Matching Items (11)
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- All Subjects: Vitamin D
- All Subjects: Cognition
- Creators: Jurutka, Peter
- Resource Type: Text
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
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
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
Abstract Chess has been a common research topic for expert-novice studies and thus for learning science as a whole because of its limited framework and longevity as a game. One factor is that chess studies are good at measuring how expert chess players use their memory and skills to approach a new chessboard con�guration. Studies have shown that chess skill is based on memory, speci�cally, "chunks" of chess piece positions that have been previously encountered by players. However, debate exists concerning how these chunks are constructed in players' memory. These chunks could be constructed by proximity of pieces on the chessboard as well as their precise location or constructed through attack-defense relations. The primary objective of this study is to support which one is more in line with chess players' actual chess abilities based off their memory, proximity or attack/defense. This study replicates and extends an experiment conducted by McGregor and Howe (2002), which explored the argument that pieces are primed more by attack and defense relations than by proximity. Like their study, the present study examined novice and expert chess players' response times for correct and error responses by showing slides of game configurations. In addition to these metrics, the present study also incorporated an eye-tracker to measure visual attention and EEG to measure affective and cognitive states. They were added to allow the comparison of subtle and unconscious behaviors of both novices and expert chess players. Overall, most McGregor and Howe's (2002) results were replicated supporting their theory on chess expertise. This included statistically significance for skill in the error rates with the mean error rates on the piece recognition tests were 70.1% for novices and 87.9% for experts, as well as significance for the two-way interaction for relatedness and proximity with error rates of 22.4% for unrelated/far, 18.8% for related/far, 15.8% for unrelated
ear, and 29.3% for related
ear. Unfortunately, there were no statistically significance for any of the response time effects, which McGregor and Howe found for the interaction between skill and proximity. Despite eye-tracking and EEG data not either support nor confirm McGregor and Howe's theory on how chess players memorize chessboard configurations, these metrics did help build a secondary theory on how novices typically rely on proximity to approach chess and new visual problems in general. This was exemplified by the statistically significant results for short-term excitement for the two-way interaction of skill and proximity, where the largest short-term excitement score was between novices on near proximity slides. This may indicate that novices, because they may lean toward using proximity to try to recall these pieces, experience a short burst of excitement when the pieces are close to each other because they are more likely to recall these configurations.
ear, and 29.3% for related
ear. Unfortunately, there were no statistically significance for any of the response time effects, which McGregor and Howe found for the interaction between skill and proximity. Despite eye-tracking and EEG data not either support nor confirm McGregor and Howe's theory on how chess players memorize chessboard configurations, these metrics did help build a secondary theory on how novices typically rely on proximity to approach chess and new visual problems in general. This was exemplified by the statistically significant results for short-term excitement for the two-way interaction of skill and proximity, where the largest short-term excitement score was between novices on near proximity slides. This may indicate that novices, because they may lean toward using proximity to try to recall these pieces, experience a short burst of excitement when the pieces are close to each other because they are more likely to recall these configurations.
ContributorsSeto, Christian Paul (Author) / Atkinson, Robert (Thesis director) / Runger, George (Committee member) / Industrial, Systems (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
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
Physical activity is something that everyone engages in at varying levels. It has been linked to positively impacting general wellbeing, as well as preparing the mind and body to learn new skills. However, the significance of physical activity remains under-explored in some areas. The purpose of this study was to determine the relationship between physical activity levels and emotional intelligence, navigation and planning skills, motor skills, memory capacity, and one’s perception of the ‘value’ of an object or an experience. During sessions, participants were equipped with two physiological sensors: the EEG B-Alert X10 or X24 headset, and the Shimmer GSR3. In addition to these, two external sensors were used: a web camera for recording and evaluating facial expressions, and the Tobii X2-30, X2-60, or Tobii T60XL eye tracking systems, used to monitor visual attention. These sensors were used to collect data while participants completed a series of tasks: the Self-Report of Emotional Intelligence Test, the Tower of London Test, the Motor Speed Test, the Working Memory Capacity Battery, watching product-centered videos, and watching experience-centered videos. Multiple surveys were also conducted, including a demographic survey, a nutritional and health survey, and a sports preference survey. Utilizing these metrics, this study found that those who exercise more experience and express higher levels of emotion, including joy, sadness, contempt, disgust, confusion, frustration, surprise, anger, and fear. This implies a difference in emotional response modulation between those who exercise more and those who exercise less, which in turn implies a difference in perception between the two groups. There were no significant findings related to navigation and planning skills, motor skills, or memory capacity from this analysis.
