Life Sciences Commons^™

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 …

Refugee Women's Needs: The Athens Case, Melissa J. Diamond

Journal of Refugee & Global Health

Medicins sans Frontiers estimates that twenty-five per cent of new asylum-seeking arrivals in Athens in 2016 were women [1]. Despite the sizable number of women asylum seekers arriving in Athens, women’s voices are often excluded from research on refugee needs. This research sought to understand the needs of women asylum seekers in Athens through the collection of qualitative data on their needs and experiences upon arriving in Athens. Twelve women from Syria, Afghanistan and other countries (background withheld for confidentiality) participated. The sampled women demonstrated an acute understanding of their own needs and the needs of their communities. While many …

Crystal Structure Of The Mitochondrial Protein Mitoneet Bound To A Benze-Sulfonide Ligand, Werner J. Geldenhuys, Timothy E. Long, Pushkar Saralkar, Toshio Iwasaki, Raisa A. A. Nunez, Rajesh R. Nair, Mary E. Konkle, Mark V. Pinti, Michael Menze, John M. Hollander, Lori A. Hazlehurst, Aaron R. Robart

Faculty Scholarship

MitoNEET (gene cisd1) is a mitochondrial outer membrane [2Fe-2S] protein and is a potential drug target in several metabolic diseases. Previous studies have demonstrated that mitoNEET functions as a redox-active and pH-sensing protein that regulates mitochondrial metabolism, although the structural basis of the potential drug binding site(s) remains elusive. Here we report the crystal structure of the soluble domain of human mitoNEET with a sulfonamide ligand, furosemide. Exploration of the high-resolution crystal structure is used to design mitoNEET binding molecules in a pilot study of molecular probes for use in future development of mitochondrial targeted therapies for a wide …

Do Rope And Washer Pumps Provide Safe Water And Satisfied Users? A Case Study Piloting New Rural Water Supply Technology In Rumphi District, Malawi, Jacob C. Mkandawire, Mavuto Tembo, Muthi Nhlema, Joel Luhanga, Rochelle H. Holm

Faculty Scholarship

Innovation is needed to develop rural water supply to support sub-Saharan Africa communities that are hard to reach. The purpose of this study was to critically review rope and washer pumps that have been installed on manually drilled boreholes in 48 communities as part of a pilot project in Rumphi District, Malawi, and which serve as a sustainable source of drinking water from both technical (water quality and functionality) and social (user satisfaction) perspectives. At each water source, an infrastructure checklist was used (n = 48); 10 users were interviewed (n = 472); and, if the pump had water, water …

"We Didn't Know": An Examination Of Health And Nutrition Knowledge, Behaviors And Clinical Risk Factors To Guide A Pilot Health Education Intervention For Refugees From Burma, Elizabeth B. Smith, Lauren R. Sastre

Journal of Refugee & Global Health

No abstract provided.

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 …

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 …

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, …

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 …

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 …

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 …

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 …

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, …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

Agent-Based Modelling For Simulation-Based Design Of Sustainable Faecal Sludge Management Systems, Adrian Mallory, Martin Crapper, Rochelle H. Holm

Faculty Scholarship

Re-using faecal sludge (FS) to generate value has the potential to contribute towards solving the issue of long term sanitation solutions in growing urban areas across sub-Saharan Africa; however, hitherto, no design tools have been available that are capable of simulating a system involving economic factors, complex social issues and environmental circumstances. We hypothesized that Agent-Based Modelling (ABM), when deployed with appropriate rigour, can provide such a tool. Extensive field work was carried out in a Malawian city, investigating the adoption of Skyloo above-ground composting toilets by households, and the operation of the municipal FS site. 65 semi-structured interviews and …

Reasons For Vaccine Declination In Healthy Individuals Attending An International Vaccine And Travel Clinic, Timothy L. Wiemken, Julio A. Ramirez, Ruth M. Carrico

Journal of Refugee & Global Health

Little is known about the vaccine-related health behaviors of healthy individuals. We surveyed healthy individuals attending a vaccine center to define the reasons behind vaccine declination when the vaccine is warranted under current guidance. Declination due to perceived risks of the vaccines were by far the most common rationale, suggesting continued need for public health educational campaigns.

Multistate Hepatitis A Outbreak: Vaccination Of Food Service Workers As Part Of The Kentucky Outbreak Response, Ruth M. Carrico, Dawn Balcom, Delanor Mason, Audria G. Denker, Alyson Holland, Kimberley A. Buckner, Stephen P. Furmanek, Wesley Trail

Journal of Refugee & Global Health

Background: In August 2017, a local outbreak of Hepatitis A was identified among homeless individuals in Louisville, Kentucky. This marked the first cases in what has now become recognized as the largest Hepatitis A outbreak in the US. When infection was identified in a Food Service Worker (FSW), vaccination efforts were expanded to target this group.

Objective: The purpose of this study was to describe: 1) the processes used to provide access to Hepatitis A vaccine for FSWs, 2) results from the immunization activities, and 3) lessons learned from the outcomes.

Methods: Through a partnership between the Louisville Metro Department …

Intestinal Parasite Burden And Pre-Departure Treatment Compliance In Kentucky Refugee Children: A Descriptive Study, Collin Russell, Annie H. Rominger

Journal of Refugee & Global Health

Objective: Children are 1/2 of the world’s refugees and often have intestinal parasites. This study seeks to determine the intestinal burden and pre-departure treatment of Kentucky pediatric refugees.

Methods: This is a chart review of Kentucky pediatric refugee health screening data from 2012-2017. Stool culture results from children arriving through refugee camps were compared to non-camp children. They were placed into 3 regional groups and analyzed based on CDC pre-departure treatment recommendations.

Results: Of the 3,199 records, 1,653 had stool testing. 354 (51%) refugee camp children tested positive compared to 326 (33.9%) non-camp children. Giardia and Blastocystis were most commonly …

Letter From The Editor-In-Chief: Journal Of Refugee & Global Health Volume 2 Issue 1, Ruth Carrico

Journal of Refugee & Global Health

No abstract provided.