Digital Commons Network^™

Using Thr Ffm To Understand And Integrate The Deficits Of Psychopathy, Karen J. Derefinko

University of Kentucky Doctoral Dissertations

Psychopathy is associated with several behavioral and psychophysiological deficits. Lynam (2002) has argued that the use of an overarching conceptualization of psychopathy can provide a parsimonious explanation of psychopathic pathology. The current study examined relations between tasks used to explore psychopathic pathology and dimensions from the Five Factor Model of personality. Undergraduate participants completed the NEO PI-R, the BART, a go/no-go task, an emotional morph task, and provided physiological responses to stimuli. While hypothesized relations to FFM psychopathy composites were generally unsupported, other interesting relations to traits were identified. Results indicated that hypoarousal to negative stimuli was negatively related to …

The Nature And Meaning Of Culture In Primary Care Medicine: Implications For Education, Clinical Practice, And Stereotypes, Madison Lamar Gates

University of Kentucky Doctoral Dissertations

The medical profession in recent decades has made culture and cross-cultural competence an issue for patient – physician relationships. Many in the profession attribute the necessity of cross-cultural competence to increased diversity, globalization, and health disparities; however, a historical analysis of medicine indicates that culture’s relevancy for health care and outcome is not new. The rise of clinics, which can be traced to 17th century France, the professionalization of physicians in 18th century U.S., and the civil rights movement of the 20th century illustrate that medicine, throughout its history, has grappled with culture and health. While medicine has a history …

Role Of P33 In Tombusvirus Replication, Jozsef Stork

University of Kentucky Doctoral Dissertations

Replication of the nonsegmented, plus-stranded RNA genome of Cucumber necrosis tombusvirus (CNV) requires two essential overlapping viral-coded replication proteins, the p33 replication co-factor and the p92 RNA-dependent RNA polymerase. In my thesis I describe (i) the effect of phosphorylation of p33, (ii) the RNA chaperone-like activity of p33, and (iii) the role of HSP70s a host proteins in the viral replication. To test the effect of phosphorylation on p33 function, I used in vitro phosphorylated p33. I found that phosphorylation inhibited the ability of p33 to bind to the viral RNA. Phosphorylation-mimicking mutations rendered p33 nonfunctional in plant protoplasts and …

Changes In Longitudinally Assessed Biomechanical Parameters Related To Increased Risk Of Anterior Cruciate Ligament (Acl) Injuries In Adolescent Female And Male Athletes, Kevin Ray Ford

University of Kentucky Doctoral Dissertations

Females suffer anterior cruciate ligament (ACL) injuries at a 2 to 10-fold greater rate compared to male athletes participating in similar sports. Altered movement patterns and inadequate knee stiffness are two interrelated factors that may increase ACL injury risk. Onset of these neuromuscular risk factors may coincide with the rapid adolescent growth that results in the divergence of a multitude of neuromuscular parameters between sexes. The overall purpose of this dissertation was to determine if neuromuscular ACL injury risk factors in female athletes increase following rapid growth and development compared to males. Male and female athletes were tested with three-dimensional …

The Interaction Between Personality Traits And Contextual Disadvantage On Criminal Behavior: A Longitudinal Study Of High Risk-Females, Lauren C. Gudonis

University of Kentucky Doctoral Dissertations

This investigation examined several dimensions of personality functioning in a longitudinal sample of females. These data are part of an existing project evaluating female development across 3 different time points starting in adolescence and transitioning into adulthood. Subjects were categorized into a clinical group (females with a high degree of psychiatric comorbidity) and a normal control group. All participants were initially recruited when they were between 14-18 years of age, and were followed up twice when they were 19-23, and 24-28. In an attempt to explore possible heterogeneity in personality trait development, the research is presented as three separate studies …

