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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Vitamin D, a bioactive lipid and essential nutrient, is obtained by humans through either endogenous synthesis in response to UV light exposure or via nutritional intake. Once activated to its hormonal form, vitamin D binds to and activates the nuclear vitamin D receptor (VDR). Activation of VDR is known to modulate gene transcription in vitamin D target tissues such as kidney, colon, and bone; however, less is known about the ability of VDR to respond to "nutritional modulators". One such potential VDR modulator is resveratrol, a plant-derived polyphenol and potent antioxidant nutrient that also functions as a chemopreventative. Resveratrol is known to activate sirtuin-1, a deacetylase enzyme with potential anti-aging properties. This study explores the potential for resveratrol, an anticancer nutraceutical, to upregulate VDR activity through its effector protein, sirtuin-1. Furthermore, due to its putative interactions with several intracellular signaling pathways, klotho has been proposed as an anti-aging protein and tumor suppressor gene, while the Wnt/β-catenin signaling pathway drives enhanced cellular proliferation leading to numerous types of cancers, especially colorectal neoplasia. Thus, the ability of klotho to cooperate with vitamin D to inhibit oncogenic β-catenin signaling was also analyzed. The experiments and resultant data presented in this thesis explore the potential role of VDR as a physiologically relevant nutritional sensor in human cells. This novel study reveals the importance of nutrient modulation of the VDR system by vitamin D and resveratrol and how this might represent a molecular mechanism that is responsible for the putative anti-cancer actions of vitamin D. Furthermore, this study enhances our understanding of how vitamin D/VDR and resveratrol interact with klotho and how this interaction affects β-catenin signaling to mitigate oncogenic growth and differentiation. This works demonstrates that the vitamin D hormone serves as a likely chemopreventive agent for various types of cancers through control of anti-oxidation and cellular proliferation pathways via its nuclear receptor. Our results also indicate the potential for resveratrol, an anticancer nutraceutical, to upregulate VDR activity through SIRT1. Furthermore, the novel data presented in this work illustrate that klotho, an anti-aging protein, cooperates with vitamin D to synergistically inhibit oncogenic β-catenin signaling. Ultimately, this study enhances our understating of the molecular pathways that underpin nutritional chemoprevention, and how modulation of these pathways via dietary intervention may lead to advances in public health strategies to eventually curb carcinogenesis.
ContributorsKhan, Zainab (Author) / Jurutka, Peter (Thesis director) / Hackney Price, Jennifer (Committee member) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Rainbowfish, Melanotaenia splendida, are a common freshwater species in tropical regions of the world. They are members of the Atheriniformes (Atherinomorpha), the silverside fishes, which are known for some unusual feeding behaviors. Their close relatives, the Cypriniformes, such as mollies, guppies, and mosquitofish, are well studied and exhibit innovative morphologies associated with feeding. The third member of the Atherinomorphs, the Beloniformes, contains the recognizably odd needlefish, halfbeaks, and flying fishes. As a group, it is fair to say that the Atherinomorpha contain some pretty unusual fishes. The purpose of this project was to gain a further understanding of the unique feeding kinematics of Atheriniform fishes using the rainbowfish as an exemplar species. Feeding kinematics were quantified using high speed video recording unrestrained feeding events. Three feeding events from five individuals were analyzed frame by frame, from the time of the mouth opening to mouth closing. The X,Y coordinates of seven specific points were used to calculate the following kinematic variables: cranial elevation, gape distance, premaxillary protrusion, and hyoid depression. The contribution of cranial elevation to the strike was inconsistent. At times the fish raised the head as they expanded the mouth for prey capture, and at other times they did not. Cranial elevation is theoretically important for expanding the head during suction prey capture. Hyoid depression was more consistent, and clearly contributed to expansion of the head elements. Premaxillary protrusion contributed strongly to the event, and the jaws are closed with the premaxilla still protruded, facilitating a ‘nipping’ style jaw closure. A nipping style of prey capture is much like the Cyprinodontiforms, however, in rainbowfish, the event was quicker, and appeared to rely heavily on suction. We used both cleared and stained specimens and CT scans to investigate the underlying morphology of rainbowfish. These images revealed nearly microscopic teeth on the exterior of the jaws, and other features associated with feeding on highly elusive prey (i.e. prey that are mobile and likely to be able to escape predation). Further examination revealed a surprisingly well developed set of pharyngeal jaws, secondary to the oral jaws. The structure of the pharyngeal jaws suggested that most of the prey processing occurred within the pharynx.
