Medicine and Health Sciences Commons^™

Role Of The Acid Sensing Ion Channel 1a In The Systemic Circulation, Selina M. Garcia

Biomedical Sciences ETDs

Acid-sensing ion channel 1a (ASIC1a) is a non-selective cation channel that is expressed in vascular smooth muscle cells. However, little is known about the contribution of ASIC1a to vascular reactivity and cardiovascular homeostasis. We have previously shown that ASIC1a contributes to pulmonary vascular smooth muscle cell (VSMC) Ca²⁺ entry and vasoconstriction as well as chronic hypoxia-induced pulmonary hypertension. However, a role of ASIC1a in the systemic circulation is unclear. Previous reports have shown that ASIC1a is expressed in femoral and cerebral arteries, however, these studies suggest that ASIC1a contributes to vascular reactivity through neuronal regulation rather than vascular. Therefore, …

The Effects Of Glycosylation On Immunogenicity And Replication Of Emerging Viral Pathogens, Elizabeth C. Clarke

Biomedical Sciences ETDs

For filoviruses, a family of hemorrhagic fever viruses, the main antigen for vaccines in development is the glycosylated glycoprotein GP1,2. How the glycosylation of GP1,2 differs when the protein is produced in different cell lines is unclear. We showed significant differences in the types of glycans conferred onto filovirus GP1,2s in produced in mammalian-origin and insect-origin cell lines. Mammalian-derived filovirus GP1,2s have diverse N-linked glycans and extensive O-linked glycans, whereas insect-derived filovirus GP1,2s have N-linked glycans that are primarily paucimannose type and have no observable O-linked glycans. We then showed that differences in glycosylation impacted how immunogenic the proteins were …

The Role Of Hud In Alternative Splicing And Alternative Polyadenylation In The Brain, Rebecca M. Sena

Biomedical Sciences ETDs

RNA binding proteins (RBPs) regulate several processes in the cell, including alternative splicing and alternative polyadenylation. Hu proteins, a class of ELAV-like RBPs, are crucial for proper development and maintenance of the nervous system. Several Hu proteins, including HuD, have been shown to regulate alternative splicing and alternative polyadenylation of neuronal transcripts. However, previous studies have relied on molecular techniques to analyze individual transcripts, which do not provide a global overview of the transcriptome. The purpose of this study was to develop a bioinformatics pipeline to analyze splicing and polyadenylation using RNA-sequencing data. Once the pipeline was developed, it was …

Developing A Virus-Like Particle (Vlp)-Based Vaccine For Neisseria Gonorrhoeae, Ashvini Vaidya

Biomedical Sciences ETDs

Neisseria gonorrhoeae (Ng) is a sexually transmitted bacterium that infects human reproductive mucosal surfaces. Due to the risk of complications in untreated cases and evolving antibiotic resistance, a prophylactic vaccine is critical for preventing infection. There are four Ng outer-membrane proteins that contribute to Ng survival and resistance: PorB, BamA, TbpA, and MtrE. Each protein contains surface-exposed loops that are targets of bactericidal antibodies. Vaccines were developed by displaying Ng epitopes on the surface of bacteriophage virus-like particles (VLP). VLPs are immunogenic, multivalent, self-assembling complexes composed of viral structural proteins. Antigenic peptide sequences can be displayed on the surface …

Suicide, Heroin Use And Protective Resiliency Factors Amongst Transgender Adolescents In New Mexico, Richard Gadomski

Biomedical Sciences ETDs

Transgender people experience significant mental health inequities. The goal of this study was to evaluate disparities related to suicide attempt in the past 12 months and ever heroin use in cisgender versus transgender adolescents, and identify specific resiliency factors associated with a decrease in the prevalence of suicide attempt and heroin use in transgender adolescents. This study is a cross-sectional, secondary analysis of the 2017 New Mexico Youth Risk and Resiliency Survey among high school students. The odds of suicide attempt were 5.5-fold greater, and the odds of lifetime heroin use were nearly 14-fold greater, for transgender compared to cisgender …

Virus-Like Particle-Based Vaccines Induce Antibody-Mediated Neutralization Of Staphylococcus Aureus Virulence, Jason Alexander Joyner

Biomedical Sciences ETDs

Staphylococcus aureus is a pathogenic bacterium that inflicts a large amount of human suffering using an arsenal of virulence factors to cause minor to life-threatening infections. Both the accessory gene regulator (agr) operon, a virulence regulatory pathway that controls expression of over 200 virulence factors, and alpha-hemolysin (Hla), a key pore-forming toxin, play a significant role in infection severity. Given the clinical trial failures of S. aureus vaccine candidates and the prevalence of antibiotic-resistant strains, novel and effective treatment options are urgently needed. Chapter 2 describes a novel virus-like particle (VLP) -based vaccine inducing agr-I-inhibiting antibodies …

