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Articles 1 - 17 of 17
Full-Text Articles in Life Sciences
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 …
Role Of Ataxia Telangiectasia Mutated Kinase In Western-Type Diet-Induced Cardiac Outcomes Under Basal And Ischemic Conditions, Mary Wingard
Role Of Ataxia Telangiectasia Mutated Kinase In Western-Type Diet-Induced Cardiac Outcomes Under Basal And Ischemic Conditions, Mary Wingard
Electronic Theses and Dissertations
Ataxia-telangiectasia mutated kinase (ATM), a serine/threonine kinase, plays a role in DNA damage repair, redox sensing, and metabolism. In the heart, ATM contributes significantly in the myocardial infarction (MI)-induced cardiac remodeling with effects on fibrosis, hypertrophy, apoptosis and inflammation. This study investigates the role of ATM deficiency in 14 weeks Western-type diet (WD)-induced cardiac outcomes prior to and 1-day post-MI in a sex-specific manner using wild-type (WT) and ATM heterozygous knockout (hKO) mice. In male mice, ATM deficiency induced rapid body weight gain and preload-associated dysfunction, while WT mice displayed afterload-associated dysfunction 14 weeks post-WD. Myocyte apoptosis and hypertrophy were …
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 …
Novel Quantification And Localization Of Water And Solute Transporters In The Tissues Of The Spiney Dogfish (Squalus Acanthias), Tolulope B. Ojo
Novel Quantification And Localization Of Water And Solute Transporters In The Tissues Of The Spiney Dogfish (Squalus Acanthias), Tolulope B. Ojo
Electronic Theses and Dissertations
The dogfish, Squalus acanthias is a marine cartilaginous elasmobranch found in the North Atlantic and Pacific oceans. Dogfish synthesize and excrete urea as a product of nitrogen metabolism. They also convert ammonia into urea and retain this urea, such that their plasma is isosmotic or slightly hyperosmotic to the surrounding seawater. To facilitate the regulation of body fluid and to maintain ionic concentrations and osmotic pressure, Dogfish use ion and solute transporters (e.g., NCC, UT-1) and aquaporin water channel proteins. Studies have identified some of the aquaporin genes in the elasmobranch genome, but their functions are mostly uncharacterized. Recent transcriptomic …
Examining The Function Of Protein Acyltransferase Via The Dhhc Domain Of The Paz5 Protein In The Organism Dictyostelium Discoideum, George M. Stuart-Ranchev
Examining The Function Of Protein Acyltransferase Via The Dhhc Domain Of The Paz5 Protein In The Organism Dictyostelium Discoideum, George M. Stuart-Ranchev
Electronic Theses and Dissertations
Protein S-palmitoylation plays a crucial role in many biological systems. S-palmitoylation involves the post-translational attachment of palmitate to a cysteine residue through a reversible thioester linkage. S-Palmitoylation is used to modify both integral and membrane proteins, many of which are involved in intracellular trafficking, membrane localization, and signal transduction pathways. Intracellular palmitoylation is mediated by a family of protein acyltransferases (PATs). PAT mutations are associated with neurological diseases and cancer progression. Proteins in the PAT family are defined by the presence of a 51-amino acid cysteine-rich domain (CRD), which contains a highly conserved aspartate-histidine-histidine-cysteine (DHHC) motif. The …
The Identification Of Long Non-Coding Rna Zfas1 Through An Exploratory Rna-Sequencing Analysis And Its Association With Epithelial-To-Mesenchymal Transition In Colon Cancer Adenocarcinoma., Stephen J. O'Brien
Electronic Theses and Dissertations
Colorectal adenocarcinoma is the fourth most common cancer diagnosed worldwide and is a significant cause of morbidity and mortality. This dissertation performed an exploratory RNA-sequencing analysis comparing gene expression between colon adenocarcinoma tissue and paired normal colon epithelium. After identification of a number of lncRNAs that were increased in expression in colon adenocarcinoma compared to normal colon epithelium, we aimed to validate the expression and investigate their function in vitro. Specifically, we focused on the lncRNA ZFAS1 and its association with epithelial-to-mesenchymal transition. These studies found the following: 1. Seven candidate lncRNAs were identified from the exploratory RNA-sequencing analysis to …
The Effects Of Branched Chained Amino Acid Supplementation On Acute Markers Of Fatigue And Performance, Joseph Walters
The Effects Of Branched Chained Amino Acid Supplementation On Acute Markers Of Fatigue And Performance, Joseph Walters
