Digital Commons Network^™

Larry Brown: Passion To Brilliance, Barry Hannah

Yalobusha Review

No abstract provided.

Between Pissworth And Papich, Patrick Michael Finn

Yalobusha Review

No abstract provided.

Four Poets On First Books, Corinna Schroeder, Douglas Ray

Yalobusha Review

No abstract provided.

The Shell Mall, Christopher Tozier

Yalobusha Review

No abstract provided.

Bedroom, Abiquiu; Cow’S Skull, Lavonne J. Adams

Yalobusha Review

No abstract provided.

United States Food Law Update: Initial Food Safety Restructuring Efforts, Poultry Production Contract Reforms And Genetically Engineered Rice Litigation, A. Bryan Endres, Michaela N. Tarr

Journal of Food Law & Policy

This edition of the food law update will address recent events that may serve as bellwether signs that significant, long sought changes to the food and agricultural production system may be on the horizon. The first section of the update focuses on several general food safety initiatives. These efforts may, in the near term, coalesce into comprehensive food safety legislation. The second section analyzes two food safety actions relating to specific product categories: oysters and eggs. Section three provides a brief overview of poultry production contracts that may signal a broader restructuring of the legal relationships between farmers and the …

Xenoestrogen-Specific Mechanisms Of Developmental Reprogramming Correlate With Gene Expression And Tumor Development, Kristen L. Greathouse

Dissertations and Theses (Open Access)

Environmental exposures during sensitive windows of development can reprogram normal physiological responses and alter disease susceptibility later in life in a process known as developmental reprogramming. We have shown that neonatal exposure to the xenoestrogen diethylstilbestrol (DES) can developmentally reprogram the reproductive tract in genetically susceptible Eker rats giving rise to complete penetrance of uterine leiomyoma. Based on this, we hypothesized that xenoestrogens, including genistein (GEN) and bisphenol A (BPA), reprogram estrogen-responsive gene expression in the myometrium and promote the development of uterine leiomyoma. We proposed the mechanism that is responsible for the developmental reprogramming of gene expression was through …

Targeted Inhibition Of Sp1 Transcription Factor And Anti-Angiogenesis Of Human Pancreatic Cancer, Zhiliang Jia

Dissertations and Theses (Open Access)

Transcription factor Specificity Protein 1(Sp1) is reported to be essential for vascular endothelial growth factor (VEGF) constitutive expression in human pancreatic adenocarcinoma. The definitive role of Sp1 in angiogenesis, the impact of anti-angiogenic therapy on the Sp1/ VEGF signaling and the Sp1 signaling alteration on the anti-angiogenic therapy effect are unclear. The understanding of Sp1 regulation on VEGF and their interactions has significant clinical implications. Sp1 and VEGF expression and microvessel density (MVD) were analyzed using pancreatic cancer patients specimens through immunohistochemistry staining. The impact of Sp1 expression alternation on angiogenesis and tumor progression in nude mice were determined by …

Preeclampsia, Autoimmunity And The At1 Receptor, Roxanna A. Irani

Dissertations and Theses (Open Access)

Preeclampsia (PE) is a disease of late pregnancy characterized by maternal hypertension and proteinuria. It is associated with preterm delivery and significant perinatal morbidity and mortality. Despite affecting ~7% of first pregnancies, there is no effective screening method to identify women at risk, nor is there a definitive treatment other than delivery of the baby and placenta. Though the pathogenesis of PE remains unclear, an imbalance in the renin-angiotensin and immune systems are thought to be major contributors. Bridging these two concepts, it has recently been shown that women with PE harbor specific autoantibodies: the angiotensin II type 1 receptor …

Analysis Of Variation In Clubfoot Candidate Genes, Audrey R. Ester

Dissertations and Theses (Open Access)

Isolated clubfoot, a common birth defect occurring in more than 135,000 livebirths worldwide each year, is associated with significant health care and financial burdens. Clubfoot is defined by forefoot adduction, hindfoot varus, midfoot cavus and hindfoot equinus. Isolated clubfoot, which is the focus of these studies, is distinct from syndromic clubfoot because there are no other associated malformations. Population, family, twin and segregation analysis studies provide evidence that genetic and environmental factors play an etiologic role in isolated clubfoot. The studies described in this thesis were performed to define the role of genetic variation in isolated clubfoot. Interrogation of a …

Damage-Induced Inflammation And Nociceptive Hypersensitivity In Drosophila Larvae, Daniel T. Babcock

Dissertations and Theses (Open Access)

Mounting an effective response to tissue damage requires a concerted effort from a number of systems, including both the immune and nervous systems. Immune-responsive blood cells fight infection and clear debris from damaged tissues, and specialized pain receptors become hypersensitive to promote behavior that protects the damaged area while it heals. To uncover the cellular and molecular mechanisms underlying these processes, we have developed a genetically tractable invertebrate model of damage-induced inflammation and pain hypersensitivity using Drosophila larvae.

