Life Sciences Commons^™

Assessing Perfectionism As A Predictor Of Exercise Dependency Over Time., Sarah E. Ernst

College of Arts & Sciences Senior Honors Theses

Exercise is generally thought to be beneficial for physical and mental health; however, when done in excess, exercise can lead to damaging physical, psychological, and social health consequences. This type of exercise is known as exercise dependency and is frequently associated with eating disorder pathology. Perfectionism (high standards and evaluative concerns) is a risk factor for eating disorders and is also associated with exercise dependency. However, no studies have examined longitudinal relationships between perfectionism and exercise dependency. The current study used a sample of adolescent females (N = 444) from a Southeastern United States high school, and participants completed …

Therapeutic Potential Of Withaferin A Against Non-Small Cell Lung Cancer., Al Hassan Kyakulaga

Electronic Theses and Dissertations

Lung cancer is the leading cause of cancer-related deaths worldwide and in the United States. Despite recent advancements in treatment approaches, chemoresistance and metastasis remain a major therapeutic challenge. Withaferin A (WFA), a plant-derived compound has recently emerged as a promising antitumor agent. In the present study, we explored the therapeutic potential of WFA against advanced NSCLC. Briefly, WFA was evaluated for its efficacy, toxicity and pharmacokinetic properties against advanced NSCLC using in vitro and in vivo models. Two human NSCLC cell lines, H1299 and A549 were used in cell culture to determine the anticancer properties of WFA. Repeat dose …

Understanding Object Motion Encoding In The Mammalian Retina., Victor Julian Depiero

Electronic Theses and Dissertations

Phototransduction, transmission of visual information down the optic nerve incurs delays on the order of 50 – 100ms. This implies that the neuronal representation of a moving object should lag behind the object’s actual position. However, studies have demonstrated that the visual system compensates for neuronal delays using a predictive mechanism called phase advancing, which shifts the population response toward the leading edge of a moving object’s retinal image. To understand how this compensation is achieved in the retina, I investigated cellular and synaptic mechanisms that drive phase advancing. I used three approaches, each testing phase advancing at a …

The Identification Of Long Non-Coding Rna Zfas1 Through An Exploratory Rna-Sequencing Analysis And Its Association With Epithelial-To-Mesenchymal Transition In Colon Cancer Adenocarcinoma., Stephen J. O'Brien

Electronic Theses and Dissertations

Colorectal adenocarcinoma is the fourth most common cancer diagnosed worldwide and is a significant cause of morbidity and mortality. This dissertation performed an exploratory RNA-sequencing analysis comparing gene expression between colon adenocarcinoma tissue and paired normal colon epithelium. After identification of a number of lncRNAs that were increased in expression in colon adenocarcinoma compared to normal colon epithelium, we aimed to validate the expression and investigate their function in vitro. Specifically, we focused on the lncRNA ZFAS1 and its association with epithelial-to-mesenchymal transition. These studies found the following: 1. Seven candidate lncRNAs were identified from the exploratory RNA-sequencing analysis to …

Investigation Of Phosphoserine Aminotransferase 1(Psat1) In Breast Cancer Progression., Stephanie Metcalf

Electronic Theses and Dissertations

This dissertation describes my research into the involvement of phosphoserine aminotransferase 1 (PSAT1) in breast cancer progression; specifically, in triple negative breast cancer (TNBC) metastasis and endocrine resistance in estrogen receptor positive breast cancer (ER+BC). Breast cancer is the most common tumor diagnosis among women. While the overall 5-year survival for breast cancer is reaching 90%, the 5-year survival for metastatic disease is only 22%. Metastasis and endocrine resistance combined can affect over 50% of patients. One of the proteins and pathways implicated in both metastasis and endocrine resistance in breast cancer is phosphoserine aminotransferase 1 (PSAT1) and the serine …

Characterizing The Roles Of Neutral Ceramidase In Cisplatin-Induced Kidney Injury., Sophia M. Sears

Electronic Theses and Dissertations

Cisplatin is a commonly used chemotherapeutic agent with a dose-limiting nephrotoxicity. 30% of patients given cisplatin develop acute kidney injury (AKI). AKI increases risk of chronic kidney disease (CKD) development and mortality. Patients that don’t develop clinical AKI are still at risk for long term declines in renal function. Currently, there are no FDA approved agents to treat or prevent cisplatin-induced kidney injury (CDDP-KI). In this study, we demonstrated that neutral ceramidase (nCDase) knockout provides protection from AKI in the high-dose model of CDDP-KI. However, in the repeated low dose cisplatin (RLDC) model of injury and we found nCDase knockout …

