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
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
While exercising mammalian muscle increasingly relies on carbohydrates for fuel as aerobic exercise intensity rises above the moderate range, flying birds are extraordinary endurance athletes and fuel flight, a moderate-high intensity exercise, almost exclusively with lipid. In addition, Aves have long lifespans compared to weight-matched mammals. As skeletal muscle mitochondria account for the majority of oxygen consumption during aerobic exercise, the primary goal was to investigate differences in isolated muscle mitochondria between these species and to examine to what extent factors intrinsic to mitochondria may account for the behavior observed in the intact tissue and whole organism. First, maximal enzyme activities were assessed in sparrow and rat mitochondria. Citrate synthase and aspartate aminotransferase activity were higher in sparrow compared to rat mitochondria, while glutamate dehydrogenase activity was lower. Sparrow mitochondrial NAD-linked isocitrate dehydrogenase activity was dependent on phosphate, unlike the mammalian enzyme. Next, the rate of oxygen consumption (JO), electron transport chain (ETC) activity, and reactive oxygen species (ROS) production were assessed in intact mitochondria. Maximal rates of fat oxidation were lower than for carbohydrate in rat but not sparrow mitochondria. ETC activity was higher in sparrows, but no differences were found in ROS production between species. Finally, fuel selection and control of respiration at three rates between rest and maximum were assessed. Mitochondrial fuel oxidation and selection mirrored that of the whole body; in rat mitochondria the reliance on carbohydrate increased as the rate of oxygen consumption increased, whereas fat dominated under all conditions in the sparrow. These data indicate fuel selection, at least in part, can be modulated at the level of the mitochondrial matrix when multiple substrates are present at saturating levels. As an increase in matrix oxidation-reduction potential has been linked to a suppression of fat oxidation and high ROS production, the high ETC activity relative to dehydrogenase activity in avian compared to mammalian mitochondria may result in lower matrix oxidation-reduction potential, allowing fatty acid oxidation to proceed while also resulting in low ROS production in vivo.
ContributorsKuzmiak, Sarah (Author) / Willis, Wayne T (Thesis advisor) / Mandarino, Lawrence (Committee member) / Sweazea, Karen (Committee member) / Harrison, Jon (Committee member) / Gadau, Juergen (Committee member) / Arizona State University (Publisher)
Created2012
Description
The Multiple Antibiotic Resistance Regulator Family (MarR) are transcriptional regulators, many of which forms a dimer. Transcriptional regulation provides bacteria a stabilized responding system to ensure the bacteria is able to efficiently adapt to different environmental conditions. The main function of the MarR family is to create multiple antibiotic resistance from a mutated protein; this process occurs when the MarR regulates an operon. We hypothesized that different transcriptional regulator genes have interactions with each other. It is known that Salmonella pagC transcription is activated by three regulators, i.e., SlyA, MprA, and PhoP. Bacterial Adenylate Cyclase-based Two-Hybrid (BACTH) system was used to research the protein-protein interactions in SlyA, MprA, and PhoP as heterodimers and homodimers in vivo. Two fragments, T25 and T18, that lack endogenous adenylate cyclase activity, were used for construction of chimeric proteins and reconstruction of adenylate cyclase activity was tested. The significant adenylate cyclase activities has proved that SlyA is able to form homodimers. However, weak adenylate cyclase activities in this study has proved that MprA and PhoP are not likely to form homodimers, and no protein-protein interactions were detected in between SlyA, MprA and PhoP, which no heterodimers have formed in between three transcriptional regulators.
ContributorsTao, Zenan (Author) / Shi, Yixin (Thesis advisor) / Wang, Xuan (Committee member) / Bean, Heather (Committee member) / Arizona State University (Publisher)
Created2018
Description
Emergence of multidrug resistant (MDR) bacteria is a major concern to global health. One of the major MDR mechanisms bacteria employ is efflux pumps for the expulsion of drugs from the cell. In Escherichia coli, AcrAB-TolC proteins constitute the major chromosomally-encoded drug efflux system. AcrB, a trimeric membrane protein is well-known for its substrate promiscuity. It has the ability to efflux a broad spectrum of substrates alongside compounds such as dyes, detergent, bile salts and metabolites. Newly identified AcrB residues were shown to be functionally relevant in the drug binding and translocation pathway using a positive genetic selection strategy. These residues—Y49, V127, D153, G288, F453, and L486—were identified as the sites of suppressors of an alteration, F610A, that confers a drug hypersensitivity phenotype. Using site-directed mutagenesis (SDM) along with the real-time efflux and the classical minimum inhibitory concentration (MIC) assays, I was able to characterize the mechanism of suppression.
