Matching Items (6)
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- All Subjects: Bexarotene
- All Subjects: Black Widows
- Creators: School of Mathematical and Natural Sciences
- Resource Type: Text
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
Urbanization rapidly alters the environment, leading to a decrease in biodiversity in urban areas. A challenge associated with urbanized areas is the increased heat caused by the urban heat island effect. Heat may have an important impact on arthropods particularly due to their status as ectotherms. Animal behavior reveals how individuals interact with their environment. A behavioral syndrome describes consistent individual differences in behaviors that are correlated across different behavioral contexts or situations. Understanding the Western Black Widow's behavioral responses to the urban heat island effect has important implications for the control of a pest species. In this study, the relationship between rising urban temperatures and voracity, web-building, and cannibalism behaviors of juvenile Western Black Widows was examined. Spiders raised in the urban temperature treatment were predicted to have more aggressive behavioral syndromes, characterized by shorter latencies to forage, greater web-building activity, and shorter latencies to cannibalize as compared to spiders raised in rural or intermediate temperature treatments. A correlation between the latency to attack the first fly and second fly was found, however there were no other correlations evidencing a behavioral syndrome. Temperature was found to affect foraging, web-building, and cannibalism behaviors where spiders in urban areas demonstrated increased activity in all behavioral contexts. The possession of behavioral plasticity rather than a behavioral syndrome is likely what allows Black Widows to be successful urban pests.
ContributorsGarver, Emily Elizabeth (Author) / Johnson, James Chadwick (Thesis director) / Foltz-Sweat, Jennifer (Committee member) / Kitchen, Kathryn (Committee member) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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
Description
With increasing urbanization, organisms face a myriad of novel ecological challenges. While the eco-evolutionary dynamics of urbanization are currently receiving a great deal of attention, the effect of urban disturbance on the microbiome of urban organisms is relatively unstudied. Indeed, studies of the microbiome may illuminate the mechanisms by which some species thrive after urbanization (pest implications), while other species go locally extinct (biodiversity implications). We investigated the gut microbiome of the Western black widow spider (Latrodectus hesperus). L. hesperus is an ideal model system as they are a pest species of medical importance in urban ecosystems, often forming dense urban infestations relative to the sparse populations found in their native Sonoran Desert. To gain insight into the composition of the microbiome in L. hesperus and its potential function, we sampled 4 urban, 4 desert, and 2 laboratory-reared spiders, and high-throughput sequencing of the 16S rRNA V4 region was used to investigate the diversity of gut microbiota. Dominant bacterial phyla across all samples were Firmicutes, Proteobacteria, and Actinobacteria. While desert widows showed more gut microbial diversity than urban widows, the difference was not statistically significant. The relative abundance of taxonomic classes Blastocatellia, Acidobacteriia, and Thermoleophilia detected in desert spiders was especially higher than those in urban and laboratory-reared spiders. However, urban spiders had a higher relative abundance of taxonomic class Actinomycetia. Differences in widow gut microbiome diversity improves our understanding of how features unique to a habitat, like prey diversity and soil microbes, may be shaping their microbiome. Additionally, this work further highlights the impact urbanization has on biodiversity loss, which indirectly develops a new biomarker for differentiating between urban and desert black widow spiders based on their gut microbiome.
ContributorsAsrari, Hasti (Author) / Johnson, Chad (Thesis director) / Sandrin, Todd (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor) / School of Life Sciences (Contributor)
Created2022-12
Description
The steroid hormone 20-hydroxyecdysone (20E) controls molting in arthropods. The timing of 20E production, and subsequent developmental transitions, is regulated by a variety of factors including nutrition and photoperiod. Environmental factors, such as temperature, play a critical role in regulation as well. The increasing prevalence of urban heat islands (UHI), or areas with elevated temperature due to retained heat by built structures, in response to rapid urbanization has made it critical to understand how organisms respond to elevating global temperatures. Some arthropods, such as the Western black widow spider, Latrodectus hesperus, appear to thrive under UHI conditions, but the physiological mechanism underlying their success has not been explored. Recently, we have shown that L. hesperus, a troublesome urban pest, in fact responds to urban heat island conditions in Phoenix, AZ with delayed development, reduced body mass, and increased mortality. Here we look at the relationship between 20E levels and development in spiderlings reared under desert (27ᵒC), intermediate (30ᵒC), and urban (33ᵒC) temperatures, filling a noticeable gap in not only understanding ecdysteroids’ role in arachnid development but how incremental changes in environmental conditions affect the regulation of this process. Developmental progression and hemolymph 20E titers were recorded for several families of spiders collected from across the urban Phoenix area with data spanning from day 55 to 75 of development, focusing on the second developmental instar. We found that 33°C, but not 30°C, led to 1) a significantly higher production of 20E throughout development, 2) a reduced and delayed molt-inducing 20E peak, and 3) noticeable reductions in growth rate and mass. At 30°C, a variable response is seen in molt timing, without the negative impacts on size and mortality as seen at 33°C, suggesting that at UHI temperatures, the optimal developmental temperature threshold has been surpassed.
ContributorsMoen, Claire Elizabeth (Author) / Hackney-Price, Jennifer (Thesis director) / Johnson, J. Chadwick (Committee member) / School of Social and Behavioral Sciences (Contributor) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05