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Articles 1 - 26 of 26
Full-Text Articles in Life Sciences
Investigation Of Human N-Acetyltransferases (Nat1 And Nat2) Genetic Polymorphisms In Susceptibility To Aromatic Amine And Alkylaniline Genotoxicity., Mariam Habil
Electronic Theses and Dissertations
Arylamine N-acetyltransferases, NAT1 and NAT2, catalyze the detoxification and/or activation of carcinogens. Single nucleotide polymorphisms or SNPs result in different human NAT1 and NAT2 genotypes. We hypothesize that different NATs alleles will impact levels of N-acetylation, HPRT mutations, DNA damage and oxidative stress induced by carcinogens. NER-deficient Chinese hamster ovary (CHO) cells transfected with human CYP1A2 and NAT1*4, NAT1*14B, NAT2*4, NAT2*5B or NAT2*7B have been used to investigate N-acetylation of benzidine, β-naphthylamine (BNA), and 4, 4’-methylene bis (2-chloroaniline) (MOCA) as aromatic amines and 3,4-dimethylaniline (3,4-DMA) as one of alkylanilines and their associated toxicity. Our …
Voltage-Gated Potassium Channel Dependent Mechanisms Of Cardiovascular Adaptation To Chronic Exercise., Sean Raph
Electronic Theses and Dissertations
Exercise increases cardiac workload, escalating the demand for oxygen. The myocardial vasculature responds to the greater demand for oxygen by increasing blood flow to match the needs of the heart during augmented work. Increasing blood flow requires the coronary arteries dilate (a.k.a. vasodilation); this is mediated predominantly by vascular smooth muscle cell relaxation. Vasodilation is driven through inhibition of calcium influx into vascular smooth muscle cells. The prevention of calcium influx is largely mediated by efflux of potassium via potassium channels causing membrane hyperpolarization, which in turn closes voltage-dependent (or gated) calcium channels (VDCC). Changes in vascular smooth muscle cell …
Death Of A Bacterium: Exploring The Inhibition Of Staphylococcus Aureus By Burkholderia Cenocepacia., Tiffany Brandt
Death Of A Bacterium: Exploring The Inhibition Of Staphylococcus Aureus By Burkholderia Cenocepacia., Tiffany Brandt
Electronic Theses and Dissertations
Antimicrobial resistance is a phenomenon of increasing concern as antimicrobial overuse and misuse eliminate current therapeutic options, ushering society into a post-antimicrobial era. Antibiotic discovery and synthesis efforts are urgently needed to counter the increasing burden of antimicrobial resistance. Staphylococcus aureus is a causative agent of a variety of clinical manifestations including bacteremia, endocarditis, soft tissue infection, osteomyelitis, and device-related infections. S. aureus infection presents additional treatment challenges due to its capacity for biofilm formation, which is a mode of growth that confers protection from antibiotics and physical elimination, and the emergence of antibiotic resistant strains, including methicillin-resistant S. aureus …
Bayesian Methods For Graphical Models With Neighborhood Selection., Sagnik Bhadury
Bayesian Methods For Graphical Models With Neighborhood Selection., Sagnik Bhadury
Electronic Theses and Dissertations
Graphical models determine associations between variables through the notion of conditional independence. Gaussian graphical models are a widely used class of such models, where the relationships are formalized by non-null entries of the precision matrix. However, in high-dimensional cases, covariance estimates are typically unstable. Moreover, it is natural to expect only a few significant associations to be present in many realistic applications. This necessitates the injection of sparsity techniques into the estimation method. Classical frequentist methods, like GLASSO, use penalization techniques for this purpose. Fully Bayesian methods, on the contrary, are slow because they require iteratively sampling over a quadratic …
The Effect Of Volatile Organic Compounds On Endothelial Function And Atherogenesis., Samantha Mcfall
The Effect Of Volatile Organic Compounds On Endothelial Function And Atherogenesis., Samantha Mcfall
Electronic Theses and Dissertations
