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Infections caused by the Hepatitis C Virus (HCV) are very common worldwide, affecting up to 3% of the population. Chronic infection of HCV may develop into liver cirrhosis and liver cancer which is among the top five of the most common cancers. Therefore, vaccines against HCV are under intense study in order to prevent HCV from harming people's health. The envelope protein 2 (E2) of HCV is thought to be a promising vaccine candidate because it can directly bind to a human cell receptor and plays a role in viral entry. However, the E2 protein production in cells is inefficient due to its complicated matured structure. Folding of E2 in the endoplasmic reticulum (ER) is often error-prone, resulting in production of aggregates and misfolded proteins. These incorrect forms of E2 are not functional because they are not able to bind to human cells and stimulate antibody response to inhibit this binding. This study is aimed to overcome the difficulties of HCV E2 production in plant system. Protein folding in the ER requires great assistance from molecular chaperones. Thus, in this study, two molecular chaperones in the ER, calreticulin and calnexin, were transiently overexpressed in plant leaves in order to facilitate E2 folding and production. Both of them showed benefits in increasing the yield of E2 and improving the quality of E2. In addition, poorly folded E2 accumulated in the ER may cause stress in the ER and trigger transcriptional activation of ER molecular chaperones. Therefore, a transcription factor involved in this pathway, named bZIP60, was also overexpressed in plant leaves, aiming at up-regulating a major family of molecular chaperones called BiP to assist protein folding. However, our results showed that BiP mRNA levels were not up-regulated by bZIP60, but they increased in response to E2 expression. The Western blot analysis also showed that overexpression of bZIP60 had a small effect on promoting E2 folding. Overall, this study suggested that increasing the level of specific ER molecular chaperones was an effective way to promote HCV E2 protein production and maturation.
ContributorsHong, Fan (Author) / Mason, Hugh (Thesis advisor) / Gaxiola, Roberto (Committee member) / Chang, Yung (Committee member) / Chen, Qiang (Committee member) / Arizona State University (Publisher)
Created2011
Description
Natural history is, and was, dependent upon the collection of specimens. In the nineteenth century, American naturalists and institutions of natural history cultivated and maintained extensive collection networks comprised of numerous collectors that provided objects of natural history for study. Effective networks were collaborative in nature, with naturalists such as Spencer Baird of the Smithsonian trading their time and expertise for specimens. The incorporation of Darwinian and Neo-Lamarckian evolutionary theory into natural history in the middle of the century led to dramatic changes in the relationship between naturalists and collectors, as naturalists sought to reconcile their observations within the new evolutionary context. This dissertation uses the careers of collectors Robert Kennicott, Frank Stephens, Edward W. Nelson, E.A. Goldman, and Edmund Heller as case studies in order to evaluate how the changes in the theoretical framework of late nineteenth century natural history led to advances in field practice by assessing how naturalists trained their collectors to meet new demands within the field. Research focused on the correspondence between naturalists and collectors, along with the field notes and applicable publications by collectors. I argue that the changes in natural history necessitated naturalists training their collectors in the basics of biogeography - the study of geographic distribution of organisms, and systematics - the study of the diversity of life - leading to a collaborative relationship in which collectors played an active role in the formation of new biological knowledge. The project concludes that the changes in natural history with regard to theory and practice gradually necessitated a more professional cadre of collectors. Collectors became active agents in the formation of biological knowledge, and instrumental in the formation of a truly systematic natural history. As a result, collectors became de facto field naturalists, the forerunners of the field biologists that dominated the practice of natural history in the early and middle twentieth century.
