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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Description
Infertility has become an increasing problem in developed countries and in many cases can be attributed to compromised sperm quality. Assessment of male fertility typically utilizes semen analysis which mainly examines sperm morphology, however many males whose sperm appear normal are sub- or infertile, suggesting that sperm from these males may be deficient in a protein or suite of proteins. To date, very little is known about the composition of sperm or the complex maturation process that confers motility and fertilization competency to sperm. Chapter 1 discusses the use of whole cell mass spectrometry to identify 1247 proteins comprising the Rhesus macaque (Macaca mulatta) sperm proteome, a commonly used model of human reproduction. This study provides a more robust proxy of human sperm composition than was previously available and facilitates studies of sperm using the rhesus macaque as a model. Chapters 2 & 3 provide a systems level overview of changes in sperm proteome composition that occurs during epididymal transit. Chapter 2 reports the proteomes of sperm collected from the caput, corpus and cauda segments of the mouse epididymis, identifying 1536, 1720 and 1234 proteins respectively. Chapter 3 reports the sperm proteome from four distinct segments of the Rhesus macaque epididymis, including the caput, proximal corpus, distal corpus and cauda, identifying 1951, 2014, 1764 and 1423 proteins respectively. These studies identify a number of proteins that are added and removed from sperm during epididymal transit which likely play an important role in the sperm maturation process. To date no comparative evolutionary studies of sperm proteomes have been undertaken. Chapter 4 compares four mammalian sperm proteomes including the human, macaque, mouse and rat. This study identified 98 proteins common to all four sperm proteomes, 82 primate and 90 rodent lineage-specific proteins and 494, 467, 566, and 193 species specific proteins in the human, macaque, mouse and rat sperm proteomes respectively and discusses how differences in sperm composition may ultimately lead to functional differences across species. Finally, chapter 5 uses sperm proteome data to inform the preliminary design of a rodent contraceptive vaccine delivered orally using recombinant attenuated Salmonella vaccine vectors.
ContributorsSkerget, Sheri Jo (Author) / Karr, Timothy L. (Thesis advisor) / Lake, Douglas (Committee member) / Petritis, Konstantinos (Committee member) / Arizona State University (Publisher)
Created2013
Description
Foraging has complex effects on whole-organism homeostasis, and there is considerable evidence that foraging behavior is influenced by both environmental factors (e.g., food availability, predation risk) and the physiological condition of an organism. The optimization of foraging behavior to balance costs and benefits is termed state-dependent foraging (SDF) while behavior that seeks to protect assets of fitness is termed the asset protection principle (APP). A majority of studies examining SDF have focused on the role that energy balance has on the foraging of organisms with high metabolism and high energy demands ("high-energy systems" such as endotherms). In contrast, limited work has examined whether species with low energy use ("low-energy systems" such as vertebrate ectotherms) use an SDF strategy. Additionally, there is a paucity of evidence demonstrating how physiological and environmental factors other than energy balance influence foraging behavior (e.g. hydration state and free-standing water availability). Given these gaps in our understanding of SDF behavior and the APP, I examined the state-dependency and consequences of foraging in a low-energy system occupying a resource-limited environment - the Gila monster (Heloderma suspectum, Cope 1869). In contrast to what has been observed in a wide variety of taxa, I found that Gila monsters do not use a SDF strategy to manage their energy reserves and that Gila monsters do not defend their energetic assets. However, hydration state and free-standing water availability do affect foraging behavior of Gila monsters. Additionally, as Gila monsters become increasingly dehydrated, they reduce activity to defend hydration state. The SDF behavior of Gila monsters appears to be largely driven by the fact that Gila monsters must separately satisfy energy and water demands with food and free-standing water, respectively, in conjunction with the timescale within which Gila monsters balance their energy and water budgets (supra-annually versus annually, respectively). Given these findings, the impact of anticipated changes in temperature and rainfall patterns in the Sonoran Desert are most likely going to pose their greatest risks to Gila monsters through the direct and indirect effects on water balance.