Regulation Of Low Density Lipoprotein Receptor Splicing Efficiency, I-Fang Ling

University of Kentucky Doctoral Dissertations

Low density lipoprotein receptor (LDLR) is an apolipoprotein E (apoE) receptor and may play a role in Alzheimer’s disease (AD) development. A single nucleotide polymorphism (SNP), rs688, that has been identified to modulate the splicing efficiency of LDLR exon 12 and is associated with higher cholesterol and AD in some case-control populations. The exon 12 deleted mRNA is predicted to produce a soluble form of LDLR that fails to mediate apoE uptake. To gain additional insights, in this study, I seek to understand the regulation of LDLR splicing efficiency. To identify functional cis-elements within LDLR exon 12, I mutated several …

Direct Products And The Intersection Map Of Certain Classes Of Finite Groups, Julia Chifman

University of Kentucky Doctoral Dissertations

The main goal of this work is to examine classes of finite groups in which normality, permutability and Sylow-permutability are transitive relations. These classes of groups are called T , PT and PST , respectively. The main focus is on direct products of T , PT and PST groups and the behavior of a collection of cyclic normal, permutable and Sylow-permutable subgroups under the intersection map. In general, a direct product of finitely many groups from one of these classes does not belong to the same class, unless the orders of the direct factors are relatively prime. Examples suggest that …

Age May Be Hazardous To Outcome Following Traumatic Brain Injury: The Mitochondrial Connection, Lesley Knight Gilmer

University of Kentucky Doctoral Dissertations

Older individuals sustaining traumatic brain injury (TBI) experience a much higher incidence of morbidity and mortality. This age-related exacerbated response to neurological insult has been demonstrated experimentally in aged animals, which can serve as a model to combat this devastating clinical problem. The reasons for this worse initial response are unknown but may be related to age-related changes in mitochondrial respiration.

Evidence is shown that mitochondrial dysfunction occurs early following traumatic brain injury (TBI), persists long after the initial insult, and is severitydependent. Synaptic and extrasynaptic mitochondrial fractions display distinct respiration capacities, stressing the importance to analyze these fractions separately. …

Vortex Model Of Open Channel Flows With Gravel Beds, Brian James Belcher

University of Kentucky Doctoral Dissertations

Turbulent structures are known to be important physical processes in gravel-bed rivers. A number of limitations exist that prohibit the advancement and prediction of turbulence structures for optimization of civil infrastructure, biological habitats and sediment transport in gravel-bed rivers. This includes measurement limitations that prohibit characterization of size and strength of turbulent structures in the riverine environment for different case studies as well as traditional numerical modeling limitations that prohibit modeling and prediction of turbulent structure for heterogeneous beds under high Reynolds number flows using the Navier-Stokes equations. While these limitations exist, researchers have developed various theories for the structure …

The Role Of The Hip Abductor Muscle Complex In The Function Of The Pathological Hip Joint, Maureen Kelly Dwyer

University of Kentucky Doctoral Dissertations

The number of patients electing to undergo total hip arthroplasty (THA) in the United States has been projected to double by the year 2030, with a growing number of these patients below the age of 65 years. This cohort of patients not only desires to return to pain free daily activity, but wishes to participate in recreation and sporting activities. However, many of these patients report pain, impairments, and functional limitations following THA. The number one deficit observed for patients who fail conventional post-operative rehabilitation is persistent weakness of the hip abductor muscles. In order to safely progress these patients …

Investigations Of S-Glutathionylation Of Brain Proteins In The Progression Of Alzheimer's Disease And Of A Potential Glutatione Mimetic As A Treatment Of Alzheimer's Disease, Shelley Faye Newman

University of Kentucky Doctoral Dissertations

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by neurofibrillary tangles, senile plaques and loss of synapses. Many studies support the notion that oxidative stress plays an important role in AD pathogenesis. Previous studies from our laboratory employed redox proteomics to identify oxidatively modified proteins in the AD inferior parietal lobule (IPL). The proteins were consistent with AD pathology and have been central to further investigations of the disease. The present study was focused on the identification of specific targets of protein S-glutathionylation in AD, early AD (EAD), and mild cognative impairment (MCI) using a redox proteomics approach. In AD …

