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: DeNardo, Dale
- Creators: Mangone, Marco
Description
Conditions during development can shape the expression of traits at adulthood, a phenomenon called developmental plasticity. In this context, factors such as nutrition or health state during development can affect current and subsequent physiology, body size, brain structure, ornamentation, and behavior. However, many of the links between developmental and adult phenotype are poorly understood. I performed a series of experiments using a common molecular currency - carotenoid pigments - to track somatic and reproductive investments through development and into adulthood. Carotenoids are red, orange, or yellow pigments that: (a) animals must acquire from their diets, (b) can be physiologically beneficial, acting as antioxidants or immunostimulants, and (c) color the sexually attractive features (e.g., feathers, scales) of many animals. I studied how carotenoid nutrition and immune challenges during ontogeny impacted ornamental coloration and immune function of adult male mallard ducks (Anas platyrhynchos). Male mallards use carotenoids to pigment their yellow beak, and males with more beaks that are more yellow are preferred as mates, have increased immune function, and have higher quality sperm. In my dissertation work, I established a natural context for the role that carotenoids and body condition play in the formation of the adult phenotype and examined how early-life experiences, including immune challenges and dietary access to carotenoids, affect adult immune function and ornamental coloration. Evidence from mallard ducklings in the field showed that variation in circulating carotenoid levels at hatch are likely driven by maternal allocation of carotenoids, but that carotenoid physiology shifts during the subsequent few weeks to reflect individual foraging habits. In the lab, adult beak color expression and immune function were more tightly correlated with body condition during growth than body condition during subsequent stages of development or adulthood. Immune challenges during development affected adult immune function and interacted with carotenoid physiology during adulthood, but did not affect adult beak coloration. Dietary access to carotenoids during development, but not adulthood, also affected adult immune function. Taken together, these results highlight the importance of the developmental stage in shaping certain survival-related traits (i.e., immune function), and lead to further questions regarding the development of ornamental traits.
ContributorsButler, Michael (Author) / McGraw, Kevin J. (Thesis advisor) / Chang, Yung (Committee member) / Deviche, Pierre (Committee member) / DeNardo, Dale (Committee member) / Rutowski, Ronald (Committee member) / Arizona State University (Publisher)
Created2012
Description
Land management practices such as domestic animal grazing can alter plant communities via changes in soil structure and chemistry, species composition, and plant nutrient content. These changes can affect the abundance and quality of plants consumed by insect herbivores with consequent changes in population dynamics. These population changes can translate to massive crop damage and pest control costs. My dissertation focused on Oedaleus asiaticus, a dominant Asian locust, and had three main objectives. First, I identified morphological, physiological, and behavioral characteristics of the migratory ("brown") and non-migratory ("green") phenotypes. I found that brown morphs had longer wings, larger thoraxes and higher metabolic rates compared to green morphs, suggesting that developmental plasticity allows greater migratory capacity in the brown morph of this locust. Second, I tested the hypothesis of a causal link between livestock overgrazing and an increase in migratory swarms of O. asiaticus. Current paradigms generally assume that increased plant nitrogen (N) should enhance herbivore performance by relieving protein-limitation, increasing herbivorous insect populations. I showed, in contrast to this scenario, that host plant N-enrichment and high protein artificial diets decreased the size and viability of O. asiaticus. Plant N content was lowest and locust abundance highest in heavily livestock-grazed fields where soils were N-depleted, likely due to enhanced erosion and leaching. These results suggest that heavy livestock grazing promotes outbreaks of this locust by reducing plant protein content. Third, I tested for the influence of dietary imbalance, in conjunction with high population density, on migratory plasticity. While high population density has clearly been shown to induce the migratory morph in several locusts, the effect of diet has been unclear. I found that locusts reared at high population density and fed unfertilized plants (i.e. high quality plants for O. asiaticus) had the greatest migratory capacity, and maintained a high percent of brown locusts. These results did not support the hypothesis that poor-quality resources increased expression of migratory phenotypes. This highlights a need to develop new theoretical frameworks for predicting how environmental factors will regulate migratory plasticity in locusts and perhaps other insects.
