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The majority of chronic myeloid leukemia (CML) and some of acute lymphocytic leukemia (ALL) cases are associated with possessing the BCR-Abl fusion protein from an oncogenic translocation, resulting in a constantly active form of Abl and rapid proliferation. CML and ALL cells that possess the BCR-Abl fusion protein are known

The majority of chronic myeloid leukemia (CML) and some of acute lymphocytic leukemia (ALL) cases are associated with possessing the BCR-Abl fusion protein from an oncogenic translocation, resulting in a constantly active form of Abl and rapid proliferation. CML and ALL cells that possess the BCR-Abl fusion protein are known as Philadelphia chromosome positive (Ph+). Currently, Imatinib (selective Abl inhibitor) is used as therapy against CML and ALL. However, some patients may have malignancies which show resistance to Imatinib. Previous work displays that the transformation of progenitor B cells with the v-Abl oncogene of Abelson murine leukemia virus results in cell cycle progression, rapid proliferation, and potentially malignant transformation while preventing any further differentiation. Progenitor B cells transformed with the temperature-sensitive form of the v-Abl oncogene have served as a model to study cellular response to Imatinib treatment. After some manipulation, very few cells were forced to progress to malignancy, forming tumor in vivo. These cells were no long sensitive to v-Abl inactivation, resembling the Imatinib resistant ALL. Autophagy is the process by which proteins and organelles are broken-down and recycled within the eukaryotic cell and has been hypothesized to play a part in cancer cell survival and drug-resistance. LC3 processing is a widely accepted marker of autophagy induction and progression. It has also been shown that Imatinib treatment of Ph+ leukemia can induce autophagy. In this study, we examined the autophagy induction in response to v-Abl inactivation in a Ph+-B-ALL cell model that shows resistance to Imatinib. In particular, we wonder whether the tumor cell line resistant to v-Abl inactivation may acquire a high level of autophagy to become resistant to apoptosis induced by v-Abl inactivation, and thus become addicted to autophagy. Indeed, this tumor cell line displays a high basal levels of LC3 I and II expression, regardless of v-Abl activity. We further demonstrated that inhibition of the autophagy pathway enhances the tumor line's sensitivity to Imatinib, resulting in cell cycle arrest and massive apoptosis. The combination of autophagy and Abl inhibitions may serve as an effective therapy for BCR-Abl positive CML.
ContributorsArkus, Nohea (Author) / Chang, Yung (Thesis advisor) / Kusumi, Kenro (Committee member) / Lake, Douglas (Committee member) / Jacobs, Bertram (Committee member) / Arizona State University (Publisher)
Created2011
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Description
Anti-retroviral drugs and AIDS prevention programs have helped to decrease the rate of new HIV-1 infections in some communities, however, a prophylactic vaccine is still needed to control the epidemic world-wide. Despite over two decades of research, a vaccine against HIV-1 remains elusive, although recent clinical trials have shown promising

Anti-retroviral drugs and AIDS prevention programs have helped to decrease the rate of new HIV-1 infections in some communities, however, a prophylactic vaccine is still needed to control the epidemic world-wide. Despite over two decades of research, a vaccine against HIV-1 remains elusive, although recent clinical trials have shown promising results. Recent successes have focused on highly conserved, mucosally-targeted antigens within HIV-1 such as the membrane proximal external region (MPER) of the envelope protein, gp41. MPER has been shown to play critical roles in the viral mucosal transmission, though this peptide is not immunogenic on its own. Gag is a structural protein configuring the enveloped virus particles, and has been suggested to constitute a target of the cellular immunity potentially controlling the viral load. It was hypothesized that HIV-1 enveloped virus-like particles (VLPs) consisting of Gag and a deconstructed form of gp41 comprising the MPER, transmembrane, and cytoplasmic domains (dgp41) could be expressed in plants. Plant-optimized HIV-1 genes were constructed and expressed in Nicotiana benthamiana by stable transformation, or transiently using a tobacco mosaic virus-based expression system or a combination of both. Results of biophysical, biochemical and electron microscopy characterization demonstrated that plant cells could support not only the formation of HIV-1 Gag VLPs, but also the accumulation of VLPs that incorporated dgp41. These particles were purified and utilized in mice immunization experiments. Prime-boost strategies combining systemic and mucosal priming with systemic boosting using two different vaccine candidates (VLPs and CTB-MPR - a fusion of MPER and the B-subunit of cholera toxin) were administered to BALB/c mice. Serum antibody responses against both the Gag and gp41 antigens could be elicited in mice systemically primed with VLPs and these responses could be recalled following systemic boosting with VLPs. In addition, mucosal priming with VLPs allowed for a robust boosting response against Gag and gp41 when boosted with either candidate. Functional assays of these antibodies are in progress to test the antibodies' effectiveness in neutralizing and preventing mucosal transmission of HIV-1. This immunogenicity of plant-based Gag/dgp41 VLPs represents an important milestone on the road towards a broadly-efficacious and inexpensive subunit vaccine against HIV-1.
ContributorsKessans, Sarah (Author) / Mor, Tsafrir S (Thesis advisor) / Matoba, Nobuyuki (Committee member) / Mason, Hugh (Committee member) / Hogue, Brenda (Committee member) / Fromme, Petra (Committee member) / Arizona State University (Publisher)
Created2011
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Description
The concept of vaccination dates back further than Edward Jenner's first vaccine using cowpox pustules to confer immunity against smallpox in 1796. Nevertheless, it was Jenner's success that gave vaccines their name and made vaccinia virus (VACV) of particular interest. More than 200 years later there is still the need

