Life Sciences Commons^™

Characterizing The Physiology And Genetics Of Contact Dependent Growth Inhibiton Systems In Burkholderia Species, Alice Elizabeth Oates

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Contact-dependent growth inhibition (CDI) systems mediate interbacterial competition. The genes encoding these systems are widespread among Gram-negative bacteria, including Burkholderia pathogens. CDI systems of Burkholderia species are composed of two-partner secretion pathway proteins and function to deliver the toxic C-terminus of a polymorphic surface-exposed exoprotein BcpA (Burkholderia CDI protein A) to the cytoplasm of neighboring recipient bacteria upon cell-cell contact. Specific outer and inner membrane proteins facilitate BcpA translocation both out of the donor bacterium and into the recipient cell cytoplasm. Most Burkholderia species-specific CDI translocation factors in recipient cells are unknown. BcpA intoxication functions as a mechanism by …

Factors Associated With Lifestyle Modification For Type 2 Diabetes Self-Management And Prevention, Leigh Anne Koonmen

Theses and Dissertations--Nursing

Diabetes is the seventh leading cause of death in the United States, affecting roughly 13% of U.S. adults aged 18 years or older. Type 2 diabetes accounts for 90-95% of all diabetes cases and is characterized by the progressive development of insulin resistance leading to sustained elevated blood glucose levels. Management of type 2 diabetes includes risk-reduction strategies and continuous medical care to prevent the development of complications.

Lifestyle is a major contributing factor to morbidity and mortality rates in the United States. Preventative health behaviors, such as engaging in physical activity, maintaining a healthy weight, and following a healthy …

Development And Clinical Validation Of Knowledge-Based Planning Models For Stereotactic Body Radiotherapy Of Early-Stage Non-Small-Cell Lung Cancer Patients, Justin David Visak

Theses and Dissertations--Radiation Medicine

Lung stereotactic body radiotherapy (SBRT) is a viable alternative to surgical intervention for the treatment of early-stage non-small-cell lung cancer (NSCLC) patients. This therapy achieves strong local control rates by delivering ultra-high, conformal radioablative doses in typically one to five fractions. Historically, lung SBRT plans are manually generated using 3D conformal radiation therapy, dynamic conformal arcs (DCA), intensity-modulated radiation therapy, and more recently via volumetric modulated arc therapy (VMAT) on a C-arm linear accelerator (linac). Manually planned VMAT is an advanced technique to deliver high-quality lung SBRT due to its dosimetric capabilities and utilization of flattening-filter free beams to improve …

Elucidating The Role Of The Tyrosine Phosphatase, Shp-2, In Regulation Of Pd-L1 Expression In Non-Small Lung Cancer Using Both Biochemical Analyses And Real-World Genomic Information, Keller Toral

Theses and Dissertations--Pharmacy

Immune checkpoint inhibitors (ICIs), especially those that target programmed cell death protein 1 (PD-1) and programmed cell death ligand-1 (PD-L1), have been shown to provide substantial clinical benefit in many patients with non-small cell lung cancer (NSCLC). While these therapeutic agents can be highly effective in the correct context, the biological systems that malignant cells draft from normal activities of the cell are poorly characterized. Tumor cell-specific expression of PD-L1 is likely important for clinical benefit from PD-1 and PD-L1 inhibitors. It is known that PD-L1 is inappropriately expressed in many cancers harboring mutations in the RAS family of genes. …

Effects Of Season And Nutrition On Insulinemic Responses In Insulin Dysregulated Horses, Erica Lyn Macon

Theses and Dissertations--Veterinary Science

Insulin dysregulation (ID) is the main risk factor for the development of hyperinsulinemia-associated laminitis (HAL). ID in the equid has been extensively researched; however, recommendations for diagnosing and managing ID horses have originated from work completed in other models, such as the ID pony and healthy horse. Therefore, our overall objective was to improve current diagnostic tools and nutritional management strategies by investigating the effect of season, the fed and fasted state on the oral sugar test (OST) and dietary nutrient content on insulinemic responses in the ID horse. To address this, four main objectives with three specific aims were …

