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Description
Is it possible to treat the mouth as a natural environment, and determine new methods to keep the microbiome in check? The need for biodiversity in health may suggest that every species carries out a specific function that is required to maintain equilibrium and homeostasis within the oral cavity. Furthermore, the relationship between the microbiome and its host is mutually beneficial because the host is providing microbes with an environment in which they can flourish and, in turn, keep their host healthy. Reviewing examples of larger scale environmental shifts could provide a window by which scientists can make hypotheses. Certain medications and healthcare treatments have been proven to cause xerostomia. This disorder is characterized by a dry mouth, and known to be associated with a change in the composition, and reduction, of saliva. Two case studies performed by Bardow et al, and Leal et al, tested and studied the relationships of certain medications and confirmed their side effects on the salivary glands [2,3]. Their results confirmed a relationship between specific medicines, and the correlating complaints of xerostomia. In addition, Vissink et al conducted case studies that helped to further identify how radiotherapy causes hyposalivation of the salivary glands [4]. Specifically patients that have been diagnosed with oral cancer, and are treated by radiotherapy, have been diagnosed with xerostomia. As stated prior, studies have shown that patients having an ecologically balanced and diverse microbiome tend to have healthier mouths. The oral cavity is like any biome, consisting of commensalism within itself and mutualism with its host. Due to the decreased salivary output, caused by xerostomia, increased parasitic bacteria build up within the oral cavity thus causing dental disease. Every human body contains a personalized microbiome that is essential to maintaining health but capable of eliciting disease. The Human Oral Microbiomics Database (HOMD) is a set of reference 16S rRNA gene sequences. These are then used to define individual human oral taxa. By conducting metagenomic experiments at the molecular and cellular level, scientists can identify and label micro species that inhabit the mouth during parasitic outbreaks or a shifting of the microbiome. Because the HOMD is incomplete, so is our ability to cure, or prevent, oral disease. The purpose of the thesis is to research what is known about xerostomia and its effects on the complex microbiome of the oral cavity. It is important that researchers determine whether this particular perspective is worth considering. In addition, the goal is to create novel experiments for treatment and prevention of dental diseases.
ContributorsHalcomb, Michael Jordan (Author) / Chen, Qiang (Thesis director) / Steele, Kelly (Committee member) / Barrett, The Honors College (Contributor) / College of Letters and 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
Bexarotene is a synthetic analog of 9-cis-retinoic acid and ligand for the retinoid X receptor which has a history of clinical success in the treatment of T-cell lymphoma. Bexarotene has also shown potential for treating a variety of other cancers, which we seek to explore in this project. The potential of bexarotene lies in its unique mechanisms and wide application, however, it has shown limited effectiveness thus far in the treatment of breast and lung cancer, with moderate levels of efficacy and symptoms such as cutaneous toxicity, hyperlipidemia, and hypothyroidism. For this project several analogs of bexarotene were synthesized with the intentions of making a more potent ligand that can be used to treat these carcinomas while minimizing harmful side effects. We were successful in synthesizing a large variety of analogs over the span of roughly two years, including iso-chroman derivatives of bexarotene and NEt-TMN, in addition to a new series of analogs of the reported NEt-TMN derivative. These analogs were analyzed via melting point determination and nuclear magnetic resonance (NMR) spectroscopy to confirm the molecular structure and determine purity, and it is our intent to continue with further testing of these compounds to determine their effectiveness as well as the side effects they are likely to cause with levels of toxicity. Recent studies suggest that continuing the analysis of these compounds and other rexinoids like the ones described herein is a worthwhile endeavor as similar rexinoids have shown in numerous assays to be more potent and less toxic in the treatment of cancers when compared with bexarotene.
ContributorsMoen, Grant Anthony (Author) / Wagner, Carl (Thesis director) / Deutch, Charles (Committee member) / School of Social and Behavioral Sciences (Contributor) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
The termite Coptotermes gestroi is a small subterranean termite originating from Southeast Asia. The hindgut of C. gestroi contains five distinct species of parabasalid: Pseudotrichonympha leei, two undescribed species from the genus Holomastigotoides, and two undescribed species from the genus Cononympha. This study investigates the protist symbionts in C. gestroi and the relationship between their relative abundance as inferred by Illumina sequence reads and the directly observed abundances for each protist genus. Illumina amplicon sequencing as a means of DNA analysis is a proven method for identification and diversity analysis, although the specific ratios of sequence reads to cell abundance in protists is not well known. In this study, protist communities were observed under light microscopy; cells were counted under hemocytometer and characterized at the molecular level using Illumina amplicon sequencing. When comparing sequence read abundances to cell abundances, some general trends were found in both analysis methods. Cononmypha repeatedly formed the majority of the community, while Holomastigotoides and Pseudotrichonympha were responsible for a smaller yet similar portion of the population. Cell counts and sequence reads were also compared using an assumed linear model, with R2 values generated to quantify the relationship between both. The results suggest that Illumina sequencing can be used to obtain rough estimates of community diversity, but the high variability within the data suggest that the read abundances should be treated with caution.