ContributorsWright, Christian (Author) / Denardo, Dale F. (Thesis advisor) / Harrison, Jon (Committee member) / McGraw, Kevin (Committee member) / Sullivan, Brian (Committee member) / Wolf, Blair (Committee member) / Arizona State University (Publisher)
Created2014
Description
For animals that experience annual cycles of gonad development, the seasonal timing (phenology) of gonad growth is a major adaptation to local environmental conditions. To optimally time seasonal gonad growth, animals use environmental cues that forecast future conditions. The availability of food is one such environmental cue. Although the importance of food availability has been appreciated for decades, the physiological mechanisms underlying the modulation of seasonal gonad growth by this environmental factor remain poorly understood.
Urbanization is characterized by profound environmental changes, and urban animals must adjust to an environment vastly different from that of their non-urban conspecifics. Evidence suggests that birds adjust to urban areas by advancing the timing of seasonal breeding and gonad development, compared to their non-urban conspecifics. A leading hypothesis to account for this phenomenon is that food availability is elevated in urban areas, which improves the energetic status of urban birds and enables them to initiate gonad development earlier than their non-urban conspecifics. However, this hypothesis remains largely untested.
My dissertation dovetailed comparative studies and experimental approaches conducted in field and captive settings to examine the physiological mechanisms by which food availability modulates gonad growth and to investigate whether elevated food availability in urban areas advances the phenology of gonad growth in urban birds. My captive study demonstrated that energetic status modulates reproductive hormone secretion, but not gonad growth. By contrast, free-ranging urban and non-urban birds did not differ in energetic status or plasma levels of reproductive hormones either in years in which urban birds had advanced phenology of gonad growth or in a year that had no habitat-related disparity in seasonal gonad growth. Therefore, my dissertation provides no support for the hypothesis that urban birds begin seasonal gonad growth because they are in better energetic status and increase the secretion of reproductive hormones earlier than non-urban birds. My studies do suggest, however, that the phenology of key food items and the endocrine responsiveness of the reproductive system may contribute to habitat-related disparities in the phenology of gonad growth.
Urbanization is characterized by profound environmental changes, and urban animals must adjust to an environment vastly different from that of their non-urban conspecifics. Evidence suggests that birds adjust to urban areas by advancing the timing of seasonal breeding and gonad development, compared to their non-urban conspecifics. A leading hypothesis to account for this phenomenon is that food availability is elevated in urban areas, which improves the energetic status of urban birds and enables them to initiate gonad development earlier than their non-urban conspecifics. However, this hypothesis remains largely untested.
My dissertation dovetailed comparative studies and experimental approaches conducted in field and captive settings to examine the physiological mechanisms by which food availability modulates gonad growth and to investigate whether elevated food availability in urban areas advances the phenology of gonad growth in urban birds. My captive study demonstrated that energetic status modulates reproductive hormone secretion, but not gonad growth. By contrast, free-ranging urban and non-urban birds did not differ in energetic status or plasma levels of reproductive hormones either in years in which urban birds had advanced phenology of gonad growth or in a year that had no habitat-related disparity in seasonal gonad growth. Therefore, my dissertation provides no support for the hypothesis that urban birds begin seasonal gonad growth because they are in better energetic status and increase the secretion of reproductive hormones earlier than non-urban birds. My studies do suggest, however, that the phenology of key food items and the endocrine responsiveness of the reproductive system may contribute to habitat-related disparities in the phenology of gonad growth.
