Matching Items (11)
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- All Subjects: Vitamin D
- All Subjects: Urbanization
- Creators: School of Mathematical and Natural Sciences
Description
Vitamin D, Klotho, and FOXO3 have all been linked to have anti-aging and anti-cancerous effects as separate pathways. Specifically, mice with knockout Klotho in their genes have displayed signs of premature aging, humans who are vitamin D deficient have been shown to develop cardiovascular disease and cognitive impairments, and those who have displayed overexpression of FOXO3 have shown to have a longer lifespan. Here we took each pathway and attempted to formulate a feedback mechanism loop linking all three separate pathways. We propose that vitamin D levels modulate klotho activity, including the expression of the s-klotho and m-klotho isoforms. Moreover, the anti-oxidation transcription factor FOXO3 is also thought to participate in crosstalk with VDR signaling. Through the connection between 1,25D and Klotho, we probed at their interactions with FOXO3 signaling in kidney and colon cells, and proposed that vitamin D and klotho may reduce oxidative stress and suppress the onset of epithelial cancers through it effects on FOXO3. Results showed a strong support for the cooperation between FOXO3 and 1,25D to stimulate both superoxide dismutase (a FOXO3 response element) and XDR3/ROC (vitamin D response elements). This cooperation was mostly seen in embryonic kidney cells (HEK293) and not in the colon cancer cells (HCT116), which has led to the conclusion that vitamin D and FOXO3 cooperation mainly occurs in kidney tissue and/or in tissue that is not yet been overtaken by cancer. Differences in the Klotho isoforms were seen when measuring FOXO3 and vitamin D activity, but experiments manipulating other components will need to be conducted to further understand the function of Klotho in maintaining reactive oxygenated species levels.
ContributorsSandoval, Ruby (Author) / Jurutka, Peter (Thesis director) / Sandrin, Todd R. (Committee member) / Heck, Michael (Committee member) / School of Social and Behavioral Sciences (Contributor) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Desert ecosystems are one of the fastest urbanizing areas on the planet. This rapid shift has the potential to alter the abundances and species richness of herbivore and plant communities. Herbivores, for example, are expected to be more abundant in urban desert remnant parks located within cities due to anthropogenic activities that concentrate food resources and reduce native predator populations. Despite this assumption, previous research conducted around Phoenix has shown that top-down herbivory led to equally reduced plant biomass. It is unclear if this insignificant difference in herbivory at rural and urban sites is due to unaltered desert herbivore populations or altered activity levels that counteract abundance differences. Vertebrate herbivore populations were surveyed at four sites inside and four sites outside of the core of Phoenix during fall 2014 and spring 2015 in order to determine whether abundances and richness differ significantly between urban and rural sites. In order to survey species composition and abundance at these sites, 100 Sherman traps and 8 larger wire traps that are designed to attract and capture small vertebrates such as mice, rats, and squirrels, were set at each site for two consecutive trap nights. Results suggest that the commonly assumed effect of urbanization on herbivore abundances does not apply to small rodent herbivore populations in a desert city, as overall small rodent abundances were statistically similar regardless of location. Though a significant difference was not found for species richness, a significant difference between small rodent genera richness at these sites was observed.
ContributorsAlvarez Guevara, Jessica Noemi (Co-author) / Ball, Becky A. (Co-author, Thesis director) / Hall, Sharon J. (Co-author) / Bateman, Heather (Committee member) / School of Sustainability (Contributor) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
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
In recent years, ecologists have begun to study the effects of urbanization on species diversity. While urban areas generally suffer decreased biodiversity, some species, termed “urban exploiters”, not only live in the city but depend on urban resources to thrive. It is hypothesized that urban exploiters may succeed in part due to phenotypic plasticity, in which organisms rapidly adjust their physiology or behavior to adapt to novel environmental contexts. In the city, it may be adaptive to display thermal plasticity, as the urban heat island effect caused by concrete and asphalt infrastructure prevents cooling at night. In this study, we observed the decorated cricket Gryllodes sigillatus, an invasive urban exploiter found in metropolitan Phoenix, in two separate experiments. We hypothesized that heat tolerance and activity are both plastic traits in this species. In Experiment 1, we predicted that knock-down time, a measure of heat tolerance, would be negatively affected by acclimation to a laboratory environment. Our results suggest that heat tolerance is affected by recent thermal regimes and that laboratory acclimation decreases knock-down time. In Experiment 2, we predicted that activity would increase with temperature until a point of extreme heat, at which point activity would decline. Statistical analysis for the second experiment reveals that activity decreases at 33°C, a natural urban extreme. This suggests either that 33°C is a thermal limit to physiology or that G. sigillatus is able to alter its behavior to exploit local thermal heterogeneity.
