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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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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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Recent data suggests that olfactory input is important for antennal lobe development in honey bees. Chronic association of a single odor to food resources during crucial stages of development results in delayed antennal lobe development for mature foraging bees. The antennal lobes of these bees instead closely resemble an immature

Recent data suggests that olfactory input is important for antennal lobe development in honey bees. Chronic association of a single odor to food resources during crucial stages of development results in delayed antennal lobe development for mature foraging bees. The antennal lobes of these bees instead closely resemble an immature network observed in young, newly emerged bees. Using an odor stimuli variance assay, learning and memory tests can be used to explore how well honey bees discriminate single odors within complex odor mixtures. Here we are validating two different odor mixtures, a Brassica rapa floral blend and a second replicate mixture composed of common molecularly dissimilar odors. Odors in each mixture are either held constant or varied in concentration over 16 conditioning trials. Subsequent memory tests are performed two hours later to observe the ability of bees to distinguish and recognize specific odor components in each mixture. So far in our assay we find high rates of generalization for both odor mixtures. In general, more bees responded to all odors in the replicate treatment group over the Brassica treatment group. Additionally, bees in the Brassica treatment group did not respond to the target odor. More data is being collected to validate this assay. In future studies, I propose to apply this behavioral assay to bees with an altered olfactory developmental in order to see the functional impacts of this chronic odor association treatment.
ContributorsHalby, Rachael (Author) / Smith, Brian (Thesis director) / Jernigan, Christopher (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
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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
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Beginning in the early 1990s, nuclear forensic science is a relatively young field that focuses on “re-establishing the history of nuclear material of unknown origin” (Mayer, et al. 2010, p. 1). Specifically, investigators compare these unknown materials, pre-detonation in this case, based on their characteristics and process history (Mayer, et

Beginning in the early 1990s, nuclear forensic science is a relatively young field that focuses on “re-establishing the history of nuclear material of unknown origin” (Mayer, et al. 2010, p. 1). Specifically, investigators compare these unknown materials, pre-detonation in this case, based on their characteristics and process history (Mayer, et al. 2010, p. 1). In 2010, the Committee of Nuclear Forensics made ten recommendations on the procedures that could lead to improvement in investigation methods. In particular, this paper discusses Recommendation 6: “The nuclear forensics community should develop and adhere to standards and procedures that are rooted in the applicable underlying principles that have been recommended for modern forensic science, including calibration using reference standards; cross-comparison with other methods; inter-laboratory comparisons; and identification, propagation, and characterization of uncertainties'' (Committee of Nuclear Forensics, 2010, p. 11). The main objective of this paper is to compile a literature review to determine how this recommendation was followed, if at all, and produce a list of suggestions that could complement any effort towards the improvement of the field. Out of the methods recommended, that which has fostered the most growth has been cross-comparison. For example, the need for human supervision has decreased, which has decreased the need for human error (Reading, et al., 2017, p. 6013). However, areas that would benefit from development are increasing the number of disciplines in the field (Croudace, et al., 2016, p. 128). These conclusions provided the basis for improvements to other existing studies like DNA and fingerprinting.

ContributorsSarraf, Yasmine (Author) / Montero, Shirly (Thesis director) / Sellner, Erin (Committee member) / van Zalen, Ed (Committee member) / Barrett, The Honors College (Contributor) / School of Social and Behavioral Sciences (Contributor) / School of Mathematical and Natural Sciences (Contributor) / School of Complex Adaptive Systems (Contributor)
Created2021-12
Description

This paper examines the effects of childhood maltreatment on attachment and development. Humans are social beings; connection is at the core of human behavior. This social nature is what drives the need to form relationships with others. Relationships help humans learn and understand the social world around them relatively safely

This paper examines the effects of childhood maltreatment on attachment and development. Humans are social beings; connection is at the core of human behavior. This social nature is what drives the need to form relationships with others. Relationships help humans learn and understand the social world around them relatively safely and securely. However, to ensure that these relationships bring safety and security, the ability to do so must be established during the first 18 months of children’s lives (Kennedy & Kennedy, 2004). The relationships humans form are based on how they establish attachments, or emotional and long-term bonds and relationships, to a primary caregiver or parent as children (Bowlby, 1969). These primary attachments include secure, anxious-preoccupied, insecure-avoidant, or fearful-avoidant attachments and can have significant effects on individuals or emerging adults in early adulthood (ages 18-25). Primary attachments act as a safe and organized view of how human interactions and relationships work and act as a secure base for children to explore and successfully understand the social world around them (Feeney & Noller, 1996). However, this depends on whether or not safety, a secure base, and an organized view of relationships are formed between the caregiver and child during the first 18 months of the child’s life. Moreover, if a child experiences maltreatment such as abuse and neglect from primary caregivers during their first 18 months of life, it can severely affect what type of attachment style is formed and how development occurs in early adulthood (Connell-Corrick, 2011). Therefore, to thoroughly understand how childhood maltreatment affects attachment and development, an overview of both attachment theory and childhood maltreatment, the effects of childhood maltreatment on both attachment and development, and the importance of protective factors, interventions, and preventions will be discussed.