ContributorsFalls, Tarryn (Author) / Atkinson, Robert (Thesis director) / Chavez-Echeagaray, Maria Elena (Committee member) / Arts, Media and Engineering Sch T (Contributor) / Computer Science and Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Psoriasis is a skin disease that affects millions of individuals. Genetic risk factors for psoriasis include a common deletion of two late cornified envelope (LCE) genes (LCE3B and LCE3C) located within a cluster of genes expressed during epithelial differentiation and skin repair. It was previously discovered that treatment with 1,25-dihydroxyvitamin D3 (1,25D) or analogs thereof can improve psoriasis symptoms in many patients, but the molecular mechanisms for this action are largely unknown. Our laboratory previously showed that 1,25D as well as low affinity ligands for the vitamin D receptor (VDR), such as delphinidin and cyanidin, are capable of upregulating the remaining LCE3A, -3D, and -3E genes to potentially compensate for the loss of LCE3B and -3C in promoting skin repair. In the current study, DHA and curcumin were tested and found to also upregulate LCE3 transcripts in a dose-dependent manner. To investigate other potential target genes for 1,25D and DHA, we tested JunB, for which low or absent expression has been reported to cause or be associated with psoriatic lesions. Our experiments showed a trend for an upregulation of JunB mRNA after DHA treatment, potentially providing benefit for psoriasis patients. Although our hypothesis is that DHA functions as a vitamin D receptor ligand to mediate upregulation of JunB and LCE3 genes, other investigators have assumed that DHA actions in skin are mediated via PPAR isoforms. We therefore utilized a selective ligand for PPAR delta (GW501516) to determine whether PPAR delta, the primary PPAR isoform in keratinocytes, is a mediator of DHA-induced LCE3 gene activation. Although a modest upregulation of LCE3 genes was seen after treatment with GW501516, our findings are still consistent with DHA acting primarily as a VDR ligand. Our results not only provide additional information about the ability of VDR ligands to upregulate specific skin genes with relevance for skin repair, but also may help provide a molecular basis for testing improved treatments for mild to moderate psoriasis.
ContributorsKarrys, Amitis (Author) / Jurutka, Peter (Thesis director) / Whitfield, Kerr (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
The significance of hormonal vitamin D in the numerous facets of health stresses the importance of elucidating the molecular mechanism(s) associated with 1,25D-VDR signaling modulators (e.g., resveratrol and sirtuin-1). Resveratrol (Res), a natural antioxidant, is a potent activator of NAD-dependent deacetylase sirtuin-1 (SIRT-1), an enzyme associated with longevity in animal models. This present study employed mammalian 2-hybrid (M2H) and vitamin D responsive element (VDRE)-based transcriptional assays to investigate the potential effects of Res and SIRT-1 on VDR signal transduction. Results from VDRE-based assays indicate that Res and SIRT-1 potentiate 1,25D-VDR activity via cell-and-promoter-specific pathways. In addition, 1,25D displacement experiments revealed an increase in VDR-bound radiolabeled 1,25D in the presence of Res, suggesting that Res may potentiate VDR transactivation by stimulating 1,25D binding. M2H assays in HEK293 cells were then utilized to assess levels of interaction between VDR and VDR comodulators, including RXR, SRC-1, and DRIP-205. Both Res and SIRT-1 increased the ability of VDR to associate with RXR; however, SRC-1 and DRIP-205 interactions were not enhanced. The activity of a novel, non-acetylatable VDR mutant, K413R, was probed revealing that K413R possesses amplified transactivation capacity over wild-type VDR. A SIRT-1 inhibitor, EX-527, was used to suppress endogenous SIRT-1, resulting in significantly decreased VDR transactivation. Finally, qPCR results in HEK293 cells revealed that the 1,25D-mediated induction of CYP24A1, an endogenous VDR target gene, was enhanced (85%) by