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Late Pleistocene-Early Holocene Colonization And Regionalization In Northern Perú: Fishtail And Paiján Complexes Of The Lower Jequetepeque Valley, Greg J. Maggard

University of Kentucky Doctoral Dissertations

Until relatively recently, the view of Late Pleistocene hunter-gatherers in the Americas was dominated by the “Clovis-first” paradigm. However, recent discoveries have challenged traditional views and forced reconsiderations of the timing, processes, and scales used in modeling the settlement of the Americas. Chief among these discoveries has been the recognition of a wide range of early cultural diversity throughout the Americas that is inconsistent with previously held notions of cultural homogeneity.

During the Late Pleistocene-Early Holocene, the development of widely varying economic, technological and mobility strategies in distinct environments is suggestive of a range of different adaptations and traditions.

It …

Local Synaptic Network Interactions In The Dentate Gyrus Of A Cortical Contusion Model Of Posttraumatic Epilepsy, Robert F. Hunt Iii

University of Kentucky Doctoral Dissertations

Posttraumatic epilepsy is a common consequence of brain trauma. However, little is known about how long-term changes in local excitatory and inhibitory synaptic networks contribute to epilepsy after closed-head brain injury. This study adapted a widely used model of experimental brain injury as a mouse model of posttraumatic epilepsy. Behavioral seizure activity and alterations in synaptic circuitry in the dentate gyrus were examined in mice after experimental cortical contusion brain injury. Spontaneous behavioral seizures were observed in 20% of mice after moderate injury and 36-40% of mice weeks after severe injury. In the dentate gyrus, most mice displayed regionally localized …

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 …

Opioid-Cannabinoid Codrugs With Enhanced Analgesic And Pharmacokinetic Profile, Harpreet Kaur Dhooper

University of Kentucky Doctoral Dissertations

The central hypothesis of the dissertation is that “the design and synthesis of a codrug of an opiate and a cannabinoid can be achieved which is stable in the gastrointestinal tract and shows a superior pharmacological and pharmacokinetic profile when compared to a physical mixture of the two parent drugs.” To prove the hypothesis, a series of novel codrugs were prepared by conjugation of the opiate drug codeine with Δ⁹-tetrahydrocannabinol (Δ⁹-THC), cannabidiol, abn-cannabidiol and an opiate prodrug 3-O-acetylmorphine with Δ⁹-THC. Codeine-cannabinoid codrugs were evaluated for analgesic activity in the rat after oral administration. 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 …

Characterization Of Soil Carbon Stabilization In Long-Term Row-Cropped Agro-Ecosystems, Soraya Patricia Alvarado-Ochoa

University of Kentucky Doctoral Dissertations

Soil organic matter (SOM) is a dynamic soil property, sensitive and responsive to many factors. The possibility of increasing soil carbon (C) sequestration by changing land use and management practices has been of great interest recently due to concerns with global changes in the atmospheric carbon dioxide (CO₂) balance. Nonetheless, as a result of the complex dynamics of SOM, there is still the need for SOM characterization procedures capable of monitoring SOM stabilization, taking into account all the factors involved.

This study characterized SOM stabilization as affected by management practices in three long-term field experiments, considering physical, chemical …

Evolution And The End Of A World, David Edward Long

University of Kentucky Doctoral Dissertations

This dissertation examines college student understanding and attitudes toward biological evolution. In ethnographic work, I followed a cohort of 31 students through their required introductory biology class. In interviews, students discuss their life history with the concept - in school, at home, at church, and in their communities. For some Creationist students, confronting evolution in class has meant confronting existential issues regarding both the basis of science and the basis of faith. For other Creationist students, claims of evolution's theoretical strength are eschewed for its direct challenge to their worldview. For most students, science holds minimal interest against other values …

Phylloplanins: Novel Antifungal Proteins On Plant Leaf Surfaces, Ryan William Shepherd

University of Kentucky Doctoral Dissertations

Secreted surface proteins are an innate immune defense component employed by animals to inhibit invading microbes. Surface proteins have not been documented in plants, even though the aerial leaf surface, or phylloplane, is a major site of pathogen ingress. We have discovered novel proteins, termed phylloplanins, which accumulate on leaf surfaces of Nicotiana tabacum, and we have isolated the gene Phylloplanin that is unique in gene databases. Natural and E. coli-expressed phylloplanins inhibit spore germination and limit leaf infection by the oomycete pathogen Peronospora tabacina.

