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: Biology
- Creators: Chandler, Douglas
- Creators: Baluch, Debra P
Description
In somatic cells, the mitotic spindle apparatus is centrosomal and several isoforms of Protein Kinase C (PKC) have been associated with the mitotic spindle, but their role in stabilizing the mitotic spindle is unclear. Other protein kinases such as, Glycogen Synthase Kinase 3â (GSK3â) also have been shown to be associated with the mitotic spindle. In the study in chapter 2, we show the enrichment of active (phosphorylated) PKCæ at the centrosomal region of the spindle apparatus in metaphase stage of 3T3 cells. In order to understand whether the two kinases, PKC and GSK3â are associated with the mitotic spindle, first, the co-localization and close molecular proximity of PKC isoforms with GSK3â was studied in metaphase cells. Second, the involvement of inactive GSK3â in maintaining an intact mitotic spindle was shown. Third, this study showed that addition of a phospho-PKCæ specific inhibitor to cells can disrupt the mitotic spindle microtubules. The mitotic spindle at metaphase in mouse fibroblasts appears to be maintained by PKCæ acting through GSK3â. The MAPK pathway has been implicated in various functions related to cell cycle regulation. MAPKK (MEK) is part of this pathway and the extracellular regulated kinase (ERK) is its known downstream target. GSK3â and PKCæ also have been implicated in cell cycle regulation. In the study in chapter 3, we tested the effects of inhibiting MEK on the activities of ERK, GSK3â, PKCæ, and á-tubulin. Results from this study indicate that inhibition of MEK did not inhibit GSK3â and PKCæ enrichment at the centrosomes. However, the mitotic spindle showed a reduction in the pixel intensity of microtubules and also a reduction in the number of cells in each of the M-phase stages. A peptide activation inhibitor of ERK was also used. Our results indicated a decrease in mitotic spindle microtubules and an absence of cells in most of the M-phase stages. GSK3â and PKCæ enrichment were however not inhibited at the centrosomes. Taken together, the kinases GSK3â and PKCæ may not function as a part of the MAPK pathway to regulate the mitotic spindle.
ContributorsChakravadhanula, Madhavi (Author) / Capco, David G. (Thesis advisor) / Chandler, Douglas (Committee member) / Clark-Curtiss, Josephine (Committee member) / Newfeld, Stuart (Committee member) / Arizona State University (Publisher)
Created2012
Description
Proper cell growth and differentiation requires the integration of multiple signaling pathways that are maintained by various post-translational modifications. Many proteins in signal transduction pathways are conserved between humans and model organisms. My dissertation characterizes four previously unknown manners of regulation in the Drosophila Decapentaplegic (Dpp) pathway, a pathway within TGF-beta family. First, I present data that the Dpp signal transducer, Mothers Against Dpp (Mad), is phosphorylated by Zeste-white 3 (Zw3), a kinase involved in the Wingless pathway. This phosphorylation event occurs independently of canonical phosphorylation of Mad by the Dpp receptor. Using ectopic expression of different alleles of Mad, I show that Zw3 phosphorylation of Mad occurs during the cell cycle in pro-neuronal cells and the loss of phosphorylation of Mad by Zw3 results in ectopic neuronal cells. Thus, Mad phosphorylation by Zw3 is necessary for cell cycle control in pro-neuronal cells. Second, I have shown that the regulator dSno, which has previously been shown to be a TGF-beta antagonist and agonist, is also a Wingless pathway antagonist. Loss of function flip-out clones and ectopic expression of dSno both resulted in changes of Wingless signaling. Further analysis revealed that dSno acts at or below the level of Armadillo (Arm) to inhibit target gene expression. Third, I have demonstrated that the protein Bonus, which is known to be involved in chromatin modification, is required in dorsal-ventral patterning. Further experiments discovered that the chromatin modifier is not only a necessary Dpp agonist, but it is also necessary for nuclear localization of Dorsal during Toll signaling. Last, I showed that longitudinal lacking-like (lola-like) is also required in dorsal-ventral patterning. The loss of maternally expressed lola-like prevents dpp transcription. This shows that lola-like is integral in the Dpp pathway. The study of these four proteins integrates different signaling pathways, demonstrating that the process of development is a web of connections rather than a linear pathway.
