Life Sciences Commons^™

Exploring The Diversity Of Microeukaryotic Communities In New England Tide Pools, Adri K. Grow, Robin S. Sleith, Taylor R. Sehein, Michaela Labare, Laura A. Katz

Biological Sciences: Faculty Publications

Though historically understudied, due in large part to most species being uncultivable, microbial eukaryotes (i.e. protists) are abundant and widespread across diverse habitats. Recent advances in molecular techniques, including metabarcoding, allow for the characterization of poorly known protist lineages. This study surveys the diversity of SAR (Stramenopila, Alveolata, and Rhizaria), a major eukaryotic clade that is estimated to represent about half of all eukaryotic diversity. SAR lineages use varied metabolic strategies like mixotrophy in dinoflagellates (Alveolata), parasitism in apicomplexans (Alveolata) and labyrinthulids (Stramenopila), and life cycle stages that include encystment and attachment (e.g. in ciliates, Alveolata) to survive in highly …

Multiomics For Elucidating The Pathogenesis Of Liver Cancers: A Transcriptomic Signature Of Fibrolamellar Hepatocellular Carcinoma, David R. Requena Anicama

Student Theses and Dissertations

Fibrolamellar Hepatocellular Carcinoma (FLC) is a rare liver cancer affecting adolescents and young adults. Almost all FLC patients present a somatic heterozygous deletion in chromosome 19p13.12, producing the chimeric transcript DNAJB1::PRKACA, which is sufficient to drive FLC in mice. Nevertheless, a few cases of liver tumors presenting FLC histopathological characteristics but missing the chimera DNAJB1::PRKACA have been reported. They have either 1) a lack of protein expression of PRKAR1A, 2) the presence of the chimeras ATP1B1::PRKACB or ATP1B1::PRKACA, or 3) a chromosome gain of PRKACA or loss of PRKAR2A, accompanied with inactivation of BAP1. A few RNA-seq studies compared FLC …

The Molecular Mechanisms Of Ifn-Γ Promoted Necroptosis In Macrophages, Meghan R. Vogt

Biotechnology Theses

Necroptosis, a form of programmed lytic cell death, has emerged as a driving factor in the pathogenesis of acute lung injury. One specific inflammatory mediator that is of interest is interferon-γ (IFN-γ). Our laboratory has reported that IFN-γ is the most potent enhancer of necroptosis in primary lung epithelial cells and macrophages by upregulating MLKL expression. How IFN-γ enhances necroptosis and MLKL upregulation is currently unknown. In this research, we utilized multiple approaches to study the potential molecular mechanisms of IFN-γ promoted necroptosis in macrophages. We found that MLKL and ZBP1 are significantly upregulated by IFN-γ through an unknown pathway …

Comparison Of Groundwater Chemistry And Associated Biodiversity Of Sulfidic Karst Habitats In Southcentral Kentucky, Kendall Wheeler

Mahurin Honors College Capstone Experience/Thesis Projects

In most ecosystems, primary production is conducted by plants or photosynthetic microbes; however, extremophilic sulfur-oxidizing bacteria can use hydrogen sulfide gas (H2S) as an electron donor to produce metabolic energy in a type of metabolism called chemoautotrophy. These ecosystems are a prominent feature of some karst landscapes, and two have been observed in the Mammoth Cave system, Sulphur River in Parker Cave and Marianne’s Pass in Mammoth Cave National Park respectively.

Sulfidic water is ubiquitous in southcentral Kentucky and is strongly associated with hydrocarbon deposits. This oil boom of the 1880s in this region predates most environmental regulation and records …

Eye Lens Β-Crystallins Are Predicted By Native Ion Mobility-Mass Spectrometry And Computations To Form Compact Higher-Ordered Heterooligomers, Amber D. Rolland, Takumi Takata, Micah T. Donor, Kirsten J. Lampi, James S. Prell

Faculty Publications - Department of Biological & Molecular Science

Eye lens crystallin proteins maintain the refractive properties of the lens but are not replaced after denucleation. Rolland et al. use native ion mobility-mass spectrometry, kinetics experiments, and computations to reveal that b-crystallins form heterodimers. These likely assemble into compact heterooligomers that enable the very high protein concentrations found in lens tissue.

