Digital Commons Network^™

Neurocalcin ẟ Response To Calcium: Which Ef Hand Matters The Most?, Trokon Fiawoo

Graduate School of Biomedical Sciences Theses and Dissertations

Changes in intracellular calcium levels play a very important role in cell signaling, in turn, affecting neuronal functions such as memory, learning and cell death. A class of proteins called Neuronal Calcium Sensor (NCS) proteins serves to modulate the functioning of the neuronal cells in response to changes in calcium levels. Structurally, all NCS proteins have 4 calcium-binding EF hand motifs, although EF I does not bind to calcium in many members. All NCS proteins are myristoylated at the N-terminus. Neurocalcin delta (NCALD) is an NCS protein, and shares 95% similarity in primary amino acid sequence with another major NCS …

Evaluation Of Protein Source At Breakfast On Energy Metabolism, Metabolic Health, And Food Intake: A Pilot Study, Lauren A. Cambias

Human Nutrition and Hospitality Management Undergraduate Honors Theses

Abstract

Over 30% of adults in the US are obese. A primary contributor to obesity is an unhealthy diet related to imbalanced macronutrients. Diets higher in protein (PRO) are associated with increased energy expenditure (EE) and reduced food intake. The objective of this pilot study was to determine if protein source at breakfast influences EE in young men (n=4; ages 18-35). Participants consumed three isocaloric (whey (WP), pea (PP), beef (BP); 275 kcal, 62% PRO, 23% CHO, 15% Fat) drinks in randomized, crossover design with a one-week washout period. Each test day EE, appetite, and cravings were assessed at 0, …

Cd4 T Cell-Derived Ifn-Γ Plays A Minimal Role In Control Of Pulmonary Mycobacterium Tuberculosis Infection And Must Be Actively Repressed By Pd-1 To Prevent Lethal Disease, Shunsuke Sakai, Keith D. Kauffman, Michelle A. Sallin, Arlene H. Sharpe, Howard A. Young, Vitaly V. Ganusov, Daniel L. Barber

United States Public Health Resources

IFN-γ–producing CD4 T cells are required for protection against Mycobacterium tuberculosis (Mtb) infection, but the extent to which IFN-γ contributes to overall CD4 T cell-mediated protection remains unclear. Furthermore, it is not known if increasing IFN-γ production by CD4 T cells is desirable in Mtb infection. Here we show that IFN-γ accounts for only ~30% of CD4 T cell-dependent cumulative bacterial control in the lungs over the first six weeks of infection, but >80% of control in the spleen. Moreover, increasing the IFN-γ–producing capacity of CD4 T cells by ~2 fold exacerbates lung infection and leads to the early death …

Impact Of Epigallocatechin-3-Gallate (Egcg), A Broad-Spectrum Anti-Inflammatory, In Controlling Intestinal Factors Contributing To Inflammatory Bowel Disease., Gerald Wayne Dryden, Jr.

Electronic Theses and Dissertations

This dissertation explores the role of epigallocatechin-3-gallate (EGCG), as a potential treatment for patients with inflammatory bowel disease (IBD). IBD is a common disorder that causes a great deal of suffering. Our understanding of the etiologies, pathogenic mechanisms, and treatment targets continues to evolve. Many new therapeutic targets are making their way through the pharmaceutical pipelines. However, not all patients benefit from these therapies. EGCG has long been studied as an anti-cancer agent. Most of our understanding of this compound comes from the oncologic literature. As the pathways of oncology and inflammation converge, new lessons can be taken from the …

Cell-Based Therapies For Ischemic Cardiomyopathy : Investigations Of Intramyocardial Retention And Safety Of High Dose Intracoronary Delivery Of C-Kit Positive Cardiac Progenitor Cells, And Therapeutic Utility Of A Novel Population Of Cardiac Mesenchymal Stem Cells Expressing Stage-Specific Embryonic Antigen-3 (Ssea-3)., Matthew C. L. Keith

