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Full-Text Articles in Medicine and Health Sciences

Assessment Of The Zoonotic Potential Of A Novel Bovine Influenza Virus, Laura Evelyn Eckard May 2016

Assessment Of The Zoonotic Potential Of A Novel Bovine Influenza Virus, Laura Evelyn Eckard

Theses and Dissertations (ETD)

A novel orthomyxovirus was recently identified from pigs, with subsequent work suggesting the natural reservoir being bovine populations. The virus had genome characteristics most similar to influenza C viruses (ICV) but, due to the extent of sequence divergence, was proposed as a new genus, influenza D virus (IDV). Current literature on IDV has largely focused on the agricultural significance of the virus and provided evidence for the agricultural impact via observation of widespread prevalence and pathology in laboratory infected cattle. However, only one study, which identified 1.3% seroprevalence in a small cohort, has addressed the zoonotic potential of IDV to …


Super-Utilization: The New Perfect Storm Of Health Reform, Jill Diane Nault May 2016

Super-Utilization: The New Perfect Storm Of Health Reform, Jill Diane Nault

Theses and Dissertations (ETD)

This three-essay dissertation was focused on geographic variation of super-utilization, or the disproportionately high healthcare utilization and costs attributed to a small sub-set of the inpatient population. For purposes of this research, super-utilization was operationalized as high repeat utilization (HRU) and referred to inpatient utilization and inpatient readmission expenditures attributed to beneficiaries with four or more 30-day readmissions per year. The overall purpose of the research was to identify geographic areas at increased risk for HRU. These areas corresponded to where beneficiaries live and were aligned with the geographically-bound healthcare delivery systems. Each essay employed an observational study design using …


Interaction Between Two E3 Ligases, Nedd8ylated Cullin And Hhari, Kheewoong Baek May 2016

Interaction Between Two E3 Ligases, Nedd8ylated Cullin And Hhari, Kheewoong Baek

Theses and Dissertations (ETD)

RBR (RING1-in between RING-RING2) is a special type of E3 ubiquitin ligase containing three zinc-binding RING (Really Interesting New Gene) domains, while adopting mechanisms of HECT (Homologous to E6-AP Carboxyl Terminus) for substrate ubiquitination. Most well known RBRs include Parkin and HOIP, which are associated with Parkinson’s disease and innate immune deficiency. However, it is not well known how the RBR proteins gain activity, as they are known to be autoinhibited. Here I show that a specific F430A, E431A, E503A triple mutation of RBR protein HHARI (Human homologue of Ariadne) and its interaction with NEDD8ylated cullin RING ligase can both …


Pten Signaling In Regulatory T Cells And Inflammatory Disease, Sharad Krishna Shrestha May 2016

Pten Signaling In Regulatory T Cells And Inflammatory Disease, Sharad Krishna Shrestha

Theses and Dissertations (ETD)

Regulatory T (Treg) cells suppress CD4+ T cell responses during homeostasis and inflammation to prevent autoimmunity and other immune disorders. Although the transcriptional and epigenetic programs impacting Treg cell function have been extensively studied, the signaling and metabolic pathways underlying Treg stability and function are not fully understood. In this study, we determined the role of the phosphatase PTEN in Treg cells. We found that specific depletion of PTEN in Treg cells results in excessive TH1 and T follicular helper cells (TFH) responses, associated with elevated germinal center (GC) B cells and spontaneous development of autoimmune and lymphoproliferative disease in …


Dissecting The Novel Roles Of Trim56 In Antiviral Innate Immunity, Baoming Liu Apr 2016

Dissecting The Novel Roles Of Trim56 In Antiviral Innate Immunity, Baoming Liu

Theses and Dissertations (ETD)

The tripartite motif-containing (TRIM) proteins have emerged as a new class of host antiviral restriction factors, with several demonstrating roles in regulating innate antiviral responses. Of >70 known TRIMs, TRIM56 inhibits replication of bovine viral diarrhea virus, a ruminant pestivirus of the family Flaviviridae, but has no appreciable effect on VSV, a rhabdovirus. We have also shown that TRIM56 forms a complex with the Toll-like receptor-3 (TLR3) adaptor, TRIF, via its C-terminal residues 621-750, and augments TLR3-mediated interferon (IFN) induction and establishment of an antiviral state. Yet, TRIM56’s antiviral spectrum and the precise underlying mechanisms by which TRIM56 executes …