ContributorsDavies, Scott (Author) / Deviche, Pierre (Thesis advisor) / Sweazea, Karen (Committee member) / McGraw, Kevin (Committee member) / Orchinik, Miles (Committee member) / Warren, Paige (Committee member) / Arizona State University (Publisher)
Created2014
Description
Antibodies are naturally occurring proteins that protect a host during infection through direct neutralization and/or recruitment of the innate immune system. Unfortunately, in some infections, antibodies present unique hurdles that must be overcome for a safer and more efficacious antibody-based therapeutic (e.g., antibody dependent viral enhancement (ADE) and inflammatory pathology). This dissertation describes the utilization of plant expression systems to produce N-glycan specific antibody-based therapeutics for Dengue Virus (DENV) and Chikungunya Virus (CHIKV). The Fc region of an antibody interacts with Fcγ Receptors (FcγRs) on immune cells and components of the innate immune system. Each class of immune cells has a distinct action of neutralization (e.g., antibody dependent cell-mediated cytotoxicity (ADCC) and antibody dependent cell-mediated phagocytosis (ADCP)). Therefore, structural alteration of the Fc region results in novel immune pathways of protection. One approach is to modulate the N-glycosylation in the Fc region of the antibody. Of scientific significance, is the plant’s capacity to express human antibodies with homogenous plant and humanized N-glycosylation (WT and GnGn, respectively). This allows to study how specific glycovariants interact with other components of the immune system to clear an infection, producing a tailor-made antibody for distinct diseases. In the first section, plant-produced glycovariants were explored for reduced interactions with specific FcγRs for the overall reduction in ADE for DENV infections. The results demonstrate a reduction in ADE of our plant-produced monoclonal antibodies in in vitro experiments, which led to a greater survival in vivo of immunodeficient mice challenged with lethal doses of DENV and a sub-lethal dose of DENV in ADE conditions. In the second section, plant-produced glycovariants were explored for increased interaction with specific FcγRs to improve ADCC in the treatment of the highly inflammatory CHIKV. The results demonstrate an increase ADCC activity in in vitro experiments and a reduction in CHIKV-associated inflammation in in vivo mouse models. Overall, the significance of this dissertation is that it can provide a treatment for DENV and CHIKV; but equally importantly, give insight to the role of N-glycosylation in antibody effector functions, which has a broader implication for therapeutic development for other viral infections.
ContributorsHurtado, Jonathan (Author) / Chen, Qiang (Thesis advisor) / Arntzen, Charles (Committee member) / Borges, Chad (Committee member) / Lake, Douglas (Committee member) / Arizona State University (Publisher)
Created2019
Description
Measles is a contagious, vaccine-preventable disease that continues to be the leading
cause of death in children younger than the age of 5 years. While the introduction of the Measles, Mumps, and Rubella vaccine (MMR) has significantly decreased morbidity and mortality rates worldwide, vaccine coverage is highly variable across global regions. Current diagnostic methods rely on enzyme immunoassays (EIA) to detect IgM or IgG Abs in serum. Commercially available Diamedix Immunosimplicity® Measles IgG test kit has been shown to have 91.1% sensitivity and 93.8% specificity, with a positive predictive value of 88.7% and a negative predictive value of 90.9% on the basis of a PRN titer of 120. There is an increasing need for rapid screening for measles specific immunity in outbreak settings. This study aims to develop a rapid molecular diagnostic assay to detect IgG reactive to three individual measles virus (MeV) proteins.
Measles virus (MeV) genes were subcloned into the pJFT7_nGST vector to generate N- terminal GST fusion proteins. Single MeV cistrons were expressed using in vitro transcription/translation (IVTT) with human cell lysate. Expression of GST-tagged proteins was measured with mouse anti-GST mAb and sheep anti-mouse IgG. Relative light units (RLUs) as luminescence was measured. Antibodies to MeV antigens were measured in 40 serum samples from healthy subjects.
Protein expression of three MeV genes of interest was measured in comparison with vector control and statistical significance was determined using the Student’s t-test (p<0.05). N expressed at the highest level with an average RLU value of 3.01 x 109 (p<0.001) and all proteins were expressed at least 50% greater than vector control (4.56 x 106 RLU). 36/40 serum samples had IgG to N (Ag:GST ratio>1.21), F (Ag:GST ratio>1.92), or H (Ag:GST ratio> 1.23).
