Theses and Dissertations
This collection includes both ASU Theses and Dissertations, submitted by graduate students, and the Barrett, Honors College theses submitted by undergraduate students.
Displaying 31 - 38 of 38
Description
As Alzheimer’s disease (AD) increases in incidence, there is an increased investigation into the pathogenesis of the disease in hopes of finding a cure to the neurodegenerative disease. The two key hallmarks of AD consist of amyloid beta plaques and hyperphosphorylated tau fibrillary tangles. Amyloid beta is a peptide that is proteolytically cleaved from the type I transmembrane glycolytic amyloid precursor protein (APP). APP is highly conserved across species, suggesting the importance of APP in healthy brain functioning. However, when APP is cleaved through the amyloidogenic pathway it produces amyloid beta. The trafficking of APP within neurons has been a new endeavor for neurodegenerative disease research, as reduced retrograde trafficking of APP has been hypothesized to increase the likelihood of the amyloidogenic cleavage of APP, resulting in increased amyloid beta presence (Ye et al., 2017). The findings of this study suggest that transport of APP within neurons is significantly inhibited by increased extracellular glutamate concentration. The addition of human primary astrocytes within a human neuron co-culture allowed for significantly increased retrograde transport of APP within neurons, even within high glutamate conditions. These finding enhance the current field of research regarding astrocytes neuroprotective role within the brain, but bring attention to the role that astrocytes have upon regulation of the axonal transport of proteins within neurons.
ContributorsKlosterman, Katja Elisabeth (Author) / Ros, Alexandra (Thesis director) / Redding, Kevin (Committee member) / Watts College of Public Service & Community Solut (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-12
Description
Coral reefs are diverse marine ecosystems, where reef building corals provide both the structure of the habitat as well as the primary production through their symbiotic algae, and alongside algae living on the reef itself, are the basis of the food web of the reef. In this way, coral reefs are the ocean's "forests" and are estimated to support 25% of all marine species. However, due to the large size of a coral reef, the relative inaccessibility and the reliance on in situ surveying methods, our current understanding of reefs is spatially limited. Understanding coral reefs from a more spatially complete perspective will offer insight into the ecological factors that contribute to coral reef vitality. This has become a priority in recent years due to the rapid decline of coral reefs caused by mass bleaching. Despite this urgency, being able to assess the entirety of a coral reef is physically difficult and this obstacle has not yet been overcome. However, similar difficulties have been addressed in terrestrial ecosystems by using remote sensing methods, which apply hyperspectral imaging to assess large areas of primary producers at high spatial resolutions. Adapting this method of remote spectral sensing to assess coral reefs has been suggested, but in order to quantify primary production via hyper spectral imaging, light-use efficiencies (LUEs) of coral reef communities need to be known. LUEs are estimations of the rate of carbon fixation compared to incident absorbed light. Here, I experimentally determine LUEs and report on several parameters related to LUE, namely net productivity, respiration, and light absorbance for the main primary producers in coral reefs surrounding Bermuda, which consist of algae and coral communities. The derived LUE values fall within typical ranges for LUEs of terrestrial ecosystems, with LUE values for coral averaging 0.022 ± 0.002 mol O2 mol photons-1 day-1 at a water flow rate of 17.5 ± 2 cm s^(-1) and 0.049 ± 0.011 mol O2 mol photons-1 day-1 at a flow rate of 32 ± 4 cm s^(-1) LUE values for algae averaged 0.0335 ± 0.0048 mol O2 mol photons-1 day-1 at a flow rate of 17.5 ± 2 cm s^(-1). These values allow insight into coral reef productivity and opens the door for future remote sensing applications.