The concept of vaccination dates back further than Edward Jenner's first vaccine using cowpox pustules to confer immunity against smallpox in 1796. Nevertheless, it was Jenner's success that gave vaccines their name and made vaccinia virus (VACV) of particular interest. More than 200 years later there is still the need to understand vaccination from vaccine design to prediction of vaccine efficacy using mathematical models. Post-exposure vaccination with VACV has been suggested to be effective if administered within four days of smallpox exposure although this has not been definitively studied in humans. The first and second chapters analyze post-exposure prophylaxis of VACV in an animal model using v50ΔB13RMγ, a recombinant VACV expressing murine interferon gamma (IFN-γ) also known as type II IFN. While untreated animals infected with wild type VACV die by 10 days post-infection (dpi), animals treated with v50ΔB13RMγ 1 dpi had decreased morbidity and 100% survival. Despite these differences, the viral load was similar in both groups suggesting that v50ΔB13RMγ acts as an immunoregulator rather than as an antiviral. One of the main characteristics of VACV is its resistance to type I IFN, an effect primarily mediated by the E3L protein, which has a Z-DNA binding domain and a double-stranded RNA (dsRNA) binding domain. In the third chapter a VACV that independently expresses both domains of E3L was engineered and compared to wild type in cells in culture. The dual expression virus was unable to replicate in the JC murine cell line where both domains are needed together for replication. Moreover, phosphorylation of the dsRNA dependent protein kinase (PKR) was observed at late times post-infection which indicates that both domains need to be linked together in order to block the IFN response. Because smallpox has already been eradicated, the utility of mathematical modeling as a tool for predicting disease spread and vaccine efficacy was explored in the last chapter using dengue as a disease model. Current modeling approaches were reviewed and the 2000-2001 dengue outbreak in a Peruvian region was analyzed. This last section highlights the importance of interdisciplinary collaboration and how it benefits research on infectious diseases.
ContributorsHolechek, Susan A (Author) / Jacobs, Bertram L (Thesis advisor) / Castillo-Chavez, Carlos (Committee member) / Frasch, Wayne (Committee member) / Hogue, Brenda (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2011
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Description

Animals encounter information from different resources simultaneously, integrating input from multiple sensory systems before responding behaviorally. When different cues interact with one another, they may enhance, diminish, or have no impact on their responses. In this project, we test how the presence of chemical cues affect the perception of visual

Animals encounter information from different resources simultaneously, integrating input from multiple sensory systems before responding behaviorally. When different cues interact with one another, they may enhance, diminish, or have no impact on their responses. In this project, we test how the presence of chemical cues affect the perception of visual cues. Zebrafish (Danio rerio) often use both chemical cues and visual cues to communicate with shoal mates, to assess predation risk, and to locate food. For example, zebrafish rely on both olfactory cues and visual cues for kin recognition, and they frequently use both chemical and visual cues to search for and to capture prey. In zebrafish, the terminal nerve (TN) constitutes the olfacto-visual centrifugal pathway and connects the olfactory bulb with the retina, thus allowing olfactory perception also to activate visual receptors. Past studies have found that the presence of an olfactory cue can modulate visual sensitivity in zebrafish through the terminal nerve pathway. Alternatively, given that zebrafish are highly social, the presence of social chemical cues may distract individuals from responding to other visual cues, such as food and predator visual cues. Foraging and predator chemical cues, including chemical food cues and alarm cues, may also distract individuals from responding to non-essential visual cues. Here, we test whether the response to a visual cue either increases or decreases when presented in concert with alanine, an amino acid that represents the olfactory cues of zebrafish prey. We found that the presence of chemical cues did not affect whether zebrafish responded to visual cues, but that the fish took longer to respond to visual cues when chemical cues were also present. These findings suggest that different aspects of behavior could be affected by the interaction between sensory modalities. We also found that this impact of delayed response was significant only when the visual cue<br/>was weak compared to the strength of the chemical cue, suggesting that the salience of interacting cues may also have an influence on determining the outcomes of the interactions. Overall, the interactive effects of chemicals on an animal’s response to visual cues may also have wide-ranging impacts on behavior including foraging, mating, and evading predators, and the interaction of cues may affect different aspects of the same behavior.

