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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
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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

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
Water is the main driver of net primary productivity (NPP) in arid ecosystems, followed by nitrogen and phosphorous. Precipitation is the primary factor in determining water availability to plants, but other factors such as surface rocks could also have an impact. Surface rocks may positively affect water availability by preventing

Water is the main driver of net primary productivity (NPP) in arid ecosystems, followed by nitrogen and phosphorous. Precipitation is the primary factor in determining water availability to plants, but other factors such as surface rocks could also have an impact. Surface rocks may positively affect water availability by preventing evaporation from soil, but at higher densities, surface rocks may also have a negative impact on water availability by limiting water infiltration or light availability. However, the direct relationship between rock cover and aboveground net primary productivity (ANPP), a proxy for NPP, is not well understood. In this research we explore the relationship between rock cover, ANPP, and soil nutrient availability. We conducted a rock cover survey on long-term fertilized plots at fifteen sites in the Sonoran Desert and used 4 years of data from annual plant biomass surveys to determine the relationship between peak plant biomass and surface rock cover. We performed factorial ANCOVA to assess the relationship among annual plant biomass, surface rocks, precipitation, and fertilization treatment. Overall we found that precipitation, nutrients, and rock cover influence growth of Sonoran Desert annual plants. Rock cover had an overall negative relationship with annual plant biomass, but did not show a consistent pattern of significance over four years of study and with varying average winter precipitation.
ContributorsShaw, Julea Anne (Author) / Hall, Sharon (Thesis director) / Sala, Osvaldo (Committee member) / Cook, Elizabeth (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
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Description
Bexarotene (Bex) is a FDA-approved drug used to treat cutaneous T-cell lymphoma (CTCL). It binds with high affinity to the retinoid-X-receptor (RXR), a nuclear receptor implicated in numerous biological pathways. Bex may have the potential to attenuate estrogenic activity by acting as an estrogen receptor alpha (ERα) signaling antagonist, and

Bexarotene (Bex) is a FDA-approved drug used to treat cutaneous T-cell lymphoma (CTCL). It binds with high affinity to the retinoid-X-receptor (RXR), a nuclear receptor implicated in numerous biological pathways. Bex may have the potential to attenuate estrogenic activity by acting as an estrogen receptor alpha (ERα) signaling antagonist, and can therefore be used to treat ERα-positive cancers, such as breast cancer. Using dual luciferase reporter assays, real-time qRT-PCR, and metabolic proliferation assays, the anti-estrogenic properties of Bex were ascertained. However, since Bex produces numerous contraindications, select novel RXR drug analogs were also evaluated. Results revealed that, in luciferase assays, Bex could significantly (P < 0.01) inhibit the transcriptional activity of ERα, so much so that it rivaled ER pan-antagonist ZK164015 in potency. Bex was also able to suppress the proliferation of two breast cancer cell models, MCF-7 and T-47D, and downregulate the expression of an estrogen receptor target gene (A-myb), which is responsible for cell proliferation. In addition, novel analogs A30, A33, A35, and A38 were evaluated as being more potent at inhibiting ERE-mediated transcription than Bex at lower concentrations. Analogs A34 and A35 were able to suppress MCF-7 cell proliferation to a degree comparable to that of Bex. Inhibition of T-47D cell proliferation, by contrast, was best achieved by analogs A34 and A36. For those with ERα – positive breast cancer who are refractory to current chemotherapeutics used to treat breast cancer, Bex and its analogs may prove to be useful alternative options.
ContributorsBains, Supreet (Author) / Jurutka, Peter (Thesis director) / Hackney Price, Jennifer (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
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

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
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Description
In the Spring of 2021, I had an internship with Butterfly Wonderland, where I worked in their conservatory and learned about the ecological relationship between butterflies and plants. As part of my internship, I encouraged guests to learn more about gardening for pollinators. That experience inspired me to complete a

