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Articles 1 - 16 of 16
Full-Text Articles in Medicine and Health Sciences
Coordination Of Airway Protective Behaviors And Swallow: Effects Of Afferent Feedback And Sex., Alyssa D. Huff
Coordination Of Airway Protective Behaviors And Swallow: Effects Of Afferent Feedback And Sex., Alyssa D. Huff
Electronic Theses and Dissertations
This dissertation represents a series of studies describing mechanisms related to breathing, upper airway behaviors and their coordination in man and animal. Chapter two transformed the cough swallow aspiration protocol from the cat (previous work) to the human introducing a new strategy, volume targeting, in swallow breathing coordination. Chapter three evaluated swallow breathing coordination at increasing altitudes. As respiratory drive altered due to hypoxia and hypocapnia, swallow breathing coordination shifted toward inspiration occurring during the transition from inspiration and expiration. The collection of the two previous studies led to development of an animal model to evaluate volume targeting and …
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 Nicotine And Cigarette Smoking On Cardiac Electrophysiology., Affan B. Irfan
The Effects Of Nicotine And Cigarette Smoking On Cardiac Electrophysiology., Affan B. Irfan
Electronic Theses and Dissertations
Cigarette smoking is a leading cause of preventable disease and premature death worldwide. The adverse effects of cigarette smoking, including proarrhythmia, are related to the mixture of chemicals, including nicotine (which sustains tobacco addiction). However, it remains unclear which individual tobacco smoke constituents and biological pathways mediate this increased risk. The purpose of this research was to explore the chronic effects of cigarette smoking, as well as compare the acute effects of nicotine and cigarette smoking, and the possible role of β-adrenoreceptors, on human cardiac electrophysiology. Chapter 1 is a comprehensive literature review of (a) the ex vivo and in …
The Effect Of Spinal Cord Injury On Sexual Function., Casey J. Steadman
The Effect Of Spinal Cord Injury On Sexual Function., Casey J. Steadman
Electronic Theses and Dissertations
Spinal cord injury (SCI) causes severe neurological impairment with widespread motor, autonomic and sensory deficits, leading to a substantial quality of life impairment. The number of individuals with SCI increases by approximately 12,500 annually, and over 80% of individuals with SCI are males. SCI individuals rate sexual function as a top priority quality of life issue, and men with SCI likely suffer from sexual dysfunction, such as erectile and ejaculatory dysfunction, as well as infertility. Regardless of the high status of importance of sexual function, limited numbers of experimental studies in SCI animal models have focused on sexual function after …
A Distinct Pattern Of Sterile Inflammation Induced By Zinc Oxide Nanowires., Ruqaih Salem Alghsham
A Distinct Pattern Of Sterile Inflammation Induced By Zinc Oxide Nanowires., Ruqaih Salem Alghsham
Electronic Theses and Dissertations
In recent years, there has been an increasing interest in nanotechnology. Engineered nanomaterials (ENMs) become an increasingly important area in nanotechnology. Recent developments in ENMs have drawn commercial and research attention in many areas such as agriculture, medicine, and Industry. High-aspect ratio zinc oxide nanowires (ZnONWs) have become one of the most significant ENMs due to their remarkable physical properties which makes them useful in a wide-range of applications. However, questions have been raised about ZnONW safety uses and biological consequences. In this dissertation, we investigated the inflammatory potential of ZnONWs in mouse models. C57BL/6 mice were exposed to ZnONW …
Motor And Sensory Characterization Of A Mouse Model Of Charcot-Marie-Tooth Type 2o Disease, Swaran Nandini
Motor And Sensory Characterization Of A Mouse Model Of Charcot-Marie-Tooth Type 2o Disease, Swaran Nandini
Electronic Theses and Dissertations
Dynein is an essential motor protein required for the maintenance and survival of cells. Dynein forms a motor complex to carry intracellular cargoes like organelles, growth factors, peptides, and hormones along the microtubules inside the cells. In neurons, the dynein is the retrograde motor protein that moves cargoes from the neuronal tip to the neuronal soma along the length of an axon. Dynein has an established role in neuronal nuclear migration, transport of neuronal survival signals and growth factors, organelle positioning inside neurons etc. Hence, it is not very surprising that numerous mutations in dynein have been reported in association …
