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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
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Description
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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Description

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

Neurocristopathies are a class of pathologies in vertebrates,
including humans, that result from abnormal expression, migration,
differentiation, or death of neural crest cells (NCCs) during embryonic development. NCCs are cells
derived from the embryonic cellular structure called the neural crest.
Abnormal NCCs can cause a neurocristopathy by chemically affecting the

Neurocristopathies are a class of pathologies in vertebrates,
including humans, that result from abnormal expression, migration,
differentiation, or death of neural crest cells (NCCs) during embryonic development. NCCs are cells
derived from the embryonic cellular structure called the neural crest.
Abnormal NCCs can cause a neurocristopathy by chemically affecting the
development of the non-NCC tissues around them. They can also affect the
development of NCC tissues, causing defective migration or
proliferation of the NCCs. There are many neurocristopathies
that affect many different types of systems. Some neurocristopathies
result in albinism (piebaldism) and cleft palate in humans. Various
pigment, skin, thyroid, and hearing disorders, craniofacial and heart
abnormalities, malfunctions of the digestive tract, and tumors can be
classified as neurocristopathies. This classification ties a variety of
disorders to one embryonic origin.

Created2014-09-19
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Description

Early in the process of development, vertebrate embryos develop a fold on the neural plate where the neural and epidermal ectoderms meet, called the neural crest. The neural crest produces neural crest cells (NCCs), which become multiple different cell types and contribute to tissues and organs as an embryo develops.

Early in the process of development, vertebrate embryos develop a fold on the neural plate where the neural and epidermal ectoderms meet, called the neural crest. The neural crest produces neural crest cells (NCCs), which become multiple different cell types and contribute to tissues and organs as an embryo develops. A few of the organs and tissues include peripheral and enteric (gastrointestinal) neurons and glia, pigment cells, cartilage and bone of the cranium and face, and smooth muscle. The diversity of NCCs that the neural crest produces has led researchers to propose the neural crest as a fourth germ layer, or one of the primary cellular structures in early embryos from which all adult tissues and organs arise. Furthermore, evolutionary biologists study the neural crest because it is a novel shared evolutionary character (synapomorphy) of all vertebrates.

Created2014-09-15
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Description

The Law of Acceleration of Growth is a theory proposed by Edward Drinker Cope in the US during the nineteenth century. Cope developed it in an attempt to explain the evolution of genera by appealing to changes in the developmental timelines of organisms. Cope proposed this law as an additional

The Law of Acceleration of Growth is a theory proposed by Edward Drinker Cope in the US during the nineteenth century. Cope developed it in an attempt to explain the evolution of genera by appealing to changes in the developmental timelines of organisms. Cope proposed this law as an additional theory to natural selection. He argued that the evolution of genera, the more general groups within which biologists group species, occurs when the individual in a species move through developmental stages faster than did their ancestors, but within the same fixed period of gestation, and thus can undergo new developmental stages and develop new traits. The Law of Acceleration compliments Cope's Law of Retardation of Growth. He described the later law as the process by which organisms revert to an ancestral stage. In these cases, forces suppress the most recent traits or stages common to the development of individuals from different species within the same genus. Cope described evolution as progressive, following a predetermined path, a perspective about evolution sometimes called orthogenetic. Cope's was one among many orthogenic theories in the second half of the nineteenth century. Furthermore, the theory was part of a trend in nineteenth century in which some biologists claimed that the changes in developmental timing of organisms could explain large changes in biological forms throughout natural history.

Created2014-07-24