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- Creators: School of Life Sciences
- Member of: Barrett, The Honors College Thesis/Creative Project Collection
Description
Memory CD8+ T-cells can persist in the absence of antigen, primed for immediate activation and proliferation if later exposed to the same antigen. These cytotoxic lymphocytes provide long-term immunity following an acute infection. Studies have observed that intermediate levels of general T cell transfer prior to infection may cause an inappropriate response resulting in increased pathology rather than prevention. Therefore, our study focused on a memory CD8 T-cell therapy using lymphocytic choriomeningitis virus (LCMV) specific splenocytes, which activate and proliferate at an accelerated pace compared to that of naive T-cells. LCMV is a natural murine pathogen which also poses a zoonotic infection threat to humans, and the effect of immune cell vaccination therapies for LCMV is not fully understood. We observed the effect of multiple memory CD8 T cell dosage levels on overall disease and memory CD8 T-cell response to the virus. Infection by exposure to a carrier was shown to have a reduced impact on mice receiving higher doses of memory T cells prior to infection compared to mice receiving less or no memory cells. Higher presence of activated memory cells were shown to correlate with less disease-related weight loss and accelerated recovery times. Survival rate after exposure to carriers was not shown to be affected by dosage level, warranting further research regarding the prevalence of the immunopathology observed in other studies in natural murine transmission models.
ContributorsMiller, Charles (Author) / Blattman, Joseph (Thesis director) / Holechek, Susan (Committee member) / Carmen, Joshua (Committee member) / W. P. Carey School of Business (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
This study examines the effect of exercise therapy on a stationary bike on cognitive function, specifically inhibition and set-switching, in adolescents with Down syndrome. 44 participants were randomly divided between the voluntary cycling therapy group (VCT) (i.e., self-selected cadence), assisted cycling therapy group (ACT) (i.e., 30% faster than self-selected cadence accomplished by a motor), and a control group (NC) in which the participants did not undergo any exercise therapy. Both cycling groups rode a stationary bicycle, for 30 minutes, three times a week, for eight-weeks. At the beginning (i.e., pretest) and end (i.e., posttest) of the eight-week session the participants completed tasks to evaluate their cognitive function. They completed three trials of the card sort test (i.e., set-switching) and three trials of the knock-tap test (i.e, inhibition) before and after eight-weeks of cycling therapy. The scores of these tests were analyzed using one-way ANOVA between groups and paired samples t-tests. The results showed that after eight-weeks of cycling therapy the participants in the VCT group performed worse in the knock-tap test, but improved in two trials of the card sort test. The results also showed that the participants in the ACT group performed worse after eight-weeks of exercise therapy in one trial of the card sort test. No significant changes were seen for the control group. Due to the fact that on average the participants in the VCT group cycled with a higher heart rate, our results suggest exercise that significantly elevates heart rate can improve cognitive function, specifically set-switching, in adolescents with Down syndrome.
ContributorsBenson, Alicia Meigh (Author) / Ringenbach, Shannon (Thesis director) / Amazeen, Eric (Committee member) / Maraj, Brian (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Influenza is a deadly disease for which effective vaccines are sorely lacking. This is largely due to the phenomena of antigenic shift and drift in the influenza virus's surface proteins, hemagglutinin (HA) and neuraminidase (NA). The ectodomain of the matrix 2 protein (M2e) of influenza A, however, has demonstrated high levels of conservation. On its own it is poorly immunogenic and offers little protection against influenza infections, but by combining it with a potent adjuvant, this limitation may be overcome. Recombinant immune complexes, or antigens fused to antibodies that have been engineered to form incredibly immunogenic complexes with one another, were previously shown to be useful, immunogenic platforms for the presentation of various antigens and could provide the boost in immunogenicity that M2e needs to become a powerful universal influenza A vaccine. In this thesis, genetic constructs containing geminiviral replication proteins and coding for a consensus sequence of dimeric M2e fused to antibodies featuring complimentary epitopes and epitope tags were generated and used to transform Agrobacterium tumefaciens. The transformed bacteria was then used to cause Nicotiana benthamiana to transiently express M2e-RICs at very high levels, with enough RICs being gathered to evaluate their potency in future mouse trials. Future directions and areas for further research are discussed.