To study wound-induced inflammation, we generated transgenic larvae with fluorescent epidermal cells and blood cells (hemocytes). Using live imaging, we monitored the …

Measurement Of The Vascular Input Function In Mice For Dce-Mri, Dustin K. Ragan

Dissertations and Theses (Open Access)

DCE-MRI is an important technique in the study of small animal cancer models because its sensitivity to vascular changes opens the possibility of quantitative assessment of early therapeutic response. However, extraction of physiologically descriptive parameters from DCE-MRI data relies upon measurement of the vascular input function (VIF), which represents the contrast agent concentration time course in the blood plasma. This is difficult in small animal models due to artifacts associated with partial volume, inflow enhancement, and the limited temporal resolution achievable with MR imaging. In this work, the development of a suite of techniques for high temporal resolution, artifact resistant …

Role Of Dopamine Of Nucleus Accumbens In Behavioral Sensitization To Methylphenidate, Sheshali J. Wanchoo

Dissertations and Theses (Open Access)

Behavioral sensitization is defined as the subsequent augmentation of the locomotor response to a drug following repeated administrations of the drug. It is believed to occur due to alterations in the motive circuit in the brain by stressors, central nervous system stimulants, and similar stimuli. The motive circuit (or mesocorticolimbic system) consists of several interconnected nuclei that determine the behavioral response to significant biological stimuli. A final target of the mesocorticolimbic system is the nucleus accumbens (NAc), which is a key structure linking motivation and action. In particular, the dopaminergic innervations of the Nac are considered to be essential in …

Gsk3 Mediates Signaling Upstream Of Akt, Debra L. Smith

Dissertations and Theses (Open Access)

The phosphatidylinositide 3 kinase (PI3K)/Akt signaling network plays a pivotal role in multiple cellular functions. PI3K links the extracellular growth factor receptors to the serine-threonine kinase Akt which, through phosphorylation of numerous intracellular proteins, mediates increased cell growth, survival, motility and proliferation. The significance of the PI3K/Akt signaling network to human malignancy is demonstrated by cancer-associated genetic aberrations at multiple levels in the PI3K/Akt pathway in many tumor lineages. These aberrations include mutation or amplification of Akt, catalytic and regulatory subunits of PI3K, and growth factor receptors upstream of PI3K. Inactivating mutations and decreased expression of the PTEN, a major …

Myogenin Modulates Exercise Endurance By Altering Skeletal Muscle Metabolism, James Eric Meadows

Dissertations and Theses (Open Access)

The function of myogenic regulatory factors (MRFs) during adult life is not well understood. The requirement of one of these MRFs, myogenin (Myog), during embryonic muscle development suggests an equally important role in adult muscle. In this study, we have determined the function of myogenin during adult life using a conditional allele of Myog. In contrast to embryonic development, myogenin is not required for adult viability, and Myog-deleted mice exhibited no remarkable phenotypic changes during sedentary life. Remarkably, sedentary Myog-deleted mice demonstrated enhanced exercise endurance during involuntary treadmill running. Altered blood glucose and lactate levels in sedentary Myog-deleted mice after …

Signaling Mechanisms That Control Gap Junctional Coupling Between Retinal Neurons, Wade Kothmann

Dissertations and Theses (Open Access)

Gap junctions between neurons form the structural substrate for electrical synapses. Connexin 36 (Cx36, and its non-mammalian ortholog connexin 35) is the major neuronal gap junction protein in the central nervous system (CNS), and contributes to several important neuronal functions including neuronal synchronization, signal averaging, network oscillations, and motor learning. Connexin 36 is strongly expressed in the retina, where it is an obligatory component of the high-sensitivity rod photoreceptor pathway. A fundamental requirement of the retina is to adapt to broadly varying inputs in order to maintain a dynamic range of signaling output. Modulation of the strength of electrical coupling …

A New Tumor Suppressor Gene Candidate Regulated By The Non-Coding Rna Pca3 In Human Prostate Cancer, Alessandro K. Lee

Dissertations and Theses (Open Access)

Prostate cancer is the second leading cause of cancer-related death and the most common non-skin cancer in men in the USA. Considerable advancements in the practice of medicine have allowed a significant improvement in the diagnosis and treatment of this disease and, in recent years, both incidence and mortality rates have been slightly declining. However, it is still estimated that 1 man in 6 will be diagnosed with prostate cancer during his lifetime, and 1 man in 35 will die of the disease.

