

Dissertations and Theses (Open Access)

Physical activity has been shown to benefit cognitive and mental health by improving cerebrovascular perfusion and regulating hormone-mediated processes on a systemic level. However, the acute effects of physical activity, such as locomotion, on the neuronal circuits underlying cognitive processes have yet to be fully characterized. This body of work seeks to rectify this gap in knowledge through analysis of how both behavioral performance and neuronal activity signatures in visual and executive brain regions are modulated post-locomotion in rhesus macaques.

To this end, we performed high-yield electrophysiological recordings simultaneously from area V4, a mid-tier visual cortical region, and the dorsolateral …

Investigating Metabolic And Mitochondrial Adaptations Triggered By Blood Flow During The Endothelial-To-Hematopoietic Transition, Paulina Horton

Dissertations and Theses (Open Access)

Hematopoietic stem cell (HSC) transplant is the standard of care for many hematologic diseases. However, many patients cannot benefit from this potentially curative treatment because they cannot find a suitable donor, contributing to a high level of unmet need. Recently, bona fide HSCs capable of robust engraftment and differentiation have been generated from iPSCs utilizing wall shear stress (WSS) to help promote HSC generation. However, the mechanisms through which WSS regulates hematopoiesis remain poorly understood. Scientists, therefore, continue to look for the mechanotransduction pathways that promote hematopoiesis, and key answers may lie in examining the role of extrinsic factors that …

Differential Progression Of Pancreatic Premalignancy In Geographically Distant Murine Transgenic Cohorts Uncovers Key Role Of Microbial Metabolites, Rian M. Howell

Dissertations and Theses (Open Access)

Cancer is a leading cause of death worldwide. Despite recent advances in diagnostic and therapeutic modalities, pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer that remains highly lethal. Efforts have been made to increase the understanding of the underlying mechanisms driving early stages of tumor development, when the cancer is most susceptible to intervention. To this end, genetically engineered mouse models (GEMMs) have been developed with the mutations most commonly seen in the patient population. Expression of these mutations in select cellular compartments has resulted in the ability to recapitulate characteristics of human pancreatic cancer such as the development of …

The Evolving Changes In The Regionalization Of Export Bans On U.S. Poultry Trade From The 2015 And 2022 Highly Pathogenic Avian Influenza Events, Kylie A. Roesler

Graduate Theses and Dissertations

As food security becomes a growing concern worldwide in a trading system dominated by globalization, the safeguarding of a bio-secure food system is at risk. One of the greatest risks to this stability of the system is, highly pathogenic avian influenza or HPAI which is growing in frequency and impact. Therefore, the global response to disease events is evolving into a newfound understanding of disease prevalence across the animal protein industries. This study will analyze the 2022 HPAI event in the United States regarding the regionalization of restrictions imposed by trading partners accounting for trade agreements executed. The examination of …

Investigating The Role Of The Hypocretin/Orexin System In A Novel Model Of Polysubstance Dependence, Tyler Zarin

Electronic Theses and Dissertations

Substance use disorders (SUD) in the United States are steadily increasing. Potent and dangerous substances such as methamphetamine (MA) and fentanyl (FEN) are often co-used as a polysubstance (POLY), either intentionally or unknowingly as FEN is a common adulterant. SUD is characterized by physiological and psychological dependence involving the negative reinforcement of anhedonia and withdrawal which drive hypermotivated drug-taking behaviors. Current theory suggests that recruitment of hypocretin/orexin (HCRT) neuropeptide in reward and stress associated brain regions contributes to drug dependence. Despite strong evidence for HCRT’s role in mono-drug dependence, a relevant model for POLY dependence has yet to be developed, …

Impacts Of Reef Fish Length On Foraging Radius: Exploring Behavioral Patterns Within A Patch Reef Ecosystem, Kilia Brawand

Undergraduate Honors Capstone Projects

Reef fish exhibit various behaviors upon the Great Barrier Reef. One of these behaviors includes that of limiting their grazing distances from a patch reef refuge to a certain maximum distance in order to avoid predators. This is defined as a ‘foraging radius’ or ‘margin of safety’. This ‘foraging radius’ varies among fish due to many factors- including species, morphology, ontogenesis, habitat complexity, and importantly: speed. Quicker fish can outswim predators to safety more efficiently than slower fish, and can therefore afford to travel farther distances to forage. Speed varies among fish for a number of reasons, including fish size …

Structural Stability Of Fgf1-Fgf2 Dimer Established Via Salt Bridges With Mutation K296q, Ashleigh Letterman

Chemistry & Biochemistry Undergraduate Honors Theses

Fibroblast Growth Factors (FGFs) are a family of cell-signaling proteins. FGF, specifically the FGF-1 subfamily, which contains FGF-1 and FGF-2, is important in several biological functions such as wound healing, cell proliferation, and angiogenesis. FGF-1 has cell proliferation properties and FGF-2 has angiogenic properties. These FGFs have great potential for wound-healing therapy medications...

