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Articles 1 - 27 of 27
Full-Text Articles in Life Sciences
Translating Particulate Hexavalent Chomium-Induced Chromosome Instability, Loss Of Homologous Recombination Repair And Targeting Of Rad51 From Human Lung Fibroblasts To Human Bronchial Epithelial Cells., Idoia Meaza Isusi
Electronic Theses and Dissertations
Particulate hexavalent chromium [Cr(VI)] is a well-established human lung carcinogen. RAD51, a key protein in homologous recombination repair pathway, is inhibited after prolonged exposure to Cr(VI), leading to an increase in chromosome instability after prolonged exposures in human lung fibroblasts. chromosome instability is the proposed driver of Cr(VI) carcinogenesis. Since tumors from chromate workers develop from epithelial cells, we sought to translate these findings from human bronchial fibroblasts to human bronchial epithelial cells. We hypothesized Cr(VI) inhibits RAD51 after prolonged exposure leading to an increase in chromosome instability in human bronchial epithelial cells (BEP2D). We characterized the cytotoxicity and measured …
Impact Of Pank1 Deletion On Mitochondrial Acetylation And Cardiac Function During Pressure Overload., Timothy N. Audam
Impact Of Pank1 Deletion On Mitochondrial Acetylation And Cardiac Function During Pressure Overload., Timothy N. Audam
Electronic Theses and Dissertations
Recent studies have associated elevated protein acetylation levels with heart failure in humans. Although mechanisms promoting elevated acetylation levels are not fully known, excess acetyl-CoA may drive enzyme-independent acetylation of cardiac proteins. Accumulation of acetyl-CoA depends on the availability of sufficient CoA, whose production is regulated by pantothenate kinases in the CoA biosynthetic pathway. We show that cardiac proteins are hyperacetylated during heart failure in humans and tested in mice whether limiting CoA abundance would improve ventricular remodeling during pressure overload-induced hypertrophy. We limited cardiac CoA levels by deleting the rate-limiting enzyme in CoA biosynthesis, Pank1 (one of three PANK-encoding …
Investigations Of Potential Mechanisms Underlying Spinal Cord Injury-Induced Polyuria., Jason H. Gumbel
Investigations Of Potential Mechanisms Underlying Spinal Cord Injury-Induced Polyuria., Jason H. Gumbel
Electronic Theses and Dissertations
Spinal cord injury (SCI) results in neurological impairments including motor, sensory, and autonomic dysfunction. These neurological deficits result in a litany of complications apart from muscular paralysis, including bladder, bowel, cardiovascular, and sexual function. SCI-induced polyuria (the overproduction/passage of urine) remains understudied, and therefore mechanisms behind it are largely unknown and require extensive investigation for potential targeted therapies to improve quality of life. The objective of this dissertation was to investigate potential mechanisms of SCI-induced polyuria and explore potential therapies to improve quality of life in the SCI population. Metabolic cages, Western blot, enzyme-linked immunoassay, and immunostaining were first used …
Investigation Of Mitochondrial Inheritance In The Smut Fungus Sporisorium Reilianum., Hector Eduardo Mendoza
Investigation Of Mitochondrial Inheritance In The Smut Fungus Sporisorium Reilianum., Hector Eduardo Mendoza
Electronic Theses and Dissertations
An important goal in evolutionary biology is to address the origin of Earth’s immense biodiversity through the evolution of complex sexual reproduction mechanisms in eukaryotes. Inheritance of mitochondria during sexual reproduction has received special attention in recent years, as these organelles cannot be synthesized de novo and must be transmitted from parent to offspring. The importance of these organelles far exceeds its common function as the energy-producing “powerhouse” of the cell, as it has been found to also be involved in fundamental processes like apoptosis, aging and metabolic homeostasis. Thus, appropriate inheritance of mitochondria is essential for growth and development …
Q-Griffithsin Interactions And Utility For The Prevention And Treatment Of Mucosal Infections., Henry Nabeta
Q-Griffithsin Interactions And Utility For The Prevention And Treatment Of Mucosal Infections., Henry Nabeta
Electronic Theses and Dissertations