Electronic Theses and Dissertations

Over the last decade attempts at reducing morbidity and mortality of patients with chronic heart failure have been made via the development and implementation of novel cell based therapies. Substantial advances in cell based therapies with indications of efficacy have been shown along with a robust safety profile. Despite these advances, there is a substantial unmet need for novel therapies, specifically addressing repair and regeneration of the damaged or lost myocardium and its vasculature. Accordingly, cardiac cell-based therapies have gained attention. Various cell-types have been utilized, including bone marrow-derived mononuclear cells, bone marrow-derived mesenchymal stem cells, mobilized CD34⁺ cells, …

Porphyromonas Gingivalis Gingipains Induce A Pro-Inflammatory Extracellular Microenvironment : The Role Of Par-2 And Fibronectin., Jeffrey S. Marschall

Electronic Theses and Dissertations

Periodontitis is a chronic inflammatory disease that is characterized by severe tissue destruction of the gingiva and other tooth supporting structures; if left untreated, tooth loss and disintegration of the alveolar bone occurs. This chronic inflammatory state has been linked to other systemic diseases such as cardiovascular disease, diabetes, rheumatoid arthritis, and Alzheimer’s disease. Porphyromonas gingivalis is the major pathogenic microbe in periodontitis. The main virulence factors of P. gingivalis are the Arg-aa and Lys-aa gingipains, which are proteolytic enzymes implicated in a plethora of activities that allow P. gingivalis to subvert the human immune system in the oral cavity …

Abin1 In The Pathogenesis Of Glomerulonephritis And The Novel Polocyte-Neutrophil Proinflammatory Axis., Erik Anderson Korte

Electronic Theses and Dissertations

Glomerulonephritis (GN) is the most common cause of end-stage renal disease worldwide and is characterized by deposition of immune complex, inflammation, proteinuria and podocyte damage. Immunosuppressive therapy is effective in less than 50% of patients, indicating that immunological activity is not the only relevant cause of kidney injury. While methods have been described for neutrophil-mediated immune activation, specific glomerular mechanisms for recruitment of neutrophils and development of GN have not been determined. Here I present a pathogenic mechanism for the development of GN involving a novel podocyte-neutrophil axis and reveal the importance of glomerular NF-κB inhibition by the ubiquitin binding …

Acrolein Is A Critical Mediator Of Alcohol-Induced Liver And Intestinal Injury In Alcoholic Liver Disease., Wei-Yang (Jeremy) Chen

Electronic Theses and Dissertations

Alcohol consumption can cause alcoholic liver disease (ALD), which remains a major cause of morbidity and mortality in the United States. Chronic alcohol consumption causes a pro-oxidant environment in the liver and increases hepatic lipid peroxidation. Acrolein is the most reactive and toxic aldehyde generated through lipid peroxidation. Acrolein forms protein adducts and triggers endoplasmic reticulum (ER) stress and hepatocyte apoptosis, which are recognized etiologic factors in ALD. Several studies have established the critical role of the gut-liver axis in ALD pathogenesis, wherein alcohol-induced gut barrier dysfunction contributes to liver injury. This study investigates, in vitro and in vivo, the …

Characterization Of The Skeletal Phenotype In Idua-W392x Knock-In Mice: Bone Metabolism Biomarkers, Christina J. Owensby

Graduate Theses/Dissertations

Mucopolysaccharidosis Type I (MPS I, Hurlers Syndrome) is a lysosomal storage disease caused by a deficiency of alpha-L-iduronidase (IDUA). IDUA catalyzes the degradation of the two glycosaminoglycans (GAGs); heparin sulfate (HS) and demantan sulfate (DS). The accumulation of HS and DS makes MPS I progressive with inevitable degeneration of multiple organ systems. Accumulated excess of GAGs on the skeletal system causes dysostosis multiplex, atlantoaxial instability, thoracolumbar kyphosis, genu valgum, acetabular dysplasia, and short stature. Skeletal biomarkers of bone formation and bone resorption were compared in wild-type, heterozygous, and IDUAW392X mice. To investigate osteoblast activity, levels of the bone formation marker …

Human Neonatal Fc Receptor Mediates Transcytosis Of Immunoglobulin-G-Bound Ovalbumin, Farah Gazi

MCB Articles

Introduction: There is increasing evidence that allergies, like many other chronic diseases of childhood, may have origins during the prenatal period. It is also known that mothers, have a stronger influence than fathers, on the development of allergic disease in their children. While the mechanisms responsible for this maternal influence are not known, studies have indicated the possibility of transplacental allergen transfer via immunoglobulin G (IgG) containing immune complexes.

