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Due to artificial selection, dogs have high levels of phenotypic diversity, yet, there appears to be low genetic diversity within individual breeds. Through their domestication from wolves, dogs have gone through a series of population bottlenecks, which has resulted in a reduction in genetic diversity, with a large amount of

Due to artificial selection, dogs have high levels of phenotypic diversity, yet, there appears to be low genetic diversity within individual breeds. Through their domestication from wolves, dogs have gone through a series of population bottlenecks, which has resulted in a reduction in genetic diversity, with a large amount of linkage disequilibrium and the persistence of deleterious mutations. This has led to an increased susceptibility to a multitude of diseases, including cancer. To study the effects of artificial selection and life history characteristics on the risk of cancer mortality, we collected cancer mortality data from four studies as well as the percent of heterozygosity, body size, lifespan and breed group for 201 dog breeds. We also collected specific types of cancer breeds were susceptible to and compared the dog cancer mortality patterns to the patterns observed in other mammals. We found a relationship between cancer mortality rate and heterozygosity, body size, lifespan as well as breed group. Higher levels of heterozygosity were also associated with longer lifespan. These results indicate larger breeds, such as Irish Water Spaniels, Flat-coated Retrievers and Bernese Mountain Dogs, are more susceptible to cancer, with lower heterozygosity and lifespan. These breeds are also more susceptible to sarcomas, as opposed to carcinomas in smaller breeds, such as Miniature Pinschers, Chihuahuas, and Pekingese. Other mammals show that larger and long-lived animals have decreased cancer mortality, however, within dog breeds, the opposite relationship is observed. These relationships could be due to the trade-off between cellular maintenance and growing fast and large, with higher expression of growth factors, such as IGF-1. This study further demonstrates the relationships between cancer mortality, heterozygosity, and life history traits and exhibits dogs as an important model organism for understanding the relationship between genetics and health.
ContributorsBalsley, Cassandra Sierra (Author) / Maley, Carlo (Thesis director) / Wynne, Clive (Committee member) / Tollis, Marc (Committee member) / School of Life Sciences (Contributor) / School of Human Evolution and Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
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This purpose of this thesis study was to examine variables of the "War on Cancer" frame, loss-gain prime, and patient gender on treatment decision for advanced cancer patients. A total of 291 participants (141 females) participated in an online survey experiment and were randomly assigned to one of eight possible

This purpose of this thesis study was to examine variables of the "War on Cancer" frame, loss-gain prime, and patient gender on treatment decision for advanced cancer patients. A total of 291 participants (141 females) participated in an online survey experiment and were randomly assigned to one of eight possible conditions, each of which were comprised of a combination of one of two levels for three total independent variables: war frame ("War on Cancer" frame or neutral frame), loss-gain prime (loss prime or gain prime), and patient gender (female or male). Each of the three variables were operationalized to determine whether or not the exposure to the war on cancer paradigm, loss-frame language, or male patient gender would increase the likelihood of a participant choosing a more aggressive cancer treatment. Participants read a patient scenario and were asked to respond to questions related to motivating factors. Participants were then asked to report preference for one of two treatment decisions. Participants were then asked to provide brief demographic information in addition to responding to questions about military history, war attitudes, and cancer history. The aforementioned manipulations sought to determine whether exposure to various factors would make a substantive difference in final treatment decision. Contrary to the predicted results, participants in the war frame condition (M = 3.85, SD = 1.48) were more likely to choose the pursuit of palliative care (as opposed to aggressive treatment) than participants in the neutral frame condition (M = 3.54, SD = 1.23). Ultimately, these significant findings suggest that there is practical information to be gained from treatment presentation manipulations. By arming healthcare providers with a more pointed understanding of the nuances of treatment presentation, we can hope to empower patients, their loved ones, and healthcare providers entrenched in the world of cancer treatment.
ContributorsKnowles, Madelyn Ann (Author) / Kwan, Virginia S. Y. (Thesis director) / Presson, Clark (Committee member) / Salamone, Damien (Committee member) / Department of Psychology (Contributor) / School of Human Evolution and Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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The influenza virus is the main cause of thousands of deaths each year in the United States, and far more hospitalizations. Immunization has helped in protecting people from this virus and there are a number of therapeutics which have proven effective in aiding people infected with the virus. However, these