Exploring The Molecular Basis Of Touch: A Comparative Analysis Of Gene Expression In Sensory Corpuscle-Rich And Corpuscle-Poor Skin Regions In The Duck, Thomas Hart

Theses and Dissertations--Biology

Cutaneous touch is facilitated by discrete cellular complexes composed of non-neuronal cells associated with mechanoreceptor neuron endings. The non-neuronal cells of these cutaneous end organ complexes (CEOCs) are believed to contribute to touch, but their role in touch sensation remains unclear. To better understand the function of CEOC cells, we sought to characterize the transcriptional profile of CEOC-rich tissue and identify genes expressed in CEOC cells. Bill skin of the tactile foraging Pekin duck (Anas platyrhynchos) is dense with CEOCs, specifically the avian analogs of mammalian Pacinian and Meissner corpuscles, while corpuscles in duck foot skin are scarce. Using RNA …

Variation In Behavioral Strategies For Coping With Environmental Uncertainty, Allison Mclaughlin

Theses and Dissertations--Biology

My dissertation investigates how animals behaviorally respond to environmental change, especially when there is limited information about that change. Uncertainty about the environment comes in various forms, including food resources which vary unpredictably and novel cues which present an unknown level of potential risk or benefit. Various behavioral strategies help animals cope with such uncertainty. Tactics to manage unpredictable variation in food include gathering information to reduce uncertainty (sampling) and strategically adjusting preference or aversion to variation in resources (variance-sensitivity). To manage the uncertainty of a novel cue, animals may generalize their previous experience with similar cues, or they may …

Investigation Of Key Mechanisms Of Contact Dependent Growth Inhibition Systems In Burkholderia Cepacia Complex Species, Zaria K. Elery

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Burkholderia cepacia complex is a group of closely related environmental bacteria that can exacerbate disease in immunocompromised individuals. B. cepacia bacteria are equipped with an arsenal of mechanisms to cooperate and compete for nutrients in various polymicrobial environments. Contact-dependent growth inhibition (CDI) systems are antagonistic mechanisms widespread among proteobacteria. CDI systems consist of Two Partner Secretion pathway proteins that function to deliver the toxic C-terminal portion of the large effector exoprotein (termed ‘BcpA’ in Burkholderia-type CDI systems) to the cytoplasm of a compatible recipient bacterial cell upon direct cell to cell contact. The translocation of BcpA out of the …

Investigating The Relationship Between Metabolic Reprogramming And Peripheral Cd4+ T-Cell Inflammation In Human Type 2 Diabetes Pathogenesis, Gabriella Kalantar

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Chronic, low-grade systemic inflammation rises in obesity and promotes type 2 diabetes (T2D). Circulating immune cells are key indicators of obesity and T2D pathogenesis. T cells outnumber monocytes, in blood, suggesting that T cells might fuel peripheral inflammation in obesity/T2D. Our lab’s work supports this idea by identification of a Th17 cytokine profile in T2D from T-cell stimulated peripheral blood mononuclear cells. Work described herein further supported this work by demonstrating that T cells dominate peripheral inflammation over monocytes across the spectrum of obesity and glycemic control. Our lab has also recently shown that inflammation changes during prediabetes (preT2D), identified …

Substrate Selection And Effector Gating In The Helicobacter Pylori Cag Type Iv Secretion System, Mackenzie E. Ryan