ContributorsLerma, Sarahi (Author) / Ferry, Lara A. (Thesis director) / Hackney Price, Jennifer (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor) / School of Social and Behavioral Sciences (Contributor)
Created2015-05
Description
Colchicine is a chemical known for inhibiting mitosis during eukaryotic cellular reproduction by halting the tubulin formation necessary for the division of the chromosomes. The meristem is the primary source of mitosis in developing flowering plants, and it was the focus of our research to determine if the hindrance of mitosis would interfere with the production of capsaicinoids within pungent pepper plants. Moruga Scorpion peppers have one of the world's highest concentration of capsaicinoids with Scoville Heat Units (SHU) averaging 1.2 million SHU (Bannister, 2012). The highest concentration of these capsaicinoids are within the placental and endocarp regions of the fruit, which are the primary location for capsaicinoid biosynthesis (Aza-Gonzalez & Nunez-Palenius, 2010). Hindering mitosis from the earliest stage of development could lead to phenotypic abnormalities within those placental and endocarp regions, quite possibly through the mechanism of the induced polyploidy. In many cases, this polymerization interference is beneficial in cultivating plants with characterized polyploidy due to its desired increased size of fruits and leaves. Due to the lethal nature of colchicine, there is threshold of effectiveness where it may induce polyploidy or it may result in fatality. This first stage of this research sought to determine which lethal dose was required to elicit a polyploid response or lead to seed unviability. The second stage was analyzing capsaicin concentration within the fruit of the mature dosed plants to determine whether there was an effect on the capsaicinoids, and whether polyploidy played a role in those effects. The final inspection of this research was in germinating the seeds from the hottest F1 pepper that had developed the fruit the slowest of all the doses, and determining whether there were any effects on the germination or seedling development.
ContributorsKeppler, Lydia Jacqueline (Author) / Cahill, Thomas (Thesis director) / Sweat, Ken G. (Committee member) / Hackney Price, Jennifer (Committee member) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Since its isolation from a rhesus monkey in the Zika forest of Uganda in 1947, Zika virus (ZIKV) has spread into many parts of the world, causing major epidemics, notably in the Americas and some parts of Europe and Asia. The flavivirus ZIKV is primarily transmitted to humans via the bite of infectious adult female Aedes mosquitoes. In the absence of effective treatment or a safe and effective vaccine against the disease, control efforts are focused on effective vector management to reduce the mosquito population and limit human exposure to mosquito bites. The work in this thesis is based on the use of a mathematical model for gaining insight into the transmission dynamics of ZIKV in a population. The model, which takes the form of a deterministic system of nonlinear differential equations, is rigorously analyzed to gain insight into its basic qualitative features. In particular, it is shown that the disease-free equilibrium of the model is locally-asymptotically stable whenever a certain epidemiological quantity (known as the reproduction number, denoted by R0) is less than unity. The epidemiological implication of this result is that a small influx of ZIKV-infected individuals or vectors into the community will not generate a large outbreak if the anti-ZIKV control strategy (or strategies) adopted by the community can reduce and maintain R0 to a value less than unity. Numerical simulations of the model, using data relevant to ZIKV transmission dynamics in Puerto Rico, shows that a control strategy that solely focuses on killing immature mosquitoes (using highly efficacious larvicides) can lead to the elimination of ZIKV if the larvicide coverage (i.e., proportion of breeding sites treated with larvicides) is high enough (over 90%). Such elimination is also feasible using a control strategy that solely focuses on the use of insect repellents (as a means of personal protection against mosquito bites) if the coverage level of the insect repellent usage in the community is high enough (at least 70%). However, it is also shown that although the use of adulticides (i.e., using insecticides to kill adult mosquitoes) can reduce the reproduction number (hence, disease burden), it fails to reduce it to a value less than unity, regardless of coverage level. Thus, unlike with the use of larvicide-only or repellent-only strategies, the population-wide implementation of an adulticide-only strategy is unable to lead to ZIKV elimination. Finally, it is shown that the combined (integrated pest management) strategy, based on using all three aforementioned strategies, is the most effective approach for combatting ZIKV in the population. In particular, it is shown that even a moderately-effective level of this strategy, which entails using only 50% coverage of both larvicides and adulticides, together with about 45% coverage for a repellent strategy, will lead to ZIKV elimination. This moderately-effective combined strategy seems attainable in Puerto Rico.
ContributorsUrcuyo, Javier (Author) / Gumel, Abba (Thesis director) / Hackney Price, Jennifer (Committee member) / School of Mathematical and Natural Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05