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- Creators: Barrett, The Honors College
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
Women are now living longer than ever before, yet the age of spontaneous menopause has remained stable. This results in an increasing realization of the need for an effective treatment of cognitive and physiological menopausal and post-menopausal symptoms. The most common estrogen component of hormone therapy, conjugated equine estrogens (CEE; Premarin) contains many estrogens that are not endogenous to the human body, and that may or may not be detrimental to cognition (Campbell and Whitehead, 1977; Engler-Chiurazzi et al., 2011; Acosta et al., 2010). We propose the use of a novel treatment option in the form of a naturally-circulating (bioidentical) estrogen called estriol. Due to estriol’s observed positive effects on synaptic functioning and neuroprotective effects in the hippocampus (Ziehn et al., 2012; Goodman et al., 1996), a brain structure important for spatial learning and memory, estriol is promising as a hormone therapy option that may attenuate menopausal- and age- related memory decline. In the current study, we administered one of the three bioidentical estrogens (17β-Estradiol, 4.0 µg/day; Estrone, 8.0 µg/day; Estriol, 8.0 µg/day) or the vehicle polyethylene glycol by subcutaneous osmotic pump to ovariectomized Fisher-344 rats. We compared these groups to each other using a battery of spatial learning tasks, including the water radial-arm maze (WRAM), Morris water maze (MM), and delayed-match-to-sample maze (DMS). We found that all estrogens impaired performance on the WRAM compared to vehicle, while 17β-estradiol administration improved overnight forgetting performance for the MM. The estriol group showed no cognitive enhancements relative to vehicle; however, there were several factors indicating that both our estriol and estradiol doses were too high, so future studies should investigate whether lower doses of estriol may be beneficial to cognition.
ContributorsStonebarger, Gail Ashley (Author) / Bimonte-Nelson, Heather (Thesis director) / Knight, George (Committee member) / Engler-Chiurrazzi, Elizabeth (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor)
Created2015-05
Description
Hormone therapy (HT) containing 17beta-estradiol (E2) can greatly reduce physiological symptoms associated with declines in ovarian hormones that are seen with menopause. HT containing E2 has also been shown to play a beneficial role in cognitive function. There is discrepancy, however, surrounding which dose of E2 is the most optimal for cognition. A previous rodent behavioral study in our laboratory evaluated the effects of different doses of E2 on spatial memory performance, and results indicated that rats treated with a low E2 dose (0.3 g E2) made fewer working memory incorrect (WMI) errors, indicating enhanced spatial memory performance, compared to vehicle (0.1ml sesame oil)- and high E2 (3.0 g E2)- treated groups. This finding warranted the present investigation with the overarching aim to evaluate underlying neuromolecular mechanisms that may be modulating these cognitive effects. Both the insulin-like growth factor-1 receptor (IGF1-R) and extracellular regulated kinase (Erk) 2 have been observed to mediate E2-induced memory enhancements. We used the Western Blot to measure IGF1-R and activated Erk1/2 expression in brain regions involved in learning and memory, including the dorsal hippocampus, ventral CA1/CA2 hippocampus, entorhinal cortex, and perirhinal cortex. Results demonstrated a linear relationship between IGF1-R expression and administered E2 dose in the perirhinal cortex, whereby IGF1-R expression increased as the dose of E2 increased. Additionally, in the perirhinal cortex, IGF1-R expression tended to increase as activated Erk1 increased for all treatment groups. Further, number of WMI errors tended to decrease as IGF1-R expression and activated Erk1 expression in the perirhinal cortex tended to increase in the low E2 treatment group. Collectively, these findings suggest a downstream-dependent relationship between IGF1-R and activated Erk1 in the perirhinal cortex that may be contributing to the enhancements in spatial memory performance observed in animals in the low E2 treatment group. These findings are a crucial piece in the greater understanding of what underlying molecular mechanisms may be modulating a cognitively beneficial dose of E2, and further contribute to the search for a HT that would be beneficial for cognition in menopausal women.