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Helicobacter pylori is a recognized carcinogen and gastric colonization by strains that harbor the cag type IV secretion system (1) is the strongest known risk factor for stomach malignancy. Gastric adenocarcinoma is the fourth leading cause of cancer-related deaths world-wide ( > 700,000 deaths annually), with H. pylori directly contributing to the development of more than one million new cases of cancer per year accounting for 5.5% of all malignancies. H. pylori exploits cag T4SS activity to alter the mucosal microenvironment by delivering diverse immunostimulatory cargo into target gastric epithelial cells. Currently, the mechanisms by which the cag T4SS …

Therapeutic Implications Of The Gut-Cns Axis In Promoting Recovery Following Cervical Spinal Cord Injury, Jessica Wilson

Theses and Dissertations--Neuroscience

Nearly 60% of all spinal cord injuries (SCI) occur at the cervical level. These high-level injuries can interrupt the descending respiratory pathways required for breathing. Indeed, therapies in animal studies have been successful at restoring breathing after SCI; however, these interventions appear to be more effective at chronic time points. One potential cause for this observation is the impact of the injury on the gut microbiome. Neurotrauma can induce gut dysbiosis, an imbalance of pathogenic and beneficial gut microbiota, which has previously been shown to negatively impact the central nervous system (CNS) and impair recovery. We aimed to build upon …

Effectiveness Of A Long-Acting Cocaine Hydrolase In Metabolizing Cocaine And Its Physiologically Active Metabolites, Linyue Shang

Theses and Dissertations--Pharmacy

Cocaine is a widely abused, hepatotoxic drug without an FDA-approved pharmacotherapy specific for cocaine addiction or overdose. Cocaine-induced toxicity in animals and humans is due to its multiple physiological effects on the central nervous system, cardiovascular system, etc. The toxicity of cocaine is highly complex, as its metabolites also contribute to the toxicity. Notably, the combination of cocaine and alcohol is common among drug users and can produce additional metabolites. Some of the metabolites are more toxic than cocaine itself. Hence, to develop an ideal therapeutic candidate, the candidate should not only account for cocaine but should also detoxify other …

Genetic And Pharmacogenetics Associations Of Cancer Disparities In Appalachia, Nan Lin

Theses and Dissertations--Pharmacy

Individuals residing in Appalachian regions have significant health disparities, including higher cancer incidence and mortality rates. Previous studies have addressed the impact of socioeconomic status and environmental risk factors on Appalachia cancer disparities, while few studies have evaluated genetic risk factors.

Germline whole exome sequencing samples from 7,078 individuals with cancer (759 Appalachians) were evaluated. Demographics and relatedness were assessed using KING. Ethnicity was verified by principal component analysis using TRACE, which included 6,034 individuals (85%) of European genetic ancestry. After QC filtering, 5,980 individuals were analyzed. To assess the overall predisposition of hereditary disease, gene level frequency of likely …

Bioinformatic Analysis Of Proteomic And Genomic Data From Nsclc Tumors On Prognostic And Predictive Factors Of Immunotherapy Treatment, Mark Wuenschel

Theses and Dissertations--Pharmacy

Recent lung cancer research has led to advancements in molecular immunology, resulting in development of small molecule inhibitors, or immune checkpoint inhibitors, that propagate an anti-tumor T cell response. Despite increased overall and progression-free survival with reduced adverse effects compared to traditional chemotherapy, treating advanced stage lung adenocarcinoma patients remains non-curative, and evidence of non-responders or tumor recurrence to immune checkpoint inhibitor therapy is growing. Also, compared to traditional chemotherapy, there is a lower percentage of patients who respond to small molecule inhibitors. In this analysis of proteomic and genomic data from The Cancer Proteome Atlas and Global Data Commons …

Developing A Biocatalytic Toolbox To Aid In Understanding Nucleoside Antibiotics, Jasmine Brianna Woods