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A Sex Comparison On The Effects Of Caveolin Scaffolding Domain On Fibrosis Formation After Chronic Sympathetic Stimulation, Crimsyn Price

Undergraduate Honors Theses

Cardiovascular disease (CVD) is the leading cause of mortality worldwide. There are various trends that influence the rates of cardiovascular disease in each country. Factors that create these trends involve diet, exercise, genetics, socioeconomic status, and geographical location. Additionally, CVD is typically higher in middle-income and lower-income classes. Hospital routes, rates of poverty, insurance policies, and lifestyle culture are all factors that can impact the time of treatment which in turn affect the rate of CVD. However, we explored in this study the shift in CVD women experience after menopause. Women were excluded from clinical trials until 1986, and the …

Unveiling The Intercompartmental Signaling Axis: Mitochondrial To Er Stress Response (Mersr) And Its Impact On Proteostasis, Jeson J Li, Nan Xin, Chunxia Yang, Bo G Kim, Larissa A Tavizon, Ruth Hong, Jina Park, Travis I Moore, Rebecca George Tharyan, Adam Antebi, Hyun-Eui Kim

Faculty, Staff and Student Publications

Maintaining protein homeostasis is essential for cellular health. Our previous research uncovered a cross-compartmental Mitochondrial to Cytosolic Stress Response, activated by the perturbation of mitochondrial proteostasis, which ultimately results in the improvement of proteostasis in the cytosol. Here, we found that this signaling axis also influences the unfolded protein response of the endoplasmic reticulum (UPRER), suggesting the presence of a Mitochondria to ER Stress Response (MERSR). During MERSR, the IRE1 branch of UPRER is inhibited, introducing a previously unknown regulatory component of MCSR. Moreover, proteostasis is enhanced through the upregulation of the PERK-eIF2α signaling pathway, increasing phosphorylation of eIF2α and …

Assessing The Implicit Prices Of Health And Wellness Product Attributes In Pet Food: A Hedonic Analysis Approach, Lonnie Hobbs Jr., Andrew Anderson

Agricultural Economics and Agribusiness Faculty Publications and Presentations

Here we examine product attributes present in dry dog food to show there exist potential price premiums and discounts associated with health and wellness attributes in dry dog food. The findings indicate price premiums are associated with attributes related to digestion and allergy care. Pricing discounts are found to be associated with immune support and dental attributes. The results of this study are anticipated to be a starting point for more sophisticated and dynamic analysis of pricing and willingness-to-pay studies in the pet food industry.

Engineering An In Vitro Hipsc-Derived Cardiac Tissue Construct For Regenerative Medicine Applications, Larry Mendoza

Electronic Theses, Projects, and Dissertations

Cardiovascular disease is the leading cause of mortality across the world with invasive surgeries and pharmaceutical intervention commonly associated with urgent care. Moreover, congenital, progressive, and hereditary heart diseases rely on many forms of medical prevention and intervention (pharmaceuticals, x-rays, bloodwork, etc.). Developing a three-dimensional (3D) cardiac tissue engineered in vitro model to study human cardiac physiology can revolutionize biomedical research. The purpose of this research is to optimize natural & synthetic biomaterials to fuse cardiac stem cells and synthesize a 3D-printed in vitro model for disease modeling, drug delivery, and regenerative medicine. Natural biopolymers needed for such innovations are …

Passive Electronic Cigarette Exposure Initiates Squamous Metaplasia In A Developing 3d Human Tracheobronchial Epithelial Tissue In-Vitro Model, Edgar Rolon

Electronic Theses, Projects, and Dissertations

The prevalence of vaping has rapidly increased. ECs are often perceived as less harmful than tobacco cigarettes. A recent meta-analysis showed electronic cigarette (EC) aerosols adversely affected the respiratory system, similar to cigarette smoke, with some effects specific to EC use. Failure to prevent these alterations could lead to life-long comorbidities, and predisposition to respiratory diseases, including COPD and squamous cell carcinoma. While these effects are the result of active vaping, EC aerosols can also settle on indoor surfaces, be absorbed passively through the skin or orally, enter the blood stream, and subsequently expose internal organs, including the airway basal …

Understanding Factors That Drive Wildlife Mortality During Prescribed Fire Management Of Prairie Restorations, Hunter M. Griffey

Crop, Soil and Environmental Sciences Undergraduate Honors Theses

Fire is a key ecological disturbance, which plays a vital role in maintaining biodiversity and early successional species. For today’s land managers, prescribed fire is key in the restoration and maintenance of prairie ecosystems, halting woody encroachment and creating habitat desperately needed by many species. However, fire may have unintended effects on wildlife populations through direct mortality. Among taxa living in fire-dependent ecosystems, reptiles are predisposed to direct mortality, and several studies have recorded significant mortality during prescribed burns. However, the few studies investigating reptile mortality in prescribed fire are limited by small sample sizes and generally have limited analysis …

Perspectives On Clinical Oncogenomics: Secondary Germline Variants Associated With Tumor Genomic Profiling In Community Cancer Care And Advanced Practitioner Oncogenomic Proficiency, Sarah Moncado

All Dissertations

Precision medicine in oncology is defined by the sequencing of tumor genomic variants that can be used to identify targeted treatment for patients. Secondary pathogenic and likely pathogenic germline variants (P/LPGVs) can incidentally be detected on tumor genomic profiling (TGP). With the rise in precision medicine over the past 15 years, secondary P/LPGVs on TGP have been an increasingly important clinical issue. However, there are factors that can lead to misidentification and underreporting of P/LPGVs. Germane to this clinical practice issue is healthcare provider oncogenomic literacy and proficiency.

