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Brain Glycogen – Beyond Energy Storage In Glycogen Storage Diseases, Kia H. Markussen

Theses and Dissertations--Molecular and Cellular Biochemistry

Glycogen is a carbohydrate molecule that is traditionally viewed as a convenient and easily accessible energy storage form of glucose. However,emerging evidence supports the role of glycogen as more than a glucose storage form. During the last 20 years, glycogen has been shown to play pivotal roles in learning and memory, signaling events, viscosity, protein glycosylation, and be acritical hallmark in devastating diseases. Not only, does glycogen play a role as an energy substrate and critical metabolite during energy deprivation, glycogen is central for neurotransmitter homeostasis, tumor initiation, and ontributes to proper protein glycosylation in the brain. In this work, …

Protein S In Coagulation And Inflammation, Martha Mega Silvia Sim

Theses and Dissertations--Molecular and Cellular Biochemistry

Protein S (PS) is a key regulator, which links inflammation and coagulation and performs multiple proposed functions in both processes. PS exists in the blood as a free soluble form (~40%), bound to complement component 4b-binding protein/ C4BP (~60%), and packaged in platelet α-granules (~2.5%). Subendothelial tissue factor (TF), upon exposure to blood, initiates coagulation, a proteolytic cascade which results in the activation of thrombin, the enzyme responsible for formation of a fibrin clot. PS is a critical anticoagulant that inhibits multiple steps of this process. Only the free fraction of PS has full anticoagulant properties, as C4BP blocks this …

Improving Baking Quality Of Soft Red Winter Wheat In Kentucky Through Breeding And Sulfur-Nitrogen Fertility Management, Maria Paula Castellari

Theses and Dissertations--Plant and Soil Sciences

Soft Red Winter (SRW) wheat is an important crop grown on about 400,000 acres in Kentucky as a pivotal cash crop in the 3-crops-in-2-years rotation of corn, wheat, and soybean. The humid environment of Kentucky generates a high yielding wheat crop, with low protein concentration and weak gluten strength. This wheat is mainly sold to millers and used by the industry for cakes, pastries, cookies, and crackers. Conversely, there is a rapidly growing interest in identifying other value-added markets for this wheat different to commodity commercialization, such as artisan-baked goods and craft-distilled beverages. Evaluating the quality characteristics of wheat grown …

Assessment Of Opioid-Induced Immunomodulation In Experimental And Clinical Sepsis, Brittany Dawn Bissell, Jamie L. Sturgill, Maria E. C. Bruno, Erick D. Lewis, Marlene E. Starr

Markey Cancer Center Faculty Publications

CONTEXT: Opioids remain a standard supportive therapy in patients admitted to the ICU with sepsis. However, as preclinical models indicate an association between opioid exposure and immunosuppression, the use of this class of drugs warrants investigation. The objective of this study was to investigate whether opioid exposure causes immunosuppression in patients with sepsis, and to use a murine sepsis model to determine the effects of opioid exposure on secondary infection.

HYPOTHESIS: We hypothesized opioid exposure would be associated with immunosuppression in patients with sepsis and secondary infection in a murine sepsis model.

METHODS AND MODELS: This was a two-phase preclinical …

Bilirubin Levels Are Negatively Correlated With Adiposity In Obese Men And Women, And Its Catabolized Product, Urobilin, Is Positively Associated With Insulin Resistance, Zachary A. Kipp, Mei Xu, Evelyn A. Bates, Wang-Hsin Lee, Philip A. Kern, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Bilirubin levels in obese humans and rodents have been shown to be lower than in their lean counterparts. Some studies have proposed that the glucuronyl UGT1A1 enzyme that clears bilirubin from the blood increases in the liver with obesity. UGT1A1 clearance of bilirubin allows more conjugated bilirubin to enter the intestine, where it is catabolized into urobilin, which can be then absorbed via the hepatic portal vein. We hypothesized that when bilirubin levels are decreased, the urobilin increases in the plasma of obese humans, as compared to lean humans. To test this, we measured plasma levels of bilirubin and urobilin, …

