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Hundreds of thousands of people die annually from malaria; a protozoan of the genus Plasmodium is responsible for this mortality. The Plasmodium parasite undergoes several life stages within the mosquito vector, the transition between which require passage across the lumen of the mosquito midgut. It has been observed that in

Hundreds of thousands of people die annually from malaria; a protozoan of the genus Plasmodium is responsible for this mortality. The Plasmodium parasite undergoes several life stages within the mosquito vector, the transition between which require passage across the lumen of the mosquito midgut. It has been observed that in about 15% of parasites that develop ookinetes in the mosquito abdomen, sporozoites never develop in the salivary glands, indicating that passage across the midgut lumen is a significant barrier in parasite development (Gamage-Mendis et al., 1993). We aim to investigate a possible correlation between passage through the midgut lumen and drug-resistance trends in Plasmodium falciparum parasites. This study contains a total of 1024 Anopheles mosquitoes: 187 Anopheles gambiae and 837 Anopheles funestus samples collected in high malaria transmission areas of Mozambique between March and June of 2016. Sanger sequencing will be used to determine the prevalence of known resistance alleles for anti-malarial drugs: chloroquine resistance transporter (pfcrt), multidrug resistance (pfmdr1) gene, dihydropteroate synthase (pfdhps) and dihydrofolate reductase (pfdhfr). We compare prevalence of resistance between abdomen and head/thorax in order to determine whether drug resistant parasites are disproportionately hindered during their passage through the midgut lumen. A statistically significant difference between resistance alleles in the two studied body sections supports the efficacy of new anti-malarial gene surveillance strategies in areas of high malaria transmission.

ContributorsPhillips, Keeley Isabella (Author) / Huijben, Silvie (Thesis director) / Gile, Gillian (Committee member) / Young, Steven (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Mosquitoes are estimated to kill roughly 700,000 people each year through the transmission of vector-borne diseases. Vector control via insecticides is a widely used method in order to combat the spread of mosquito populations; however, this comes at a cost. Resistance to insecticides has the potential to increase vector-borne disease

Mosquitoes are estimated to kill roughly 700,000 people each year through the transmission of vector-borne diseases. Vector control via insecticides is a widely used method in order to combat the spread of mosquito populations; however, this comes at a cost. Resistance to insecticides has the potential to increase vector-borne disease rates. Aedes aegypti is an invasive mosquito species in Arizona and is a known potential vector for a variety of infectious diseases including dengue, chikungunya, Zika, and yellow fever. In contrast to many other mosquito species Ae. aegypti mosquito eggs can undergo quiescence, an active state of dormancy, over long periods of time. Variation in quiescent periods correlates to climatic rainfall alterations and can ultimately influence hatching and mating between multiple generations. I have studied the effect of quiescence on larvicide (i.e., temephos) susceptibility using mosquito eggs collected from a susceptible lab strain and stored under optimal temperature and humidity conditions. After undergoing various quiescent periods (3, 7, 14, 28, 84, and 182 days), the experimental eggs as well as 7-day quiescent control eggs were hatched and reared to 3rd instar larvae. Temephos susceptibility was tested using the WHO bioassay procedure at lethal concentration (LC) 20, LC50, LC80, diagnostic dose (twice LC99), plus an untreated control. Each concentration dose was replicated four times with 20 larvae each. The 3-day experimental group was excluded from analysis because the mortality was significantly lower than the 7-day for both the experimental and control groups. The 3 day experimental eggs displayed decreased mortality which did not align with the hypothesis, as the quiescence period elongates under optimal conditions, susceptibility to insecticides decreases, and this could have likely resulted from unintentional selection for increased fitness and faster developing eggs because the larvae that developed to 3rd instar first were those used for larvicide testing. ANOVA testing demonstrates variability in the LC80 experimental group which suggests the need for further investigation into high dose temephos concentrations. For the experimental LC20 linear regression, there were significant differences in mortality. The results indicate mortality gradually decreases when the quiescence period elongates, therefore there are significant differences in insecticide susceptibility when quiescence is 182 days (or longer), compared to when quiescence is 7 days. Further investigation into field mosquito’s genetic diversity, insecticide resistance profile, and environmental conditions should be considered.