Theses and Dissertations--Pharmacy

Antibiotic resistance happens when bacteria develop the ability to survive medications that normally terminate them. Instead, these super germs are able to survive in the body and produce a community of antibiotic resistance germs which can cause human fatalities. It is important to discover and develop new compounds and molecules that will improve this clinical obstacle. This research focused on analyzing the biosynthesis that incorporates distinctive chemical characteristic of various nucleoside antibiotics, ß-hydroxy amino acids and α-methyl-amino acids. ß-hydroxy amino acids and α-methyl-amino acids are considered an important class of industrially useful compounds, particularly for pharmaceutical development, and are found …

Age- And Sex-Dependent Alterations In Primary Somatosensory Neuronal Calcium Network Dynamics During Locomotion, Sami L. Case

Theses and Dissertations--Pharmacology and Nutritional Sciences

Over the past 30 years, the calcium (Ca2+) hypothesis of brain aging has provided clear evidence that hippocampal neuronal Ca2+ dysregulation is a key biomarker of aging. Indeed, age-dependent Ca2+-mediated changes in intrinsic excitability, synaptic plasticity, and activity have helped identify some of the mechanisms engaged in memory and cognitive decline. However, much of this work has been done at the single-cell level, mostly in slice preparations, and in restricted structures of the brain. Recently, our lab identified age- and Ca2+-related neuronal network dysregulation in the cortex of the anesthetized animal. Still, investigations in the awake animal are needed to …

Relative Adrenal Insufficiency In Sepsis, Dan Hao

Theses and Dissertations--Pharmacology and Nutritional Sciences

Sepsis is a leading cause of death in children. Glucocorticoid (GC) therapy had been strongly recommended for the pediatric sepsis (grade 1A). However, the recommendation was changed to grade 2C in 2020 due to weak evidence. Relative adrenal insufficiency (RAI) is a condition characterized by impaired inducible glucocorticoid (iGC) production in response to stress. It develops in 32.8% of pediatric septic patients. Unfortunately, little is known about the pathogenesis of RAI in pediatric sepsis, and whether GC therapy should be based on the status of RAI is controversial. In this study, we utilized 21-day-old SF1CreSRBI^fl/fl mice as the first …

Age-Associated Increase Of Gamma Delta T Cells In Visceral Adipose Tissue And Mechanisms Of Their Accumulation, Sujata Mukherjee

Theses and Dissertations--Pharmacology and Nutritional Sciences

Chronic systemic inflammation, known as inflammaging is considered a hallmark of aging and associated diseases. While adipose tissue has long been considered only as a caloric reservoir regulating systemic energy homeostasis, research in the past couple of decades substantiate its endocrine function to secrete an array of inflammatory mediators and hormones, which have physiological effects on multiple organ systems, and contribute to inflammaging. Redistribution of adipose tissue from subcutaneous to visceral depots, changes in the immune profile and the chronic inflammatory state are among the major sources of adipose tissue dysfunction with aging.

This dissertation is focused on identifying and …

The Role Of Renal-Derived Human Soluble Prorenin Receptor In Blood Pressure Regulation And Kidney Function, Gertrude Arthur

Theses and Dissertations--Pharmacology and Nutritional Sciences

The soluble prorenin receptor (sPRR) is a cleaved form of the full-length prorenin receptor (PRR). It has been demonstrated to activate the renin-angiotensin system (RAS) independent of its full-length receptor and mediate similar physiological and pathophysiological processes, albeit via different mechanisms.

The sPRR hormone, a component of RAS, has been identified as a plasma biomarker for hypertension and cardiovascular diseases in humans. In mice, sPRR infusion has been shown to mediate blood pressure elevation through competitive AT1R binding and activation. However, the biological contribution of renal-derived human sPRR to blood pressure regulation and kidney function remains unknown. Therefore, this study …

Effects Of Traumatic Brain Injury On The Intestinal Tract And Gut Microbiome, Anthony Desana

