Matching Items (15)
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- All Subjects: Forensics
- All Subjects: Vitamin D
- Creators: School of Mathematical and Natural Sciences
- Member of: Barrett, The Honors College Thesis/Creative Project Collection
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
Bloodstain pattern analysis can provide telling evidence from a crime scene based on the clues left in the blood, but the field itself is highly problematic since the evidence extracted is dependent upon the interpretation of the analyst. Although some aspects of this type of analysis have been scientifically supported, most are not seen as positively accurate. Since certainty is the basis for acceptance of courtroom testimony, it is important that these unsettled aspects become more understood. This experiment examines the diameter of a weapon and how it affects its cast-off pattern. Weapons with four different diameters were used to generate 5 sample patterns under controlled conditions from each weapon diameter for a total of 20 patterns consisting of 3,367 droplets. The length and width of the pattern, the total number of droplets in the pattern, and the percentage of each droplet type (classified into low-velocity, medium-velocity, and high-velocity droplets) were recorded, averaged, and compared to each other individually using a t-test difference of two means assuming unequal variances. The results reveal that a higher percentage of droplets greater than 4 mm may indicate the use of a weapon with a wider diameter. The data also shows differences between the weapons that may be related to other factors besides the diameter of the weapon such as surface area or the curvature of the weapon. Still, more testing must be conducted to support these theories.
ContributorsBetz, Alexandra Marie (Author) / Kobojek, Kimberly (Thesis director) / Jacobson, David (Committee member) / School of Humanities, Arts, and Cultural Studies (Contributor) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Bexarotene is a commercially produced drug commonly known as Targetin presecribed to treat cutaneous T-cell lymphoma (CTCL). Bex mimics the actions of natural 9-cis retinoic acid in the body, which are derived from Vitamin A in the diet and boost the immune system. Bex has been shown to be effective in the treatment of multiple types of cancer, including lung cancer. However, the disadvantages of using Bex include increased instances of hypothyroidism and excessive concentrations of blood triglycerides. If an analog of Bex can be developed which retains high affinity RXR binding similar to the 9-cis retinoic acid while exhibiting less interference for heterodimerization pathways, it would be of great clinical significance in improving the quality of life for patients with CTCL. This thesis will detail the biological profiling of additional novel (Generation Two) analogs, which are currently in submission for publication, as well as that of Generation Three analogs. The results from these studies reveal that specific alterations in the core structure of the Bex "parent" compound structure can have dramatic effects in modifying the biological activity of RXR agonists.
ContributorsYang, Joanna (Author) / Jurutka, Peter (Thesis director) / Wagner, Carl (Committee member) / Hibler, Elizabeth (Committee member) / Barrett, The Honors College (Contributor)
Created2012-05
Description
Bexarotene (Targretin®) is an FDA approved drug used to treat cutaneous T-cell lymphoma (CTCL), as well as off-label treatments for various cancers and neurodegenerative diseases. Previous research has indicated that bexarotene has a specific affinity for retinoid X receptors (RXR), which allows bexarotene to act as a ligand-activated-transcription factor and in return control cell differentiation and proliferation. Bexarotene targets RXR homodimerization to drive transcription of tumor suppressing genes; however, adverse reactions occur simultaneously when bound to other nuclear receptors. In this study, we used novel bexarotene analogs throughout 5 iterations synthesized in the laboratory of Dr. Wagner to test for their potency and ability to bind RXR. The aim of our study is to quantitatively measure RXR homodimerization driven by bexarotene analogs using a yeast two-hybrid system. Our results suggests there to be several compounds with higher protein activity than bexarotene, particularly in generations 3.0 and 5.0. This higher affinity for RXR homodimers may help scientists identify a compound that will minimize adverse effects and toxicity of bexarotene and serve as a better cancer treatment alternative.
ContributorsSeto, David Hua (Author) / Marshall, Pamela (Thesis director) / Wagner, Carl (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor) / School of Social and Behavioral Sciences (Contributor)
Created2015-05
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
As human beings we go through the world interpreting – seeing a situation, gathering context, and making a decision on the meaning of the thing we just experienced. The philosopher Martin Heidegger calls this way of being hermeneutics – a practice of interpretation. This method of approach does not ignore a person’s bias, instead bias is highlighted, understood, and possibly even overcome. In the following pages the basic definition and process of hermeneutics will be discussed. Leading into the difference between calculative and meditative thought – scientific and philosophical – in order to later discuss the possibility and need to merge the two in the field of Forensic Science. Forensic Scientist uses hermeneutic thought by way of merging calculative and meditative thinking. In order to support this claim artistic renderings of ‘the pieces of an unknowable whole’ were created to literally illustrate this truth.