ContributorsCease, Arianne (Author) / Harrison, Jon (Thesis advisor) / Elser, James (Thesis advisor) / DeNardo, Dale (Committee member) / Quinlan, Michael (Committee member) / Sabo, John (Committee member) / Arizona State University (Publisher)
Created2012
Description
There is considerable recent interest in the dynamic nature of immune function in the context of an animal’s internal and external environment. An important focus within this field of ecoimmunology is on how availability of resources such as energy can alter immune function. Water is an additional resource that drives animal development, physiology, and behavior, yet the influence hydration has on immunity has received limited attention. In particular, hydration state may have the greatest potential to drive fluctuations in immunity and other physiological functions in species that live in water-limited environments where they may experience periods of dehydration. To shed light on the sensitivity of immune function to hydration state, I first tested the effect of hydration states (hydrated, dehydrated, and rehydrated) and digestive states on innate immunity in the Gila monster, a desert-dwelling lizard. Though dehydration is often thought to be stressful and, if experienced chronically, likely to decrease immune function, dehydration elicited an increase in immune response in this species, while digestive state had no effect. Next, I tested whether dehydration was indeed stressful, and tested a broader range of immune measures. My findings validated the enhanced innate immunity across additional measures and revealed that Gila monsters lacked a significant stress hormone response during dehydration (though results were suggestive). I next sought to test if life history (in terms of environmental stability) drives these differences in dehydration responses using a comparative approach. I compared four confamilial pairs of squamate species that varied in habitat type within each pair—four species that are adapted to xeric environments and four that are adapted to more mesic environments. No effect of life history was detected between groups, but hydration was a driver of some measures of innate immunity and of stress hormone concentrations in multiple species. Additionally, species that exhibited a stress response to dehydration did not have decreased innate immunity, suggesting these physiological responses may often be decoupled. My dissertation work provides new insight into the relationship between hydration, stress, and immunity, and it may inform future work exploring disease transmission or organismal responses to climate change.
ContributorsMoeller, Karla T (Author) / DeNardo, Dale (Thesis advisor) / Angilletta, Michael (Committee member) / French, Susannah (Committee member) / Rutowski, Ronald (Committee member) / Sabo, John (Committee member) / Arizona State University (Publisher)
Created2016
Description
Desert environments provide considerable challenges to organisms because of high temperatures and limited food and water resources. Accordingly, desert species have behavioral and physiological traits that enable them to cope with these constraints. However, continuing human activity as well as anticipated further changes to the climate and the vegetative community pose a great challenge to such balance between an organism and its environment. This is especially true in the Arabian Desert, where climate conditions are extreme and environmental disturbances substantial. This study combined laboratory and field components to enhance our understanding of dhub (Uromastyx aegyptius) ecophysiology and determine whether habitat protection influences dhub behavior and physiology.
Results of this study showed that while body mass and body condition consistently diminished as the active season progressed, they were both greater in protected habitats compared to non-protected habitats, regardless of season. Dhubs surface activity and total body water decreased while evaporative water loss and body temperature increased as the active season progressed and ambient temperature got hotter. Total body water was also significantly affected by habitat protection.
Overall, this study revealed that, while habitat protection provided more vegetation, it had little effect on seasonal changes in surface activity. While resource availability in protected areas might allow for larger dhub populations, unprotected areas showed similar body morphometrics, activity, and body temperatures. By developing an understanding of how different coping strategies are linked to particular ecological, morphological, and phylogenetic traits, we will be able to make more accurate predictions regarding the vulnerability of species. By combining previous studies pertaining to conservation of protected species with the results of my study, a number of steps in ecosystem management are recommended to help in the preservation of dhubs in the Kuwaiti desert.
Results of this study showed that while body mass and body condition consistently diminished as the active season progressed, they were both greater in protected habitats compared to non-protected habitats, regardless of season. Dhubs surface activity and total body water decreased while evaporative water loss and body temperature increased as the active season progressed and ambient temperature got hotter. Total body water was also significantly affected by habitat protection.
Overall, this study revealed that, while habitat protection provided more vegetation, it had little effect on seasonal changes in surface activity. While resource availability in protected areas might allow for larger dhub populations, unprotected areas showed similar body morphometrics, activity, and body temperatures. By developing an understanding of how different coping strategies are linked to particular ecological, morphological, and phylogenetic traits, we will be able to make more accurate predictions regarding the vulnerability of species. By combining previous studies pertaining to conservation of protected species with the results of my study, a number of steps in ecosystem management are recommended to help in the preservation of dhubs in the Kuwaiti desert.