Objective: In this study, we investigated the ability of the neonatal Fc receptor for IgG transport (FcRn) to bind and transport the model allergen ovalbumin in the form of an IgG-ovalbumin …

Evaluating Dietary Quality And Taste Preferences With A Simple Liking Survey: Application To Studying Individuals With Morbid Obesity, Marina L. Zoghbi

Honors Scholar Theses

Feasible ways are needed to screen for dietary behaviors and taste preferences in clinical settings. We examined the internal validity and reliability of a brief survey to assess food preferences and dietary behaviors among morbidly obese individuals considering bariatric surgery. Survey-reported liking is a proxy for dietary intake, correlating with reported food intake and biomarkers of nutritional status (Sharafi et al, 2015) and linking taste genetics with diet and health (Pallister et al, 2015). Methods –Enrolled were 138 morbidly obese patients awaiting bariatric surgery, who completed a 100-item liking survey of foods/beverages, physical/sedentary activities, and pleasurable/unpleasurable experiences. They were oriented …

Pituitary Adenylate Cyclase-Activating Polypeptide Orchestrates Neuronal Regulation Of The Astrocytic Glutamate-Releasing Mechanism System XC−, Linghai Kong, Rebecca Albano, Aric Madayag, Nicholas Raddatz, John R. Mantsch, Sujean Choi, Doug Lobner, David A. Baker

Biomedical Sciences Faculty Research and Publications

Glutamate signaling is achieved by an elaborate network involving neurons and astrocytes. Hence, it is critical to better understand how neurons and astrocytes interact to coordinate the cellular regulation of glutamate signaling. In these studies, we used rat cortical cell cultures to examine whether neurons or releasable neuronal factors were capable of regulating system x_c^-(Sxc), a glutamate-releasing mechanism that is expressed primarily by astrocytes and has been shown to regulate synaptic transmission. We found that astrocytes cultured with neurons or exposed to neuronal-conditioned media displayed significantly higher levels of Sxc activity. Next, we demonstrated that the pituitary …

Estrogen's Effects On Oxidative Stress Levels In Glial Cells, Jacob J. Dirkman

Theses and Dissertations

A decrease in astrocyte function and viability has been linked to many neurodegenerative diseases, including schizophrenia, major depressive disorders, Alzheimer’s disease, and Amyotrophic Lateral Sclerosis (ALS). Previous research indicates that some estrogens may have a positive effect on neuron and astrocyte viability. Estrogens’ effects on the brain are of interest as estrogens are commonly prescribed as hormone replacement therapy to reduce the symptoms of menopause in women. Unfortunately, these effects on are not completely understood. The goal of the project was to discover if estrogen has any protective effect on astrocytes exposed to oxidative stress. We measured the oxidative stress …

The Effect Of Increased Exposure Of Uvc Light On Human Skin Microbiota, T'Kylia S. Moss

Honors Theses

Many methods have been employed to prevent infections from opportunistic pathogens in immunocompromised individuals. Among these are the use of ultraviolet light (UV). In this study, UVC light, was found to have a deleterious effect on specific skin flora. Organisms tested included Acinetobacter baumanii, Candida albicans, Candida kefyr, Corynebacterium renale, Enterococcus faecalis, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pyogenes. Nutrient agar was used to cultivate most organisms. Blood agar was used for the cultivation of Streptococcus pyogenes and Enterococcus faecalis. Bacterial suspensions were made and utilized to plate each organism onto a set of 7 nutrient agar or …

The Effects Of Hypohydration On Neurocognitive, Balance, Vestibular Ocular Motor Functions And Mood State, Satoshi Iida

Graduate Theses and Dissertations

Inconsistent findings have been observed on the impact of hydration state on cognitive functions. The isolated effect of hypohydration on neurocognitive performance, balance, vestibular ocular motor function and mood outcomes in widely used concussion assessment tools has not been studied. The purpose of this study was to investigate how hypohydration affected the results in concussion testing batteries. A single-blind randomized crossover design was used. Thirteen healthy males (22 ± 4y, 180.9 ± 5.7cm) without history of concussion within the past six months or any condition or disease that could influence outcome measurements participated in this study. Each subject completed concussion …