Role Of Atm In T Cell Dysfunction During Chronic Viral Infections, Juan Zhao
Role Of Atm In T Cell Dysfunction During Chronic Viral Infections, Juan Zhao
Electronic Theses and Dissertations
Hepatitis C virus (HCV) or human immunodeficiency virus (HIV) infection leads to a phenomenon of inflammaging, in which chronic infection or inflammation induces an immune aged phenotype with T cell dysfunction. Thus, HCV or HIV infection has been deemed as a model to study the mechanisms of T cell infammaging and viral persistence in humans. In this dissertation, T cell homeostasis, DNA damage and repair machineries were investigated in patients with chronic HCV or HIV infection at risk for inflammaging. We found a significant depletion in CD4 T cells, which was correlated with their apoptosis in chronically HCV/HIVinfected patients, compared …
Novel Mechanisms And Biomarkers In Alcohol-Induced Organ Injury., Christine E. Dolin
Novel Mechanisms And Biomarkers In Alcohol-Induced Organ Injury., Christine E. Dolin
Electronic Theses and Dissertations
Background. Ethanol (EtOH) consumption is known to affect multiple organs; this is unsurprising, as the concentration of EtOH in the blood at relevant doses reaches the millimolar range. The overarching goal of this dissertation was to elucidate mechanisms of alcohol-induced organ injury, specifically the effects of alcohol on the hepatic extracellular matrix (ECM) proteome, the alcoholic hepatitis (AH) plasma peptidome, and the effects of alcohol on the renal cortex proteome and transcriptome. Methods. Mice were pair-fed ethanol-containing liquid diet chronically, and then some mice were administered lipopolysaccharide (LPS). Liver sections from these mice were processed in a series of increasingly …
Novel Hybrid Analogs Of Estrone Origin Exhibits Cytotoxic Effects Against Egfr-Dependent Cancers, Felix Acheampong
Novel Hybrid Analogs Of Estrone Origin Exhibits Cytotoxic Effects Against Egfr-Dependent Cancers, Felix Acheampong
Electronic Theses and Dissertations
Cancer is second only to cardiovascular illnesses as the deadliest human disease globally. Currently, non-small cell lung cancer (NSCLC) and triple negative breast carcinoma (TNBC) are the most frequent types of cancer and have the highest mortalities. Epidermal growth factor receptor (EGFR), a central regulator of tumor progression, is frequently overexpressed in both cancers and is a key clinical target for therapeutic intervention. Natural products and their synthetic analogs have been utilized as EGFR tyrosine kinase inhibitors (TKIs) with potent antitumor effects. However, acquired resistance limits the long-term efficacy of these drugs. Estrone has been used as a scaffold in …
Ab Toxins: Recovery From Intoxication And Relative Potencies, Patrick Cherubin
Ab Toxins: Recovery From Intoxication And Relative Potencies, Patrick Cherubin
Electronic Theses and Dissertations
AB-type protein toxins have a catalytic A subunit attached to a cell-binding B subunit. Ricin, Shiga toxin (Stx), exotoxin A, and diphtheria toxin are AB toxins that act within the host cytosol and kill the host cell through pathways involving the inhibition of protein synthesis. Our overall goal is to help elucidate the cellular basis of intoxication for therapeutic development. According to the current model of intoxication, the effect of AB toxins is irreversible. To test this model, we developed a system that uses flow cytometry and a fluorescent reporter to examine the cellular potency of toxins that inhibit protein …
Unraveling Pdi And Its Interaction With Ab Toxins, Jessica Guyette
Unraveling Pdi And Its Interaction With Ab Toxins, Jessica Guyette
Electronic Theses and Dissertations
Protein disulfide isomerase (PDI) is an essential endoplasmic reticulum (ER) protein that acts as both an oxidoreductase and chaperone. It exhibits substantial flexibility and undergoes cycles of unfolding and refolding in its interaction with cholera toxin (Ctx), which is a unique property of PDI. This unfolding allows PDI to disassemble the Ctx holotoxin, which is required for Ctx activity. Here, we investigated the unfolding and refolding property of PDI and how this affects its interaction with bacterial toxins. PDI showed remarkable redox-linked conformational resilience that allows it to refold after being thermally stressed. Deletion constructs of PDI showed that both …