ContributorsFavre, Brandon Chetan (Author) / Mason, Hugh (Thesis director) / Mor, Tsafrir (Committee member) / Diamos, Andrew (Committee member) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
This study examines the one month retention of executive function benefits gained by adolescents with Down syndrome after an 8-week aerobic exercise intervention. Sixteen participants were randomly divided between voluntary (VC) (i.e., self-selected cadence) and assisted (AC) (i.e., 30% faster than self-selected cadence accomplished by a motor) cycling groups, with one participant used as a control (NC). Both cycling groups rode a stationary bicycle, for 30 minutes, three times a week, for eight weeks. At the beginning (i.e., pretest) and end (posttest) of the 8-week session, three executive functions including: set-switching, inhibition, and cognitive planning, were tested. Approximately one month after the posttest, all participants underwent the cognitive testing again. The results showed that for the AC group cognitive planning improved after eight weeks of assisted cycling and these improvements were maintained after one month of no cycling. However, no significant differences were found between the cycling groups for our measure of inhibition. Set-switching appeared to be improved by both types of exercise, rather than only assisted, but the improvements were not maintained during the one month retention period for either group. Thus, our results suggest that Assisted Cycling causes potentially permanent changes in the brain in regards to cognitive planning.
ContributorsRichter, Madeline B. (Author) / Ringenbach, Shannon (Thesis director) / Amazeen, Eric (Committee member) / Maraj, Brian (Committee member) / Barrett, The Honors College (Contributor) / School of International Letters and Cultures (Contributor) / School of Life Sciences (Contributor)
Created2014-05
Description
Persons with Down Syndrome (DS) have been repeatedly shown to have timing deficits, to move slowly, and to not follow metronomes. This timing deficit in persons with DS requires further study because timing is fundamental to movement control. Furthermore, brain imaging studies have proposed a rate effect in which increased cortical activation in the primary motor cortex was observed during increased finger movement frequency. The aim of the current study was to determine if the rate effect was present in persons with DS by comparing brain activation in self-selected and as fast as possible rates. Eight participants with DS performed unimanual drumming at their self-selected and maximal rates. Movement rate was measured at EEG was collected in the alpha (8-12 Hz) and Beta (13-30 Hz) frequencies from C3 and C4. The results showed that overall, their self-selected rates were slower than their maximal rates, indicating that they are capable of modifying their movement rate with general instructions. Furthermore, there were significant differences in Beta in which there was more activation during as fast as possible than self-selected tapping in both sides of the primary motor cortex in persons with DS. This suggests that their brains are activated in a similar manner as the typical population with respect to movement rate. Overall, our results suggest that while interventions that involve timing to specific rates are difficult, people with DS can perform at self-selected and maximal rates. The results of our study show that they can alter movement rate when provided with general instruction or additional motivation.
ContributorsCarrington, Elise Almader (Author) / Ringenbach, Shannon (Thesis director) / Crews, Debbie (Committee member) / Hillman, Charles (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / School of Nutrition and Health Promotion (Contributor)
Created2013-05
Description
Vaccine opposition is a growing problem in developed countries where dropping vaccination rates threaten general public health by laying the foundation for resurgence and reemergence of previously eradicated infectious diseases. This thesis argues that the current movement is only the most recent incarnation of opposition that has co-evolved with vaccine practices for the duration of their mutual histories. Part one provides a historical context for the current movement using the example of the development and deployment of the smallpox vaccine as a representative timeline of vaccine acceptance and opposition. Part two describes the current movement in the United States and the United Kingdom, interprets the reasons for the conclusions drawn by vaccine-concerned parents, and provides a framework for public health officials to approach the issues.
ContributorsKost, Stephanie Michelle (Author) / Lynch, John (Thesis director) / Hurlbut, Ben (Committee member) / Robert, Jason (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / School of Life Sciences (Contributor)
Created2013-12
Description
Dengue virus infects millions of people every year. Yet there is still no vaccine available to prevent it. Here we use a neutralizing epitope determinant on the dengue envelope (E) protein as an immunogen to be vectored by a measles virus (MV) vaccine. However the domain III (DIII) of the dengue 2 E protein is too small to be immunogenic by itself. In order for it to be displayed on a larger particle, it was inserted into the amino terminus of small hepatitis B surface antigen (HBsAg, S) coding sequence. To generate the recombinant MV vector and verify the efficiency of this concept, a reverse genetics system was used where the MV vectors express one or two additional transcription units to direct the assembly of hybrid HBsAg particles. Two types of recombinant measles virus were produced: pB(+)MVvac2(DIII-S,S)P and pB(+)MVvac2(DIII-S)N. Virus recovered from pB(+)MVvac2(DIII-S,S)P was viable. An ELISA assay was performed to demonstrate the expression and secretion of HBsAg. Supernatant from MVvac2(DIII-S,S)P infected cells confirmed that hybrid HBsAg-domain III particles with a density similar to traditional HBsAg particles were released. Characteristics of the subviral particle have been analyzed for the successful incorporation of domain III. The replication fitness of the recombinant MV was evaluated using multi-step growth kinetics and showed reduced replication fitness when compared to the parental strain MVvac2. This demonstrates that viral replication is hindered by the addition of the two inserts into MV genome. Further analysis of MVvac2(DIII-S)N is needed to justify immune response studies in a small animal model using both of the generated recombinant vectors.