ContributorsKayce, Brenna Jean (Author) / Huijben, Silvie (Thesis director) / Paaijmans, Krijn (Committee member) / Jensen, Brook (Committee member) / School of Life Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description
The study of bacterial resistance to antimicrobial peptides (AMPs) is a significant area of interest as these peptides have the potential to be developed into alternative drug therapies to combat microbial pathogens. AMPs represent a class of host-mediated factors that function to prevent microbial infection of their host and serve

The study of bacterial resistance to antimicrobial peptides (AMPs) is a significant area of interest as these peptides have the potential to be developed into alternative drug therapies to combat microbial pathogens. AMPs represent a class of host-mediated factors that function to prevent microbial infection of their host and serve as a first line of defense. To date, over 1,000 AMPs of various natures have been predicted or experimentally characterized. Their potent bactericidal activities and broad-based target repertoire make them a promising next-generation pharmaceutical therapy to combat bacterial pathogens. It is important to understand the molecular mechanisms, both genetic and physiological, that bacteria employ to circumvent the bactericidal activities of AMPs. These understandings will allow researchers to overcome challenges posed with the development of new drug therapies; as well as identify, at a fundamental level, how bacteria are able to adapt and survive within varied host environments. Here, results are presented from the first reported large scale, systematic screen in which the Keio collection of ~4,000 Escherichia coli deletion mutants were challenged against physiologically significant AMPs to identify genes required for resistance. Less than 3% of the total number of genes on the E. coli chromosome was determined to contribute to bacterial resistance to at least one AMP analyzed in the screen. Further, the screen implicated a single cellular component (enterobacterial common antigen, ECA) and a single transporter system (twin-arginine transporter, Tat) as being required for resistance to each AMP class. Using antimicrobial resistance as a tool to identify novel genetic mechanisms, subsequent analyses were able to identify a two-component system, CpxR/CpxA, as a global regulator in bacterial resistance to AMPs. Multiple previously characterized CpxR/A members, as well as members found in this study, were identified in the screen. Notably, CpxR/A was found to transcriptionally regulate the gene cluster responsible for the biosynthesis of the ECA. Thus, a novel genetic mechanism was uncovered that directly correlates with a physiologically significant cellular component that appears to globally contribute to bacterial resistance to AMPs.
ContributorsWeatherspoon-Griffin, Natasha (Author) / Shi, Yixin (Thesis advisor) / Clark-Curtiss, Josephine (Committee member) / Misra, Rajeev (Committee member) / Nickerson, Cheryl (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2013
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Description
The Philadelphia chromosome in humans, is on oncogenic translocation between chromosomes 9 and 22 that gives rise to the fusion protein BCR-Abl. This protein is constitutively active resulting in rapid and uncontrolled cell growth in affected cells. The BCR-Abl protein is the hallmark feature of chronic myeloid leukemia (CML) and