Griffithsin (GRFT) is a carbohydrate binding agent (lectin) that was originally identified in the red alga Griffithsia sp. Q-Griffithsin (Q-GRFT) is an oxidation stable analog of GRFT. GRFT has demonstrated inhibitory activity against HIV-1, Coronaviruses, Hepatitis C, influenza and Ebola viruses. The broad-spectrum activity suggests the potential utility of this lectin in a wide range of viral infections. However, the lectin’s activity in mucosal infections has not been extensively studied. Using in vitro, ex vivo and in vivo assays, we have demonstrated that Q-GRFT maintains the ability to bind glycosylated ligands following incubation in murine, macaque and human rectal …
Role Of Meibum And Tear Phospholipids In The Evaporative Water Loss Associated With Dry Eye., Samiyyah M. Sledge
Role Of Meibum And Tear Phospholipids In The Evaporative Water Loss Associated With Dry Eye., Samiyyah M. Sledge
Electronic Theses and Dissertations
It is generally believed that the tear film lipid surface film inhibits the rate of evaporation (Revap) of the underlying tear aqueous. It is also generally believed that changes in the composition of the tear film lipid layer is responsible for an increase in Revap in patients with dry eye. Both of these ideas have never been proven. The purpose of the current studies was to test these ideas. Revap was measured in vitro gravimetrically. Lipid spreading was measured using Raman spectroscopy and microscopy. The influence of the following surface films on the Revap of the sub phase of physiologically …
Visualizing Anhydrobiosis: Liquid-Liquid Phase Separation, Membraneless Organelles, And Cellular Reorganization., Clinton J. Belott
Visualizing Anhydrobiosis: Liquid-Liquid Phase Separation, Membraneless Organelles, And Cellular Reorganization., Clinton J. Belott
Electronic Theses and Dissertations
Water is an integral and necessary component of life. It is then, exceedingly remarkable that some species are capable of surviving virtually complete water loss for extended periods of time. Several decades of intense research into anhydrobiosis, or life without water, have given significant insights into the molecular mechanisms governing this phenomenon. Anhydrobiosis-related intrinsically disordered (ARID) proteins have been demonstrated to be critically important for desiccation tolerance in many anhydrobiotic species and exhibit a considerably wide range of protective properties that include membrane stabilization, reinforcing bioglass formation, and protein stabilization. This dissertation begins with cellular dielectrophoresis suggesting that two ARID …
Computational And Biochemical Characterizations Of Anhydrobiosis-Related Intrinsically Disordered Proteins., Brett R. Janis
Computational And Biochemical Characterizations Of Anhydrobiosis-Related Intrinsically Disordered Proteins., Brett R. Janis
Electronic Theses and Dissertations
Anhydrobiosis is the remarkable phenomenon of “life without water”. It is a common technique found in plant seeds, and a rare technique utilized by some animals to temporarily stop the clock of life and enter a stasis for up to several millennia by removing all of their cellular water. If this phenomenon can be replicated, then biological and medical materials could be stored at ambient temperatures for centuries, which would address research challenges as well as enhance the availability of medicine in areas of the world where refrigeration, freezing, and cold-chain infrastructure are not developed or infeasible. Furthermore, modifying crop …
How Do Cover Crops Change Soil Health In A No-Till System?, Aysha Kirsten Tapp Ross
How Do Cover Crops Change Soil Health In A No-Till System?, Aysha Kirsten Tapp Ross
Electronic Theses and Dissertations
Nutrient levels and aggregation measurements are currently the most accurate means to measure soil health. It has been suggested that bacterial and fungal communities may prove to be a more accurate measure of soil health. In this study soil microbe communities and nutrient levels were compared in rye cover cropped soils to measure for differences between treatments. Effects between the microbial communities and environmental measurements were also measured within those treatments to test for correlations between soil health measures and microbial communities. The plots were put in a biennial corn (Zea mays L.) and soybean (Glycine max …
