Digital Commons Network^™

Zebrafish Models To Uncover Targetable Mechanisms Of Self-Renewal In T-Cell Acute Lymphoblastic Leukemia, Majd Al-Hamaly

Theses and Dissertations--Pharmacology and Nutritional Sciences

Relapsed T-cell Acute Lymphoblastic Leukemia (T-ALL) patients have dismal prognosis, with 5-year overall survival rates of 10% for adults and 36% for children. Relapse is attributed to the inability of chemotherapy agents to eliminate Leukemia Stem Cells (LSCs) that can repopulate the leukemia. Those cells exist with a unique genetic, transcriptomic, and metabolic profile compared to the rest of the leukemia and thus, finding targeted therapies toward this population of cells can result in disease eradication and elimination of relapse. However, investigating LSCs is challenging-particularly in T-ALL- for two reasons: 1) the lack of robust surface markers that define LSCs …

Cell-Type Specific Apoe4 To Apoe2 ‘Switching’ In Astrocytes And Microglia Alters Alzheimer’S Disease Neuropathology, Lesley R. Golden

Theses and Dissertations--Physiology

Apolipoprotein E (APOE) is the strongest genetic risk factor for late-onset Alzheimer’s disease (LOAD). APOE exists in three common protein isoforms throughout the population: ApoE2 (E2), ApoE3 (E3), and ApoE4 (E4). While APOE allele frequencies and the degree of AD-associated risk vary across different ethnic groups, when compared to the ‘neutral’ and most common E3 allele, the E4 allele confers up to a 33-fold increase in Alzheimer’s Disease (AD) risk. Conversely, the neuroprotective E2 allele decreases AD risk by up to 67%. Here, we aimed to determine the therapeutic potential of cell-type specific APOE allele ‘switching’ and explore …

Biochemical And Biophysical Properties Of Failing Myocardium In Rare Patient Populations, Gregory Nathaniel Milburn

Theses and Dissertations--Physiology

Heart failure has diverse underlying etiologies, complicating research. While some types, like ischemic disease or inherited mutations, are well-studied, research on rarer forms has lagged. Understanding the molecular drivers in these populations may enhance diagnostics and therapies. This work examines two rare groups: patients with ATTR cardiac amyloidosis and those receiving mechanical assist device support. We show that myocardium from patients with amyloidosis has increased fibrosis and reduced force production without changes in cross-bridge kinetics. Additionally, we show that the passive stiffness of amyloidosis myocardium is not different from non-failing myocardium, indicating increased ventricular wall thickness may cause restrictive filling. …

Biochemical Properties Of Cardiac Sarcomeres In Human Heart Failure, Austin Grey Wellette-Hunsucker

Theses and Dissertations--Physiology

Heart failure (HF) exhibits considerable heterogeneity, posing significant challenges for research involving human cohorts. Diastolic dysfunction is a common pathophysiological feature; however, its molecular mechanisms remain incompletely elucidated. Sarcomeric proteins are integral to cardiac contraction and relaxation. Nonetheless, the phosphoproteome and the structural remodeling effects of these proteins on diastolic function within the context of HF have not been comprehensively characterized. This study examined sarcomeric modifications in diastolic dysfunction in human HF, focusing on Dilated and Ischemic HF, with non-failing donor hearts as controls. Analyzing myocardial samples from ~150 patients using electrophoretic and biochemical techniques, it found significant titin remodeling …

Dinotefuran Resistance In The German Cockroach (Blattella Germanica L.), Hannah F. Blevins

Theses and Dissertations--Entomology

German cockroaches (Blattella germanica L.) are one of the most prevalent and pervasive indoor pest species in the world. Infestations can lead to many negative impacts on humans, including sensitization to allergens, increase in asthmatic symptoms, mental health declines, and potentially, the spread of diseases. While insecticides remain the most effective and affordable option for German cockroach control, resistance to many commonly used insecticide active ingredients (AIs), such as pyrethroids, has been observed globally at high levels across different populations. Given such resistance to pyrethroids, inclusion of insecticides with alternative modes of action into insecticidal treatments could potentially improve cockroach …

Bed Bugs: Health Risks And Control, Simona Principato

Theses and Dissertations--Entomology

Bed bugs are blood-feeding hemipterans strongly associated with humans. Their detection in indoor environments, such as homes, hotels, trains, and public facilities, has increased gradually over the past 20 years. The exact cause of their resurgence is still unclear, but the increase of international travel and insecticide resistance are thought to have contributed to it.

