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Studies Of The Effects Of Dopamine Neuron Stimulating Peptides In Rodent Models Of Normal And Dysfunctional Dopaminergic Systems, Joshua Lee Fuqua

University of Kentucky Doctoral Dissertations

A theoretical post-translational processing model of the proprotein form of glial cell line-derived neurotrophic factor (GDNF) likely produces three biologically active peptides. The three prospective peptides formed are 5, 11, and 17 amino acid peptides, entitled dopamine neuron stimulating peptide -5 (DNSP-5), -11 (DNSP-11), and -17 (DNSP-17), respectively. The DNSPs were hypothesized to increase dopaminergic neuron function because of their relationship to GDNF: a molecule with established neurotrophic actions on dopaminergic neurons. The DNSPs have the potential to provide a therapeutic molecule similar to GDNF, but with increased ease of delivery and improved bioavailability.

Neurochemical effects of DNSPs were examined …

Dissecting The Biosyntheses Of Gilvocarcins And Ravidomycins, Madan Kumar Kharel

University of Kentucky Doctoral Dissertations

Gilvocarcin V (GV) and ravidomycin (RMV) exhibit excellent antitumor activities in the presence of near-UV light at low concentration maintaining a low in vivo cytotoxicity. Although, the exact molecular mechanism for in vivo actions of these antibiotics has yet to be determined, a [2+2] cycloaddition reaction of the vinyl side chain with DNA thymidine residues in addition to the inhibition of topoisomerase II and DNAhistone H3 cross-linking are reported for the GV’s mechanism of action. Such activities have made these molecules interesting candidates for the biosynthetic investigation to generate analogues with improved activity/solubility. Previous biosynthetic studies have suggested that the …

Social Categories And Health Care Outcomes: African American Women And Hiv Survival In The Urban South, Alyson J. O'Daniel

University of Kentucky Doctoral Dissertations

This ethnographic research examines the daily life and institutional conditions under which low-income Black women in urban North Carolina perceived and attended to HIV health-related needs. I focus specifically on the interplay among women’s living conditions, programmatic service needs, and their strategies for navigating the local system of care to explore and refine the categorical label “low income.” I found that there were significant differences among study participants in terms of their monthly incomes and financial resources, housing quality and status, and personal experiences with incarceration and substance abuse. The economic differences among women translated into social differences within the …

Development Of Novel Ahr Antagonists, Hyosung Lee

University of Kentucky Doctoral Dissertations

Aryl hydrocarbon receptor (AHR) is a sensor protein, activated by aromatic chemical species for transcriptionally regulating xenobiotic metabolizing enzymes. AHR is also known to be involved in a variety of pathogenesis such as cancer, diabetes mellitus, cirrhosis, asthma, etc. The AHR signaling induced by xenobiotics has been intensively studied whereas its physiological role in the absence of xenobiotics is poorly understood. Despite a number of ligands of AHR have been reported thus far, further applications are still hampered by the lack of specificity and/or the partially agonistic activity. Thus, a pure AHR antagonist is needed for deciphering the AHR cryptic …

Public Higher Education Governance: An Empirical Examination, Jacob Fowles

University of Kentucky Doctoral Dissertations

Public higher education is a large enterprise in the United States. Total state expenditures for higher education totaled nearly $152 billion dollars in FY2008, accounting for over ten percent of total state expenditures and representing the single largest category of discretionary spending in most states (NASBO, 2009). The last three decades have witnessed the introduction of hundreds of pieces of legislation across states which make structural changes to state higher education governance systems (Marcus, 1997; McLendon, Deaton, and Hearn, 2007). Despite the ubiquity of state higher education governance change much remains unknown, both in terms of why states choose to …

Function Of Androgen Receptor In Prostate Cancer Epithelial Mesenchymal Transition And Microtubule Targeting, Menglei Zhu

University of Kentucky Doctoral Dissertations

Prostate cancer is the most frequently diagnosed non-skin cancer and the third leading cause of cancer mortality among men in the US. Androgens are functionally required for the normal growth of the prostate gland and play a critical role in prostate tumor development and progression. Epithelial-mesenchymal-transition (EMT) is an important process during normal development, and cancer cell metastasis.