Pyridine Nucleotide Redox Potential In Coronary Smooth Muscle Couples Myocardial Blood Flow To Cardiac Metabolism., Marc Matthew Dwenger
Pyridine Nucleotide Redox Potential In Coronary Smooth Muscle Couples Myocardial Blood Flow To Cardiac Metabolism., Marc Matthew Dwenger
Electronic Theses and Dissertations
The maintenance of myocardial oxygen supply during stress is essential for sustaining cardiac health. Enhancement of coronary blood flow upon increases in myocardial oxygen demand (i.e., hyperemia) relies on regulation of voltage-gated K+ (Kv) channels by their intracellular β subunits (i.e., Kvβ proteins). Considering that, Kvβ proteins are aldo-keto reductases (AKRs) and regulate Kv channel gating, we tested the hypothesis that elevation of myocardial oxygen demand modifies intracellular NAD(H) in arterial myocytes. Furthermore, we tested whether the resultant change in the redox state of the pyridine nucleotide pool directly regulates coronary Kv1 channel activity. High-resolution imaging mass spectrometry and …
Characterizing The Role Of Macrophages In Cisplatin-Induced Kidney Injury And Progression To Chronic Kidney Disease., Sophia M. Sears
Characterizing The Role Of Macrophages In Cisplatin-Induced Kidney Injury And Progression To Chronic Kidney Disease., Sophia M. Sears
Electronic Theses and Dissertations
Cisplatin is a commonly used chemotherapeutic for treatment of many solid-organ cancers. Unfortunately, 30% of patients treated with cisplatin develop acute kidney injury (AKI), and even patients who do not develop AKI are at risk for long term declines in kidney function and development of chronic kidney disease (CKD). While traditional rodent toxicity studies have utilized a single, lethal dose of cisplatin, new models of cisplatin-induced kidney injury have revealed that repeated, low doses of cisplatin lead to development of kidney fibrosis. This model can be used to examine AKI-to-CKD transition processes. C57BL/6 mice are one of the most used …
The Role Of Sphingolipids In Aki And The Progression To Ckd: Potential Therapuetic Targets., Nicholas A. Hoffman
The Role Of Sphingolipids In Aki And The Progression To Ckd: Potential Therapuetic Targets., Nicholas A. Hoffman
Electronic Theses and Dissertations
Acute Kidney Injury (AKI) is most simply defined as a rapid decline in kidney function over a period of hours to days. There is currently a lack of effective treatment options for patients with AKI, highlighting the need to identify new therapeutic targets. Sphingolipids play a number of roles in different models of AKI, suggesting they could be promising future targets for treating kidney injury. Specifically, sphingosine-1-phosphate (S1P) and its receptors (S1PRs) have been implicated in numerous inflammatory disorders and models of AKI. The purpose of this review is to better characterize the role of S1P receptors in models of …
A Method For Identifying Ancient Introgression Between Caballine And Non-Caballine Equids Using Whole Genome High Throughput Data., Kalpani De Silva
A Method For Identifying Ancient Introgression Between Caballine And Non-Caballine Equids Using Whole Genome High Throughput Data., Kalpani De Silva
Electronic Theses and Dissertations
Introgression is one of the main mechanisms that transfer adapted alleles between species. The advantageous variants will get positively selected and retained in the recipient population while rest of the variants undergo negative selection. When analyzing horse genome, two alleles were found in CXCL16 gene, one associated with susceptibility and one with resistance to developing persistent shedding of the Equine Arteritis Virus. The two alleles differ by 4 non-synonymous variants in exon 1 of the gene. Comparison with 3 non-caballine equids (zebras, asses and hemiones) revealed that one haplotype was almost identical to the haplotype found in non-caballines while the …
Community Structure And Dynamics Of Benthic Macroinvertebrates In A Recreated Headwater Stream System On A Valley Fill In A Retrofitted Watershed Located In The Appalachian Coalfields Of Southeastern Kentucky (U.S.A.), Steven W. Bailey
Electronic Theses and Dissertations
