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Investigating The Role Of Nuclear Foxo3 In Pten-Null Glioblastomas, Lilia Sanchez

Theses and Dissertations

The PI3K pathway activates AKT, leading to inactivation of FOXO transcription factors. Loss of PTEN results in constitutive inactivation of tumor suppressor FOXO. There is increasing evidence that FOXO resides and promotes transcriptional activity in the nucleus despite high PI3K output within certain advanced cancers and embryonic stem cells. Here, we investigate the regulation and roles of FOXO transcription factors in glioblastoma and basal breast cancer. First, we built and published genetic models to investigate the roles of FOXO transcription factors in cancer cell lines for glioblastoma (U87MG). We examined the function of FOXO transcription factors using these genetic models …

2018 Summer Newsletter, Morehead State University. Nursing Department.

Nursing Department Publications Archive

2018 Summer Newsletter of the Department of Nursing at Morehead State University.

With Some Risk-Taking And Luck: A Veterinarian's Adventures In Viral Immunology., Luis J. Sigal

Department of Microbiology and Immunology Faculty Papers

No abstract provided.

Retrograde Axonal Transport Of Rabies Virus Is Unaffected By Interferon Treatment But Blocked By Emetine Locally In Axons., Margaret A. Macgibeny, Orkide O. Koyuncu, Christoph Wirblich, Matthias J. Schnell, Lynn W. Enquist

Department of Microbiology and Immunology Faculty Papers

Neuroinvasive viruses, such as alpha herpesviruses (αHV) and rabies virus (RABV), initially infect peripheral tissues, followed by invasion of the innervating axon termini. Virus particles must undergo long distance retrograde axonal transport to reach the neuron cell bodies in the peripheral or central nervous system (PNS/CNS). How virus particles hijack the axonal transport machinery and how PNS axons respond to and regulate infection are questions of significant interest. To track individual virus particles, we constructed a recombinant RABV expressing a P-mCherry fusion protein, derived from the virulent CVS-N2c strain. We studied retrograde RABV transport in the presence or absence of …

Extended Poisson Models For Count Data With Inflated Frequencies, Monika Arora

Mathematics & Statistics Theses & Dissertations

Count data often exhibits inflated counts for zero. There are numerous papers in the literature that show how to fit Poisson regression models that account for the zero inflation. However, in many situations the frequencies of zero and of some other value k tends to be higher than the Poisson model can fit appropriately. Recently, Sheth-Chandra (2011), Lin and Tsai (2012) introduced a mixture model to account for the inflated frequencies of zero and k. In this dissertation, we study basic properties of this mixture model and parameter estimation for grouped and ungrouped data. Using stochastic representation we show …

An Exploration Of Practicum Students' Experiences Of Meaning-Making Through Altruism, Debra Paige Lewis

Counseling & Human Services Theses & Dissertations

Finding meaning in one’s work as a counselor has been demonstrated as an important step in the development of altruism, an essential component of counselor effectiveness. Previous studies in counselor education-related research involving program outcomes focus on the core skills of counseling such as knowledge, skill building, self-appraisal and self-efficacy. Yet little investigation has concentrated on the internal rewards of the clinical experience, such as the meaning found in or the altruism development derived specifically from the practicum or internship. This dissertation research took a phenomenological approach to explore the meaning-making and altruism development of counselor education practicum students providing …

Plastics And Microplastics As Vectors For Bacteria And Human Pathogens, Amanda Lee Laverty

OES Theses and Dissertations

Since plastics degrade very slowly, they remain in the environment on much longer timescales than most natural substrates and can thus provide a novel habitat for colonization by bacterial communities. The full spectrum of relationships between plastics and bacteria, however, is little understood. The objective of this study was to examine marine plastic pollution as a substrate for bacteria, with particular focus on Vibrio spp., including the human pathogens, Vibrio cholerae, Vibrio parahaemolyticus, and Vibrio vulnificus.

Colonization experiments were set up in a tributary of the lower Chesapeake Bay to follow Vibrio spp. colonization and …

Sequence-Based Simulation-Optimization Framework With Application To Port Operations At Multimodal Container Terminals, Mariam Aladdin Kotachi

Engineering Management & Systems Engineering Theses & Dissertations

It is evident in previous works that operations research and mathematical algorithms can provide optimal or near-optimal solutions, whereas simulation models can aid in predicting and studying the behavior of systems over time and monitor performance under stochastic and uncertain circumstances. Given the intensive computational effort that simulation optimization methods impose, especially for large and complex systems like container terminals, a favorable approach is to reduce the search space to decrease the amount of computation.

