Matching Items (27)
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
Scientific literacy is a critical part of the education of high school students. Students can demonstrate literacy in science by being able to read and write scientific reports as well as recognize and discuss how science affects daily lives. However, many teachers are not familiar with the topic and do not have the resources necessary to implement it into their classrooms. This project attempts to create a website that compiles information from many sources to one concise location that is simple for teachers to use. The goal of the website is to provide teachers with a resource that they can access and use quickly despite their busy schedules. The information provided is easily translatable into a classroom, and examples of lessons as well as links to resources are provided. Considerations of difficulties such as the need to prepare students for standardized tests as well as limited budgets were brought into consideration when choosing the concepts suggested for teachers. Aspects of scientific literacy addressed are: project based learning, virtual labs, apprenticeship programs, and peer mediated learning strategies. The project also addresses how demographics that are represented at lower levels in science can be aided. These groups include female students, minorities, and students with High Functioning Autism (HFA). The website portion of the project is accompanied by a paper that summarizes the research findings as well as the personal reaction of the author and how her teaching has been affected by the study. Upon completion of the project the website will be shared with school districts across Phoenix to provide teachers with access to the resources compiled in it.
ContributorsBlome, Rebecca Ellen (Author) / Marshall, Pamela (Thesis director) / Hart, Juliet (Committee member) / Division of Teacher Preparation (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12
Description
In humans, infections, disease, inflammation, and other injuries to specific tissues have been shown to cause delays in the onset of puberty. It is known that steroid hormones and insulin play a role in these delays, yet it is not understood what is happening with the immune system during this response. Similar results have been found in the fruit fly, Drosophila melanogaster, in which damage to adult precursor tissues triggers developmental delays. This project addresses the immune component of the injury response in Drosophila. The goal is to identify which immune response genes, if any, show a significant change in expression after injury. The general methodologies used were first inducing injury via a temperature- sensitive expression of cell death genes in wing precursor tissues, then examining changes in gene expression of immune response genes before and after injury using real-time PCR. The results show that injury increases the expression of genes Drs, CecA1, and Def while decreasing expression of Rel, Dpt, PGRP-LE, and Tl. The changes in immune gene expression following injury suggest the possibility of an immune component to the systemic injury response. These results can further be explored by using mutations of the immune genes to examine their direct effects on the systemic injury response. This research can eventually lead to preventative measures to protect against developmental delays due to infections and diseases in humans.
ContributorsDuprey, Deanna Jeanette (Author) / Hackney, Jennifer (Thesis director) / Marshall, Pamela (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor) / School of Social and Behavioral Sciences (Contributor)
Created2014-12
Description
This project details the synthesis and analysis of five analogs of model compound NEt-4IB (6-[ethyl(4-isobutoxy-3-isopropylphenyl)amino]nicotinic acid), that target the retinoid-X-receptor (RXR). These molecules were synthesized by substituting, adding, or removing substituents in the nitrogen-containing ring of NEt-4IB. The parent compound is a RXR partial agonist and has proven to be effective in the treatment of type II diabetes without the unwanted side effects seen with full agonists. Many of the current drugs used to treat type II diabetes are accompanied by adverse effects including increased triglyceride levels, weight gain, and hypoglycemia. Biological evaluation with KK-Ay (obese diabetic) model mice indicates that NEt-4IB may even be more effective than current drugs on the market, like pioglitazone. As a result, it is predicted that due to such structural similarity, the analogs synthesized for this work will perform equally, if not better than, NEt-4IB.
ContributorsMaiorella, Emma Lauren (Author) / Wagner, Carl (Thesis director) / Marshall, Pamela (Committee member) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Virtually all animals require relatively predictable developmental schedules in order to fulfill the cycle of life. Cell death and severe inflammation alter steroid hormone production and can disrupt the timing of developmental transitions such as puberty. In the fruit fly, Drosophila melanogaster, injury to wing precursor tissues has been shown to result in decreased steroid hormone levels and delay development. The effects of damage to other tissues have not yet been explored. Here, the larval salivary glands were damaged in order to observe how injuring these specific tissues affect the timing of developmental transitions. Damage was induced by tissue-specific, temperature sensitive activation of cell death genes. The results indicated that death to salivary gland cells accelerates the Drosophila time to adult eclosion and that the observed acceleration of development is age-dependent. Insight into the effects of injury on development in Drosophila can potentially lead to information about development in other organisms, including humans, following injury or chronic inflammation.