The extraction of coal from steep-gradient surface mining sites such as in the Appalachian Coalfields of the U.S. produces excess debris that is often placed in adjacent valleys resulting in the creation of valley fills. Not only are headwater streams buried in the process, but watershed functions are either destroyed outright, or become fragmented and disconnected from adjacent ecosystems resulting in adverse effects to downstream biological communities. In this dissertation, the dynamics of stream macroinvertebrate community structure, composition, diversity, and biotic integrity are assessed at a “proof of concept” stream system recreated on a retrofitted valley fill. For comparison, two …
Investigating The Effects Of Perfluorooctanoic Sulfonate (Pfos) And Ethanol On Fatty Liver Disease Using A Modified Niaaa Model., Tyler Charles Gripshover
Investigating The Effects Of Perfluorooctanoic Sulfonate (Pfos) And Ethanol On Fatty Liver Disease Using A Modified Niaaa Model., Tyler Charles Gripshover
Electronic Theses and Dissertations
Perfluoroalkyl Substances (PFAS) are a family of man-made, surfactant-like compounds that are a major environmental contaminant. A multitude of studies have indicated that PFAS are able to induce fatty liver disease and modulate lipid metabolism. However, the distinct mechanism of PFAS influence on the liver and metabolism disruption remains to be elucidated. On the other hand, it is well documented that alcohol consumption has various adverse health impacts including fatty liver disease and subsequent progression to more adverse liver states. To date, there are no published studies on whether PFAS and alcohol can jointly exacerbate fatty liver progression or interact …
Investigations Of Elastin Recoil On Molecular And Macroscopic Levels., Nour Mohammad Jamhawi
Investigations Of Elastin Recoil On Molecular And Macroscopic Levels., Nour Mohammad Jamhawi
Electronic Theses and Dissertations
Elastin is one of the most hydrophobic proteins, and it is extremely flexible when hydrated. The driving force for recoil is the decrease in entropy of the protein and/or the hydrating solvent. This dissertation is a study of both mechanisms. Following an introduction (Chapter 1), Chapters 2 and 3 investigate the recoil mechanism on the molecular level in the hydrating solvent and in the protein, respectively. Chapter 4 examines macroscopic properties of recoil by thermomechanics. Conclusions are discussed in Chapter 5. Using double quantum NMR, the deuterated water ordering at the elastin surface was studied quantitatively as a function of …
Assessing The Role Of Chronic Arsenite Exposure In Disrupting The Egfr Signaling Axis., Christine Kim
Assessing The Role Of Chronic Arsenite Exposure In Disrupting The Egfr Signaling Axis., Christine Kim
Electronic Theses and Dissertations
Chronic arsenic exposure is a risk factor for the development of pulmonary diseases, including lung cancer, but the exact mechanism is not yet fully understood. Many previous studies have relied on acute arsenic exposure (i.e. 1-10 uM arsenic for 24 hours) to study arsenic toxicological effects. However, acute exposure does not reflect the levels or duration of arsenic associated with environmental exposure, or drinking of contaminated well water. This dissertation differentiates the effects of acute versus chronic arsenic exposures on the EGFR signaling axis and suggests possible mechanisms for chronic arsenic-induced pulmonary diseases. The EGFR is a receptor tyrosine kinase …
Harnessing The Power Of Trained Immunity In The Setting Of Pancreatic Cancer: A Novel Mechanism Of Immune Trafficking And Tumor Control., Anne Elena Geller
Harnessing The Power Of Trained Immunity In The Setting Of Pancreatic Cancer: A Novel Mechanism Of Immune Trafficking And Tumor Control., Anne Elena Geller
Electronic Theses and Dissertations
Despite the success of immunotherapy in many types of cancer, pancreatic adenocarcinoma (PDAC) has yet to benefit. Innate immune cells are critical to antitumor immunosurveillance and recent studies have revealed that these populations possess a form of memory, termed trained innate immunity, which occurs through transcriptomic, epigenetic, and metabolic reprograming. Though trained innate immunity has mostly been investigated in the context of infection, the induction of trained innate immunity could also protect against tumors, and specifically pancreatic tumors. Here, we demonstrate that yeast-derived particulate β-glucan, a known inducer of trained immunity, traffics to the pancreas following IP administration. This causes …