The Philadelphia chromosome in humans, is on oncogenic translocation between chromosomes 9 and 22 that gives rise to the fusion protein BCR-Abl. This protein is constitutively active resulting in rapid and uncontrolled cell growth in affected cells. The BCR-Abl protein is the hallmark feature of chronic myeloid leukemia (CML) and is seen in Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) cases. Currently, the first line of treatment is the Abl specific inhibitor Imatinib. Some patients will, however, develop resistance to Imatinib. Research has shown how transformation of progenitor B cells with v-Abl, an oncogene expressed by the Abelson murine leukemia virus, causes rapid proliferation, prevents further differentiation and produces a potentially malignant transformation. We have used progenitor B cells transformed with a temperature-sensitive form of the v-Abl protein that allows us to inactivate or re-activate v-Abl by shifting the incubation temperature. We are trying to use this line as a model to study both the progression from pre-malignancy to malignancy in CML and Imatinib resistance in Ph+ ALL and CML. These progenitor B cells, once v-Abl is reactivated, in most cases, will not return to their natural cell cycle. In this they resemble Ph+ ALL and CML under Imatinib treatment. With some manipulation these cells can break this prolonged G1 arrested phenotype and become a malignant cell line and resistant to Imatinib treatment. Cellular senescence can be a complicated process requiring inter-play between a variety of players. It serves as an alternate option to apoptosis, in that the cell loses proliferative potential, but does not die. Treatment with some cancer therapeutics will induce senescence in some cancers. Such is the case with Imatinib treatment of CML and Ph+ ALL. By using the S9 cell line we have been able to explore the possible routes for breaking of prolonged G1 arrest in these Ph+ leukemias. We inhibited the DNA damage sensor protein ataxia telangiectasia mutated (ATM) and found that prolonged G1 arrest in our S9 cells was broken. While previous research has suggested that the DNA damage sensor protein ataxia-telangiectasia mutated (ATM) has little impact in CML, our research indicates that ATM may play a role in either senescence induction or release.
ContributorsDixon, Sarah E (Author) / Chang, Yung (Thesis advisor) / Clark-Curtiss, Josephine (Committee member) / Touchman, Jeffrey (Committee member) / Arizona State University (Publisher)
Created2011
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In 2016, the news of the protests at Standing Rock broke through the nation. The Sioux Falls tribe of North Dakota embarked on a fight to protect their sacred lands and water from potential desecration and pollution. The documentary film, Awake, a Dream from Standing Rock, was released the following

In 2016, the news of the protests at Standing Rock broke through the nation. The Sioux Falls tribe of North Dakota embarked on a fight to protect their sacred lands and water from potential desecration and pollution. The documentary film, Awake, a Dream from Standing Rock, was released the following year depicting the resistance movement created at the camps at Standing Rock. This film became the subject matter for my project in which a film screening followed by a post-show discussion to explore the resistance movement and creative choices of the film as they pertain to indigenous rights, climate change, and corporations. The panel included Leroy Hollenback, a corporate social responsibility director from a Global 500 company, and Monte Yazzie, a Phoenix activist and film critic. The panel analyzed the artistic choices the filmmakers took and how that shaped the message of the film. Furthermore, the panel discussed what policy implications the film brought to light. In the end, indigenous resistance in efforts to protect Earth's biodiversity is present globally, making Standing Rock a modern case study that can instruct future movements.
ContributorsSalas, Anna C. (Author) / Sandoval, Mathew (Thesis director) / Hsueh, Lily (Committee member) / School of Public Affairs (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
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Every day we pass people without thinking everyone has a story. If an individual looks “normal,” any struggles faced living with an invisible disability are left without words or thoughts due to the dominant norm—ableism. Conversely, a more visible disability may not be dismissed as quickly. Who

Every day we pass people without thinking everyone has a story. If an individual looks “normal,” any struggles faced living with an invisible disability are left without words or thoughts due to the dominant norm—ableism. Conversely, a more visible disability may not be dismissed as quickly. Who are unseen, ignored, and misunderstood are those who live with invisible disabilities not only in a dominant able-bodied society, but also within academic scholarship as well, because they do not fit into the dominant definition of disability. In turn, binaries form between power relations and within knowledge production that create exclusion. This thesis is an intersectional analysis on expanding the definition of disability, specifically invisible disability, in order to deconstruct, challenge, and transform the hegemonic conceptualization of disability and break binaries in order to give voice to ignored and misunderstood narratives of invisible disabilities as well as foster and create nuanced understanding within knowledge production and power itself. I particularly use an autoethnographic approach to conduct this analysis of my own everyday, lived experience as a young, mixed race woman living with an invisible disability, or chronic illness, on how ableism operates in the medical sphere and at the academy, further exploring what it means to be a “good” or “bad” chronic illness patient and categorized and labeled by the stigmas attached to the definition of disability.
ContributorsGarcia, Jordan Marie (Author) / Behl, Natasha (Thesis director) / Watrous, Lisa (Committee member) / School of Social and Behavioral Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
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Police use of force and race often garners a good deal of attention, however it is also important to understand the influence of gender when dealing with male-dominate populations, like police officers. The current study aims to add to the current body of literature by using data from seven cities