ContributorsRippere, Alicia Leann (Author) / Hackney, Jennifer (Thesis director) / Marshall, Pamela (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor)
Created2015-05
Description
Calcium is the only ion capable of triggering electrical and chemical reactions in cells which are part of essential biomolecular processes, such as gene transcription and ion flux. Calcium homeostasis, the control of concentration levels, is therefore crucial for the proper functioning of cells. For example, cardiomyocytes, the cells that form cardiac muscle, rely on calcium transfer process to produce muscle contraction.
The purpose of this work is to study aspects of calcium homeostasis in the model organism Saccharomyces cerevisiae, common yeast. Using luminometric techniques, the response of the yeast was monitored against a set of changes in the environment calcium abundance. The results indicate a complex response as both increase and decreases of external calcium induce elevations in cytosolic calcium concentrations.
Calcium is transferred across compartments by means of channels. In Saccharomyces cerevisiae, many of them have been identified; Cch1p-Mid1p, Vcx1p, Pmc1p, Pmr1p, and Yvc1p. Their participation in calcium homeostasis is well established. Observations of cytosolic calcium increase after a hypertonic shock are mainly associated with influx of ions from the environment though the Cch1p-Mid1p. This process is generally considered as driven by calcium concentration gradients. However, recent studies have suggested that the plasma membrane channel, Cch1p-Mid1p, may possess more sophisticated regulation and sensory mechanisms. The results of our experiments support these ideas.
We carried out experiments that subjected yeast to multiple shocks: a hypertonic shock followed by either a second hypertonic shock, a hypotonic shock, or a yeast dilution pulse where the solution volume increases by the calcium concentration has only a small change. The cytosolic calcium concentration of a yeast population was monitored via luminometry.
The main result of this study is the observation of an unexpected response to the combination of hypertonic and hypotonic shocks. In this case it was observed that the cytosolic calcium concentration increased after both shocks. This indicates that cytosolic calcium increases are not solely driven by the presence of concentration gradients. The response after the hypotonic pulse arises from more complex mechanisms that may include sensor activity at the membrane channels and the release of calcium from internal storages.
The purpose of this work is to study aspects of calcium homeostasis in the model organism Saccharomyces cerevisiae, common yeast. Using luminometric techniques, the response of the yeast was monitored against a set of changes in the environment calcium abundance. The results indicate a complex response as both increase and decreases of external calcium induce elevations in cytosolic calcium concentrations.
Calcium is transferred across compartments by means of channels. In Saccharomyces cerevisiae, many of them have been identified; Cch1p-Mid1p, Vcx1p, Pmc1p, Pmr1p, and Yvc1p. Their participation in calcium homeostasis is well established. Observations of cytosolic calcium increase after a hypertonic shock are mainly associated with influx of ions from the environment though the Cch1p-Mid1p. This process is generally considered as driven by calcium concentration gradients. However, recent studies have suggested that the plasma membrane channel, Cch1p-Mid1p, may possess more sophisticated regulation and sensory mechanisms. The results of our experiments support these ideas.
We carried out experiments that subjected yeast to multiple shocks: a hypertonic shock followed by either a second hypertonic shock, a hypotonic shock, or a yeast dilution pulse where the solution volume increases by the calcium concentration has only a small change. The cytosolic calcium concentration of a yeast population was monitored via luminometry.
The main result of this study is the observation of an unexpected response to the combination of hypertonic and hypotonic shocks. In this case it was observed that the cytosolic calcium concentration increased after both shocks. This indicates that cytosolic calcium increases are not solely driven by the presence of concentration gradients. The response after the hypotonic pulse arises from more complex mechanisms that may include sensor activity at the membrane channels and the release of calcium from internal storages.