Three approaches were used for the characterization of these suppressors. The first approach focused on side chain specificity. The results showed that certain suppressor sites prefer a particular side chain property, such as size, to overcome the F610A defect. The second approach focused on the effects of efflux pump inhibitors. The results showed that though the suppressor residues were able to overcome the intrinsic defect of F610A, they were unable to overcome the extrinsic defect caused by the efflux pump inhibitors. This showed that the mechanism by which F610A imposes its effect on AcrB function is different than that of the efflux pump inhibitors. The final approach was to determine whether suppressors mapping in the periplasmic and trans-membrane domains act by the same or different mechanisms. The results showed both overlapping and distinct mechanisms of suppression.
To conclude, these approaches have provided a deeper understanding of the mechanisms by which novel suppressor residues of AcrB overcome the functional defect of the drug binding domain alteration, F610A.
Three approaches were used for the characterization of these suppressors. The first approach focused on side chain specificity. The results showed that certain suppressor sites prefer a particular side chain property, such as size, to overcome the F610A defect. The second approach focused on the effects of efflux pump inhibitors. The results showed that though the suppressor residues were able to overcome the intrinsic defect of F610A, they were unable to overcome the extrinsic defect caused by the efflux pump inhibitors. This showed that the mechanism by which F610A imposes its effect on AcrB function is different than that of the efflux pump inhibitors. The final approach was to determine whether suppressors mapping in the periplasmic and trans-membrane domains act by the same or different mechanisms. The results showed both overlapping and distinct mechanisms of suppression.
To conclude, these approaches have provided a deeper understanding of the mechanisms by which novel suppressor residues of AcrB overcome the functional defect of the drug binding domain alteration, F610A.
ContributorsBlake, Mellecha (Author) / Misra, Rajeev (Thesis advisor) / Stout, Valerie (Committee member) / Wang, Xuan (Committee member) / Arizona State University (Publisher)
Created2016
Description
Male reproductive dysfunction accounts for almost half of male infertility cases, yet the signaling mechanisms involved in the male reproductive system remain unclear. Although the exact cause of male reproductive dysfunction varies, obtaining a better understanding of the modulators of smooth muscle contractions may provide new targets for the treatment of male reproductive conditions. The male reproductive tract, consisting of the testes, epididymis, vas deferens, and penis, is lined with innervated smooth muscle fibers that transport spermatozoa through the system. Contractions of these smooth muscle fibers can be modulated by neurotransmitters and hormones, like dopamine and norepinephrine, as well as biogenic amines. The focus of this study is on the biogenic amine tyramine, which is produced by the breakdown of tyrosine via decarboxylation. Tyramine has been shown to modulate vasoconstriction and increase blood pressure due to its effect on smooth muscle contractions. This study has found that tyramine localizes in male reproductive tissues and modulates smooth muscle contractions. Age and environment were also found to play a significant role in the expression of tyramine and its associated receptor, TAAR1.
ContributorsSteadman, Solange (Author) / Baluch, Debra (Thesis advisor) / Roberson, Robert (Committee member) / Sweazea, Karen (Committee member) / Arizona State University (Publisher)
Created2023
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
Characterization and Manipulation of Microbiomes From Arid Landfills for Improved Methane Production
Description
Environmentally harmful byproducts from solid waste’s decomposition, including methane (CH4) emissions, are managed through standardized landfill engineering and gas-capture mechanisms. Yet only a limited number of studies have analyzed the development and composition of Bacteria and Archaea involved in CH4 production from landfills. The objectives of this research were to compare microbiomes and bioactivity from CH4-producing communities in contrasting spatial areas of arid landfills and to tests a new technology to biostimulate CH4 production (methanogenesis) from solid waste under dynamic environmental conditions controlled in the laboratory. My hypothesis was that the diversity and abundance of methanogenic Archaea in municipal solid waste (MSW), or its leachate, play an important role on CH4 production partially attributed to the group’s wide hydrogen (H2) consumption capabilities. I tested this hypothesis by conducting complementary field observations and laboratory experiments. I describe niches of methanogenic Archaea in MSW leachate across defined areas within a single landfill, while demonstrating functional H2-dependent activity. To alleviate limited H2 bioavailability encountered in-situ, I present biostimulant feasibility and proof-of-concepts studies through the amendment of zero valent metals (ZVMs). My results demonstrate that older-aged MSW was minimally biostimulated for greater CH4 production relative to a control when exposed to iron (Fe0) or manganese (Mn0), due to highly discernable traits of soluble carbon, nitrogen, and unidentified fluorophores found in water extracts between young and old aged, starting MSW. Acetate and inhibitory H2 partial pressures accumulated in microcosms containing old-aged MSW. In a final experiment, repeated amendments of ZVMs to MSW in a 600 day mesocosm experiment mediated significantly higher CH4 concentrations and yields during the first of three ZVM injections. Fe0 and Mn0 experimental treatments at mesocosm-scale also highlighted accelerated development of seemingly important, but elusive Archaea including Methanobacteriaceae, a methane-producing family that is found in diverse environments. Also, prokaryotic classes including Candidatus Bathyarchaeota, an uncultured group commonly found in carbon-rich ecosystems, and Clostridia; All three taxa I identified as highly predictive in the time-dependent progression of MSW decomposition. Altogether, my experiments demonstrate the importance of H2 bioavailability on CH4 production and the consistent development of Methanobacteriaceae in productive MSW microbiomes.
