Theses and Dissertations
This collection includes both ASU Theses and Dissertations, submitted by graduate students, and the Barrett, Honors College theses submitted by undergraduate students.
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- Creators: Deviche, Pierre
- Creators: Jasbi, Paniz
Description
Metabolomics focuses on the study of metabolic changes occurring in varioussystems and utilizes quantitative and semi-quantitative measurements of multiple metabolites in parallel. Mass spectrometry (MS) is the most ubiquitous platform in this field, as it provides superior sensitivity regarding measurements of complex metabolic profiles in biological systems. When combined with MS, multivariate statistics and advanced machine learning algorithms provide myriad opportunities for bioinformatics insights beyond simple univariate data comparisons. In this dissertation, the application of MS-based metabolomics is introduced with an emphasis on biomarker discovery for human disease detection. To advance disease diagnosis using MS-based metabolomics, numerous statistical techniques have been implemented in this research including principal component analysis, factor analysis, partial least squares-discriminant analysis (PLS-DA), orthogonal PLS-DA, random forest, receiver operating characteristic analysis, as well as functional pathway/enzyme enrichment analyses. These approaches are highly useful for improving classification sensitivity and specificity related to disease-induced biological variation and can help identify useful biomarkers and potential therapeutic targets. It is also shown that MS-based metabolomics can distinguish between clinical and prodromal disease as well as similar diseases with related symptoms, which may assist in clinical staging and differential diagnosis, respectively. Additionally, MS-based metabolomics is shown to be promising for the early and accurate detection of diseases, thereby improving patient outcomes, and advancing clinical care. Herein, the application of MS methods and chemometric statistics to the diagnosis of breast cancer, coccidioidomycosis (Valley fever), and senile dementia (Alzheimer's disease) are presented and discussed. In addition to presenting original research, previous efforts in biomarker discovery will be synthesized and appraised. A Comment will be offered regarding the state of the science, specifically addressing the inefficient model of repetitive biomarker discovery and the need for increased translational efforts necessary to consolidate metabolomics findings and formalize purported metabolic markers as laboratory developed tests. Various factors impeding the translational throughput of metabolomics findings will be carefully considered with respect to study design, statistical analysis, and regulation of biomedical diagnostics. Importantly, this dissertation will offer critical insights to advance metabolomics from a scientific field to a practical one including targeted detection, enhanced quantitation, and direct-to-consumer considerations.
ContributorsJasbi, Paniz (Author) / Johnston, Carol S (Thesis advisor) / Gu, Haiwei (Thesis advisor) / Lake, Douglas F (Committee member) / Sweazea, Karen (Committee member) / Tasevska, Natasha (Committee member) / Arizona State University (Publisher)
Created2022
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
Description
Reproduction is energetically costly and seasonal breeding has evolved to capitalize on predictable increases in food availability. The synchronization of breeding with periods of peak food availability is especially important for small birds, most of which do not store an extensive amount of energy. The annual change in photoperiod is the primary environmental cue regulating reproductive development, but must be integrated with supplementary cues relating to local energetic conditions. Photoperiodic regulation of the reproductive neuroendocrine system is well described in seasonally breeding birds, but the mechanisms that these animals use to integrate supplementary cues remain unclear. I hypothesized that (a) environmental cues that negatively affect energy balance inhibit reproductive development by acting at multiple levels along the reproductive endocrine axis including the hypothalamus (b) that the availability of metabolic fuels conveys alterations in energy balance to the reproductive system. I investigated these hypotheses in male house finches, Haemorhous mexicanus, caught in the wild and brought into captivity. I first experimentally reduced body condition through food restriction and found that gonadal development and function are inhibited and these changes are associated with changes in hypothalamic gonadotropin-releasing hormone (GnRH). I then investigated this neuroendocrine integration and found that finches maintain reproductive flexibility through modifying the release of accumulated GnRH stores in response to energetic conditions. Lastly, I investigated the role of metabolic fuels in coordinating reproductive responses under two different models of negative energy balance, decreased energy intake (food restriction) and increased energy expenditure (high temperatures). Exposure to high temperatures lowered body condition and reduced food intake. Reproductive development was inhibited under both energy challenges, and occurred with decreased gonadal gene expression of enzymes involved in steroid synthesis. Minor changes in fuel utilization occurred under food restriction but not high temperatures. My results support the hypothesis that negative energy balance inhibits reproductive development through multilevel effects on the hypothalamus and gonads. These studies are among the first to demonstrate a negative effect of high temperatures on reproductive development in a wild bird. Overall, the above findings provide important foundations for investigations into adaptive responses of breeding in energetically variable environments.
ContributorsValle, Shelley (Author) / Deviche, Pierre (Thesis advisor) / McGraw, Kevin (Committee member) / Orchinik, Miles (Committee member) / Propper, Catherine (Committee member) / Sweazea, Karen (Committee member) / Arizona State University (Publisher)
Created2018
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
This study is an exploration of the nutritional physiology of Gambel's quail, Callipepla gambelii, in terms of the comparison of rural and urban area populations of this gallinaceous species, and the employment of in situ study by design. The health of quail populations is of interest as a resource to recreational enthusiasts, hunters, stakeholders, as well as agencies charged with their management. Quail are the only resident small avian game species known to be native to the southwest that is depended upon by management agencies for recreational opportunities. The condition of the Gambel's quail populations determine regulatory actions with respect to recreational quailing opportunities and these quail represent a species which shows adjustment to human expansion. The combination of morphologic, physical, and plasma nutrient data gathered from samples during this study are hypothesized to show a difference between rural and urban populations of C. gambelii. The hypothesis is that urban quail will display morphological differences, and nutrient differences that are crucial to quail fitness, therefore, potential selective differences. Ground and ambient air temperatures are hypothesized to be higher in urban areas andthus these measurements were taken for site comparison. Plasma nutrient concentrations between rural and urban populations of adult male Gambel's quail were compared for potential existing variations in nutrition. The blood nutrient assays are expected to display increased plasma concentrations of constituents such as glucose, lipids, and proteins, which are known to be involved in growth, reproductive success, and general fitness in the urban quail populations. Morphological data was collected to examine the potential differences in the physical attributes of the sampled quail. A fitness advantage in male Gambel's quail living within urban areas is hypothesized to be associated with differences in plasma nutrients and morphology. The potentially differing plasma nutrients in samples of the C. gambelii in urban versus rural environments is believed to be affected by, and to indicate, differing nutrient availability. Body mass and length, chest circumference as well as skin temperatures were measured to assess potential differences in these outward physical attributes. The urban quail are hypothesized to have reproductive and/or natural selective advantages where their measured morphology may show physical size differences. Differences in the physical attributes of the male Gambel's quail that live in urban areas may be supported through measured morphologic attributes.
ContributorsFunk, Alexander L (Author) / Deviche, Pierre (Thesis director) / Sweazea, Karen (Committee member) / Hutton, Pierce (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12