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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

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
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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

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

Pollution causes many health problems in the modern world and the desert climates struggle with pollution in unique ways. In the Sonoran Desert, the research was conducted with the purpose of expanding the knowledge of the topic in this area. A literature review was conducted based on air, soil and

Pollution causes many health problems in the modern world and the desert climates struggle with pollution in unique ways. In the Sonoran Desert, the research was conducted with the purpose of expanding the knowledge of the topic in this area. A literature review was conducted based on air, soil and noise pollution in the region. The Sonoran Desert has high levels of carcinogenic elements along with other pollutants due to the main industries of mining, agriculture and manufacturing. Overall, these findings show people in desert climates deal with high levels of pollutants.

ContributorsWest, Katherine (Author) / Hackney Price, Jennifer (Thesis director) / Savalli, Udo (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor)
Created2023-05
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

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
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Description

Aboveground-belowground relationships between vegetation and its associated soil biotic community play an important role in every terrestrial ecosystem for nutrient cycling and soil health maintenance. Deserts are especially sensitive to change and little is known about Sonoran Desert soil microbiota, while exotic herbaceous species are increasingly invading into the ecosystem

Aboveground-belowground relationships between vegetation and its associated soil biotic community play an important role in every terrestrial ecosystem for nutrient cycling and soil health maintenance. Deserts are especially sensitive to change and little is known about Sonoran Desert soil microbiota, while exotic herbaceous species are increasingly invading into the ecosystem with other harmful effects. In many other environments, soil communities have been associated with both plant species and plant functional type. The soil community food web depends on the sustenance brought by vegetation, and different soil community members are adapted to different diets. In this paper, we hypothesized that invasive plants would cause belowground soil communities to have greater abundance and lesser diversity than those under native, more locally established plants. To test this hypothesis, we selected four desert understory plant taxa: one native grass, one native forb, one invasive grass, and one invasive forb. We predicted that the invasive plants would be associated with a greater count of microarthropods per unit mass of soil but lesser microarthropod species diversity. The invasive plants were not statistically associated with a greater count of microarthropods per kilogram of soil nor lesser microarthropod species diversity. There was not a significant difference in abundance in the microarthropod categories between native and invasive plants, so the hypothesis was rejected. However, the invasive Erodium cicutarium was found to harbor high soil mite abundance, which warrants further study, and it is yet to be seen whether soil moisture and proximity to trees played a role in the data. The results of this study should help in generating more informed hypotheses regarding desert aboveground-belowground relationships.

ContributorsStern, Argon (Author) / Ball, Becky (Thesis director) / Sanin, Maria (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor)
Created2022-05
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Description
The use of DNA testing has been focused primarily on biological samples such as blood or saliva found at crime scenes. These types of evidence in the forensic field are sometimes difficult to come by, especially when there is no body to find to verify things such as identity or

The use of DNA testing has been focused primarily on biological samples such as blood or saliva found at crime scenes. These types of evidence in the forensic field are sometimes difficult to come by, especially when there is no body to find to verify things such as identity or status of a person. In the case of the burial of a body, they can be remote and relocated multiple times depending on each situation. Clandestine burials are not uncommon especially in the Arizona desert by the United States and Mexico border. Since there is no physical body to find the next best avenue to finding a clandestine burial is through search teams which can take weeks to months or other expensive technology such as ground penetrating radar (GPR). A new more interesting avenue to search for bodies is using the most found material–soil. Technology has allowed the possibility of using soil DNA microbiome testing initially to study the varieties of microbes that compose in soil. Microbiomes are unique and plentiful and essentially inescapable as humans are hosts of millions of them. The idea of a microbiome footprint at a crime scene seems out of reach considering the millions of species that can be found in various areas. Yet it is not impossible to get a list of varieties of species that could indicate there was a body in the soil as microbiomes seep through from decomposition. This study determines the viability of using soil microbial DNA as a method of locating clandestine graves by testing 6 different locations of a previous pig decomposition simulation. These two locations give two different scenarios that a body may be found either exposed to the sun in an open field or hidden under foliage such as a tree in the Sonoran Desert. The experiment will also determine more factors that could contribute to a correlation of microbiome specific groups associated with decomposition in soil such as firmicutes. The use of soil microbial DNA testing could open the doors to more interpretation of information to eventually be on par with the forensic use of biological DNA testing which could potentially supplement testimonies on assumed burial locations that occurs frequently in criminal cases of body relocation and reburial.
ContributorsMata Salinas, Jennifer (Author) / Marshall, Pamela (Thesis director) / Bolhofner , Katelyn (Committee member) / Wang, Yue (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor) / School of Humanities, Arts, and Cultural Studies (Contributor)
Created2022-05