Regulation Of Irf-3-Dependent Innate Immune Signaling Pathway By The Plpro Domain Of Non-Structural Protein 3 (Nsp3) Of Severe Acute Respiratory Syndrome (Sars) Coronavirus, Sandra Nicole Lester

Theses and Dissertations (ETD)

The induction of Type I Interferons (IFNs) is a powerful and rapid innate defense mechanism against viral infection, and many viruses have developed elaborate strategies to overcome the antiviral effects of IFN, ensuring their survival and replication. Severe acute respiratory syndrome coronavirus (SARS-CoV) is a highly pathogenic virus that causes severe lung disease in humans and is associated with high mortality rates. SARS-CoV, like all other successful viruses, encode proteins that counteract the innate immune response. A number of reports have indicated the papain-like protease (PLpro) domain of SARS-CoV Non-Structural Protein 3 (NSP3) as a powerful interferon antagonist, by suppressing …

Redesigning Gfp Reporter System For Utilization In Clostridium Difficile, Laura E. Fitzgerald

Biological Sciences Undergraduate Honors Theses

Clostridium difficile (C. difficile) is a gram-positive bacterium that comprises part of the healthy human gut microbiome. When it gains sufficient access to peptides, C. difficile flourishes and releases tissue-damaging toxins, which cause inflammation of the colon that can develop into a Clostridium difficile Infection (CDI).¹⁰ The Ivey Laboratory believes that the best tactic in preventing CDIs is stopping peptide ingestion, which theoretically could be accomplished by manipulating the oligopeptide permease (App) system.⁷ In order to verify that altering the App system would successfully impede peptide uptake, first the expression of the app Promoter Region ( …

Friendly Fire: Biological Functions And Consequences Of Chromosomal Targeting By Crispr-Cas Systems, Gary E. Heussler, George A. O'Toole

Dartmouth Scholarship

Clustered regularly interspaced short palindromic repeat (CRISPR)-associated (Cas) systems in bacteria and archaea target foreign elements, such as bacteriophages and conjugative plasmids, through the incorporation of short sequences (termed spacers) from the foreign element into the CRISPR array, thereby allowing sequence-specific targeting of the invader. Thus, CRISPR-Cas systems are typically considered a microbial adaptive immune system. While many of these incorporated spacers match targets on bacteriophages and plasmids, a noticeable number are derived from chromosomal DNA. While usually lethal to the self-targeting bacteria, in certain circumstances, these self-targeting spacers can have profound effects in regard to microbial biology, including functions …

Microrna-186 And Metastatic Prostate Cancer., Dominique Zilpha Jones

Electronic Theses and Dissertations

MicroRNA (miR) dysregulation alters cancer-associated gene expression, which contributes to cancer pathogenesis. For example, miR-186 over expression lead to enhanced proliferation and migration in pancreatic cancer cell models. However, the role of miR-186 in prostate cancer (PCa) remains controversial. Previously, miR-186-5p was up-regulated in PCa patient serum (stage III/IV) compared to controls. Furthermore, miR-186-5p was up-regulated in metastatic PCa (PC-3, MDA PCa 2b, LNCaP) relative to normal prostate epithelial cells (RWPE1). We hypothesized miR-186 inhibition will reduce aggressive PCa using metastatic cell models. To test this, we evaluated whether miR-186-5p inhibition would reduce aggressive PCa behavior and overexpression induce malignant …

Role Of Microrna-21 In Atherogenesis., Rihab Hamed-Berair

Electronic Theses and Dissertations

MicroRNA-21 (miR-21) is an evolutionarily conserved microRNA, abundant in most cardiovascular tissues. It has been implicated in the pathogenesis of several cardiovascular diseases including restenosis, myocardial infarction, and heart failure. However, little is known about the contribution of miR-21 in atherosclerosis. My data show that expression of miR-21 is increased by >1.5-fold in murine atherosclerotic lesions and by 1.5-2.0-fold in the macrophages of Western diet (WD)-fed LDLR-KO mice (for 12-20 weeks). In vitro, LDL, oxidized LDL, acetylated LDL and LPS induced miR-21 by 2-4-fold and down-regulated its target protein, PDCD4, in bone marrow-derived macrophages. Basally, macrophages isolated from miR-21-KO …