A maritime port can consist of multiple terminals with specific functionalities and specialized equipment. A container terminal is one of several facilities in a port …

Psychometric Properties Of The Satisfaction With Life Scale Among Arab Americans, Afnan Musaitif

Dissertations (1934 -)

The body of literature on the Arab American population is growing both in breadth and depth. A biopsychosocial perspective has been applied in a review of the research on this population revealing gaps in the area of well-being among Arab Americans. Particularly, few studies have investigated well-being as defined by positive constructs, positive psychology, subjective well-being, or psychological wellbeing. More specifically, measures of these conceptualizations of well-being beyond the deficit model have not been validated among Arab Americans. This study aims to investigate the psychometric properties of one of the most commonly used subjective well-being instruments, the Satisfaction With Life …

The Photodynamic And Structural Analyses Of Advanced Materials For Solar Fuel Conversion, Brian Pattengale

Dissertations (1934 -)

Mitigating the current and future climate and pollution issues that have been brought on by the combustion of fossil fuels is of utmost importance and will rely on, in part, the availability of renewable fuel sources. Of the possible sources of energy, solar is abundant, but must be harnessed efficiently and stored as a solar fuel to overcome the current storage issues that limit photovoltaic cells. One such fuel, H2(g), represents a carbon-neutral source of energy if it can be efficiently liberated from water via the water splitting reaction. Thus, much attention is focused on designing materials to perform the …

Strategies For The Modulation Of Protease Activated Receptors (Pars), Disha M. Gandhi

Dissertations (1934 -)

Protease-activated receptors (PARs) are class A G protein-coupled receptors (GPCRs) with 4 subtypes (PAR 1 – 4) and with a unique mode of action. PARs are cleaved by extracellular proteases at the N-terminus, creating a new tethered ligand that activates the receptor and transduces biological signals into the cell. PARs have been implicated in various productive and pathological signals, including those related to thrombosis, inflammation, reperfusion injury, and cancer cell metastasis. Despite the fact that PARs are attractive as drug targets, their intramolecular mode of activation makes it challenging to modulate them with drugs in a selective manner, and only …

Photochemical Expulsion Of Leaving Groups From A Naphthothiophene-2-Carboxamide Linked To A Chromophore, Lingzi Li

Dissertations (1934 -)

Two bichromophoric systems were synthesized which have thioxanthone as the chromophore that absorbs the incident light and a naphthothiophene-2-carboxanilide, which serves as a triplet excited state energy acceptor. Upon excitation the triplet excited state of the thioxanthone is populated via intersystem crossing, which is efficient with isc = 0.68. Based on the relative energies of the triplet excited states of thioxanthone (ET = 65 kcal mol-1) and naphthothiophene (ET = 51 kcal mol-1), the subsequent triplet excited state energy transfer to generate the triplet excited state of the naphthothiophene-2-carboxamide should be a very rapid process that is 14 kcal mol1 …

Change In Bone Mineral Density Among High Frequency Apheresis Blood Donors, Walter Bialkowski

Dissertations (1934 -)

Exposure to citrate anticoagulant during apheresis blood donation induces significant decreases in serum ionized calcium with subsequent perturbations to parathyroid hormone, vitamin D, and markers of bone remodeling. Cross-sectional studies of bone mineral density (BMD) among apheresis donors exhibit conflicting results. Resolving the potential impact of the highest apheresis donation frequency represents a significant knowledge gap in ensuring adequate protections for volunteer apheresis blood donors. ALTRUYST (NCT02655055) was a randomized, longitudinal, controlled clinical trial designed to determine if repeated exposure to citrate through apheresis donation reduces BMD. Male donors, 18-65 years of age with no more than five previous apheresis …

The Discovery And Characterization Of Small Molecule Inhibitors Of Pyruvate Carboxylase, Brittney Wyatt

Dissertations (1934 -)