ContributorsHarahap, Indira Saridewi (Author) / Reyes del Valle, Jorge (Thesis director) / Hogue, Brenda (Committee member) / Misra, Rajeev (Committee member) / Barrett, The Honors College (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (Contributor)
Created2014-05
Description
In the United States, a dispute has arisen over the safety and need for vaccination, particularly in regard to compulsory vaccination laws. New outlets and social media sites publish countless reports about the dangers of vaccines or of known adverse reactions as well as imagined or unproven worries. Individuals' rights to choose to get vaccinated or allow their children to be vaccinated comes to direct conflict with measures needed to protect communities from preventable viral diseases. The controversy surrounding vaccines is not new, nor necessarily are the fundamental reasons for skepticism. Looking back through the history of vaccines as a medical tool, the evolution of the controversy can be observed taking place with each new historical context, scientific development, and social conditions. Despite scientific research and assurances of vaccine safety, opposition and unease about vaccination appear to take Looking individually at the development and distribution of the smallpox (variola virus), polio (poliovirus) and human papilloma virus(HPV) vaccines, concerns regarding the violation of personal rights, safety of vaccines themselves, and social stigmas and connotations surrounding vaccines can be seen to evolve and change. Due to the way doubt can manifest in different ways over time, it may be impossible to fully end the vaccine debate. However, nderstanding the sociological factors behind anti-vaccine sentiment may allow healthcare professionals to work with concerned people with a particular care to address these visceral and sometimes irrational fears surrounding vaccination.
ContributorsStevens, Luke Christian (Author) / Jacobs, Bertram (Thesis director) / Washo-Krupps, Delon (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2014-05
Description
Agrobacterium tumefaciens has the ability to transfer its tumor inducing (Ti) plasmid into plant cells. In the last decade, agroinfiltration of Nicotiana benthamiana plants has shown promising results for recombinant protein production. However, A. tumefaciens produce endotoxins in the form of lipopolysaccharides (LPS), a component of their outer membrane that can induce organ failure and septic shock. Therefore, we aimed to detoxify A. tumefaciens by modifying their Lipid A structure, the toxic region of LPS, via mutating the genes for lipid A biosynthesis. Two mutant strains of A. tumefaciens were infiltrated into N. benthamiana stems to test for tumor formation to ensure that the detoxifying process did not compromise the ability of gene transfer. Our results demonstrated that A. tumefaciens with both single and double mutations retained the ability to form tumors. Thus, these mutants can be utilized to generate engineered A. tumefaciens strains for the production of plant-based pharmaceuticals with low endotoxicity.
ContributorsHaseefa, Fathima (Author) / Chen, Qiang (Thesis director) / Mason, Hugh (Committee member) / Hurtado, Jonathan (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Individuals with Down Syndrome (DS) are subject to a spectrum of behavioral, cognitive and physical impairments. This population is more predisposed to comorbidity and typically has an increased risk of inactivity resulting in a lower level of fitness. Previous studies on physical activity have shown that routine exercise has similar health benefits for those with DS as those individuals without a disability and in turn progresses their balance ability. Due to limited exercise program opportunities and studies that intentionally investigate the benefits of specific modes of exercise on the DS population, a community-based Exercise Program for Adults with DS (ExDS) was created with the goal of improving their physical and mental health and measuring changes in their balance capabilities throughout the program. ExDS partnered with Arizona State University (ASU) students to create biweekly customized workouts, that followed exercise prescription guidelines, consisting of an aerobic warm-up, main aerobic exercise bout, resistance training, balance training, and stretching for each participant with DS. Participant dynamic and static balance ability was measured using the Berg Balance Scale (BBS) during program pre- and post-assessments. The BBS composite score did not change and no significant improvement was seen in the p-values for each line item of the BBS from pre- to post-testing. For follow-up analyses, the participants with low treatment fidelity were removed. Follow-up analyses showed significant increases in BBS composite score and line item 13 from pre- to post-testing. Treatment fidelity was a limitation in this study and future studies should aim to increase fidelity and consistency of tester for pre- and post-testing. In conclusion, holistic exercise programming for adults with DS appears to benefit balance as long as treatment fidelity is high. It is unclear which mode of exercise had the greatest impact on changes in balance.
ContributorsShikles, Ann Kelly (Author) / Holzapfel, Simon (Thesis director) / Ringenbach, Shannon (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12