ContributorsNeeley, Rachel Elizabeth (Author) / Bimonte-Nelson, Heather (Thesis director) / George, Andrew (Committee member) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Abstract Older adults and people with disabilities are two unique populations, though they intersect in their need for mobility options that are often not met by traditional transportation services. There is consensus that the government should provide assistance for older adults and people with disabilities to achieve and maintain independence. However, the challenge lies in addressing the many forms of mobility inequity. Population projections for the twenty-first century have sparked interest in the rights of these two populations. As the population of the United States of America ages, supporting the mobility of seniors and individuals with disabilities will become imperative to maintaining their quality of life. One existing federal grant, Section 5310: Enhanced Mobility for Seniors and Individuals with Disabilities (49 U.S.C. 5310) provides formula funding for services that provide transportation options to older adults and people with disabilities. While the 5310 program provides crucial funding to non-profits and government agencies to support mobility options for older adults and people with disabilities, it does not address the full scope of mobility issues faced by these two communities. This thesis project provides a thorough analysis of this grant from the federal legislation it is founded on, to the local administration of this grant as applied by the Maricopa Association of Governments (MAG). Finally, this thesis looks at emerging technology with the potential to revolutionize mobility, along with sobering historical context of the barriers faced older adults and people with disabilities.
ContributorsValencia, Martin J. (Author) / Kelley, Jason (Thesis director) / Voorhees, Matthew (Committee member) / School of Sustainability (Contributor) / School of Geographical Sciences and Urban Planning (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Abstract Latent fingerprints are a critical component of the evidence that is captured and analyzed from crime scenes and presented for convictions in court. Although fingerprint science has been used for many years in forensics, it is not without many criticisms and critiques from those that believe it is too subjective. Researchers from many disciplines have tried to refute this claim by completing experiments that would eventually lead to a fingerprint aging technique as well as providing statistical models and mathematical support. In this literature review, the research that has been widely published and talked about in this field was reviewed and analyzed to determine what aspects of the experiments are benefitting the study of degradation. By carefully combing through the methods and results of each study, it can be determined where future focuses should be and what disciplines need to be exploited for knowledge. Lastly, an important aspect of the experiments in recent years have depended on the collaboration with statistics so this evidence was examined to identify what models are realistic in determining error rates and likelihood ratios to support latent fingerprint evidence in court. After a thorough review, it is seen that although large strides have been taken to study the degradation of fingerprints, the day where fingerprints will be able to be definitively aged may be ways away. The current experiments have provided methods such as three-dimensional and visual parameters that could potentially find the solution, but also uncovered methods such as immunolabeling and chemical composition that face major challenges. From the statistically point of view, researchers are very close in developing equations that exploit the likelihood ratios of similarity and even calculate the various possible error rates. The evidence found in this review shows that science is one step closer to the age determination of fingerprints.
ContributorsPorter, Lindsey Jordan (Author) / De Alcaraz Fossoul, Josep (Thesis director) / Mancenido, Michelle (Committee member) / School of Criminology and Criminal Justice (Contributor) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Sarcopenia, a disease defined by age-related muscle loss and function, impacts each and every one of us as we age. Medical research over the past 40 years has identified dozens of factors that contribute to Sarcopenia, including, hormonal changes, deficiencies in nutrition, denervation, changes in physical activity and diseases. Developing effective therapeutic treatments for Sarcopenia is dependent on identifying the mechanisms by which these factors affect muscle loss and understanding the interrelationship of these mechanisms. I conducted my research by compiling and analyzing several previous studies on many different mechanisms that contribute to Sarcopenia. Of these mechanisms, I determined the most significant mechanisms and mapped them out on a visual presentation. In addition to the contributing factors listed above, I found that dysregulated cell signaling, mitochondrial abnormalities, impaired autophagy/protein regulation, altered nitric oxide production, and systemic inflammation all contribute to Sarcopenia. Their impact on skeletal muscle is manifested by reduced satellite function, reduced regenerative capacity, loss of muscle mass, accumulation of damaged products, and fibrosis. My research clearly demonstrated that there was not a one-to-one correlation between factors and specific pathological characteristics of Sarcopenia. Instead, factors funneled into a discrete number of cellular processes, including cell proliferation, protein synthesis, and autophagy and apoptosis. Based on my findings, the overall cause of Sarcopenia appears to be a loss of balance between these pathways. The results of my thesis indicate that Sarcopenia is a multifactorial disorder, and therefore, effective therapy should consist of those that prevent necrosis associated with autophagy and apoptosis.