A scoping review was conducted to evaluate the variability of the prevalence …

A System And Method For Measuring Spatially Varying Surface Appearances With A Study Of Feathers, Jessica Baron-Lis

All Dissertations

Real-world materials, particularly biological structures such as feathers exhibit complex appearances that vary spatially across their surfaces. The field of computer graphics provides a means of understanding such surfaces through material modeling which uses both analytical models and data acquired from light-surface interactions. There are many efforts within the past decade in measuring materials for graphics, but common limitations in these works include not accounting for spatially varying properties and reliance on neural networks and synthetic datasets.

Feathers from modern birds present diverse appearances due to how light interacts with their unique hierarchical microstructures. Variations in those structures lead to …

Investigate The Use Of Nucleic Acids As Pesticides To Manage Major Pests And Pathogens Of Crops In South Carolina, Prasanna Valavanur Shekar

All Dissertations

The sugarcane aphid (SCA, Melanaphis sorghi), first discovered on grain sorghum in late 2013, has gradually become a major insect pest of sorghum. It inflicts significant damage to the crop year after year, causing millions of dollars in losses throughout the sorghum-producing regions of the United States. Similarly, Armillaria root rot—also referred to as oak root rot—is a major cause of decline in peach (Prunus persica) production in the southeastern United States. This disease is caused by Armillaria mellea and Armillaria tabescens. Current management practices for controlling M. sorghi include the use of synthetic pesticides, resistant varieties, and regular scouting. …

State Case Count As An Indicator Of Successful Multistate Outbreak Investigation, Lorisa M. Pennell

Capstone Experience: Master of Public Health

Background/Objectives: Shiga-Toxin producing Escherichia coli (STEC) is a contaminant found in multiple food types and causes multistate outbreaks due to the industrialization of food production. In this report I examine the differences in outbreaks categorized by the regulating agency responsible in outbreak prevention and compare outbreak case counts when organized by positive outbreak investigation and response outcomes.

Methods: STEC Multistate outbreak data was obtained from the Center for Disease Control’s National Outbreak Reporting System (NORS) for outbreaks occurring from 2006-2023. Outbreaks were organized into those regulated by either the US Food and Drug Administration (FDA) or the US Department of …

Evaluating The Economic Viability Of Feeding Hydroponic Barley Fodder To Growing Wethers, Fallon Johnson

All Graduate Reports and Creative Projects, Fall 2023 to Present

As the livestock industry combats challenges including rising feed costs and ensuring sustainable production practices, some attention is being given to hydroponic fodder as a feed source. Hydroponic fodder offers a potential alternative to traditional feed sources. Research has demonstrated hydroponic fodder production has increased water efficiency while providing a sustainable green feed source throughout the year. This study seeks to understand how using hydroponically produced barley fodder in a total mixed ration for growing wethers compares economically to feeding traditional feed sources. A stochastic simulation model is used to determine the expected total feed costs, costs of gain, and …

The Effect Of Dietary Protein Source On Gut Health, Spencer Lawson Schow

All Graduate Theses and Dissertations, Fall 2023 to Present

We investigated the impact of protein source in a western-style diet on colon cancer, colitis, and the gut microbiome. The Western dietary pattern is energy-dense, low in fiber, and has a sub-optimal micronutrient profile. Our group has formulated the Total Western Diet (TWD) that emulates the Western dietary pattern using survey data (NHANES), and we have demonstrated that this diet increases gut inflammation and colorectal cancer relative to a healthy control diet (AIN-93G), which is optimized for mouse health. However, the effect of protein source in the TWD and its effects on gut health have yet to be investigated.

Recent …

Greater Sage-Grouse Habitat Dynamics And Grazing, A Study Of Vegetation Indices And Survival, Codi R. Backen

All Graduate Theses and Dissertations, Fall 2023 to Present

North American rangelands are vast, open landscapes that support diverse ecosystems and provide many ecosystem services. Many wildlife call sagebrush rangelands home, including the Greater sage-grouse (sage-grouse; Centrocercus urophasianus). Sage-grouse habitat encompasses 165 million acres across western North America, and this bird has been of conservation concern as their populations drastically declined since the 1960s. Rangelands are also grazed by livestock, which has the potential to negatively affect sagebrush ecosystems when overgrazed or overstocked, which could be detrimental to sage-grouse nesting habitat. Additionally, sagebrush rangelands undergo annual variations in precipitation, temperature, growing season length, and vegetation vigor, which has …