Medicine and Health Sciences Commons^™

Mechanoregulation Of Leading Edge Pka Activity During Ovarian Cancer Cell Migration, Andrew J. Mckenzie

Graduate College Dissertations and Theses

Ovarian cancer is the deadliest of all the gynecologic cancers and is known for its clinically occult and asymptomatic dissemination. Most ovarian malignancies are diagnosed in the late stages of the disease and the high rate of morbidity is thought to be due, in part, to the highly metastatic nature of ovarian carcinomas. Cancer metastasis relies on the ability of cells to migrate away from primary tumors and invade into target tissues. Though the processes are distinct, cancer cell invasion relies on the underlying migration machinery to invade target tissues.

Cell migration requires the coordinated effort of numerous spatially-regulated signaling …

A Novel Approach For The Identification Of Cytoskeletal And Adhesion A-Kinase Anchoring Proteins, Laura Taylor Director

Graduate College Dissertations and Theses

A-kinase anchoring proteins (AKAPs) are signaling scaffolds which provide spatial and temporal organization of signaling pathways in discrete subcellular compartments. Through tethering the cyclic-AMP dependent protein kinase A (PKA), AKAPs target PKA activity to distinct regions in the cell, bringing PKA in close proximity to its target proteins. This provides a high level of specificity and regulation of PKA and its role in mediating a number of biological processes, one of which is cell migration. Cell migration is a highly dynamic and fundamental process, when misregulated can lead to a number of pathologies. The process of cell migration requires integration …

Classical And Alternative Nuclear Factor-Kappab In Epithelium: Impacts In Allergic Airway Disease And Avenues For Redox Regulation, Jane Elizabeth Tully

Graduate College Dissertations and Theses

Nuclear Factor kappaB (NF-êB) is a transcription factor whose activation is increased in settings of allergic asthma. At least two parallel NF-êB pathways exist: the classical pathway, which plays a role in inflammation and cell survival, and the alternative pathway, which regulates lymphoid cell development and organogenesis. The classical NF-êB pathway regulates inflammatory responses derived from lung epithelial cells; however, the role of the alternative pathway in lung epithelial cells remains unclear. We demonstrate that both classical and alternative NF-êB are activated in lung epithelial cells in response to multiple pro-inflammatory agonists, and siRNA-mediated knockdown of alternative NF-êB proteins largely …

Provision Of Reproductive Health Care Services By Nurse Practitioners And Certified Nurse Midwives: Unintended Pregnancy Prevention And Management In Vermont, Erica Lyons

Graduate College Dissertations and Theses

Background: In the United States, currently about half (49%) of the 6.7 million pregnancies are reported as mistimed or unplanned, and this rate of unintended pregnancy is significantly higher than the rate in most other developed countries. Abortion services are critical to the prevention and management of unintended pregnancies. Abortion in the United States has been legal since the 1973; however this right has little meaning without access to safe abortion care and access is declining. Medication abortion, the use of medications to induce abortion and terminate an early pregnancy, has been legal in the United States since 2000, is …

Meta-Analysis Of Studies Investigation Of The Effect Of Smoking Cessation On Impatience, Miriam Claire Dash

Graduate College Dissertations and Theses

(DSM-IV-TR/) nor in withdrawal scales. However, a related term, "impatience" is listed in some nicotine withdrawal scales. (Hughes J. R., Measurements of the Effects of Abstinence from Tobacco: A Qualitative Review, 2007). Although impatience is not a synonym of impulsivity, both share the synonym "impetuous". Therefore, impatience can be considered a measure of impulsivity. Although some reviews of the effect of smoking cessation on impatience have occurred, we know of no quantitative review of prospective studies of whether smoking cessation increases impatience.

Purpose: To evaluate the effect of smoking cessation on impatience as measured by the Minnesota Nicotine Withdrawal Scale-Revised …

Mitochondrial Structure And Function As A Therapeutic Target In Malignant Mesothelioma, Brian Cunniff

Graduate College Dissertations and Theses

Malignant mesothelioma (MM) is a rare tumor associated with occupational exposure to asbestos with no effective treatment regime. Evaluation of mitochondrial function in human MM cell lines revealed a common tumor phenotype: in comparison to immortalized or primary human mesothelial cells, MM tumor cells displayed a more oxidized mitochondrial environment, increased expression of mitochondrial antioxidant enzymes, and altered mitochondrial metabolism. Earlier work by our laboratory indicated that increases in mitochondrial reactive oxygen species (mROS) in MM cell lines supports expression of FOXM1, an oncogenic transcription factor that contributes to increased cell proliferation and chemoresistance. These studies sought to investigate targeting …