ContributorsMarasinghe, Parami (Author) / Arce, Alma (Thesis director) / Visconti, Kari (Committee member) / Barrett, The Honors College (Contributor) / School of Social and Behavioral Sciences (Contributor) / Sanford School of Social and Family Dynamics (Contributor)
Created2023-05
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Aristotle studied developing organisms, among other things, in ancient Greece, and his writings shaped Western philosophy and natural science for greater than two thousand years. He spent much of his life in Greece and studied with Plato at Plato's Academy in Athens, where he later established his own school called

Aristotle studied developing organisms, among other things, in ancient Greece, and his writings shaped Western philosophy and natural science for greater than two thousand years. He spent much of his life in Greece and studied with Plato at Plato's Academy in Athens, where he later established his own school called the Lyceum. Aristotle wrote greater than 150 treatises on subjects ranging from aesthetics, politics, ethics, and natural philosophy, which include physics and biology. Less than fifty of Aristotle's treatises persisted into the twenty-first century. In natural philosophy, later called natural science, Aristotle established methods for investigation and reasoning and provided a theory on how embryos generate and develop. He originated the theory that an organism develops gradually from undifferentiated material, later called epigenesis.

Created2016-07-07
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Description
While some stress during pregnancy is normal, continuous stress during pregnancy could have negative lasting impacts on a child’s health. The type of stress that is harmful during pregnancy is “the kind that doesn’t let up” (Watson). This type of stress is chronic and is more intense than the normal

While some stress during pregnancy is normal, continuous stress during pregnancy could have negative lasting impacts on a child’s health. The type of stress that is harmful during pregnancy is “the kind that doesn’t let up” (Watson). This type of stress is chronic and is more intense than the normal stresses of everyday life. Researchers have shown that when fetuses are continuously exposed to such levels of stress, their bodies react in unhealthy ways. Given all the data showing that varying stressors experienced by pregnant women negatively affect their children’s postnatal health and development, it is important to identify the specific impacts of these stressors in order to understand how they affect the health of children.
By conducting a literature review, I have found a number of studies reporting links between a pregnant woman’s stress and the development of health issues in her child. For example, researchers of one study found that infants born to women who were depressed during pregnancy had early brain development issues and difficulty regulating emotions and stress (Hayes, et. al). In another study, researchers observed a positive association between maternal anxiety during pregnancy and asthma in offspring (Cookson, et. al). Such findings indicate the significance of the prenatal period in healthy child development. However, while we may suspect that there are some negative outcomes for children born to chronically stressed women, there was interestingly a lack of information in areas where we may expect to find effects on the child. This gap in the literature indicates that we do not fully understand the effects of stress during pregnancy, and it seems that we do not know what really seems important to know about mental health during pregnancy. Thus, the results reflect that the existing knowledge in this area is lacking, making it challenging for medical specialists to understand how they may best intervene in order to promote the healthiest pregnancies and children.
ContributorsKeller, Carrie Angelique (Author) / Maienschein, Jane (Thesis director) / Abboud, Carolina (Committee member) / Historical, Philosophical & Religious Studies (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
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This research study evaluated the effects of early childhood environment and the influence parenting style has on the life outcomes among university students who varied in psychopathic traits; demonstrating evidence to show students who scored highly in measures of psychopathy used antisocial success seeking strategies to attain common life goals.

This research study evaluated the effects of early childhood environment and the influence parenting style has on the life outcomes among university students who varied in psychopathic traits; demonstrating evidence to show students who scored highly in measures of psychopathy used antisocial success seeking strategies to attain common life goals. This study examined the prospect of parenting styles and childhood environment as possible influences on important differences between psychopaths who become involved in the American legal system and those who do not. These differences were identified by asking participants to describe how often they engage in success seeking behaviors by using either prosocial or antisocial methods. Results were based on a hierarchical regression analysis and illustrated psychopathy as a significant predictor for utilizing antisocial success seeking strategic behavior. Such strategies include lying on job applications, accepting credit for the work of others, or winning a competition by cheating. In contrast, our Model determined that parental influence based on measures of paternal and maternal warmth, financial support, and physical and emotional abuse, did not significantly predict either prosocial success seeking strategies or antisocial success seeking strategies. Possible trends relating to childhood environment were identified but were undoubtedly restricted due to the evidently small sample size in this study. Conclusions into this investigation affirm the necessity for additional research into this view of psychopathy and how some psychopaths may be able to utilize their unique traits to their advantage.
ContributorsMcSweeney, Christy Anne (Author) / Black, Candace J. (Thesis director) / Pardini, Dustin A. (Committee member) / School of Social and Behavioral Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
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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),

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.
Created2019-05