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Cancer is a disease that occurs in many and perhaps all multicellular organisms. Current research is looking at how different life history characteristics among species could influence cancer rates. Because somatic maintenance is an important component of a species' life history, we hypothesize the same ecological forces shaping the life

Cancer is a disease that occurs in many and perhaps all multicellular organisms. Current research is looking at how different life history characteristics among species could influence cancer rates. Because somatic maintenance is an important component of a species' life history, we hypothesize the same ecological forces shaping the life history of a species should also determine its cancer susceptibility. By looking at varying life histories, potential evolutionary trends could be used to explain differing cancer rates. Life history theory could be an important framework for understanding cancer vulnerabilities with different trade-offs between life history traits and cancer defenses. Birds have diverse life history strategies that could explain differences in cancer suppression. Peto's paradox is the observation that cancer rates do not typically increase with body size and longevity despite an increased number of cell divisions over the animal's lifetime that ought to be carcinogenic. Here we show how Peto’s paradox is negatively correlated for cancer within the clade, Aves. That is, larger, long-lived birds get more cancer than smaller, short-lived birds (p=0.0001; r2= 0.024). Sexual dimorphism in both plumage color and size differ among Aves species. We hypothesized that this could lead to a difference in cancer rates due to the amount of time and energy sexual dimorphism takes away from somatic maintenance. We tested for an association between a variety of life history traits and cancer, including reproductive potential, growth rate, incubation, mating systems, and sexual dimorphism in both color and size. We found male birds get less cancer than female birds (9.8% vs. 11.1%, p=0.0058).
ContributorsDolan, Jordyn Nicole (Author) / Maley, Carlo (Thesis director) / Harris, Valerie (Committee member) / Boddy, Amy (Committee member) / School of Molecular Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
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The concept of the Mediterranean Diet was described by Ancel Keys from the Seven Countries study, occurring in the 1960s. Unlike other diets, the Mediterranean Diet is a cultural tradition of nations surrounding the Mediterranean Sea. It involves the healthy pattern of food consumption and physical activity, which developed as

The concept of the Mediterranean Diet was described by Ancel Keys from the Seven Countries study, occurring in the 1960s. Unlike other diets, the Mediterranean Diet is a cultural tradition of nations surrounding the Mediterranean Sea. It involves the healthy pattern of food consumption and physical activity, which developed as an outcome of the locality's available food, other environmental resources, and overall cultural characteristics such as the polychromic time orientation of the Mediterranean nations. The Mediterranean Diet is a lifestyle structured around understanding a locality's natural conditions and resources and sustaining positive relationships between individuals, the community, and the components of their environment. The diet is largely plant based, where daily foods include grains, fruits, vegetables, olive oil, and dairy products. Seafood is eaten several times a week, while other animal products (poultry, meats, eggs) and sweets are eaten less often and in moderation. Alcohol, for those who drink it, is consumed several times a week. Research has shown a variety of health benefits from this diet. These benefits include preventing cardiovascular disease, certain cancers, Type 2 diabetes, Alzheimer's disease, age related macular degeneration of the eyes, kidney disease and osteoporosis. It also has been shown to improve conditions of metabolic syndrome, obesity, and depression. These favorable health outcomes are a result of the beneficial components within the foods commonly eaten. Fruits and vegetables are excellent sources of vitamins and minerals, which are needed to support cellular and overall organismal functioning, and nuts, vegetables, and fish also provide essential fatty acids like omega-3 and omega-6. The unifying component for all regions adhering to the Mediterranean Diet is the use of olive oil. Beyond being a healthy source of fat, it contains numerous chemical components with antioxidant properties. The Mediterranean region is an optimal region for olive tree growth and olive harvest, based on temperature and soil conditions. However, geographic differences, nutrient availability and age of olive trees can impact the quality of olive fruits and olive oil. Furthermore, climate change presents a challenge for sustaining the Mediterranean diet as it adds stress to plants and aquatic life environments. However, the diet shows promise of protecting the environment, as plant-based diets are found to have lower negative environmental impacts. In conclusion, the Mediterranean diet is an interconnected system of relationships that adapts to a locality's community, land, and climate.
ContributorsKaneris, Marianna Irene (Author) / Vitullo, Juliann (Thesis director) / Dal Martello, Chiara (Committee member) / Department of Psychology (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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While specific resistance mechanisms to targeted inhibitors in BRAF-mutant cutaneous melanoma have been identified, surprisingly little is known about the rate at which resistance develops under different treatment options. There is increasing evidence that resistance arises from pre-existing clones rather than from de novo mutations, but there remains the need