Pyruvate carboxylase is a metabolically important enzyme that has been implicated in a wide range of diseases and infections such as cancer, diabetes and listeriosis. Despite the importance of pyruvate carboxylase in these diseases and infections, there are no selective and potent small molecule effectors available to study pyruvate carboxylase both in vitro and in vivo. Effective small molecule effectors of pyruvate carboxylase will expand the biochemical toolkit to facilitate the investigation of the structure, regulation and specific cellular role of pyruvate carboxylase. To discover small molecule effectors of pyruvate carboxylase, a novel fixed time assay was developed. The assay …

Pituitary Adenylate Cyclase-Activation Polypeptide (Pacap) Regulates Feeding In The Rat Striatum And Hypothalamus, Matthew M. Hurley

Dissertations (1934 -)

The following dissertation focuses on preclinical rodent feeding paradigms that were designed to examine the mechanisms by which the brain regulates caloric (homeostatic) and palatability (hedonic)-driven feeding. Taken together, my findings suggest differentially motivated feeding can, in part, signal through isolated non-overlapping mechanisms in the brain. Furthermore, some of these mechanisms occur in similar neurocircuits that have been implicated in other compulsive behaviors, such as drug abuse. In an effort to support the argument that binge eating disorder (BED) and substance abuse share similar behavioral and molecular targets, we first demonstrate that the development of BED in rodents is attenuated …

Inhibition Of Ferrochelatase Impairs Vascular Enos/No And Sgc/Cgmp Signaling, Bin Zhang, Norah Alruwaili, Sharath Kandhi, Wensheng Deng, An Huang, Michael S. Wolin, Dong Sun

NYMC Faculty Publications

Ferrochelatase (FECH) is an enzyme necessary for heme synthesis, which is essential for maintaining normal functions of endothelial nitric oxide synthase (eNOS) and soluble guanylyl cyclase (sGC). We tested the hypothesis that inhibition of vascular FECH to attenuate heme synthesis downregulates eNOS and sGC expression, resulting in impaired NO/cGMP-dependent relaxation. To this end, isolated bovine coronary arteries (BCAs) were in vitro incubated without (as controls) or with N-methyl protoporphyrin (NMPP; 10-5-10-7M; a selective FECH antagonist) for 24 and 72 hours respectively. Tissue FECH activity, heme, nitrite/NO and superoxide levels were sequentially measured. Protein expression of FECH, eNOS and sGC was …

Practical Application Of Microrna Markers In The Diagnosis Of Multiple Sclerosis In The Realm Of Routine Clinical Neurology, Robert A. Ollar

NYMC Faculty Publications

No abstract provided.

The Combination Of Human Urinary Kallidinogenase And Mild Hypothermia Protects Adult Rats Against Hypoxic-Ischemic Encephalopathy-Induced Injury By Promoting Angiogenesis And Regeneration, Xiaoya Gao, Haiting Xie, Shuzhen Zhu, Bin Yu, Ying Xian, Penghua Wang, Qing Wang

NYMC Faculty Publications

Objectives: Human Urinary Kallidinogenase (HUK) is a tissue kallikrein that plays neuroprotective role in ischemic conditions via different mechanisms. Mild hypothermia (MH) is another robust neuroprotectant that reduces mortality but does not profoundly ameliorate the neurological outcome in hypoxic-ischemic encephalopathy (HIE) patients. However, whether the combination of HUK and MH can be used as a promising neuroprotective treatment in HIE is unknown. Methods: One-hundred and forty-four adult Wistar rats were randomly divided into five groups: Sham, HIE, HUK, MH and a combination of HUK and MH treatment. The HIE rat model was established by right carotid dissection followed by hypoxia …

In Vitro And In Silico Liver Models: Current Trends, Challenges And Opportunities, Andrey Poloznikov, Irina Gazaryan, Maxim Shkurnikov, Sergey Nikulin, Oxana Drapkina, Ancha Baranova, Alexander Tonevitsky

NYMC Faculty Publications

Most common drug development failures originate from either bioavailability problems, or unexpected toxic effects. The culprit is often the liver, which is responsible for biotransformation of a majority of xenobiotics. Liver may be modeled using "liver on a chip" devices, which may include established cell lines, primary human cells, and stem cell-derived hepatocyte-like cells. The choice of biological material along with its processing and maintenance greatly influence both the device performance and the resultant toxicity predictions. Impediments to the development of "liver on a chip" technology include the problems with standardization of cells, limitations imposed by culturing and the necessity …