ContributorsLaubacher, Matthew (Author) / Green, Monica (Thesis advisor) / Laubichler, Manfred (Thesis advisor) / Wright, Johnson Kent (Committee member) / Arizona State University (Publisher)
Created2011
Description
Once perceived as an unimportant occurrence in living organisms, cell degeneration was reconfigured as an important biological phenomenon in development, aging, health, and diseases in the twentieth century. This dissertation tells a twentieth-century history of scientific investigations on cell degeneration, including cell death and aging. By describing four central developments in cell degeneration research with the four major chapters, I trace the emergence of the degenerating cell as a scientific object, describe the generations of a variety of concepts, interpretations and usages associated with cell death and aging, and analyze the transforming influences of the rising cell degeneration research. Particularly, the four chapters show how the changing scientific practices about cellular life in embryology, cell culture, aging research, and molecular biology of Caenorhabditis elegans shaped the interpretations about cell degeneration in the twentieth-century as life-shaping, limit-setting, complex, yet regulated. These events created and consolidated important concepts in life sciences such as programmed cell death, the Hayflick limit, apoptosis, and death genes. These cases also transformed the material and epistemic practices about the end of cellular life subsequently and led to the formations of new research communities. The four cases together show the ways cell degeneration became a shared subject between molecular cell biology, developmental biology, gerontology, oncology, and pathology of degenerative diseases. These practices and perspectives created a special kind of interconnectivity between different fields and led to a level of interdisciplinarity within cell degeneration research by the early 1990s.
ContributorsJiang, Lijing (Author) / Maienschein, Jane (Thesis advisor) / Laubichler, Manfred (Thesis advisor) / Hurlbut, James (Committee member) / Creath, Richard (Committee member) / White, Michael (Committee member) / Arizona State University (Publisher)
Created2013
Description
Gene-centric theories of evolution by natural selection have been popularized and remain generally accepted in both scientific and public paradigms. While gene-centrism is certainly parsimonious, its explanations fall short of describing two patterns of evolutionary and social phenomena: the evolution of sex and the evolution of social altruism. I review and analyze current theories on the evolution of sex. I then introduce the conflict presented to gene-centric evolution by social phenomena such as altruism and caste sterility in eusocial insects. I review gene-centric models of inclusive fitness and kin selection proposed by Hamilton and Maynard Smith. Based their assumptions, that relatedness should be equal between sterile workers and reproductives, I present several empirical examples that conflict with their models. Following that, I introduce a unique system of genetic caste determination (GCD) observed in hybrid populations of two sister-species of seed harvester ants, Pogonomyrmex rugosus and Pogonomyrmex barbatus. I review the evidence for GCD in those species, followed by a critique of the current gene-centric models used to explain it. In chapter two I present my own theoretical model that is both simple and extricable in nature to explain the origin, evolution, and maintenance of GCD in Pogonomyrmex. Furthermore, I use that model to fill in the gaps left behind by the contributing authors of the other GCD models. As both populations in my study system formed from inter-specific hybridization, I review modern discussions of heterosis (also called hybrid vigor) and use those to help explain the ecological competitiveness of GCD. I empirically address the inbreeding depression the lineages of GCD must overcome in order to remain ecologically stable, demonstrating that as a result of their unique system of caste determination, GCD lineages have elevated recombination frequencies. I summarize and conclude with an argument for why GCD evolved under selective mechanisms which cannot be considered gene-centric, providing evidence that natural selection can effectively operate on non-heritable genotypes appearing in groups and other social contexts.