Ethnic Identity And Teratogenic Risk Perceptions, Katie M. Chan

Dissertations and Theses (Open Access)

Elevated perceptions of teratogenic risk can cause anxiety and confusion among pregnant women. To assess whether ethnic identity and demographic factors can influence teratogenic risk perceptions, 194 pregnant women in Houston were surveyed using the Multigroup Ethnic Identity Measure (MEIM) and visual analog scales to quantify perceptions of teratogenic risk for common exposures during pregnancy. Overall, participants estimated an elevated baseline risk of 25% for birth defects among the general population. In addition, participants overestimated birth defect risks for specific exposures, such as alcohol and marijuana. Based on the MEIM scores, ethnic identity was not significantly associated with teratogenic risk …

Stabilization Of Gp120 Outer Domain For Hiv-1-1 Vaccine Immunogen Design, Duoyi Hu

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

The sole envelope glycoprotein spike on the surface of Human Immunodeficiency Virus (HIV-1) is composed of two subunits: gp120 and gp41. The gp120 consists of three domains: the inner domain, outer domain and bridging sheet, to which the viral primary receptor CD4 binds and induces a conformational change in gp120 to expose the co-receptor binding site. Previous studies have found that the outer domain of gp120 is relatively more stable than the inner domain and bridging sheet. When superimposed, the co-crystal structures of CD4-gp120 complex and VRC01-gp120 complex revealed that the CD4-binding site (CD4-BS) antibody VRC01 actually mainly bound to …

A Novel And Rapid Staphylococcus Aureus Bacterial Identification Method Utilizing Immunomagnetic Beads And Single Cell Laser-Light Scattering, Kaylagh Hollen

All NMU Master's Theses

Staphylococcus aureus is the most commonly isolated human associated bacterial pathogen. It plays an important role in skin and soft-tissue infections, pneumonia, endocarditis, osteomyelitis, foreign-body infections, and sepsis. S. aureus diagnosis and treatment requires a minimum of 24-48. With this in mind, previous studies suggest that faster pathogen identification has been linked to improved patient outcomes. Improved patient outcomes including a reduction in hospitalization time, decreased risk of nosocomial infections, and decreased in medical costs. The impact of faster identification on patient outcome has led us to develop an alternative method of S. aureus identification via ImmunoMagnetic Separation (IMS) and …

Examination Of Cd133 And Cd147 As Cancer Stem Cell Markers, Christopher Mcmahon

All NMU Master's Theses

To date, as many as 14,000 patients in the United States per year are diagnosed with glioblastoma, the most common and most malignant primary brain tumor. Glioblastomas are characterized by their ability to evade treatment on many fronts, thus a novel approach to curative therapies is imperative. A population of cells with stem cell-like properties are found within glioblastoma tumors and drive their initiation and progression. Identification of extracellular markers on these tumor stem cells is thus paramount. The cell surface glycoproteins CD133 and CD147 were examined as potential markers of cancer stem cells found in glioblastoma. Here we found …

Multiphoton Imaging Of Labeled Breast Cancer Cells To Quantify Intra And Extracellular Receptors, Sydney C. Wiggins

Biomedical Engineering Undergraduate Honors Theses

Every year 200,000 women in the United States are diagnosed with breast cancer. Of the cases diagnosed, 10% -15% are classified as triple negative breast cancer (TNBC) due to the absence of estrogen, progesterone, and HER-2/Neu receptors. This breast cancer sub-type is markedly more aggressive and twice as likely to develop in premenopausal women. TNBC is resistant to endocrine therapies and current targeted agents, making clinical need for the development of validated therapeutics for TNBC a pressing matter. To initiate drug development, the internalization of directly immunolabeled epidermal growth factor receptors (EGFR) in SK-BR-3 human breast adenocarcinoma cells was quantitated …