Polycomb Deficiency Drives A Foxp2-High Aggressive State Targetable By Epigenetic Inhibitors, Fan Chen, Aria Byrd, Jinpeng Liu, Robert M. Flight, Tanner Ducote, Kassandra J. Naughton, Xiulong Song, Abigail R Edgin, Alexsandr Lukyanchuk, Danielle T. Dixon, Christian M. Gosser, Dave-Preston Esoe, Rani Jayswal, Stuart H. Orkin, Hunter N. B. Moseley, Chi Wang, Christine Fillmore Brainson

Markey Cancer Center Faculty Publications

Inhibitors of the Polycomb Repressive Complex 2 (PRC2) histone methyltransferase EZH2 are approved for certain cancers, but realizing their wider utility relies upon understanding PRC2 biology in each cancer system. Using a genetic model to delete Ezh2 in KRAS-driven lung adenocarcinomas, we observed that Ezh2 haplo-insufficient tumors were less lethal and lower grade than Ezh2 fully-insufficient tumors, which were poorly differentiated and metastatic. Using three-dimensional cultures and in vivo experiments, we determined that EZH2-deficient tumors were vulnerable to H3K27 demethylase or BET inhibitors. PRC2 loss/inhibition led to de-repression of FOXP2, a transcription factor that promotes migration and stemness, and FOXP2 …

Suppressing Hepatic Ugt1a1 Increases Plasma Bilirubin, Lowers Plasma Urobilin, Reorganizes Kinase Signaling Pathways And Lipid Species And Improves Fatty Liver Disease, Evelyn A. Bates, Zachary A. Kipp, Genesee J. Martinez, Olufunto O. Badmus, Mangala M. Soundarapandian, Donald Foster, Mei Xu, Justin F. Creeden, Jennifer R. Greer, Andrew J. Morris, David E. Stec, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Several population studies have observed lower serum bilirubin levels in patients with non-alcoholic fatty liver disease (NAFLD). Yet, treatments to target this metabolic phenotype have not been explored. Therefore, we designed an N-Acetylgalactosamine (GalNAc) labeled RNAi to target the enzyme that clears bilirubin from the blood, the UGT1A1 glucuronyl enzyme (GNUR). In this study, male C57BL/6J mice were fed a high-fat diet (HFD, 60%) for 30 weeks to induce NAFLD and were treated subcutaneously with GNUR or sham (CTRL) once weekly for six weeks while continuing the HFD. The results show that GNUR treatments significantly raised plasma bilirubin levels and …

Xylazine Suppresses Fentanyl Consumption During Self-Administration And Induces A Unique Sex-Specific Withdrawal Syndrome That Is Not Altered By Naloxone In Rats, Shailesh N. Khatri, Safiyah M. Sadek, Percell T. Kendrick, Emma O. Bondy, Mei Hong, Sally Pauss, Dan Luo, Thomas E. Prisinzano, Kelly E. Dunn, Julie A. Marusich, Joshua S. Beckmann, Terry D. Hinds Jr., Cassandra D. Gipson

Markey Cancer Center Faculty Publications

Prescription and illicit opioid use are a public health crisis, with the landscape shifting to fentanyl use. Since fentanyl is 100-fold more potent than morphine, its use is associated with a higher risk of fatal overdose that can be remediated through naloxone (Narcan) administration. However, recent reports indicate that xylazine, an anesthetic, is increasingly detected in accidental fentanyl overdose deaths. Anecdotal reports suggest that xylazine may prolong the fentanyl “high,” alter the onset of fentanyl withdrawal, and increase resistance to naloxone-induced reversal of overdose. To date, no preclinical studies have evaluated the impacts of xylazine on fentanyl self-administration (SA; 2.5 …

Nitrogen Behavior In A No-Tillage Agroecosystem Located In The Inner Bluegrass Of Kentucky, Alec William Besinger Mr.

