Life Sciences Commons^™

Death Of A Bacterium: Exploring The Inhibition Of Staphylococcus Aureus By Burkholderia Cenocepacia., Tiffany Brandt

Electronic Theses and Dissertations

Antimicrobial resistance is a phenomenon of increasing concern as antimicrobial overuse and misuse eliminate current therapeutic options, ushering society into a post-antimicrobial era. Antibiotic discovery and synthesis efforts are urgently needed to counter the increasing burden of antimicrobial resistance. Staphylococcus aureus is a causative agent of a variety of clinical manifestations including bacteremia, endocarditis, soft tissue infection, osteomyelitis, and device-related infections. S. aureus infection presents additional treatment challenges due to its capacity for biofilm formation, which is a mode of growth that confers protection from antibiotics and physical elimination, and the emergence of antibiotic resistant strains, including methicillin-resistant S. aureus …

Voltage-Gated Potassium Channel Dependent Mechanisms Of Cardiovascular Adaptation To Chronic Exercise., Sean Raph

Electronic Theses and Dissertations

Exercise increases cardiac workload, escalating the demand for oxygen. The myocardial vasculature responds to the greater demand for oxygen by increasing blood flow to match the needs of the heart during augmented work. Increasing blood flow requires the coronary arteries dilate (a.k.a. vasodilation); this is mediated predominantly by vascular smooth muscle cell relaxation. Vasodilation is driven through inhibition of calcium influx into vascular smooth muscle cells. The prevention of calcium influx is largely mediated by efflux of potassium via potassium channels causing membrane hyperpolarization, which in turn closes voltage-dependent (or gated) calcium channels (VDCC). Changes in vascular smooth muscle cell …

Bayesian Methods For Graphical Models With Neighborhood Selection., Sagnik Bhadury

Electronic Theses and Dissertations

Graphical models determine associations between variables through the notion of conditional independence. Gaussian graphical models are a widely used class of such models, where the relationships are formalized by non-null entries of the precision matrix. However, in high-dimensional cases, covariance estimates are typically unstable. Moreover, it is natural to expect only a few significant associations to be present in many realistic applications. This necessitates the injection of sparsity techniques into the estimation method. Classical frequentist methods, like GLASSO, use penalization techniques for this purpose. Fully Bayesian methods, on the contrary, are slow because they require iteratively sampling over a quadratic …

The Effect Of Volatile Organic Compounds On Endothelial Function And Atherogenesis., Samantha Mcfall

Electronic Theses and Dissertations

Volatile organic compounds (VOCs) are a group of pervasive air pollutants that are released into the atmosphere from both anthropogenic and environmental sources. Recent epidemiological studies suggest that exposure to various VOCs is associated with an increased risk of cardiovascular disease. However, the relationship between VOCs and cardiovascular disease is not well-studied. Using animal models and three select VOCs, benzene, xylene, and trichloroethylene, we studied the effects of VOCs on endothelial injury and benzene-induced atherogenesis. We found that exposure to benzene and xylene increased circulating endothelial microparticles, depleted progenitor cells, and increased platelet activation. Following the exposure to the representative …

Re-Engineering Cardio-Oncology Testing Using Biomimetic Heart Slice Cultures., Jessica Miller

Electronic Theses and Dissertations

28% of drug withdrawal from the market are due to unforeseen disruptions in cardiomyocyte contractility and electrophysiology. The most commonly used platforms for drug testing are in vivo animal models and in vitro cell culture models. While both have been of paramount importance for the discovery and detection of many cardiotoxicities and mechanisms of action, they lack the ability to model an intact human myocardium. This work aims to establish cardiac tissue slices, which are 300-micron thin tissue sections taken from the left ventricular myocardium, as an alternative platform for cardio-oncology studies, specifically cardiotoxicity testing. Additionally, this work aims to …

Metabolic Foundations Of Exercise-Induced Cardiac Growth., Kyle Fulghum

Electronic Theses and Dissertations

Regular aerobic exercise promotes physiological cardiac growth, which is an adaptive response thought to enable the heart to meet higher physical demands. Cardiac growth involves coordination of catabolic and anabolic activities to support ATP generation, macromolecule biosynthesis, and myocyte hypertrophy. Although previous studies suggest that exercise-induced reductions in cardiac glycolysis are critical for physiological myocyte hypertrophy, it remains unclear how exercise influences the many interlinked pathways of metabolism that support adaptive remodeling of the heart. In this thesis project, we tested the general hypothesis that aerobic exercise promotes physiological cardiac growth by coordinating myocardial metabolism to promote glucose-supported anabolic pathway …

