Life Sciences Commons^™

Investigating The Regulation Of Epithelial-Mesenchymal Transition Through Fibronectin-Mediated Tgf-Β1 Mechanotransduction Using In Vitro Models Of Triple-Negative Breast Cancer, Michael M. Sofroniou

Theses and Dissertations

TGF-β1 is a potent regulator of epithelial-mesenchymal transtion (EMT), a cellular
transdifferentation process that promotes cellular motility and matrix remodeling, critical to tumorigenesis and metastasis. TGF-β1-induced EMT promotes the assembly of FN, which synergistically binds latent TGF-β1 to aid in its activation. The purpose of of this work is to further probe the effects of autocrine TGF-β1 signaling during EMT progression by utilizing CRISPR-Cas9 deletion of the TGFB1 gene in in vitro models of triple-negative breast cancer. The studies outlined in this work demonstrate that autocrine TGF-β1 maintains a baseline level of mesenchymal marker expression. It also functions to desensitize …

Illuminating Function And Enabling Inhibition At The Protein-Membrane Interface Of Glutathione Peroxidase 4., Courtney L. Labrecque

Theses and Dissertations

Membrane proteins act as gateways to cells and are responsible not only for signaling, lipid transport, and cellular homeostasis, but they are also integral in disease pathologies. One class of membrane proteins, peripheral membrane proteins (PMPs), reside in aqueous compartments of the cell until they are recruited to the membrane to perform their function. Glutathione peroxidase 4 (GPx4) is a PMP enzyme responsible for engaging the membrane and reducing lipid hydroperoxides, thereby preventing cellular death via ferroptosis. Due to its central function surrounding ferroptosis, GPx4 is an interesting drug target that has recently gained interest for inflammatory diseases as well …

Mathematical Modeling And Analysis Of Inflammation And Tissue Repair: Lung Inflammation And Wound Healing In Corals Under Stress, Quintessa Hay

Theses and Dissertations

A variety of insults, including tissue injury and/or exposure to pathogen, elicit an immune response in many organisms. An improperly regulated immune response can result in deleterious effects to the organism. Here we present models for lung injury in young and old mice and models for wound healing in coral reefs.

It is well known that the immune response becomes less effective in older individuals. This is of particular interest in pulmonary insults such as ventilator induced lung injury (VILI) or lung infection. We extended a mathematical model for the inflammatory response to VILI and used experimental data to select …

Sphingosine Kinase 2 Depletion Dysregulates Hepatic Redox Metabolism And Enhances Inflammation In Early Metabolic Dysfunction-Associated Steatohepatitis (Mash), Kaitlyn Georgene Jackson

Theses and Dissertations

Metabolic dysfunction-associated steatotic liver disease (MASLD) currently affects one in three people worldwide; its prevalence is growing alongside other cardiometabolic disorders. Aberrations to redox and sphingolipid metabolism contribute to MASLD pathologic progression. Sphingosine-1-phosphate (S1P) is an active lipid, meaning that S1P participates in biochemical processes within the cell. S1P is generated by two distinct isoenzymes, sphingosine kinase (SphK)1 and SphK2. The localization of the SphK enzyme dictates S1P function. While cytosolic SphK1-generated S1P is well-characterized, nuclear and mitochondrial SphK2-generated S1P is less known. Moreover, SphK2 depletion effects on cellular redox processes and inflammation are not well-defined.

This study defines the …

The Role Of Hdac6 In Periodontal Inflammation, Hannah S. Lohner

Theses and Dissertations

Periodontal disease is a polymicrobial infection-induced chronic inflammatory disease and results in irreversible tissue damage and bone loss. While bacteria play a large role in the initiation of this disease, excessive and prolonged inflammatory immune responses are fundamental for its progression, making host directed therapy (HDT) a possible and potentially valuable treatment. Histone Deacetylase 6 (HDAC6) is an enzyme that removes acetyl groups from both histone and non-histone proteins, giving it a potential role in regulating inflammation initiated by pathogenic oral bacteria. Previous studies indicated that HDACs act as a bivalent regulator in inflammatory responses; however, the role that HDAC6 …

Role Of Human Intermediate Form Prl Receptor I-Tail In The Pathogenesis Of Breast Cancer, Shanwei Shen