Volatile organic compounds (VOCs) are a group of pervasive air pollutants that are released into the atmosphere from both anthropogenic and environmental sources. Recent epidemiological studies suggest that exposure to various VOCs is associated with an increased risk of cardiovascular disease. However, the relationship between VOCs and cardiovascular disease is not well-studied. Using animal models and three select VOCs, benzene, xylene, and trichloroethylene, we studied the effects of VOCs on endothelial injury and benzene-induced atherogenesis. We found that exposure to benzene and xylene increased circulating endothelial microparticles, depleted progenitor cells, and increased platelet activation. Following the exposure to the representative …
Metabolic Foundations Of Exercise-Induced Cardiac Growth., Kyle Fulghum
Metabolic Foundations Of Exercise-Induced Cardiac Growth., Kyle Fulghum
Electronic Theses and Dissertations
Regular aerobic exercise promotes physiological cardiac growth, which is an adaptive response thought to enable the heart to meet higher physical demands. Cardiac growth involves coordination of catabolic and anabolic activities to support ATP generation, macromolecule biosynthesis, and myocyte hypertrophy. Although previous studies suggest that exercise-induced reductions in cardiac glycolysis are critical for physiological myocyte hypertrophy, it remains unclear how exercise influences the many interlinked pathways of metabolism that support adaptive remodeling of the heart. In this thesis project, we tested the general hypothesis that aerobic exercise promotes physiological cardiac growth by coordinating myocardial metabolism to promote glucose-supported anabolic pathway …
Re-Engineering Cardio-Oncology Testing Using Biomimetic Heart Slice Cultures., Jessica Miller
Re-Engineering Cardio-Oncology Testing Using Biomimetic Heart Slice Cultures., Jessica Miller
Electronic Theses and Dissertations
28% of drug withdrawal from the market are due to unforeseen disruptions in cardiomyocyte contractility and electrophysiology. The most commonly used platforms for drug testing are in vivo animal models and in vitro cell culture models. While both have been of paramount importance for the discovery and detection of many cardiotoxicities and mechanisms of action, they lack the ability to model an intact human myocardium. This work aims to establish cardiac tissue slices, which are 300-micron thin tissue sections taken from the left ventricular myocardium, as an alternative platform for cardio-oncology studies, specifically cardiotoxicity testing. Additionally, this work aims to …
Establishing The Efficacy Of Non-Cellular Components Of Adipose-Derived Stromal Vascular Fraction In Promoting Angiogenesis., Daniel Benson
Establishing The Efficacy Of Non-Cellular Components Of Adipose-Derived Stromal Vascular Fraction In Promoting Angiogenesis., Daniel Benson
Electronic Theses and Dissertations
Microvascular disease is hallmarked by pathophysiological conditions such as endothelial senescence, intimal thickening which impairs vasodilation, and regression of the capillary beds causing tissue ischemia in the myocardium or in peripheral vascular networks. Adipose-derived stromal vascular fraction (SVF) has previously demonstrated the ability to revascularize tissue. Increasing evidence shows that regenerative cells elicit their therapeutic benefit by paracrine mechanisms, leaving open extracellular vesicles (EVs) as a potential crux of the cell therapy paradigm. To test this idea, three types of gelatin methacrylate hydrogels were employed: SVF gels, EV gels derived from SVF, and blank control gels, which were used in-vitro …
Characterization Of Microbotryum Lychnidis-Dioicae Secreted Effector Proteins That Manipulate Its Host Plant, Silene Latifolia., Ming-Chang Tsai
Characterization Of Microbotryum Lychnidis-Dioicae Secreted Effector Proteins That Manipulate Its Host Plant, Silene Latifolia., Ming-Chang Tsai
Electronic Theses and Dissertations