Designing And Sample Size Calculation In Presence Of Heterogeneity In Biological Studies Involving High-Throughput Data., Sudhir Srivastava

Electronic Theses and Dissertations

The designing and determination of sample size are important for conducting high-throughput biological experiments such as proteomics experiments and RNA-Seq expression studies, thus leading to better understanding of complex mechanisms underlying various biological processes. The variations in the biological data or technical approaches to data collection lead to heterogeneity for the samples under study. We critically worked on the issues of technical and biological heterogeneity. The quantitative measurements based on liquid chromatography (LC) coupled with mass spectrometry (MS) often suffer from the problem of missing values (MVs) and data heterogeneity. We considered a proteomics data set generated from human kidney …

Plant Protein Prenylation In Environmental Responses And Protein Production., Parul Singh

Electronic Theses and Dissertations

Lipid post-translational modifications enhance a protein’s interaction with membranes and other proteins. In this dissertation, I studied a recently identified Arabidopsis gene, PROTEIN PRENYLTRANSFERASE ALPHA SUBUNIT-LIKE (PPAL), by mapping a second-site mutation that rescues the original mutation phenotype and could be an additional factor involved in sugar homeostasis/sensing. I found that mutant phenotype associated with suppressor line was too weak and variable to consistently score, which resulted in not finding any linked markers. I also generated crosses between ppal-1 and ABA biosynthesis and signal transduction mutants to find any possible connection between these pathways and PPAL. By …

Transforming Moss P. Patens With Lignin Peroxidase Through Heterologous Protein Expression., Jesse Lee Rozsa

Electronic Theses and Dissertations

Lignin peroxidase is an enzyme secreted by white-rot fungi Phanerochaete chrysosporium. Our laboratory is attempting to produce several lignin degrading enzymes in our protein expression system that utilizes the moss, Physcomitrella patens. During our experiments we discovered that this particular species of fungus produces altered splicing variants that are not represented in the previously reported reference sequence. Despite several attempts to produce a positive transformant containing a desired transgene encoding; lignin peroxidase, production of the proper construct eluded our efforts, possibly due to toxic effects associated with lignin peroxidase expression. Our laboratory has created a stepping stone for other laboratories …

Characterization Of A More Clinically Relevant Human Leukemia Xenograft Model To Examine Perturbation Of Met/Sam Metabolism As A Novel Therapeutic Paradigm For Mll-R Leukemia In Vivo., Aditya Barve

Electronic Theses and Dissertations

Acute myeloid leukemia (AML), is a heterogeneous clonal disorder characterized by an accumulation of malignant myeloid progenitors in the bone marrow (BM), hindering normal hematopoiesis. AML exhibits dramatic heterogeneity in terms of cytogenetics, morphology, and chemotherapeutic sensitivity. Therefore, the investigation of novel, efficacious AML therapeutics will require advanced preclinical in vivo model systems, capable of recapitulating patient specific disease heterogeneity, and induction chemotherapy outcomes. A major focus and eventual outcome of this work was the establishment and development of a more clinically relevant mouse xenograft model of patient AML, that efficiently harbors patient derived xenografts (PDXs), and unlike more prevalent …

Transcriptional Influence Of Retinoic Acid And Its Effects On Angiogenesis Of Murine Salivary Glands., Isaac Feinn

College of Arts & Sciences Senior Honors Theses

Salivary gland hypofunction is a major disorder of salivary glands, and can arise either from diseases such as xerostomia, or from defective epithelial morphogenesis during embryogenesis. Hundreds of thousands of individuals suffer from dry mouth, and there is currently no restorative therapy for these patients. Investigation of salivary gland developmental biology will inform regenerative therapies. Currently it is known that retinoic acid (RA), the biologically active form of Vitamin A, is required for proper development of the salivary gland, but little is known about its cellular mechanism regulating organogenesis. This study sought to analyze salivary gland development in Rdh10 knock …

Relationships Of Protein Biomarkers Of The Urokinase Plasminogen Activator System With Expression Of Their Cognate Genes In Primary Breast Carcinomas., Seth B. Sereff

College of Arts & Sciences Senior Honors Theses

Background: Urokinase plasminogen activator (uPA), its receptor uPAR and serine protease inhibitors PAI-1 or PAI-2 play key roles in tissue membrane remodeling and invasion of basement membranes by induction of a fibrinolytic pathway. Earlier studies reported that uPA and PAI-1 protein levels in breast carcinomas assist in prediction of response to chemotherapy. Our goal is to develop molecular signatures of candidate genes and identify novel relationships with these four protein biomarkers that demonstrate clinical utility for assessment of breast carcinoma outcomes.