In order to identify novel strategies and effective therapeutic approaches in the fight against prostate cancer, it …

The Consequences Of Disrupting The Mdm2-P53 Balance In Hematopoiesis, Hussein A. Abbas

Dissertations and Theses (Open Access)

The bone marrow accommodates hematopoietic stem cells and progenitors. These cells provide an indispensible resource for replenishing the blood constituents throughout an organism’s life. A tissue with such a high turn-over rate mandates intact cycling checkpoint and apoptotic pathways to avoid inappropriate cell proliferation and ultimately the development of leukemias. p53, a major tumor suppressor, is a transcription factor that regulates cell cycle, and induces apoptosis and senescence. Mice inheriting a hypomorphic p53 allele in the absence of Mdm2, a p53 inhibitor, have elevated p53 cell cycle activity and die by postnatal day 13 due to hematopoietic failure. Hematopoiesis progresses …

Eye Movement Measures Of Cognitive Control In Children With To Urette Syndrome, Cameron B. Jeter

Dissertations and Theses (Open Access)

Tourette Syndrome begins in childhood and is characterized by uncontrollable repetitive actions like neck craning or hopping and noises such as sniffing or chirping. Worst in early adolescence, these tics wax and wane in severity and occur in bouts unpredictably, often drawing unwanted attention from bystanders. Making matters worse, over half of children with Tourette Syndrome also suffer from comorbid, or concurrent, disorders such as attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). These disorders introduce anxious thoughts, impulsivity, inattention, and mood variability that further disrupt children with Tourette Syndrome from focusing and performing well at school and home. …

The Role Of Mucosal Epithelial Cells In Hiv-1 Infection, Danielle Fontenot

Dissertations and Theses (Open Access)

The predominant route of human immunodeficiency virus type 1 (HIV-1) transmission is infection across the vaginal mucosa. Epithelial cells, which form the primary barrier of protection against pathogens, are the first cell type at these mucosal tissues to encounter the virus but their role in HIV infection has not been clearly elucidated. Although mucosal epithelial cells express only low levels of the receptors required for successful HIV infection, productive infection does occur at these sites. The present work provides evidence to show that HIV exposure, without the need for productive infection, induces human cervical epithelial cells to produce Thymic Stromal …

Ampa Receptor Allosterism: Measurement Of The Conformational Changes In The Ligand Binding Domain Of A Functional Receptor, Jennifer Gonzalez-Mcgehee

Dissertations and Theses (Open Access)

Ionotropic glutamate receptors are important excitatory neurotransmitter receptors in the mammalian central nervous system that have been implicated in a number of neuropathologies such as epilepsy, ischemia, and amyotrophic lateral sclerosis. Glutamate binding to an extracellular ligand binding domain initiates a series of structural changes that leads to the formation of a cation selective transmembrane channel, which consequently closes due to desensitization of the receptor. The crystal structures of the AMPA subtype of the glutamate receptor have been particularly useful in providing initial insight into the conformational changes in the ligand binding domain; however, these structures are limited by crystallographic …

Type I Insulin-Like Growth Factor Receptor Tyrosine Kinase As A Molecular Target In Mantle Cell Lymphoma, Deeksha Vishwamitra

Dissertations and Theses (Open Access)

Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoid malignancy representing 5-10% of all non-Hodgkin’s lymphomas. It is distinguished by the t(11;14)(q13;q32) chromosomal translocation that juxtaposes the proto-oncogene CCND1, which encodes cyclin D1 at 11q13 to the IgH gene at 14q32. MCL patients represent about 6% of all new cases of Non-Hodgkin’s lymphomas per year or about 3,500 new cases per year. MCL occurs more frequently in older adults – the average age at diagnosis is the mid-60s with a male-to-female ratio of 2-3:1. It is typically characterized by the proliferation of neoplastic B-lymphocytes in the mantle zone of the …

The Expression And Cellular Localization Of Cc-Chemokine Receptor 5 (Ccr5) After Traumatic Brain Injury, Vuvi H. Nguyen

Dissertations and Theses (Open Access)

Traumatic brain injury results from a primary insult and secondary events that together result in tissue injury. This primary injury occurs at the moment of impact and damage can include scalp laceration, skull fraction, cerebral contusions and lacerations as well as intracranial hemorrhage. Following the initial insult, a delayed response occurs and is characterized by hypoxia, ischemia, cerebral edema, and infection. During secondary brain injury, a series of neuroinflammatory events are triggered that can produce additional damage but may also help to protect nervous tissue from invading pathogens and help to repair the damaged tissue. Brain microglia and astrocytes become …

Molecular Basis Of Corynebacterium Diphtheriae Virulence And Infection In The Caenorhabditis Elegans Model Host, Melissa M. Broadway

Dissertations and Theses (Open Access)

Corynebacterium diphtheriae is the causative agent of cutaneous and pharyngeal diphtheria in humans. While lethality is certainly caused by diphtheria toxin, corynebacterial colonization may primarily require proteinaceous fibers called pili, which mediate adherence to specific tissues. The type strain of C. diphtheriae possesses three distinct pilus structures, namely the SpaA, SpaD, and SpaH-type pili, which are encoded by three distinct pilus gene clusters. The pilus is assembled onto the bacterial peptidoglycan by a specific transpeptidase enzyme called sortase. Although the SpaA pili are shown to be specific for pharyngeal cells in vitro, little is known about functions of the three …