These data indicate that the in vitro expression of MeV antigens, N, F, and H, were markedly improved by subcloning into pJFT7_nGST vector to generate N-terminal GST fusion proteins. The expression of single MeV genes N, F and H, are suitable antigens for serologic capture analysis of measles-specific antibodies. These preliminary data can be used to design a more intensive study to explore the possibilities of using these MeV antigens as a diagnostic marker.
cause of death in children younger than the age of 5 years. While the introduction of the Measles, Mumps, and Rubella vaccine (MMR) has significantly decreased morbidity and mortality rates worldwide, vaccine coverage is highly variable across global regions. Current diagnostic methods rely on enzyme immunoassays (EIA) to detect IgM or IgG Abs in serum. Commercially available Diamedix Immunosimplicity® Measles IgG test kit has been shown to have 91.1% sensitivity and 93.8% specificity, with a positive predictive value of 88.7% and a negative predictive value of 90.9% on the basis of a PRN titer of 120. There is an increasing need for rapid screening for measles specific immunity in outbreak settings. This study aims to develop a rapid molecular diagnostic assay to detect IgG reactive to three individual measles virus (MeV) proteins.
Measles virus (MeV) genes were subcloned into the pJFT7_nGST vector to generate N- terminal GST fusion proteins. Single MeV cistrons were expressed using in vitro transcription/translation (IVTT) with human cell lysate. Expression of GST-tagged proteins was measured with mouse anti-GST mAb and sheep anti-mouse IgG. Relative light units (RLUs) as luminescence was measured. Antibodies to MeV antigens were measured in 40 serum samples from healthy subjects.
Protein expression of three MeV genes of interest was measured in comparison with vector control and statistical significance was determined using the Student’s t-test (p<0.05). N expressed at the highest level with an average RLU value of 3.01 x 109 (p<0.001) and all proteins were expressed at least 50% greater than vector control (4.56 x 106 RLU). 36/40 serum samples had IgG to N (Ag:GST ratio>1.21), F (Ag:GST ratio>1.92), or H (Ag:GST ratio> 1.23).
These data indicate that the in vitro expression of MeV antigens, N, F, and H, were markedly improved by subcloning into pJFT7_nGST vector to generate N-terminal GST fusion proteins. The expression of single MeV genes N, F and H, are suitable antigens for serologic capture analysis of measles-specific antibodies. These preliminary data can be used to design a more intensive study to explore the possibilities of using these MeV antigens as a diagnostic marker.
ContributorsMushtaq, Zuena (Author) / Anderson, Karen (Thesis advisor) / Blattman, Joseph (Committee member) / Lake, Douglas (Committee member) / Arizona State University (Publisher)
Created2016
Description
Why do many animals possess multiple classes of photoreceptors that vary in the wavelengths of light to which they are sensitive? Multiple spectral photoreceptor classes are a requirement for true color vision. However, animals may have unconventional vision, in which multiple spectral channels broaden the range of wavelengths that can be detected, or in which they use only a subset of receptors for specific behaviors. Branchiopod crustaceans are of interest for the study of unconventional color vision because they express multiple visual pigments in their compound eyes, have a simple repertoire of visually guided behavior, inhabit unique and highly variable light environments, and possess secondary neural simplifications. I first tested the behavioral responses of two representative species of branchiopods from separate orders, Streptocephalus mackini Anostracans (fairy shrimp), and Triops longicaudatus Notostracans (tadpole shrimp). I found that they maintain vertical position in the water column over a broad range of intensities and wavelengths, and respond behaviorally even at intensities below those of starlight. Accordingly, light intensities of their habitats at shallow depths tend to be dimmer than terrestrial habitats under starlight. Using models of how their compound eyes and the first neuropil of their optic lobe process visual cues, I infer that both orders of branchiopods use spatial summation from multiple compound eye ommatidia to respond at low intensities. Then, to understand if branchiopods use unconventional vision to guide these behaviors, I took electroretinographic recordings (ERGs) from their compound eyes and used models of spectral absorptance for a multimodel selection approach to make inferences about the number of photoreceptor classes in their eyes. I infer that both species have four spectral classes of photoreceptors that contribute to their ERGs, suggesting unconventional vision guides the described behavior. I extended the same modeling approach to other organisms, finding that the model inferences align with the empirically determined number of photoreceptor classes for this diverse set of organisms. This dissertation expands the conceptual framework of color vision research, indicating unconventional vision is more widespread than previously considered, and explains why some organisms have more spectral classes than would be expected from their behavioral repertoire.
