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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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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
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The goal of this project was to design and create a genetic construct that would allow for <br/>tumor growth to be induced in the center of the wing imaginal disc of Drosophila larvae, the <br/>R85E08 domain, using a heat shock. The resulting transgene would be combined with other <br/>transgenes in

The goal of this project was to design and create a genetic construct that would allow for <br/>tumor growth to be induced in the center of the wing imaginal disc of Drosophila larvae, the <br/>R85E08 domain, using a heat shock. The resulting transgene would be combined with other <br/>transgenes in a single fly that would allow for simultaneous expression of the oncogene and, in <br/>the surrounding cells, other genes of interest. This system would help establish Drosophila as a <br/>more versatile and reliable model organism for cancer research. Furthermore, pilot studies were <br/>performed, using elements of the final proposed system, to determine if tumor growth is possible <br/>in the center of the disc, which oncogene produces the best results, and if oncogene expression <br/>induced later in development causes tumor growth. Three different candidate genes were <br/>investigated: RasV12, PvrACT, and Avli.

ContributorsSt Peter, John Daniel (Author) / Harris, Rob (Thesis director) / Varsani, Arvind (Committee member) / School of Molecular Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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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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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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Description
Tumor-stroma interactions significantly influence cancer cell metastasis and disease progression. These interactions partly comprise crosstalk between tumor and stromal fibroblasts, but the key molecular mechanisms within the crosstalk governing cancer invasion are still unclear. Here we develop a 3D in vitro organotypic microfluidic to model tumor-stroma interaction by mimicking the

Tumor-stroma interactions significantly influence cancer cell metastasis and disease progression. These interactions partly comprise crosstalk between tumor and stromal fibroblasts, but the key molecular mechanisms within the crosstalk governing cancer invasion are still unclear. Here we develop a 3D in vitro organotypic microfluidic to model tumor-stroma interaction by mimicking the spatial organization of the tumor microenvironment on a chip. We co-culture breast cancer and patient-derived fibroblast cells in 3D tumor and stroma regions respectively and combine functional assessments, including cancer cell migration, with transcriptome profiling to unveil the molecular influence of tumor-stroma crosstalk on invasion. This led to the observation that cancer associated fibroblasts enhanced invasion in 3D by inducing the expression of a novel gene of interest, GPNMB, in breast cancer cells resulting in increased migration speed. Importantly, knockdown of GPNMB blunted the influence of CAFs on enhancing cancer invasion. Overall, these results demonstrate the ability of our model to recapitulate patient specific tumor microenvironment to investigate cellular and molecular consequences of tumor-stroma interactions.
ContributorsBarrientos, Eric Salvador (Author) / Nikkhah, Mehdi (Thesis director) / Veldhuizen, Jaime (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
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Trichoplax adhaerens (Placozoa) is the simplest multicellular animal to be described. This organism lacks nervous tissue, muscle tissue and organs, and is composed of only five cell types organized into three layers. Placozoa are gaining popularity as a model organism due to their simple make-up and completely sequenced genome. The

Trichoplax adhaerens (Placozoa) is the simplest multicellular animal to be described. This organism lacks nervous tissue, muscle tissue and organs, and is composed of only five cell types organized into three layers. Placozoa are gaining popularity as a model organism due to their simple make-up and completely sequenced genome. The complete sequencing of this organism’s genome has revealed the presence of important genes in cancer such as TP53 and MDM2 genes. Along with the presence of these genes, there are also additional pathways commonly deregulated in cancer that are well conserved in this organism. T. adhaerens are able to survive exposure to 160Gy and even 240Gy of X-ray radiation. Though small dark bodies form within the main body, they tend to extrude those masses, and continue to reproduce afterwards. After exposure to both grades of radiation, there was a greater increase in the apparent population size of the treated population than the control population. There was also a greater decrease in surface area of the organisms exposed to 160Gy than the control organisms. This increase in population and decrease in surface area of the treated organisms could be due to the extruded bodies. We hypothesize that the observed extrusion is a novel cancer defense mechanism for ridding the animal of damaged or mutated cells. This hypothesis should be tested through longitudinal observation and genetic analysis of the extruded bodies.
ContributorsYi, Avalon (Author) / Fortunato, Angelo (Thesis director) / Maley, Carlo (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-12
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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
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Developments in structural biology has led to advancements in drug design and vaccine development. By better understanding the macromolecular structure, rational choices can be made to improve factors in such as binding affinity, while reducing promiscuity and off-target interactions, improving the medicines of tomorrow. The majority of diseases have a

Developments in structural biology has led to advancements in drug design and vaccine development. By better understanding the macromolecular structure, rational choices can be made to improve factors in such as binding affinity, while reducing promiscuity and off-target interactions, improving the medicines of tomorrow. The majority of diseases have a macromolecular basis where rational drug development can make a large impact. Two challenging protein targets of different medical relevance have been investigated at different stages of determining their structures with the ultimate goal of advancing in drug development. The first protein target is the CapBCA membrane protein complex, a virulence factor from the bacterium Francisella tularensis and the causative agent of tularemia and classified as a potential bioterrorism weapon by the United States. Purification of the individual protein targets from the CapBCA complex is a key and challenging step that has been, so far, a limiting factor towards the structure determination of the whole complex. Here, the purification protocols for the CapB and CapC subunits have been establish, which will allow us to progress towards biophysical and structural studies. The second protein target investigated in this thesis is the catalytically active Taspase1. Taspase1 functions as a non-oncogene addiction protease that coordinates cancer cell proliferation and apoptosis and has been found to be overexpressed in many primary human cancers. Here the structure is presented to 3.04A with the goal of rational drug design of Taspase1 inhibitors. Development of Taspase1 inhibitors has no completion in the drug discovery arena and would function as a new anti-cancer therapeutic. Solving the structures of medically relevant proteins such as these is critical towards rapidly developing treatments and prevention of old and new diseases.
ContributorsJernigan, Rebecca J. (Author) / Fromme, Petra (Thesis director) / Hansen, Debra T. (Committee member) / Martin-Garcia, Jose M. (Committee member) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05