Theses and Dissertations--Plant and Soil Sciences

Nitrogen (N) is a crucial element, often limiting productivity in ecosystems. This limitation is relieved N fertilizer additions. No-tillage (NT) agroecosystems are prone to lower N availability translating to lower crop yields. The default explanation for lower N availability in NT is microbial immobilization of added N fertilizer. Historically, N availability is often assessed using chemical extractions such as KCl to evaluate levels of inorganic N in the soil. The possibility of this abiotic clay mineral fixation as mechanism in well-drained NT soils has been overlooked. The objectives of this study are to quantify N availability using KCl, NaCl, and …

Comparison Of Botanical Composition Methods And Change Over Time In Kentucky Pastures, Echo Elizabeth Gotsick

Theses and Dissertations--Plant and Soil Sciences

Botanical composition of pastures has been measured with numerous methods over the last century, but there have been limited direct comparisons between methods. The objective of this study was to compare botanical composition methods, to determine the most accurate and efficient method, and to access pasture composition change over time. Six farms with two pastures each were monitored across the state of Kentucky. Sampling occurred fall 2020 through fall 2022, three times a year using the following methods: step point, visual estimation, occupancy grid, and point quadrat (used as a reference method). The occupancy grid showed the highest similarity to …

Lateral Spacing Of Subsurface Poultry Litter Bands: Effect On Gaseous Nitrogen Emissions, Nutrient Uptake, And Maize Yield, Jason R. Simmons

Theses and Dissertations--Plant and Soil Sciences

Poultry litter (PL) is traditionally applied to no-till maize (Zea mays L.) cropping systems by surface broadcast. Poultry litter is nutrient dense, and it has been repeatedly shown that surface applied PL nitrogen (N) is vulnerable to losses to the atmosphere and nearby water systems. An application method was developed by USDA-Agricultural Research Service scientists for banding poultry litter (PL) below the soil surface with minimal soil disturbance to reduce ammonia (NH₃) volatilization and surface run-off. It is well documented that subsurface applied poultry litter (PL) reduces N losses by ammonia (NH₃) volatilization; however, the …

Evaluation Of Chemical Control Options, Environmental Factors, And Management Practices Associated With Angular Leaf Spot (Pseudomonas Syringae Pv. Tabaci), Andrea Brooke Webb

Theses and Dissertations--Plant and Soil Sciences

Pseudomonas syringae pv. tabaci tox^- is the causal agent of angular leaf spot in dark tobacco. Since 2015, angular leaf spot has become the most significant foliar disease in dark tobacco production in Kentucky and Tennessee. Dark tobacco producers utilize one main tool, streptomycin sulfate, for the management of this bacterial disease. Resistance to streptomycin sulfate in P. syringae pv. tabaci isolates from dark tobacco fields in western Kentucky was first observed in 2015.

Field spray trials were developed to evaluate the efficacy of alternative active ingredients compared to the grower’s standard, streptomycin sulfate. Two separate field trials were …

Secondary Traumatic Stress Is An Occupational Hazard For Pet Hospice Support Staff: Psychoeducational Support Groups Provide The Cure, Kari Hayden

DSW Capstone Projects

There are three separate yet interrelated products presented in this final capstone product. The completed product is focused on pet hospice veterinary support staff and the need for an evidence-based social work intervention to combat secondary traumatic stress. This capstone uses the andragogical approach to adult learning theory as the foundation to construct a psychoeducational peer support group specific to this population. Implications for clinical social work in veterinary medicine are presented within this project.

The first scholarly product presented is the Systematic Literature Review (SLR). The SLR utilizes a scoping review process in an attempt to locate prior research …

Investigating Ru(Ii) Anticancer Agents With Non-Canonical Mechanisms Of Action, Richard Joseph Mitchell

Theses and Dissertations--Chemistry

Platinum(Pt)-based agents are used in approximately 50% of all cancers that are treated with chemotherapy. Unfortunately, the dose-limiting toxicity of these agents remains problematic for patients undergoing treatment. Additionally, Pt(II) therapeutics suffer from transporter-dependent uptake, limited chemical functionalization, and high susceptibility to inactivation by free thiols within the cytosol. Developing small molecules with non-canonical mechanisms of action is one strategy that can be employed to circumvent these limitations. Utilization of coordination complexes with ruthenium(Ru) metal centers is one attractive strategy. Ru(II) compounds are often octahedral, facilitating greater accessibility for chemical diversity; Ru(II) complexes use passive transport and transferrin-mediated transport for …