Lipid-Based Paclitaxel And Doxorubicin Nanoparticles To Overcome P-Gp-Mediated Drug Resistance In Solid Tumors, Xiaowei Dong

University of Kentucky Doctoral Dissertations

Multidrug resistance (MDR) is a major obstacle limiting chemotherapeutic efficacy. The purpose of these studies was to investigate the potential application of injectable paclitaxel (PX) and doxorubicin (Dox)-loaded nanoparticles (NPs) engineered from oil-in-water microemulsion precursors for overcoming P-glycoprotein (P-gp)- mediated drug resistance in solid tumors.

An in-vitro study was performed to test whether the oil (stearyl alcohol and cetyl alcohol) used to make lipid nanoparticles could be metabolized. The results showed that the concentrations of the fatty alcohols within nanoparticles, which were quantitatively determined over time by gas chromatography, decreased to only 10-20% of the initial concentration after 15-24 h …

Studies On The Role Of Acid Sphingomyelinase And Ceramide In The Regulation Of Tace Activity And Tnfα Secretion By Macrophages, Krasimira Rozenova

University of Kentucky Doctoral Dissertations

Acid Sphingomyelinase (ASMase) activity has been proposed to mediate LPS signaling in various cell types. This study shows that in macrophages, ASMase is a negative regulator of LPS-induced TNFα secretion. ASMasedeficient (asm^-/-) mice and isolated peritoneal macrophages produce several fold more TNFα than their wild-type (asm^+/+) counterparts when stimulated with LPS. The mechanism for these differences however is not transcriptional but post-translational.

The TNFα converting enzyme (TACE) catalyzes the maturation of the 26kD precursor (proTNFα) to the active 17kD form (sTNFα). In mouse peritoneal macrophages, the activity of TACE rather than the rate of TNFα mRNA …

Computational Design Of 3-Phosphoinositide Dependent Kinase-1 Inhibitors As Potential Anti-Cancer Agents, Mohamed Diwan Mohideen Abdulhameed

University of Kentucky Doctoral Dissertations

Computational drug design methods have great potential in drug discovery particularly in lead identification and lead optimization. 3-Phosphoinositide dependent kinase-1 (PDK1) is a protein kinase and a well validated anti-cancer target. Inhibitors of PDK1 have the potential to be developed as anti-cancer drugs. In this work, we have applied various novel computational drug design strategies to design and identify new PDK1 inhibitors with potential anti-cancer activity. We have pursued novel structure-based drug design strategies and identified a new binding mode for celecoxib and its derivatives binding with PDK1. This new binding mode provides a valuable basis for rational design of …

Biology And Management Of The Bed Bug, Cimex Lectularius L. (Heteroptera: Cimicidae), Alvaro Romero

University of Kentucky Doctoral Dissertations

The near absence of bed bugs from human dwellings for fifty or more years has left us with limited knowledge of its biology and few answers to eliminate populations. I explored a diverse set of objectives to answer key questions concerning bed bug biology and control. Major objectives were studies of circadian rhythmicity, pyrethroid resistance, sublethal effects of insecticides, synergism of pyrethroids, and evaluation of a pyrrole insecticides, chlorfenapyr. Additional studies included persistence of Borrelia in bed bugs after ingestion, and aggregation factors from feces.

In the absence of host stimuli, insects were much more active in the dark than …

Synthesis And Evaluation Of Prouteolysis Taurgeting Chimeras (Protacs): A Potential Chemical Genetic Approach To Breast Cancer Therapy, Kedra C. Cyrus

University of Kentucky Doctoral Dissertations

The use of small molecules to probe the function of proteins is referred to as chemical genetics. The Proteolysis Targeting Chimera (PROTAC) is a chemical genetic tool that contains the ligand for a target protein of interest and the recognition motif for an E3 ubiquitin ligase attached by a linker. The PROTAC is capable of binding to and recruiting specific target proteins to the intracellular degradation system, the ubiquitin proteasome system (UPS). While the approach has had success it has not been optimized to be used on a broader scale.