Investigation Of Human N-Acetyltransferases (Nat1 And Nat2) Genetic Polymorphisms In Susceptibility To Aromatic Amine And Alkylaniline Genotoxicity., Mariam Habil

Electronic Theses and Dissertations

Arylamine N-acetyltransferases, NAT1 and NAT2, catalyze the detoxification and/or activation of carcinogens. Single nucleotide polymorphisms or SNPs result in different human NAT1 and NAT2 genotypes. We hypothesize that different NATs alleles will impact levels of N-acetylation, HPRT mutations, DNA damage and oxidative stress induced by carcinogens. NER-deficient Chinese hamster ovary (CHO) cells transfected with human CYP1A2 and NAT1*4, NAT1*14B, NAT2*4, NAT2*5B or NAT2*7B have been used to investigate N-acetylation of benzidine, β-naphthylamine (BNA), and 4, 4’-methylene bis (2-chloroaniline) (MOCA) as aromatic amines and 3,4-dimethylaniline (3,4-DMA) as one of alkylanilines and their associated toxicity. Our …

Establishing The Efficacy Of Non-Cellular Components Of Adipose-Derived Stromal Vascular Fraction In Promoting Angiogenesis., Daniel Benson

Electronic Theses and Dissertations

Microvascular disease is hallmarked by pathophysiological conditions such as endothelial senescence, intimal thickening which impairs vasodilation, and regression of the capillary beds causing tissue ischemia in the myocardium or in peripheral vascular networks. Adipose-derived stromal vascular fraction (SVF) has previously demonstrated the ability to revascularize tissue. Increasing evidence shows that regenerative cells elicit their therapeutic benefit by paracrine mechanisms, leaving open extracellular vesicles (EVs) as a potential crux of the cell therapy paradigm. To test this idea, three types of gelatin methacrylate hydrogels were employed: SVF gels, EV gels derived from SVF, and blank control gels, which were used in-vitro …

Wellness Review 2022, Part 1, Martin Huecker, Brian A. Ferguson, Jacob Shreffler

Journal of Wellness

Introduction: This article represents the first of a two-part assessment of 2022 literature addressing wellness in healthcare professionals published from January 1, 2022 to June 30, 2022.

Methods: Three editors conducted a similar keyword search in Pubmed, also adding manually curated articles. Focusing chiefly on clinical trials and other prospective research, we settled on a final 25 significant papers focusing on wellness in medical professionals to include in this review.

Literature Review: Recent literature into HCW wellness continues to describe burnout factors and COVID-19 impact, but includes more resilience-targeting interventions and systematic reviews of trials seeking bolstering of well-being. Subsections …

Association Of Hypomagnesemia And Liver Injury, Role Of Gut-Barrier Dysfunction And Inflammation: Efficacy Of Abstinence, And 2-Week Medical Management In Alcohol Use Disorder Patients., Evan J. Winrich, Khushboo S. Gala, Abhas Rajhans, Christian D. Rios-Perez, Amor J. Royer, Zarlakhta Zamani, Ranganathan Parthasarathy, Luis S. Marsano-Obando, Ashutosh J. Barve, Melanie L. Schwandt, Vatsalya Vatsalya

Faculty Scholarship

(1) We investigated the involvement of serum magnesium level in early alcoholic liver disease (ALD), gut barrier dysfunction, and inflammation in alcohol use disorder (AUD) patients; and lastly, the efficacy of 2-week abstinence and medical management to alleviate hypomagnesemia. (2) Forty-eight heavy drinking AUD patients (34 males (M)/14 females (F)) participated in this study. Patients were grouped by serum alanine aminotransferase (ALT) level (a marker of liver injury) as group 1 (Group 1 (Gr.1); ALT ≤ 40 U/L, 7M/8F, without any indication of early-stage ALD) and group 2 (Group 2 (Gr.2); ALT > 40 U/L, 27M/6F or early-stage ALD). These patients …

Wastewater-Informed Public Health Intervention Playbook

Sustain Magazine

As the SARS-CoV-2 pandemic quickly spread from country to country and continent to continent in 2020, governments and scientists needed a way to track COVID-19 through populations in order to position public health interventions in the most impactful locations. Having a decision-based risk framework may help to guide policy creation that could minimize or prevent possible outbreaks and surges of infection within communities. The University of Louisville in partnership with Louisville’s Department of Public Health and Wellness tested this strategy in 2021 and 2022. This Wastewater-Informed Public Health Intervention Playbook describes the decisions and actions of that academic and public …

The Intersection Between Toxicology And Aging Research: A Toxic Aging Coin Perspective., John P. Wise Jr.