Development Of An Effective Au:Pd Bimetallic Heterogeneous Catalyst For Oxidative Lignin Depolymerization To Low Molecular Weight Aromatics, Gayan P. Karunasinghe

Theses and Dissertations--Chemistry

The principal concept behind biorefining involves the transformation of lignocellulosic biomass into valuable products and energy resources. Historically, biorefinery strategies for lignocellulosic biomass have primarily focused on improving the conversion of cellulose into ethanol, often neglecting the underutilized lignin component. Lignin consists of phenolic subunits, from which it follows that value-added products can be obtained from lignin depolymerization. Unfortunately, lignin utilization is particularly challenging due to its high structural irregularity and recalcitrance. The goal of this study was to develop an AuPd/Li-Al layered double hydroxide (LDH) bimetallic catalyst for efficient lignin depolymerization, resulting in the production of high-value aromatic compounds. …

The Effects Of Escalated Fentanyl Intake On Decision-Making Dynamics, Trinity Shaver

Theses and Dissertations--Psychology

Opioid Use Disorder is characterized partially as a decision-making disorder. Decision-making theories, such as habit theory and relative value theory, have aimed to better understand the shift in preference for drug over other alternatives. In order to compare these two contrasting theories, an allomorphic concurrent choice task will run in tandem with an escalation procedure. Male and female Sprague-Dawley rats were tested for choice differences in an allomorphic choice procedure. Reward dimensions, such as relative reward rate, were manipulated within sessions, and magnitude (remifentanil dose), was manipulated between sessions. To study the effects of escalated fentanyl intake on relative valuation, …

Effects Of Social Isolation And Adolescent Ethanol Exposure On Adult Drinking And Nicotine Co-Use, Jakob Shaykin

Theses and Dissertations--Psychology

Alcohol use often begins in adolescence and can lead to increased susceptibility to AUD in adulthood. Stress in the form of social isolation during adolescence can also prompt substance use disorders later in adulthood. This thesis determined if exposure to ethanol (EtOH) during adolescence and social isolation alters the trajectory of alcohol and nicotine intake during adulthood. In Experiment 1, adolescent male and female Sprague-Dawley rats were administered intermittent injections of EtOH (2g/kg 20% EtOH, IP) or saline (PND 28-41). EtOH consumption was measured in adulthood (PND 49-55) using a 2-bottle choice procedure where one bottle contained a 0.2% saccharin/15% …

Prenatal Ethanol Exposure Impairs Performance On Spatial And Tactile Sequential Discrimination Task In Juvenile Rats, Caleb S. Bailey

Theses and Dissertations--Psychology

Fetal alcohol spectrum disorders (FASDs) are a set of cognitive and behavioral abnormalities that arise in ~5% of children who have been prenatally-exposed to alcohol. Prenatal alcohol exposure (PAE) can cause impairments in learning acquisition, working memory, response inhibition, and attentional-set shifting that result in exaggerated deficits in executive function and impairments in goal-seeking behavior. There are standard procedures used in rodent research to address some components of these deficits, but few procedures are sensitive enough to comprehensively assess such deficits. To address this issue in FASDs research techniques, we developed a procedure that requires prolonged executive function in a …

Effect Of Menstrual Cycle Phase On The Rewarding Properties Of Alcohol In Women, Annie K. Griffith

Theses and Dissertations--Psychology

Compared with men, women are disproportionately affected by alcohol, including greater risks of behavioral impairment and relapse. One likely mechanism underlying this disparity is fluctuations of ovarian hormones, particularly estradiol (E2), across phases of the menstrual cycle. Pre-clinical and clinical studies have shown that higher E2 levels correlate with heavier patterns of alcohol consumption, suggesting E2 may modulate drinking. This relationship is thought to be mediated by the rewarding properties of alcohol. The present thesis tested the hypothesis that elevated E2 during the late follicular phase would increase the rewarding properties of alcohol. Fifty young-adult women participated in a within-subjects …

