Medicine and Health Sciences Commons^™

Inflammation In The Neovaginal Microenvironment Of Transfeminine Individuals, Hannah M.J. Wilcox

Electronic Thesis and Dissertation Repository

Transfeminine individuals are assigned male at birth but do not identify as male. Some transfeminine individuals may choose to undergo the gender affirming surgery vaginoplasty to create a neovagina. There is a paucity of data on the neovaginal microenvironment to inform best gynecological practices. Vaginal and penile inflammation is modulated by local microbiota, but drivers of inflammation in the neovagina are poorly understood. The compositions of the neovaginal microbiota and immune milieu were elucidated from neovaginal swabs, using 16s rRNA gene sequencing and multiplex immunoassay, respectively. Immune data reduction and clustering was performed, and six unique immune profile types (IPTs) …

Functional Characterization Of A High-Throughput In Vitro Model To Predict Faecal Microbiota Transplantation (Fmt) Donor Success, Catherine M. Andary

Undergraduate Student Research Internships Conference

Faecal microbiota transplantation (FMT) involves the administration of donor faecal matter to a diseased recipient with the goal of remodeling the host microbiome to provide health benefits. In recent years, FMT has emerged as a potential therapy for a variety of microbiome-associated diseases such as atherosclerosis. Trimethylamine (TMA) is an atherosclerosis-linked metabolite generated by the gut microbiota from dietary precursors which is then oxidized to trimethylamine N-oxide (TMAO) by the liver, contributing to increased gut permeability. It has been shown that FMT may alter or restore the gut microbiome of recipients to reduce plasma TMAO levels. Despite its potential, the …

The Role Of Urinary Modulators In The Development Of Infectious Kidney Stones, Brendan Wallace

Electronic Thesis and Dissertation Repository

The pathogenesis of infectious kidney stones is poorly understood, while equally unclear is the role of urinary modulators and bacteria. An experimental model was created and utilized to test a variety of urinary modulators and bacterial strains commonly associated with struvite and calcium phosphate stones to evaluate their potential roles in influencing crystal formation. Modulators such as acids, citrate, and osteopontin had strong inhibitory effects on infectious crystal formation while the remaining modulators had neutral, mixed, or positive effects. Lastly, it was determined that the presence of urease may not directly lead to calcium phosphate and struvite stones in all …

The Role Of Coagulase-Negative Staphylococcal Secreted Products On Staphylococcus Aureus And Staphylococcus Lugdunensis Infections, Denny Chin

Electronic Thesis and Dissertation Repository

The Staphylococcus genus is comprised of over 40 bacterial species. The most well-studied species in this genus is the notorious human pathogen Staphylococcus aureus, a bacterium that produces coagulase among many other virulence factors. Since S. aureus is a major health burden and causes a plethora of diseases in humans, it has received significant attention and much research has been done to understand its biology to treat diseases caused by this pathogen. However, the coagulase-negative staphylococci (CoNS) make up most of the staphylococcal species and have received less attention since they are thought to have a lesser impact on …

Ex Vivo Thrombus Magnetic Resonance Imaging Features And Patient Clinical Data Enable Prediction Of Acute Ischemic Stroke Cause, Spencer D. Christiansen, Junmin Liu, Maria Bres Bullrich, Manas Sharma, Sachin K. Pandey, Melfort Boulton, Sebastian Fridman, Luciano A. Sposato, Maria Drangova

Robarts Vascular Research Publications

The cause of ischemic stroke often remains elusive even after full stroke workup is completed. Cardioembolic mechanisms in particular are frequently presumed but challenging to definitively diagnose. Quantitative thrombus texture analysis is emerging as a powerful tool for stroke characterization, having shown the ability to predict response to stroke treatment,1 but its ability to predict stroke cause and complement machine learning models built from standard clinical features has not been studied.2, 3 The purpose of this study is to evaluate the ability of radiomics features extracted from quantitative magnetic resonance images of retrieved ischemic stroke thrombi (R2*(=1/T2*), …

Hiv-1 Drug Resistance To Integrase Strand Transfer Inhibitors In Hiv-1 Non-B Subtypes, Emmanuel Ndashimye

Electronic Thesis and Dissertation Repository

Human immunodeficiency syndrome (HIV-1) has infected over 75 million people and over 35 million have succumbed to virus related illnesses. Despite access to a variety of antiretroviral therapy (ART) options, ART programs have been disproportionally spread in the world with low-and middle-income countries (LMICs) facing challenges to access the most potent ART options. With less potent ART remaining in use in LMICs, HIV-1 drug resistance (HIVDR) presents a growing challenge in LMICs. Since approval of the first-generation integrase strand transfer inhibitor (INSTIs), Raltegravir (RAL) in 2007, INSTIs remain the best choice as a backbone of ART. Access to second generation …

The Development Of Bacterial Magnetic Resonance Imaging For Microbiota Analyses, Sarah C. Donnelly