We investigated the site of phylloplanin biosynthesis using biochemical techniques. These techniques …

Targeted Polymeric Biomaterials For The Prevention Of Post Surgical Adhesions, John M. Medley

University of Kentucky Doctoral Dissertations

Despite recent advances in surgical technique and the development of numerous therapeutic agents, the formation post surgical adhesions (PSA) continues to cause complications for many patients. In this research, we have employed a rational system to develop a novel treatment to address this clinical need. Based on an understanding of the biochemical events that lead to PSA formation, a series of targeted polymeric biomaterials was designed to interrupt the fibrin gel matrix propagation and suppress PSA formation.

Using group transfer polymerization, a series of well controlled block copolymers of polyacrylic acid and poly(ethylene glycol-methacrylate) based materials was synthesized. Subsequent functionalization …

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 …

Environmental Effects On Behavior And Physiology In Crayfish, Sonya M. Bierbower

University of Kentucky Doctoral Dissertations

Despite dramatic morphological differences between animals from different taxa, several important features in organization and sensory system processing are similar across animals. Because of this similarity, a number of different organisms including mammals, insects, and decapod crustaceans serve as valuable model systems for understanding general principles of environmental effects. This research examines intrinsic and extrinsic factors by behaviorally and physiologically means to identify the impact of environmental conditions on two distinct crayfish species- Procambarus clarkii (surface) and Orconectes australis packardi (cave).

The research identified behavioral and physiological responses in these two morphological and genetically distinct species. The studies also examined …

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 …

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 …

In Vivo Oxidative Stress In Alzheimer Disease Brain And A Mouse Model Thereof: Effects Of Lipid Asymmetry And The Single Methionine Residue Of Amyloid-Β Peptide, Miranda Lu Bader Lange

University of Kentucky Doctoral Dissertations

Studies presented in this dissertation were conducted to gain more insight into the role of phospholipid asymmetry and amyloid-β (Aβ)-induced oxidative stress in brain of subjects with amnestic mild cognitive impairment (aMCI) and Alzheimer disease (AD). AD is a largely sporadic, age-associated neurodegenerative disorder clinically characterized by the vast, progressive loss of memory and cognition commonly in populations over the age of ~65 years, with the exception of those with familial AD, which develop AD symptoms as early as ~30 years-old. Neuropathologically, both AD and FAD can be characterized by synapse and neuronal cell loss in conjunction with accumulation of …

The Rhetoric Of Destruction: Racial Identity And Noncombatant Immunity In The Civil War Era, James M. Bartek

University of Kentucky Doctoral Dissertations

This study explores how Americans chose to conduct war in the mid-nineteenth century and the relationship between race and the onset of “total war” policies. It is my argument that enlisted soldiers in the Civil War era selectively waged total war using race and cultural standards as determining factors. A comparative analysis of the treatment of noncombatants throughout the United States between 1861 and 1865 demonstrates that nonwhites invariably suffered greater depredations at the hands of military forces than did whites. Five types of encounters are examined: 1) the treatment of white noncombatants by regular Union and Confederate forces; 2) …

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 …

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 …

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 …

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.

