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Description
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
The primary objective of this project is to further the knowledge about SCL26 family of anion transporters. The goals of the experiment were to find the lowest sulfate concentration where the yeast without Sulp1 and Sulp2 is able to grow, but it grows very slowly, and to find a higher

The primary objective of this project is to further the knowledge about SCL26 family of anion transporters. The goals of the experiment were to find the lowest sulfate concentration where the yeast without Sulp1 and Sulp2 is able to grow, but it grows very slowly, and to find a higher sulfate concentration where the yeast grows quickly, with or without the sulfate transporters. The lowest sulfate concentration where the yeast without the sulfate transporters is able to grow was determined to be 2-4 mM, however, this range can likely be refined by more quantitative analytical methods. At a sulfate concentration of 20 mM sulfate or higher, the yeast is able to grow quickly without high-affinity sulfate transporters. The next step in the project is to re-introduce the Sulp1 and Sulp2 genes into the yeast, so that growth in low and high sulfate conditions can be compared with and without the Sulp1 and Sulp2 proteins. The long-term goals of the project are to bring experience with yeast to Dr. Nannenga’s structural discovery lab, to determine if yeast sulfate transporters respond in the same way to drug candidates as human sulfate transporters, and to determine the structure of the proteins using cryo-electron microscopy.
ContributorsCall, Nicolas I (Author) / Nannenga, Brent (Thesis director) / Wang, Xuan (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
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Description
The aims of this project are: (i) to identify structural and molecular changes in the brains of 3xTg-AD mice and (ii) to determine whether decreasing S6K1 protects the brain from these changes. To achieve our goals, we decided to remove one copy of the S6K1 gene in 3xTg-AD mice by

The aims of this project are: (i) to identify structural and molecular changes in the brains of 3xTg-AD mice and (ii) to determine whether decreasing S6K1 protects the brain from these changes. To achieve our goals, we decided to remove one copy of the S6K1 gene in 3xTg-AD mice by breeding them with S6K1 knockout mice (S6K1+/-). In previous studies, we have seen that reducing S6K1 levels in 3xTg-AD mice improved spatial memory and synaptic plasticity which was associated with reduced A and tau pathology. Here, we used a multiparametric MRI to assess volumetric and blood flow changes in the brain of 20-month-old 3xTg-AD mice. We found that 3xTg-AD/S6K1+/- mice had higher blood flow and cortical volume compared to 3xTg-AD mice. However, we saw no significant differences between 3xTg-AD mice and NonTg mice. We further found A levels and plaque numbers were significantly lower in 3xTg-AD/S6K1+/- mice compared to 3xTg-AD mice. This reduction in plaques could account for the improvement in blood flow in 3xTg-AD/S6K1+/- mice. To try to understand the reason behind the increase in cortical volume in the 3xTg-AD/S6K1+/- when compared to the 3xTg-AD, we measured markers of synaptic density, PSD95, and synaptophysin. We found that PSD95 levels were not different between the four groups. However, synaptophysin levels were significantly lower in 3xTg-AD mice compared to NonTg levels and returned to baseline levels in 3xTg-AD mice lacking one copy of the S6K1 gene. This difference in synaptophysin could explain, at least in part, the difference in volume between the four groups analyzed. Overall, this represents the first evidence showing that reducing mTOR signaling improves blood flow and cortical volume in a mouse model of AD.
ContributorsShukla, Prakriti (Author) / Oddo, Salvatore (Thesis director) / Caccamo, Antonella (Committee member) / Jankowsky, Joanna (Committee member) / School of Molecular Sciences (Contributor) / School of Public Affairs (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
Currently, many patients suffer from post-circumcision complications caused by poor patient selection and/or poor technique of the practicing physician. In addition, the majority of medical practitioners are incapable of/unwilling to conduct specific circumcision procedures on their patients. In the end, this either results in unsatisfied patient families, who unwillingly have