Electronic Thesis and Dissertation Repository

Current microbial analyses to assess either the commensal microbiota or microorganism infection and disease typically require ex vivo techniques that risk contamination and are not undertaken in real time. The possibilities for employing imaging techniques in the microbiology field is becoming more prominent as studies expand on the use of positron emission tomography, ultrasound and numerous microscopy techniques. However, magnetic resonance imaging (MRI), a non-invasive in vivo modality that can produce real-time results is falling behind. Here, we examined the feasibility of detecting bacteria using clinical field strength MRI. Commensal, probiotic and uropathogenic Escherichia coli were scanned by 3 Tesla …

Characterizing The Role Of The Microbiome In Kidney Stone Disease, Kaitlin F. Al

Electronic Thesis and Dissertation Repository

The goal of this thesis was to increase understanding of the role of the human microbiome in kidney stone disease, from stone nidus formation through to surgical stone treatment, using a combination of in vitro, in vivo, and human clinical investigations.

We first optimized our methods of sample collection for the use of such protocols in clinical studies involving urinary and gut microbiota investigations. We developed a novel method of fecal sampling that is amenable to study participants, inexpensive, and results in reliable downstream sequencing results.

We then utilized this sampling methodology in clinical investigations into the microbiota of …

Potential Role Of Extracellular Atp Released By Bacteria In Bladder Infection And Contractility, Behnam Abbasian

Electronic Thesis and Dissertation Repository

Urgency urinary incontinence (UUI), the result of conditions such as overactive bladder (OAB), could potentially be influenced by both commensal and urinary tract infection-associated bacteria. The sensing of bladder filling involves interplay between various parts of the nervous system eventually resulting in contraction of the detrusor muscle during micturition. Here we model host responses to various urogenital bacteria, firstly by using urothelial bladder cell lines and then with myofibroblast contraction assays. To measure responses, we examined calcium influx, gene expression and alpha smooth muscle actin deposition assays. We found that organisms such as Escherichia coli IA2 and Gardnerella vaginalis ATCC …

Understanding The Impact Of Hiv-1 Genetic Diversity On The Function Of Nef And Its Role In Serinc5 Antagonism, Aaron Leslie Johnson

Electronic Thesis and Dissertation Repository

HIV-1 Nef is a key pathogenic protein, allowing HIV-1 to evade the host immune system by downregulating MHC-I and CD4. Furthermore, it was recently discovered that Nef counteracts the host factor SERINC5 to increase HIV-1 infectivity, but the mechanistic details of the Nef:SERINC5 interaction still need to be explored. Throughout this dissertation, I will explore the hypothesis that the genetic diversity that defines HIV-1 has a pronounced effect on the HIV-1 protein Nef, altering its function between and within group M subtypes. To address this hypothesis I investigated how MHC-I and CD4 downregulation differ among all non-recombinant group M subtypes. …

Characterization Of Urinary Microbiome And Their Association With Health And Disease, Yige Bao

Electronic Thesis and Dissertation Repository

There has been a growing interest in human microbiome studies in the past decade, with the development of high-throughput sequencing techniques. These microorganisms interact and respond to the host as an entity, and are involved in various homeostatic functions including nutrition digestion, immune response, metabolism and endocrine regulation. The urinary microbiome, however, remains relatively under-investigated.

One of the technical challenges of urinary microbiome studies is the samples usually contain a large number of host cells and low microbial biomass. These samples with the high host, low microbial abundance (“high-low” samples) are associated with increased risk of compromised quality of …

Oncolytic Virus Therapy For The Treatment Of Metastatic Ovarian Cancer, Jessica Tong

Electronic Thesis and Dissertation Repository

The management of patients with epithelial ovarian cancer (EOC) faces two major challenges which standard treatments fail to effectively address: 1) Diffuse metastasis as a consequence of late stage diagnosis and 2) intra-tumoral heterogeneity, which fuels tumor evolution and drives the acquisition of chemotherapeutic resistance. In this thesis, we tested new therapeutic strategies using a 3-dimensional in vitro spheroid culture model that mimics key steps of epithelial ovarian cancer metastasis; and another model that mimics both temporal and cellular heterogeneity by establishing multiple cell lines from a single patient over the course of disease progression. Using these models, we investigated …

Characterization Of The Atsr/Atst Global Regulatory Pathway In Burkholderia Ceocepacia, Maryam Khodai-Kalaki

Electronic Thesis and Dissertation Repository

Phosphorylation cascades governed by two-component signal transduction systems provide key signalling mechanisms in bacteria, simple eukaryotes and higher plants, allowing them to translate signals into adaptive responses. These regulatory pathways consist of a transmembrane sensor protein that responds to an environmental cue leading to autophosphorylation, followed by the transfer of the phosphate to a cytoplasmic response regulator. Here, I study AtsR, a membrane-bound hybrid sensor kinase of Burkholderia cenocepacia, that negatively regulates quorum sensing related virulence factors such as biofilm, type 6-secretion and protease secretion. B. cenocepacia is a Gram-negative opportunistic pathogen which causes severe, chronic respiratory infections in …