Police use of force and race often garners a good deal of attention, however it is also important to understand the influence of gender when dealing with male-dominate populations, like police officers. The current study aims to add to the current body of literature by using data from seven cities to examine the relationship between officer gender and police use of force, as well as officer gender and citizen resistance. In relation to use of force, the results show that male officers used significantly less force than female officers. In terms of citizen resistance, the results indicate that officer gender had no effect. Additionally, a number of control variables were significantly related to police use of force and citizen resistance. The implications of these findings are discussed.
ContributorsWeiser, Marah Brooke (Author) / William, Terrill (Thesis director) / Trinkner, Rick (Committee member) / School of Criminology and Criminal Justice (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
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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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Theories of resistance have been investigated by various researchers as an explanation for student empowerment, achievement, and activism. Similar research on youth empowerment has been conducted with Critical Race Theory and the development of culturally relevant curriculums in classrooms. Culturally relevant pedagogy has been studied by many due to its

Theories of resistance have been investigated by various researchers as an explanation for student empowerment, achievement, and activism. Similar research on youth empowerment has been conducted with Critical Race Theory and the development of culturally relevant curriculums in classrooms. Culturally relevant pedagogy has been studied by many due to its ability to foster student empowerment and transform students into agents of social change within their communities, allowing them to pursue opportunities they hadn't considered otherwise. However, there is not much research that studies how culturally relevant pedagogy and culturally relevant school programs foster student activism. This study focuses on assessing how the culturally relevant curriculum fosters student activism within the Mexican American Studies program in Tucson, Arizona. Following the changes made after HB2281, which temporarily banned the program. It was reinstated and renamed Ethnic Studies following the court ruling, Arce v Douglas. Using theories of resistance and activism, data gathered from the Ethnic Studies course through student surveys and interviews was analyzed, in addition to a brief content analysis of the course reading lists. Though focusing on community engagement, political/social justice awareness, and concepts of identity, interview and survey data demonstrated significant levels of student resistance. Further research will confirm if this program fosters student activism.
ContributorsRodriguez, Felina Milagros (Author) / Woodall, Gina (Thesis director) / Scott, Kimberly (Committee member) / Department of Information Systems (Contributor) / School of International Letters and Cultures (Contributor) / School of Politics and Global Studies (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description

Activist burnout theory has produced minimal but meaningful literature and research that explores the dynamics of burnout culture, movement in-fighting, marginalized identities, and dimensions of burnout symptoms. Black feminist visionaries and writers such as Audre Lorde and bell hooks have developed theories of love, self-care and community as central to

Activist burnout theory has produced minimal but meaningful literature and research that explores the dynamics of burnout culture, movement in-fighting, marginalized identities, and dimensions of burnout symptoms. Black feminist visionaries and writers such as Audre Lorde and bell hooks have developed theories of love, self-care and community as central to resistance that have informed my research approach. Thus, my study aims to investigate activist burnout from a perspective that marries popular activist burnout theory with these frameworks of self-care and community. I conducted a survey of Arizona State University student organizers and activists (N=34) to address the following research questions: What are the causes and symptoms of burnout for Arizona State University activists and organizers? How have self-care and community played a role in their work and countered burnout? Can working conceptions of self-care and community serve as resistance in ways that feel meaningful to activists? The survey was broken into three dimensions: “Demographics and Experience,” “Burnout,” and “Self-Care and Community.” The results reinforced prior findings on established toxic cultures and burnout symptoms but introduced complications to working theories, such as the connections between cycles of burnout and the cyclical nature of electoral politics along with the roles of chronic and mental illness. Respondents largely demonstrated conceptions of self-care and community as resistance but also demonstrated personal and professional barriers to putting these conceptions into practice.

ContributorsKittridge, Rebecca (Author) / Lee, Charles (Thesis director) / Boyles, David (Committee member) / Krysik, Judy (Committee member) / Barrett, The Honors College (Contributor) / School of International Letters and Cultures (Contributor) / Department of Psychology (Contributor) / School of Social Transformation (Contributor)
Created2023-05