ContributorsJacobson, Neal (Author) / Gadau, Juergen (Thesis advisor) / Laubichler, Manfred (Committee member) / Pratt, Stephen (Committee member) / Arizona State University (Publisher)
Created2012
Description
Is it possible to treat the mouth as a natural environment, and determine new methods to keep the microbiome in check? The need for biodiversity in health may suggest that every species carries out a specific function that is required to maintain equilibrium and homeostasis within the oral cavity. Furthermore, the relationship between the microbiome and its host is mutually beneficial because the host is providing microbes with an environment in which they can flourish and, in turn, keep their host healthy. Reviewing examples of larger scale environmental shifts could provide a window by which scientists can make hypotheses. Certain medications and healthcare treatments have been proven to cause xerostomia. This disorder is characterized by a dry mouth, and known to be associated with a change in the composition, and reduction, of saliva. Two case studies performed by Bardow et al, and Leal et al, tested and studied the relationships of certain medications and confirmed their side effects on the salivary glands [2,3]. Their results confirmed a relationship between specific medicines, and the correlating complaints of xerostomia. In addition, Vissink et al conducted case studies that helped to further identify how radiotherapy causes hyposalivation of the salivary glands [4]. Specifically patients that have been diagnosed with oral cancer, and are treated by radiotherapy, have been diagnosed with xerostomia. As stated prior, studies have shown that patients having an ecologically balanced and diverse microbiome tend to have healthier mouths. The oral cavity is like any biome, consisting of commensalism within itself and mutualism with its host. Due to the decreased salivary output, caused by xerostomia, increased parasitic bacteria build up within the oral cavity thus causing dental disease. Every human body contains a personalized microbiome that is essential to maintaining health but capable of eliciting disease. The Human Oral Microbiomics Database (HOMD) is a set of reference 16S rRNA gene sequences. These are then used to define individual human oral taxa. By conducting metagenomic experiments at the molecular and cellular level, scientists can identify and label micro species that inhabit the mouth during parasitic outbreaks or a shifting of the microbiome. Because the HOMD is incomplete, so is our ability to cure, or prevent, oral disease. The purpose of the thesis is to research what is known about xerostomia and its effects on the complex microbiome of the oral cavity. It is important that researchers determine whether this particular perspective is worth considering. In addition, the goal is to create novel experiments for treatment and prevention of dental diseases.
ContributorsHalcomb, Michael Jordan (Author) / Chen, Qiang (Thesis director) / Steele, Kelly (Committee member) / Barrett, The Honors College (Contributor) / College of Letters and Sciences (Contributor)
Created2015-05
Description
Pressure from fiduciary duty leads agents within organizational systems to make decisions that result in positive feedback loops that often have inimical unintended consequences. The current corporate climate that often puts the bottom line ahead of environmental and social concerns in the name of fiduciary duty is doing so based on a revised interpretation of the term that is clearly to the benefit of the corporations. It is important to note that this modern interpretation is a radical misinterpretation of the intent of the law as our forefathers defined it. However, in spite of the fact that the modern interpretation is leading to inimical unintended consequences, providing the systems agents with the proper training and tools necessary to recognize the cost benefit of implementing sustainable solutions may mitigate some of these positive feedback loops and their associated unintended consequences. By developing tools based on sustainable frameworks we may be able to return these organizations to the original intent of fiduciary duty, which was designed to encourage investment in organizations that worked for the public benefit. A concept that is remarkably similar to the triple bottom line framework that many sustainability professionals advocate on behalf of today.
ContributorsJohnson, Lyle Eric (Author) / Laubichler, Manfred (Thesis director) / Dooley, Kevin (Committee member) / O'Neill, Dan (Committee member) / Barrett, The Honors College (Contributor) / W. P. Carey School of Business (Contributor) / School of Sustainability (Contributor)
Created2015-05
Description
Influenza has shown its potential to affect and even kill millions of people within an extremely short time frame, yet studies and surveys show that the general public is not well educated about the facts about influenza, including prevention and treatment. For this reason, public perception of influenza is extremely skewed, with people generally not taking the disease as seriously as they should given its severity. To investigate the inconsistencies between action and awareness of best available knowledge regarding influenza, this study conducted literature review and a survey of university students about their knowledge, perceptions, and action taken in relationship to influenza. Due to their dense living quarters, constant daily interactions, and mindset that they are "immune" to fairly common diseases like influenza, university students are a representative sample of urban populations. According to the World Health Organization (WHO), 54% of the world's population lived in cities as of 2014 (Urban population growth). Between 2015 and 2020, the global urban population is expected to grow 1.84% per year, 1.63% between 2020 and 2025, and 1.44% between 2025 and 2030 (Urban population growth). Similar projections estimate that by 2017, an overwhelming majority of the world's population, even in less developed countries, will be living in cities (Urban population growth). Results of this study suggest possible reasons for the large gap between best available knowledge and the perceptions and actions of individuals on the other hand. This may lead to better-oriented influenza education initiatives, more effective prevention and treatment plans, and generally raise excitement and awareness surrounding public health and scientific communication.
