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

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

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

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

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

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Capitalism and Mental Illness: An Investigation of How Our Culture Makes Us Sick

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The purpose of this thesis is to examine the relationship between mental illness and capitalist consumer society. Many Americans are suffering from mental illness and there has to be something causing it besides a chemical imbalance in the brain. A

The purpose of this thesis is to examine the relationship between mental illness and capitalist consumer society. Many Americans are suffering from mental illness and there has to be something causing it besides a chemical imbalance in the brain. A capitalist society creates a set of expectations that conflict with human desires. The thesis takes a historical, economical, and psychological approach to answering the following question: Does a capitalist society make its citizens mentally sick? A brief history of capitalism over the past century is discussed, as well as a more in depth look at capitalism and the creation of neoliberalism during the 1980s. The psychological effects capitalism has on human beings is discussed for the majority of the thesis and focuses on ideas from the 1950s as well as the early 2000s. To show the effect capitalism has on modern day society, an analysis of a psychopharmaceutical drug commercial is given. The concluding thoughts attempt to offer solutions to the problems of human unhappiness in a consumer culture.

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2014-05

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The Importance of Studying Interactions With Ovarian Hormones: Implications for Depressive Symptoms in Premenopausal and Menopausal Women

Description

The relevance of depression in the clinical realm is well known, as it is one of the most common mental disorders in the United States. Clinical depression is the leading cause of disease for women worldwide. The sex difference in

The relevance of depression in the clinical realm is well known, as it is one of the most common mental disorders in the United States. Clinical depression is the leading cause of disease for women worldwide. The sex difference in depression and anxiety has guided the research of not just recent studies but older studies as well, supporting the theory that gonadal hormones are associated with the mechanisms of emotional cognition. The scientific literature points towards a clear correlative relationship between gonadal hormones, especially estrogens, and emotion regulation. This thesis investigates the neural pathways that have been indicated to regulate mood and anxiety. Currently, the research points to the hypothalamic-pituitary-adrenal axis, which regulates the stress response through its ultimate secretion of cortisol through the adrenal cortex, and its modulated response when exposed to higher levels of estrogen. Another mechanism that has been investigated is the interaction of estrogen and the serotonergic system, which is noteworthy because the serotonergic system is known for its importance in mood regulation. However, it is important to note that the research seeking to determine the neurobiological underpinnings of estrogen and the serotonergic system is not expansive. Future research should focus on determining the direct relationship between cortisol hypersecretion and estrogens, the specific neurobiological effects of serotonergic receptor subtypes on the antidepressant actions of estrogens, and the simultaneous effects of the stress and serotonergic systems on depressive symptoms.

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2021-05

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Today's Toxicity Tale: An Analysis of Depression Culture and American Society

Description

Depression is a prominent world disorder. Many prior studies have examined the biological, cognitive, and social elements of depression; however, few studies attempt to examine what role culture plays in this disorder. If culture plays such a large role in

Depression is a prominent world disorder. Many prior studies have examined the biological, cognitive, and social elements of depression; however, few studies attempt to examine what role culture plays in this disorder. If culture plays such a large role in human development, it only makes sense that it would have an impact on a society's depression experience. Furthermore, conformity has been found to play a large role in the behaviors and mood states of adolescents. If conformity holds such control within this population, it is likely that said conformity could be adapted to any decided behavior. Although there has been research conducted on depression, culture, and conformity separately, these concepts are not often looked at in unison. For this reason, the current thesis focuses on the interaction between depression, culture, and conformity by defining depression-culture and depression-conformity, examining the manifestation of these concepts within American society, and analyzing the effects of these concepts.

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2016-12

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Abnormal Psychology Trends in Social Psychology: Depression and Anxiety Correlate with Aggression

Description

In the last 10 years there has been an increase in the number of mental health disorders in the United States. As these individuals with abnormal behavior start to become the norm, psychological research will need to adapt. The present

In the last 10 years there has been an increase in the number of mental health disorders in the United States. As these individuals with abnormal behavior start to become the norm, psychological research will need to adapt. The present work seeks to explore how to solve this problem by introducing abnormal behavior into social psychology. This can be done by measuring how depression and anxiety are related to aggression. The results from this study show that depression, anxiety, and aggression are all significantly correlated with each other and that only depression was a significant predictor for aggression. Although there are some limitations to this study, the results still suggest that the field of social psychology may need to start looking at how abnormal behavior can affect peoples’ behaviors.

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2022-05

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A Literature Review on the Effectiveness of Art Therapy for Treating Depression and Anxiety Among Individuals in the Correctional System

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A recent analysis has predicted that close to a million Americans will have died from contracting COVID-19 (Sullivan, 2021, para. 1). Unsurprisingly, the most vulnerable people, like those who have been incarcerated, have been hit the hardest (Brennan Center for

A recent analysis has predicted that close to a million Americans will have died from contracting COVID-19 (Sullivan, 2021, para. 1). Unsurprisingly, the most vulnerable people, like those who have been incarcerated, have been hit the hardest (Brennan Center for Justice, 2020, para. 1). The ongoing COVID-19 pandemic has created additional stress affecting inmates both physically and mentally. Therefore, the maintenance of good mental health among inmates should be a concern. However, the nature of the correctional environment limits the therapeutic options available to health care professionals. Among the challenges mental health professionals face in ensuring quality care are a poor rapport between the care provider and client, having a client living in an environment where distressing factors are omnipresent, and a lack of resources (Gussak, 2015, p. 2). All of these issues are exacerbated when the client requiring mental health care is in the correctional system. Depression and anxiety are some of the most common disorders affecting the prison population. However, in the correctional system, therapies that have been found effective among a general population have been shown to not benefit 30% to 60% of clients (Abbing, Baars, Van Haastrecht, & Ponstein, 2019, p. 1). Effectively treating depression is of great concern because, as Gussak (2007) found, depression can lead to self-harming behaviors and suicide when left untreated (p. 2). Additionally, addressing and treating anxiety is of particular importance today as COVID-19 has been a significant source of distress; explicitly, one incarcerated journalist reported witnessing entire units of inmates experiencing high levels of anxiety and panic attacks (Popperl et al., 2020, para. 5). Thus, a critical review of the available literature can reveal the particular effectiveness of art therapy in treating depression and anxiety in prison populations. The impacts of implementing more effective therapies in the correctional system are a reduction in recidivism and successful reintegration into society. Consequently, this literature review will suggest a potential application of art therapy for improving the mental health of those incarcerated in the correctional system with the intent of engendering positive social impact.

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2021-12