Muscle Mass And Immune Function In The Senior Horse, Alisa Christina Herbst

Theses and Dissertations--Veterinary Science

Senior horses (≥ 15 years) represent up to one-third of the global equine population, and the proportion of old horses (≥ 20 years) in the U.S. has been steadily increasing. Aging is associated with a loss of skeletal muscle mass in horses, and while age-related muscle loss is comparingly well characterized in humans, little is currently known concerning underlying mechanisms, adverse outcomes, or the prevalence of low muscle mass in senior horses. One factor proposed to play a role in the development of age-related muscle atrophy in humans is inflamm-aging, a low-grade inflammation that affects elderly people and that has …

Therapeutic Targeting Of Leukemia Stem Cells To Prevent T-Cell Acute Lymphoblastic Leukemia Relapse, Meghan G. Haney

Theses and Dissertations--Molecular and Cellular Biochemistry

The survival rate of T-cell Acute Lymphoblastic Leukemia (T-ALL) relapse is a dismal 10% of affected adults and 30% of children, largely due to the relapsed disease being more aggressive and treatment resistant than the initial disease. Relapse is thought to occur because conventional chemotherapies are unable to reliably eliminate a unique cell type known as leukemia stem (or propagating) cells (LSCs). LSCs are the only cells within the leukemia with the ability to self-renew and remake or replenish the ALL from a single cell. Currently, the pathways governing self-renewal in LSCs are largely unknown, precluding our ability to successfully …

Reversible Glucan Phosphorylation In The Red Alga, Cyanidioschyzon Merolae, Corey Owen Brizzee

Theses and Dissertations--Molecular and Cellular Biochemistry

Starch and glycogen are an essential component for the majority of species and have been developed to maintain homeostasis in response to environmental changes. Water-soluble glycogen is an excellent source of quick, short-term energy in response to energy demands. In contrast, plants and algae have developed the macromolecule starch that is elegantly suitable for their dependence on external circumstances. Semi-crystalline starch is water-insoluble and inaccessible to most amylolytic enzymes, thus plants and algae have developed a coordinated system so that these enzymes can gain access to the denser starch energy cache. Starch-like semi-crystalline polysaccharides are also found in red algae, …

Cloning And Functional Characterizations Of Circular Rnas From The Human Mapt Locus, Justin R. Welden

Theses and Dissertations--Molecular and Cellular Biochemistry

Under pathophysiological conditions, the microtubule protein tau (MAPT) forms neurofibrillary tangles that are the hallmark of sporadic Alzheimer’s disease as well as familial frontotemporal dementias linked to chromosome 17 (FTDP-17). In this work, I report that MAPT forms circular RNAs through backsplicing of exon 12 to either exon 10 or exon 7 (12→10; 12→7), and that these circular RNAs are translated into proteins.

Using stable cell lines overexpressing the circular tau RNAs 12→7 and 12→10, we have discovered that the tau circular RNA 12→7 is translated in a rolling circle, giving rise to multiple proteins. This circular RNA …

Human Regulatory T Cells Control Inflammation From Effector T Cells In Prediabetes, Rui Liu

Theses and Dissertations--Pharmacy

Type 2 diabetes (T2D) is a chronic low-grade inflammatory disease. A T cell cytokine profile (Th17) from PBMCs can distinguish obese T2D from obese non-diabetes subjects. Individual T cell subsets interact with each other and the diverse subsets jointly determine overall inflammation. Cellular metabolism drives cytokine production of CD4⁺ T cells, and therefore contributes to inflammation in T2D. However, specific changes in metabolism and function of CD4⁺ T cells during the progression from lean healthy to obese and diabetic stages in people have not been clarified.