The smut fungal species Microbotryum lychnidis-dioicae is an obligate phytopathogen colonizing the plant host, Silene latifolia. A significant feature of M. lychnidis-dioicae infection is that the fungus can replace pollen on the anthers of susceptible host plants with fungal teliospores, thus earning the fungus the name: anther smut disease of flowers. The fungus synthesizes and secretes effector proteins into the cells of the plant host during infection, and the protein-protein interactions may interfere with and modify metabolism, plant development, and gene expression of the host to allow fungal colonization. Two potential fungal effector proteins, MVLG_06175 and MVLG_05122, were identified …
Determination Of The Functional Role Of Rab-Ggt In Physcomitrium Patens., Hyun Jin Jung
Determination Of The Functional Role Of Rab-Ggt In Physcomitrium Patens., Hyun Jin Jung
Electronic Theses and Dissertations
Protein prenylation, a common lipid post-translational modification, is required for growth and development in eukaryotes. Rab geranylgeranylation involves the addition of one or two 20-carbon geranylgeranyl moieties to Rab-GTPase target proteins, which regulate intracellular vesicle trafficking. The reaction is carried out by heterodimeric Rab geranylgeranyltransferase (Rab-GGT), which is composed of two associated α- and β-subunits, with the assistance of an additional protein called Rab escort protein (REP). Loss of function of the Rab-GGT α subunit RGTA1 has not been reported in any plant. While knockout of either of the two β subunits RGTB1 or RGTB2 results in …
Applications Of Nuclear Magnetic Resonance Spectroscopy: From Drug Discovery To Protein Structure And Dynamics., Mark Vincent C. Dela Cerna
Applications Of Nuclear Magnetic Resonance Spectroscopy: From Drug Discovery To Protein Structure And Dynamics., Mark Vincent C. Dela Cerna
Electronic Theses and Dissertations
The versatility of nuclear magnetic resonance (NMR) spectroscopy is apparent when presented with diverse applications to which it can contribute. Here, NMR is used i) as a screening/ validation tool for a drug discovery program targeting the Phosphatase of Regenerating Liver 3 (PRL3), ii) to characterize the conformational heterogeneity of p53 regulator, Murine Double Minute X (MDMX), and iii) to characterize the solution dynamics of guanosine monophosphate kinase (GMPK). Mounting evidence suggesting roles for PRL3 in oncogenesis and metastasis has catapulted it into prominence as a cancer drug target. Yet, despite significant efforts, there are no PRL3 small molecule inhibitors …
Effect Of Dorsal Quadrant Or Ventral Quadrant Spinal Cord Injury On Gait Features During Locomotion., Anya Nicole Trell
Effect Of Dorsal Quadrant Or Ventral Quadrant Spinal Cord Injury On Gait Features During Locomotion., Anya Nicole Trell
Electronic Theses and Dissertations
In the Unites States, approximately 1.5 million people currently have a spinal cord injury and suffer permanent sensory and motor loss due to the disruption of the spinal cord. Due to the significant morbidity, it is vital to understand the functional impact of disrupting neural descending pathways that modulate spinal neurons involved in intermuscular coordination critical for gait behaviors. Tasks that are more difficult require additional input from these neural pathways; therefore, fourteen feline subjects were familiarized with level overground locomotion and stair descent gait tasks. After collection of baseline kinematic data, the subjects received either a dorsal or ventral …
Unraveling Dna And Identity: A Humanistic Perspective On Epistemologies And Ethics Of Genetic Ancestry Testing., Eve Carlisle Polley
Unraveling Dna And Identity: A Humanistic Perspective On Epistemologies And Ethics Of Genetic Ancestry Testing., Eve Carlisle Polley
Electronic Theses and Dissertations
The advent of DNA ancestry testing motivated a burst of human activities that constitute a scientific-technological-industrial-personal-social movement of immense scale, infused with epistemological and ethical questions of great and important variety. This movement has motivated many discourses in the social sciences, with study subjects ranging from the language usage of geneticists, to moral conundrums faced by test-takers, to potential ramifications in global structures of political power. At the same time, and especially in recent decades, the discourses of the comparative humanities have included with increasing frequency and urgency research and theorization about concepts and consequences of human social identities, alongside …