Faculty Scholarship

We are imminently faced with the challenges of an increasingly aging population and longer lifespans due to improved health care. Concomitantly, we are faced with ubiquitous environmental pollution linked with various health effects and age-related diseases which contribute to increased morbidity with age. Geriatric populations are rarely considered in the development of environmental regulations or in toxicology research. Today, life expectancy is often into one’s 80s or beyond, which means multiple decades living as a geriatric individual. Hence, adverse health effects and late-onset diseases might be due to environmental exposures as a geriatric, and we currently have no way of …

A Study Of Multiple Sclerosis, Christine Chen

The Cardinal Edge

No abstract provided.

Targeting Of The Hedgehog Signaling Pathway In Cancer Treatment, Andrew J. Hawes

The Cardinal Edge

The Hedgehog (Hh) signaling pathway is a developmental pathway that is highly conserved evolutionarily. While typically only displaying high activity during embryogenesis, overactivation of the Hh pathway in adults has been linked to multiple forms of cancer including acute myeloid leukemia, myelofibrosis, basal-cell carcinoma, pancreatic ductal adrenal carcinoma, and triple negative breast cancer. The prevalence of Hh activation in many different cancers has made it a prime target for inhibition of these cancers through novel therapies. This literature review sought to assess the current state of cancer treatment through inhibition of Hh signaling. Most current clinical trials involving the pathway …

Characterization Of The Function Of Pprgtb2 From Mutant Phenotypes, Briana L. Seibert, Hyun Jin Jung, Mark P Running

The Cardinal Edge

Protein prenylation, a common lipid post-translational modification, is required for growth and development in eukaryotes. One type, , but its biological function is not well known. The moss Physcomitrella patens (P. patens) was used as a model organism due to its simple structure, limited cell types, sequenced genome, and its high gene targeting efficiency. P. patens has one copy of Rab-GGT α subunit (PpRGTA1) and two copies of β subunit (PpRGTB1 and PpRGTB2). It has been found that the knockout of either PpRGTB1 or PpRGTB2 results in no visible phenotype, which indicates that these …

An Interdisciplinary Discussion On Climate Change, Aamira Shah, Jaley F. Adkins, Kelsey Littrell, Priyadarshini Chandrashekhar

The Cardinal Edge

No abstract provided.

Meditation Program For First Year Medical Undergraduate Students: A Feasibility Study, Anumeha Bhagat, Anita Sinha Malhotra, Ajeet Kumar Sidana

Journal of Wellness

Introduction: Prevalence of stress among Indian medical undergraduate students is currently higher than the global stress level. Notably, although India is considered home to yogic practices, attempts at incorporating them in the daily routines of medical students have been lacking. In Raj Yoga Meditation (RYM), the steps for meditation are clear and explicit, so it is easy to practice. The study aimed to assess the feasibility of daily practice of RYM by medical undergraduates and find out if there is an improvement in the mental health and stress levels of the participants.

Methods: We chose 80 students randomly from two …

Defining The Importance Of The Hnrnp I Interaction To The Sindbis Virus Subgenomic Viral Rna Using An Innovative Tethering Approach., Claire Westcott

Electronic Theses and Dissertations

Old World alphaviruses cause significant outbreaks of illness and debilitating multi-joint arthritis for prolonged periods. Currently, there are no FDA approved vaccines or antiviral therapies; and thus, there is a critical need to identify and characterize the molecular biology of alphaviruses. Alphaviruses rely on the host cell machinery to complete the viral lifecycle and are dependent on interactions with host RNA binding proteins. Accordingly, several host heterogenous nuclear ribonucleoprotein proteins (hnRNPs) have been found to bind to the Sindbis virus (SINV) RNAs. Disrupting the interaction sites in the viral RNAs of these RNA:Protein interactions results in decreased viral titers in …

Ecological And Phenotypic Diversification After A Continental Invasion In Neotropical Freshwater Stingrays, Matthew Kolmann, Fernando Pl Marques, James C. Weaver, Mason N. Dean, Joao Pedro Fontenelle, Nathan R. Lovejoy