This study examined the ability of androgens to influence EMT of prostate cancer epithelial cells and evaluate the effect of taxol chemotherapy on androgen signaling in prostate cancer cells in prostate cancer. The EMT pattern was evaluated on the basis of expression …

Executive Deficits In Amyotrophic Lateral Sclerosis: Examining The Consequences Of Self-Regulatory Impairment On Quality Of Life, Abbey R. Roach

University of Kentucky Doctoral Dissertations

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that attacks the motor system and contributes to a range of cognitive and behavioral impairments (e.g., behavioral and emotional disinhibition, planning and problem solving difficulties, impulsivity, attention, and personality change). This executive dysfunction may contribute to selfregulatory impairment across several domains, including cognitive skills, thought processes, emotion regulation, interpersonal skills, and physiology, that may be crucial to the quality of life (QOL), or well being, of patients and their caregivers. Given the relentless course and prognosis of ALS, palliative treatments for ALS should target the full range of self-regulatory deficits. Thirty-seven …

Progress Towards The Synthesis Of Type B Polycyclic Polyprenylated Acylphloroglucinol 7-Epi-Clusianone, Pushpa Suresh Jayasekara Mudiyanselage

University of Kentucky Doctoral Dissertations

Plants of the family Guttiferae produce polycyclic polyprenylated acylphloroglucinols (PPAPs), which have interesting biological activities including anticancer and antibacterial properties. The main structural features of PPAPs comprise of bicyclo[3.3.1]nonane-2,4,9-triketone with one acyl group together with prenyl, geranyl, or other C₁₀H₁₇ groups. 7-epi-Clusianone, a type B PPAP with C-7 endo stereochemistry, is being approached by establishing the cis relationship with C(4) allyl group and C(2) methyl ester in the early stage of the synthesis. Then C(2) methyl ester is converted to alkyne aldehyde and syn reduction followed by intramolecular aldol reaction to give bicyclo[3.3.1]nonane structure with …

The Radiosensitization Effect Of Parthenolide In Prostate Cancer: Implications For Selective Cancer Killing By Modulation Of Intracellular Redox State, Yulan Sun

University of Kentucky Doctoral Dissertations

Parthenolide (PN), a major active component of the traditional herbal medicine feverfew, has been shown to have anti-inflammatory and anti-tumor properties. More remarkably, the cytotoxicity of PN seems selective to tumor cells but not their normal cell counterparts. In the present study, we investigate whether and how PN selectively enhances tumor sensitivity to radiation therapy by using prostate cancer cells LNCaP, DU145 and PC3, as well as normal prostate epithelial cells PrEC.

Our study demonstrates that inhibition of NF-κB pathway and suppression of its downstream target MnSOD are common mechanisms for the radiosensitization effect of PN in prostate cancer cells. …

Considering The Power Of Context: Racism, Sexism, And Beloging In The Vicarious Traumatization Of Counselors, Katharine J. Hahn

University of Kentucky Doctoral Dissertations

Recent concerns have arisen about the effects on counselors of working with trauma survivors. Vicarious traumatization may be a normal developmental process of adapting to client trauma material and may ultimately result in vicarious posttraumatic growth, or positive changes arising from vicarious trauma. Most studies have focused on individual variables or clinician coping strategies that predict vicarious traumatization. Taking a feminist approach to vicarious traumatization, this study examined the role of workplace context variables, such as sense of belonging in the workplace and support for vicarious trauma at work, on counselor vicarious traumatization and vicarious posttraumatic growth. Stratified random sampling …