We hypothesize that human regulatory T cells (Treg) impact metabolism of effector …

Abc Transporters In Glioblastoma: Anticancer Drug Transport And Transporter Regulation At The Blood-Brain Barrier, Julia A. Schulz

Theses and Dissertations--Pharmacy

Glioblastoma is one of the deadliest cancers, with a median survival of only one year. Even after aggressive treatment consisting of surgical resection, radiation, and chemotherapy, most glioblastoma patients suffer from tumor recurrence within 6-9 months. One reason for treatment failure of anticancer drugs is the blood-brain barrier that protects the brain by impeding xenobiotic uptake from the blood. To this end, efflux transporters at the human blood-brain barrier, such as P-glycoprotein (ABCB1) and Breast Cancer Resistance Protein (ABCG2), prevent many compounds, including anticancer drugs, from entering the brain. Thus far, approaches to deliver anticancer drugs across the blood-brain barrier …

Science-Based Regulation Of Pharmacological Substances In Competition Horses, Jacob Machin

Theses and Dissertations--Toxicology and Cancer Biology

Current testing methodologies within equine forensic toxicology focus on arbitrary thresholds and zero-tolerance policy. Modern analytical chemistry’s limits of detection are low enough that oftentimes femtogram-per-milliliter amounts of a substance can readily be identified in both blood and urine of a horse. For most pharmacologically relevant compounds, these concentrations have no relevance to pharmacological effect. It is therefore crucial that testing methodologies to determine appropriate thresholds and cut-offs be developed that are driven by biological activity rather than arbitrary limits of detection. This dissertation looks to address this by suggesting a system of calculated Effective Plasma Concentrations by which a …

Novel Mammalian Models For Understanding And Treating Spinal Cord Injury, Michael B. Orr

Theses and Dissertations--Physiology

Spinal cord injury (SCI) is devastating and often leaves the injured individual with persistent dysfunction. The injury persists because humans have poor wound repair and there are no pharmacologic treatments to induce wound repair after SCI. The continued efforts to discover therapeutic targets and develop treatments heavily relies on animal models. The purpose of this project is to develop and study novel mammalian models of SCI to provide insights for the development and effective implementation of SCI therapies.

Lab mice (Mus musculus) are a powerful tool for recapitulating the progression and persistent damage evident in human SCI, but …

Maternal Proximity To Mountaintop Removal Mining And Birth Defects In Appalachian Kentucky, 1997-2003, Daniel B. Cooper

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Background: Extraction of coal through mountaintop removal mining (MTR) alters many dimensions of the landscape, and explosive blasts, exposed rock, and coal washing have the potential to pollute air and water with substances known to increase risk of developmental and birth anomalies. Previous research suggests that infants born to mothers living in MTR coal mining counties have higher prevalence of most types of birth defects.

Objectives: This study seeks to examine further the relationship between MTR activity and birth defects by employing individual level exposure estimation through precise satellite data of MTR activity in the Appalachian region and maternal residence …

Comparison Of The Times To Exhaustion, Physiological, Perceptual, And Neuromusuclar Responses During Constant Heart Rate, Constant Vo2, And Constant Power Exercise, Pasquale Jiovanni Succi

Theses and Dissertations--Kinesiology and Health Promotion

The purposes of this study were to: 1) Determine if there are differences in the sustainability of exercise when anchored at critical heart rate (CHR), the VO₂ associated with CHR (VO₂CHR), or the power output associated with CHR (PCHR); 2) examine the patterns of responses in power output, metabolic (heart rate [HR], VO₂, respiration rate [RR]), neuromuscular (electromyographic [EMG] amplitude [AMP], mean power frequency [MPF], mechanomyographic [MMG] AMP and MPF, perceptual (rating of perceived exertion [RPE]), and muscle oxygenation responses (%SmO₂) during exercise anchored by HR, VO₂, and power output; and …

Examination Of Sex- And Intensity-Specific Fatigue During Bilateral Leg Extension Exercise, Taylor Kayln Dinyer

Theses and Dissertations--Kinesiology and Health Promotion

The purposes of this study were to: 1) examine sex-related differences in the performance of repetitions to failure below (CL_-10%, CL_-20%) and above (50%, 60%, 70%, and 80% 1RM) the critical load (CL) to make inferences regarding the mechanisms responsible for variability in the performance of repetitions to failure at varying loads; 2) examine the time course of neuromuscular and muscle oxygen saturation responses during the performance of repetitions to failure below and above the CL; 3) to make inferences regarding motor unit activation strategies used to maintain force during the completion of repetitions below and …

