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A Systems Approach to Dissecting the Role of the Mucosal Microbiome in Disease
Get PDFThe microbial community harbored by the mammalian gastrointestinal tract, collectively called the gut microbiota, plays a critical role in host health, metabolism, and immunity. Quantifiable changes in the gut microbiota have been implicated in a myriad of pathologies, including autoimmune, metabolic, and neurodegenerative diseases. Because of the gut microbiota’s plasticity, manipulating this community for therapeutic benefit presents as a novel strategy to combat modern diseases. Yet, only a fraction of the total microbial diversity that exists within the gut has been successfully cultured in a laboratory, leaving the clinical implications and functional attributes of many gut microbes undetermined. To address this issue, studies in this dissertation focused on bioinformatically investigating (i) the role of dietary and genetic factors on the gut microbiota in metabolic syndrome and (ii) the anatomic niche and immunomodulating antigens of the culture-resistant commensal, Segmented Filamentous Bacteria (SFB). Comprehensive characterization of the cecal microbial community in normal and metabolic syndrome-susceptible mice revealed that dietary factors overshadow the effects of host genetics and are determinist of the microbial patterns that emerge in metabolically healthy or diseased hosts. Moreover, we identified a microbial community proximal to the Peyer’s Patches that was phylogenetically distinct from the cecum. Through a multi-omics approach, we show that independent of mouse genetics, vendor, age, or gender, SFB are highly abundant in the Peyer’s Patches mucosa. Our in silico antigen prediction analyses identified thirty-five potential antigens within the reference proteome of SFB. Shotgun proteomics of the murine ileal mucosa confirmed the in situ presence of several potential antigens expressed by SFB, of which included multiple flagellar proteins. To experimentally valid bioinformatically-inferred antigen targets, we developed a collection of broad-host bacterial vectors to enable microbial products of interest to be precisely expressed in vitro, ex vivo, and in vivo. Collectively, our studies reveal important findings about the mechanisms by which (i) exogenous factors modulate the gut microbiota and (ii) an endogenous microbe modulates the host immune system and provides a novel molecular platform by which microbial products of interest can be causally investigated in polymicrobial communities
Using the Protection Motivation Theory to Understand the Mental Health Impact of Surviving COVID-19
Get PDFDue to the widespread effects of COVID-19, mental health professionals need to understand the lived experiences of survivors. Data were collected from YouTube videos (N = 52), which contained firsthand perspectives from COVID-19 survivors. Survivors understood the high stakes of COVID-19, reported the dual threat to physical and mental health, entered “survival mode,” and had both positive and negative reflections on the experience. Implications for mental health professionals and future research directions are included
Spontaneous Pneumothorax: A Rare Complication of Neurofibromatosis Type 1 Associated Diffuse Lung Disease
Get PDFThe visually striking neurocutaneous findings of neurofibromatosis type 1 (NF1) are well recognized and have been well documented throughout scientific literature. While not uncommon, the pulmonary manifestations of NF1 are unknown to many physicians. Complications of NF1 associated diffuse lung disease (NF-DLD) include pulmonary hypertension, pulmonary artery stenosis, subpleural cysts, and spontaneous pneumothorax. We present a case of a 34-year-old male with NF-DLD found incidentally in adolescence with previous apical bleb repair, presenting nearly twenty years later with spontaneous pneumothorax. In NF1 patients with pulmonary complaints, NF-DLD should be assessed with computed tomography (CT) and physicians should be familiar with associated complications
Funding, Supporting, & Sustaining OER
Get PDFBefore you approach the Administration or an external entity for financial support, get those ducks lined up on your campus! Faculty | Librarians | IT Support | Proposed Courses | Registrar