ContributorsReynolds, Mark Christian (Author) / Cadillo-Quiroz, Hinsby (Thesis advisor) / Krajmalnik-Brown, Rosa (Thesis advisor) / Wang, Xuan (Committee member) / Kavazanjian, Edward (Committee member) / Arizona State University (Publisher)
Created2022
Description
Biomass synthesis is a competing factor in biological systems geared towards generation of commodity and specialty chemicals, ultimately limiting maximum titer and yield; in this thesis, a widely generalizable, modular approach focused on decoupling biomass synthesis from the production of the phenylalanine in a genetically modified strain of E. coli BW25113 was explored with the use of synthetic trans-encoded small RNA (sRNA) to achieve greater efficiency. The naturally occurring sRNA MicC was used as a scaffold, and combined on a plasmid with a promoter for anhydrous tetracycline (aTc) and a T1/TE terminator. The coding sequence corresponding to the target binding site for fourteen potentially growth-essential gene targets as well as non-essential lacZ was placed in the seed region of the of the sRNA scaffold and transformed into BW25113, effectively generating a unique strain for each gene target. The BW25113 strain corresponding to each gene target was screened in M9 minimal media; decreased optical density and elongated cell morphology changes were observed and quantified in all induced sRNA cases where growth-essential genes were targeted. Six of the strains targeting different aspects of cell division that effectively suppressed growth and resulted in increased cell size were then screened for viability and metabolic activity in a scaled-up shaker flask experiment; all six strains were shown to be viable during stationary phase, and a metabolite analysis showed increased specific glucose consumption rates in induced strains, with unaffected specific glucose consumption rates in uninduced strains. The growth suppression, morphology and metabolic activity of the induced strains in BW25113 was compared to the bacteriostatic additives chloramphenicol, tetracycline, and streptomycin. At this same scale, the sRNA plasmid targeting the gene murA was transformed into BW25113 pINT-GA, a phenylalanine overproducer with the feedback resistant genes aroG and pheA overexpressed. Two induction times were explored during exponential phase, and while the optimal induction time was found to increase titer and yield amongst the BW25113 pINT-GA murA sRNA variant, overall this did not have as great a titer or yield as the BW25113 pINT-GA strain without the sRNA plasmid; this may be a result of the cell filamentation.