Optimization efforts focused on elucidating the ideal linker length between …

Towards Elimination And Genetic Manipulation Of Ergot Alkaloid Production In Fungal Endophytes, Simona Florea

University of Kentucky Doctoral Dissertations

Clavicipitaceous fungal endophytes provide several ecological benefits to their hosts. Besides improving host’s growth characteristics, Neotyphodium coenophialum, the endophyte of tall fescue (Lolium arundinaceum), produces ergot alkaloids that have been proposed to be involved in fescue toxicosis. One approach to address the toxicosis problem is to genetically manipulate and modify N. coenophialum by knocking out a pair of homologous genes, (dmaW1 and dmaW2), encoding dimethylallyltryptophan synthase, the enzyme for the first and determinant step in ergot-alkaloid biosynthesis. In this study, disruption of dmaW2 was attempted using several disruption methods. Out of 1522 transformants screened, three …

Regeneration Of Damaged Growth Plate Using Igf-I Plasmid-Releasing Porous Plga Scaffolds, Nirmal Ravi

University of Kentucky Doctoral Dissertations

Growth plate injuries account for 15-30% of long bone fractures in children. About 10% of these result in significant growth disturbances due to formation of a boney bar. If not treated correctly, this can lead to life-lasting consequences of limb length inequalities and angular deformities. Current treatments for growth plate injuries include removal of boney bar and insertion of fat, silicone, bone cement, etc.. This treatment y is inadequate, leaving almost half of these patients with continued deformities. This dissertation reports characterization of a DNA–containing porous poly(lactic-co-glycolic acid) (PLGA) scaffold system, chondrogenesis using insulin-like growth factor I (IGF-I) plasmid-releasing scaffolds …

The Pharmacogenomics Of Egfr-Dependent Nsclc: Predicting And Enhancing Response To Targeted Egfr Therapy, Justin M. Balko

University of Kentucky Doctoral Dissertations

The introduction of tyrosine kinase inhibitors (TKI) targeting the epidermal growth factor receptor (EGFR) inhibitors to the clinic has resulted in an improvement in the treatment of non small cell lung cancer (NSCLC). However, many patients treated with EGFR TKIs do not respond to therapy. The burden of failed treatment is largely placed on the healthcare field, limiting the effectiveness of EGFR TKIs. Furthermore, responses are hindered by the emergence of resistance. Thus, two questions must be addressed to achieve maximum benefit of EGFR inhibitors: How can patients who will benefit from EGFR TKIs be selected a priori? How …

The Interplay Between The Expression And Functions Of Wnt13 Isoforms During Apoptosis In Bovine Aortic Endothelial Cells, Tao Tang

University of Kentucky Doctoral Dissertations

Wnt proteins are crucial for development/homeostasis by controlling cell fate including apoptosis (Moon RT et al. 1997). Three humanWnt13 isoforms were identified: the secreted Wnt13A, mitochondrial Wnt13B, and nuclear Wnt13C forms; and nuclear Wnt13 had an increased sensitivity to LPS/TNF-induced apoptosis in primary endothelial cells (EC); both Wnt13B and C mRNA contain two start codons (AUG+1 and +74), but the same protein encoded from AUG+74 by Wnt13C was expressed lower than Wnt13B (Struewing IT et al.2006). We hypothesize that during EC apoptosis, the nuclear Wnt13C expression is regulated translationally; nuclear Wnt13 favors apoptosis through regulating the activity/expression of apoptosis-related factors; …

A Comparative Study Of Larval Gene Expression Between A Paedomorphic And Metamorphic Species Of Ambystomatid Salamander, Meredith A. Boley

