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Proper cell growth and differentiation requires the integration of multiple signaling pathways that are maintained by various post-translational modifications. Many proteins in signal transduction pathways are conserved between humans and model organisms. My dissertation characterizes four previously unknown manners of regulation in the Drosophila Decapentaplegic (Dpp) pathway, a pathway within

Proper cell growth and differentiation requires the integration of multiple signaling pathways that are maintained by various post-translational modifications. Many proteins in signal transduction pathways are conserved between humans and model organisms. My dissertation characterizes four previously unknown manners of regulation in the Drosophila Decapentaplegic (Dpp) pathway, a pathway within TGF-beta family. First, I present data that the Dpp signal transducer, Mothers Against Dpp (Mad), is phosphorylated by Zeste-white 3 (Zw3), a kinase involved in the Wingless pathway. This phosphorylation event occurs independently of canonical phosphorylation of Mad by the Dpp receptor. Using ectopic expression of different alleles of Mad, I show that Zw3 phosphorylation of Mad occurs during the cell cycle in pro-neuronal cells and the loss of phosphorylation of Mad by Zw3 results in ectopic neuronal cells. Thus, Mad phosphorylation by Zw3 is necessary for cell cycle control in pro-neuronal cells. Second, I have shown that the regulator dSno, which has previously been shown to be a TGF-beta antagonist and agonist, is also a Wingless pathway antagonist. Loss of function flip-out clones and ectopic expression of dSno both resulted in changes of Wingless signaling. Further analysis revealed that dSno acts at or below the level of Armadillo (Arm) to inhibit target gene expression. Third, I have demonstrated that the protein Bonus, which is known to be involved in chromatin modification, is required in dorsal-ventral patterning. Further experiments discovered that the chromatin modifier is not only a necessary Dpp agonist, but it is also necessary for nuclear localization of Dorsal during Toll signaling. Last, I showed that longitudinal lacking-like (lola-like) is also required in dorsal-ventral patterning. The loss of maternally expressed lola-like prevents dpp transcription. This shows that lola-like is integral in the Dpp pathway. The study of these four proteins integrates different signaling pathways, demonstrating that the process of development is a web of connections rather than a linear pathway.
ContributorsQuijano, Janine C (Author) / Newfeld, Stuart J (Thesis advisor) / Goldstein, Elliott (Committee member) / Chandler, Douglas (Committee member) / Capco, David (Committee member) / Arizona State University (Publisher)
Created2014
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Past studies have shown that exercise in the form of high intensity interval training (HIIT) is the "ideal form of exercise to improve health and performance without overstressing the immune system" (Fisher et. al, 2011, p. 5). Additionally, HIIT has been found to promote cardiovascular health and immunity (Fisher et.

Past studies have shown that exercise in the form of high intensity interval training (HIIT) is the "ideal form of exercise to improve health and performance without overstressing the immune system" (Fisher et. al, 2011, p. 5). Additionally, HIIT has been found to promote cardiovascular health and immunity (Fisher et. al, 2011). The proposed study will evaluate the neuropsychological effects of HIIT on breast cancer patients undergoing anthracycline-based chemotherapy. The intervention group (n = 17) will receive a HIIT protocol concurrent with chemotherapy treatment. There will also be a control group (n= 17) to compare the effects of the intervention. Breast cancer survivorship is often ridden with various health and mental problems, the implementation of HIIT procedures could help to reduce these issues. It is expected that knowledge from this study will be useful in the healthcare setting to benefit breast cancer patients. This study will uniquely add to the limited research base by introducing an intervention for neuropsychological declines in breast cancer patients.

ContributorsNguyen, Ha Vi Song (Author) / Tran, Alisia (Thesis director) / Capco, David (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Phosphoinositol-Dependent Kinase 1 (PDK1) acts in conjunction with phosphorylated lipids such as Phosphoinositol-3,4,5-triphosphate (PIP3) to activate a variety of proteins that regulate mechanisms ranging from cell growth and survival to cytoskeletal rearrangement. In this investigation PDK1 was examined in the context of cellular division. The techniques of immunocytochemistry and live