A Computational Model Of The Line-1 Retrotransposon Life Cycle And Visualization Of Metabolic Networks In 3-Dimensions., Michael D. Martin
A Computational Model Of The Line-1 Retrotransposon Life Cycle And Visualization Of Metabolic Networks In 3-Dimensions., Michael D. Martin
Electronic Theses and Dissertations
Computational modeling of metabolic reactions and cellular systems is evolving as a tool for quantitative prediction of metabolic parameters and reaction pathway analysis. In this work, the basics of computational cell biology are presented as well as a summary of physical processes within the cell, and the algorithmic methods used to find time dependent solutions. Protein-protein and enzyme-substrate interactions are mathematically represented via mass action kinetics to construct sets of linear differential equations that describe reaction rates and formation of protein complexes. Using mass action methods, examples of reaction networks and their solutions are presented within the Virtual Cell simulation …
Application Of Cannabidol To Ocular Pharmacokinetics And Pharmacodynamics., Alyssa Laun
Application Of Cannabidol To Ocular Pharmacokinetics And Pharmacodynamics., Alyssa Laun
Electronic Theses and Dissertations
Cannabidiol (CBD) is the most abundant non-psychotropic cannabinoid constituent of Cannabis sativa. CBD is potentially therapeutic for the eye through antioxidant, anti-inflammatory, and neuroprotective effects. However, the effect of CBD on intraocular pressure (IOP)- the major risk factor for glaucoma- is controversial and large variability exists in the literature. IOP is regulated through aqueous humor (AH) dynamics in trabecular meshwork (TM) tissues. Measurement of CBD in AH and correlation with effects on IOP would clarify what concentrations mediate changes to IOP. Therefore, the overall goal of this dissertation is to measure CBD in ocular tissues and correlate concentrations with …
Defining The Importance Of The Hnrnp I Interaction To The Sindbis Virus Subgenomic Viral Rna Using An Innovative Tethering Approach., Claire Westcott
Defining The Importance Of The Hnrnp I Interaction To The Sindbis Virus Subgenomic Viral Rna Using An Innovative Tethering Approach., Claire Westcott
Electronic Theses and Dissertations
Old World alphaviruses cause significant outbreaks of illness and debilitating multi-joint arthritis for prolonged periods. Currently, there are no FDA approved vaccines or antiviral therapies; and thus, there is a critical need to identify and characterize the molecular biology of alphaviruses. Alphaviruses rely on the host cell machinery to complete the viral lifecycle and are dependent on interactions with host RNA binding proteins. Accordingly, several host heterogenous nuclear ribonucleoprotein proteins (hnRNPs) have been found to bind to the Sindbis virus (SINV) RNAs. Disrupting the interaction sites in the viral RNAs of these RNA:Protein interactions results in decreased viral titers in …
Lysosomal Evasion Of Legionella Pneumophilia The Effector., Bethany Vaughn
Lysosomal Evasion Of Legionella Pneumophilia The Effector., Bethany Vaughn
Electronic Theses and Dissertations
Legionella pneumophila is a Gram-negative facultative intracellular bacterium found in freshwater environments that has co-evolved to survive and proliferate in various amoeba and protozoan species, which serve as the natural host for the bacterium. Humans are an accidental host of L. pneumophila, where infection occurs upon inhalation of aerosolized water droplets that contain the bacteria. Intracellular proliferation of L. pneumophila in alveolar macrophages is essential for manifestation of pneumonia, designated as Legionnaires’ Disease. Biogenesis of the legionella containing vacuole (LCV) occurs via interception of ER-Golgi vesicle trafficking and avoids the default endosomal/lysosomal degradation pathway. Intracellular proliferation of L. pneumophila …
Plant-Pollinator Communities Responsive To Local And Landscape Level Factors In Grassland Restorations., Aaron Sexton
Plant-Pollinator Communities Responsive To Local And Landscape Level Factors In Grassland Restorations., Aaron Sexton
