Matching Items (123)
Description
Ebola hemorrhagic fever (EHF) is a severe and often fatal disease in human and nonhuman primates, caused by the Ebola virus. Approximately 30 years after the first epidemic, there is no vaccine or therapeutic medication approved to counter the Ebola virus. In this dissertation, a geminiviral replicon system was used to produce Ebola immune complex (EIC) in plant leaves and tested it as an Ebola vaccine. The EIC was produced in Nicotiana benthamiana leaves by fusing Ebola virus glycoprotein (GP1) to the C-terminus of heavy chain of 6D8 monoclonal antibody (mAb), which is specific to the 6D8 epitope of GP1, and co-expressing the fusion with the light chain of 6D8 mAb. EIC was purified by ammonium sulfate precipitation and protein A or protein G affinity chromatography. EIC was shown to be immunogenic in mice, but the level of antibody against Ebola virus was not sufficient to protect the mice from lethal the Ebola challenge. Hence, different adjuvants were tested in order to improve the immunogenicity of the EIC. Among several adjuvants that we used, Poly(I:C), which is a synthetic analog of double-stranded ribonucleic acid that can interact with a Toll-like receptor 3, strongly increased the efficacy of our Ebola vaccine. The mice immunized with EIC co-administered with Poly(I:C) produced high levels of neutralizing anti-Ebola IgG, and 80% of the mice were protected from the lethal Ebola virus challenge. Moreover, the EIC induced a predominant T-helper type 1 (Th1) response, whereas Poly(I:C) co-delivered with the EIC stimulated a mixed Th1/Th2 response. This result suggests that the protection against lethal Ebola challenge requires both Th1 and Th2 responses. In conclusion, this study demonstrated that the plant-produced EIC co-delivered with Poly(I:C) induced strong and protective immune responses to the Ebola virus in mice. These results support plant-produced EIC as a good vaccine candidate against the Ebola virus. It should be pursued further in primate studies, and eventually in clinical trials.
ContributorsPhoolcharoen, Waranyoo (Author) / Mason, Hugh S (Thesis advisor) / Chen, Qiang (Thesis advisor) / Arntzen, Charles J. (Committee member) / Change, Yung (Committee member) / Ma, Julian (Committee member) / Arizona State University (Publisher)
Created2010
Description
Coronavirus disease 2019 (COVID-19), an illness caused by severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2), has been responsible for significant social and economic
disruption, prompting an urgent search for therapeutic solutions. The spike protein of the virus
has been examined as an immunogenic target because of its role in viral binding and fusion
necessary for infection of host cells. Previous studies have identified a recombinant protein
(denoted as S1) that has been shown to potentially induce a neutralizing antibody response by
mimicking the structure of the SARS-CoV-2 spike protein. We have produced the S1 in plants
using agroinfiltration, a plant transformation technique whereby plasmid-containing
Agrobacterium tumefaciens is injected into Nicotiana benthamiana plants, resulting in transfer of
the desired gene from bacteria to plant cells. S1 was expressed to high levels within 5 days of
infiltration, and Western blot analysis showed recognition of the S1 by an anti-S1 antibody.
ELISA results exhibited increased binding activity to anti-S1 with increasing concentrations of
S1, indicating their specific interaction. This ongoing study will demonstrate the potential of a
plant-produced S1 as a vaccine, therapeutic, and diagnostic tool against COVID-19 that is not
only effective, but also cost-efficient and scalable in comparison to conventional mammalian cell
culture production methods.
coronavirus 2 (SARS-CoV-2), has been responsible for significant social and economic
disruption, prompting an urgent search for therapeutic solutions. The spike protein of the virus
has been examined as an immunogenic target because of its role in viral binding and fusion
necessary for infection of host cells. Previous studies have identified a recombinant protein
(denoted as S1) that has been shown to potentially induce a neutralizing antibody response by
mimicking the structure of the SARS-CoV-2 spike protein. We have produced the S1 in plants
using agroinfiltration, a plant transformation technique whereby plasmid-containing
Agrobacterium tumefaciens is injected into Nicotiana benthamiana plants, resulting in transfer of
the desired gene from bacteria to plant cells. S1 was expressed to high levels within 5 days of
infiltration, and Western blot analysis showed recognition of the S1 by an anti-S1 antibody.
ELISA results exhibited increased binding activity to anti-S1 with increasing concentrations of
S1, indicating their specific interaction. This ongoing study will demonstrate the potential of a
plant-produced S1 as a vaccine, therapeutic, and diagnostic tool against COVID-19 that is not
only effective, but also cost-efficient and scalable in comparison to conventional mammalian cell
culture production methods.