Phosphoinositol-Dependent Kinase 1 (PDK1) acts in conjunction with phosphorylated lipids such as Phosphoinositol-3,4,5-triphosphate (PIP3) to activate a variety of proteins that regulate mechanisms ranging from cell growth and survival to cytoskeletal rearrangement. In this investigation PDK1 was examined in the context of cellular division. The techniques of immunocytochemistry and live cell imaging were used to visualize the effects of the inhibition of PDK1 on division in HeLa cells. Division was impaired at metaphase of mitosis. The inhibited cells were unable to initiate anaphase cell-elongation ultimately leading to the flattening of spherical, metaphase cells. Preliminary studies with imunocytochemistry and live cell imaging suggested that insulin treatment reversed PDK1 inhibition, but the results were not statistically significant. Therefore, the recovery of PDK1 inhibition by insulin treatment could not be confirmed. Based on these observations a possible reason for the inability of the treated cells to complete cytokinesis could be the role of PDK1 in the Rho-kinase pathway that is required for the processes cell-elongation necessary for anaphase of mitosis.
ContributorsMasserano, Benjamin Max (Author) / Capco, David (Thesis director) / Baluch, Debra (Committee member) / Chandler, Douglas (Committee member) / Barrett, The Honors College (Contributor) / School of International Letters and Cultures (Contributor) / School of Life Sciences (Contributor)
Created2014-05
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Description
First-semester student retention is a constant priority for undergraduate institutions. The transition to the collegiate level, and to a new scholastic program and format, is frequently challenging academically and socially—for this reason, many first-semester course schedules for incoming freshman undergraduates feature an introductory seminar to ease transition to an undergraduate

First-semester student retention is a constant priority for undergraduate institutions. The transition to the collegiate level, and to a new scholastic program and format, is frequently challenging academically and socially—for this reason, many first-semester course schedules for incoming freshman undergraduates feature an introductory seminar to ease transition to an undergraduate lifestyle. Arizona State University features a required “Careers in the Life Sciences” course for its first-semester School of Life Sciences students, which has had tractable results in first semester student retention and academic success. Here, we evaluate a component of the seminar, the peer-mentorship program, for its efficacy in students’ first semester experience. Analysis of self-reports from 168 first-semester “mentees” and their 25 mentors indicates frequency of mentee-mentor contact was the best indicator of a higher first semester GPA, comfort with academic resources and study habits, and desire to engage in extracurricular activities and internships. These data indicate that access to a mentor who actively engages and verbally connects with their mentees is a valuable component of first-semester student academic integration and retention.
ContributorsMathews, Ian T. (Author) / Capco, David (Thesis director) / Clark-Curtiss, Josephine (Committee member) / Harrell, Carita (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2014-05
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The Cannabis plant has historical roots with human beings. The plant produces compounds called cannabinoids, which are responsible for the physiological affects of Cannabis and make it a research candidate for medicinal use. Analysis of the plant and its components will help build a better database that could be used

The Cannabis plant has historical roots with human beings. The plant produces compounds called cannabinoids, which are responsible for the physiological affects of Cannabis and make it a research candidate for medicinal use. Analysis of the plant and its components will help build a better database that could be used to develop a complete roster of medicinal benefits. Research regarding the cellular protein receptors that bind the cannabinoids may not only help provide reasons explaining why the Cannabis plant could be medicinally relevant, but will also help explain how the receptors originated. The receptors may have been present in organisms before the present day Cannabis plant. So why would there be receptors that bind to cannabinoids? Searching for an endocannabinoid system could help explain the purpose of the cannabinoid receptors and their current structures in humans. Using genetic technologies we are able to take a closer look into the evolutionary history of cannabinoids and the receptors that bind them.
ContributorsSalasnek, Reed Samuel (Author) / Capco, David (Thesis director) / Mangone, Marco (Committee member) / Stump, Edmund (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2014-05
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Tai Chi Chuan is an internal Chinese martial arts that practitioners believe provide will provide health benefits. This thesis attempts to summarize and analyze scientific studies that test Tai Chi Chuan as a therapeutic exercise. Systemic reviews and meta-analysis were included were based on the following criteria: studied Tai Chi