ContributorsSmith, Cameron Isaiah (Co-author) / Rawls, Alan (Co-author, Thesis director) / Wilson-Rawls, Jeanne (Committee member) / School of Life Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
As one of the first attempts to research multimedia platforms for older adults when learning an online photo-editing software, this study examined whether an audio only, a text only, or a combination of an audio and text tutorial would be the most effective teaching method. Elderly adults aged 65 and older (N-45) were randomly assigned to one of the three conditions. They first went through a training phase that utilized their assigned condition to teach five tasks within the photo-editing program, and they were then tested on how well they learned these tasks as well as a transfer task. It was predicted that the multimedia condition would increase learning efficiency, produce more successes in the transfer task, and decrease cognitive load compared to the two unimodal conditions. The multimedia condition (text and audio) had no significant effect on transfer task successes or decreases in cognitive load compared to the unimodal conditions (text only and audio only). The multimedia condition, however, did produce significantly less errors on Tasks 2, 4, and 5 than the unimodal conditions. This suggests that redundancy principles may play an important role when designing learning platforms for elderly users, and that age needs to be considered as an additional factor during the technological design process.
ContributorsSwieczkowski, Hannah Elizabeth (Author) / Atkinson, Robert (Thesis director) / Chavez, Helen (Committee member) / Computer Science and Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Estradiol (E2) and Levonorgestrel (Levo) are two hormones commonly used in hormone therapy (HT) to decrease symptoms associated with menopause. Both of these hormones have been shown to have beneficial effects on cognition when given alone in a rodent model of menopause. However, it is unknown whether these hormones, when taken in combination, are beneficial or harmful to cognition. This is a critically important question given that these hormones are most often given in combination versus separately. This thesis is composed of two studies examining the cognitive effects of E2 and Levo using a rat model of surgical menopause. Study 1 assessed how the dose of E2 treatment in rats impacted cognitive performance, and found that low dose E2 enhanced working memory performance. Next, based on the results from Study 1, Study 2 used low dose E2 in combination with different doses of Levo to examine the cognitive effects of several E2 to Levo ratio combinations. The results from Study 2 demonstrated that the combination of low dose E2 with a high dose of Levo at a 1:2 ratio impaired cognition, and that the ratio currently used in HT, 3:1, may also negatively impact cognition. Indeed, there was a dose response effect indicating that working and reference memory performance was incrementally impaired as Levo dose increased. The findings in this thesis suggest that the E2 plus Levo combination is likely not neutral for cognitive function, and prompts further evaluation in menopausal women, as well as drug discovery research to optimize HT using highly controlled preclinical models.
ContributorsBerns-Leone, Claire Elizabeth (Co-author) / Prakapenka, Alesia (Co-author) / Pena, Veronica (Co-author) / Northup-Smith, Steven (Co-author) / Melikian, Ryan (Co-author) / Ladwig, Ducileia (Co-author) / Patel, Shruti (Co-author) / Croft, Corissa (Co-author) / Bimonte-Nelson, Heather (Thesis director) / Glenberg, Arthur (Committee member) / Conrad, Cheryl (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Background: Gait disturbance, clumsiness, and other mild movement problems are often observed in children with autism spectrum disorder (ASD) (Maurer and Damasio 1982). As the brain ages, these symptoms may persist or worsen in late adulthood in those diagnosed with ASD. This study focused on older adults with ASD to study motor behavior and underlying brain integrity. Using a finger tapping task, motor performance was measured in a cross-sectional study comparing older adults with ASD and age-matched typically developing (TD) controls. We hypothesized that older adults with ASD would show poorer motor performance (slower finger tapping speed). We also hypothesized that underlying brain differences, measured using MRI, in regions associated with motor function including the primary motor cortex, basal ganglia, and cerebellum, as well as the white matter connecting tracts would exist between groups and be associated with the proposed disparity in motor performance.
Method: A finger oscillation (Finger Tapping) test was administered to both ASD (n=21) and TD (n=20) participants aged 40-70 year old participants as a test of fine motor speed. Magnetic resonance (MR) images were collected using a Philips 3 Tesla scanner. 3D T1-weighted and diffusion tensor images (DTI) were obtained to measure gray and white matter volume and white matter integrity, respectively. FreeSurfer, an automated volumetric measurement software, was used to determine group volumetric differences. Mean, radial, and axial diffusivity, fractional anisotropy, and local diffusion homogeneity were measured from DTI images using PANDA software in order to evaluate white matter integrity.