Modulation Of The Alpha-7 Nicotinic Acetylcholine Receptor Following Experimental Rat Brain Injury Improves Cellular And Behavioral Outcomes, Thomas Matt Woodcock

University of Kentucky Doctoral Dissertations

Traumatic brain injury (TBI) is a leading cause of death and long-term disability worldwide, and survivors are often left with cognitive deficits and significant problems with day to day tasks. To date, therapeutic pharmacological treatments of TBI remain elusive despite numerous clinical trials. An improved understanding of the molecular and cellular response to injury may help guide future treatment strategies. One promising marker for brain injury is the translocator protein (TSPO), which is normally expressed at a low level, but is highly expressed following brain damage and is associated with neuroinflammation. The isoquinoline carboxamide PK11195 binds selectively to the TSPO …

Integration Of The Regression-Based Land Use Model And The Combined Trip Distribution-Assignment Transportation Model, Meiwu An

University of Kentucky Doctoral Dissertations

Regional growth caused the emergence of traffic congestion and pollution in the past few decades, which have started to affect small urban areas. These problems are not only related to transportation system design but also to land use planning. There has been growing recognition that the relationship between land use and transportation needs to be understood and analyzed in a consistent and systematic way. Integrated urban models have recently been introduced and implemented in several metropolitan areas to systematically examine the relationship between land use and transportation. The general consensus in the field of integrated urban models is that each …

Grazing Evaluation Of A Novel Endophyte Tall Fescue Developed For The Upper Transition Zone, Jennifer Michelle Johnson

University of Kentucky Doctoral Dissertations

A wild-type endophyte (Neotyphodium coenophialum [(Morgan-Jones & Gams) Glen Bacon & Hanlin]) that infects tall fescue [Lolium arundinaceum (Schreb.) Darbysh. = Schedonorous arundinaceum (Schreb.) Dumort.] imparts tolerances to moisture, heat, and grazing stresses, but also produces ergot alkaloids that adversely affect performance and physiology of cattle. Novel endophytes, developed by AgResearch Ltd. NZ, can sustain fescue persistence and productivity, but do not produce toxic ergot alkaloids. University of Kentucky Plant Breeder, T. D. Phillips Ph.D, developed a tall fescue experimental population (KYFA9301) for the upper transition zone. A 2-yr grazing experiment was conducted with steers to evaluate steer …

Improvement Of New Oil Crops For Kentucky, Watchareewan Jamboonsri

University of Kentucky Doctoral Dissertations

Three oil crops, chia (Salvia hispanica L.), flax (Linum usitatissimum L.), and castor (Ricinus communis L.), were studied because of their nutritional and industrial values. Chia and flax are rich in an ω3 fatty acid, α-linolenic acid, and castor is a very high oil producer and high in a hydroxy fatty acid. Ethyl methanesulfonate (EMS) and gamma rays were employed to mutagenize chia seeds to produce early flowering mutants. The M₁ population was grown and induced to flower by short-day photoperiods. The M₂ population was planted in the field in Lexington, KY in 2008. Early …

Modeling Water Use In Nursery Crops, Amy Fulcher

University of Kentucky Doctoral Dissertations

Water use is an important topic in the global agriculture community and is a critical input in nursery crop production. Several plants in the genus Cornus are important nursery crops. Not only are they economically relevant, they are found in grafted and seedling forms and parents and their hybrid are readily available in the trade, facilitating an assessment of water requirements. Anecdotal information suggests that Cornus taxa have differing stress tolerance and water use requirements. Research was conducted to characterize and model water use among Cornus taxa. Scanning electron microscopy and anatomy‐based micromorphological studies as well as transpiration chamber‐based studies …

Evaluation And Enhancement Of Seed Lot Quality In Eastern Gamagrass [Tripsacum Dactyloides (L.) L.], Cynthia Hensley Finneseth

University of Kentucky Doctoral Dissertations

Eastern gamagrass [Tripsacum dactyloides (L.) L.] is a warm-season, perennial grass which is native to large areas across North America. Cultivars, selections and ecotypes suitable for erosion control, wildlife planting, ornamental, forage and biofuel applications are commercially available. Plantings are commonly established from seed; however, seed quality and dormancy are barriers to establishment. The objective here was to investigate parameters that contribute to inconsistent performance of this seed kind to subsequently improve seed lot quality.