SIRT-1 while Res increased CYP24A1 expression by 294%. The combination of 1,25D, SIRT-1, and Res amplified CYP24A1 expression by 326% over 1,25D, although this effect did not reach statistical significance when compared to the Res only treated group. We conclude that acetylation of VDR comprises a negative feedback loop that attenuates 1,25D-VDR signaling. This loop is suppressed by resveratrol/SIRT-1-catalyzed deacetylation of VDR, restoring VDR activity. The two compounds, 1,25-dihydroxyvitamin D (1,25D, vitamin D) and 5-hydroxytryptamine (5-HT, serotonin), have been proposed to play a significant role in abnormal social behavior associated with psychological conditions including autism spectrum disorders (ASDs) and depression; however, the mechanism underlying these associations has yet to be elucidated. Deficiencies in 1,25D or 5-HT have been linked to the increased incidence of ASDs. Thus, examining the modulation of genes involved in 5-HT biosynthesis, reuptake, and degradation is fundamental in linking low 1,25D levels to the increased incidence of psychiatric disorders. We propose that 1,25D regulates tryptophan hydroxylase-2 (TPH2), the initial and rate-limiting enzyme in the biosynthetic pathway of 5-HT. In order to evaluate the regulation of TPH2 in neuronal cells, three formulations of media were examined to optimize the cell culture conditions necessary for growth and morphology of embryonic rat medullary raphe (B14) serotonergic neurons. Next, quantitative real time-PCR (qPCR) was utilized to examine TPH2 expression in cultured human glioblastoma (U-87) cells and rat serotonergic neurons (B-14). Human TPH2 mRNA in U-87 cells was induced dose-dependently resulting in a 2.4-fold increase at 10 nM 1,25D. Strikingly, TPH2 mRNA in B-14 cells was observed to be 26- to 86-fold upregulated at 10 nM 1,25D; however, 1 nM and 100 nM 1,25D elicited significantly smaller inductions (8-fold and 1.2-fold, respectively).
ContributorsSabir, Marya Sabah (Author) / Jurutka, Peter (Thesis director) / Hackney Price, Jennifer (Committee member) / Sandrin, Todd R. (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12
Description
The relevance of depression in the clinical realm is well known, as it is one of the most common mental disorders in the United States. Clinical depression is the leading cause of disease for women worldwide. The sex difference in depression and anxiety has guided the research of not just recent studies but older studies as well, supporting the theory that gonadal hormones are associated with the mechanisms of emotional cognition. The scientific literature points towards a clear correlative relationship between gonadal hormones, especially estrogens, and emotion regulation. This thesis investigates the neural pathways that have been indicated to regulate mood and anxiety. Currently, the research points to the hypothalamic-pituitary-adrenal axis, which regulates the stress response through its ultimate secretion of cortisol through the adrenal cortex, and its modulated response when exposed to higher levels of estrogen. Another mechanism that has been investigated is the interaction of estrogen and the serotonergic system, which is noteworthy because the serotonergic system is known for its importance in mood regulation. However, it is important to note that the research seeking to determine the neurobiological underpinnings of estrogen and the serotonergic system is not expansive. Future research should focus on determining the direct relationship between cortisol hypersecretion and estrogens, the specific neurobiological effects of serotonergic receptor subtypes on the antidepressant actions of estrogens, and the simultaneous effects of the stress and serotonergic systems on depressive symptoms.
ContributorsArroyo, Mariana (Author) / Bimonte-Nelson, Heather (Thesis director) / Jurutka, Peter (Committee member) / School of International Letters and Cultures (Contributor) / School of Social and Behavioral Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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