Although bed bugs are not known to transmit diseases, the EPA, CDC, and USDA have classified them as a pest of significant public health concern, mainly due to the dermatitis that they can cause. Beyond the dermatological burden of the bites, other health implications often …

The Role Of Nutrition In Managing Honey Bee Viral Pathogen, Caroline Wylie Kane

Theses and Dissertations--Entomology

This study evaluated the impact of nutritional supplements on viral infections in honey bee colonies, focusing on Lake Sinai Virus 2 (LSV2), Deformed Wing Virus A (DWVA), and Deformed Wing Virus B (DWVB). I partnered with 32 hobbyist beekeepers across Kentucky, who volunteered 138 colonies for a month-long field study. Half of the colonies received weekly commercial supplements, while the other half served as controls. Viral titers were measured before and after the supplementation period using qPCR. Supplements did not significantly reduce viral titers for any of the three viruses, suggesting that short-term supplementation may not be effective in lowering …

Exportin 1 Is The Central Hub In Antiviral Defensive Mobilization Of Nuclear Factors And The Target Of Counter-Defence By Tombusviruses, Biao Sun Dr.

Theses and Dissertations--Plant Pathology

Positive-strand RNA viruses, such as coronaviruses and flaviviruses, are obligate parasites whose genomic RNAs function as mRNAs. These viruses infect a wide range of hosts-including plants, animals, and humans-resulting in significant economic losses and posing serious threats to public health. Due to the relatively simple structure of the genome of positive-strand RNA viruses, many host factors and physiological processes are co-opted to support virus infection and replication. In our previous studies, we identified numerous host factors and associated physiological processes involved in the replication of tombusviruses, a cytosolic-replicating model that includes tomato bushy stunt virus (TBSV) and carnation Italian ringspot …

Gene Expression In Relation To Bone Fractures In Throughbred Racehorses, Anna M. Rauber-Ramos

Theses and Dissertations--Veterinary Science

Evidence that fractures in Thoroughbred racehorses are outcomes of chronic bone microdamage has led to extensive research into identifying horses at increased risk of fracture. This includes the use of biomarkers and messenger RNA (mRNA) as a measure of bone turnover. Previous research has found expression differences in horses with fractures compared to controls. Utilizing pre-race whole blood samples collected over an 18-month period from Thoroughbred racehorses in Southern California, RNA-sequencing was conducted on horses with bone fractures and race-matched controls to identify differences in gene expression. Focusing on third metacarpal (MC3) and proximal sesamoid bone (PSB) fractures, differentially expressed …

Engineering Novel Biomimetic Models Of Equine Host-Microbe Interactions, Lynn M. Leedhanachoke

Theses and Dissertations--Veterinary Science

One major limitation to the study of equine disease is the lack of in vitro models that accurately reflect the dynamic physiology of the horse. Thus, there is a pressing need to develop in vitro systems that recapitulate diverse equine tissue and organ microenvironments. To overcome this deficiency, we developed multiple biomimetic equine organoid systems that can be employed for a variety of investigations aimed at resolving outstanding questions in infectious disease pathogenesis, therapeutic development and drug metabolism, host defense mechanisms, immune-modulated disease, and equine developmental biology. Our innovative platform incorporates novel equine intestinal enteroid and airway organoid models derived …

Avian Response To Legacy Coal Mine Reforestation In The Cumberland Plateau, Kentucky, Madoline J. Varias

Theses and Dissertations--Forestry and Natural Resources

Surface coal mining and reclamation processes alter the ecological characteristics of landscapes, which affects the presence and distribution of native wildlife. The Forestry Reclamation Approach (FRA) is a coal mine reclamation method that aims to establish native forests on surface mines and has been widely implemented across the Central Appalachian region. Avian response the FRA, in particular, is unknown in Kentucky and limited throughout Appalachia. Thus, the goal of this project was to assess the effects of the FRA on avian community occupancy, species richness, and abundance in the Cumberland Plateau of Kentucky. Point count surveys were conducted across three …

Does Participation In An Innovative Livestock Exhibition Program Foster The Development Of Grit In Youth Across Rural, Micro, And Metropolitan Communities?, Reba V. Prather