Developmental Changes In The Structure And Composition Of The Postsynaptic Density, Matthew T. Swulius

Dissertations and Theses (Open Access)

The development of the brain and its underlying circuitry is dependent on the formation of trillions of chemical synapses, which are highly specialized contacts that regulate the flow of information from one neuron to the next. It is through these synaptic connections that neurons wire together into networks capable of performing specific tasks, and activity-dependent changes in their structural and physiological state is one way that the brain is thought to adapt and store information. At the ultrastructural level, developmental and activity-dependent changes in the size and shape of dendritic spines have been well documented, and it is widely believed …

The Role Of Platelets In Ovarian Carcinoma, Rebecca L. Stone

Dissertations and Theses (Open Access)

Platelets represent one of the largest storage pools of angiogenic and oncogenic growth factors in the human body. The observation that thrombocytosis (platelet count >450,000/uL) occurs in patients with solid malignancies was made over 100 years ago. However, the clinical and biological implications as well as the underlying mechanism of paraneoplastic thrombocytosis associated with ovarian carcinoma remains unknown and were the focus of the current study.

Following IRB approval, patient data were collected on 619 patients from 4 U.S. centers and used to test associations between platelet count at initial diagnosis, clinicopathologic factors, and outcome. In vitro effects of plasma-purified …

Cellular And Developmental Functions Of The Xenopus Arvcf-Catenin:Kazrin Complex, Kyucheol Cho

Dissertations and Theses (Open Access)

Xenopus ARVCF (xARVCF), a member of p120-catenin subfamily, binds cadherin cytoplasmic domains to enhance cadherin metabolic stability, or when dissociated, modulates Rho-family GTPases. We previously found that xARVCF binds directly to Xenopus KazrinA (xKazrinA), a widely expressed, conserved protein that bears little homology to established protein families. xKazrinA is also known to influence keratinocyte proliferation-differentiation and cytoskeletal activity. In my study, I first evaluated the expression pattern of endogenous Kazrin RNA and protein in Xenopus embryogenesis as well as in adult tissues. We then collaboratively predicted the helical structure of Kazrin’s coiled-coil domain, and I obtained evidence of Kazrin’s dimerization/oligomerization. …

Biodegradation And Bioremediation Of Hexachlorocyclohexane Isomers, Chlorinated Ethenes, Chlorinated Benzenes And Benzene, Vijaikrishnah Elango

All Dissertations

ABSTRACT
Groundwater at an industrial site is contaminated with γ -hexachlorocyclohexane (HCH) and α-HCH (i.e., lindane) (0.3-0.5 ppm). Other contaminants in the 1-15 ppm range include 1,2,4-trichlorobenezene (TCB), 1,2-dichlorobenzene (DCB), 1,3-DCB, 1,4-DCB, chlorobenzene (CB), benzene, trichloroethene (TCE) and cis-1,2-dichloroethene (cDCE). The aquifer consists of a shallow layer of soil over fractured dolomite, where most of the contaminant mass resides. The objective of this study was to compare 1) anaerobic reductive dechlorination of the polychlorinated contaminants, followed by aerobic biodegradation of the daughter products (mainly DCBs, CB, and benzene); and 2) aerobic biodegradation of α- and γ-HCH, TCB, DCBs, CB and …

Understanding The Biological And Environmental Implications Of Nanomaterials, Sijie Lin

All Dissertations

The last two decades have witnessed the discovery, development, and large-scale manufacturing of novel nanomaterials. While nanomaterials bring in exciting and extraordinary properties in all areas of materials, electronics, mechanics, and medicine, they also could generate potential adverse effects in biological systems and in the environment. The currently limited application of nanomaterials in biological and ecological systems results from the insufficient and often controversial data on describing the complex behaviors of nanomaterials in living systems. The purpose of this dissertation intends to fill such a knowledge void with methodologies from the disciplines of biophysics, biology, and materials science and engineering. …

Sustainable Community Tourism Development: The Case Of Tanzania, Susan Slocum

All Dissertations

This dissertation's objective is to understand the constraints to economic participation by indigenous Tanzanians living in and around current and/or future tourism destinations. Using qualitative methods, this study investigated local perceptions and involvement in tourism economies by comparing independent case studies in three destinations differing in land tenure. Fifteen village-based focus groups were employed in villages around Pangani District (Tanga Region), Amani Nature Reserve (Tanga Region), and Arumeru District (Arusha Region). The purpose of the village-based focus groups was to evaluate local access to physical, financial, human, social, and natural capital as a means to encourage economic participation in the …