Electronic Theses and Dissertations
As humans continue to degrade natural ecosystems via greenhouse gas emissions and habitat destruction, many species are being pushed to the brink of extinction. In hopes to offset this degradation, habitat restoration attempts to restore ecosystem function to an improved state resembling intact, remnant values. This is a difficult, but important, undertaking with factors to consider at multiple spatial and temporal scales. The restoration and conservation of pollinator communities has garnered heightened attention because of the valuable ecosystem services they provide. This dissertation investigates the local and landscape level factors of grassland restorations that influence plant-pollinator communities. I used a …
Aggregatibacter Actinomycetemcomitans Exploits And Modulates The Immune Response By Human Neutrophils For Survival In The Anaerobic Environment., Hazel Ozuna
Electronic Theses and Dissertations
Aggregatibacter actinomycetemcomitans (Aa) is a Gram-negative facultative anaerobe and an opportunistic oral pathogen, strongly associated with localized periodontitis and other inflammatory diseases. Periodontitis is a chronic inflammation of the periodontium resulting from the inflammatory response of the host towards the dysbiotic microbial community present at the gingival crevice. The host immune response creates a hostile environment for microorganisms; therefore, it is important for Aa to be able to regulate the necessary genes to survive and thrive in such an environment. Aaexpresses several virulence factors such as a cytolethal distending toxin (Cdt), lipopolysaccharide (LPS) and leukotoxin A (LtxA), …
Genomic Tools And Models For Investigating The Role Of Germline Diversity In Mouse Antibody Repertoire Development., Justin T. Kos
Genomic Tools And Models For Investigating The Role Of Germline Diversity In Mouse Antibody Repertoire Development., Justin T. Kos
Electronic Theses and Dissertations
Given the diversity and complexity within immunoglobulin (IG) loci, effective mouse models first require characterization of intra-strain differences and construction of high-quality reference assemblies for IG loci in several representative strains. To understand light chain germline diversity across biomedically significant mouse strains, we profiled the expressed IGK and IGL repertoires of 18 commonly used laboratory mouse strains using AIRR-seq. Across strains, we observed germline IGKV sequences shared by three different IGK haplotypes and a more conserved IGLV germline repertoire among common laboratory strains. Pacific Biosciences (PacBio) Single-Molecule Real-Time (SMRT) sequencing was used to sequence and assemble bacterial artificial chromosomes (BAC) …
Functional Role Of Ppal And Potential For Moss In Industrial Applications., Susana Perez Martinez
Functional Role Of Ppal And Potential For Moss In Industrial Applications., Susana Perez Martinez
Electronic Theses and Dissertations
This dissertation is an examination and characterization of the functional roles of PPAL. PROTEIN PRENYLTRANSFERASE ALPHA SUBUNIT-LIKE (PPAL) is a recently discovered gene. PPAL homologs are present in all plants and many animals, where its function is largely unknown. It is possible that PPAL could participate in prenylation processes since it shares similarity to the α subunits of known prenylation enzymes. Prenylation is a post-translational modification of proteins that involves the addition of a lipid moiety to proteins to facilitate membrane targeting and association and promote protein-protein interactions. Prenylation has important roles in plant growth and development, including …
Role Of Galactose, Thiazolidinediones, And Neet Proteins In Mitochondrial Physiology And Therapeutic Development., Robert Anthony Skolik
Role Of Galactose, Thiazolidinediones, And Neet Proteins In Mitochondrial Physiology And Therapeutic Development., Robert Anthony Skolik
Electronic Theses and Dissertations