Theses and Dissertations--Physiology

Traumatic brain injury (TBI) initiates not only complex neurovascular and glial changes within the brain but also pathophysiological responses that extend beyond the central nervous system. The peripheral response to TBI has become an intensive area of research, as these systemic perturbations can induce dysfunction in multiple organ systems. As there are no approved therapeutics for TBI, it is imperative that we investigate the peripheral response to TBI to identify targets for future intervention. Of particular interest is the gastrointestinal (GI) system. Even in the absence of polytrauma, brain-injured individuals are at increased risk of suffering from GI-related morbidity and …

Clinical And Biological Factors Determine Spinal Cord Injury Outcomes: Liquor To Lipids, Ethan Glaser

Theses and Dissertations--Physiology

Spinal cord injuries (SCI) are debilitating and life altering events that can lead to permanent motor and sensory loss. SCI outcomes are impacted by both clinical factors such as blood alcohol content (BAC) at the time of injury as well as biological factors like the lipid-rich myelin debris that accumulates in the injury site. Both clinical and biological factors contribute to SCI recovery, impacting neuroinflammation, locomotor recovery, and histopathology. The purpose of the studies described here is to investigate the role of acute alcohol intoxication and intracellular lipid processing pathways on SCI outcomes in a rodent model.

An elevated BAC …

Rewired Metabolism In Apoe4 Microglia: Implications For Inflammation And Neurodegeneration, Nicholas A. Devanney

Theses and Dissertations--Physiology

Among the earliest changes to occur in Alzheimer’s disease, metabolic dysfunction and chronic neuroinflammation are now known to be major driving forces in disease progression. The paradigm of ‘immunometabolism’ seeks to bridge these two facets, positing that metabolic transformations are indispensable in determining the response of immune cells, such as microglia – the brain’s resident immune population. Proinflammatory stimulation of microglia leads to a shift away from mitochondrial respiration towards a dramatic upregulation of the glycolysis pathway for energy production. This glycolytic burst provides microglia with a rapid supply of ATP, but comes at a cost, as utilizing glucose to …

Understanding The Effects Of Age, Environmental Conditions, And Placement On Cockroach Gel Bait Performance, Isabelle Lucero

Theses and Dissertations--Entomology

Cockroach baits are one of the most effective tools used for German cockroach (Blattella germanica L.) control. This is due in part to the number of cockroach baits on the market with various matrix compositions and active ingredients, aiding in the control of resistant (physiologically and behaviorally) cockroach populations through bait rotation. However, it remains unclear how cockroach gel baits perform over time and under different environmental conditions. Therefore, we aged six cockroach gel baits for varying times (24 hours, one month, three months, six months) and at three relative humidities (15%, 40%, and 80%), and tested their performance …

Examining The Utility Of A Kentucky Fcs Cooperative Extension Curriculum On Community Members’ Healthy And Sustainable Diet-Related Behaviors, Catharine Pickford

Theses and Dissertations--Nutrition and Food Systems

Experts recommend individuals adopt healthy and sustainable dietary behaviors to improve human and environmental health. The objective of this study was to pilot a sustainable eating Family and Consumer Sciences (FCS) Cooperative Extension curriculum and evaluate the effectiveness of the lesson series by measuring participants’ changes in knowledge, perceptions, and intentions towards healthy and sustainable dietary behaviors as well as overall satisfaction with lessons. A five-lesson sustainable eating curriculum was developed with topics focused on: reducing food waste; eating more seasonal, local plant-based foods; varying protein sources; maintaining energy balance; and consuming fewer highly processed and packaged foods. To assess …

Mechanisms Of Rnai In Insects, Jin Mo Koo

Theses and Dissertations--Entomology

RNA interference (RNAi) mechanism is found in many eukaryotes and animal cells, with its endogenous functions as defense against transposable elements and viruses, as well as post transcriptional regulation of gene expression. Since its first discovery, RNAi has contributed enormously as a reverse genetic tool for functional genomic studies. In application, RNAi is used in therapeutics, as well as agricultural crop and livestock protection. Yet, for the wider application of RNAi, improvement of its potency and delivery technologies is needed. Deeper mechanistic understanding of every step of RNAi, from cellular uptake of RNAi trigger molecule to targeted mRNA degradation is …