Forty-two seed lots were used, with seed fill and germination potential ranging from 78- 100% and 11-91%, respectively. Actual germination and dormant seed ranged …

Cognitive Therapy For The Treatment Of Depressive Symptoms In Patients With Heart Failure, Rebecca L. Dekker

University of Kentucky Doctoral Dissertations

Depressive symptoms are common in patients with heart failure (HF) and adversely affect mortality, morbidity, and health-related quality of life. Cognitive therapy (CT) has been proposed as a non-pharmacological treatment for depressive symptoms in patients with HF. However, there is currently little evidence to support use of CT in patients with HF.

The purpose of this dissertation was to develop and test a brief, nurse-delivered CT intervention for the treatment of depressive symptoms in patients with HF. Prior to testing the intervention, preliminary work was conducted resulting in four manuscripts: 1) a review of the evidence for CT in treating …

Impact Of Dietary Diversification On Invasive Slugs And Biological Control With Notes On Slug Species Of Kentucky, Anna K. Thomas

University of Kentucky Master's Theses

Increasing introductions of non-native terrestrial slugs (Mollusca: Gastropoda) are a concern to North American regulatory agencies as these generalists impact the yield and reduce the aesthetic value of crop plants. Understanding how the increase in diversification in North American cropping systems affects non-native gastropods and finding effective biological control options are imperative for pest management; however, little research has been done in this area. This study tested the hypothesis that dietary diversification affects the biological control capacity of a generalist predator and allows the slug pest Deroceras reticulatum (Müller) (Stylommatophora: Agriolimacidae) to more effectively fulfill its nutritional requirements. Results showed …

Time-Dependence Of Distal-To-Proximal Hippocampal Neurodegeneration Produced By N-Methyl-D-Aspartate Receptor Activation, Jennifer Nicole Berry

University of Kentucky Master's Theses

Excitotoxicity is the overexcitation of neurons due to the excessive activation of excitatory amino acid receptors and is thought to be involved in many neurodegenerative states. The manner in which the neuron breaks down during excitotoxicity is still unclear. The current study used the organotypic hippocampal slice culture model to examine the time-dependent loss of the synaptic vesicular protein synaptophysin and the loss of N-methyl-D-aspartate (NMDA) receptor NR1 subunit availability following an excitotoxic insult (20 μM NMDA) to provide a better understanding of the topographical nature of neuronal death following NMDA receptor activation. Significant NMDA-induced cytotoxicity in the CA1 …

Feasibility Of Using 15N-Enriched Escherichia Coli As A Bacterial Tracer In The Cane Run/Royal Spring Basin, Kentucky, John G. Warden

University of Kentucky Master's Theses

A novel tracer method has used ¹⁵N to label Escherichia coli and track the transport of bacteria, a common contaminant, through karst aquifers. Use of this method could provide valuable insight into the movement of bacteria in aquifers, which would help improve remediation methods and strategies. A wild strain of E. coli was isolated from the Cane Run/Royal Spring basin in the Inner Bluegrass region of Kentucky. The strain was serotyped O^-:H^- and virulence testing showed the strain did not have virulence factors of E. coli commonly pathogenic to humans. Five karst microcosms were filled with …

Lifting As We Climb: Experiences Of Black Diversity Officers At Three Predominantly White Institutions In Kentucky, Erica Nićcole Johnson