Exploring The Relationships Between Cultural Values And Diet Patterns Among Mexican And Cuban Immigrants In Kentucky, Nasreen Omran

Theses and Dissertations--Nutrition and Food Systems

The number of Latinx in the U.S. is expected to grow to about 28 percent of the population by the year 2060. As the number of Latinx increases in the U.S. it is important to understand how cultural beliefs influence dietary behaviors as Latinx are disproportionately affected by diet related disease such as diabetes mellitus, cancer, and cardiovascular disease. The aim of this secondary data analysis is to examine the relationship between family values, gender roles, and religious values on diet patterns in adult Mexican and Cuban immigrants in Kentucky utilizing the Mexican American Cultural Values Scale. The study findings …

Cognitive Abilities In Hearing Loss: Perceived And Performance Abilities Of Adults Related To Attention, Memory, And Social Cognition, Karah Gottschalk

Theses and Dissertations--Gerontology

Hearing loss is the most common sensory deficit noted in aging adults. It is commonly known to reduce an individual’s ability to detect, identify, and localize sounds and speech and to cause issues in communication. However, there are other less commonly discussed impacts that hearing loss has beyond the auditory system. Literature suggests a correlation between hearing loss and cognition in aging adults. Similar to hearing loss, the domains of cognition experience performance and functional changes across the life span. In an aging adult, changes related to cognition are also suggested to be associated with hearing loss. This study aimed …

Characterization Of Spontaneous Preeclampsia In The African Green Monkey (Chlorocebus Aethiops Sabaeus), Chelsea Christina Weaver

Theses and Dissertations--Biology

Hypertensive pregnancy disorders are a major contribution to maternal and neonatal mortality worldwide. Two of these disorders, preeclampsia and chronic hypertension in pregnancy, affect up to 10% of all pregnancies. These hypertensive disorders of pregnancy are associated with long-term, postnatal risk factors for both mother and offspring. Despite numerous recent advances in preeclampsia research, the underlying mechanisms are still not understood. This could be due to lack of a spontaneous animal model. This dissertation presents the African Green Monkey (AGM; Chlorocebus aethiops sabaeus) as the first known spontaneous animal model of preeclampsia and a highly translational model of chronic …

Cellular Bioenergetics Regulates Cell Proliferation During Mammalian Regeneration, Sandeep Saxena

Theses and Dissertations--Biology

Mammalian system consists of stress-sensing molecules that regulates their cellular response against damage, injury and oncogenic stress. During vertebrate regeneration, cells responding to injury re-enter the cell cycle and proliferate to form new tissue. Cell cycle re-entry or arrest is at least partly regulated by cellular senescence which negatively impacts the proliferative pool of cells during regeneration. What remains unclear is whether cells in regenerating systems possess an increased propensity to proliferate and are refractory to signals that induce senescence. My thesis work has focused on how fibroblasts from the ear pinna differentially regulate healing in highly regenerative mammals (e.g., …

Examination Of Sex- And Limb-Specific Fatigue During Unilateral, Isometric Forearm Exercise, Caleb Christian Voskuil

Theses and Dissertations--Kinesiology and Health Promotion

The purpose of this study was to examine the effects of unilateral, isometric handgrip holds to failure for the dominant (Dm) and non-dominant (NDm) limb on ipsilateral ([IPS] exercised side) and contralateral ([CON] non-exercised side) performance fatigability. Twenty individuals participated in this study (Men [n =10]; Women [n = 10; Composite Demographics: Age: 22.2 years; Height: 174.4 cm; Body Mass: 75.0 kg) and completed three visits. Two, 6 s maximal voluntary isometric contractions (MVICs) for the Dm and NDm limb were performed during visit 1, followed by a familiarization of the fatigue test. Visits 2 and 3 included an isometric, …