Methods: This retrospective study used de-identified biomarker results and clinical outcomes from primary breast cancers that were stored in …

Genetic Crosstalk And Its Effects On Virulence And Mating In Ustilago Maydis., John S. Desmarais

College of Arts & Sciences Senior Honors Theses

Ustilago maydis is a model organism for study of fungal mating and host infection. Two compatible haploid mating types must mate to form a dikaryon in order for the fungus to infect its host, corn (Zea mays). There are a variety of genetic mechanisms that regulate mating and infection in the fungus, many of which coregulate both processes. The aim of this study was to investigate how alteration of certain regulatory proteins in U. maydis affects these basic processes as well as how alteration of genes involved in signaling pathways can affect the expression of one another. Primarily, …

The Effect Of Stenotrophomonas Maltophilia On Gram-Negative Cystic Fibrosis Pathogens., Joshua D Stewart

College of Arts & Sciences Senior Honors Theses

Cystic Fibrosis (CF) is the most common lethal genetic disorder in the Caucasian population with an incidence of 1 per 3,000 live births and a median predicted survival of only 47 years. Respiratory failure due to repeated pathological insults to lung tissue by infection is the ultimate cause of mortality in the majority of patients. The lung microenvironment created by CF highly favors colonization by opportunistic pathogens such as Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Burkholderia cenocepacia, and Achromobacter xylosoxidans. Biofilm formation by multiple bacterial species contributes to the chronic, persistent, and difficult to treat nature of CF infections. This study seeks …

A Bug Eat Bug World : Does Urbanization Decrease Survivorship Of Pollinators., Amy L. Cherry

College of Arts & Sciences Senior Honors Theses

Human impact on the environment is responsible for the sixth mass extinction on Earth as well as rapid population declines in many taxa. Land use change, via increasing urbanization and intensity of agricultural practices, is the most important aspect of human impact on the environment, and it is associated with population decline and extinction in several taxa, but especially in pollinator species. Pollinators, which are essential for crop production, are experiencing declines as a result of the loss of habitat and host plants associated with urbanization. Urbanization negatively affects pollinators, but in the wake of lost naturalized habitat, some researchers …

Insect Populations Across An Urban-To-Suburban Land Use Gradient., Jacob T. Lawson

College of Arts & Sciences Senior Honors Theses

Insect populations, especially those of pollinators, have been steadily declining across the globe in recent decades, a trend that is intensified in cities. Since the conservation of pollinators is crucial for maintaining ecosystems and ecological processes, new approaches are being promoted beyond those of conserving large natural areas. Urban native plant gardens could potentially offset some of these losses locally. This research attempts to set a local baseline for the insect diversity in urban gardens in Louisville and determine whether differences exist in garden insects in cities versus suburbs in Jefferson County, Kentucky. To address the land-use question we established …

Reactive Glutamines And A Binding Site Region Contribute To Fxiii Substrate Specificity For Fibrinogen Αc, Mohammed Hindi

College of Arts & Sciences Senior Honors Theses

The reaction between transglutaminase factor XIII (FXIII) and fibrin is a key process in the final stages of blood coagulation. The αC region of fibrin contains three reactive glutamines (Q237, Q328, and Q366) which are crosslinked by FXIII, as well as a FXIII anchoring site (E396). Previous work has helped elucidate the FXIII-αC interaction, but much is still unknown about the key residues in the αC region.