Theses and Dissertations--Community & Leadership Development

This research examined whether livestock exhibition could be used to foster grit in youth across rural, micropolitan, and metropolitan communities. More specifically, the researcher sought to evaluate the impact an innovative livestock exhibition program had on youth resilience. Through partnerships with 4-H clubs and agricultural organizations, the initiative encourages community-driven involvement, allowing youth to take ownership of their growth and development. The program utilized agricultural animal husbandry experiences as a mechanism for youth development, exploring the broader impact of livestock engagement on character-building. By assessing the outcomes of these experiences, the research highlights the trials and tribulations associated with fostering …

Exploring Belongingness, Loneliness, And Distinctiveness On A College Of Agriculture Campus, Sophia Jaramillo-Vasconez

Theses and Dissertations--Community & Leadership Development

The purpose of this study was to explore how sense of belonging, loneliness, and distinctiveness affect students in the Martin-Gatton College of Agriculture, Food and Environment (M-G CAFE). By examining the intersection of student demographics and their experiences, this research aimed to provide a deeper understanding of the dynamics that shape students’ agricultural experiences at the postsecondary level. This study investigates the relationship between student characteristics and their reported levels of belonging and loneliness, and how these factors influence perceptions of their representation and distinctiveness within the M-G CAFE program. An explanatory sequential mixed methods design was employed, beginning with …

Influence Of Agrochemical Mixtures On Nitrogen Transformations In Floating Treatment Wetlands, Matthew Russell

Theses and Dissertations--Biosystems and Agricultural Engineering

Controlling losses of nitrate-N from agricultural fields to ground and surface water environments is one of the most pressing water resources problems today. Increasing levels of nitrate-N pollution in surface and groundwater is a critical threat to human and environmental health across the globe. To mediate nitrate-N losses, natural and constructed wetlands have been increasingly used as nutrient mitigation technologies and strategies. The use of wetlands as a treatment approach for nitrogen in runoff is a common practice in agroecosystems, however, nitrate-N is not the sole constituent present in agricultural runoff, and other biologically active contaminants have the potential to …

Development Of A Cultivation System For Producing Pure Mycelium Materials From Distillers' Spent Grains, Keya Rani Roy

Theses and Dissertations--Biosystems and Agricultural Engineering

Stillage is a byproduct of distilleries which is rich in organic matter, minerals, and acidic components. It is commonly used as animal feed and has high potential for use as an alternative substrate for microorganisms. Filamentous fungi are saprophytes that can utilize stillage solids to grow as threadlike mycelium. The structure and composition of the filamentous mycelium has shown promise to produce pure mycelium materials (PMM), which might have many potential applications, for instance as a leather-like material or alternative protein food ingredient. Basidiomycota fungi (including true mushrooms) species are presently used in industry to produce PMM due to the …

Impact Of Obesity On The Gut Microbiome And Inflammatory Markers During Siv Infection And Antiretroviral Therapy, Casey M. Mcguire, Isaac R. Cinco, Diana Takahashi, Kristin A. Sauter, Melissa Kirigiti, Ilhem Messaoudi, Jonah B. Sacha, Charles T. Roberts, Paul Kievit

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Dysbiosis and impaired gut barrier integrity contribute to chronic immune activation associated with both obesity and HIV infection. Given the increased incidence of obesity in people living with HIV, we explored the impact of obesity on the gut microbiome and microbial translocation (MT) biomarkers during HIV infection and antiretroviral therapy (ART). Lean and obese rhesus macaques were infected with simian immunodeficiency virus (SIV) and subsequently treated with ART. Obese animals exhibited higher initial MT and inflammation biomarkers that remained constant throughout the study, while lean animals exhibited significant increases in these biomarkers that approached levels observed in obese animals. Lean …

Clinical Criteria For Limbic-Predominant Age-Related Tdp-43 Encephalopathy, David A. Wolk, Peter T. Nelson, Liana Apostolova, Konstantinos Arfanakis, Patricia A. Boyle, Cynthia M. Carlsson, Nick Corriveau-Lecavalier, Penny Dacks, Bradford C. Dickerson, Kimiko Domoto-Reilly, Brittany N. Dugger, Rebecca Edelmayer, David W. Fardo, Michel J. Grothe, Timothy J. Hohman, David J. Irwin, Gregory A. Jicha, David T. Jones, Claudia H. Kawas, Edward B. Lee, Karen Lincoln, Gladys E. Maestre, Elizabeth C. Mormino, Chiadi U. Onyike, Ronald C. Petersen, Gil D. Rabinovici, Rosa Rademakers, Rema Raman