ContributorsFlesher, David A (Author) / Neuer, Susanne (Thesis director) / Redding, Kevin (Committee member) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Diabesity is a global epidemic affecting millions worldwide. Diabesity is the term given to the link between obesity and Type II diabetes. It is estimated that ~90% of patients diagnosed with Type II diabetes are overweight or have struggled with excess body fat in the past. Type II diabetes is characterized by insulin resistance which is an impaired response of the body to insulin that leads to high blood glucose levels. Adipose tissue, previously thought of as an inert tissue, is now recognized as a major endocrine organ with an important role in the body's immune response and the development of chronic inflammation. It is speculated that adipose tissue inflammation is a major contributor to insulin resistance particular to Type II diabetes. This literature review explores the popular therapeutic targets and marketed drugs for the treatment of Type II diabetes and their role in decreasing adipose tissue inflammation. rAGE is currently in pre-clinical studies as a possible target to combat adipose tissue inflammation due to its relation to insulin resistance. Metformin and Pioglitazone are two drugs already being marketed that use unique chemical pathways to increase the production of insulin and/or decrease blood glucose levels. Sulfonylureas is one of the first FDA approved drugs used in the treatment of Type II diabetes, however, it has been discredited due to its life-threatening side effects. Bariatric surgery is a form of invasive surgery to rid the body of excess fat and has shown to normalize blood glucose levels. These treatments are all secondary to lifestyle changes, such as diet and exercise which can help halt the progression of Type II diabetes patients.
ContributorsRobles, Alondra Maria (Author) / Woodbury, Neal (Thesis director) / Redding, Kevin (Committee member) / Allen, James (Committee member) / Hendrickson, Kirstin (Committee member) / Sanford School of Social and Family Dynamics (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
This thesis is about how Fe catalysts can be degraded using photocatalysis and how Fe catalysts can degrade small molecules in conjunction with light. The goal of this paper is to look further into more sustainable methods of organic chemistry. Many current organic chemistry practices involve the use of precious metals. Iron is a more sustainable catalyst because it is abundant and inexpensive which is important for preserving the earth and making the organic chemistry more accessible. Along the same lines, light is a renewable energy source and has demonstrated its ability to aid in reactions. Overall, the goal of this paper is to explore the more sustainable alternatives to harsh and toxic organic chemistry practices through the use of Iron and light.
ContributorsBlenker, Grace (Author) / Ackerman-Biegasiewicz, Laura (Thesis director) / Redding, Kevin (Committee member) / Biegasiewicz, Kyle (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / School of International Letters and Cultures (Contributor)
Created2022-05
Description
Ribulose-1,5-bisphosphate carboxylase/oxygenase enzyme (Rubisco) is responsible for the majority of carbon fixation and is also the least efficient enzyme on Earth. Rubisco assists 1,5-ribulose bisphosphate (RuBP) in binding CO2, however CO2 and oxygen have similar binding affinities to Rubisco, resulting in a low enzymatic efficiency. Rubisco activase (Rca) is an enzyme that removes inhibiting molecules from Rubisco’s active sites, promoting the Rubisco activity. The binding of Rubisco and Rca stimulates a high-rate of carbon fixation and lowers the overall CO2 concentration in the atmosphere. To study the interaction between the two complexes, Rubisco was extracted from baby spinach (Spinacia oleracea) and purified using anion-exchange chromatography and size-exclusion chromatography. Rca was designed to use a recombinant gene and overexpressed in Escherichia coli (E. coli). The purified proteins were verified using SDS-PAGE. The two proteins were assembled in vitro and the interaction of the protein complex was stabilized using glutaraldehyde cross-linking. The samples were then deposited on a carbon-coated electron microscopy (EM) grid, stained with uranyl formate, and observed under a transmission electron microscope (TEM). The ultimate goal is to image the specimen and reconstruct the structure of the protein complex at high resolution.
ContributorsHart, Hayden (Author) / Chiu, Po-Lin (Thesis director) / Redding, Kevin (Committee member) / Van Horn, Wade (Committee member) / Barrett, The Honors College (Contributor) / School of Molecular Sciences (Contributor) / Department of Military Science (Contributor)
Created2022-05
Description
Arsenic contamination in groundwater is a serious problem both in local Arizonan communities and abroad: prolonged exposure to arsenic contamination can cause cancer, vascular damage, and liver failure. This project aims to engineer the microalgae Chlamydomonas reinhardtii to sequester arsenic out of water. Metallothionein, arsenate reductase, and ferritin were integrated into the microalgae via the pASapI plasmid. The plasmid rescues function of the photosystem II gene, leveraging the ability to photosynthesize as a selective trait. Metallothionein and ferritin bind the two most common forms of arsenic: arsenite and arsenate, respectively. Arsenate reductase catalyzes the reduction of arsenate to arsenite, allowing for the ultimate sequestration of the toxic metal to occur in the chloroplast. The algae was transformed using a biolistic device, to create three mutant strains, expressing Metallothionein (MT), Arsenate Reductase (ArsC)-HA, and MT-6xHIS plasmids respectively. When testing the fluorescence output of these three strains, they showed a maximum quantum yield of photosystem II comparable to that of the wildtype algae, indicating that the rescue gene had been incorporated into the chloroplast genome properly. Strains were exposed to arsenic-containing media at 50ppb and 500 ppb for 48 and 72 hours to determine the arsenic sequestration rate. Arsenic concentration in the supernatant was measured using ICP-MS analysis and sequestration rate was calculated in terms of arsenic concentration per fold growth of algae. The normalized arsenic sequestration rates of tagged protein expressing strains at 50 ppb were significantly higher than wildtype.