Results: All participants were right-handed and there were no significant differences in demographic variables (ASD/TD, means) including age (51.9/49.1 years), IQ (107/112) and years education (15/16). Total brain volume was not significantly different between groups. No statistically significant group differences were observed in finger tapping speed. ASD participants compared to TDs showed a trend of slower finger tapping (taps/10 seconds) speed on the dominant hand (47.00 (±11.2) vs. (50.5 (±6.6)) and nondominant hand (44.6 (±7.6) vs. (47.2 (±6.6)). However, a large degree of variability was observed in the ASD group, and the Levene’s test for homogeneity of variance approached significance (p=0.053) on the dominant, but not the nondominant, hand. No significant group differences in gray matter regional volume were found for brain regions associated with performing motor tasks. In contrast, group differences were found on several measures of white matter including the corticospinal tract, anterior internal capsule and middle cerebellar peduncle. Brain-behavior correlations showed that dominant finger tapping speed correlated with left hemisphere white matter integrity of the corticospinal tract and right hemisphere cerebellar white matter in the ASD group.
Conclusions: No significant differences were observed between groups in finger tapping speed but the high degree of variability seen in the ASD group. Differences in motor performance appear to be associated with observed brain differences, particularly in the integrity of white matter tracts contributing to motor functioning.
Method: A finger oscillation (Finger Tapping) test was administered to both ASD (n=21) and TD (n=20) participants aged 40-70 year old participants as a test of fine motor speed. Magnetic resonance (MR) images were collected using a Philips 3 Tesla scanner. 3D T1-weighted and diffusion tensor images (DTI) were obtained to measure gray and white matter volume and white matter integrity, respectively. FreeSurfer, an automated volumetric measurement software, was used to determine group volumetric differences. Mean, radial, and axial diffusivity, fractional anisotropy, and local diffusion homogeneity were measured from DTI images using PANDA software in order to evaluate white matter integrity.
Results: All participants were right-handed and there were no significant differences in demographic variables (ASD/TD, means) including age (51.9/49.1 years), IQ (107/112) and years education (15/16). Total brain volume was not significantly different between groups. No statistically significant group differences were observed in finger tapping speed. ASD participants compared to TDs showed a trend of slower finger tapping (taps/10 seconds) speed on the dominant hand (47.00 (±11.2) vs. (50.5 (±6.6)) and nondominant hand (44.6 (±7.6) vs. (47.2 (±6.6)). However, a large degree of variability was observed in the ASD group, and the Levene’s test for homogeneity of variance approached significance (p=0.053) on the dominant, but not the nondominant, hand. No significant group differences in gray matter regional volume were found for brain regions associated with performing motor tasks. In contrast, group differences were found on several measures of white matter including the corticospinal tract, anterior internal capsule and middle cerebellar peduncle. Brain-behavior correlations showed that dominant finger tapping speed correlated with left hemisphere white matter integrity of the corticospinal tract and right hemisphere cerebellar white matter in the ASD group.
Conclusions: No significant differences were observed between groups in finger tapping speed but the high degree of variability seen in the ASD group. Differences in motor performance appear to be associated with observed brain differences, particularly in the integrity of white matter tracts contributing to motor functioning.
ContributorsDeatherage, Brandon R. (Co-author) / Braden, B. Blair (Co-author, Committee member) / Smith, Christopher J. (Co-author) / McBeath, Michael (Co-author, Thesis director) / Thompson, Aimee M. (Co-author) / Wood, Emily G. (Co-author) / McGee, Samuel C. (Co-author) / Sinha, Krishna (Co-author) / Baxter, Leslie (Co-author, Committee member) / Barrett, The Honors College (Contributor) / School of Nutrition and Health Promotion (Contributor) / Department of Information Systems (Contributor)
Created2017-05
Description
Currently conventional Subtitle D landfills are the primary means of disposing of our waste in the United States. While this method of waste disposal aims at protecting the environment, it does so through the use of liners and caps that effectively freeze the breakdown of waste. Because this method can keep landfills active, and thus a potential groundwater threat for over a hundred years, I take an in depth look at the ability of bioreactor landfills to quickly stabilize waste. In the thesis I detail the current state of bioreactor landfill technologies, assessing the pros and cons of anaerobic and aerobic bioreactor technologies. Finally, with an industrial perspective, I conclude that moving on to bioreactor landfills as an alternative isn't as simple as it may first appear, and that it is a contextually specific solution that must be further refined before replacing current landfills.
ContributorsWhitten, George Avery (Author) / Kavazanjian, Edward (Thesis director) / Allenby, Braden (Committee member) / Houston, Sandra (Committee member) / Civil, Environmental and Sustainable Engineering Programs (Contributor) / Barrett, The Honors College (Contributor)
Created2013-05