Degree Department

Impact of a Genetically Engineered Probiotic Therapy and IGF-1 Genomics in the PAHenu2 Mouse Model of PKU (open access)

Impact of a Genetically Engineered Probiotic Therapy and IGF-1 Genomics in the PAHenu2 Mouse Model of PKU

Absence of functional phenylalanine hydroxylase results in phenylketonuria (PKU). Viable treatments remain few, expensive and secondary conditions such as osteopenia occur in most PKU patients. Objective 1: Given the recently described roles of gut microbes to aid host digestion, an orally administered genetically engineered probiotic as the delivery vehicle for enzyme replacement therapy was created. The engineered probiotic, pHENOMMenal, produced phenylalanine ammonia lyase with significant production of trans-cinnamate (phenylalanine cleavage product) in vitro and resulted in a reduction of 515 μM in blood phenylalanine when fed to PKU animals for 14 days (from 2307µM ± 264µM to 1792µM ± 261µM, n = 6, P < 0.05). The control probiotic produced no change in blood phenylalanine. Thus, pHENOMMenal treatment in PKU mice demonstrated engineered microbes could compensate for a metabolic deficiency of the host. Objective 2: Evaluate the PAHenu2 mouse model of PKU for a genetic discrepancy causing ocular enlargement and delayed development observed only after the PAHenu2 mutation was crossed to the C57BL/6J mouse. When compared to healthy littermates, ELISA indicated a consistent but insignificant decrease in plasma IGF-1 and an increase in ocular IGF-1 in PKU animals. SNP screening demonstrated a differential inheritance of IGF-1 alleles in healthy and …
Date: December 2015
Creator: Durrer, Katherine Elaine
System: The UNT Digital Library
Spatially Explicit Modeling of West Nile Virus Risk Using Environmental Data (open access)

Spatially Explicit Modeling of West Nile Virus Risk Using Environmental Data

West Nile virus (WNV) is an emerging infectious disease that has widespread implications for public health practitioners across the world. Within a few years of its arrival in the United States the virus had spread across the North American continent. This research focuses on the development of a spatially explicit GIS-based predictive epidemiological model based on suitable environmental factors. We examined eleven commonly mapped environmental factors using both ordinary least squares regression (OLS) and geographically weighted regression (GWR). The GWR model was utilized to ascertain the impact of environmental factors on WNV risk patterns without the confounding effects of spatial non-stationarity that exist between place and health. It identifies the important underlying environmental factors related to suitable mosquito habitat conditions to make meaningful and spatially explicit predictions. Our model represents a multi-criteria decision analysis approach to create disease risk maps under data sparse situations. The best fitting model with an adjusted R2 of 0.71 revealed a strong association between WNV infection risk and a subset of environmental risk factors including road density, stream density, and land surface temperature. This research also postulates that understanding the underlying place characteristics and population composition for the occurrence of WNV infection is important for …
Date: December 2015
Creator: Kala, Abhishek K.
System: The UNT Digital Library