Currently, many patients suffer from post-circumcision complications caused by poor patient selection and/or poor technique of the practicing physician. In addition, the majority of medical practitioners are incapable of/unwilling to conduct specific circumcision procedures on their patients. In the end, this either results in unsatisfied patient families, who unwillingly have their children circumcised using methods contrary to their belief, or results in individuals who are not certified practitioners of medicine conducting the procedures, greatly increasing the risk of the patients experiencing preventable complications. In order to locally address the aforementioned problems, this thesis committee, consisting of Dr. Frank Infurna, Dr. Justin Ryan, and Dr. Zachary Zuniga, and I, developed a training module that standardized the instruction that interns, residents, attendings, fellows, hospitalists, and other interested physicians will receive regarding neonatal circumcision at Phoenix Children's Hospital. To begin, the pre-operative, intra-operative, and post-operative procedures related to the Gomco clamp neonatal circumcision procedure were heavily researched using literature sourced from library databases and consultation of specialists, such as Dr. Zuniga. Given that the training was developed to instruct individuals within the medical field, the material was then truncated to promote succinctness and specificity towards the targeted population. In order to convey the specific techniques that are clinically preferred to be used in the procedure, one of Dr. Zuniga's Gomco clamp neonatal circumcision procedures was recorded and converted into GIFs, with each GIF depicting a specific technique of the procedure. The aforementioned materials were then arranged into a slide deck in order to mitigate the need for future training facilitators to tamper with the material in the process of creating visuals to be used during the training. Given the sensitivity of the material included in the slide deck, it will only be available for use on Phoenix Children's Hospital premises. To incorporate instruction regarding both the traditional (Gomco clamp) and religiously-preferred circumcision techniques into the training module, appointments, consisting of discussions regarding the procedural, cultural, and social facets that must be taken into consideration when conducting a circumcision procedure on a patient from a Muslim family, were set-up with pediatric physicians, currently practicing in Abu Dhabi, United Arab Emirates, who have specialized knowledge of conducting circumcisions in the Middle East. Since Brit Milah, the Jewish circumcision ceremony, is, unlike in Islam, required to be conducted by a Mohel in either a synagogue or house, it was not covered as holistically as "Khtan", Islamic circumcision, which is less heavily regulated. Thus far, the training module has been piloted twice, once with a group of medical students and physicians and once with medical education program directors and instructors. The critique from both sessions has been used to prepare the material for use in neonatal circumcision training sessions that will be introduced in clerkship and residency curriculum. In the future, the results of this implementation can be used to prepare the module for submission to the American Academy of Pediatrics to be made a prerequisite for physicians to undergo before conducting neonatal circumcisions.
ContributorsMeraban, Amir Reza (Author) / Infurna, Frank (Thesis director) / Ryan, Justin (Committee member) / Zuniga, Zachary (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
I investigated if race/ethnicity was associated with self- and peer-reported victimization and aggression in a sample of 5th through 8th graders (N = 383, 51% males) from two schools in which Hispanic/Latino students were the ethnic-racial majority. Self-reported victimization did not differ between races. In contrast, White students often had

I investigated if race/ethnicity was associated with self- and peer-reported victimization and aggression in a sample of 5th through 8th graders (N = 383, 51% males) from two schools in which Hispanic/Latino students were the ethnic-racial majority. Self-reported victimization did not differ between races. In contrast, White students often had higher peer-reported victimization relative to Hispanic and Multi-racial students. Few significant associations were found for aggression. There was some, albeit inconsistent, support for the idea that power imbalance based on race/ethnicity is shifted by numbers. In the future, researchers should conduct studies aimed verifying this notion and that are tailored toward answering questions of mechanism.
ContributorsMitiku, Helen (Author) / Wilkens, Natalie (Thesis director) / Lindstrom Johnson, Sarah (Committee member) / White, Rebecca (Committee member) / School of Molecular Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
Intrauterine devices (IUDs) have become one of the most common types of contraception in the United States. In the last decade, the American College of Obstetricians and Gynecologists, the World Health Organization, and the Food and Drug Administration (FDA) updated IUD recommendations to include placement in younger populations and nulliparous

Intrauterine devices (IUDs) have become one of the most common types of contraception in the United States. In the last decade, the American College of Obstetricians and Gynecologists, the World Health Organization, and the Food and Drug Administration (FDA) updated IUD recommendations to include placement in younger populations and nulliparous women. Research has shown that younger, nulliparous women may have smaller uterine dimensions and it is possible that larger IUDs are not suitable for those populations. This study retrospectively evaluated follow-up pelvic ultrasounds showing uterine dimensions and IUD positions of 57 women who had IUDs placed in a clinic. The largest IUD, the Paragard, showed a significantly higher rate of malpositioning than the Kyleena, Liletta, and Mirena IUDs. There is concern that the Paragard IUD, which is most commonly malpositioned, is also the IUD most dependent on position for adequate contraception. There was no correlation between uterine dimensions and IUD position at the time of analysis, however. Further data collection will continue in hopes that a larger sample size will reveal a parameter which affects IUD placement. Should further data analysis show that uterine width plays an important role in IUD position, the design for a device which can measure the width of patient's uterus (without the need for pelvic ultrasound) has been included. The concept generation for this measurement device includes laser measurements of uterine cavity width at different known lengths from the fundal wall, which output to an LED screen for recording.
ContributorsGrayson, Claire Elise (Co-author) / Kilgore, Brody (Co-author) / Reifsnider, Elizabeth (Thesis director) / Stabenfeldt, Sarah (Committee member) / Grayson, Robert (Committee member) / School of Molecular Sciences (Contributor) / Sanford School of Social and Family Dynamics (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
Neuroinflammation is mediated by activated microglia, the chief immune response of the central nervous system. Mitochondrial 18kDa translocator protein (TSPO) is upregulated in activated microglia and has been used in PET scans to analyze peripheral and central inflammation with TSPO radioligand [18F]DPA-714. To test the hypothesis that TSPO is involved