Identifying The Cardiovascular Effects Of Multiple Pollutants., Katlyn Elizabeth Mcgraw
Identifying The Cardiovascular Effects Of Multiple Pollutants., Katlyn Elizabeth Mcgraw
Electronic Theses and Dissertations
Cardiovascular disease (CVD) is the leading cause of death from environmental exposures. Although exposure to PM2.5 is an established risk factor for CVD, the contribution of other hazardous pollutant exposure to CVD is less clear. Overall, this work aimed to examine the effect of pollutants with lesser documented effects on cardiovascular disease using a multi-pronged approach to exposure assessment. The three aims were to examine the relationship between county-level toxic chemical releases and CVD mortality in the contiguous United States between 2002 and 2012, to assess the relationship between individual-level VOC metabolites and vascular function, and to build multipollutant …
The Neural Architecture Of Emotional Intelligence., Teodora Stoica
The Neural Architecture Of Emotional Intelligence., Teodora Stoica
Electronic Theses and Dissertations
Emotional Intelligence (EI) is a nebulous concept that permeates daily interpersonal communication. Despite prolific research into its benefits, EI subjective measurement is difficult, contributing to an enigmatic definition of its core constructs. However, neuroimaging research probing socioaffective brain mechanisms underlying putative EI constructs can add an objective perspective to existing models, thereby illuminating the nature of EI. Therefore, the primary aim of this dissertation is to identify brain networks underlying EI and examine how EI arises from the brain’s functional and structural neuroarchitecture. EI is first defined according to behavioral data, which suggests EI is made up of two core …
Preclinincal Development Of Avaren-Fc: A Novel Lectin-Fc Fusion Protein Targeting Cancer-Associated High-Mannose Glycans., Matthew William Dent
Preclinincal Development Of Avaren-Fc: A Novel Lectin-Fc Fusion Protein Targeting Cancer-Associated High-Mannose Glycans., Matthew William Dent
Electronic Theses and Dissertations
This dissertation explores the anticancer activity of Avaren-Fc (AvFc), a novel lectin-Fc fusion protein or “lectibody” targeting cancer and virus-associated high-mannose glycans. Previously, we have shown that AvFc recognizes a broad selection of established cancer cell lines from a wide array of tissue types, can potently induce antibody-dependent cell-mediated cytotoxicity (ADCC) against them, and exhibits anti-cancer activity in vivo. However, the exact mechanism of action remains elusive. We hypothesized that the primary mechanism of action is through Fc-mediated effector functions, and the purpose of this dissertation is to explore this question through the use of Fc variants that either …
Investigating A Novel Function For Phosphoserine Aminotransferase 1 (Psat1) In Epidermal Growth Factor Receptor (Egfr)-Mediated Lung Tumorigenesis., Rumeysa Biyik-Sit
Investigating A Novel Function For Phosphoserine Aminotransferase 1 (Psat1) In Epidermal Growth Factor Receptor (Egfr)-Mediated Lung Tumorigenesis., Rumeysa Biyik-Sit
Electronic Theses and Dissertations
Phosphoserine aminotransferase 1 (PSAT1) catalyzes the second enzymatic step within the serine synthetic pathway (SSP) and its expression is elevated in numerous human cancers, including non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutant NSCLC is characterized by activating mutations within its tyrosine kinase domain and accounts for 17% of lung adenocarcinomas. Although elevated SSP activity has been observed in EGFR-mutant lung cancer cells, the involvement of PSAT1 in EGFR-mediated oncogenesis is still unclear. Here, we explore a putative non-canonical function for PSAT1 using biochemical approaches to elucidate unknown interacting proteins and genomic RNA-seq profiling to identify cellular …
Ecological, Evolutionary, And Molecular Mechanisms Driving Pyocin Diversity In Pseudomonas Aeruginosa., Aubrey A. Mojesky
Ecological, Evolutionary, And Molecular Mechanisms Driving Pyocin Diversity In Pseudomonas Aeruginosa., Aubrey A. Mojesky
Electronic Theses and Dissertations