ContributorsAl-Sayegh, Mohammed (Author) / DeNardo, Dale (Thesis advisor) / Angilletta, Michael (Committee member) / Smith, Andrew (Committee member) / Sabo, John (Committee member) / Majeed, Qais (Committee member) / Arizona State University (Publisher)
Created2017
Description
Advances in sequencing technology have generated an enormous amount of data over the past decade. Equally advanced computational methods are needed to conduct comparative and functional genomic studies on these datasets, in particular tools that appropriately interpret indels within an evolutionary framework. The evolutionary history of indels is complex and often involves repetitive genomic regions, which makes identification, alignment, and annotation difficult. While previous studies have found that indel lengths in both deoxyribonucleic acid and proteins obey a power law, probabilistic models for indel evolution have rarely been explored due to their computational complexity. In my research, I first explore an application of an expectation-maximization algorithm for maximum-likelihood training of a codon substitution model. I demonstrate the training accuracy of the expectation-maximization on my substitution model. Then I apply this algorithm on a published 90 pairwise species dataset and find a negative correlation between the branch length and non-synonymous selection coefficient. Second, I develop a post-alignment fixation method to profile each indel event into three different phases according to its codon position. Because current codon-aware models can only identify the indels by placing the gaps between codons and lead to the misalignment of the sequences. I find that the mouse-rat species pair is under purifying selection by looking at the proportion difference of the indel phases. I also demonstrate the power of my sliding-window method by comparing the post-aligned and original gap positions. Third, I create an indel-phase moore machine including the indel rates of three phases, length distributions, and codon substitution models. Then I design a gillespie simulation that is capable of generating true sequence alignments. Next I develop an importance sampling method within the expectation-maximization algorithm that can successfully train the indel-phase model and infer accurate parameter estimates from alignments. Finally, I extend the indel phase analysis to the 90 pairwise species dataset across three alignment methods, including Mafft+sw method developed in chapter 3, coati-sampling methods applied in chapter 4, and coati-max method. Also I explore a non-linear relationship between the dN/dS and Zn/(Zn+Zs) ratio across 90 species pairs.
ContributorsZhu, Ziqi (Author) / Cartwright, Reed A (Thesis advisor) / Taylor, Jay (Committee member) / Wideman, Jeremy (Committee member) / Mangone, Marco (Committee member) / Arizona State University (Publisher)
Created2022
Description
Pollinator populations globally have declined at concerning rates in recent years, which is problematic given that roughly a third of all food production depends on them. Managed honey bee colony losses in particular have alarmed beekeepers and scientists, especially in the United States. Widespread agrochemical use has been implicated as one of the major causes of these colony losses. While the lethal effects of agrochemicals often receive the most attention, sublethal effects can occur at lower doses and can substantially weaken colonies over time. Impaired associative learning ability is a sublethal effect of a number of agrochemicals, and is particularly concerning, as it may hinder the abilities of bees to forage for food or find their way back to the colony. Here, I focus on the fungicide Pristine® (active ingredients: 25.2% boscalid, 12.8% pyraclostrobin), which is sprayed on honey bee-pollinated crops during bloom and is known to poison bee mitochondria at ppm levels. First, I show that Pristine® impairs performance on an associative learning assay in the laboratory. Next, I show that Pristine® alters carbohydrate absorption in honey bees, providing a possible mechanism underlying this impaired learning performance. Finally, I demonstrate that Pristine® interacts with high temperatures to induce homing failure in exposed bees. My results raise concerns that this common fungicide may not be safe for pollinators and will be relevant to policymakers as they make decisions surrounding the regulation of fungicide use in agriculture.