ContributorsGur-Arie, Rachel Ellen Haviva (Author) / Maienschein, Jane (Thesis director) / Laubichler, Manfred (Committee member) / Creath, Richard (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2014-12
Description
This project focuses on the history of how teratogens, or agents which have the potential to cause birth defects, have been understood and tested for teratogenic potential in the US over the twentieth century. Prior to this time, teratogen studies were primarily concerned with cataloguing defects rather than exploring possible causes. At the turn of the twentieth century, experimental teratogen studies with the aim of elucidating mechanisms commenced. However, these early studies did not aim to discover human pregnancy outcomes and ways to prevent them, but simply focused on the results of exposing pregnant mammals to various physical and chemical insults. My project documents the change in understanding of teratogens over the twentieth century, the advancement of testing methods, and the causes of these advancements. Through the Embryo Project at Arizona State University (embryo.asu.edu), a digital encyclopedia for topics related to embryology, development, and reproductive medicine, I wrote ten encyclopedic articles that focused on chemical mechanisms of various teratogens, testing limitations in animal models, and legal and regulatory responses to well-known teratogens. As an extension of my previous work, this project bridges the current gap in research and focuses on contextualizing major events in the field of teratology to determine how these events led to various shifts in the understanding of birth defects and their causes, and how those conceptual shifts led to the creation of teratological testing guidelines. Results show that throughout the twentieth century, there are four distinct shifts in the understanding of teratogens: the first being 1900-1945, the second being 1946-1960, the third being 1961-1980, and the fourth being 1981-2000.
ContributorsTantibanchachai, Chanapa (Author) / Maienschein, Jane (Thesis director) / Laubichler, Manfred (Committee member) / O'Neil, Erica (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2014-05
Description
The objectives of this review include a discussion of the West Nile Virus phylogeny, transmission history, how the virus functions in the body and how it is a threat to public health, and then discusses these items related to vaccine technology surrounding West Nile Virus. This will include past developments, current research in the field and what it may take to develop such a vaccine safe and economical for human usage.
ContributorsSlinker, Haleigh Renee (Author) / Chen, Qiang (Thesis director) / Huffman, Holly (Committee member) / Oberstein, Bruce (Committee member) / Barrett, The Honors College (Contributor) / School of Letters and Sciences (Contributor)
Created2013-05
Description
The field of biologic research is particularly concerned with understanding nature's complex dynamics. From deducing anatomical structures to studying behavioral patterns, evolutionary theory has developed greatly beyond the simple notions proposed by Charles Darwin. However, because it rarely considers the concept of complexity, modern evolutionary theory retains some descriptive weakness. This project represents an explorative approach for considering complexity and whether it plays an active role in the development of biotic systems. A novel theoretical framework, titled the Genesis Mechanism, was formulated reconsidering the major tenets of evolutionary theory to include complexity as a universal tendency. Within this framework, a phenomenon, referred to as "social transitioning," occurs between higher orders of complexity. Several potential properties of social transitions were proposed and analyzed in order to validate the theoretical concepts proposed within the Genesis Mechanism. The successful results obtained through this project's completion help demonstrate the scientific necessity for understanding complexity from a more fundamental, biologic standpoint.
ContributorsMcAuliffe, Jacob (Author) / Laubichler, Manfred (Thesis director) / Armendt, Brad (Committee member) / Barrett, The Honors College (Contributor)
Created2013-05