ContributorsMintz, David Anthony (Co-author) / Parker, Augustus (Co-author) / Solis, Francisco (Thesis director) / Marshall, Pamela (Committee member) / School of Mathematical and Natural Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Calcium is the only ion capable of triggering electrical and chemical reactions in cells which are part of essential biomolecular processes, such as gene transcription and ion flux. Calcium homeostasis, the control of concentration levels, is therefore crucial for the proper functioning of cells. For example, cardiomyocytes, the cells that form cardiac muscle, rely on calcium transfer process to produce muscle contraction.
The purpose of this work is to study aspects of calcium homeostasis in the model organism Saccharomyces cerevisiae, common yeast. Using luminometric techniques, the response of the yeast was monitored against a set of changes in the environment calcium abundance. The results indicate a complex response as both increase and decreases of external calcium induce elevations in cytosolic calcium concentrations.
Calcium is transferred across compartments by means of channels. In Saccharomyces cerevisiae, many of them have been identified; Cch1p-Mid1p, Vcx1p, Pmc1p, Pmr1p, and Yvc1p. Their participation in calcium homeostasis is well established. Observations of cytosolic calcium increase after a hypertonic shock are mainly associated with influx of ions from the environment though the Cch1p-Mid1p. This process is generally considered as driven by calcium concentration gradients. However, recent studies have suggested that the plasma membrane channel, Cch1p-Mid1p, may possess more sophisticated regulation and sensory mechanisms. The results of our experiments support these ideas.
We carried out experiments that subjected yeast to multiple shocks: a hypertonic shock followed by either a second hypertonic shock, a hypotonic shock, or a yeast dilution pulse where the solution volume increases by the calcium concentration has only a small change. The cytosolic calcium concentration of a yeast population was monitored via luminometry.
The main result of this study is the observation of an unexpected response to the combination of hypertonic and hypotonic shocks. In this case it was observed that the cytosolic calcium concentration increased after both shocks. This indicates that cytosolic calcium increases are not solely driven by the presence of concentration gradients. The response after the hypotonic pulse arises from more complex mechanisms that may include sensor activity at the membrane channels and the release of calcium from internal storages.
The purpose of this work is to study aspects of calcium homeostasis in the model organism Saccharomyces cerevisiae, common yeast. Using luminometric techniques, the response of the yeast was monitored against a set of changes in the environment calcium abundance. The results indicate a complex response as both increase and decreases of external calcium induce elevations in cytosolic calcium concentrations.
Calcium is transferred across compartments by means of channels. In Saccharomyces cerevisiae, many of them have been identified; Cch1p-Mid1p, Vcx1p, Pmc1p, Pmr1p, and Yvc1p. Their participation in calcium homeostasis is well established. Observations of cytosolic calcium increase after a hypertonic shock are mainly associated with influx of ions from the environment though the Cch1p-Mid1p. This process is generally considered as driven by calcium concentration gradients. However, recent studies have suggested that the plasma membrane channel, Cch1p-Mid1p, may possess more sophisticated regulation and sensory mechanisms. The results of our experiments support these ideas.
We carried out experiments that subjected yeast to multiple shocks: a hypertonic shock followed by either a second hypertonic shock, a hypotonic shock, or a yeast dilution pulse where the solution volume increases by the calcium concentration has only a small change. The cytosolic calcium concentration of a yeast population was monitored via luminometry.
The main result of this study is the observation of an unexpected response to the combination of hypertonic and hypotonic shocks. In this case it was observed that the cytosolic calcium concentration increased after both shocks. This indicates that cytosolic calcium increases are not solely driven by the presence of concentration gradients. The response after the hypotonic pulse arises from more complex mechanisms that may include sensor activity at the membrane channels and the release of calcium from internal storages.