ContributorsQuijano, Janine C (Author) / Newfeld, Stuart J (Thesis advisor) / Goldstein, Elliott (Committee member) / Chandler, Douglas (Committee member) / Capco, David (Committee member) / Arizona State University (Publisher)
Created2014
Description
Engineered nanoparticles (NP; 10-9 m) have found use in a variety of consumer goods and medical devices because of the unique changes in material properties that occur when synthesized on the nanoscale. Although many definitions for nanoparticle exist, from the perspective of size, nanoparticle is defined as particles with diameters less than 100 nm in any external dimension. Examples of their use include titanium dioxide added as a pigment in products intended to be ingested by humans, silicon dioxide NPs are used in foods as an anticaking agent, and gold or iron oxide NPs can be used as vectors for drug delivery or contrast agents for specialized medical imaging. Although the intended use of these NPs is often to improve human health, it has come to the attention of investigators that NPs can have unintended or even detrimental effects on the organism. This work describes one such unintended effect of NP exposure from the perspective of exposure via the oral route. First, this Dissertation will explain an event referred to as brush border disruption that occurred after nanoparticles interacted with an in vitro model of the human intestinal epithelium. Second, this Dissertation will identify and characterize several consumer goods that were shown to contain titanium dioxide that are intended to be ingested. Third, this Dissertation shows that sedimentation due to gravity does not artifactually result in disruption of brush borders as a consequence of exposure to food grade titanium dioxide in vitro. Finally, this Dissertation will demonstrate that iron oxide nanoparticles elicited similar effects after exposure to an in vitro brush border expressing model of the human placenta. Together, these data suggest that brush border disruption is not an artifact of the material/cell culture model, but instead represents a bona fide biological response as a result of exposure to nanomaterial.
ContributorsFaust, James J (Author) / Capco, David G. (Thesis advisor) / Ugarova, Tatiana (Committee member) / Chandler, Douglas (Committee member) / Baluch, Page (Committee member) / Herman, Richard (Committee member) / Arizona State University (Publisher)
Created2014
Description
Though for most of the twentieth century, dogma held that the adult brain was post-mitotic, it is now known that adult neurogenesis is widespread among vertebrates, from fish, amphibians, reptiles and birds to mammals including humans. Seasonal changes in adult neurogenesis are well characterized in the song control system of song birds, and have been found in seasonally breeding mammals as well. In contrast to more derived vertebrates, such as mammals, where adult neurogenesis is restricted primarily to the olfactory bulb and the dentate gyrus of the hippocampus, neurogenesis is widespread along the ventricles of adult amphibians. I hypothesized that seasonal changes in adult amphibian brain cell proliferation and survival are a potential regulator of reproductive neuroendocrine function. Adult, male American bullfrogs (Rana catesbeiana; aka Lithobates catesbeianus), were maintained in captivity for up to a year under season-appropriate photoperiod. Analysis of hormone levels indicated seasonal changes in plasma testosterone concentration consistent with field studies. Using the thymidine analogue 5-bromo-2-deoxyuridine (BrdU) as a marker for newly generated cells, two differentially regulated aspects of brain cell neogenesis were tracked; that is, proliferation and survival. Seasonal differences were found in BrdU labeling in several brain areas, including the olfactory bulb, medial pallium, nucleus accumbens and the infundibular hypothalamus. Clear seasonal differences were also found in the pars distalis region of the pituitary gland, an important component of neuroendocrine pathways. BrdU labeling was also examined in relation to two neuropeptides important for amphibian reproduction: arginine vasotocin and gonadotropin releasing hormone. No cells co-localized with BrdU and either neuropeptide, but new born cells were found in close proximity to neuropeptide-containing neurons. These data suggest that seasonal differences in brain and pituitary gland cell neogenesis are a potential neuroendocrine regulatory mechanism.
