Date of Graduation
8-2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy in Engineering (PhD)
Degree Level
Graduate
Department
Chemical Engineering
Advisor/Mentor
Hestekin, Christa
Committee Member
Servoss, Shannon
Second Committee Member
Adams, Paul
Third Committee Member
Beitle, Robert Jr.
Fourth Committee Member
Millet, Francis
Keywords
Amyloid beta; Chronic kidney disease; Nanofiltration; Proteomics
Abstract
Due to the drastic differences in the projects involved, this dissertation will be split into two sections: Alzheimer’s disease and chronic kidney disease. Each chapter will contain an introduction, materials and methods section, results and discussion, conclusions, and works cited section. The Alzheimer’s disease chapter will also have a supplemental figures section containing the polyacrylamide gels that were silver stained and quantified via ImageJ. The presence of elevated levels of amyloid beta oligomeric species in the brain has been related to the pathology of Alzheimer’s disease. As these oligomeric species are transient in nature, their kinetics pose a challenge to study. Also seen in the literature, mutations in the primary sequence of the proteins lead to differences in aggregation kinetics. In this study, we investigated the application of PICUP to study the early aggregation patterns of Wildtype amyloid beta compared to three sequences variants: Flemish, Arctic, and scrambled. To explore the influence of steric hindrance on aggregation kinetics, two naturally occurring mutations of amyloid beta called Arctic and Flemish were selected. To determine if primary amino acid sequence affects aggregation, a lab designed scrambled variant was tested. This study revealed that each mutation of Wildtype amyloid beta did indeed cause variation in aggregation with scrambled differing the most while Arctic and Flemish followed behind and behaved similarly. Chronic kidney disease is a growing healthcare concern inflicting approximately 37 million people in the United States alone. Currently, the only options for patients are either a kidney transplant or dialysis. While dialysis provides a way to separate larger metabolites, there appears to be a limitation with the ability for dialyzers to separate smaller components due to the passive transport performed in dialysis. Unlike the passive transport in dialysis, nanofiltration membranes utilize active transport via pressure to drive separation, allowing for smaller components to be separated. This study explored six commercial nanofiltration membranes with different characteristics on their ability to separate glucose, urea, Na+, K+, Mg2+, and Ca2+ while also investigating the effects of feed ( increased glucose and salt concentration) and operating (pressure and temperature) conditions. Depending on the properties of the membrane, feed composition and pressure had varying effects. Finally chemical modification utilizing polyethylenimine to potentially decrease the pore size was explored on one of the commercial membranes for its potential to improve the membranes’ ability to maintain a high glucose rejection while also keeping a low urea rejection. This study confirmed that membranes with different properties like pore size and charge separated components rather differently under the varying feed and operating conditions tested.
Citation
Duncan, H. M. (2024). Investigating the Detection and Transport of Low Molecular Weight Species to Better Understand Their Impact on Disease Pathology and Treatment. Graduate Theses and Dissertations Retrieved from https://scholarworks.uark.edu/etd/5472