ContributorsPuffer, Georgie Delilah (Author) / Martins, Emilia (Thesis director) / Suriyampola, Piyumika (Committee member) / Gerkin, Richard (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

Humans use emotions to communicate social cues to our peers on a daily basis. Are we able to identify context from facial expressions and match them to specific scenarios? This experiment found that people can effectively distinguish negative and positive emotions from each other from a short description. However, further

Humans use emotions to communicate social cues to our peers on a daily basis. Are we able to identify context from facial expressions and match them to specific scenarios? This experiment found that people can effectively distinguish negative and positive emotions from each other from a short description. However, further research is needed to find out whether humans can learn to perceive emotions only from contextual explanations.

ContributorsCulbert, Bailie (Author) / Hartwell, Leland (Thesis director) / McAvoy, Mary (Committee member) / School of Life Sciences (Contributor) / School of Criminology and Criminal Justice (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

Locusts are generalist herbivores meaning that they are able to consume a variety of plants. Because of their broad diet, and ability to respond rapidly to a favorable environment with giant swarms of voracious insects, they are dangerous pests. Their potential impacts on humans increase dramatically when individuals switch from

Locusts are generalist herbivores meaning that they are able to consume a variety of plants. Because of their broad diet, and ability to respond rapidly to a favorable environment with giant swarms of voracious insects, they are dangerous pests. Their potential impacts on humans increase dramatically when individuals switch from their solitarious phase to their gregarious phase where they congregate and begin marching and eventually swarming together. These swarms, often billions strong, can consume the vegetation of enormous swaths of land and can travel hundreds of kilometers in a single day producing a complex threat to food security. To better understand the biology of these important pests we explored the gut microbiome of the South American locust (Schistocerca cancellata). We hypothesized generally that the gut microbiome in this species would be critically important as has been shown in many other species. We extracted and homogenized entire guts from male S. cancellata, and then extracted gut microbiome genomic DNA. Genomic DNA was then confirmed on a gel. The initial extractions were of poor quality for sequencing, but subsequent extractions performed by collaborators during troubleshooting at Southern Illinois University Edwardsville proved more useful and were used for PCR. This resulted in the detections of the following bacterial genera in the gut of S. cancellata: Enterobacter, Enterococcus, Serratia, Pseudomonas, Actinobacter, and Weisella. With this data, we are able to speculate about the physiological roles that they hold within the locust gut generating hypotheses for further testing. Understanding the microbial composition of this species’ gut may help us better understand the locust in general in an effort to more sustainably manage them.

ContributorsGrief, Dustin (Author) / Overson, Rick (Thesis director) / Cease, Arianne (Committee member) / Peterson, Brittany (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

Over 40% of adults in the United States are considered obese. Obesity is known to cause abnormal metabolic effects and lead to other negative health consequences. Interestingly, differences in metabolism and contractile performance between obese and healthy weight individuals are associated with differences in skeletal muscle fiber type composition between

Over 40% of adults in the United States are considered obese. Obesity is known to cause abnormal metabolic effects and lead to other negative health consequences. Interestingly, differences in metabolism and contractile performance between obese and healthy weight individuals are associated with differences in skeletal muscle fiber type composition between these groups. Each fiber type is characterized by unique metabolic and contractile properties, which are largely determined by the myosin heavy chain isoform (MHC) or isoform combination that the fiber expresses. In previous studies, SDS-PAGE single fiber analysis has been utilized as a method to determine MHC isoform distribution and single fiber type distribution in skeletal muscle. Herein, a methodological approach to analyze MHC isoform and fiber type distribution in skeletal muscle was fine-tuned for use in human and rodent studies. In the future, this revised methodology will be implemented to evaluate the effects of obesity and exercise on the phenotypic fiber type composition of skeletal muscle.