Validation Of The Use Of Doubly Labeled Water For Measuring Metabolic Rate In Timber Rattlesnakes (Crotalus Horridus), Caitlin Hirsh

Biological Sciences Undergraduate Honors Theses

The doubly labeled water method is an isotopic technique for measuring field metabolic rate and water flux rates of free-living animals. We present a validation of the use doubly labeled water for measuring metabolic rate and water loss in Timber Rattlesnakes (Crotalus horridus). For this study seven animals of varying body size were used with masses ranging from 148 to 650 grams. Prior to dosing, blood samples were taken to establish background isotope levels for each animal. Snakes were injected with water enriched with isotopes of oxygen (18O) and hydrogen (2H, deuterium). The injected isotopes were then allowed to equilibrate …

Investigating The Regulation And Function Of The Nr4a Nuclear Receptors In Cancer, Jordan A. Beard

Theses and Dissertations (ETD)

The nuclear receptor (NR) superfamily represents a structurally-conserved group of ligand-regulated transcription factors. These proteins have critical roles in various physiological and pathological processes, including cancer, and have been targets of drug therapy. The orphan NR subfamily 4A (NR4A), which includes the NR4A1 (Nur77), NR4A2 (Nurr1), and NR4A3 (Nor-1) genes, has been implicated in adult solid tumors and has been characterized as pro-tumorigenic mediator of cell proliferation, transformation, migration, and drug resistance. Alternatively, in leukemia, NR4A1 and NR4A3 have been described as tumor suppressors in hematologic malignancies. Members of the NR4A family are commonly overexpressed in cancer and this has …

Novel Oncogenic Drivers In Pediatric Gliomagenesis, Alexander K. Diaz

Theses and Dissertations (ETD)

Pediatric high-grade gliomas (pHGGs), with a two-year survival rate of less than 20%, are some of the most aggressive human cancers. This dissertation begins with our analysis of 127 pHGGs, including brainstem (BS) and non-brainstem (NBS) tumors, from 118 patients using next-generation sequencing technologies. Nearly one-third of BS-HGGs, also known as diffuse intrinsic pontine gliomas (DIPGs), harbored somatic heterozygous missense mutations in ACVR1, coding for a receptor serine-threonine kinase involved in bone morphogenetic protein (BMP) signaling. These alterations led to gain-of-function as evidenced by increased phosphorylation of downstream targets in primary astrocytes and zebrafish embryo ventralization. Whole-genome sequencing and …

Antibodies To Heterogenous Nuclear Ribonucleoprotein A1 Penetrate Neurons Leading To Multiple Downstream Effects Resulting In Neurodegeneration, Joshua Nathan Douglas

Theses and Dissertations (ETD)

Multiple sclerosis (MS) is the most common demyelinating disorder of the central nervous system. MS is believed to occur in genetically susceptible individuals due to an unknown environmental stimulus. MS patients produce autoantibodies to heterogenous nuclear ribonuclearprotein A1 (hnRNP A1), an RNA binding protein (RBP) highly expressed in neurons. hnRNP A1 functions in pre-mRNA splicing, mRNA trafficking, and translation. Furthermore, the anti-hnRNP A1 antibodies are specific to a N-terminal region termed ‘M9’ which serves as a nuclear export sequence/nuclear localization sequence (NES/NLS) responsible for nuclear/cytoplasmic transport of the protein. In this manuscript we will provide data revealing that anti-hnRNP A1 …

Hit Identification For Pkcζ Inhibitors: Structure-Based Optimization, Virtual Screening, And Biological Evaluation, Xiaoxin Wu

Theses and Dissertations (ETD)

Protein kinase C ζ (PKCζ) is believed to be a promising target for the treatment of some diseases, including inflammatory diseases, obesity and diabetes. Hit identification of PKCζ inhibitors was conducted by structure-based modification, virtual screening and biological evaluation. Among all the compounds selected and synthesized, compound JW-1-60A showed moderate activity against PKCζ at 30 μM and 100 μM. The molecular modeling studies showed that the binding mode of JW-1-61A was very close to the binding mode of JP-3-149, a reported PKCζ inhibitor with very potent activity, which might partially explain the moderate activity of JW-1-61A. Based on the structure …