ContributorsLessios, Nicolas (Author) / Rutowski, Ronald L (Thesis advisor) / Cohen, Jonathan H (Thesis advisor) / Harrison, John (Committee member) / Neuer, Susanne (Committee member) / McGraw, Kevin (Committee member) / Arizona State University (Publisher)
Created2016
Description
The molt from pupae to adult stage, called eclosion, occurs at specific times of the day in many holometabolous insects. These events are not well studied within Lepidopteran species. It was hypothesized that the eclosion timing in a species may be shaped by strong selective pressures, such as sexual selection in the context of male-male competition. The daily timing of eclosion was measured for six species of nymphalid butterflies. This was done by rearing individuals to pupation, placing the pupa in a greenhouse, and video recording eclosion to obtain the time of day at which it occurred. Four species exhibited clustered eclosion distributions that were concentrated to within 201 minutes after sunrise and were significantly different from one another. The other two species exhibited eclosion times that were non-clustered. There were no differences between sexes within species. The data support a relationship between the timing of eclosion each day and the timing of mating activities, but other as of yet undetermined selective pressures may also influence eclosion timing.
ContributorsSencio, Kaylon (Author) / Rutowski, Ron (Thesis advisor) / McGraw, Kevin (Committee member) / Pratt, Stephen (Committee member) / Arizona State University (Publisher)
Created2017
Description
Though it is a widespread adaptation in humans and many other animals, parental care comes in a variety of forms and its subtle physiological costs, benefits, and tradeoffs related to offspring are often unknown. Thus, I studied the hydric, respiratory, thermal, and fitness dynamics of maternal egg-brooding behavior in Children's pythons (Antaresia childreni). I demonstrated that tight coiling detrimentally creates a hypoxic developmental environment that is alleviated by periodic postural adjustments. Alternatively, maternal postural adjustments detrimentally elevate rates of egg water loss relative to tight coiling. Despite ventilating postural adjustments, the developmental environment becomes increasingly hypoxic near the end of incubation, which reduces embryonic metabolism. I further demonstrated that brooding-induced hypoxia detrimentally affects offspring size, performance, locomotion, and behavior. Thus, parental care in A. childreni comes at a cost to offspring due to intra-offspring tradeoffs (i.e., those that reflect competing offspring needs, such as water balance and respiration). Next, I showed that, despite being unable to intrinsically produce body heat, A. childreni adjust egg-brooding behavior in response to shifts in nest temperature, which enhances egg temperature (e.g., reduced tight coiling during nest warming facilitated beneficial heat transfer to eggs). Last, I demonstrated that A. childreni adaptively adjust their egg-brooding behaviors due to an interaction between nest temperature and humidity. Specifically, females' behavioral response to nest warming was eliminated during low nest humidity. In combination with other studies, these results show that female pythons sense environmental temperature and humidity and utilize this information at multiple time points (i.e., during gravidity [egg bearing], at oviposition [egg laying], and during egg brooding) to enhance the developmental environment of their offspring. This research demonstrates that maternal behaviors that are simple and subtle, yet easily quantifiable, can balance several critical developmental variables (i.e., thermoregulation, water balance, and respiration).