Faculty Scholarship

Habitat transitions are key potential explanations for why some lineages have diversified and others have not—from Anolis lizards to Darwin's finches. The ecological ramifications of marine-to-freshwater transitions for fishes suggest evolutionary contingency: some lineages maintain their ancestral niches in novel habitats (niche conservatism), whereas others alter their ecological role. However, few studies have considered phenotypic, ecological, and lineage diversification concurrently to explore this issue. Here, we investigated the macroevolutionary history of the taxonomically and ecologically diverse Neotropical freshwater river rays (subfamily Potamotrygoninae), which invaded and diversified in the Amazon and other South American rivers during the late Oligocene to early …

Effect Of Dorsal Quadrant Or Ventral Quadrant Spinal Cord Injury On Gait Features During Locomotion., Anya Nicole Trell

Electronic Theses and Dissertations

In the Unites States, approximately 1.5 million people currently have a spinal cord injury and suffer permanent sensory and motor loss due to the disruption of the spinal cord. Due to the significant morbidity, it is vital to understand the functional impact of disrupting neural descending pathways that modulate spinal neurons involved in intermuscular coordination critical for gait behaviors. Tasks that are more difficult require additional input from these neural pathways; therefore, fourteen feline subjects were familiarized with level overground locomotion and stair descent gait tasks. After collection of baseline kinematic data, the subjects received either a dorsal or ventral …

A Computational Model Of The Line-1 Retrotransposon Life Cycle And Visualization Of Metabolic Networks In 3-Dimensions., Michael D. Martin

Electronic Theses and Dissertations

Computational modeling of metabolic reactions and cellular systems is evolving as a tool for quantitative prediction of metabolic parameters and reaction pathway analysis. In this work, the basics of computational cell biology are presented as well as a summary of physical processes within the cell, and the algorithmic methods used to find time dependent solutions. Protein-protein and enzyme-substrate interactions are mathematically represented via mass action kinetics to construct sets of linear differential equations that describe reaction rates and formation of protein complexes. Using mass action methods, examples of reaction networks and their solutions are presented within the Virtual Cell simulation …

Application Of Cannabidol To Ocular Pharmacokinetics And Pharmacodynamics., Alyssa Laun

Electronic Theses and Dissertations

Cannabidiol (CBD) is the most abundant non-psychotropic cannabinoid constituent of Cannabis sativa. CBD is potentially therapeutic for the eye through antioxidant, anti-inflammatory, and neuroprotective effects. However, the effect of CBD on intraocular pressure (IOP)- the major risk factor for glaucoma- is controversial and large variability exists in the literature. IOP is regulated through aqueous humor (AH) dynamics in trabecular meshwork (TM) tissues. Measurement of CBD in AH and correlation with effects on IOP would clarify what concentrations mediate changes to IOP. Therefore, the overall goal of this dissertation is to measure CBD in ocular tissues and correlate concentrations with …

Determination Of The Functional Role Of Rab-Ggt In Physcomitrium Patens., Hyun Jin Jung

Electronic Theses and Dissertations

Protein prenylation, a common lipid post-translational modification, is required for growth and development in eukaryotes. Rab geranylgeranylation involves the addition of one or two 20-carbon geranylgeranyl moieties to Rab-GTPase target proteins, which regulate intracellular vesicle trafficking. The reaction is carried out by heterodimeric Rab geranylgeranyltransferase (Rab-GGT), which is composed of two associated α- and β-subunits, with the assistance of an additional protein called Rab escort protein (REP). Loss of function of the Rab-GGT α subunit RGTA1 has not been reported in any plant. While knockout of either of the two β subunits RGTB1 or RGTB2 results in …

Unraveling Dna And Identity: A Humanistic Perspective On Epistemologies And Ethics Of Genetic Ancestry Testing., Eve Carlisle Polley

Electronic Theses and Dissertations

The advent of DNA ancestry testing motivated a burst of human activities that constitute a scientific-technological-industrial-personal-social movement of immense scale, infused with epistemological and ethical questions of great and important variety. This movement has motivated many discourses in the social sciences, with study subjects ranging from the language usage of geneticists, to moral conundrums faced by test-takers, to potential ramifications in global structures of political power. At the same time, and especially in recent decades, the discourses of the comparative humanities have included with increasing frequency and urgency research and theorization about concepts and consequences of human social identities, alongside …

Characterization Of Microbotryum Lychnidis-Dioicae Secreted Effector Proteins That Manipulate Its Host Plant, Silene Latifolia., Ming-Chang Tsai