Forensic science is tasked with using calculative thinking with scientifically accepted methods of measurement and detection as well as the meditative task of applying their data to messy, real-world events. In order to support my supposition of forensic scientists being hermeneutical workers, three paintings were created. The three paintings can be considered a tryptic of sorts due to the context in which they are presented: forensic science. They each tell a story that is weaved within each other – spatter indicating violence long past, the empty void of a body gone, and the cold decomposition of a victim found. It is the forensic scientist that must interpret each piece separately and is tasked with finding how and why they are put together. The hermeneutical work of the forensic scientist interpreting a crime scene uses the same methods as one who interprets text. A forensic scientist opens possibilities of meaning in the same way that Martin Heidegger’s hermeneutic circle does. There is interplay between the interpreter (the forensic scientist) and the text (the crime scene), questions are formed (what happened here?) and responses are made (evidence found at the scene). This question and response outlook is what make the forensic scientist a hermeneutic thinker.
Forensic science is tasked with using calculative thinking with scientifically accepted methods of measurement and detection as well as the meditative task of applying their data to messy, real-world events. In order to support my supposition of forensic scientists being hermeneutical workers, three paintings were created. The three paintings can be considered a tryptic of sorts due to the context in which they are presented: forensic science. They each tell a story that is weaved within each other – spatter indicating violence long past, the empty void of a body gone, and the cold decomposition of a victim found. It is the forensic scientist that must interpret each piece separately and is tasked with finding how and why they are put together. The hermeneutical work of the forensic scientist interpreting a crime scene uses the same methods as one who interprets text. A forensic scientist opens possibilities of meaning in the same way that Martin Heidegger’s hermeneutic circle does. There is interplay between the interpreter (the forensic scientist) and the text (the crime scene), questions are formed (what happened here?) and responses are made (evidence found at the scene). This question and response outlook is what make the forensic scientist a hermeneutic thinker.
ContributorsCraig, Catherine Anne (Author) / Kobojek, Kimberly (Thesis director) / Watrous, Lisa (Committee member) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The effects that forensic-themed programs such as CSI: Crime Scene Investigation has on the public's understanding and expectations of the criminal justice system has been a main focus of study in recent years. This phenomenon was coined by the media and termed the "CSI Effect." This study aimed to research the correlations between age, gender, and program-watching habits on potential juries' evidence expectations in court. To do so, 70 people were surveyed and asked a series of demographic questions, as well as questions about how often they watch forensic-themed shows and their experience with the criminal justice system. They were given a mock crime scene scenario and asked about their scientific and non-scientific evidence expectations in this particular case. The most notable results showed that a longer exposure time to forensic-themed programs correlated to high evidence expectations. However, how often viewers watch forensic-themed programs did not seem to affect their evidence expectations. It was concluded that the higher evidence expectations by modern jurors may be due to a combination of the "CSI Effect" and the newly hypothesized "Tech Effect," instead of just being the consequence of the watching too much forensic-themed television.
ContributorsJones, Kristin Taylor (Author) / Kobojek, Kimberly (Thesis director) / Lafond, Sue (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor)
Created2014-05
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
Due to the nature of animals, even domesticated pets, animal scavenging of human remains is an important taphonomic factor. This area of study has, however, been undercounted in the current literature. The purpose of this study was to begin the first step in creating a taphonomic profile for urban / household animal scavenging as distinguishable from manmade tool marks. Using volunteered animals and regularly available tools, alterations were made on beef ribs in order to characterize the distinguishing profiles between the two groups. It was found that animal scavenging alterations, in the short term (20 minutes used in this study) have a distinctly different appearance than tool mark alterations. Animal scavenging has less visible alterations, consistent bite morphology across different species, and symmetrical cut marks along the midsection of the long bones. Ultimately, this study was a successful first step in furthering taphonomic alteration database research across various biomes and conditions.
ContributorsLittle, Cody Lee (Author) / Kobojek, Kimberly (Thesis director) / Falsetti, Anthony (Committee member) / Ball, Becky (Committee member) / School of Human Evolution and Social Change (Contributor) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05