Tai Chi Chuan is an internal Chinese martial arts that practitioners believe provide will provide health benefits. This thesis attempts to summarize and analyze scientific studies that test Tai Chi Chuan as a therapeutic exercise. Systemic reviews and meta-analysis were included were based on the following criteria: studied Tai Chi Chuan in context of a specific disease, must include random control trials, and statistical analysis. Overall, Tai Chi Chuan studies portray the martial art as a low intensity exercise with numerous health benefits in pain management, emotional health, fall prevention, cardiopulmonary and cognitive function.
ContributorsTsai, Andrew Roy (Author) / Capco, David (Thesis director) / Tillman, Hoyt (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Abstract The BIO 189 Life Sciences Career Paths course is a seminar course that is intended to acclimate incoming freshmen into the School of Life Sciences (SOLS). While there are instructors who organize and present in the class, upper division undergraduate students are primarily responsible for facilitating lectures and discussions

Abstract The BIO 189 Life Sciences Career Paths course is a seminar course that is intended to acclimate incoming freshmen into the School of Life Sciences (SOLS). While there are instructors who organize and present in the class, upper division undergraduate students are primarily responsible for facilitating lectures and discussions and mentoring the freshmen. Prior research has demonstrated that the mentor-mentee relationship is a very important predictor of success and retention within all university first-year programs. While past studies focused on the student mentor-mentee relationships, there is limited research that measures student satisfaction within freshmen seminar courses, especially in areas of science, technology, engineering, and mathematics (STEM). The purpose of this project is to survey students about their perception of the BIO 189 course. The effort of the project is on pre-health students, as they initiate their undergraduate careers and attempt to achieve acceptance into professional school four years later. Analysis of Likert scale surveys distributed to 561 freshmen revealed that students with an emphasis on "medicine" in their majors preferred a BIO 189 course geared to pre-health interests whereas students seeking an emphasis on research (ecology and cell biology/genetics) sought a BIO 189 course focused on internship and employment opportunities. Assessment of the mentor-mentee relationship revealed that students (n = 561) preferred one-on-one meetings with mentors outside of class (44%) compared to those who preferred interaction in class (30%). A sizable 61.68% of students (n = 548) were most concerned with attaining favorable GPAs, highlighting strong emphasis on academic performance. Overall, 61% of respondents (n = 561) expressed satisfaction with SOLS resources and involvement opportunities, which was hypothesized. These results give substantial insight into the efficacy of a first-year success seminar-mentoring program for college freshmen in STEM.
ContributorsMaalouf, Nicholas Elie (Author) / Haydel, Shelley (Thesis director) / Harrell, Carita (Committee member) / Capco, David (Committee member) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
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Description
Triple-negative breast cancer (TNBC) is defined by the lack of three receptors (estrogen, progesterone, and HER2 receptors) and accounts for 12-17% of breast cancers. TNBC is an aggressive form of the disease associated with high rates of recurrence and mortality within five years. Inhibitor of Growth 4 (ING4)

Triple-negative breast cancer (TNBC) is defined by the lack of three receptors (estrogen, progesterone, and HER2 receptors) and accounts for 12-17% of breast cancers. TNBC is an aggressive form of the disease associated with high rates of recurrence and mortality within five years. Inhibitor of Growth 4 (ING4) is a gene deleted in 16.5% and downregulated in 34% of breast tumors. The correlation between ING4 deficiencies and advanced tumors and poor patient survival implicates its tumor suppressive function in breast cancer. Low ING4 expression has been correlated with NFκB activation in metastatic breast tumors. Moreover, ING4 has been shown to inhibit NFkB-mediated gene transcription in various cancers, suggesting that ING4 may suppress cancer by inhibiting NFkB activation. However, the contribution of ING4 deficiencies and NFkB activation to aggressive TNBC progression is currently not well understood. We investigated the role of ING4 in the MDAmb231 TNBC cell line by genetically engineering the cells to overexpress or delete ING4. Cell growth and sensitivity to the chemotherapeutic agent doxorubicin were evaluated between the ING4-modified cell lines with or without TNFα to activate NFκB. The results showed that cell growths were comparable between the vector controls and ING4 overexpressing or deleted cell lines. In addition, TNFα treatment did not alter the growths of all cell lines, indicating that ING4 with or without NFkB activation did not play a role in determining the growth rates of TNBC. However, ING4 overexpressing cells were 20-30% more sensitive to 10 μM doxorubicin treatment, whereas ING4-deleted cells were 20-50% more resistant, suggesting that ING4 may determine chemotherapy response in TNBC. These findings suggest that tumors with low levels of ING4 may be more resistant to chemotherapy, thus requiring higher dosage and/or additional chemotherapy in patient treatment. Unexpectedly, TNFα sensitized all cell lines to doxorubicin regardless of ING4 expression levels, suggesting a TNFα function outside of NFκB activation in increasing doxorubicin sensitivity. It implicates that TNFα treatment may increase chemotherapy response in TNBC patients.
ContributorsUngor, Ashley Jordyn (Author) / Capco, David (Thesis director) / Kim, Suwon (Committee member) / Compton, Carolyn (Committee member) / Sanford School of Social and Family Dynamics (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
Description
In medical field today, current diagnostic tools for neurodegenerative diseases fail to diagnose patients prior to the occurrence of damaging neuronal loss. Oftentimes, this means that by the time a patient has been diagnosed with a disease such as Alzheimer's disease (AD) or Parkinson's disease (PD), they have already suffered