Reward And Punishment: The Neural Correlates Of Reinforcement Feedback During Motor Learning, Christopher Mark Hill
Reward And Punishment: The Neural Correlates Of Reinforcement Feedback During Motor Learning, Christopher Mark Hill
Electronic Theses and Dissertations
‘By the carrot or the stick’ reward or punishment has been contemplated by instructors to motivate their pupils to learn a new motor skill. The reinforcements of reward and punishment have demonstrated dissociable effects on motor learning with punishment enhancing the learning rate and reward increasing retention of the motor task. However it is still unclear how the brain processes reward and punishment during motor learning. This study sought to investigate the role of reinforcement feedback in cortical neural activity associated with motor learning. A novel visuomotor rotation task was employed with reward punishment or null feedback as the participants …
It Takes Two To Tango: The Toxin-Chaperone Relationship, Alisha Kellner
It Takes Two To Tango: The Toxin-Chaperone Relationship, Alisha Kellner
Electronic Theses and Dissertations
Cholera toxin (CT) enters the cell via receptor-mediated endocytosis and travels in a retrograde fashion to the endoplasmic reticulum (ER). The catalytic A1 subunit (CTA1) is then displaced from the rest of the holotoxin, unfolds, and is exported to the cytosol where it regains an active conformation for the ADP-ribosylation of its G-protein target. We have shown that the cytosolic chaperones Hsp90 and Hsc70 are required for CTA1 translocation to the cytosol. We have also shown that both are able to independently bind and refold CTA1. Using libraries of CTA1-derived peptides, we have identified a single Hsc70 binding site, YYIYVI …
Development Of A Functional Testing Platform For The Sensory Segment Of The Neuromuscular Reflex Arc, Alisha Colon
Development Of A Functional Testing Platform For The Sensory Segment Of The Neuromuscular Reflex Arc, Alisha Colon
Electronic Theses and Dissertations
Investigations of human biology and disease have been hindered by the use of animal models. The information obtained from such studies often results in clinically irrelevant results and drug trial failures. Additionally, several governing bodies have been formulating legislation to move away from animal models and toward more ethical and efficient testing platforms for drug discovery and cosmetic research. As an answer to these issues, "body-on-a-chip" systems have been a rapidly developing field which easily recapitulates in vivo functionality, providing a more relevant, repeatable, and ethical testing platform to better predict biology. These systems can be used as human-based testing …
Synthesis And Bioevaluation Of Methionine Depletion Agents, Houssine Ikhlef
Synthesis And Bioevaluation Of Methionine Depletion Agents, Houssine Ikhlef
Electronic Theses and Dissertations
The native polyamines (putrescine, spermidine, and spermine) are low molecular weight amines that exist as polycations at physiological pH. These polycations interact with DNA, RNA, and influence many cellular processes. Intracellular polyamine levels are maintained via a balance of polyamine biosynthesis, catabolism, and transport. Ornithine, an amino acid obtained from L-arginine, is decarboxylated by ornithine decarboxylase (ODC) to form putrescine. The biosynthesis of the higher polyamines, spermidine and spermine, requires the addition of an amino-propyl group donated by decarboxylated S-adenosylmethionine (dc-SAM), which itself is derived from the amino acid L-methionine (Met). Tumor cells are heavily reliant on methionine because it …
Mechanism Of Nanogp8 In Glioblastoma Multiforme, Jonhoi Smith
Mechanism Of Nanogp8 In Glioblastoma Multiforme, Jonhoi Smith
Electronic Theses and Dissertations
Glioblastoma multiforme (GBM) is an incurable brain tumor, with patients only expecting to live 15 to 16 months post-diagnosis with the most current treatments options including surgery, chemotherapy, and radiation. How GBM resist treatment is still not very well known. However, cancer stem cells (CSCs), a subset of cells in GBM tissue considered responsible for therapeutic resistance and the poor patient prognosis. NANOG, a homeobox gene, is responsible for maintaining pluripotency of embryonic stem cells and is observed in CSCs. NANOGP8, a retrogene in the NANOG family is expressed in CSCs and provides cells with stem-like characteristics previously observed in …