ContributorsLieberman, Emma (Author) / Bartelle, Benjamin (Thesis director) / Redding, Kevin (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2022-05
Description
In algae, the Mutant Affecting Retrograde Signaling (MARS1) Kinase plays a critical role in the chloroplast unfolded protein response (cpUPR) when the chloroplast faces proteotoxic stress4. The MARS1 protein is relatively unknown in terms of structure and function. However, there has been ample research performed on the main pathway associated with the MARS1 protein, the cpUPR. The exact mechanism of why MARS1 is necessary for the cpUPR is still unknown. Our structural and biochemical studies will help develop a better understanding of the MARS1 structure, and the role it plays in the cpUPR. The MARS1 expression construct will be assembled following the yeast golden gate (yGG) assembly protocol. Here, we will attempt to recombinantly express MARS1 kinase in Saccharomyces cerevisiae to provide insights into the protein.
ContributorsHeeres, Nicholas (Author) / Mazor, Yuval (Thesis director) / Chiu, Po Lin (Committee member) / Redding, Kevin (Committee member) / Barrett, The Honors College (Contributor) / School of Molecular Sciences (Contributor)
Created2022-05
Description
The FOF1 ATP synthase is responsible for generating the majority of adenosine triphosphate (ATP) in almost all organisms on Earth. A major unresolved question is the mechanism of the FO motor that converts the transmembrane flow of protons into rotation that drives ATP synthesis. Using single-molecule gold nanorod experiments, rotation of individual FOF1 were observed to measure transient dwells (TDs). TDs occur when the FO momentarily halts the ATP hydrolysis rotation by the F1-ATPase. The work presented here showed increasing TDs with decreasing pH, with calculated pKa values of 5.6 and 7.5 for wild-type (WT) Escherichia coli (E. coli) subunit-a proton input and output half-channels, respectively. This is consistent with the conclusion that the periplasmic proton half-channel is more easily protonated than the cytoplasmic half-channel. Mutation in one proton half-channel affected the pKa values of both half-channels, suggesting that protons flow through the FO motor via the Grotthuss mechanism. The data revealed that 36° stepping of the E. coli FO subunit-c ring during ATP synthesis consists of an 11° step caused by proton translocations between subunit-a and the c-ring, and a 25° step caused by the electrostatic interaction between the unprotonated c-subunit and the aR210 residue in subunit-a. The occurrence of TDs fit to the sum of three Gaussian curves, which suggested that the asymmetry between the FO and F1 motors play a role in the mechanism behind the FOF1 rotation. Replacing the inner (N-terminal) helix of E. coli c10-ring with sequences derived from c8 to c17-ring sequences showed expression and full assembly of FOF1. Decrease in anticipated c-ring size resulted in increased ATP synthesis activity, while increase in c-ring size resulted in decreased ATP synthesis activity, loss of Δψ-dependence to synthesize ATP, decreased ATP hydrolysis activity, and decreased ACMA quenching activity. Low levels of ATP synthesis by the c12 and c15-ring chimeras are consistent with the role of the asymmetry between the FO and F1 motors that affects ATP synthesis rotation. Lack of a major trend in succinate-dependent growth rates of the chimeric E. coli suggest cellular mechanisms that compensates for the c-ring modification.
ContributorsYanagisawa, Seiga (Author) / Frasch, Wayne D (Thesis advisor) / Misra, Rajeev (Committee member) / Redding, Kevin (Committee member) / Singharoy, Abhishek (Committee member) / Wideman, Jeremy (Committee member) / Arizona State University (Publisher)
Created2023