In medical field today, current diagnostic tools for neurodegenerative diseases fail to diagnose patients prior to the occurrence of damaging neuronal loss. Oftentimes, this means that by the time a patient has been diagnosed with a disease such as Alzheimer's disease (AD) or Parkinson's disease (PD), they have already suffered severe, irreversible neurodegeneration. One of the significant weaknesses in the diagnosis and treatment of patients with AD and PD is the lack of viable biomarkers. Biomarkers are vital tools that can be utilized to identify patients who are in presymptomatic stages of a disease, track and quantify disease progression, and also determine whether or not a patient is responding to a particular treatment. RNAs are involved in all cellular processes, and due to their very specific spatial, temporal, and even cellular-level expression, abnormal expression signatures serve as key indicators of many diseases. Recently, cells have been shown to secrete nanometer-sized microvesicles, called exosomes, which moderate the horizontal transfer of mRNAs and miRNAs between cells. We hypothesize that exosomes obtained from human biofluids, such as cerebral spinal fluid (CSF) and blood plasma, can be used to determine extracellular RNA (exRNA) expression signatures associated with neurodegenerative disease. This experiment used pooled samples of CSF and plasma in order to investigate which of 3 sample enrichment methods would be most conducive to studying exRNA contained within exosomes. The results from this preliminary investigation will be used in later investigations that will seek to determine exRNA biomarkers of neurodegenerative disease.
ContributorsBeecroft, Taylor Alexandria (Author) / Capco, David (Thesis director) / Van Keuren-Jensen, Kendall (Committee member) / Huentelman, Matt (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2013-05
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Description

Thousands of mothers are at risk of transmitting mitochondrial diseases to their offspring each year, with the most severe form of these diseases being fatal [1]. With no cure, transmission prevention is the only current hope for decreasing the disease incidence. Current methods of prevention rely on low mutant maternal

Thousands of mothers are at risk of transmitting mitochondrial diseases to their offspring each year, with the most severe form of these diseases being fatal [1]. With no cure, transmission prevention is the only current hope for decreasing the disease incidence. Current methods of prevention rely on low mutant maternal mitochondrial DNA levels, while those with levels close to or above threshold (>60%) are still at a very high risk of transmission [2]. Two novel approaches may offer hope for preventing and treating mitochondrial disease: mitochondrial replacement therapy, and CRISPR/Cas9. Mitochondrial replacement therapy has emerged as a promising tool that has the potential to prevent transmission in patients with higher mutant mitochondrial loads. This method is the subject of many ethical concerns due its use of a donor embryo to transplant the patient’s nuclear DNA; however, it has ultimately been approved for use in the United Kingdom and was recently declared ethically permissible by the FDA. The leading-edge CRISPR/Cas9 technology exploits the principles of bacterial immune function to target and remove specific sequences of mutated DNA. This may have potential in treating individuals with disease caused by mutant mitochondrial DNA. As the technology progresses, it is important that the ethical considerations herein emerge and become more established. The purpose of this review is to discuss current research surrounding the procedure and efficacy of the techniques, compare the ethical concerns of each approach, and look into the future of mitochondrial gene replacement therapy.

ContributorsFogelman, Sarah (Author) / Santana, Casey (Author) / Bishop, Casey (Author) / Miller, Alyssa (Author) / Capco, David (Author) / College of Liberal Arts and Sciences (Contributor)
Created2016-08-30