Four crosslinking assays were carried out to characterize the contribution of the αC anchoring site and reactive glutamines in crosslinking by FXIII. The effects of individual E396A, Q366N, and Q328P (Fibrinogen Seoul II …

Pparγ And High Molecular Weight Adiponectin In White Adipose Tissue In An Obesity Model., Katelyn M. Mcdowell

College of Arts & Sciences Senior Honors Theses

Adiponectin is a protein secreted from adipose (fat) tissue. It is secreted into the blood as either a trimer (low molecular weight), hexamer (middle molecular weight) or an 18-mer (high molecular weight). Adiponectin, particularly the high molecular weight (HMW) isoform, has been shown to increase insulin sensitivity, which is important for maintaining healthy blood glucose levels. Adiponectin levels have been shown to be decreased in individuals who are obese, and this may play a role in the diabetes which often accompanies obesity. PPARγ is a protein that is highly expressed in white adipose tissue and is responsible for regulating portions …

The Role Of Ppal In The Moss Physcomitrella Patens., Noela M. Botaka

College of Arts & Sciences Senior Honors Theses

Protein prenylation is a post-translational modification that involves the addition of lipid groups to the carboxy end of a target protein and is necessary for protein activity. Prenylation has important roles in the cell: targeting and localizing proteins to subcellular compartments and promoting protein-protein interactions. As a highly conserved process in eukaryotes, prenylation is especially important for plant development. In contrast to other eukaryotes, in which loss of prenylation components can be lethal, in the flowering plant Arabidopsis thaliana and the moss Physcomitrella patens, most are viable. Prior studies have shown that prenylation is involved in ABA hormone responses, …

Exploring The Role Of Ptn1 In Ustilago Maydis., Lalu Murali Krishna Vijayakrishna Pillai

Electronic Theses and Dissertations

Signal transduction is a key aspect of biological life. Cell signaling involves a series of biochemical and molecular steps that regulate the normal cellular functions, and any disruption at any of these steps is likely to have substantial impacts on cell physiology. The current study was aimed at the characterization of ptn1 of Ustilago maydis, a basidiomycete fungus. When the U. maydis, ptn1 gene was either deleted or overexpressed, it was found that the deletion of this gene lead to reduced virulence, spore production, and germination rate; effects of the overexpression were more subtle or not discernable. Previous studies …

Paraoxonase 2 Is Critical For Non-Small Cell Lung Carcinoma Proliferation., Aaron Whitt

Electronic Theses and Dissertations

Non-small cell lung carcinoma (NSCLC) comprises 85% of lung cancer diagnoses and is plagued by drug resistance. Thus, elucidating the underlying mechanisms of NSCLC is paramount to expand future treatment options. Paraoxonase 2 (PON2), an intracellular enzyme with arylesterase and lactonase functions, has well-established anti-atherosclerotic activity. Recent studies show PON2 is overexpressed in a variety of tumors and confers drug resistance, although these interactions have not been thoroughly examined in NSCLC. Thus, we sought to investigate the role of PON2 in cellular proliferation using PON2-knockout mice, primary mouse cells, and NSCLC cell lines. Using these approaches, we demonstrate that PON2 …

Defects In Fetal Mouth Movement And Pharyngeal Patterning Underlie Cleft Palate Caused By Retinoid Deficiency., Regina Friedl

Electronic Theses and Dissertations

Cleft palate is a common birth defect. Etiologic mechanisms of palate cleft include defects in palate morphogenesis, mandibular growth, or spontaneous fetal mouth movement. Cleft palate linked to deficient fetal mouth movement has been demonstrated directly only in a single experimental model of loss of neurotransmission. Here, using retinoid deficient mouse embryos, we demonstrate directly for the first time that deficient fetal mouth movement and cleft palate occurs as a result of mis-patterned development of pharyngeal peripheral nerves and cartilages. Retinoid deficient embryos were generated by inactivation of retinol dehydrogenase 10 (Rdh10), which is critical for production of …

Indole Sensitivity In Various Insect Herbivores., Rakhi Patel

College of Arts & Sciences Senior Honors Theses

When plants in nature are attacked by herbivores, they frequently release airborne volatiles. These herbivore-induced plant volatiles (HIPVs) help plants defend themselves against herbivore attack by calling in natural enemies, but HIPVs may also be directly toxic to herbivores. Indole (C₈H₇N) is a common HIPV that is toxic to caterpillars, but its relative toxicity to different caterpillars has not been explored. I tested the toxicity of indole on six caterpillar species (Spodoptera frugiperda, Trichoplusia ni, Spodoptera exigua, Anticarsia gemmatalis, Heliothis virescens, and Helicoverpa zea). Results show that indole is …

Development Of Bar-Peptide Nanoparticles And Electrospun Fibers For The Prevention And Treatment Of Oral Biofilms., Mohamed Yehia Mahmoud