ContributorsMumaw, Luke (Author) / Orchinik, Miles (Thesis advisor) / Deviche, Pierre (Committee member) / Chandler, Douglas (Committee member) / Arizona State University (Publisher)
Created2012
Description
The distinguishing feature of the filamentous fungi is the hyphae - tube-like microscopic cells that exhibit polarized growth via apical extension and allow the fungus to interact with its environment. Fungi elongate at the hyphal apex, through the localized construction of new plasma membrane and cell wall through the exocytosis of secretory vesicles. One population of these vesicles have been identified as chitosomes, containing chitin synthase isoenzymes, which are responsible for the polymerization of N-acetylglucosamine from UDP N-acetylglucosamine into chitin, the primary fibrillar component of the fungal cell wall. The chitosomes, in addition to other vesicles, can be observed aggregating in the hyphal tip in most filamentous fungi. In the Ascomycota and Basidiomycota, this collection of vesicles exhibits discrete organization and has been termed a Spitzenkörper. Although accumulations of vesicles can be observed in the hyphal tip of many growing filamentous fungi, some debate continues as to what precisely defines a Spitzenkörper. This study reports the details of three separate projects: first, to document the effects of deleting a single chitin synthase, CHS-1 and CHS-6 in Neurospora crassa with regards to hyphal ultrastructure, cytoplasmic organization, and growth in comparison to the wild-type. Given the importance of chitin synthesis in fungal cell growth, deletion of a critical chitin synthase presumably impacts cell wall structure, fungal growth and cytoplasmic organization. Second, an examination of the ultrastructure of four zygomycetous fungi - Coemansia reversa, Mortierella verticillata, Mucor indicus, and Gilbertella persicaria has been conducted. Utilization of cryofixation and freeze-substitution techniques for electron microscopy has produced improved preservation of cytoplasmic ultrastructure, particularly at the hyphal apex, allowing detailed analysis of vesicle size, contents, and organization. Lastly, hyphal tip organization was reviewed in a broad range of fungi. Previous studies had either focused on a few select fungi or representative groups. Vesicle organization, composition and size do appear to vary among the classes of fungi, but some trends, like the vesicle crescent in the zygomycetous fungi have been documented.
ContributorsFisher, Karen Elizabeth (Author) / Roberson, Robert W. (Thesis advisor) / Chandler, Douglas (Committee member) / Riquelme, Meritxell (Committee member) / Stutz, Jeam (Committee member) / Wojciechowski, Martin (Committee member) / Arizona State University (Publisher)
Created2015
Description
Pregnancy and childbirth are both natural occurring events, but still little is known about the signaling mechanisms that induce contractions. Throughout the world, premature labor occurs in 12% of all pregnancies with 36% of infant deaths resulting from preterm related causes. Even though the cause of preterm labor can vary, understanding alternative signaling pathways, which affect muscle contraction, could provide additional treatment options in stopping premature labor. The uterus is composed of smooth muscle, which is innervated, with a plexus of nerves that cover the muscle fibers. Smooth muscle can be stimulated or modulated by many sources such as neurotransmitters [i.e. dopamine], hormones [i.e. estrogen], peptides [i.e. oxytocin] and amines. This study focuses on the biogenic monoamine tyramine, which is produced in the tyrosine catecholamine biosynthesis pathway. Tyramine is known to be associated with peripheral vasoconstriction, increased cardiac output, increased respiration, elevated blood glucose and the release of norepinephrine. This research has found tyramine, and its specific receptor TAAR1, to be localized within mouse uterus and that this monoamine can induce uterine contractions at levels similar to oxytocin.
ContributorsObayomi, SM Bukola (Author) / Baluch, Debra P (Thesis advisor) / Deviche, Pierre (Thesis advisor) / Smith, Brian H. (Committee member) / Arizona State University (Publisher)
Created2017
Description
Human preterm labor is the single most significant issue in modern obstetrics andgynecology, affecting ten percent of pregnancies, constituting the leading cause of infant death, and contributing significantly to chronic childhood disease. Obstetricians and reproductive scientists are faced with the major challenge of trying to increase the understanding of the complex molecular and cellular signals that regulate uterine activity during human pregnancy and labor. Even though preterm labor accounts for a large portion of perinatal mortality and morbidity, there still is not an effective therapeutic strategy for the treatment or prevention of preterm labor. This dissertation presents tyramine as an alternative modulator of uterine activity. In this dissertation the aims were as follows: 1) to investigate the localization of tyramine and trace amine associated receptor 1 (TAAR1) in the mouse uterine horn using immunohistochemistry as well as confirm the presence of tyramine in the uterine tissue using high performance liquid chromatography, 2) identify which TAAR 1-9 subtypes were present in the mouse uterine horn using RT-qPCR, 3) investigate ultrastructural differences in the mouse uterine horn following tyramine and dopamine treatment using transmission electron microscopy and 4) investigate pinopod ultrastructure as well as pinopod ultrastructural differences following tyramine and dopamine treatment. The research presented in this dissertation showed: 1) tyramine has very specific localization in the mouse endometrium, mainly in the uterine glands, TAAR1 is localized all throughout the perimetrium, myometrium and endometrium, and that tyramine was confirmed and quantified using HPLC, 2) TAAR 1- 9 genes are expressed in trace levels in the mouse uterine horn, 3) tyramine influences changes in endometrial ultrastructure, and 4) tyramine influences changes in pinopod ultrastructure. Ultimately these findings can help with identifying novel treatment options not only for spontaneous preterm labor contractions but also for other uterine related disorders.