Biostatistics Faculty Publications

Limbic predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is highly prevalent in late life and a common co-pathology with Alzheimer's disease neuropathologic change (ADNC). LATE-NC is a slowly progressive, amnestic clinical syndrome. Alternatively, when present with ADNC, LATE-NC is associated with a more rapid course. With the emergence of anti-amyloid therapeutics, discrimination of LATE-NC from ADNC is critical and will lead to greater clinical recognition of amnestic patients without ADNC. Furthermore, co-pathology with LATE-NC may influence outcomes of these therapeutics. Thus there is a need to identify patients during life with likely LATE-NC. We propose criteria for clinical diagnosis of …

A Myostatin Inhibitory Antibody Combined With Insulin, Partially Rescues The Musculoskeletal Phenotype Of Female Insulin-Deficient Diabetic Mice, R. Clay Bunn, Reuben Adatorwovor, Philip D. Ray, Alexander R. Keeble, Christopher S. Fry, Sasidhar Uppuganti, Jeffry S. Nyman, John L. Fowlkes, Evangelia Kalaitzoglou

Biostatistics Faculty Publications

Introduction: Type 1 diabetes is associated with deficits in both skeletal muscle and bone. Inhibition of myostatin, a negative regulator of muscle mass, was explored as a druggable target to improve the musculoskeletal phenotype associated with insulin-deficient diabetes in female mice. Methods: We investigated whether administration of an inhibitory myostatin antibody (MyoAb) in streptozotocin-induced diabetes in female mice is protective for skeletal muscle and bone. DBA/2J female mice were injected with low-dose streptozotocin or with citrate buffer (vehicle). Subsequently, mice were implanted with insulin-containing or vehicle pellets, with groups being randomized to myostatin or control antibody for 8 weeks. At …

Cloning, Expression, And Characterization Of Collagen Galactosyltransferases From Human, Sponge, And Sea Walnut, Jeong Seon Kim, Tingfei Chen, Botao Zhang, Tristin M. Miller, Marisa E. Gilliam, Houfu Guo

Molecular and Cellular Biochemistry Faculty Publications

Collagen is an extracellular matrix protein conserved across animals and viruses, with its function regulated by post-translational modifications of lysine residues. Specifically, certain lysine residues in collagen are hydroxylated to form hydroxylysine, which serves as an attachment site for hydroxylysine-linked glycosylation. This glycosylation process is initiated by collagen galactosyltransferases from the GT25 family, also known as GLT25D or COLGALT proteins. Despite their biological importance, efficient methods for expressing and isolating GLT25Ds have yet to be fully developed, and the biochemical mechanisms underlying their function still need to be better understood. To address this, we performed sequence alignment and phylogenetic analyses …

Optimization, Machine Learning, And Networking Solutions For Cyber-Physical Systems, Xu Tao

Theses and Dissertations--Computer Science

Cyber-Physical Systems (CPS) represent a transformative paradigm that integrates sensing, computation, and actuation through networked systems to enable intelligent, context-aware applications across various domains. Despite their growing potential, CPS still face critical challenges, particularly in maintaining reliable, low-latency communication and efficient data processing in resource-constrained and dynamic environments. These challenges are further magnified in rural or remote deployments, where traditional network infrastructure is often unavailable or unreliable. This dissertation addresses these challenges through the development of optimization and inference algorithms that enhance network performance in Software-Defined Networks (SDN), using techniques such as reinforcement learning and network tomography for efficient routing. …

Rad Reduction Reveals Therapeutic Potential Of Targeting Cardiomyocyte L-Type Calcium Channel Regulation For Heart Failure, Garrett Elmore

Theses and Dissertations--Physiology

Heart failure (HF) is prevalent and is predicted to increase with the aging population. Dilated cardiomyopathy (DCM) is a common cause of systolic HF. Current therapies fail to address principal issues: compromised systolic function and dysfunctional Ca²⁺ handling. No therapeutic approach exists for direct, positive modulation of cardiomyocyte L-type calcium channels (LTCC). RAD (Ras associated with diabetes) is a key regulator of the cardiac LTCC. RAD is a downstream phosphorylated target of the ß-adrenergic receptor (ß-AR)/cAMP/protein kinase A pathway; phosphorylation augments LTCC activity, contributing to chronotropy, inotropy, and lusitropy. RAD overexpression results in LTCC inhibition, whereas knockout positively modulates …