University of Kentucky Master's Theses

Ambystoma tigrinum undergoes an obligatory metamorphosis while A. mexicanum fails to metamorphose and exhibits paedomorphosis. While it is clear that salamander paedomorphosis is associated with genetic changes that delay developmental timing, it is not clear when and how these changes manifest during development. It is possible that paedomorphic and metamorphic larvae show equivalent patterns of developmental until late in the larval period, when brain regions become competent to stimulate the release of metamorphic hormones. To test this hypothesis, I compared gene expression patterns between the brains of A. mexicanum and A. t. tigrinum larvae. In support of the developmental equivalence …

Comparison Of Rope-Wick And Broadcast Treatments For Control Of Canada Thistle And Tall Ironweed, Daisy M. Fryman

University of Kentucky Master's Theses

Tall ironweed (Vernonia altissima) and Canada thistle (Cirsium arvense) control in cool season grass pastures was evaluated in 2007 and 2008. Tall ironweed was evaluated in Fayette and Boone Counties, KY and Canada thistle was evaluated at Spindletop Research Farm. Herbicides applied selectively with a rope-wick were compared to a broadcast foliar spray. Treatments were a broadcast treatment, of aminopyralid + 2, 4-D and six rope-wick treatments: aminopyralid at three concentrations, glyphosate, triclopyr and clopyralid at one concentration each. The Boone County location had five broadcast foliar treatments: aminopyralid at three rates, triclopyr + fluroxpyr, and …

Towards Reducing Fungicide Use In The Control Of Dollar Spot (Sclerotinia Homoeocarpa F.T. Bennett) Disease On Creeping Bentgrass (Agrostis Stolonifera L.), Kenneth Lee Cropper

University of Kentucky Master's Theses

Creeping bentgrass (Agrostis stolonifera L.) is commonly used on golf course greens and fairways in cool-humid regions but is plagued by numerous fungal diseases, one of which is dollar spot disease (Sclerotinia homoeocarpa F. T. Bennett). Dollar spot occurs frequently throughout the growing season requiring biweekly fungicide applications for complete control. The objective of this study was to investigate methods of reducing the number of fungicide applications needed to maintain dollar spot at acceptable levels through dew removal and potential mechanisms of resistance in bentgrass. In the first study, a combination of mowing three times a week and …

Design And Analysis Of Nano-Gap Enhanced Surface Plasmon Resonance Sensors, Phillip Donald Keathley

University of Kentucky Master's Theses

Surface plasmon resonance (SPR) sensors are advantageous to other techniques of sensing chemical binding, offering quantitative, real-time, label-free results. Previous work has demonstrated the effectiveness of using dual-mode SPR sensors to differentiate between surface and background effects, making the sensors more robust to dynamic environments. This work demonstrates a technique that improves upon a previously optimized planar film dual-mode SPR sensor’s LOD by introducing a periodic array of subwavelength nano-gaps throughout the plasmon supporting material. First, general figures of merit for a sensor having an arbitrary number of modes are studied. Next, the mode effective index dispersion and magnetic field …

Low Density Lipoprotein Receptor And Alzheimers Disease, Rangaraj K. Gopalraj

University of Kentucky Doctoral Dissertations

Since apoE allele status is the predominant Alzheimers disease (AD) genetic risk factor, functional single nucleotide polymorphisms (SNPs) in brain apoE receptors represent excellent candidates for association with AD. Therefore, three low density lipoprotein receptor (LDLR) SNPs were evaluated by TaqMan allelic discrimination assays for association with AD and I found that certain haplotypes alter the odds of AD. A SNP within LDLR exon 12, rs688, was identified in silico as neutralizing a putative exon splicing enhancer (ESE). Since LDLR is a major apoE receptor in the brain, I hypothesized that rs688 modulates LDLR splicing in neural tissues and associates …