ContributorsNguyen, Katherine (Author) / Chen, Qiang (Thesis director) / Ghirlanda, Giovanna (Committee member) / Jugler, Collin (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-12
Description
Honey bee workers display remarkable flexibility in the aging process. This plasticity is closely tied to behavioral maturation. Workers who initiate foraging behavior at earlier ages have shorter lifespans, and much of the variation in total lifespan can be explained by differences in pre-foraging lifespan. Vitellogenin (Vg), a yolk precursor protein, influences worker lifespan both as a regulator of behavioral maturation and through anti-oxidant and immune functions. Experimental reduction of Vg mRNA, and thus Vg protein levels, in wild-type bees results in precocious foraging behavior, decreased lifespan, and increased susceptibility to oxidative damage. We sought to separate the effects of Vg on lifespan due to behavioral maturation from those due to immune and antioxidant function using two selected strains of honey bees that differ in their phenotypic responsiveness to Vg gene knockdown. Surprisingly, we found that lifespans lengthen in the strain described as behaviorally and hormonally insensitive to Vg reduction. We then performed targeted gene expression analyses on genes hypothesized to mediate aging and lifespan: the insulin-like peptides (Ilp1 and 2) and manganese superoxide dismutase (mnSOD). The two honey bee Ilps are the most upstream components in the insulin-signaling pathway, which influences lifespan in Drosophila melanogaster and other organisms, while manganese superoxide dismutase encodes an enzyme with antioxidant functions in animals. We found expression differences in the llps in fat body related to behavior (llp1 and 2) and genetic background (Ilp2), but did not find strain by treatment effects. Expression of mnSOD was also affected by behavior and genetic background. Additionally, we observed a differential response to Vg knockdown in fat body expression of mnSOD, suggesting that antioxidant pathways may partially explain the strain-specific lifespan responses to Vg knockdown.
ContributorsIhle, Kate (Author) / Fondrk, M. Kim (Author) / Page, Robert (Author) / Amdam, Gro (Author) / College of Liberal Arts and Sciences (Contributor) / School of Life Sciences (Contributor)
Created2015-01-01
Description
Plant viral vectors have previously been used to produce high expression levels of antibodies and other proteins of interest. By utilizing a transformed Agrobacterium with the vector containing the protein of interest for infiltration, viral vectors can easily reach the plant cells making it an effective form of transient protein expression. For this project two different plant viral vectors were compared; the geminiviral vector derived from Bean yellow dwarf virus (BeYDV) and the MagnICON vector system derived from Tobacco Mosaic Virus(TMV) and Potato Virus X(PVX). E16, an antibody against West Nile virus, has previously been expressed using both systems but expression levels between the systems were not directly compared. Agrobacterium tumefaciens EHA105 cells were transformed with both systems and expression levels of E16 were quantified using ELISAs. Results showed very low expression levels of E16 using the geminiviral vector indicating a need for further investigation into the clone used as previous studies reported much higher expression levels with the system.
ContributorsMurphy, Skylar (Author) / Chen, Qiang (Thesis director) / Jugler, Collin (Committee member) / College of Health Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
The main purpose of this investigation is to determine the intensity, economic costs, and potential solutions to HIV/AIDS stigma in the United States and Tanzania. In order to accomplish this goal, a literature review was conducted, and an economic model was created to determine how HIV/AIDS treatment deterrence manifests and affects these countries. The results of the economic model suggested that Tanzania suffers greater economic loss due to HIV treatment deterrence than the United States, however, both countries lose a significant portion of GDP due to HIV treatment deterrence. Stigma materializes differently in each country based on a variety of sociocultural factors. These include the demographic groups most affected, the perception of those living with HIV, and how sexually transmitted infections are perceived within communities. The solutions to HIV stigma must be tailored to the country, culture, and context that it arises for interventions to be effective. To further prevent HIV/AIDS stigma and its economic consequences, the etiology of stigma and how it presents in different communities must be understood.
ContributorsSangha, Pooja (Co-author) / Hopewell, Sophia (Co-author) / Baldwin, Marjorie (Thesis director) / Hruschka, Daniel (Committee member) / Department of Psychology (Contributor) / Department of Economics (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
This paper explores the impacts of dam-induced displacement on the health of populations. By the start of the 21st century, an estimated 40-80 million people worldwide were forced to resettle due to the construction of large dams. The process of displacement and resettlement is connected to numerous social impacts on communities such as decreases in household income, natural resources, and social connectivity, but less seems to be known about specific health impacts. Analyzing literature in a formal review allowed for increased understanding about what information already exists in published research regarding the connections between dams, displacement, and health. Some negative health impacts as a result of forced displacement were identified, including increases in infectious disease transmission, depression, and mortality rates as well as losses of food and water sources. However, the small amount of cases found in the literature review when compared to the massive scale of dam development worldwide indicates a gap in knowledge in the dam industry and research field specifically about the health of the vast majority of populations forcibly displaced by dams. Health impacts must be considered and systematically studied in dam projects involving displacement to fully understand the needs of resettled populations and move towards equitable processes in development projects worldwide.
ContributorsWalker, Erika (Author) / Hruschka, Daniel (Thesis director) / Brian, Jennifer (Committee member) / Drake, Alexandria (Committee member) / School of Human Evolution & Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
The brain is considered the crux of identity, yet human behavior may be influenced by bacteria in gut microbiomes. Honeybees can exchange bacteria through their many social behaviors, making their microbiomes, and the effect they have on honeybee behavior, of interest. There is recent evidence suggesting the presence of bacteria existing in human brains, which can be investigated in honeybee brains due to their well-documented structure. The purpose of this study is to establish if lipopolysaccharide—a molecule on bacteria membranes—is present in the honeybee brain and if it colocalizes with vitellogenin—an immune mediator. Additionally, this study also seeks to establish the efficacy of embedding tissue samples in resin and performing immunohistochemistry for vitellogenin and lipopolysaccharide on sections.