Ethanol Decreases Expression Of Developing Neurons, But Not Neuronal Viability, In A Cultured Rat Hippocampus, Cassidy Count

Theses and Dissertations--Psychology

As of 2019, alcohol use disorders (AUDs) affect roughly 14.1 million individuals over the age of 18 and cost up to $249 billion in economic burden in the United States. In addition to central nervous system (CNS), those affected by AUDs can present with cognitive and behavioral abnormalities. Specifically, those affected by AUDs experience deficits in memory consolidation and retrieval as well as executive functioning, which may be due to cellular changes within the hippocampus. There are at least two prominent and contended theories which explain the mechanism of functional impairment caused by alcohol: 1) alcohol induces excitotoxic neuronal death …

Birds Of A Feather: Exploring Social Facilitation Effects On Learning And Suboptimal Choice In Pigeons (Columba Livia), Peyton Mueller

Theses and Dissertations--Psychology

The social facilitation effect describes a change in the behavior of an individual due to the presence of another organism of the same species (i.e., a conspecific). Many theories exist that attempt to explain why this change in behavior exists across species. A set of four experiments were executed to best explain how pigeons learn in the presence of non-competing conspecifics. The first experiment sought to replicate an interesting effect previously found in cockroaches and rats, such that conspecific presence inhibits performance early in training but facilitates it with increased training. The second experiment placed the novel response acquired in …

The Effects Of Social And Nonsocial Contextual Stimuli On The Renewal Of Cocaine Seeking, Bree Humburg

Theses and Dissertations--Psychology

Those with substance use disorders can undergo craving and relapse when re-exposed to a drug-associated context. This study determined if renewal of cocaine seeking is differentially controlled by contexts consisting of social and/or nonsocial stimuli. Experiment 1, rats self-administered cocaine in Context A which included a social peer and house light illumination. Following self-administration, rats were randomly assigned to an AAA or ABA group for extinction and renewal. For the AAA rats, context was similar to self-administration; for ABA rats, the drug-associated stimuli (peer and house light) were removed (Context B). Following extinction, renewal of cocaine seeking was examined by …

The Effects Of Extended Fructose Access On Relative Value And Demand For Fructose, Saccharin, And Ventral Tegmental Stimulation, Megan Halloran

Theses and Dissertations--Psychology

Globally, food addiction (FA) is a growing area of research and is largely attributed to the availability of foods that are both energy dense and high in fats and sugars. Further, it has been suggested, that sugar and fat, when consumed frequently, have properties similar to drugs of abuse. While the validity of FA is questioned, researchers have drawn parallels between substance use disorder (SUD) and FA. For example, sugar binge models emphasize craving, withdrawal and binging as primary components of FA, which are also hallmarks of SUD. Additionally, both natural rewards, like sugars, and drug rewards act on the …

Personalized Longitudinal Network Models Of Alcohol Use: A Mechanistic Approach, Stephen Semcho

Theses and Dissertations--Psychology

AUD and high-risk drinking are significant public health concerns, and prevailing diagnostic models fail to account for the within-person variability in AUD presentation and the role of functional mechanisms that maintain drinking outcomes. The ETOH Framework highlights the importance of three primary superdomains that maintain and characterize AUD – reward salience, cognitive dyscontrol, and negative emotionality. The current study was the first attempt to investigate the role of the primary ETOH mechanisms, along with positive and negative affect, on alcohol use outcomes, using a novel approach to model individual-level networks of relations over time. This study gathered twice-daily diary data …

Calcium Imaging Of Central Amygdala Activity After Fentanyl Escalation, Samantha Malone

Theses and Dissertations--Psychology

Evidence suggests that rats given long access (LgA) sessions to self-administer (SA) opioids escalate their intake, while also showing greater withdrawal severity and drug-induced reinstatement compared to rats maintained on short access (ShA) daily SA sessions. Little is known about the neural changes that occur during opioid escalation that may impact withdrawal and relapse. Past work examining opioid SA using ShA sessions in rodents has identified the central amygdala (CeA) as an area of interest that becomes hyperactive in acute withdrawal and may be involved in the incubation of craving that occurs after protracted withdrawal. However, these studies have not …