Electronic Theses and Dissertations

Background: Periodontal diseases are globally prevalent inflammatory disorders that affect ~47% of U.S adults. Porphyromonas gingivalis (Pg) has been identified as a “keystone” pathogen that disrupts host-microbe homeostasis and contributes to the initiation and progression of periodontitis. Pg associates with oral streptococci in supragingival plaque and this interaction represents a potential target for therapeutic intervention. Previously our group developed a peptide (designated BAR), that potently inhibits Pg/Streptococcus gordonii (Sg) adherence in vitro and Pg virulence in a murine model of periodontitis. While efficacious, BAR (SspB Adherence Region) provided transient inhibition and required higher concentrations of BAR to disrupt established …

Eyes In The Field, A Seat At The Table, A Voice At The Ranch : A Study On Optimal Farm Labor Conditions., Christine Wiggins-Romesburg

Electronic Theses and Dissertations

The field of human resource development has twin obligations to promote the performance of organizations and the satisfaction and welfare of all workers. Nevertheless, agriculture appears to be an understudied industry in the field, despite this obligation and the potential for suffering experienced by workers performing crop work. This case study sought to understand the process through which a single agricultural operation fosters optimal conditions for workers engaged in labor-intensive crop production. This study found employees experienced better treatment compared to other agricultural operations, and that conditions were rich in both intrinsic and extrinsic factors. Intrinsic factors were marked by …

Preference For Odor-Taste Mixtures Is Dependent On Previous Experience., Kelsey Allison Mcqueen

Electronic Theses and Dissertations

The perception of flavors occurs when a tastant is simultaneously detected and associated with an odorant (i.e., odor-taste mixture). Sampling an odor and taste together results in a congruent odor-taste mixture. Mixing an odor and taste from different congruent odor-taste pairs results in incongruent odor-taste mixtures. Creation of a flavor percept requires sampling a novel chemosensory stimulus; however, mammals exhibit robust neophobic behavior when presented with new chemosensory stimuli. To determine preferences for novel odorants and experienced odor-taste mixtures, we employ a two-bottle brief-access preference task where two chemosensory stimuli are presented simultaneously. We found that rats show a preference …

Glycine Receptor Expression Across Identified Retinal Ganglion Cell Types., Ian Scot Pyle

Electronic Theses and Dissertations

Retinal ganglion cells (RGCs) represent the culmination of all retinal signaling and their output forms the substrate for vision throughout the rest of the brain. About 40 different RGC types have been defined by differences in their visually evoked responses, morphology, and genetic makeup. These responses arise from interactions between inhibition and excitation throughout the retinal circuit (Franke et al., 2017; Masland, 2012; Sanes & Masland, 2015; Werblin, 2011). Unlike most other areas of the central nervous system (CNS), the retina utilizes both GABA and glycine inhibitory neurotransmitters to refine glutamatergic excitatory signals (Franke & Baden, 2017; Werblin, 2011; C. …

The Q Rule In Bacteriodetes And The Identification And Characterization Of Porphyromonas Gingivalis Glutaminyl Cyclase., John Andrew Houston

Electronic Theses and Dissertations

Background: Porphyromonas gingivalis, a major pathogen associated with chronic periodontitis, secretes variety of proteins, majority of which begins with glutamine. Several of these proteins were found with pyroglutamate (pGlu) at N-terminus suggesting the presence of this posttranslational modification pathway in P.gingivalis. The observation that N-terminal glutamine is over-represented as the first amino acid after signal peptide cleavage, and subsequent confirmation of pGlu formation on the nascent protein via mass spectrometry, led us to conclude that an enzyme must be present as the executor of this reaction. Hypothesis: PG2157 is a glutaminyl cyclase and is responsible for the cyclization of …

Development Of A Lectin-Fc Fusion Protein With Antiviral And Anti-Cancer Activity., Matthew William Dent

Electronic Theses and Dissertations

This thesis describes the development of a novel lectin-Fc fusion protein and its antiviral and anti-cancer activity. The molecule, Avaren-Fc (AvFc), is a fusion of a variant of the actinomycete lectin actinohivin (Avaren) and the Fc region of human IgG1, and is selective for the terminal α1,2-mannose residues found at the ends of high-mannose-type glycans that can be found on the surface of certain heavily glycosylated viruses and cancer cells. Here, AvFc was found to be able to neutralize simian immunodeficiency virus as well as Hepatitis C virus with nanomolar IC₅₀ values. Furthermore, AvFc recognizes a number of cell …