Theses and Dissertations

Breast cancer continues to be the second most common cancer in women in the United States. The neuroendocrine hormone human prolactin (hPRL) plays an important role in normal mammary gland development and growth, stimulating normal breast tissue proliferation and differentiation. Considerable evidence has shown that hPRL is involved in the malignant transformation of human breast tissue. hPRL enhances viability, invasiveness, and proliferation of breast cancer cells in vitro. Evidence from epidemiologic and genetic studies also implicates role of hPRL in the pathogenesis of breast cancer. Its cognate receptor the human prolactin receptor (hPRLr) is required for the action of hPRL. …

Investigation Of Brain Function And Structural Development As Risk Factors Of Suicidal Thoughts And Behaviors, Yi Zhou

Theses and Dissertations

Background: Identifying risk factors for suicidal thoughts and behaviors, especially causal ones, will be imperative to improving screening and treatment interventions. To identify replicable brain-based risk factors, there is increasing evidence indicating the need for large sample sizes, in the hundreds to thousands, in order to achieve a sufficient level of statistical power to detect them. Furthermore, longitudinal studies of brain and behavioral factors will be essential to understanding how suicide develops, especially the transition from suicide ideation to attempt. While experimental studies may not be feasible or ethical, genetically informed methods for testing evidence for causation are an alternative …

Mild Traumatic Brain Injury In Yucatan Minipigs: Assessing Changes In Approachability And Mechanical Nociception Following Diffuse Central Fluid Percussion Injury, Mark D. Pavlichenko

Theses and Dissertations

Traumatic brain injury (TBI) is a major healthcare concern affecting millions. Symptoms of TBI include sensory sensitivity and social changes that may persist long-term. Due to similarities in cytoarchitecture, metabolism, and inflammation, higher order minipig models are advantageous for translational TBI research, however, there remains a shortage of information regarding their behavioral and sensory sequelae following injury. Therefore, in this study, we assessed changes in sociability and somatosensation in adult male and female Yucatan minipigs for up to one-week following a sham or central fluid percussion injury (cFPI). Specifically, the voluntary human approach task (VHAT) and the forced human approach …

Re-Programming Transcription Factor Function For Neuroscience Research Of Addiction: Investigating The Role Of Zinc Finger Proteins In Driving Cocaine Reinforcement In Mice, Joseph A. Picone

Theses and Dissertations

Administration of addictive drugs like cocaine or morphine initiates aberrant gene transcription within brain reward circuitry neurons, which contributes to the lasting behavioral maladaptations that define addiction. The drug-induced expression and function of key brain transcription factors (TFs) is one major mechanism through which these drugs are able to regulate transcription, and as a consequence, lasting damaging drug-related behaviors including compulsive drug use. The goal of this dissertation is to more fully understand the molecular mechanistic drug-specific actions of TFs within the rodent nucleus accumbens (NAc). The findings from these studies could serve as the basis to identify novel candidate …

Improving Nutrition Screening Practice In The Hospitalized Heart Failure Patient Population, Amanda J. Bourgeois

DNP Projects

Background: Heart Failure is a disease known to affect nearly 6.5 million adults in the United States. Characterized by recurrent hospitalizations, heart failure significantly contributes to morbidity, mortality, and healthcare costs in the United States and worldwide. Because malnutrition is prevalent in the heart failure population, healthcare providers must perform nutritional assessments on admission to intervene in the case of malnutrition, prevent deterioration, and improve patient prognosis. Without intervention and early identification of malnutrition, heart failure hospitalizations will remain a significant problem.