Smooth Muscle-Specific Bcl6+/- Knockout Abrogates Sex Bias In Chronic Hypoxia-Induced Pulmonary Arterial Hypertension In Mice, Yang-Ming Yang, Pravin B. Sehgal

NYMC Faculty Publications

The "estrogen paradox" in pulmonary arterial hypertension (PAH) refers to observations that while there is a higher incidence of idiopathic PAH in women, rodent models of PAH show male dominance and estrogens are protective. To explain these differences, we previously proposed the neuroendocrine-STAT5-BCL6 hypothesis anchored in the sex-biased and species-specific patterns of growth hormone (GH) secretion by the pituitary, the targeting of the hypothalamus by estrogens to feminize GH secretion patterns, and the role of the transcription factors STAT5a/b and BCL6 as downstream mediators of this patterned GH-driven sex bias. As a test of this hypothesis, we previously reported that …

Dynamical Patterning Modules, Biogeneric Materials, And The Evolution Of Multicellular Plants, Mariana Benitez, Valeria Hernandez-Hernandez, Stuart A. Newman, Karl Niklas

NYMC Faculty Publications

Comparative analyses of developmental processes across a broad spectrum of organisms are required to fully understand the mechanisms responsible for the major evolutionary transitions among eukaryotic photosynthetic lineages (defined here as the polyphyletic algae and the monophyletic land plants). The concepts of dynamical patterning modules (DPMs) and biogeneric materials provide a framework for studying developmental processes in the context of such comparative analyses. In the context of multicellularity, DPMs are defined as sets of conserved gene products and molecular networks, in conjunction with the physical morphogenetic and patterning processes they mobilize. A biogeneric material is defined as mesoscale matter with …

Development Of Nash In Obese Mice Is Confounded By Adipose Tissue Increase In Inflammatory Nov And Oxidative Stress, David Sacerdoti, Shailendra P. Singh, Joseph Schragenheim, Lars Bellner, Aliza Meissner, Ilana Grant, Nader G. Abraham

NYMC Faculty Publications

Aim: Nonalcoholic steatohepatitis (NASH) is the consequence of insulin resistance, fatty acid accumulation, oxidative stress, and lipotoxicity. We hypothesize that an increase in the inflammatory adipokine NOV decreases antioxidant Heme Oxygenase 1 (HO-1) levels in adipose and hepatic tissue, resulting in the development of NASH in obese mice. Methods: Mice were fed a high fat diet (HFD) and obese animals were administered an HO-1 inducer with or without an inhibitor of HO activity to examine levels of adipose-derived NOV and possible links between increased synthesis of inflammatory adipokines and hepatic pathology. Results: NASH mice displayed decreased HO-1 levels and HO …

Comparative Effectiveness Of Secukinumab And Etanercept In Biologic-Naïve Patients With Psoriatic Arthritis Assessed By Matching-Adjusted Indirect Comparison., Philip Mease, Ernest Choy, Peter Nash, Chrysostomos Kalyvas, Matthias Hunger, Luminita Pricop, Kunal K Gandhi, Steffen M Jugl, Howard Thom

Articles, Abstracts, and Reports

OBJECTIVE: Matching-adjusted indirect comparison (MAIC) can be used to assess the comparative effectiveness of two treatments indirectly using data from randomized placebo-controlled trials. This MAIC assessed the comparative effectiveness of secukinumab (an anti-interleukin-17A) and etanercept (a tumor necrosis factor inhibitor) in a target population of biologic-naïve patients with psoriatic arthritis (PsA).

METHODS: Individual patient data pooled from FUTURE 2 (NCT01752634), FUTURE 3 (NCT01989468), and FUTURE 5 (NCT02404350) (secukinumab: 150 mg, n=458 and 300 mg, n=461) were matched to data from the population in the NCT00317499 trial (etanercept 25 mg, n=101) using MAIC methodology, by adjusting for clinical and demographic baseline …

July 2018 News Releases, University Of Montana--Missoula. Office Of University Relations

University of Montana News Releases, 1928, 1956-present

No abstract provided.