Neuroinflammation is mediated by activated microglia, the chief immune response of the central nervous system. Mitochondrial 18kDa translocator protein (TSPO) is upregulated in activated microglia and has been used in PET scans to analyze peripheral and central inflammation with TSPO radioligand [18F]DPA-714. To test the hypothesis that TSPO is involved in microglial mediation of inflammatory responses to Aβ and other Alzheimer’s pathological elements, TSPO expression was evaluated in relation to microglia specific markers (IBA1 and LN3 antibodies) and markers for AD pathology, Aβ (6E10 antibody) and hyperphosphorylated tau (AT8 antibody). To test that TSPO is involved in inflammatory pathways, HEK cells transfected with TSPO plasmids were assessed for oxidative stress in response to Alzheimer’s disease pathogenic agents, β Amyloid (Aβ), and Parkinson’s disease α-synuclein (α-syn).

Fluorescence microscopy of TSPO transfected HEK cell cultures labeled with Carboxy-H2DCFDA and treated with Beta Amyloid (Aβ) and α-synuclein (α-syn) resulted in DAPI fluorescing Human Embryonic Kidney (HEK) nuclei in blue and Green Fluorescent Protein (GFP) fluorescing reactive oxygen species (ROS) or oxidative stress in cell cytoplasm in green. Preliminary study suggests TSPO transfected cells may be used to test oxidative stress with disease pathological elements (Aβ and α-synuclein). In IHC, TSPO immunoreactivity was observed in IBA1 and LN3 marked microglia with varying degrees of expression. Beaded structures were also observed with TSPO immunoreactivities, possibly representing microglia processes. TSPO immunoreactivity was observed in and surrounding amyloid plaques and p-tau immunoreactive neurites. This demonstrates that TSPO is predominantly expressed in microglia and are closely associated with Alzheimer’s disease pathological elements, suggesting involvement of TSPO-expressing microglia in neurodegenerative processes.
ContributorsWu, Michael (Author) / Lue, Lih-Fen (Thesis director) / Washo-Krupps, Delon (Committee member) / School of Life Sciences (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
Esophageal adenocarcinoma (EAC) is the most prevalent type of esophageal malignancy in the United States (US) and the rate of occurrence continues to grow rapidly. As the prevalence of risk factors such as obesity and gastroesophageal reflux disease (GERD) rises, the rates of EAC are expected to continue rising as

Esophageal adenocarcinoma (EAC) is the most prevalent type of esophageal malignancy in the United States (US) and the rate of occurrence continues to grow rapidly. As the prevalence of risk factors such as obesity and gastroesophageal reflux disease (GERD) rises, the rates of EAC are expected to continue rising as well. Unfortunately, the 5-year survival rate remains low and the lack of targetable, oncogenic drivers presents challenges in developing more effective and less toxic therapeutics. The current standard of care for EAC involves combinations of chemotherapeutics and radiation therapy that can cause severe side effects and often leads to refractory and relapsed disease. According to the cancer stem cell model, a small subset of the tumor cell population is responsible for cancer's ability to replicate, metastasize, and relapse. These cancer stem cells (CSCs) can self-renew and differentiate. Napabucasin, a "stemness" inhibitor, which works by inhibiting STAT3, has shown promising results in pre-clinical and clinical investigations across a variety of solid tumor types. Because a major barrier in treatment of EAC is the likelihood of relapse, targeting the CSC population that results in this phenotype is a therapeutic strategy of great interest. We hypothesize that employment of napabucasin to inhibit stemness through STAT3 represents a viable therapeutic strategy in the EAC setting. In this study, we investigated the efficacy of napabucasin on EAC cells. Napabucasin was shown to reduce phosphorylation of STAT3 as well as levels of MCL1, a cell survival protein downstream of STAT3, and levels of "stemness" markers Nanog, Sox2, and B-catenin via immunoblot analysis. Napabucasin monotherapy showed high efficacy in some EAC settings, with IC50 values in a clinically achievable range. The treatment in combination with cisplatin, a standard of care chemotherapeutic, resulted in reduced cell viability than either treatment alone indicating that a combination strategy could reduce the dosage of each drug needed. The data suggests that STAT3 inhibition in combination with current standard of care treatments could be a viable therapeutic strategy in EAC, and improve the dismal survival for these patients.
ContributorsDarwin, Alicia H. (Author) / Stout, Valerie (Thesis director) / Whitsett, Timothy (Committee member) / Carson, Vashti (Committee member) / School of Transborder Studies (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
Home Base Initiative is a student-led venture project co-founded by Madison Sutton and Sonia Sabrowsky in January 2018. As an organization, Home Base Initiative addresses the problem of teen suicide by educating parents, teachers, and students about the research-backed mental health resources currently available to them and by implementing peer-based