While specific resistance mechanisms to targeted inhibitors in BRAF-mutant cutaneous melanoma have been identified, surprisingly little is known about the rate at which resistance develops under different treatment options. There is increasing evidence that resistance arises from pre-existing clones rather than from de novo mutations, but there remains the need for a better understanding of how different drugs affect the fitness of clones within a tumor population and promote or delay the emergence of resistance. To this end, we have developed an assay that defines the in vitro rate of adaptation by analyzing the progressive change in sensitivity of a melanoma cell line to different treatments. We performed a proof-of-theory experiment based on the hypothesis that drugs that cause cell death (cytotoxic) impose a higher selection pressure for drug-resistant clones than drugs that cause cell-cycle arrest (cytostatic drugs), thereby resulting in a faster rate of adaptation. We tested this hypothesis by continuously treating the BRAFV600E melanoma cell line A375 with the cytotoxic MEK inhibitor E6201 and the cytostatic MEK inhibitor trametinib, both of which are known to be effective in the setting of constitutive oncogenic signaling driven by the BRAF mutation. While the identification of confounding factors prevented the direct comparison between E6201-treated and trametinib-treated cells, we observed that E6201-treated cells demonstrate decreased drug sensitivity compared to vehicle-treated cells as early as 18 days after treatment begins. We were able to quantify this rate of divergence at 2.6% per passage by measuring the increase over time in average viability difference between drug-treated and vehicle-treated cells within a DDR analysis. We argue that this value correlates to the rate of adaptation. Furthermore, this study includes efforts to establish a barcoded cell line to allow for individual clonal tracking and efforts to identify synergistic and antagonist drug combinations for use in future experiments. Ultimately, we describe here a novel system capable of quantifying adaptation rate in cancer cells undergoing treatment, and we anticipate that this assay will prove helpful in identifying treatment options that circumvent or delay resistance through future hypothesis-driven experiments.
ContributorsDe Luca, Valerie Jean (Author) / Wilson Sayres, Melissa (Thesis director) / Trent, Jeff (Committee member) / Hendricks, William (Committee member) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
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This study was conducted to observe the effects of vitamin C supplementation upon the expression of sICAM-1 in asthmatic subject. Two groups were created, each with a sample size of 4 subjects. One group was the vitamin C group (VC) and the other was the placebo group (PL). The study

This study was conducted to observe the effects of vitamin C supplementation upon the expression of sICAM-1 in asthmatic subject. Two groups were created, each with a sample size of 4 subjects. One group was the vitamin C group (VC) and the other was the placebo group (PL). The study was analyzed through observing concentrations of biomolecules present within samples of blood plasma and nasal lavages. These included vitamin C, sICAM-1 expression, and histamine. The following P-values calculated from the data collected from this study. The plasma vitamin C screening was p=0.3, and after 18 days of supplementation, p=0.03. For Nasal ICAM p=0.5 at Day 0, p=0.4 at Day 4, and p=0.9 at Day 18. For the Histamine samples p=0.9 at Day 0 and p=0.9 at Day 18. The following P-values calculated from the data collected from both studies. The plasma vitamin C screening was p=0.8, and after 18 days of supplementation, p=0.03. The change of vitamin C at the end of this study and the combined data both had a P-value that was calculated to be lower than 0.05, which meant that this change was significant because it was due to the intervention and not chance. For Nasal ICAM samples p=0.7 at Day 0, p=0.7 at Day 4, and p=1 at Day 18. For the Histamine p=0.7 at Day 0 and p=0.9 at Day 18. This study carries various implications although the study data was unable to show much significance. This was the second study to test this, and as more research is done, and the sample size grows, one will be able to observe whether this really is the mechanism through which vitamin C plays a role in immunological functions.
ContributorsKapadia, Chirag Vinay (Author) / Johnston, Carol (Thesis director) / LaBaer, Joshua (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12
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Current studies in Multiple Myeloma suggest that patient tumors and cell lines cluster separately based on gene expression profiles. Hyperdiploid patients are also extremely underrepresented in established human myeloma cell lines (HMCLs). This suggests that the average HMCL model system does not accurately represent the average myeloma patient. To investigate