ContributorsObayomi, SM Bukola (Author) / Baluch, Debra P (Thesis advisor) / Roberson, Robert (Thesis advisor) / Sweazea, Karen (Committee member) / Brent, Colin (Committee member) / Arizona State University (Publisher)
Created2023
Description
According to the World Health Organization, obesity has nearly tripled since 1975 and forty-one million children under the age of 5 are overweight or obese (World Health Organization, 2018). Exercise is a potential intervention to prevent obesity-induced cardiovascular complications as exercise training has been shown to aid nitric oxide (NO) production as well as preserving endothelial function in obese mice (Silva et al., 2016). A soil-derived organic mineral compound (OMC) has been shown to lower blood sugar in diabetic mice (Deneau et al., 2011). Prior research has shown that, while OMC did not prevent high fat diet (HFD)-induced increases in body fat in male Sprague-Dawley rats, it was effective at preventing HFD-induced impaired vasodilation (M. S. Crawford et al., 2019). Six-weeks of HFD has been shown to impair vasodilation through oxidative-stress mediated scavenging of NO as well as upregulation of inflammatory pathways including inducible nitric oxide synthase (iNOS) and cyclooxygenase (Karen L. Sweazea et al., 2010). Therefore, the aim of the present study was to determine whether OMC alters protein expression of iNOS and endothelial NOS (eNOS) in the vasculature of rats fed a control or HFD with and without OMC supplementation. Six-week old male Sprague-Dawley rats were fed either a standard chow diet (CHOW) or a HFD composed of 60% kcal from fat for 10 weeks. The rats were administered OMC at doses of 0 mg/mL (control), 0.6 mg/mL, or 3.0 mg/mL added to their drinking water. Following euthanasia with sodium pentobarbital (200 mg/kg, i.p.), mesenteric arteries and the surrounding perivascular adipose tissue were isolated and prepared for Western Blot analyses. Mesenteric arteries from HFD rats had more uncoupled eNOS (p = 0.006) and iNOS protein expression (p = 0.027) than rats fed the control diet. OMC was not effective at preventing the uncoupling of eNOS or increase in iNOS induced by HFD. Perivascular adipose tissue (PVAT) showed no significant difference in iNOS protein expression between diet or OMC treatment groups. These findings suggest that OMC is not likely working through the iNOS or eNOS pathways to improve vasodilation in these rats, but rather, appears to be working through another mechanism.
ContributorsNelson, Morgan Allen (Author) / Sweazea, Karen L (Thesis advisor) / Katsanos, Christos S (Committee member) / Baluch, Debra P (Committee member) / Arizona State University (Publisher)
Created2020
Description
The desire to start a family is something millions of people around the globe strive to achieve. However, many factors such as the societal changes in family planning due to increasing maternal age, use of birth control, and ever-changing lifestyles have increased the number of infertility cases seen in the United States each year. Infertility can manifest as a prolonged inability to conceive, or inability to carry a pregnancy full-term. Modern advancements in the field of reproductive medicine have begun to promote the use of Assisted Reproductive Technologies (ART) to circumvent reduced fertility in both men and women. Implementation of techniques such as In Vitro Fertilization, Intracytoplasmic Sperm Injection, and Pre-Implantation Genetic Testing have allowed many couples to conceive. There is continual effort being made towards developing more effective and personalized fertility treatments. This often begins in the form of animal research—a fundamental step in biomedical research. This dissertation examines infertility as a medical condition through the characterization of normal reproductive anatomy and physiology in the introductory overview of reproduction. Specific pathologies of male and female-factor infertility are described, which necessitates the use of ARTs. The various forms of ARTs currently utilized in a clinical setting are addressed including history, preparations, and protocols for each technology. To promote continual advancement of the field, both animal studies and human trials provide fundamental stepping-stones towards the execution of new techniques and protocols. Examples of research conducted for the betterment of human reproductive medicine are explored, including an animal study conducted in mice exploring the role of tyramine in ovulation. With the development and implementation of new technologies and protocols in the field, this also unearths ethical dilemmas that further complicate the addition of new technologies in the field. Combining an extensive review in assisted reproduction, research and clinical fieldwork, this study investigates the history and development of novel research conducted in reproductive medicine and explores the broader implications of new technologies in the field.
ContributorsPeck, Shelbi Marie (Author) / Baluch, Debra P (Thesis advisor) / Maienschein, Jane (Thesis advisor) / Sweazea, Karen (Committee member) / Ellison, Karin (Committee member) / Arizona State University (Publisher)
Created2021