Purpose: The purpose of this study is to evaluate the effect of an evidence-based educational program for cardiac …

Evaluation Of Winter Cereal Cover Crops Across Nitrogen Management Strategies In No-Till Corn Production, Robert Nalley

Theses and Dissertations--Plant and Soil Sciences

Rye (Secale cereale L.) is the most popular winter cereal cover crop utilized before corn, but wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.) may provide a comparable value due to their similar fibrous root systems. Despite the benefits associated with winter cereal cover crops, drawbacks are possible for the subsequent corn crop. A field study was conducted with three site-years in Kentucky to measure the impact of the three winter cereals across nitrogen (N) management strategies. Wheat produced the most biomass compared with barley or rye cover crops. Wheat and rye needed approximately 100 more …

From Code To Crops: Harnessing Bioinformatics And Artificial Intelligence (Ai) In Agricultural Omics, Lakshay Anand

Theses and Dissertations--Plant and Soil Sciences

Global agricultural faces numerous challenges, such as climate change, resource limitations, novel pests and diseases, increasing costs, and the ever-increasing human population. To tackle these challenges, we need innovative strategies that combine new technologies and data analytics approaches to enhance agricultural output, promote sustainable methods, and optimize resource allocation. The key to this innovation lies in understanding the complex molecular web within plants that governs their growth, defense, and adaptability mechanisms. By mastering this molecular network, we can cultivate crops that are more resilient, sustainable, and suitable for different climatic terrains. Moreover, studying the symbiotic relationship between plants and microorganisms …

The Effects Of Potassium Fertilization Regime On High Tunnel Tomato Production, Sapana Pandey

Theses and Dissertations--Plant and Soil Sciences

A two-year field experiment (2022-2023) was conducted at the University of Kentucky Horticulture Research Farm in Lexington, KY to study the effects of potassium (K2O) fertilization rates on tomato yield and ripening disorders in determinate and indeterminate varieties (‘BHN-589’ and ‘Big Beef’, respectively). In the first year, K2O rates representing the soil test result-based commercial recommendation (0 lbs/acre) and sequentially greater rates (150, 300, and 450 lbs K2O/acre) were applied. In the second year, K2O rates were increased based on lack of fruit quality response and were 0, 300, 600, and 900 lbs K2O/acre. Leaf tissue nutrients, tomato yield, and …

Surveys, Field Studies, And Laboratory Incubation Experiments To Improve Alfalfa Production In The Mid-South, William Fleming

Theses and Dissertations--Plant and Soil Sciences

The objective of the alfalfa survey was to determine the role of soil fertility in the alfalfa yield plateau. Soil samples at depths of 10, 15, and 30 cm and tissue samples were collected from 114 alfalfa stands across Kentucky and surrounding states. Results indicate that soil fertility is likely contributing but not driving the alfalfa yield plateau. The main objective of the polyhalite incubation study is to determine if POLY4 was soluble enough to support potassium (K) and sulfur (S) for plant growth. The design of the study included four fertilizer treatments, three soil types, and four incubation times. …

Identifying Physiological, Morphological, And Genetic Drivers Of Key Intermediary Phenotypic Traits Associated With Stalk Lodging Resistance Within Genetically Diverse Maize Germplasm And Sorghum, Norbert Bokros

Theses and Dissertations--Plant and Soil Sciences

Maize stalk lodging reduces grain yields due to the permanent breakage or deformation of stalk tissue before grain harvest. To reveal new insights into the complex problem of maize stalk lodging, this dissertation will examine three primary objectives. First, the direct, diurnal influence of turgor pressure will be shown to have only marginal effects on stalk bending strength, a key trait associated with stalk lodging resistance. Up to a dozen individual stalks, grown to physiological maturity within the same field, were tested using a DARLING testing device. In parallel, stalk turgor status as measured by leaf water potential and turgor …

The Effect Of Spring And Winter Killed Cover Crops On Soil Physical Properties And Soil Organic Carbon, Danielle Doering

Theses and Dissertations--Plant and Soil Sciences

Maintaining soil organic carbon (SOC) and healthy soil physical structure in agroecosystems is crucial to sustainable production. To assess medium term impacts of cover crops on soil health in the top 90 cm, we conducted a field experiment in central Kentucky with varying levels of winter cover: spring and winter kill cover crops, weedy and bare winter fallows. After eight years of cover crop use, some soil physical properties improved: 35% greater mean weight aggregate diameter at 0-30 cm with spring kill covers and 5.2% more C held within large aggregates for both cover crop treatments compared to winter fallow. …

The Roles Of Mrna Polyadenylation Factors In Plant Growth And Development, Lichun Zhou