ContributorsStrange, Amalie Sofie (Co-author) / Strange, Amalie (Co-author) / Amdam, Gro (Thesis director) / Baluch, Page (Committee member) / School of International Letters and Cultures (Contributor) / School of Life Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Mitochondrial methionyl-tRNA-formyltransferase (MTFMT) is essential for mitochondrial protein translation. The MTFMT gene encodes for an enzyme of the same name, which acts to formylate the methionine of mitochondrial Met-tRNA(Met). In Homo sapiens, MTFMT-formylated-tRNA is an initiator and elongator for the synthesis of 13 mitochondrially-encoded proteins in complexes I, III and IV of the ETC. To understand this mechanism, it is necessary to perform a comprehensive analysis of energy metabolism and oxidative phosphorylation (OXPHOS) among impacted patients. Alterations to this gene vary, with the most documented as a single-splice-site mutation (c.626C>T). Here, we discuss MTFMT involvement in mitochondrial protein translation and neurodegenerative disorders, such as Leigh Syndrome and combined OXPHOS deficiency, in two families. We aim to delineate the impact of OXPHOS dysfunction in patients presenting with MTFMT mutation.
ContributorsChain, Kelsey (Author) / Chen, Qiang (Thesis director) / Rangasamy, Sampathkumar (Committee member) / Narayanan, Vinodh (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
In Western medicine, the hard sciences have generally been understood as the sole guiding force in patient care and treatment. However, both history and the present day suggest another strong influence on Western medicine: folklore. The term folklore can easily be dismissed as a term representing beliefs and stories of the past, but its relevance transcends time and continues to impact people daily. It “involves values, traditions, ways of thinking and behaving. It’s about art. It’s about people and the way people learn. It helps us learn who we are and how to make meaning in the world around us” (Sims & Stephens, 2011, pp. 1-2). With its wide range of influence, folklore exists as the umbrella term encompassing several categories. Folk beliefs are one of these categories and can develop from “observation, memory, testimony or inference” (Hutton, 1942, p. 83). Given that each of these forms are subject to some sort of error, folk beliefs become “a jumble of the true and the erroneous” (p. 84). Similarly, contemporary legends are narratives that often combine the physical and supernatural world to explain nuances or uncertainty present in the relevant experiences of a people. Folk beliefs can result in the formation of contemporary legends and they can also stem from contemporary legends. These two categories are often associated with subjects that promote fear and uncertainty, and thus play an essential role in navigating folklore’s application to biomedicine. This paper explores the historical and modern effects that folklore has had on two separate maladies: Hansen’s Disease (leprosy) and Major Depressive Disorder (depression). While these conditions do not resemble each other in physical presentations, Hansen’s Disease and Major Depressive Disorder patients both have faced and continue to face discrimination. Andrea Wiley and John Allen’s three-part definition of a malady: society’s perception (sickness), the individual’s experience (illness), and medical professionals’ diagnosis and treatment (disease); was utilized as a tool for analyzing the application of folklore to modern medicine. The way that a society views a particular malady often dictates the sick role expected of a diagnosed individual. Additionally, the public’s view can directly affect medical professionals’ understanding of a malady. This then can drastically shape a patient’s diagnosis, treatment, and prognosis. This anthropological analysis acts as an interdisciplinary bridge between medicine and the humanities.
ContributorsPeake, Ashley E (Co-author) / Peake, Ashley (Co-author) / Ellis, Lawrence (Thesis director) / Hoyt, Heather (Committee member) / Hruschka, Daniel (Committee member) / School of Molecular Sciences (Contributor) / Department of English (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Menstruation - a stigmatized topic and a social taboo- has led to a lack of menstrual hygiene awareness and improper practices impacting women’s health adversely over generations in India. Akshara aims to increase menstrual hygiene education and reduce stigma in India. A creative children’s illustrated book, and interactive workshop curriculum about menstruation were designed and published in Hindi and English. Menstrual hygiene workshops, utilizing the designed tools, were conducted in Delhi and Ghaziabad, India to over 230 students through NGO partnerships in December 2018. The response to the menstrual hygiene and stigma workshops was overwhelmingly positive, and a significant increase in the knowledge and awareness survey scores was observed after the curriculum teachings and classroom discussions. This evaluation highlights and provides a potential solution path to eradicate the root cause of the menstruation stigma in underprivileged women through education and open conversations on the topic starting at a pivotal young age. The main aim of the workshop was to help eradicate the stigma associated with menstruation and menstrual health in India through education.
ContributorsBhalla, Jahnavi (Co-author) / Dani, Advika (Co-author) / Schuster, Roseanne (Thesis director) / Hruschka, Daniel (Thesis director) / School of Molecular Sciences (Contributor) / School of Human Evolution & Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05