ASU Electronic Theses and Dissertations
This collection includes most of the ASU Theses and Dissertations from 2011 to present. ASU Theses and Dissertations are available in downloadable PDF format; however, a small percentage of items are under embargo. Information about the dissertations/theses includes degree information, committee members, an abstract, supporting data or media.
In addition to the electronic theses found in the ASU Digital Repository, ASU Theses and Dissertations can be found in the ASU Library Catalog.
Dissertations and Theses granted by Arizona State University are archived and made available through a joint effort of the ASU Graduate College and the ASU Libraries. For more information or questions about this collection contact or visit the Digital Repository ETD Library Guide or contact the ASU Graduate College at gradformat@asu.edu.
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- All Subjects: Biochemistry
- Creators: Johnston, Stephen
- Creators: Vega-Lopez, Sonia
ormoglycemic controls (NC), dyslipidemic
ormoglycemic (DN), dyslipidemic/prediabetic (DPD) and dyslipidemic/diabetic (DD). Total cholesterol (TC) was 30% higher among DD than in NC participants (p<0.0001). The DPD group had 27% and 12% higher LDL-C concentrations than the NC and DN groups, respectively. Similarly, LDL-C was 29% and 13% higher in DD than in NC and DN participants (p=0.013). An increasing trend was observed in %10-year CVD risk with increasing degree of hyperglycemia (p<0.0001). The NC group had less cholesterol in sdLDL particles than dyslipidemic groups, regardless of glycemic status (p<0.0001). When hyperglycemia was part of the phenotype (DPD and DD), there was a greater proportion of total and HDL-C in sHDL particles in dyslipidemic individuals than in NC (p=0.023; p<0.0001; respectively). Percent 10-year CVD risk was positively correlated with triglyceride (TG) (r=0.384, p<0.0001), TC (r=0.340, p<0.05), cholesterol in sdLDL(r=0.247; p<0.05), and TC to HDL-C ratio (r=0.404, p<0.0001), and negatively correlated with HDL-C in intermediate and large HDL(r=-0.38, p=0.001; r=0.34, p=0.002, respectively). The TC/HDL-C was positively correlated with cholesterol in sdLDL particles (r=0.698, p<0.0001) and HDL-C in sHDL particles (r=0.602, p<0.0001), and negatively correlated with cholesterol in small (r=-0.35, p=0.002), intermediate (r=-0.91, p<0.0001) and large (r=-0.84, p<0.0001) HDL particles, and HDL-C in the large HDL particles (r=-0.562, p<0.0001). No significant association was found between %10-year CVD risk and hsCRP. Collectively, these results corroborate that dyslipidemic Mexican-American adults have higher CVD risk than normolipidemic individuals. Hyperglycemia may further affect CVD risk by modulating cholesterol in LDL and HDL subfractions.
Next, the nonstructural protein μNS of avian reoviruses was investigated using in vivo crystallization and serial femtosecond X-ray crystallography. Avian reoviruses infect poultry flocks causing significant economic losses. μNS is crucial in viral factory formation facilitating viral replication within host cells. Thus, structure-based targeting of μNS has the potential to disrupt intracellular viral propagation. Towards this goal, crystals of EGFP-tagged μNS (EGFP-μNS (448-605)) were produced in insect cells. The crystals diffracted to 4.5 Å at X-ray free electron lasers using viscous jets as crystal delivery methods and initial electron density maps were obtained. The resolution reported here is the highest described to date for μNS, which lays the foundation towards its structure determination.
Finally, structural, and functional studies of human Threonine aspartase 1 (Taspase1) were performed. Taspase1 is overexpressed in many liquid and solid malignancies. In the present study, using strategic circular permutations and X-ray crystallography, structure of catalytically active Taspase1 was resolved. The structure reveals the conformation of a 50 residues long fragment preceding the active side residue (Thr234), which has not been structurally characterized previously. This fragment adopted a straight helical conformation in contrast to previous predictions. Functional studies revealed that the long helix is essential for proteolytic activity in addition to the active site nucleophilic residue (Thr234) mediated proteolysis. Together, these findings enable a new approach for designing anti-cancer drugs by targeting the long helical fragment.