Electronic Theses and Dissertations

The smut fungal species Microbotryum lychnidis-dioicae is an obligate phytopathogen colonizing the plant host, Silene latifolia. A significant feature of M. lychnidis-dioicae infection is that the fungus can replace pollen on the anthers of susceptible host plants with fungal teliospores, thus earning the fungus the name: anther smut disease of flowers. The fungus synthesizes and secretes effector proteins into the cells of the plant host during infection, and the protein-protein interactions may interfere with and modify metabolism, plant development, and gene expression of the host to allow fungal colonization. Two potential fungal effector proteins, MVLG_06175 and MVLG_05122, were identified …

Applications Of Nuclear Magnetic Resonance Spectroscopy: From Drug Discovery To Protein Structure And Dynamics., Mark Vincent C. Dela Cerna

Electronic Theses and Dissertations

The versatility of nuclear magnetic resonance (NMR) spectroscopy is apparent when presented with diverse applications to which it can contribute. Here, NMR is used i) as a screening/ validation tool for a drug discovery program targeting the Phosphatase of Regenerating Liver 3 (PRL3), ii) to characterize the conformational heterogeneity of p53 regulator, Murine Double Minute X (MDMX), and iii) to characterize the solution dynamics of guanosine monophosphate kinase (GMPK). Mounting evidence suggesting roles for PRL3 in oncogenesis and metastasis has catapulted it into prominence as a cancer drug target. Yet, despite significant efforts, there are no PRL3 small molecule inhibitors …

Leafing Through Literature: Late Embryogenesis Abundant Proteins Coming Of Age – Achievements And Perspectives, Itzell E. Hernandez-Sanchez, Israel Maruri Lopez, Coral Martinez-Martinez, Brett Janis, Juan Francisco Jimenez Bremont, Alejandra A. Covarrubias, Michael A. Menze, Steffen P. Graether, Anja Thalhammer

Faculty Scholarship

To deal with increasingly severe periods of dehydration related to global climate change, it becomes increasingly important to understand the complex strategies many organisms have developed to cope with dehydration and desiccation. While it is undisputed that late embryogenesis abundant (LEA) proteins play a key role in the tolerance of plants and many anhydrobiotic organisms to water limitation, the molecular mechanisms are not well understood. In this review we recap the current knowledge of the physiological roles of LEA proteins and discuss their potential molecular functions. As these are ultimately linked to conformational changes in the presence of binding partners, …

Influences Of Drosophila Circadian Clock On Sugar-Mediated Physiological Changes, Erica E Hassoun

College of Arts & Sciences Senior Honors Theses

It is widely known that high sugar consumption and poor sleep are detrimental to human health. Both are risk factors for obesity, which can lead to conditions such as heart disease. Despite this connection between sugar and sleep, little is known about how circadian clock dysfunction affects the physiological changes caused by increased sugar consumption. In this thesis, a mutant line of the model organism Drosophila melanogaster (Clk^Jrk, which contains a nonfunctional circadian rhythm gene known as Clk) that leads to circadian dysfunction, was exposed to a high sugar diet to observe how Clk affects sugar-related changes to …

Functional Role Of Ppal And Potential For Moss In Industrial Applications., Susana Perez Martinez

Electronic Theses and Dissertations

This dissertation is an examination and characterization of the functional roles of PPAL. PROTEIN PRENYLTRANSFERASE ALPHA SUBUNIT-LIKE (PPAL) is a recently discovered gene. PPAL homologs are present in all plants and many animals, where its function is largely unknown. It is possible that PPAL could participate in prenylation processes since it shares similarity to the α subunits of known prenylation enzymes. Prenylation is a post-translational modification of proteins that involves the addition of a lipid moiety to proteins to facilitate membrane targeting and association and promote protein-protein interactions. Prenylation has important roles in plant growth and development, including …

Adjusting For Speaking Rate When Perceiving Speech In Background Noise., Dawson C Stephens

College of Arts & Sciences Senior Honors Theses

Speech perception is a very relevant concept occurring every day. Acoustic context effects such as temporal contrast effects (TCEs) influence perception significantly. For instance, when a faster context sentence is spoken, the participant should perceive the following target word as slower and more like /t/ in “tier”; when a slower context sentence is spoken, the participant should perceive the following target sound as faster and more like /d/ in “deer”. Recent work by Bosker et al. (2020) concluded that selective attention (directing attention to a specific stimulus while ignoring surrounding stimuli) had no effect on TCEs, suggesting they were automatic …