Sexual Dimorphism In Host Innate Response To Staphylococcus Aureus: Mechanisms Driving Sex Differences In Immune Cell Function And Host-Directed Interventions, Srijana Pokhrel

Biomedical Sciences ETDs

With the emerging antibiotic resistance, Staphylococcus aureus, primary causative agent of skin and soft tissue infections (SSTIs) as well as other life-threatening conditions has become a global health concern. While factors contributing to host defense against S. aureus SSTIs has been well studied, impact of sex as a variable has not been reported. In Chapter 2, we uncover the sex-specific differences in host response to S. aureus SSTIs and the contribution of female sex hormone, estrogen (E2) in providing protection in females. In Chapter 3, we identify mechanisms of innate differences in neutrophils bactericidal efficacy between sexes and in …

Association Between Self-Reported Dyspnea And Depressive Symptoms In New Mexico Uranium Workers, Shiva Sharma

Biomedical Sciences ETDs

BACKGROUND: Uranium workers risk experiencing dyspnea, a lung disease symptom. Previous studies found associations between dyspnea and depressive symptoms in lung disease, but this requires further study in occupational cohorts.

METHODS: This study evaluated the association between dyspnea and depressive symptoms in former uranium workers screened by New Mexico Radiation Exposure Screening & Education Program. Dyspnea and depressive symptoms were evaluated through questionnaires, Modified Medical Research Council Dyspnea Scale and a modified Patient Health Questionnaire-2, respectively. Logistic regression models were applied to cross-sectional analyses. Generalized linear models were applied to longitudinal analyses.

RESULTS: Cross-sectional analyses demonstrated higher dyspnea scores were …

Exosomal Secretion Of A Psychosis-Altered Microrna Regulates Glutamate Receptor Expression; Effects Of Antipsychotics And Maternal Immune Activation, Stephen Amoah

Biomedical Sciences ETDs

MicroRNAs are a subcategory of evolutionarily conserved small non-coding RNAs that are altered in psychiatric conditions. The ability of small secretory microvesicles known as exosomes to influence neuronal and glial function via their microRNA (miRNA) cargo has positioned them as a novel and effective method of cell-to-cell communication. Inflammation, which is evident in schizophrenia (SCZ) and bipolar disorder (BD), and antipsychotics usage may alter miRNA expression in the brain. However, little is known about the role of exosome-secreted miRNAs in the regulation of neuronal gene expression and their relevance for SCZ and BD. Here, we used miRNA profiling and qRT-PCR …

Translating Touches: New Approaches For Modeling And Rescuing Executive Function Deficits After Prenatal Alcohol Exposure, Johnny A. Kenton

Biomedical Sciences ETDs

Background: With a recent meta-analysis indicating that 9.8% of women worldwide consume alcohol during pregnancy, understanding the effects of fetal alcohol spectrum disorder (FASD) is critical for both identifying and treating those afflicted. Traditional preclinical research investigating the behavioral effects of neurodevelopmental disorders, such as FASD, has utilized tasks designed for specific animal models. For this reason, preclinical research into FASD requires a shift into clinically relevant behavioral testing. One such method involves touch-sensitive screens integrated into an operant box to emulate clinical computer-based tasks, such as the Cambridge Neuropsychological Test Automated Battery.

Methods: Here, we utilized a mouse model …

Zinc Finger Dna Repair Protein Targets Of Arsenite In The Nucleotide Excision Repair Pathway, Juliana M. Huestis

Biomedical Sciences ETDs

Environmental arsenic exposure affects around 100 million people worldwide. Recent evidence shows that arsenite, even at low concentrations, may act as a co-carcinogen, by displacing zinc from the zinc finger motifs of certain DNA repair proteins, leaving them vulnerable to redox modification and loss of protein function. This study probes the physical chemistry underlying arsenite and zinc binding to XPA and PARP1, in the hope of illuminating some of the aspects of protein structure that determine susceptibility to arsenite binding. In this study, dissociation constants are determined for zinc and arsenite binding to peptides corresponding to the C4 zinc finger …

Cold-Inducible Rna Binding Protein (Cirp) Impedes Proliferation And Inflammation In The Pymt Mouse Model For Breast Cancer, Daniel Albino Lujan

Biomedical Sciences ETDs

RNA binding proteins (RBPs) regulate gene expression by controlling mRNA export, translation, and stability. When altered, some RBPs allow cancer cells to grow, survive, and metastasize. Cold-inducible RNA binding protein (CIRP) is overexpressed in a subset of breast cancers, induces proliferation in breast cancer cell lines, and inhibits apoptosis. We generated a transgenic mouse model overexpressing human CIRP in the mammary epithelium to ask if it plays a role in mammary gland development. We also assessed the effects of CIRP on breast tumorigenesis using breeding crosses with the PyMT mouse model for breast cancer. CIRP decreased proliferation at the lactational …