ContributorsOhr, Jalonna Rose (Author) / Katsanos, Christos (Thesis director) / Tucker, Derek (Committee member) / Serrano, Nathan (Committee member) / School of Life Sciences (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

In the United States, clinical testing is monitored by the federal and state governments, held to standards to ensure the safety and efficacy of these tests, as well as maintaining privacy for patients receiving a test. In order for the ABCTL to lawfully operate in the state of Arizona, it

In the United States, clinical testing is monitored by the federal and state governments, held to standards to ensure the safety and efficacy of these tests, as well as maintaining privacy for patients receiving a test. In order for the ABCTL to lawfully operate in the state of Arizona, it had to meet various legal criteria. These major legal considerations, in no particular order, are: Clinical Laboratory Improvement Amendments compliance; FDA Emergency Use Authorization (EUA); Health Insurance Portability and Accountability Act compliance; state licensure; patient, state, and federal result reporting; and liability. <br/>In this paper, the EUA pathway will be examined and contextualized in relation to the ABCTL. This will include an examination of the FDA regulations and policies that affect the laboratory during its operations, as well as a look at the different authorization pathways for diagnostic tests present during the COVID-19 pandemic.

ContributorsJenkins, Landon James (Co-author) / Espinoza, Hale Anna (Co-author) / Filipek, Marina (Co-author) / Ross, Nathaniel (Co-author) / Salvatierra, Madeline (Co-author) / Compton, Carolyn (Thesis director) / Rigoni, Adam (Committee member) / Stanford, Michael (Committee member) / School of Life Sciences (Contributor) / School of Politics and Global Studies (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

Within the pediatric hospitalization experience, fear and anxiety are two emotions commonly felt by children of all ages. Hospitalized children can greatly benefit from interventions designed to help them cope with these emotions throughout their medical experiences. This study draws on each of our clinical experiences as volunteers at Phoenix

Within the pediatric hospitalization experience, fear and anxiety are two emotions commonly felt by children of all ages. Hospitalized children can greatly benefit from interventions designed to help them cope with these emotions throughout their medical experiences. This study draws on each of our clinical experiences as volunteers at Phoenix Children’s Hospital, and uses a qualitative analysis of three semi-structured interviews with currently employed Child Life Specialists to understand and analyze the use of medical play, a form of play intervention with a medical theme or medical equipment. We explore the goals and benefits of medical play for hospitalized pediatric patients, the process of using medical play as an intervention, including the activity design process, the assessments and adjustments made throughout the child’s hospitalization, and the considerations and limitations to implementing medical play activities. Ultimately, we found that the element of fun that defines play can be channeled into medical play activities implemented by skilled Child Life Specialists, who are experts in their field, in clinical settings to promote several different and beneficial goals, including pediatric patient coping.

ContributorsAguiar, Lara (Co-author) / Garciapeña, Danae (Co-author) / Loebenberg, Abby (Thesis director) / Swanson, Jodi (Committee member) / School of Life Sciences (Contributor) / Sanford School of Social and Family Dynamics (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

What is being done to promote cultural sensitivity in healthcare settings? To find answers and solutions to the widespread deficit of cultural competence in the health care industry, this case study interviews a varied sample of five physicians consisting of three men and two women in clinical, academic, and administrative

What is being done to promote cultural sensitivity in healthcare settings? To find answers and solutions to the widespread deficit of cultural competence in the health care industry, this case study interviews a varied sample of five physicians consisting of three men and two women in clinical, academic, and administrative positions. The hypothesis was physicians do not receive cultural sensitivity training in medical school and as a result, they have to find other ways to learn about the cultures of their patients. None of the participants had received formal cultural competency training in medical school and all of them found methods to improve their cultural literacy. The study uncovered the cultural training physicians do receive is sporadic and inconsistent, which can cause some disconnect between education and real-life clinical practice. Many solutions to improve cultural competency in health care delivery are presented. The results of this exploratory research should be used to inspire future conversations about cultural competency in health care as well as the creation of support and educational services and materials to medical students and health care workers on improving cultural sensitivity in clinical practice.

ContributorsWilson, Diane Kathleen (Author) / Cortese, Denis (Thesis director) / Estevez, Dulce (Committee member) / School of International Letters and Cultures (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05