This dissertation explores the relationship between mitochondrial physiology and development of therapeutics. Mitochondrial dysfunction is associated with both acute and chronic forms of pathophysiology. This work aims to address development efforts at the cell culture and drug-target levels with respect to mitochondria. At the cell culture level, I characterize an approach that has been shown to improve the physiological dependency on mitochondria in tumor-derived cells. I demonstrate that prolonged replacement of glucose with galactose in culture medium induces a global metabolic shift in hepatocellular carcinoma (HepG2) cells to closer reflect a primary hepatocyte phenotype (Chapter 2). I characterize this shift …
The Roles Of Pon2 In Mitochondrial Physiology, Lung Tumor Cell Proliferation, And Lung Tumorigenesis., Aaron Whitt
The Roles Of Pon2 In Mitochondrial Physiology, Lung Tumor Cell Proliferation, And Lung Tumorigenesis., Aaron Whitt
Electronic Theses and Dissertations
Paraoxonase 2 (PON2) is an intracellular, multifunctional enzyme with near-ubiquitous tissue distribution. Within cells, PON2 is localized to mitochondria and endoplasmic reticulum (ER), where it mitigates the formation of reactive oxygen species (ROS). PON2’s chief enzymatic function is its lactonase activity, through which it catalyzes the hydrolysis of a bacterial quorum-sensing molecule, N-(3-oxododecanoyl)-l-homoserine lactone (C12), effectively disrupting bacterial intercellular communication and protecting against infection. C12 is produced by the opportunistic pathogen Pseudomonas aeruginosa and has been shown to disrupt various aspects of eukaryotic host cell physiology and evoke apoptotic cell death through the activity of PON2. Additionally, PON2 has garnered …
Cannabinoids And Retinal Fibrotic Disorders., Lucy June Sloan
Cannabinoids And Retinal Fibrotic Disorders., Lucy June Sloan
Electronic Theses and Dissertations
Retinal fibrosis is detrimental to vision. Retinal pigment epithelial (RPE) cells contribute to several retinal fibrotic diseases. Upon exposure to TGF-β, a key fibrotic cytokine, RPE cells trans-differentiate to myofibroblasts marked by the integration of α-SMA fibers into F-actin stress fibers, which confer strong contractility. Myofibroblasts produce and contract the collagen-rich fibrotic scar and disrupt retinal architecture. In this study, we investigated the in vitro effects of the putative endocannabinoid compound N-oleoyl dopamine (OLDA) on TGF-β2 induced porcine RPE cell contraction and α-SMA expression. Using an in vitro collagen matrix contraction assay, we found that OLDA inhibited TGF-β2 induced contraction …
Particulate Hexavalent Chromium Inhibits Homologous Recombination Repair By Targeting Rad51 Paralogs In Human Lung Fibroblasts., Aggie R. Williams
Particulate Hexavalent Chromium Inhibits Homologous Recombination Repair By Targeting Rad51 Paralogs In Human Lung Fibroblasts., Aggie R. Williams
Electronic Theses and Dissertations
Hexavalent Chromium [Cr(VI)] is a known human lung carcinogen and general health hazard. The mechanism of carcinogenesis remains poorly understood, but chromosome instability (CIN) is the major theory in its carcinogenic mechanism. Homologous recombination (HR) repair is a DNA repair pathway that prevents CIN by repairing DNA double-strand breaks. RAD51, a key mediator protein of HR repair, along with the RAD51 paralogs (RAD51B, C, D, XRCC2, and 3) are required for HR repair. During HR, RAD51 loads and forms a helical nucleoprotein filament structure to promote DNA strand exchange and stimulate pairing activity of DNA. Cr(VI) exposures have been shown …
Discovering The Pathways And Go Terms Associated With Mettl3 Modified Circular Rnas In The Embryonic Cerebral Cortex Of Mice., Dunia Zedan
Electronic Theses and Dissertations
Circular RNAs (cirRNAs) are a class of RNA molecules that result from the alternative back-splicing events that join the 3’ and 5’ ends normally present in the linear RNA molecules. It has been published that cirRNAs can function as gene regulators and as “microRNA sponges” to negatively control the functions of microRNAs. While many studies have been conducted to understand the regulatory roles of Mettl3 in linear messenger RNAs, fewer contributions were applied to understand the impact of Mettl3 modified cirRNAs on gene expression and on the regulation of different KEGG biological pathways and GO terms. This thesis was conducted …