Physiological Genomics Of Spinal Cord And Limb Regeneration In A Salamander, The Mexican Axolotl, James Robert Monaghan

University of Kentucky Doctoral Dissertations

Salamanders have a remarkable ability to regenerate complex body parts including the limb, tail, and central nervous system. Although salamander regeneration has been studied for several hundred years, molecular-level studies have been limited to a relatively few important transcription factors and signaling molecules that are highly conserved among animals. Physiological genomic approaches were used here to investigate spinal cord and limb regeneration. Chapter 2 reports that hundreds of gene expression changes were identified during spinal cord regeneration, showing that a diverse injury response is activated in concert with extracellular matrix remodeling mechanisms during the early acute phase of natural spinal …

Down-Regulation Of Ppargamma1 Suppresses Cell Growth And Induces Apoptosis In Mcf-7 Breast Cancer Cells, Yekaterina Y. Zaytseva, Xin Wang, R. Chase Southard, Natalie K. Wallis, Michael W. Kilgore

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear hormone receptor superfamily and is highly expressed in many human tumors including breast cancer. PPARgamma has been identified as a potential target for breast cancer therapy based on the fact that its activation by synthetic ligands affects the differentiation, proliferation, and apoptosis of cancer cells. However, the controversial nature of current studies and disappointing results from clinical trials raise questions about the contribution of PPARgamma signaling in breast cancer development in the absence of stimulation by exogenous ligands. Recent reports from both in vitro and in vivo studies …

Borderline Personality Disorder: An Overview Of History, Diagnosis And Treatment In Adolescents, Linah Al-Alem, Hatim A. Omar

Pharmacology and Nutritional Sciences Faculty Publications

Borderline personality disorder (BPD) is a cluster B personality disorder. It is characterized by erratic behaviors, emotional instability and one of its hallmarks is self injurious behavior, which starts in adolescence. Patients with BPD are difficult to treat, most have a history of child sexual abuse, about a quarter present with sexual abuse from a caretaker. Although personality disorders are diagnosed only in adults, BPD manifests itself in adolescence in the form of uncontrollable anger, self mutilations, dissociation and other such behaviors. Hence, there is a growing number of scientists discussing the possibility of diagnosing BPD in adolescents. Here, we …

Aluminum Bioavailability From Tea Infusion, Robert A. Yokel, Rebecca L. Florence

Pharmaceutical Sciences Faculty Publications

The objective was to estimate oral Al bioavailability from tea infusion in the rat, using the tracer ²⁶Al. ²⁶Al citrate was injected into tea leaves. An infusion was prepared from the dried leaves and given intra-gastrically to rats which received concurrent intravenous ²⁷Al infusion. Oral Al bioavailability (F) was calculated from the area under the ²⁶Al, compared to ²⁷Al, serum concentration × time curves. Bioavailability from tea averaged 0.37%; not significantly different from water (F = 0.3%), or basic sodium aluminum phosphate (SALP) in cheese (F = 0.1 to 0.3%), but greater than acidic SALP …

Manufactured Aluminum Oxide Nanoparticles Decrease Expression Of Tight Junction Proteins In Brain Vasculature, Lei Chen, Robert A. Yokel, Bernhard Hennig, Michal Toborek

Pharmaceutical Sciences Faculty Publications

Manufactured nanoparticles of aluminum oxide (nano-alumina) have been widely used in the environment; however, their potential toxicity provides a growing concern for human health. The present study focuses on the hypothesis that nano-alumina can affect the blood-brain barrier and induce endothelial toxicity. In the first series of experiments, human brain microvascular endothelial cells (HBMEC) were exposed to alumina and control nanoparticles in dose- and time-responsive manners. Treatment with nano-alumina markedly reduced HBMEC viability, altered mitochondrial potential, increased cellular oxidation, and decreased tight junction protein expression as compared to control nanoparticles. Alterations of tight junction protein levels were prevented by cellular …