ContributorsDesJardins, Nicole (Author) / Harrison, Jon F (Thesis advisor) / Smith, Brian H (Thesis advisor) / DeGrandi-Hoffman, Gloria (Committee member) / DeNardo, Dale (Committee member) / Pratt, Stephen (Committee member) / Arizona State University (Publisher)
Created2023
Description
Cocaine induces long-lasting changes in mesolimbic ‘reward’ circuits of the brain after cessation of use. These lingering changes include the neuronal plasticity that is thought to underlie the chronic relapsing nature of substance use disorders. Genes involved in neuronal plasticity also encode circular RNAs (circRNAs), which are stable, non-coding RNAs formed through the back-splicing of pre-mRNA. The Homer1 gene family, which encodes proteins associated with cocaine-induced plasticity, also encodes circHomer1. Based on preliminary evidence from shows cocaine-regulated changes in the ratio of circHomer1 and Homer1b mRNA in the nucleus accumbens (NAc), this study examined the relationship between circHomer1 and incentive motivation for cocaine by using different lengths of abstinence to vary the degree of motivation. Male and female rats were trained to self-administer cocaine (0.75 mg/kg/infusion, IV) or received a yoked saline infusion. Rats proceeded on an increasingly more difficult variable ratio schedule of lever pressing until they reached a variable ratio 5 schedule, which requires an average of 5 lever presses, and light and tone cues were delivered with the drug infusions. Rats were then tested for cocaine-seeking behavior in response to cue presentations without drug delivery either 1 or 21 days after their last self-administration session. They were sacrificed immediately after and circHomer1 and Homer1b expression was then measured from homogenate and synaptosomal fractions of NAc shell using RT-qPCR. Lever pressing during the cue reactivity test increased from 1 to 21 days of abstinence as expected. Results showed no group differences in synaptic circHomer1 expression, however, total circHomer1 expression was downregulated in 21d rats compared to controls. Lack of change in synaptic circHomer1 was likely due to trends toward different temporal changes in males versus females. Total Homer1b expression was higher in females, although there was no effect of cocaine abstinence. Further research investigating the time course of circHomer1 and Homer1b expression is warranted based on the inverse relationship between total circHomer1and cocaine-seeking behavior observed in this study.
ContributorsJohnson, Michael Christian (Author) / Neisewander, Janet L (Thesis advisor) / Perrone-Bizzozero, Nora (Thesis advisor) / Mangone, Marco (Committee member) / Arizona State University (Publisher)
Created2022
Description
The splicing of precursor messenger RNAs (pre-mRNAs) plays an essential role in dictating the mature mRNA profiles of eukaryotic cells. Mis-regulation of splicing, due to mutations in pre-mRNAs or in components of the splicing machinery, is associated with many diseases. Therefore, knowledge of pre-mRNA splicing mechanisms is required to understand gene expression regulation during states of homeostasis and disease, and for the development of therapeutic interventions.Splicing is catalyzed by the spliceosome, a dynamic and protein-rich ribozyme composed of five small nuclear ribonucleoproteins (snRNPs) and ~170 auxiliary factors. Early interactions that occur in prespliceosomal complexes formed by the 5′- and 3′-splice-site bound U1 and U2 snRNPs are responsible for committing introns for removal. However, the mechanisms underlying these early interactions remain to be fully characterized for understanding the influence of alternative splicing factors and the impact of recurrent disease-associated mutations in prespliceosomal proteins. The goal of my dissertation research was to delineate the role of the U1 small nuclear RNA (snRNA) during prespliceosome assembly. By applying a cellular minigene reporter assay and a variety of in vitro techniques including cell-free protein expression, UV-crosslinking, electrophoretic mobility shift assays, surface plasmon resonance, and RNA affinity purification, my work establishes critical roles for the U1 snRNA stem-loops 3 (SL3) and 4 (SL4) in formation of intron definition interactions during prespliceosome assembly. Previously, the SL4 of the U1 snRNA was shown to form a molecular bridge across introns by contacting the U2-specific splicing factor 3A1 (SF3A1). I identified the Ubiquitin-like domain of SF3A1 as a non-canonical RNA binding domain responsible for U1-SL4 binding. I also determined a role for the SL3 region of the U1 snRNA in splicing and characterized the spliceosomal RNA helicase UAP56 as an SL3 interacting protein. By knocking-down the SL3- and SL4-interacting proteins, I confirmed that U1 splicing activity in vivo relies on UAP56 and SF3A1 and that their functions are interdependent. These findings, in addition to the observations made using in vitro splicing assays, support a model whereby UAP56, through its interaction with U1-SL3, enhances the cross-intron interaction between U1-SL4 and SF3A1 to promote prespliceosome formation.