ContributorsAvilucea, Erin L. (Author) / Gile, Gillian (Thesis director) / DeMartini, Francesca (Committee member) / Taerum, Stephen Joshua (Committee member) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Cancer, a disease which affects many lives, has been the topic of interest for this research. Treatment options are often available to help lessen the effects of the disease and in regards to cutaneous T-cell lymphoma (CTCL), no cure currently exists. An FDA approved drug by the name of Bexarotene has been developed to provide chemotherapeutic effects within CTCL. Bexarotene has also been used in trials of breast cancer, lung cancer, glioblastoma multiforme and various neurodegenerative diseases. Yet the medication often causes serious side effects including hyperthyroidism, raised triglyceride levels and cutaneous toxicity. The focus of this research is to synthesize a hydroxylated analog compound of Bexarotene in efforts to produce a molecule that provides better chemotherapeutic effects while also lessening the various side effects caused. Synthesis of the molecule followed various organic chemistry techniques and reactions to create the final product. Melting point analysis, NMR and other various characterization data helped to confirm the synthesis of the intended molecule. Preliminary bioassay data results of the analog compound showed similar potency to that of Bexarotene. Further testing, however, will be required to determine the full pharmacokinetic profile of the molecule. Future direction of the research focuses on both further testing of the hydroxylated analog as well synthesizing newer analog compounds to find a molecule that can provide the best effects within cutaneous T-cell lymphoma and the various other diseases as well.
ContributorsMinasian, Ani Christina (Author) / Wagner, Carl (Thesis director) / Marshall, Pamela (Committee member) / School of Social and Behavioral Sciences (Contributor) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The need for new tuberculocidal drugs is crucial with drug resistance on the rise as the tuberculosis epidemic rages on. One new potential drug target is the PrrAB two component system (TCS) since it does not exist in humans and is essential to viability in Mycobacterium tuberculosis. This project examines Mycobacterium smegmatis, and this nonpathogenic and fast-growing organism possesses two full length PrrAB orthologs, in addition to an orphaned PrrB sensor histidine kinase. While it was determined that PrrAB1 and PrrAB2 are nonessential, the lone PrrB3 is not yet characterized for essentiality. To confirm individual dispensability of PrrAB1 and PrrAB2 and investigate the essentiality of PrrB3 and the full M. smegmatis PrrAB multiplex, we utilized CRISPRi dCas9 to repress the expression (knockdown) of prrAB1 (MSMEG_5662-5663), prrAB2 (MSMEG_0244-0246), and the lone prrB3 (MSMEG_2793) in M. smegmatis independently and simultaneously. Repression of prrAB1 resulted in the greatest growth defect, with a lag of 17 cellular division cycles compared to the control, a strain generated with an empty vector. However, the knockdown of prrAB1 was not lethal to M. smegmatis. The inhibition of all three prrAB orthologs simultaneously, also known as a multiplex knockdown, lagged the control by 13 cellular division cycles. At the 48-hour point, both the single ortholog repression of prrAB1 as well as the whole prrAB system knockdown had a growth defect of 13 replication cycles behind the control. However, the multiplex knockdown stabilized growth at 48 hours, revealing a possible compensatory mechanism in M. smegmatis. Conclusively, we show that the PrrAB TCS is globally inessential for viability in M. smegmatis.
ContributorsHeiligenstein, Piper (Author) / Haydel, Shelley (Thesis director) / Shrivastava, Abhishek (Committee member) / Haller, Yannik (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / School of Mathematical and Natural Sciences (Contributor)
Created2023-12
Description
The ever-increasing importance of cancer and neurodegenerative diseases continues to grow as populations across the world are affected by death and aging. The vitamin A (RXR) and vitamin D (VDR) receptor pathways offer promising potential to aid in treatment of cancer and Alzheimer’s disease. This thesis discusses the potential application of novel analogs of Bexarotene (RXR agonist), MeTC7 (a new potent VDR antagonist), and vitamin D as possible therapeutics for cancer and Alzheimer’s disease.
ContributorsHong, Jennifer (Author) / Jurutka, Peter (Thesis director) / Wagner, Carl (Committee member) / Marshall, Pamela (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor)
Created2023-05
Description
The use of DNA testing has been focused primarily on biological samples such as blood or saliva found at crime scenes. These types of evidence in the forensic field are sometimes difficult to come by, especially when there is no body to find to verify things such as identity or status of a person. In the case of the burial of a body, they can be remote and relocated multiple times depending on each situation. Clandestine burials are not uncommon especially in the Arizona desert by the United States and Mexico border. Since there is no physical body to find the next best avenue to finding a clandestine burial is through search teams which can take weeks to months or other expensive technology such as ground penetrating radar (GPR). A new more interesting avenue to search for bodies is using the most found material–soil. Technology has allowed the possibility of using soil DNA microbiome testing initially to study the varieties of microbes that compose in soil. Microbiomes are unique and plentiful and essentially inescapable as humans are hosts of millions of them. The idea of a microbiome footprint at a crime scene seems out of reach considering the millions of species that can be found in various areas. Yet it is not impossible to get a list of varieties of species that could indicate there was a body in the soil as microbiomes seep through from decomposition. This study determines the viability of using soil microbial DNA as a method of locating clandestine graves by testing 6 different locations of a previous pig decomposition simulation. These two locations give two different scenarios that a body may be found either exposed to the sun in an open field or hidden under foliage such as a tree in the Sonoran Desert. The experiment will also determine more factors that could contribute to a correlation of microbiome specific groups associated with decomposition in soil such as firmicutes. The use of soil microbial DNA testing could open the doors to more interpretation of information to eventually be on par with the forensic use of biological DNA testing which could potentially supplement testimonies on assumed burial locations that occurs frequently in criminal cases of body relocation and reburial.
ContributorsMata Salinas, Jennifer (Author) / Marshall, Pamela (Thesis director) / Bolhofner , Katelyn (Committee member) / Wang, Yue (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor) / School of Humanities, Arts, and Cultural Studies (Contributor)
Created2022-05