Current studies in Multiple Myeloma suggest that patient tumors and cell lines cluster separately based on gene expression profiles. Hyperdiploid patients are also extremely underrepresented in established human myeloma cell lines (HMCLs). This suggests that the average HMCL model system does not accurately represent the average myeloma patient. To investigate this question we performed a combined CNA and SNV evolutionary comparison between four myeloma tumors and their established HMCLs (JMW-1, VP-6, KAS-6/1-KAS-6/2 and KP-6). We identified copy number changes shared between the tumors and their cell lines (mean of 74 events - 59%), those unique to patients (mean of 21.25 events - 17%), and those only in the cell lines (mean of 30.75 events \u2014 24%). A relapse sample from the JMW-1 patient showed 58% similarity to the primary diagnostic tumor. These data suggest that, on the level of copy number abnormalities, HMCLs show equal levels of evolutionary divergence as that observed within patients. By exome sequencing, patient tumors were 71% similar to their representative HMCLs, with ~12.5% and ~16.5% of SNVs unique to the tumors and HMCLs respectively. The HMCLs studied appear highly representative of the patient from which they were derived, with most differences associated with an enrichment of sub-populations present in the primary tumor. Additionally, our analysis of the KP-6 aCGH data showed that the patient's hyperdiploid karyotype was maintained in its respective HMCL. This discovery confirms the establishment and validation of a novel and potentially clinically relevant hyperdiploid HMCL that could provide a major advance in our ability to understand the pathogenesis and progression of this prominent patient population.
ContributorsBenard, Brooks Avery (Author) / Keats, Jonathan (Thesis director) / Anderson, Karen (Committee member) / Jelinek, Diane (Committee member) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description

One of the largest problems facing modern medicine is drug resistance. Many classes of drugs can be rendered ineffective if their target is able to acquire beneficial mutations. While this is an excellent showcase of the power of evolution, it necessitates the development of increasingly stronger drugs to combat resistant

One of the largest problems facing modern medicine is drug resistance. Many classes of drugs can be rendered ineffective if their target is able to acquire beneficial mutations. While this is an excellent showcase of the power of evolution, it necessitates the development of increasingly stronger drugs to combat resistant pathogens. Not only is this strategy costly and time consuming, it is also unsustainable. To contend with this problem, many multi-drug treatment strategies are being explored. Previous studies have shown that resistance to some drug combinations is not possible, for example, resistance to a common antifungal drug, fluconazole, seems impossible in the presence of radicicol. We believe that in order to understand the viability of multi-drug strategies in combating drug resistance, we must understand the full spectrum of resistance mutations that an organism can develop, not just the most common ones. It is possible that rare mutations exist that are resistant to both drugs. Knowing the frequency of such mutations is important for making predictions about how problematic they will be when multi-drug strategies are used to treat human disease. This experiment aims to expand on previous research on the evolution of drug resistance in S. cerevisiae by using molecular barcodes to track ~100,000 evolving lineages simultaneously. The barcoded cells were evolved with serial transfers for seven weeks (200 generations) in three concentrations of the antifungal Fluconazole, three concentrations of the Hsp90 inhibitor Radicicol, and in four combinations of Fluconazole and Radicicol. Sequencing data was used to track barcode frequencies over the course of the evolution, allowing us to observe resistant lineages as they rise and quantify differences in resistance evolution across the different conditions. We were able to successfully observe over 100,000 replicates simultaneously, revealing many adaptive lineages in all conditions. Our results also show clear differences across drug concentrations and combinations, with the highest drug concentrations exhibiting distinct behaviors.

ContributorsApodaca, Samuel (Author) / Geiler-Samerotte, Kerry (Thesis director) / Schmidlin, Kara (Committee member) / Huijben, Silvie (Committee member) / School of Life Sciences (Contributor) / School of Molecular Sciences (Contributor) / School of Politics and Global Studies (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

Since 1975, the prevalence of obesity has nearly tripled around the world. In 2016, 39% of adults, or 1.9 billion people, were considered overweight, and 13% of adults, or 650 million people, were considered obese. Furthermore, Cardiovascular disease remains to be the leading cause of death for adults in the

Since 1975, the prevalence of obesity has nearly tripled around the world. In 2016, 39% of adults, or 1.9 billion people, were considered overweight, and 13% of adults, or 650 million people, were considered obese. Furthermore, Cardiovascular disease remains to be the leading cause of death for adults in the United States, with 655,000 people dying from related conditions and consequences each year. Including fiber in one’s dietary regimen has been shown to greatly improve health outcomes in regards to these two areas of health. However, not much literature is available on the effects of corn-based fiber, especially detailing the individual components of the grain itself. The purpose of this preliminary study was to test the differences in influence on both LDL-cholesterol and triglycerides between treatments based on whole-grain corn flour, refined corn flour, and 50% refined corn flour + 50% corn bran derived from whole grain cornmeal (excellent fiber) in healthy overweight (BMI ≥ 25.0 kg/m2) adults (ages 18 - 70) with high LDL cholesterol (LDL ≥ 120mg/dL). 20 participants, ages 18 - 64 (10 males, 10 females) were involved. Data was derived from blood draws taken before and after each of the three treatments as well as before and after each treatment’s wash out periods. A general linear model was used to assess the effect of corn products on circulating concentrations of LDL-cholesterol and triglycerides. From the model, it was found that the whole-grain corn flour and the 50% refined corn flour + 50% corn bran drive from whole grain cornmeal treatments produced a higher, similar benefit in reductions in LDL-cholesterol. However, the whole grain flour, refined flour, and bran-based fiber treatments did not influence the triglyceride levels of the participants throughout this study. Further research is needed to elucidate the effects of these fiber items on cardiometabolic disease markers in the long-term as well as with a larger sample size.