The influenza virus is the main cause of thousands of deaths each year in the United States, and far more hospitalizations. Immunization has helped in protecting people from this virus and there are a number of therapeutics which have proven effective in aiding people infected with the virus. However, these therapeutics are subject to various limitations including increased resistance, limited supply, and significant side effects. A new therapeutic is needed which addresses these problems and protects people from the influenza virus. Synbodies, synthetic antibodies, may provide a means to achieve this goal. Our group has produced a synbody, the 5-5 synbody, which has been shown to bind to and inhibit the influenza virus. The direct pull down and western blot techniques were utilized to investigate how the synbody bound to the influenza virus. Our research showed that the 5-5 synbody bound to the influenza nucleoprotein (NP) with a KD of 102.9 ± 74.48 nM. It also showed that the synbody bound strongly to influenza viral extract from two different strains of the virus, the Puerto Rico (H1N1) and Sydney (H3N2) strains. This research demonstrated that the 5-5 synbody binds with high affinity to NP, which is important because influenza NP is highly conserved between various strains of the virus and plays an important role in the replication of the viral genome. It also demonstrated that this binding is conserved between various strains of the virus, indicating that the 5-5 synbody potentially could bind many different influenza strains. This synbody may have potential as a therapeutic in the future if it is able to demonstrate similar binding in vivo.
ContributorsKombe, Albert E. (Author) / Diehnelt, Chris (Thesis director) / Woodbury, Neal (Committee member) / Legutki, Bart (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of International Letters and Cultures (Contributor)
Created2014-05
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Description
The influenza virus, also known as "the flu", is an infectious disease that has constantly affected the health of humanity. There is currently no known cure for Influenza. The Center for Innovations in Medicine at the Biodesign Institute located on campus at Arizona State University has been developing synbodies as

The influenza virus, also known as "the flu", is an infectious disease that has constantly affected the health of humanity. There is currently no known cure for Influenza. The Center for Innovations in Medicine at the Biodesign Institute located on campus at Arizona State University has been developing synbodies as a possible Influenza therapeutic. Specifically, at CIM, we have attempted to design these initial synbodies to target the entire Influenza virus and preliminary data leads us to believe that these synbodies target Nucleoprotein (NP). Given that the synbody targets NP, the penetration of cells via synbody should also occur. Then by Western Blot analysis we evaluated for the diminution of NP level in treated cells versus untreated cells. The focus of my honors thesis is to explore how synthetic antibodies can potentially inhibit replication of the Influenza (H1N1) A/Puerto Rico/8/34 strain so that a therapeutic can be developed. A high affinity synbody for Influenza can be utilized to test for inhibition of Influenza as shown by preliminary data. The 5-5-3819 synthetic antibody's internalization in live cells was visualized with Madin-Darby Kidney Cells under a Confocal Microscope. Then by Western Blot analysis we evaluated for the diminution of NP level in treated cells versus untreated cells. Expression of NP over 8 hours time was analyzed via Western Blot Analysis, which showed NP accumulation was retarded in synbody treated cells. The data obtained from my honors thesis and preliminary data provided suggest that the synthetic antibody penetrates live cells and targets NP. The results of my thesis presents valuable information that can be utilized by other researchers so that future experiments can be performed, eventually leading to the creation of a more effective therapeutic for influenza.
ContributorsHayden, Joel James (Author) / Diehnelt, Chris (Thesis director) / Johnston, Stephen (Committee member) / Legutki, Bart (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2014-05
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Description
Through a standpoint feminist perspective (Harding 2009) I conducted a situational analysis (Clarke, 2015) that examined academic literature and cancer support discussion boards (DBs) to identify how Western biomedicine, specifically oncology, can integrate complementary and alternative medicine (CAM) to improve cancer treatment in children. The aims of this project were:

Through a standpoint feminist perspective (Harding 2009) I conducted a situational analysis (Clarke, 2015) that examined academic literature and cancer support discussion boards (DBs) to identify how Western biomedicine, specifically oncology, can integrate complementary and alternative medicine (CAM) to improve cancer treatment in children. The aims of this project were: 1) to identify the CAM treatments that are being used to alleviate the side effects from oncological treatments and/or treat pediatric cancers; 2) to compare the subjective experience of CAM to Western biomedicine of cancer patients who leave comments on Group Loop, Cancer Compass and Cancer Forums, which are online support groups (N=20). I used grounded theory and situational mapping to analyze discussion threads. The participants identified using the following CAM treatments: herbs, imagery, prayer, stinging nettle, meditation, mind-body therapies and supplements. The participants turned to CAM treatments when their cancer was late-stage or terminal, often as an integrative and not exclusively to treat their cancer. CAM was more "effective" than biomedical oncology treatment at improving their overall quality of life and functionality. We found that youth on discussion boards did not discuss CAM treatments like the adult participants, but all participants visited these sites for support and verification of their cancer treatments. My main integration recommendation is to combine mind-body CAM therapies with biomedical treatment. This project fills the gap in literature that ignores the ideas of vulnerable populations by providing the experiences of adult and pediatric cancer patients, and that of their families. It is applicable to areas of the social studies of medicine, patient care, and families suffering from cancer. KEYWORDS: Cancer; Complementary and Alternative Medicine; Situational Analysis; Standpoint Feminism
ContributorsEsposito, Sydney Maria (Author) / Martinez, Airín (Thesis director) / Hruschka, Daniel (Committee member) / School of Human Evolution and Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
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Description
Laboratory animals represent an invaluable, yet controversial, resource in the field of biomedical research. Animal research has been behind many influential discoveries in the field of emerging therapeutics. They provide the link between the theory of the lab bench and the functional application of medicine to influence human health. The

Laboratory animals represent an invaluable, yet controversial, resource in the field of biomedical research. Animal research has been behind many influential discoveries in the field of emerging therapeutics. They provide the link between the theory of the lab bench and the functional application of medicine to influence human health. The use of animals in research is a consideration which must be heavily weighed, and the implementation must be carried out at a very high standard in order to retain research integrity and responsibility. We are in the process of conducting an experiment using laboratory mice to demonstrate cancer treatment using vaccinia (VACV) mutants as a possible oncolytic therapy for certain strains of melanoma. VACV is a double-stranded DNA poxvirus with a large and easily altered genome. This virus contains many genes dedicated to immune evasion, but has shown sensitivity to cell death by necroptosis in mouse studies (5). We have identified the absence of the kinase RIP3 which is vital in the necroptosis pathway as a potential target for oncolytic therapy using VACV mutants in specific strains of melanoma. Multiple groups of SCID Beige mice were inoculated with different melanoma cell lines and observed for tumor growth. Upon reaching 1 cm3 in volume, tumors were injected with either VACV- Δ83N, VACV- Δ54N, or PBS, and observed for regression. It was hypothesized that melanoma tumors that are RIP3-/- such as the MDA5 cell line will show regression, but melanoma tumors that are RIP3-positive and capable of necroptosis, such as the 2427 cell line, will resist viral replication and continue to proliferate. Our results so far tentatively support this hypothesis, but the data collection is ongoing. Strict and specific protocols with regard to the ethical and responsible use of mice have been implemented and upheld throughout the experiment. Animals are closely monitored, and if their quality of life becomes too poor to justify their continued use in the experiment, they are humanely euthanized, even at the expense of valuable data. The importance of commitment to a high ethical standard is pervasive throughout our work. Animals represent an invaluable contribution to research, and it is important to maintain high standards and transparency with regard to their use. Education and engagement in critical discussions about the use and care of animals in the laboratory contribute to the overall merit and legitimacy of biomedical research in the public and professional eye as a whole, and give legitimacy to the continued use of animals as models to advance science and health.
ContributorsBergamaschi, Julia (Author) / Kibler, Karen (Thesis director) / Jacobs, Bertram (Committee member) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
Advancements in both the medical field and public health have substantially minimized the detrimental impact of infectious diseases. Health education and disease prevention remains a vital tool to maintain and propagate this success. In order to determine the relationship between knowledge of disease and reported preventative behavior 180 participants amongst

