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Bite Force Analysis of Leucoraja erinacea Skates to Understand Morphological Evolution of Different Cartilaginous Fish

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By studying organismal performance, one can gain insight regarding the evolutionary and developmental processes that shape the adult organism. Bite force is an important trait that can be linked to performance, and therefore survival, of the entire organism. In order

By studying organismal performance, one can gain insight regarding the evolutionary and developmental processes that shape the adult organism. Bite force is an important trait that can be linked to performance, and therefore survival, of the entire organism. In order for an animal to successfully feed upon its prey, the components of the jaw, such as the skeleton and attached muscles, must be strong enough to withstand the forces required for capturing and then processing (masticating) the prey. Because sharks and skates have a fully cartilaginous skeleton, they theoretically bite off more than deemed biologically possible, these organisms, therefore, are excellent models for study when trying to understand bite performance. The goal was to measure the bite force of Leucoraja erinacea. Dissections were completed for 14 individuals, in order to expose the muscles beneath the skin. The muscles were then removed, and the mass was recorded. Calculations derived from the literature were used to determine total bite force. Linear regression was used to determine the relationship between bite force and size of the organism. The average maximum bite force of Leucoraja erinacea was determined to be roughly 23.3 Newtons (N). There was a positive relationship between bite force and size. This skate produces a much smaller bite force than many other organisms, providing insight into its ecological role in food webs. Many of the shells of commercially important prey were also much stronger than the bite forces estimated for these skates, suggesting that either the skates were not mature or large enough to feed on these prey, or, perhaps this species is unable to feed on these organisms entirely.

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2018-05

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Analysis of Retinoid X Receptor (RXR) Homodimerization Driven by RXR Ligands Using Yeast Two-Hybrid

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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

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.

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2015-05

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Characterization of Second and Third Generation, Novel RXR Selction Agonists for the Treatment of Cutaneous T-Cell Lymphoma

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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

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.

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2012-05