Electronic Theses and Dissertations
The purposes of this dissertation were to investigate the acute effects of branched-chain amino acids on psychological, physiological, and subsequent performance changes following high volume resistance training. The rationale for this study design was based on abrupt or contiguous training/ competitions that specific athletes encounter in a competitive season. This study design also sought to fill some gaps in the scientific literature concerning the efficacy of BCAAs for subjective fatigue in a resistance training paradigm. To address the purposes of this dissertation, a one-week study was conducted on resistance trained males, in which half of the subjects were randomly selected …
Quantification Of Aqp11 Paralog Expression In The Osmoregulatory Organs Of Anguilla Rostrata, Keith C. Kurt
Quantification Of Aqp11 Paralog Expression In The Osmoregulatory Organs Of Anguilla Rostrata, Keith C. Kurt
Electronic Theses and Dissertations
Osmoregulation is facilitated by using an assortment of ion and water channels to assist acclimation to changing conditions and to maintain cellular homeostasis. Euryhaline fish can be found in both seawater and freshwater (SW and FW) environments. Expression of ion and water channels have been experimentally demonstrated to change as a fish acclimates to different environmental conditions. Relatively recently, a new group of water channels has been discovered that are primarily intracellular and includes aquaporin 11 (AQP11). Typically, AQPs are located on the cell plasma membrane to allow water to flow in and out of the cell by osmosis to …
The Effect Of Alcohol Consumption On Adipokine Secretion, Ashley Degroat
The Effect Of Alcohol Consumption On Adipokine Secretion, Ashley Degroat
Electronic Theses and Dissertations
Alcoholic Fatty Liver Disease (AFLD) is caused by excessive alcohol consumption and is a leading cause of liver related mortalities, with currently no treatments available. The goal of this project was to establish the effect of alcohol consumption on adipose tissue-derived secreted factors, adiponectin and C1q TNF Related Proteins 1-3 (CTRP1-3). We propose that excessive alcohol consumption will reduce circulating levels of adiponectin and CTRPs 1-3. Mice were fed a Lieber-Decarli control or alcohol diet for 10-days with a gavage (NIAAA model) or 6-weeks with no gavage (chronic model). Serum and adipose tissue were collected and CTRPs 1-3 and adiponectin …
Exogenous Ubiquitin: Role In Myocardial Inflammation And Remodeling Post- Ischemia/Reperfusion Injury, Stephanie Scofield
Exogenous Ubiquitin: Role In Myocardial Inflammation And Remodeling Post- Ischemia/Reperfusion Injury, Stephanie Scofield
Electronic Theses and Dissertations
Sympathetic stimulation occurs in the heart after injuries such as ischemia/reperfusion (I/R) and myocardial infarction and affects myocardial remodeling. Prolonged sympathetic stimulation can result in myocardial dysfunction through its effects on cardiac myocyte apoptosis and myocardial fibrosis. Ubiquitin (UB) is well known for its role of tagging old or damaged proteins for degradation via the UB-proteosome pathway. The role of exogenous UB however, is not fully understood. Previously, our lab showed that β-adrenergic receptor (β-AR) stimulation increased levels of extracellular UB in the conditioned media of adult rat ventricular myocytes and that UB inhibits β-AR-stimulated apoptosis. This study investigates the …
Mitochondrial Transcription Factor A'S Role In Heart Failure., George H. Kunkel
Mitochondrial Transcription Factor A'S Role In Heart Failure., George H. Kunkel
Electronic Theses and Dissertations
Background: An essential mitochondrial component, Mitochondrial Transcription Factor A (TFAM) is reduced within the failing heart. TFAM maintains regulatory functions of cardiomyocyte physiology and stability. Mitochondrial Transcription Factor A forms a mitochondrial nucleoid anti-oxidant structure and reduces pathophysiological abnormalities to structural and contractile proteins. Overall, this functions to physically stabilize mtDNA. Significant molecular changes such as a loss of TFAM drive pathophysiological concentrations of cytoplasmic Ca2+ and reactive oxygen species. Both of these factors induce proteolytic enzymes to degrade the physiological cardiomyocyte. In TFAMs absence, heart function deteriorates and hypertrophic expansion ensues: thereby changing the physiological myocardium to a pathological …
Divergent Responses Of Larval And Juvenile Blue Mussels To Low Salinity Exposure, Melissa A. May
Divergent Responses Of Larval And Juvenile Blue Mussels To Low Salinity Exposure, Melissa A. May