University of Kentucky Doctoral Dissertations

Recently, colleges and universities across the country have created executive level positions responsible for institutional diversity. The origins of this work within higher education lay in the civil rights movements and its consequences for desegregation of higher education. Early diversity officer positions usually resided within student affairs. However, as the responsibilities of these offices have changed, the reporting lines have also changed such that diversity officers are now commonly situated within academic affairs. This exploratory study examines these administrative positions responsible for diversity at southern white institutions. The research takes an in-depth look at how these positions have shifted over …

Anomalous Constitutive Src Kinase Activity Promotes B Lymphoma Survival And Growth, Jiyuan Ke, R. Lakshman Chelvarajan, Vishal Sindhava, Darrell A. Robertson, Lazaros Lekakis, C. Darrell Jennings, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Background: Previously we have shown that B cell receptor (BCR) expression and B cell receptor signaling pathways are important for the basal growth of B lymphoma cells. In particular we have shown that the activation of Syk, a non-src family protein tyrosine kinase and the mitogen activated protein kinases (MAPK), ERK and JNK that mediate BCR signals are required for the constitutive growth of B lymphoma cells. Since src family protein tyrosine kinases (SFKs) like Lyn are known to be needed for the phosphorylation of BCR co-receptors, Ig-alpha and Ig-beta, we hypothesized that one or more SFKs will be constitutively …

Fagerstrom Test For Nicotine Dependence Vs Heavy Smoking Index In A General Population Survey, M. Pérez-Ríos, M. I. Santiago-Pérez, B. Alonso, A. Malvar, X. Hervada, Jose De Leon

Psychiatry Faculty Publications

BACKGROUND: The Fagerström Test for Nicotine Dependence (FTND) is used for assessing nicotine dependence. A shorter test derived from the FTND used for the general population is the Heavy Smoking Index (HSI) (six questions vs. two). The objective of this study is to compare the validity of the HSI versus the FTND.

METHODS: A survey of tobacco use in the general population was carried out in the northern Spanish region of Galicia using both the FTND and the HSI to study a representative sample of 1655 daily smokers. The HSI was compared with the FTND, considered the gold standard. Measures …

Transcriptional Adaptations Following Exercise In Thoroughbred Horse Skeletal Muscle Highlights Molecular Mechanisms That Lead To Muscle Hypertrophy, Beatrice A. Mcgivney, Suzanne S. Eivers, David E. Machugh, James N. Macleod, Grace M. O'Gorman, Stephen D.E. Park, Lisa M. Katz, Emmeline W. Hill

Veterinary Science Faculty Publications

BACKGROUND: Selection for exercise-adapted phenotypes in the Thoroughbred racehorse has provided a valuable model system to understand molecular responses to exercise in skeletal muscle. Exercise stimulates immediate early molecular responses as well as delayed responses during recovery, resulting in a return to homeostasis and enabling long term adaptation. Global mRNA expression during the immediate-response period has not previously been reported in skeletal muscle following exercise in any species. Also, global gene expression changes in equine skeletal muscle following exercise have not been reported. Therefore, to identify novel genes and key regulatory pathways responsible for exercise adaptation we have used equine-specific …

A Unique Role For The Host Escrt Proteins In Replication Of Tomato Bushy Stunt Virus, Daniel Barajas, Yi Jiang, Peter D. Nagy

Plant Pathology Faculty Publications

Plus-stranded RNA viruses replicate in infected cells by assembling viral replicase complexes consisting of viral- and host-coded proteins. Previous genome-wide screens with Tomato bushy stunt tombusvirus (TBSV) in a yeast model host revealed the involvement of seven ESCRT (endosomal sorting complexes required for transport) proteins in viral replication. In this paper, we show that the expression of dominant negative Vps23p, Vps24p, Snf7p, and Vps4p ESCRT factors inhibited virus replication in the plant host, suggesting that tombusviruses co-opt selected ESCRT proteins for the assembly of the viral replicase complex. We also show that TBSV p33 replication protein interacts with Vps23p ESCRT-I …