ContributorsStahlschmidt, Zachary R (Author) / DeNardo, Dale F (Thesis advisor) / Harrison, Jon (Committee member) / McGraw, Kevin (Committee member) / Rutowski, Ronald (Committee member) / Walsberg, Glenn (Committee member) / Arizona State University (Publisher)
Created2011
Description
Adoptive transfer of T cells engineered to express synthetic antigen-specific T cell receptors (TCRs) has provocative therapeutic applications for treating cancer. However, expressing these synthetic TCRs in a CD4+ T cell line is a challenge. The CD4+ Jurkat T cell line expresses endogenous TCRs that compete for space, accessory proteins, and proliferative signaling, and there is the potential for mixed dimer formation between the α and β chains of the endogenous receptor and that of the synthetic cancer-specific TCRs. To prevent hybridization between the receptors and to ensure the binding affinity measured with flow cytometry analysis is between the tetramer and the TCR construct, a CRISPR-Cas9 gene editing pipeline was developed. The guide RNAs (gRNAs) within the complex were designed to target the constant region of the α and β chains, as they are conserved between TCR clonotypes. To minimize further interference and confer cytotoxic capabilities, gRNAs were designed to target the CD4 coreceptor, and the CD8 coreceptor was delivered in a mammalian expression vector. Further, Golden Gate cloning methods were validated in integrating the gRNAs into a CRISPR-compatible mammalian expression vector. These constructs were transfected via electroporation into CD4+ Jurkat T cells to create a CD8+ knockout TCR Jurkat cell line for broadly applicable uses in T cell immunotherapies.
ContributorsHirneise, Gabrielle Rachel (Author) / Anderson, Karen (Thesis advisor) / Mason, Hugh (Committee member) / Lake, Douglas (Committee member) / Arizona State University (Publisher)
Created2020
Description
To combat the global antimalarial resistance crisis effective resistance management strategies are needed. To do so, I need to gain a better understanding of the ecological interactions occurring within malaria infections. Despite the importance of the complex interplay among co-infecting strains, our current knowledge and empirical data of within-host diversity and malaria disease dynamics is limited. In this thesis, I explore the multifaceted dynamics of malaria infections through an ecological lens. My overall research question is: "How do ecological interactions, including niche complementarity, competition dynamics, and the cost of resistance, shape the outcomes of malaria infections, and what implications does this have on understanding and improving resistance management strategies?” In Chapter II, titled “Niche Complementarity in Malaria Infections” I demonstrate that ecological principles are observed in malarial infections by experimentally manipulating the biodiversity of rodent malaria P. chabaudi infections. I observed that some parasites experienced competitive suppression, others experienced competitive facilitation, while others were not impacted. Next, in Chapter III, titled “Determining the Differential Impact of Competition Between Genetically Distinct Plasmodium falciparum Strains” I investigate the differential effect of competition among six genetically distinct strains. The impact of competition varied between strain combinations, and both suppression and facilitation were observed, but most pairings had no competitive interactions. Lastly, in Chapter IV, titled “Assessing Fitness Costs in Malaria Parasites: A Comprehensive Review and Implications for Drug Resistance Management”, I summarize where the field currently stands and what evidence there is for the presence of a fitness cost, or lack thereof, and I highlight the current gaps in knowledge. I found that evidence from field, in vitro, and animal models are overall suggestive of the presence of a fitness cost, however, these costs were not always found. Amid the current focus on malaria eradication, it is crucial to understand the impact of biodiversity on disease severity. By incorporating an ecological approach to infectious disease systems, I can gain insights on within-host interactions and how they impact parasite fitness and transmissibility.
ContributorsSegovia, Xyonane (Author) / Huijben, Silvie (Thesis advisor) / Bean, Heather (Committee member) / Gile, Gillian (Committee member) / Hogue, Ian (Committee member) / Lake, Douglas (Committee member) / Arizona State University (Publisher)
Created2024