Electronic Theses and Dissertations
In this study, we compared the osmotic stress response of larval and juvenile blue mussels (Mytilus edulis) at the transcriptomic, metabolomic, and whole organism levels. Blue mussels inhabit coastal areas, where they face climate-induced reductions in nearshore salinity. Despite their ecological and economic importance, scientists do not fully understand the underlying transcriptomic and cellular mechanisms of the osmotic stress response in blue mussels or how the ability to respond to stress changes throughout development. Blue mussels spend the first weeks of life developing through several larval stages in the plankton. These early life history stages are more vulnerable …
Enhancing Cell Therapy For Ischemic Cardiomyopathy., Michael J. Book
Enhancing Cell Therapy For Ischemic Cardiomyopathy., Michael J. Book
Electronic Theses and Dissertations
Cardiac cell therapy using cardiac mesenchymal cells (CMC) significantly reduces ventricular dysfunction in patients with ischemic cardiomyopathy. Despite the improvement in function, a modest number of CMCs survive in the heart post-transplantation. In this study, we sought to improve the survival and retention of transplanted CMCs to prolong the therapeutic benefits afforded by cardiac cell therapy. To do this, we targeted the enzyme telomerase (TERT), known to be active in some highly proliferating cells (e.g. germ, stem). TERT is responsible for preventing telomere attrition, thereby allowing continued proliferation. TERT has also been shown to be protective, improve cell migration and …
Cardiovascular And Hematopoietic Responses To Volatile Benzene Exposure., Wesley Tyler Abplanalp
Cardiovascular And Hematopoietic Responses To Volatile Benzene Exposure., Wesley Tyler Abplanalp
Electronic Theses and Dissertations
The rapid and recent increase in the global epidemic of diabetes and cardiovascular disease suggests a strong component of the environment is contributing. Benzene is a ubiquitous volatile pollutant generated by cigarette smoke, automobile exhaust, wildfires and industrial activities. Consequently, it is found in almost all urban and rural air samples. Benzene is known to cause hematotoxicity and its metabolism generates oxidative stress. Although, benzene has been studied for many years, few investigations have probed what influence benzene exposure may have on other physiological processes. Here we hypothesize that benzene metabolism by hepatic-CYP450 2E1 generates oxidative stress and inflammation, which …
The Physiological Stress Response Caused By Hypoxia And Reperfusion Injury In Striped Bass (Morone Saxatilis) And Nile Tilapia (Oreochromis Niloticus), Amanda C. Reynolds
The Physiological Stress Response Caused By Hypoxia And Reperfusion Injury In Striped Bass (Morone Saxatilis) And Nile Tilapia (Oreochromis Niloticus), Amanda C. Reynolds
Electronic Theses and Dissertations
Approximately five million people in the United States are affected by cardiovascular related diseases yearly contributing to 300,000 annual deaths, making CVD the leading cause of mortality worldwide. It has been suggested that apoptosis (programmed cell death) contributes to the pathogenesis of cardiovascular diseases. When blood flow is reduced or cut off from the heart, usually by a thrombus, this results in oxygen deprivation (hypoxia) to the cardiomyocytes (heart cells). In response to this hypoxic stress, cardiomyocytes will undergo apoptosis. Since many species of fish can survive levels of hypoxia that would be fatal to mammals, fish are an ideal …
Enabling Sum Frequency Spectroscopy And Fluorescence Correlation Spectroscopy Of Model Cellular Membranes, Sarah M. Sterling
Enabling Sum Frequency Spectroscopy And Fluorescence Correlation Spectroscopy Of Model Cellular Membranes, Sarah M. Sterling
Electronic Theses and Dissertations
The majority of proteins secreted from cells contain a signal peptide sequence that is required for secretion mediated by the endoplasmic reticulum and Golgi apparatus. However, many proteins lack the essential signal peptide sequence, yet still undergo secretion. Such proteins are known to regulate cell proliferation, differentiation, and migration. Fibroblast growth factor 1 (FGF-1) is one protein which undergoes non-classical protein transport. The role of its interactions with the cellular membrane during non-classical protein transport is not fully understood, although FGF-1 has shown preferential destabilizing effects on artificial membranes composed of acidic phospholipids. In the present work, physiologically relevant model …