Chylomicrons Promote Intestinal Absorption And Systemic Dissemination Of Dietary Antigen (Ovalbumin) In Mice, Yuehui Wang, Sarbani Ghoshal, Martin Ward, Willem De Villiers, Jerold Woodward, Erik Eckhardt

Internal Medicine Faculty Publications

BACKGROUND: A small fraction of dietary protein survives enzymatic degradation and is absorbed in potentially antigenic form. This can trigger inflammatory responses in patients with celiac disease or food allergies, but typically induces systemic immunological tolerance (oral tolerance). At present it is not clear how dietary antigens are absorbed. Most food staples, including those with common antigens such as peanuts, eggs, and milk, contain long-chain triglycerides (LCT), which stimulate mesenteric lymph flux and postprandial transport of chylomicrons through mesenteric lymph nodes (MLN) and blood. Most dietary antigens, like ovalbumin (OVA), are emulsifiers, predicting affinity for chylomicrons. We hypothesized that chylomicron …

Documentation Of Body Mass Index And Control Of Associated Risk Factors In A Large Primary Care Network, Stephanie A. Rose, Alexander Turchin, Richard W. Grant, James B. Meigs

Internal Medicine Faculty Publications

BACKGROUND: Body mass index (BMI) will be a reportable health measure in the United States (US) through implementation of Healthcare Effectiveness Data and Information Set (HEDIS) guidelines. We evaluated current documentation of BMI, and documentation and control of associated risk factors by BMI category, based on electronic health records from a 12-clinic primary care network.

METHODS: We conducted a cross-sectional analysis of 79,947 active network patients greater than 18 years of age seen between 7/05 - 12/06. We defined BMI category as normal weight (NW, 18-24.9 kg/m²), overweight (OW, 25-29.9), and obese (OB, ≥ 30). We measured documentation …

Vectors And Methods For Enhanced Cell Longevity And Protein Expression, Bruce A. Webb, Jeremy Kroemer

Entomology Faculty Patents

It is the object of the current invention to provide methods and compositions relating to the expression of vankyrin proteins in cell lines to increase their viability, longevity and capacity for protein production. The inventors have discovered that the expression of P-ank-1 and I²-ank-3 proteins in cell culture has increased the cells' longevity and capacity for endogenous and/or heterologous target protein production. Specifically, the present invention relates to the enhanced expression of endogenous and/or heterologous target proteins/polypeptides in recombinant cells that are also expressing P-ank-1 and/or I²-ank-3 protein compared to expression host cells that are not …

Stimuli-Responsive Hydrogel Microdomes Integrated With Genetically Engineered Proteins For High-Throughput Screening Of Pharmaceuticals, Sylvia Daunert, Sapna K. Deo, Jason Douglas Ehrick, Tyler William Browning, Leonidas G. Bachas

Chemistry Faculty Patents

A hydrogel microdome that can swell in response to a stimuli or target molecule is formed by polymerizing a mixture comprising a monomer capable of forming a hydrogel with a biopolymer. An array of hydrogel microdomes can be formed on a substrate by microspotting the mixture and polymerizing. The array can be used for high-throughput screening of analytes as well as for use as an actuator and biosensor using the swelling property of the hydrogel.

Fiscal Year 2009 Fhwa-536 Report For The Kentucky Transportation Cabinet, Steven Douglas Kreis, Candice Y. Wallace

Kentucky Transportation Center Research Report

The Federal Highway Administration (FHWA) requires state transportation agencies to submit a biennial report on local highway finances. The purpose of these reports is to provide FHWA with the data it needs to capture the financing of highway activities at the local level. Based on this information, it can identify trends in revenue, expenditures, investments, and program development, and in turn make decisions about future investments. The report, FHWA-536, asks agencies to report on four areas of local highway finance: 1) disposition of highway-user revenues; 2) revenues used for roads and streets identified by source and funding type; 3) road …