Manganese Flux Across The Blood-Brain Barrier, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Manganese (Mn) is essential for brain growth and metabolism, but in excess can be a neurotoxicant. The chemical form (species) of Mn influences its kinetics and toxicity. Significant Mn species entering the brain are the Mn²⁺ ion and Mn citrate which, along with Mn transferrin, enter the brain by carrier-mediated processes. Although the divalent metal transporter (DMT-1) was suggested to be a candidate for brain Mn uptake, brain Mn influx was not different in Belgrade rats, which do not express functional DMT-1, compared to controls. Brain Mn influx was not sodium dependent or dependent on ATP hydrolysis, but was …

Proteomic Analysis Of Blastema Formation In Regenerating Axolotl Limbs, Nandini Rao, Deepali Jhamb, Derek J. Milner, Bingbing Li, Fengyu Song, Mu Wang, S. Randal Voss, Mathew Palakal, Michael W. King, Behnaz Saranjami, Holly L.D. Nye, Jo Ann Cameron, David L. Stocum

Biology Faculty Publications

BACKGROUND: Following amputation, urodele salamander limbs reprogram somatic cells to form a blastema that self-organizes into the missing limb parts to restore the structure and function of the limb. To help understand the molecular basis of blastema formation, we used quantitative label-free liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS)-based methods to analyze changes in the proteome that occurred 1, 4 and 7 days post amputation (dpa) through the mid-tibia/fibula of axolotl hind limbs.

RESULTS: We identified 309 unique proteins with significant fold change relative to controls (0 dpa), representing 10 biological process categories: (1) signaling, (2) Ca2+ binding and translocation, (3) transcription, …

Characterization Of Genes Encoding Poly(A) Polymerases In Plants: Evidence For Duplication And Functional Specialization, Lisa R. Meeks, Bala Subrahmanyam Addepalli, Arthur G. Hunt

Plant and Soil Sciences Faculty Publications

Background: Poly(A) polymerase is a key enzyme in the machinery that mediates mRNA 3′ end formation in eukaryotes. In plants, poly(A) polymerases are encoded by modest gene families. To better understand this multiplicity of genes, poly(A) polymerase-encoding genes from several other plants, as well as from Selaginella, Physcomitrella, and Chlamydomonas, were studied.

Methodology/Principal Findings: Using bioinformatics tools, poly(A) polymerase-encoding genes were identified in the genomes of eight species in the plant lineage. Whereas Chlamydomonas reinhardtii was found to possess a single poly(A) polymerase gene, other species possessed between two and six possible poly(A) polymerase genes. With the exception …

Detection Of Sub-Clinical Cwd Infection In Conventional Test-Negative Deer Long After Oral Exposure To Urine And Feces From Cwd+ Deer, Nicholas J. Haley, Candace K. Mathiason, Mark D. Zabel, Glenn C. Telling, Edward A Hoover

Microbiology, Immunology, and Molecular Genetics Faculty Publications

BACKGROUND: Chronic wasting disease (CWD) of cervids is a prion disease distinguished by high levels of transmissibility, wherein bodily fluids and excretions are thought to play an important role. Using cervid bioassay and established CWD detection methods, we have previously identified infectious prions in saliva and blood but not urine or feces of CWD+ donors. More recently, we identified very low concentrations of CWD prions in urine of deer by cervid PrP transgenic (Tg[CerPrP]) mouse bioassay and serial protein misfolding cyclic amplification (sPMCA). This finding led us to examine further our initial cervid bioassay experiments using sPMCA.

OBJECTIVES: We sought …

Modulation Of Outer Hair Cell Electromotility By Cochlear Supporting Cells And Gap Junctions, Ning Yu, Hong-Bo Zhao

Surgery Faculty Publications

Outer hair cell (OHC) or prestin-based electromotility is an active cochlear amplifier in the mammalian inner ear that can increase hearing sensitivity and frequency selectivity. In situ, Deiters supporting cells are well-coupled by gap junctions and constrain OHCs standing on the basilar membrane. Here, we report that both electrical and mechanical stimulations in Deiters cells (DCs) can modulate OHC electromotility. There was no direct electrical conductance between the DCs and the OHCs. However, depolarization in DCs reduced OHC electromotility associated nonlinear capacitance (NLC) and distortion products. Increase in the turgor pressure of DCs also shifted OHC NLC to the negative …