Determining The Role Of The Ergic-53 Cargo Receptor Complex In Arenavirus Propagation, Joseph P. Klaus

Graduate College Dissertations and Theses

Arenaviruses and hantaviruses are human pathogens that cause significant morbidity and mortality. The current lack of vaccines and treatment options for these viruses is a global concern. Despite producing only 4 proteins, these viruses are able to maintain a persistent and asymptomatic infection in wild rodents while being continuously shed into the environment. In humans, these viruses cause a spectrum of diseases ranging from aseptic meningitis to severe hemorrhagic fever syndromes. Little is known about how arenavirus and hantavirus proteins engage and interact with the human proteome during the complex process of viral biogenesis, or how the interactions with human …

An Investigation Of Epigenetic Contributions To Inter-Animal And Age Dependent Variation In The Bovine Innate Immune Response., Benjamin Green

Graduate College Dissertations and Theses

Mastitis represents a major issue within the dairy industry responsible for economic loss via decreased animal productivity and associated veterinary costs. Currently, there is a push to identify a phenotypic innate immune response that will yield dairy cows with an enhanced resistance to mastitis. Bovine dermal fibroblasts were used as a cell model to measure the response of individuals to Gram-negative bacterial stimuli through the TLR4 signaling pathway. Fibroblast cultures were isolated from 15 dairy heifers at 5, 11, and 16 months of age in order to determine the variability in responsiveness to LPS as well as to monitor the …

An Analysis Of The Effect Of Ss-Hydroxy-Ss-Methylbutyrate On The Flight Ability And Lifespan Of Drosophila Melanogaster, Alexandra Elizabeth Beattie

Graduate College Dissertations and Theses

As muscle function deteriorates with age, the discovery of new ways to enhance the quality of human life by stunting inevitable aging processes, such as sarcopenia, is a subject of great interest to aging populations, to health care professionals and to nutritional companies. β-hydroxy-β-methylbutyrate (HMB) enhances muscle strength in humans and attenuates disease-induced and disuse-dependent atrophy in rodents. We investigated the feasibility of utilizing Drosophila as a model organism to study the biological effects of HMB in aging muscle. Using flight ability as an index of muscle function and monitoring the lifespan of flies, we found that normal food supplemented …

Direct And Indirect Targets Of Jagged1/Notch1 Signaling In Reactive Astrocytes., Matthew David Lecomte

Graduate College Dissertations and Theses

Stroke or cerebral vascular accident (CVA) is the 4th leading cause of mortality and the principle cause of long-term disability in the United States. Unfortunately, current reperfusion-based treatments (e.g. thrombolysis, tPA) cannot be administered to the majority of patients presenting with ischemic stroke. Accordingly, new treatments for ischemic stroke are desperately needed.

Reactive astrocytes perform key roles in tissue repair and remodeling following stroke such as preservation and repair of the blood-brain barrier, modulation of immune cell invasion, glutamate uptake and neuroprotection, and glial scar formation. The proliferative subpopulation of reactive astrocytes found immediately adjacent to the infarct core after …

The Contribution Of Purinergic P2x And P2y Receptors To The Excitability Of Mouse Vomeronasal Sensory Neurons, Jonathan Vick

Graduate College Dissertations and Theses

Olfaction, the sense of smell, allows animals to perceive the multitude of volatile and nonvolatile molecules present in the environment. In many mammals, such as mice and rats, there are four unique chemosensory organs including the (1) main olfactory epithelium (MOE), (2) septal organ, (3) Grüneberg ganglion, and (4) vomeronasal organ (VNO). While the VNO detects some general volatile odorants, it is further specialized for the detection of behaviorally relevant nonvolatile odorants or pheromones. In rodents, the VNO is encased within a bony capsule and located at the base of the nasal cavity. Odorants are detected by vomeronasal sensory neuron …

Investigation Of Dna And Rna Markers By Novel Technologies Demonstrates Dna Content Intratumoral Heterogeneity And Long Non-Coding Rna Aberrations In Breast Tumors, Zhouwei Zhang

Graduate College Dissertations and Theses

BACKGROUND:

Breast cancer is the most commonly diagnosed cancer and second leading cancer death cause among females in the U.S.A. About 1 in 8 women in U.S will develop invasive breast cancer over the course of her lifetime. In 2013, 234,580 new invasive breast cancer cases are expected to occur in women within the US and approximately 64,640 non-invasive carcinomas in situ were diagnosed in 2013, most of which were ductal carcinoma in situ (DCIS). Along with technological advances, a wide variety of candidate biomarkers have been proposed for cancer diagnosis and prognosis, including DNA content and non-coding RNA. Current …