ContributorsVannan, Annika (Author) / Johnson, James Chadwick (Thesis director) / Angilletta, Michael (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor) / School of Social and Behavioral Sciences (Contributor)
Created2015-05
Description
The spread of urbanization leads to habitat fragmentation and deterioration and changes the composition of ecosystems for species all over the world. Different groups of organisms are impacted differently, and insects have experienced loss in diversity and abundance due to changing environmental factors. Here, I collected seed beetles across 12 urban and rural sites in Phoenix, Arizona, to analyze the effects of urbanization and habitat variation on beetle diversity and abundance. I found that urbanization, host tree origin, and environmental factors such as tree diversity and density had no impact on overall beetle diversity and abundance. Beetles were found to have higher density on hosts with a higher density of pods. In assessing individual beetle species, some beetles exhibited higher density in rural sites with native trees, and some were found more commonly on nonnative tree species. The observed differences in beetle density demonstrate the range of effects urbanization and environmental features can have on insect species. By studying ecosystem interactions alongside changing environments, we can better predict the role urbanization and human development can have on different organisms.
ContributorsPaduano, Gabrielle (Author) / Savalli, Udo (Thesis director) / Sweat, Ken (Committee member) / Division of Teacher Preparation (Contributor) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The diagnosis of irritable bowel syndrome (IBS) is currently based on symptomatic criteria that exclude other conditions affecting the gastrointestinal tract, such as celiac disease, food allergies, and infections. The absence of appropriate diagnostic and therapeutic approaches for IBS places a significant burden on the patient and the health care system due to direct and indirect costs of care. Limitations associated with the application of symptomatic criteria include inappropriate use and/or intrinsic limitations such as the population to which these criteria are applied. The lack of biomarkers specific for IBS, non-specific abdominal symptoms, and considerable variability in the disease course creates additional uncertainty during diagnosis. This project involved screening tissue samples from patients with verified IBS to identify gene expression-based biomarkers associated with IBS. Through validation of microarray gene chip data on the tissue samples using PCR, it was determined that a number of genes within the diseased IBS patient tissue samples were differentially expressed in comparison to the healthy subjects. These findings could potentially lead to the diagnosis of IBS on the basis of a genetic "fingerprint".
ContributorsHockley, Maryam (Author) / Jurutka, Peter (Thesis director) / Sandrin, Todd (Committee member) / Zhang, Lin (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor)
Created2013-12
Description
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that afflicts more than 20% of the population in the United States. Symptoms include mild to severe abdominal discomfort accompanied by a change in stool character and form ranging from constipation to diarrhea. Additionally, IBS is associated with secondary effects including depression, anxiety, poor quality of life, insomnia and sexual dysfunction. Despite the known association of secondary effects, patients are often tested for potential illnesses that share similar pathological symptoms. This process can be costly and protracted and yet not deliver a completely accurate diagnosis. The aim of this research is to identify gene expression-based biological signatures and unique biomarkers for the detection of IBS. Through the use of quantitative polymerase chain reaction (qPCR), comparison of pooled samples of non-IBS patient-derived RNA were used to identify differentially expressed genes in patients with IBS. Data obtained from preliminary DNA microarray analysis demonstrated a degree of success in differentiating between IBS and asymptomatic patients. Additional comprehensive DNA microarray analyses have led to the identification of a series of 858 differentially expressed genes, including genes associated with serotonin metabolism, which may characterize the IBS pathological state. The microarray results were screened using a combination of gene ontological analysis and qPCR. Real-time PCR revealed repressed levels of tryptophan hydroxylase (TPH1), an enzyme involved in the rate- limiting step in serotonin biosynthesis, in IBS patients relative to controls. Lower concentrations of serum 25(OH)D were also observed among the IBS cohort relative to asymptomatic patients, especially among IBS-D subtype. Vitamin D was shown to modulate differentially expressed genes in IBS patients, suggesting that IBS pathophysiology may involve vitamin D insufficiency and/or an irregularity in serotonin metabolism. Additional qPCR analysis of 32 differentially expressed genes in IBS patients identified 7 putative genetic biomarkers proposed for a potential IBS diagnostic panel. Based on the quality of these results, we may be able to develop, test, and market a diagnostic kit for IBS.