Assessment Of Cerebrospinal Fluid And Blood-Based Biomarkers In Degenerative Cervical Myelopathy: Systematic Review And Meta-Analysis, Harshit Arora, Hassan Darabi, Cassandra C. Wolsh, Kelsey N. Karnik, John C. Gensel, Francis Farhadi

Neurosurgery Faculty Publications

Study Design: Systematic Review and Meta-Analysis.

Objectives: Degenerative cervical myelopathy (DCM), the leading cause of spinal cord injury globally, may clinically manifest with hand numbness and tingling, loss of hand dexterity and impaired balance and gait. Biomarkers have been identified as disease indicators with recent studies exploring the role of structural and inflammatory biomarkers in diagnostic and treatment outcome prediction. The review aims to identify relevant cerebrospinal fluid (CSF) and blood-based biomarkers associated with DCM diagnosis and prognostication.

Methods: The systematic review was conducted as per PRISMA guidelines. A comprehensive search strategy was devised to identify articles evaluating biomarkers in …

Molecular Mechanisms And Comparative Transcriptomics Of Diapause In Two Corn Rootworm Species (Diabrotica Spp.), Melise C. Lecheta, Chad Nielson, B. Wade French, Emily Nadeau, Nicholas M. Teets

Entomology Faculty Publications

Diapause is a programmed developmental arrest that can occur at any developmental stage depending on species, but the mechanisms that underscore embryonic diapause are poorly understood. Here, we identified molecular mechanisms underscoring distinct phases of diapause in the Diabrotica spp. complex. This species complex in- cludes economically significant agricultural pests, notably the western corn rootworm (WCR) and northern corn rootworm (NCR), which cause major losses in maize production. Rootworms undergo an obligate embryonic diapause to synchronize their life cycles with host plants, and we sequenced transcriptomes from both species at five time points (pre-diapause, diapause initiation, diapause maintenance, diapause termination, …

Sex-Specific Roles Of The Adipocyte Mineralocorticoid Receptor In Obesity And Early Life Stress, Meghan B. Turner

Theses and Dissertations--Pharmacology and Nutritional Sciences

Obesity is a burgeoning health epidemic caused by chronic overnutrition and exacerbated by genetic, environmental and developmental factors. The adipocyte mineralocorticoid receptor (MR), a transcriptionally active nuclear receptor, is speculated to contribute to metabolic dysfunction in the obese state. MR expression is increased in obese adipose tissue, and MR modulates the expression of fat-derived hormones such as leptin and adiponectin. In women, obesity can be exacerbated by early life stress, such as adverse childhood experiences (ACEs). Studies show that women display a positive association between cumulative ACE exposures and increased body mass index. Previously, we demonstrated that maternal separation and …

Examples Of Storytelling In Tan Dun’S The Banquet Piano Sonata, Ni Zhan

Theses and Dissertations--Music

The Banquet is a 2006 Chinese martial arts film directed by Feng Xiaogang. Chinese-American composer Tan Dun was invited to create the film's original soundtrack. In 2016, Tan adapted the music from the soundtrack into a four-movement piano sonata, also titled The Banquet, using melodies from the original film score. This document examines The Banquet Piano Sonata’s connection to the film’s narrative. It explores ways in which the storytelling of the film is used in the sonata; this is accomplished through three key aspects depicted in the music: culture, atmosphere, and inner emotions.

Hardcore And Metal Music In Music Therapy: A Functional Guide For Music Therapists And Music Therapy Students, Caroline Nc Wood

Theses and Dissertations--Music

Hardcore and metal music have long been misrepresented, stigmatized, and dismissed in music academia, and overlooked in music therapy literature and education. However, these genres hold significant emotional, cultural, and therapeutic value for many listeners, offering unique opportunities for connection, expression, catharsis, and healing. This thesis presents a practical, introductory guide to help music therapists and music therapy students gain an understanding of why, when, and how to effectively and authentically incorporate hardcore and metal music into clinical practice. The project explores the historical development of these genres; sociocultural associations and considerations, including stigmatization, sensationalism, and the juxtaposing sociopolitical dynamics …