Bacteriocins are narrow-spectrum antibiotics produced in nearly all lineages of bacteria, meaning that these antimicrobials target closely related individuals. The bacteriocins of Pseudomonas aeruginosa, called pyocins, are highly prevalent and diverse in populations of this species. Laboratory studies have shown that pyocins can function to mediate the outcome of interactions, often allowing for the coexistence of multiple strains, as no one pyocin genotype is competitively superior. Although this has been demonstrated under laboratory conditions, the function of pyocins in natural settings and the ecological, evolutionary, and genetic mechanisms underlying pyocin diversity remains unclear. As such, for my dissertation, I …
Saving Butterflies In The City: Gardens As Conservation Spaces In Urban Landscapes., Lindsay D. Nason
Saving Butterflies In The City: Gardens As Conservation Spaces In Urban Landscapes., Lindsay D. Nason
Electronic Theses and Dissertations
Butterfly populations are declining, and habitat degradation due to urbanization is a major contributing factor. Gardens represent a large proportion of land area in many cities, and thus may be important for conserving butterflies in urban environments. In this dissertation, I examine how garden features (ex: size, level of urbanization, plant diversity) affect adult butterfly diversity/abundance, behavior, and the predation risk faced by caterpillars. My study sites were native plant gardens in Jefferson, Bullitt, and Hardin Cos.,KY. In Chapter One, I used clay caterpillars to assess differences in predation pressure in gardens along a gradient of percent impervious surface (%IS). …
Harmful Algal Blooms In The Ohio River: Spatial And Temporal Differences., Bevin Hardy
Harmful Algal Blooms In The Ohio River: Spatial And Temporal Differences., Bevin Hardy
Electronic Theses and Dissertations
The frequency of harmful algal blooms (HABs) has been increasing across the globe, especially in river ecosystems. Although more common in lakes, more HABs have been reported in rivers in the past decade, particularly in the Ohio River. In 2019, a HAB stretched 200 to 300 miles throughout the Ohio River from September to October. Samples were collected for the duration of the 2019 bloom (August-October) in the McAlpine Pool in Louisville, KY to compare microcystis toxin (microcystin) concentrations on a temporal and spatial scale. Different habitats (bay, creek, river) were sampled throughout the bloom, and two additional sampling days, …
Determination Of The Biological Functions Of Undefined Domains Of Veev Nsp2., Andrew Michael Skidmore
Determination Of The Biological Functions Of Undefined Domains Of Veev Nsp2., Andrew Michael Skidmore
Electronic Theses and Dissertations
Alphaviruses are positive sense, single strand, RNA viruses. These viruses occur on every populated continent. Alphaviruses are divided into two clades, the New-World and Old-World viruses. The New-World viruses include Eastern (EEEV), Western (WEEV), and Venezuelan equine encephalitis viruses (VEEV), and cause neuroinvasive disease. The Old-World viruses include Chikungunya (CHIKV) and Ross River viruses (RRV), and typically cause multijoint arthralgia. There are currently no approved antiviral therapeutics or vaccines for any alphavirus, making them a high priority for antiviral drug design and discovery. A benzamidine inhibitor (ML336) of VEEV was characterized, and determined to inhibit replication of VEEV RNA during …
Distribution And Ecological Effects Of Azteca Chartifex/Trigona In The Barro Colorado Nature Monument., Rachel Leann Wells
Distribution And Ecological Effects Of Azteca Chartifex/Trigona In The Barro Colorado Nature Monument., Rachel Leann Wells
Electronic Theses and Dissertations
This dissertation explores the behavior and ecology of a conspicuous and behaviorally dominant ant species in the tropical rainforest of Panama. Competition with aggressive species is an important factor that shapes local community structure. Eavesdropping on the chemical communication systems of such behaviorally dominant species can help heterospecific species to avoid negative interactions. I review the chemical communication system and known ecological effects of the Neotropical canopy ant, Azteca chartifex/trigona (Chapter 1). There are over 40 known compounds produced by Azteca workers, yet how these compounds impact heterospecific species is unclear in many circumstances. I assessed if heterospecific …