ContributorsParker, Augustus Carrucciu (Co-author) / Mintz, David (Co-author) / Solis, Francisco (Thesis director) / Marshall, Pamela (Committee member) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
A long personal struggle with Lyme disease prompted me to review the current literature to better understand what remains elusive to researchers and physicians. Lyme disease was first discovered in Connecticut in the mid-1970’s, however, in Europe, it was already being treated with antibiotics. The disease is caused by a spirochete bacteria named Borrelia burgdorferi after the scientist who married the European syndromes associated with the microbe to the disease found in the United States. Borrelia burgdorferi is capable of evading the immune system through a variety of methods, some of which are still not clearly understood. Treatment for Lyme disease is effective and involves antibiotics over a variable duration depending on the presentation of the disease. Post-treatment Lyme Disease Syndrome (PTLDS) is the heart of the controversy surrounding this disease as patients continue to have debilitating symptoms with no clear cause.
ContributorsBailey, Susan Caroline (Author) / Hackney Price, Jennifer (Thesis director) / Marshall, Pamela (Committee member) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Rexinoids such as Bexarotene have been developed as effective treatments of different diseases including lymphoma, breast cancer, lung cancer, Alzheimer’s disease, and diabetes. This is due to the widespread nature of the retinoid X receptor, which is the target of these drugs, throughout the body. However, Bexarotene is not infallible and has many negative side effects which limit the use of the drug to only a short period of time. This may be fine for chemotherapy, but rexinoids have been proposed to also be effective at preventing cancer as well. This is not currently possible with the side effects seen with approved rexinoids. Due to this, six novel rexinoids were created in hopes of reducing the side effect profile of rexinoids. The idea of dual agonism was also explored with two of the compounds created as well. All six of these compounds, after creation and purification, were sent off for in vitro and in vivo testing to confirm side effect profile and efficacy.
ContributorsFrazier, Madison S (Author) / Wagner, Carl (Thesis director) / Marshall, Pamela (Committee member) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Exposure of harmful ultraviolet rays (UV) is a great concern in many locations around the world, as skin diseases and cancer continue to surge. With the number of skin cancer skyrocketing past all the types of known cancers, a vast majority of cases are reported daily. When the skin is exposed to UVA or UVB radiation, primarily from the sun, the UV radiation damages the DNA within the cells, which results in skin cancer. However, most damaged DNA of cells can undergo nucleotide excision repair. This involves a nuclease molecule that cuts the damaged bases. Preliminary research has developed other ways of repairing DNA damage in cells by implementing organic compounds. An organic chemical such as, ferulic acid has the ability to aid the mechanisms involved in nucleotide excision repair that takes place in your cells after DNA damage.
To test this, Saccharomyces cerevisiae was utilized. This is a primary model used in most medicinal studies due to the resemblance to human cells. This study evaluates the effect of ferulic acid, concentrations on ultraviolet radiated Rad 1 (mutant) and HB0 (wild type) yeast cells. The yeast strains were grown in two different concentrations for ferulic acid and treated with long-wave UV light under 30 seconds, 45 seconds, and 60 seconds. It is observed that, Rad 1 had heavier growth in the presence of high concentration of ferulic acid after UV treatment than HB0. But, HB0 yeast had heavier growth in the presence of lower concentrations of ferulic acid after UV treatment. Ferulic acid concentrations of 1 mM can influence cell repair after UV application by mRNA expression during nucleotide excision repair and higher absorption of UV.
To test this, Saccharomyces cerevisiae was utilized. This is a primary model used in most medicinal studies due to the resemblance to human cells. This study evaluates the effect of ferulic acid, concentrations on ultraviolet radiated Rad 1 (mutant) and HB0 (wild type) yeast cells. The yeast strains were grown in two different concentrations for ferulic acid and treated with long-wave UV light under 30 seconds, 45 seconds, and 60 seconds. It is observed that, Rad 1 had heavier growth in the presence of high concentration of ferulic acid after UV treatment than HB0. But, HB0 yeast had heavier growth in the presence of lower concentrations of ferulic acid after UV treatment. Ferulic acid concentrations of 1 mM can influence cell repair after UV application by mRNA expression during nucleotide excision repair and higher absorption of UV.
ContributorsSabir, Zhino Lashkry (Author) / Marshall, Pamela (Thesis director) / Quaranta, Kimberly (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-12