Theses and Dissertations--Plant and Soil Sciences

Messenger RNA polyadenylation, the process wherein the primary RNA polymerase II transcript is cleaved and a poly(A) tract added, is a key step in the expression of genes in plants. Polyadenylation is mediated by a complex (the polyadenylation complex, or PAC) that consists of between 15 and 20 subunits. To learn the roles of PAC in regulation of the polyadenylation in plants, I conducted a survey of variability in the plant PAC. For this, I drew upon a database of naturally-occurring variation in numerous geographic isolates of Arabidopsis thaliana. The results show that many subunits of the PAC are …

Silicon Fertilization In Cool-Season Turfgrasses, Cheng Qian

Theses and Dissertations--Plant and Soil Sciences

Previous studies of the benefits of silicon (Si) supplementation in turfgrass have yielded inconsistent results. This dissertation aimed to assess the benefits if Si supplementation in cool-season turfgrass under more well controlled conditions than many previous studies. The first study assessed the effect of Si supplementation on biomass production and Si accumulation of tall fescue (Festuca arundinacea) and bentgrass (Agrostis stolonifera) in buffered Hoagland’s media (pH 6) with four sodium silicate (Na2SiO3) treatments (0, 0.5, 1, 2, and 4 mM Si). The two species responded differently to Si supplementation in terms of biomass. Bentgrass biomass was …

An Assessment Of User Satisfaction On Remote Court Hearings In The Brunei Civil Court, Hazwani Masli, Seyed M. Buhari

ASEAN Journal on Science and Technology for Development

Remote court hearings (RCHs) have significantly benefited the Brunei Civil Court in maintaining its judicial system and reducing backlogs as a preventative measure, during COVID-19. RCHs have enhanced the judicial system's accessibility, saving resources and increasing court performance and productivity. However, technical problems and mistrust have slowed the RCH's adoption. This study assessed user satisfaction with remote court hearings using the Technology Acceptance Model (TAM) framework. Three external variables influenced the perceived usefulness of remote court hearings: trust, perceived risk, and fairness expectations. This study also included moderator variables such as age group and professions. This study showed that trust, …

Exploiting Quadratic Unconstrained Binary Optimization And Column Generation For Solving Vehicle Routing Problem With Discretized Time Windows, Krittin Phornsiricharoenphant

Chulalongkorn University Theses and Dissertations (Chula ETD)

No abstract provided.

Quantifying Resource Nexus: Virtual Water Flows, Water Stress Indices, And Unsustainable Import Fraction In South Korea's Grain Trade Landscape, Golden Odey, Bashir Adelodun, Qudus Adeyi, Akinsoji Adisa Hammed, Salau Rahmon Abiodun, Kyung Sook Choi

Arusha Climate and Environmental Research Centre

This study delves into the intricate dynamics of South Korea’s grain production and trade, specifically scrutinizing water resource management and sustainability trends from 1991 to 2022. The primary objective was to assess the temporal evolution of South Korea’s agricultural virtual water trade in maize, soybeans and wheat. Employing the virtual water flows assessment method, water stress index, and an unsustainable import fraction (UIF) analysis, this research aimed to uncover key patterns and dynamics within the agricultural grain trade landscape. Utilizing comprehensive datasets encompassing grain trade, as well as water and land footprint data, this study assessed the intricate interplay between …

Effects Of The Cb1 Receptor Antagonist, Am251, On Maternal Behavior In Long-Evans Rat Dams, Jennifer Aguilera-Fonseca, Karla Colley, Eddie Galarza, Atoria Hamm, Joe Morse, Rachel Ntor, Destiny Pichardo, Vincent P. Markowski

McNair Scholars Program

No abstract provided.

Investigating The Roles Of Dapk, P53/Cep-1, And Mitochondrial Damage In Necrotic Neurodegeneration In C. Elegans, Anil Singh

Dissertations and Theses

Stroke is one of the leading causes of death in the U.S., with minority groups, suffering higher fatality rates. Stroke is caused by ischemia, where occlusion of blood supply to the brain results in neurodegeneration. Most of the damage is attributed to excitotoxicity, where an accumulation of the neurotransmitter glutamate in the synapse overstimulates postsynaptic neurons and ultimately leads to cell death (largely by necrosis). Stroke treatments are often ineffective, due to the delay between the onset of stroke and the delivery of effective treatment. To address this, we focus our study on putative later-acting mediators of excitotoxicity such as …