ContributorsLe, Justin (Author) / Whisner, Corrie (Thesis director) / Ortega Santos, Carmen (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

Cancer rates vary between people, between cultures, and between tissue types, driven by clinically relevant distinctions in the risk factors that lead to different cancer types. Despite the importance of cancer location in human health, little is known about tissue-specific cancers in non-human animals. We can gain significant insight into

Cancer rates vary between people, between cultures, and between tissue types, driven by clinically relevant distinctions in the risk factors that lead to different cancer types. Despite the importance of cancer location in human health, little is known about tissue-specific cancers in non-human animals. We can gain significant insight into how evolutionary history has shaped mechanisms of cancer suppression by examining how life history traits impact cancer susceptibility across species. Here, we perform multi-level analysis to test how species-level life history strategies are associated with differences in neoplasia prevalence, and apply this to mammary neoplasia within mammals. We propose that the same patterns of cancer prevalence that have been reported across species will be maintained at the tissue-specific level. We used a combination of factor analysis and phylogenetic regression on 13 life history traits across 90 mammalian species to determine the correlation between a life history trait and how it relates to mammary neoplasia prevalence. The factor analysis presented ways to calculate quantifiable underlying factors that contribute to covariance of entangled life history variables. A greater risk of mammary neoplasia was found to be correlated most significantly with shorter gestation length. With this analysis, a framework is provided for how different life history modalities can influence cancer vulnerability. Additionally, statistical methods developed for this project present a framework for future comparative oncology studies and have the potential for many diverse applications.

ContributorsFox, Morgan Shane (Author) / Maley, Carlo C. (Thesis director) / Boddy, Amy (Committee member) / Compton, Zachary (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description

Chutneys are a form of Indian condiment that can be made in many different flavors and paired with various foods. However, the availability of chutneys in the United States is very limited and many people have not tried them before. With this observation in mind, we founded A2Z Chutneys, which

Chutneys are a form of Indian condiment that can be made in many different flavors and paired with various foods. However, the availability of chutneys in the United States is very limited and many people have not tried them before. With this observation in mind, we founded A2Z Chutneys, which is a business that aims to distribute a variety of organic and locally produced chutneys. Through the Founders Lab program, A2Z Chutneys was created and research was conducted to justify the viability of our business. We were able to gather and interpret data from potential customers, which allowed us to identify a target market. Additionally, time was spent identifying and creating a variety of authentic and unique chutneys that have proven to be desired. This report demonstrates and outlines the feasibility of A2Z Chutneys in providing unique and desirable flavors to the population.

ContributorsPatel, Javin (Author) / Macha, Sankshay (Co-author) / Byrne, Jared (Thesis director) / Patel, Manish (Committee member) / Pierce, John (Committee member) / Barrett, The Honors College (Contributor) / School of Molecular Sciences (Contributor) / School of Politics and Global Studies (Contributor) / School of Life Sciences (Contributor)
Created2023-05
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Description
As a college student, living in an apartment or home with a kitchen, making your own food decisions can be daunting. After spending so much time either living at home and having food cooked for you or living in a dorm where food is provided, it is difficult to suddenly

As a college student, living in an apartment or home with a kitchen, making your own food decisions can be daunting. After spending so much time either living at home and having food cooked for you or living in a dorm where food is provided, it is difficult to suddenly have to put so much thought into something that for so long you didn’t have to think about at all. Not only that, it sometimes feels like the media is screaming from all sides that you need to eat a certain way to be ‘healthy’ or ‘fit’. I hope to be able to make this process a bit easier for you through this guide I have put together from my own experience and education.
‘Healthy’ foods always seem like the best choice, but what does it really mean to be healthy? A ‘healthy diet’ can mean any number of things depending on who you ask and where you look. Media provides an endless sea of tips, tricks, and diets for ‘eating healthy’. Oxford defines health as a state of physical, mental, and social well-being with the absence of disease and infirmity; and healthy as indicative of, conducive to, or promoting good health1. It is easy to get caught up in the excitement of fad diets, but maintaining a healthy eating pattern can be quite simple when put into practice.
ContributorsCarlson, BreeAnna Marion (Author) / Kniskern, Megan (Thesis director) / Vega-Lopez, Sonia (Committee member) / College of Health Solutions (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05