Molecular Characterization Of Herc5: A Novel Multifunctional Antiviral Protein, Matthew W. Woods

Electronic Thesis and Dissertation Repository

Interferon (IFN)-induced proteins serve as one of the first lines of defense against viral pathogens such as Human Immunodeficiency Virus (HIV)-1. IFN treatment has been shown to restrict multiple stages of HIV-1 replication. The identities and functions of IFN-induced proteins involved in the inhibition of HIV-1 and other viruses are not fully understood. Homologous to the E6-AP C-terminus (HECT) and regulator of chromosome condensation 1 (RCC1)-like domain (RLD) containing protein 5 (HERC5) is strongly upregulated by the Type I IFN response. HERC5, a member of the small HERC family, is composed of an N-terminus RLD domain and a C-terminus HECT …

Granulocyte Colony-Stimulating Factor: Its Role In Gut-Homing Macrophage Generation And Colitis, And Production By Probiotics, Shahab Meshkibaf

Electronic Thesis and Dissertation Repository

The pleiotropic cytokine granulocyte-colony stimulatory factor (G-CSF) is mainly required for the generation of neutrophils, but its role in macrophage generation has also been reported. In addition, G-CSF is effective for the down-regulation of inflammatory cytokines and ameliorating gut disorders, such as colitis. However, the G-CSF function in macrophage generation and gut immunity remains unclear. The first focus of this thesis was to assess the role of G-CSF in macrophage generation and its contribution to gut immunity. G-CSF was found to promote the generation of Gr-1high/F4/80+ macrophages in macrophage (M)-CSF-treated bone marrow cells, most likely through suppressing cell death. Gr-1high …

Efficacy Of Novel Antifouling/Antimicrobial Coatings For The Prevention Of Urinary Device Associated Infection And Encrustation, Thomas O. Tailly

Electronic Thesis and Dissertation Repository

Device associated urinary tract infections are a very important healthcare issue. Despite best efforts in preventing and treating these infections, many patients and physicians are still confronted with this problem. Our research group is involved in testing and evaluating new stent coatings for the prevention of device associated infections and device encrustation. In the current project, we tested two new coating copolymers, both based on a long chain polymer backbone and mussel adhesive protein to this purpose in a rabbit and porcine model. The results demonstrate efficiency of one copolymer in preventing infections in the rabbit model. Interestingly there is …

Structure-Function Analysis Of Udp-Sugar: Polyisoprenyl Phosphate Sugar-1-Phosphate Transferases, Sarah E. Furlong

Electronic Thesis and Dissertation Repository

The synthesis of lipid-linked glycans is a conserved process in eukaryotes and prokaryotes that is initiated by two major enzyme families: the polyisoprenyl-phosphate hexose-1-phosphate transferases (PHPTs) and the polyisoprenyl-phosphate N-acetylaminosugar-1-phosphate transferases (PNPTs). These enzymes contain multiple membrane domains and transfer a sugar-1-phosphate from a nucleotide sugar precursor to a lipid carrier. The prototypic PNPT member used in this study is the E. coli WecA, which initiates the synthesis of O antigen and enterobacterial common antigen in Enterobacteriaceae by transferring N-acetylglucosamine-1-P to undecaprenyl phosphate (Und-P). We investigated the topology and function of the highly conserved VFMGD motif. Our results revealed that …

Evaluating The Co-Commensal Lifestyles Of Staphylococcus Aureus And Staphylococcus Epidermidis, Piraveina Gnanasuntharam

Electronic Thesis and Dissertation Repository

Staphylococcus epidermidis is a ubiquitous skin commensal, and produces a serine protease Esp that can eradicate nasal carriage of the opportunistic pathogen, Staphylococcus aureus. We evaluated the ability of S. epidermidis and S. aureus to express serine protease and compete with one another in response to acidic pH and unsaturated free fatty acids; conditions encountered on human skin. The hypervirulent USA300 strain of S. aureus was more competitive in co-culture conditions of acidic pH or 25 µM palmitoleic acid alone, but could not compete with S. epidermidis when these conditions were combined. Conversely, in pure culture, these conditions promoted …

Systematic Assessment Of The Contribution Of Superantigens To Nasopharyngeal Colonization In A Mouse Model Of Streptococcal Infection, Katherine J. Kasper

Electronic Thesis and Dissertation Repository

Streptococcus pyogenes is adapted for persistence in humans. It typically colonizes the tonsils and skin, and humans are the only known reservoir. S. pyogenes can cause a wide range of mild to serious infections. Most streptococci-related deaths are due to complications of rheumatic fever and invasive infections. S. pyogenes produces virulence factors that contribute to the pathogen’s ability to colonize and cause disease, including streptococcal superantigens (SAgs), also known as streptococcal pyrogenic exotoxins (Spes). SAgs function by cross-linking T cells and antigen presenting cells (APC) which may cause a massive inflammatory response, and as such have been found to contribute …