A Multidimensional View On The Emission-Line Diagnostics Of The Warm Ionized Gas In Nearby Galaxies, Xihan Ji

Theses and Dissertations--Physics and Astronomy

The baryonic cycle, being a fundamental process that shapes the cosmic ecosystem, describes the transformation and migration of baryonic matter in different phases. The warm ionized interstellar medium (ISM), defined as low-density gas that has temperature of the order of 10,000 K, represents an important link of the baryonic cycle and can be produced by a variety of energetic activities in galaxies, such as star formations, active galactic nuclei, and so forth. More importantly, the formation and evolution of the warm ionized gas not only traces the ongoing activities of the galaxies, but also reveals the past evolution of galaxies …

Moral Foundations And Student Perceptions Of Academic Dishonesty: A Mixed Methods Study, Carla Spires Hargus

Theses and Dissertations--Curriculum and Instruction

This mixed methods study explored students’ hypothetical choices of behavior in a series of ten academic vignettes. In addition, it examined student judgments of academic behaviors as acceptable or dishonest. Finally, it compared scores on the Moral Foundations Questionnaire-2 to the importance of factors that might influence student behavioral choices in real world scenarios and explored the differences in perceptions among demographic groups.

Twenty-five undergraduate students participated in the study. In a semi-structured interview, each student discussed ten academic vignettes: predicting their own hypothetical behavioral choice, judging target behaviors as honest or dishonest, and identifying factors that would most influence …

Investigating The Relationship Between Empowerment And Secondary Science Teachers’ Technology Integration Knowledge, Jane Elizabeth Walsh

Theses and Dissertations--Educational Leadership Studies

Empowered teachers believe they can improve their work conditions and positively impact student outcomes. Likewise, teachers with technology integration knowledge can effectively use technology to enhance lessons and improve student learning. This quantitative correlational study investigated teachers’ empowerment, teachers’ technology integration knowledge, and associations between empowerment and technology integration knowledge. Two hundred fourteen randomly selected high school science teachers from across the United States responded to a survey intended to measure empowerment and technology integration knowledge. The teachers' average responses indicate that teachers generally agree with statements surrounding empowerment (M = 3.93, SD = 0.54) and technology integration knowledge …

Responses To Exercise Anchored To Vigorous Intensity Heart Rates, Djadmann Gustave

Theses and Dissertations--Kinesiology and Health Promotion

Exercise prescription to improve cardiorespiratory endurance (CE) is often based on percentages of the reserve or maximum heart rate (HR_peak) or oxygen consumption rate (V̇O_2peak)that reflect vigorous intensities (77-95% HR_peak, 64-90% V̇O_2peak). These intensities elicit a rating of perceived exertion [RPE] response between 14-17 on the 6-20 Borg Scale. It is recommended that exercise within these ranges be sustained for 20-60min per session. The purposes of this study were to: 1) Determine the metabolic (V̇O₂) and perceptual (RPE) responses as well as the sustainability of exercise (time to exhaustion [T …

Investigation Of Lower Extremity Neuromuscular Function In Individuals With And Without Diabetes, Roya Hoveizavi

Theses and Dissertations--Kinesiology and Health Promotion

Background: Diabetes mellitus is associated with notable neuromuscular and motor dysfunctions that could lead to an increased risk of plantar ulcers and amputations. Several contributing factors, including increased muscle-tendon stiffness and abnormal muscle activation pattern may influence the kinematics and kinetics of walking in people with diabetes and promote formation of plantar ulcers. Hyperglycemia and the resultant accelerated rate of glycation have been recognized as the leading cause of muscle and tendon degeneration, yet the precise mechanisms by which diabetes affects the biomechanical properties of the muscle-tendon unit remains unclear. Altered muscle activity during gait is observed in people with …