ContributorsHerschel, Daniel Jordan (Author) / Nielsen, David R (Thesis advisor) / Torres, César I (Committee member) / Wang, Xuan (Committee member) / Arizona State University (Publisher)
Created2016
Description
Lipolysis or hydrolysis of triglyceride (TG) stored within intracellular lipid droplets (LD), is vital to maintaining metabolic homeostasis in mammals. Regulation of lipolysis and subsequent utilization of liberated fatty acids impacts cellular and organismal functions including body fat accumulation and thermogenesis. Adipose triglyceride lipase (ATGL) is the intracellular rate-limiting enzyme responsible for catalyzing hydrolysis of TG to diacylglycerol (DAG), the initial step of the lipolytic reaction. G0/G1 switch gene-2 (G0S2) and hypoxia-inducible gene-2 (HIG2) are selective inhibitors of ATGL. G0S2 facilitates accumulation of TG in the liver and adipose tissue, while HIG2 functions under hypoxic conditions. Sequence analysis and mutagenesis were used to confirm the presence of conserved domains between these proteins, and that these domains are required for efficient binding and inhibition of ATGL. Further analysis revealed a Positive sequence (Pos-Seq)-LD binding motif in G0S2 but not HIG2. The Pos-Seq mediated ATGL-independent localization to LD and was required for achieving maximal inhibition of ATGL activity by G0S2. Identification and mutational analysis of this motif revealed distinct mechanisms for HIG2 and G0S2 LD association. In addition to molecular characterization of known protein inhibitors of lipolysis, an intracellular member of the apolipoprotein L (ApoL) family, ApoL6, was also identified as a LD and mitochondria associated protein expressed in adipose tissue. Brown adipose tissue uses fatty acids as fuel for increasing its energy output as heat during acute responses to cold exposure. A Comprehensive Lab Animal Monitoring System was used to compare heat production at room temperature (RT) and 4oC in transgenic animals overexpressing ApoL6 in brown adipose tissue. Overexpression of ApoL6 delayed utilization of long-chain fatty acids (LCFAs) as a fuel source while promoting an enhanced thermogenic response during initial cold exposure. ApoL6 mediated inhibition of LCFA utilization results from binding of ApoL6 to Mitochondrial Trifunctional Protein (MTP/TFP), which catalyzes mitochondrial β-oxidation. Indirect calorimetry and fasting acute cold exposure experiments suggest the augmented thermogenic profile of ApoL6 transgenic animals is a result of enhanced utilization of medium-chain fatty acids (MCFAs), glucose, and amino acids as fuel sources. Cumulatively these results indicate multiple mechanisms for regulation lipolysis and fatty acid utilization.
ContributorsCampbell, Latoya E (Author) / Lake, Douglas (Thesis advisor) / Liu, Jun (Committee member) / Folmes, Clifford (Committee member) / Sweazea, Karen (Committee member) / Baluch, Debra (Committee member) / Arizona State University (Publisher)
Created2021
Description
Organisms regularly face the challenge of having to accumulate and allocate limited resources toward life-history traits. However, direct quantification of how resources are accumulated and allocated is rare. Carotenoids are among the best systems for investigating resource allocation, because they are diet-derived and multi-functional. Birds have been studied extensively with regard to carotenoid allocation towards life-history traits, but direct quantification of variation in carotenoid distribution on a whole-organism scale has yet to be done. Additionally, while we know that scavenger receptor B1 (SCARB1) is important for carotenoid absorption in birds, little is known about the factors that predict how SCARB1 is expressed in wild populations. For my dissertation, I first reviewed challenges associated with statistically analyzing tissue distributions of nutrients (nutrient profiles) and tested how tissue carotenoid distributions (carotenoid profiles) varied by sex, season, health state, and coloration in two bird species, house finches (Haemorhous mexicanus) and zebra finches (Taeniopygia guttata). Then, I investigated the relationship between dietary carotenoid availability, relative expression of SCARB1, and extent of carotenoid-based coloration in a comparative study of wood-warblers (Parulidae). In my review of studies analyzing nutrient profiles, I found that multivariate analyses were the most common, but studies rarely reported intercorrelations among nutrient types. In house finches, all tissue carotenoid profiles varied by sex, season, and coloration. For example, males during autumn (molt) had higher concentrations of 3-hydroxyechinenone (the major red carotenoid in sexually attractive male feathers) in most but not all tissues compared to other season and sex combinations. However, the relationship between color and carotenoid profiles depended on the color metric. In zebra finches, only muscle and spleen carotenoid profiles varied between immune-challenged and control birds. In wood-warblers, I found that capacity to absorb carotenoids was positively correlated with the evolution of carotenoid-based coloration but negatively associated with liver carotenoid accumulation. Altogether, my dissertation illustrates (a) the context-dependence of tissue carotenoid profile variation, (b) that carotenoid-based integumentary coloration is a reflection of tissue carotenoid profiles, and (c) that digestive physiology (e.g., carotenoid absorption) is an important consideration in the study of diet and coloration in wild birds.
ContributorsWebb, Emily (Author) / McGraw, Kevin J (Thesis advisor) / Deviche, Pierre (Committee member) / Martins, Emilia (Committee member) / Sweazea, Karen (Committee member) / Arizona State University (Publisher)
Created2021