Bacteriophages For Treating American Foulbrood And The Neutralization Of Paenibacillus Larvae Spores, Thomas Scott Brady

Theses and Dissertations

The causative agent of the most devastating honeybee disease, American foulbrood (AFB), is the spore-forming bacterium Paenibacillus larvae. To prevent AFB outbreaks beekeepers prophylactically treat their hives with antibiotics even though it decreases the overall health of uninfected hives. A new treatment for AFB is needed due to recent legislation against using antibiotics, antibiotic resistance developing in P. larvae, and the resilience of P. larvae spores. Bacteriophages, or phages, are an attractive alternative to traditional antibiotics because of their specificity and ability to evolve alongside their target bacterium. In this study, two phage cocktails were developed for the …

Data Assimilation In The Boussinesq Approximation For Mantle Convection, Shane Alexander Mcquarrie

Theses and Dissertations

Many highly developed physical models poorly approximate actual physical systems due to natural random noise. For example, convection in the earth's mantle—a fundamental process for understanding the geochemical makeup of the earth's crust and the geologic history of the earth—exhibits chaotic behavior, so it is difficult to model accurately. In addition, it is impossible to directly measure temperature and fluid viscosity in the mantle, and any indirect measurements are not guaranteed to be highly accurate. Over the last 50 years, mathematicians have developed a rigorous framework for reconciling noisy observations with reasonable physical models, a technique called data assimilation. …

A Functionalist Account Of Human Uniqueness, Anthony Bolos

Faith and Philosophy: Journal of the Society of Christian Philosophers

No abstract provided.

Plasticity Reveals Hidden Resistance To Extinction Under Climate Change In The Global Hotspot Of Salamander Diversity, Eric A. Riddell, Jonathan P. Odom, Jason D. Damm, Michael W. Sears

Publications

Extinction rates are predicted to rise exponentially under climate warming, but many of these predictions ignore physiological and behavioral plasticity that might buffer species from extinction. We evaluated the potential for physiological acclimatization and behavioral avoidance of poor climatic conditions to lower extinction risk under climate change in the global hotspot of salamander diversity, a region currently predicted to lose most of the salamander habitat due to warming. Our approach integrated experimental physiology and behavior into a mechanistic species distribution model to predict extinction risk based on an individual’s capacity to maintain energy balance with and without plasticity. We assessed …

Characterization Of A Soybean (Glycine Max L. Merr.) Germplasm Collection For Root Traits, Harrison Gregory Fried, Sruthi Narayanan, Benjamin Fallen

Publications

Root systems that improve resource uptake and penetrate compacted soil (hardpan) are important for improving soybean (Glycine max L. Merr.) productivity in optimal and sub-optimal environments. The objectives of this research were to evaluate a soybean germplasm collection of 49 genotypes for root traits, determine whether root traits are related with plant height, shoot dry weight, chlorophyll index, and seed size, and identify genotypes that can penetrate a hardpan. Plants were maintained under optimal growth conditions in a greenhouse. Single plants were grown in mesocosms, constructed of two stacked columns (top and bottom columns had 25 and 46 cm …

High Circulatory Leptin Mediated Nox-2-Peroxynitrite-Mir21 Axis Activate Mesangial Cells And Promotes Renal Inflammatory Pathology In Nonalcoholic Fatty Liver Disease, Firas Alhasson, Ratanesh K. Seth, Sutapa Sarkar, Diana A. Kimono, Muayad S. Albadrani, Diptadip Dattaroy, Varun Chandrashekaran, Geoffry Scott, Samir Raychoudhury, Mitzi Nagarkatti, Prakash Nagarkatti, Anna Mae Diehl, Saurabh Chatterjee

Faculty Publications

High circulatory insulin and leptin followed by underlying inflammation are often ascribed to the ectopic manifestations in non-alcoholic fatty liver disease (NAFLD) but the exact molecular pathways remain unclear. We have shown previously that CYP2E1-mediated oxidative stress and circulating leptin in NAFLD is associated with renal disease severity. Extending the studies, we hypothesized that high circulatory leptin in NAFLD causes renal mesangial cell activation and tubular inflammation via a NOX2 dependent pathway that upregulates proinflammatory miR21. High-fat diet (60% kcal) was used to induce fatty liver phenotype with parallel insulin and leptin resistance. The kidneys were probed for mesangial cell …