ContributorsGrozic, Aleksandra (Author) / Jurutka, Peter (Thesis director) / Sandrin, Todd (Committee member) / Foxx-Orenstein, Amy (Committee member) / School of Mathematical and Natural Sciences (Contributor) / School of Social and Behavioral Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
Description
Urban Heat Island (UHI) is considered as one of the major problems in the 21st century posed to human beings as a result of urbanization and industrialization of human civilization. The large amount of heat generated from urban structures, as they consume and re-radiate solar radiations, and from the anthropogenic heat sources are the main causes of UHI. The two heat sources increase the temperatures of an urban area as compared to its surroundings, which is known as Urban Heat Island Intensity (UHII). The problem is even worse in cities or metropolises with large population and extensive economic activities. The estimated three billion people living in the urban areas in the world are directly exposed to the problem, which will be increased significantly in the near future. Due to the severity of the problem, vast research effort has been dedicated and a wide range of literature is available for the subject. The literature available in this area includes the latest research approaches, concepts, methodologies, latest investigation tools and mitigation measures. This study was carried out to review and summarize this research area through an investigation of the most important feature of UHI. It was concluded that the heat re-radiated by the urban structures plays the most important role which should be investigated in details to study urban heating especially the UHI. It was also concluded that the future research should be focused on design and planning parameters for reducing the effects of urban heat island and ultimately living in a better environment.
ContributorsRizwan, Ahmed Memon (Author) / Dennis, Leung Y.C. (Author) / Liu, Chunho (Author)
Created2007-09-27
Description
The ever-increasing importance of cancer and neurodegenerative diseases continues to grow as populations across the world are affected by death and aging. The vitamin A (RXR) and vitamin D (VDR) receptor pathways offer promising potential to aid in treatment of cancer and Alzheimer’s disease. This thesis discusses the potential application of novel analogs of Bexarotene (RXR agonist), MeTC7 (a new potent VDR antagonist), and vitamin D as possible therapeutics for cancer and Alzheimer’s disease.
ContributorsHong, Jennifer (Author) / Jurutka, Peter (Thesis director) / Wagner, Carl (Committee member) / Marshall, Pamela (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor)
Created2023-05
Description
With increasing urbanization, organisms face a myriad of novel ecological challenges. While the eco-evolutionary dynamics of urbanization are currently receiving a great deal of attention, the effect of urban disturbance on the microbiome of urban organisms is relatively unstudied. Indeed, studies of the microbiome may illuminate the mechanisms by which some species thrive after urbanization (pest implications), while other species go locally extinct (biodiversity implications). We investigated the gut microbiome of the Western black widow spider (Latrodectus hesperus). L. hesperus is an ideal model system as they are a pest species of medical importance in urban ecosystems, often forming dense urban infestations relative to the sparse populations found in their native Sonoran Desert. To gain insight into the composition of the microbiome in L. hesperus and its potential function, we sampled 4 urban, 4 desert, and 2 laboratory-reared spiders, and high-throughput sequencing of the 16S rRNA V4 region was used to investigate the diversity of gut microbiota. Dominant bacterial phyla across all samples were Firmicutes, Proteobacteria, and Actinobacteria. While desert widows showed more gut microbial diversity than urban widows, the difference was not statistically significant. The relative abundance of taxonomic classes Blastocatellia, Acidobacteriia, and Thermoleophilia detected in desert spiders was especially higher than those in urban and laboratory-reared spiders. However, urban spiders had a higher relative abundance of taxonomic class Actinomycetia. Differences in widow gut microbiome diversity improves our understanding of how features unique to a habitat, like prey diversity and soil microbes, may be shaping their microbiome. Additionally, this work further highlights the impact urbanization has on biodiversity loss, which indirectly develops a new biomarker for differentiating between urban and desert black widow spiders based on their gut microbiome.
ContributorsAsrari, Hasti (Author) / Johnson, Chad (Thesis director) / Sandrin, Todd (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor) / School of Life Sciences (Contributor)
Created2022-12