Costs And Benefits Of Integrating Poultry Into Cover Crop - Vegetable Rotations, Viktor Halmos

Theses and Dissertations--Entomology

Integrated livestock systems were once common leading up to the 20th century where livestock generated manure that was then used to fertilizer crop production in a closed- or semi-closed system. However, with the industrialization of agriculture in the mid to late 20th century, specialization drove simplified systems that segregated livestock from cropping systems. This segregation led to nutrient surpluses occurring in livestock operations, and nutrient demands in cropping systems creating a plethora of environmental issues. With the increased awareness of environmental issues, a renewed interest in integration has driven producers and researchers to experiment with integration again. For research, the …

The Role Of Map Kinases, Transcription Factors, Callose Binding Proteins In Systemic Acquired Resistance, Xinyu Yuan

Theses and Dissertations--Plant Pathology

Systemic acquired resistance (SAR) is a broad-spectrum disease resistance induced upon local infections that provides protection against secondary infections. Earlier work has shown that SAR is regulated by two parallel pathways, one of which is regulated by salicylic acid (SA), and the other one involves pipecolic acid (Pip), nitric oxide (NO), reactive oxygen species (ROS), azelaic acid (AzA), and glycerol-3-phosphate (G3P). Pip acts upstream of NO, ROS, AzA, and G3P in the local leaves but the distal accumulation of Pip depends on the biosynthesis and transport of SA and G3P.

Normal induction of SAR also requires mitogen-activated protein kinase (MPK) …

Exploring The Effects Of Environmental Factors On Rice Blast Disease, April Ellen Lamb

Theses and Dissertations--Plant Pathology

Rice blast disease, caused by the ascomycete fungus Magnaporthe oryzae, occurs in over 85 countries and results in an annual crop loss of 10-30%, a corresponding nutrient value of meals for 60 million people. As a result, it is listed as a critical plant disease by the United Nations. Understanding factors affecting disease severity is of critical concern for food security. M. oryzae has been used as a model system for studying effector-triggered immunity (ETI) by understanding that ETI is primarily a plant response. M. oryzae has been used as a model to study fungal pathogenicity, host specificity, genome …

Molecular Genetic Studies Of Horses, Especially With Reference To Aggrecan And Dwarfism, John Edmund Eberth

Theses and Dissertations--Veterinary Science

This work consists of studies on dwarfism in Miniature horses and a study on breakdowns in Thoroughbreds in relation to gene aggrecan. A correction of the description and designation of D3 dwarf variant in aggrecan (ACAN) from the master’s thesis Chondrodysplasia-like dwarfism in the Miniature horse (2013). Commercial sequencing showed previous sequencing reads presented an artifact and not a single base deletion. Analysis showed a single base missense mutation in exon 8 identified as D3* was the actual cause. Multiple alleles of ACAN associated with chondrodysplastic dwarfism in Miniature horses by Eberth et al. (2018), corrected the …

Effects Of High-Speed Training On Messenger Rna Expression In Two-Year-Old Thoroughbred Racehorses, Mackenzie Grace Johnson

Theses and Dissertations--Veterinary Science

Accumulating high-speed exercise has been identified as a significant risk factor for catastrophic injuries in racing Thoroughbreds. Injuries, regardless of severity, are a main cause of withdrawal from the racing industry, raising animal welfare concerns and resulting in significant economic losses. While most of the current literature focuses on catastrophic injuries incurred during racing rather than training, the present study aims to help fill this gap as well as discuss the associated risk factors. The evaluation of messenger RNA (mRNA) expression changes provides an efficient and straightforward approach to identifying horses at risk for catastrophic injury. While alternative injury risk …