Atm-/-Ung-/- Mice Present Reduced Levels Of Switched Immunoglobulin Isotypes Igg1 And Igg3, Lyric M. Haughton

Dissertations and Theses

B cells excise and recombine the immunoglobulin heavy chain gene locus during class switch recombination (CSR). CSR is mediated by activation induced cytidine deaminase (AID) and results in a new immunoglobulin isotype that B cells will secrete and present. AID produces mutations that convert cytosines to uracils within the intronic switch regions that precede and follow the target immunoglobulin isotype coding sequence. To resolve the mutations, B cells conduct either base excision repair (BER) or mismatch repair (MMR). Inactivating genetic mutations in BER or MMR reduce CSR. For example, a knock-out of uracil DNA glycosylase (UNG) causes a 50% reduction …

Synthesis Of Novel 5-Aryl 2’-Deoxyuridine And 2’-Deoxycytidine Analogues, Kevin E. Persaud

Dissertations and Theses

Briefly, the following report details a synthetic route to prepare 5-phenyl-2’-deoxycytidine analogues. This multistep synthesis began with silyl protection of the 3’- and 5’-hydroxyl groups of 5-iodo-2’-deoxyuridine. Next, the installation of a phenyl ring at the C5 position of the nucleobase via a Suzuki-Miyaura cross-coupling reaction, yielding 5-phenyl-2’-deoxyuridine (5-PdU). After that, modification of the obtained 5-PdU at the C4 position was performed with benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (BOP, a peptide-coupling agent) and a base (cesium carbonate) to activate the amide group of the uridine nucleobase for subsequent displacement with a variety of amines. Modification of the C4 position resulted in protected 5-phenyl-2’-deoxycytidine …

The Role Of The Vibrio Cholerae Type Vi Secretion System During Kin Cell Interaction, Biofilm Formation And Priority Effects, Karen A. Castro

Dissertations and Theses

Vibrio cholerae’s Type VI secretion system (T6SS) is one of the arsenals used by the bacteria for its long-term survival in different environments, against a variety of opponents, and for its maintained pathogenicity in vulnerable regions of the world. Therefore, the more we understand about the activity of the T6SS, the closer we get to understanding its role in bacterial competition; inter-and-intra, and how this shapes a bacterial niche. Further, although the probiotic-like effect in the V. cholerae vaccine is described to work fast due to niche uptake hindering colonization of toxigenic strains, it is not yet clear if there …

An Exploratory Study Of The Effects Of Bis-Substituted Triazolium Bromide Salts On The Proliferation Of Wi-38 Lung Cells And H-1299 Lung Cancer Cells, Rakaiya Martin

Theses and Dissertations

Lung cancer is the leading cause of cancer deaths worldwide. The battle against this disease continues to challenge physicians and scientists daily, due to its various forms, treatments, and responses. Depending on the grade and stage of the disease, treatments can be extensive, encompassing surgery, chemotherapy, and radiation therapy. Though these therapeutics can prolong a patient’s life, they often have significant ramifications. For instance, radiation therapy has an extensive list of side effects, from organ damage to loss of fertility. These outcomes have driven scientists to explore the applicability of novel cancer treatments. Imidazolium and benzimidazolium salts have been shown …

The Effect Of Nanoconfined Liquid Properties On The Water-Responsive Behavior Of Bacterial Cell Walls, Seungri Kim

Dissertations and Theses

Water-responsive (WR) materials have the ability to mechanically swell and shrink in response to changes in relative humidity (RH). These WR materials are used by many biological systems to perform essential tasks; for example, pinecones use WR materials to release their seeds in dry environments, and wheat awns open and close to propel seeds into the soil, driven by daily RH changes. The WR actuation of some biomaterials is extremely powerful, for example Bacillus subtilis cell walls display record-high actuation energy and power densities of 72 MJ m^-3 and 9.1 MW m^-3, surpassing those of all existing …

Keynote Address And Meeting Program, Academy Editors

Journal of the Arkansas Academy of Science

No abstract provided.

Instructions To Authors, Academy Editors

Journal of the Arkansas Academy of Science

No abstract provided.