Home Base Initiative is a student-led venture project co-founded by Madison Sutton and Sonia Sabrowsky in January 2018. As an organization, Home Base Initiative addresses the problem of teen suicide by educating parents, teachers, and students about the research-backed mental health resources currently available to them and by implementing peer-based support programs in local high schools. With the belief that positive mental health habits are for everyone, not just individuals with a clinical diagnosis, Home Base Initiative aims to encourage positive conversations about mental health and to increase social and emotional resilience among adolescents to help them navigate the challenges in their lives. In addition to identifying the community problem our organization aims to solve, this document outlines the initial conception, development, and future outlook Home Base Initiative by describing the methods by which the organization has researched other like-minded programs, formed strategic partnerships with community members, piloted its peer-based program at a local high school, and established a foundation for future success as a student organization at Arizona State University. Currently, the Home Base Initiative team consists of 10 undergraduate students at ASU with diverse backgrounds and academic interests as well as credible mentors who are involved in the ASU Tillman Scholars Program, ASU Counseling Services, and The Courage Lab at ASU. We are united by our passion for supporting others’ mental health, and we are dedicated to playing an active role in the healthy development of our fellow community members through mental health advocacy and the facilitation of positive peer-to-peer interactions.
ContributorsSabrowsky, Sonia (Co-author, Co-author) / Sutton, Madison (Co-author) / Mokwa, Michael (Thesis director) / Eaton, John (Committee member) / School of Molecular Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
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Description
The synthesis of the bis(2-diphenylphosphinoethyl)amine chelating ligand (1) was a crucial component in the preparation of non-canonical amino acids (NCAAs) throughout the project. Studies in this project indicated the need to isolate the ligand from its hydrochloride salt form seen in (1) which led to the synthesis of the brown

The synthesis of the bis(2-diphenylphosphinoethyl)amine chelating ligand (1) was a crucial component in the preparation of non-canonical amino acids (NCAAs) throughout the project. Studies in this project indicated the need to isolate the ligand from its hydrochloride salt form seen in (1) which led to the synthesis of the brown oil, (Ph2PCH2CH2)2NH, (2). The ligand features a phosphine-nitrogen-phosphine group that is not observed in existing NCAAs. Phosphine groups are rarely seen in existing NCAAs and avoided by biochemists because they tend to oxidize before metal addition. In this project, (1) was used in a 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU) mediated method and palladium-catalyzed method to tether an amino acid to the nitrogen atom of the ligand framework. Both methods were monitored through the use of Nuclear Magnetic Resonance (NMR) spectroscopy. While the palladium catalyzed method exhibited little to no coupling, the 31P NMR spectrum obtained for the HATU mediated method did reveal that some coupling had occurred. The unsuccessful attempts to tether an amino acid to (1) led to the hypothesis that the phosphine groups were interfering with the palladium catalyst during the cross-coupling reaction. In an effort to test this hypothesis, (2) was reacted with the dimer, [Rh(nbd)Cl]2, to coordinate the rhodium metal to the free phosphorous arms and the nitrogen atom of the isolated PNP ligand. The PNP-based metal complex was used in the palladium catalyzed method, but cross-coupling was not observed. The new PNP-based metal complex was investigated to demonstrate that it exhibits moisture and air stability.
ContributorsManjarrez, Yvonne (Author) / Trovitch, Ryan (Thesis director) / Stephanopoulos, Nicholas (Committee member) / Herckes, Pierre (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05