ContributorsMartelly, William (Author) / Sharma, Shalini (Thesis advisor) / Mangone, Marco (Thesis advisor) / Gustin, Kurt (Committee member) / Chen, Julian (Committee member) / Arizona State University (Publisher)
Created2021
Description
The partitioning of photosynthates between their sites of production (source) and their sites of utilization (sink) is a major determinant of crop yield and the potential of regulating this translocation promises substantial opportunities for yield increases. Ubiquitous overexpression of the plant type I proton pyrophosphatase (H+-PPase) in crops improves several valuable traits including salt tolerance and drought resistance, nutrient and water use efficiencies, and increased root biomass and yield. Originally, type I H+-PPases were described as pyrophosphate (PPi)-dependent proton pumps localized exclusively in vacuoles of mesophyll and meristematic tissues. It has been proposed that in the meristematic tissues, the role of this enzyme would be hydrolyzing PPi originated in biosynthetic reactions and favoring sink strength. Interestingly, this enzyme has been also localized at the plasma membrane of companion cells in the phloem which load and transport photosynthates from source leaves to sinks. Of note, the plasma membrane-localized H+-PPase could only function as a PPi-synthase in these cells due to the steep proton gradient between the apoplast and cytosol. The generated PPi would favor active sucrose loading through the sucrose/proton symporter in the phloem by promoting sucrose hydrolysis through the Sucrose Synthase pathway and providing the ATP required to maintain the proton gradient. To better understand these two different roles of type I H+-PPases, a series of Arabidopsis thaliana transgenic plants were generated. By expressing soluble pyrophosphatases in companion cells of Col-0 ecotype and H+-PPase mutants, impaired photosynthates partitioning was observed, suggesting phloem-localized H+-PPase could generate the PPi required for sucrose loading. Col-0 plants expressed with either phloem- or meristem-specific AVP1 overexpression cassette and the cross between the two tissue specific lines (Cross) were generated. The results showed that the phloem-specific AVP1-overexpressing plants had increased root hair elongation under limited nutrient conditions and both phloem- and meristem-overexpression of AVP1 contributed to improved rhizosphere acidification and drought resistance. It was concluded that H+-PPases localized in both sink and source tissues regulate plant growth and performance under stress through its versatile enzymatic functions (PPi hydrolase and synthase).
ContributorsLi, Lin (Author) / Park, Yujin (Thesis advisor) / Mangone, Marco (Committee member) / Roberson, Robert (Committee member) / Vermaas, Willem (Committee member) / Arizona State University (Publisher)
Created2022
Description
Glioblastoma (GBM), the most common and aggressive primary brain tumor affecting adults, is characterized by an aberrant yet druggable epigenetic landscape. The Histone Deacetylases (HDACs), a major family of epigenetic regulators, favor transcriptional repression by mediating chromatin compaction and are frequently overexpressed in human cancers, including GBM. Hence, over the last decade there has been considerable interest in using HDAC inhibitors (HDACi) for the treatment of malignant primary brain tumors. However, to date most HDACi tested in clinical trials have failed to provide significant therapeutic benefit to patients with GBM. This is because current HDACi have poor or unknown pharmacokinetic profiles, lack selectivity towards the different HDAC isoforms, and have narrow therapeutic windows. Isoform selectivity for HDACi is important given that broad inhibition of all HDACs results in widespread toxicity across different organs. Moreover, the functional roles of individual HDAC isoforms in GBM are still not well understood. Here, I demonstrate that HDAC1 expression increases with brain tumor grade and is correlated with decreased survival in GBM. I find that HDAC1 is the essential HDAC isoform in glioma stem cells and its loss is not compensated for by its paralogue HDAC2 or other members of the HDAC family. Loss of HDAC1 alone has profound effects on the glioma stem cell phenotype in a p53-dependent manner and leads to significant suppression of tumor growth in vivo. While no HDAC isoform-selective inhibitors are currently available, the second-generation HDACi quisinostat harbors high specificity for HDAC1. I show that quisinostat exhibits potent growth inhibition in multiple patient-derived glioma stem cells. Using a pharmacokinetics- and pharmacodynamics-driven approach, I demonstrate that quisinostat is a brain-penetrant molecule that reduces tumor burden in flank and orthotopic models of GBM and significantly extends survival both alone and in combination with radiotherapy. The work presented in this thesis thereby unveils the non-redundant functions of HDAC1 in therapy- resistant glioma stem cells and identifies a brain-penetrant HDACi with higher selectivity towards HDAC1 as a potent radiosensitizer in preclinical models of GBM. Together, these results provide a rationale for developing quisinostat as a potential adjuvant therapy for the treatment of GBM.
ContributorsLo Cascio, Costanza (Author) / LaBaer, Joshua (Thesis advisor) / Mehta, Shwetal (Committee member) / Mirzadeh, Zaman (Committee member) / Mangone, Marco (Committee member) / Paek, Andrew (Committee member) / Arizona State University (Publisher)
Created2022