Advancements in both the medical field and public health have substantially minimized the detrimental impact of infectious diseases. Health education and disease prevention remains a vital tool to maintain and propagate this success. In order to determine the relationship between knowledge of disease and reported preventative behavior 180 participants amongst the ASU student population were surveyed about their knowledge and prevention behavior for 10 infectious diseases. Of the 180 participants only 138 were completed surveys and used for analysis. No correlation was found between knowledge or perceived risk and preventative measures within the total sample of 138 respondents, however there was a correlation found within Lyme disease and Giardia exposure to information and prevention. Additionally, a cultural consensus analysis was used to compare the data of 17 US-born and 17 foreign-born participants to analyze patterns of variation and agreement on disease education based on national origins. Cultural consensus analysis showed a strong model of agreement among all participants as well as within the US-born and foreign-born student groups. There was a model of agreement within the questions pertaining to transmission and symptoms. There was not however a model of agreement within treatment questions. The findings suggest that accurate knowledge on infectious diseases may be less impactful on preventative behavior than social expectations.
ContributorsVernon, Samantha (Author) / Maupin, Jonathan (Thesis director) / Jehn, Megan (Committee member) / Barrett, The Honors College (Contributor) / School of Human Evolution and Social Change (Contributor)
Created2018-05
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Description
The anthracycline drug Doxorubicin (DOX) is a highly effective treatment for breast cancer, but its clinical utility is limited by dose-dependent cardiovascular toxicity. The toxic effects are partly attributed to DOX-induced generation of reactive oxygen species, which may impair nitric oxide-mediated vasodilation. Exercise training activates antioxidant defense mechanisms and is

The anthracycline drug Doxorubicin (DOX) is a highly effective treatment for breast cancer, but its clinical utility is limited by dose-dependent cardiovascular toxicity. The toxic effects are partly attributed to DOX-induced generation of reactive oxygen species, which may impair nitric oxide-mediated vasodilation. Exercise training activates antioxidant defense mechanisms and is thus hypothesized to counteract oxidative stress when initiated prior to DOX administration. Adult 8-week old, ovariectomized female Sprague-Dawley rats were divided into 4 groups: sedentary + vehicle (Sed+Veh); Sed+DOX; exercise + veh (Ex+Veh); and Ex+DOX. Rats in the exercise groups were preconditioned with high intensity interval training consisting of 4x4 minute bouts of exercise at 85-95% of VO2peak separated by 2 minutes of active recovery performed 5 days per week. Exercise was implemented one week prior to the first injection and continued throughout the study. Animals received either DOX (4mg/kg) or veh (saline) intraperitoneal injections bi-weekly for a cumulative dose of 12 mg/kg per animal. Five days following the final injection, animals were anesthetized with isoflurane, decapitated and aortas and perivascular adipose tissue (PVAT) were removed for western blot analyses. No significant differences in aortic protein expression were detected for inducible nitric oxide synthase (iNOS) or the upstream activator of endothelial nitric oxide synthase (eNOS), Akt, across groups (p>0.05), whereas eNOS protein expression was significantly downregulated in Sed+DOX (p=0.003). In contrast, eNOS expression was not altered in Ex+DOX treated animals. Protein expression of iNOS in PVAT was upregulated with exercise in the DOX-treated groups (p=0.039). These findings suggest that exercise preconditioning may help mitigate vascular effects of DOX by preventing downregulation of eNOS in the aorta.
ContributorsO'Neill, Liam Martin (Author) / Sweazea, Karen (Thesis director) / Angadi, Siddhartha (Committee member) / Dickinson, Jared (Committee member) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12