In the Spring of 2021, I had an internship with Butterfly Wonderland, where I worked in their conservatory and learned about the ecological relationship between butterflies and plants. As part of my internship, I encouraged guests to learn more about gardening for pollinators. That experience inspired me to complete a creative project in which I would design a butterfly garden of my own that would highlight wildlife benefits and be accessible to people like myself, who do not have their own gardens and don’t have hundreds of dollars to spend on gardening supplies. In collaboration with Dr. Gwen Iacona and Liz Makings (director and second committee member respectively), I planted accessible gardens. By “accessible”, I mean that the gardens were affordable (less than $100 total), included free/upcycled materials wherever possible, and are easily replicable. For my project, I made ‘prototypes’ of the gardens by using freely available seeds and soil sources, germinating those seeds in the ASU Greenhouses, and documenting my process so that it could be shared. Freely available seeds and other materials came from a variety of places including the ASU seed library, local Free Little Libraries, donations, as well as purchases from on campus fundraisers. The germination and growth of seeds in the ASU greenhouse took place over the course of several months in the fall and winter. That documentation has taken on several forms, including an informational pamphlet about wildlife gardening and flyers specific to locally available plant seeds. I find this to be very important because my end goal was to create something that other students or people in our community can use in a practical way. I wanted to create something that will bring gardening into the homes of people who didn’t think they were able to participate in it.
ContributorsBernat, Isabella (Author) / Iacona, Gwen (Thesis director) / Makings, Elizabeth (Committee member) / Barrett, The Honors College (Contributor) / School of International Letters and Cultures (Contributor) / School of Life Sciences (Contributor)
Created2022-05
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
Description
The decision to disclose or not disclose information is a personal choice. When medical information is learned, a patient has to make decisions about disclosure. This qualitative research project has the goal of understanding how Latinx participants' cultural values, experiences from this community, and other factors influence the decision to

The decision to disclose or not disclose information is a personal choice. When medical information is learned, a patient has to make decisions about disclosure. This qualitative research project has the goal of understanding how Latinx participants' cultural values, experiences from this community, and other factors influence the decision to disclose in a romantic relationship. Twelve interviews were conducted using a semi-structured interview guide and the main themes found from analysis of the data cultural and relational influencers. This thesis serves as a resource for healthcare professionals to better understand their Latinx patient population in times where disclosure is encountered.
ContributorsPetersen, Claire (Author) / Cayetano, Catalina (Thesis director) / Flores, Valerie (Committee member) / Sellner, Erin (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor)
Created2022-05
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Description
Arid and semiarid ecosystems (known as drylands) cover 45% of global land area and are predicted to expand to encompass half of the world’s land area by the end of the century. Litter decomposition plays a large role in nutrient and carbon cycling in dryland ecosystems, yet it remains poorly

Arid and semiarid ecosystems (known as drylands) cover 45% of global land area and are predicted to expand to encompass half of the world’s land area by the end of the century. Litter decomposition plays a large role in nutrient and carbon cycling in dryland ecosystems, yet it remains poorly understood. Models that accurately predict decomposition in mesic ecosystems fail to accurately describe decomposition in drylands due to differing drivers of decomposition but also because litter in drylands accumulates around litter retention elements (LREs). LREs can be any object or surface that inhibits the movement vectors (e.g., wind) that push litter across drylands, creating a “pool” of litter around the LRE. Litter pooling increases the amount of mixing between litter and soil, creating a microclimate more conducive to microbial decomposition. Due to the increase in microbial decomposition, the decomposition rate for litter around LREs can be markedly different than that of litter not in LREs. To further understand how much litter accumulates in LREs, I studied the differences in litter accumulation between LREs and open areas in five drylands across the Southwestern United States. To do this, I visually analyzed photos of 424 litterbags to determine the cover percentages of four different types of organic litter (grass, broadleaf, reproductive, woody) and rock litter. Visual analysis of litterbags consisted of manually delineating the percent coverage of each of these litter categories. Litterbags had been placed in both open intercanopy areas as well as woody sub-canopy areas in which the plant canopy acted as the LRE. Additionally, 45 of these litterbags were randomly selected for analysis in the computer program FIJI (FIJI is Just ImageJ) to assess the litter area find the percent difference between visual and digital analysis. Areas underneath woody sub-canopies accumulated far more organic matter litter over time than open areas between canopies did but displayed a similar amount of rock litterbag cover. Shrub microsites also displayed far more varied litterbag cover percentages than open microsites. Data also suggested that litter does not always accumulate underneath shrubs or open intercanopy areas and may dissipate as time progresses. These results support the idea that litter accumulation varies throughout drylands, and that soil and litter mix frequently in LREs such as under woody plant canopies. The percent difference between FIJI analysis and visual analysis was generally negative, reflecting that visual estimation of litterbag cover was typically smaller than digital estimates. Cumulatively, litter was shown to accumulate much more around LREs and even move from them – supporting the idea that litter decomposition models need to account for litter movement in drylands to be accurate.
ContributorsNelson, Benjamin (Author) / Throop, Heather (Thesis director) / Ball, Becky (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2022-05