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Description
Fluoroquinolone antibiotics have been known to cause severe, multisystem adverse side effects, termed fluoroquinolone toxicity (FQT). This toxicity syndrome can present with adverse effects that vary from individual to individual, including effects on the musculoskeletal and nervous systems, among others. The mechanism behind FQT in mammals is not known, although various possibilities have been investigated. Among the hypothesized FQT mechanisms, those that could potentially explain multisystem toxicity include off-target mammalian topoisomerase interactions, increased production of reactive oxygen species, oxidative stress, and oxidative damage, as well as metal chelating properties of FQs. This review presents relevant information on fluoroquinolone antibiotics and FQT and explores the mechanisms that have been proposed. A fluoroquinolone-induced increase in reactive oxygen species and subsequent oxidative stress and damage presents the strongest evidence to explain this multisystem toxicity syndrome. Understanding the mechanism of FQT in mammals is important to aid in the prevention and treatment of this condition.
ContributorsHall, Brooke Ashlyn (Author) / Redding, Kevin (Thesis director) / Wideman, Jeremy (Committee member) / Borges, Chad (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Like individual organisms, complex social groups are able to maintain predictable trajectories of growth, from initial colony foundation to mature reproductively capable units. They do so while simultaneously responding flexibly to variation in nutrient availability and intake. Leafcutter ant colonies function as tri-trophic systems, in which the ants harvest vegetation to grow a fungus that, in turn, serves as food for the colony. Fungal growth rates and colony worker production are interdependent, regulated by nutritional and behavioral feedbacks. Fungal growth and quality are directly affected by worker foraging decisions, while worker production is, in turn, dependent on the amount and condition of the fungus. In this dissertation, I first characterized the growth relationship between the workers and the fungus of the desert leafcutter ant Acromyrmex versicolor during early stages of colony development, from colony foundation by groups of queens through the beginnings of exponential growth. I found that this relationship undergoes a period of slow growth and instability when workers first emerge, and then becomes allometrically positive. I then evaluated how mass and element ratios of resources collected by the ants are translated into fungus and worker population growth, and refuse, finding that colony digestive efficiency is comparable to digestive efficiencies of other herbivorous insects and ruminants. To test how colonies behaviorally respond to perturbations of the fungus garden, I quantified activity levels and task performance of workers in colonies with either supplemented or diminished fungus gardens, and found that colonies adjusted activity and task allocation in response to the fungus garden size. Finally, to identify possible forms of nutrient limitation, I measured how colony performance was affected by changes in the relative amounts of carbohydrates, protein, and phosphorus available in the resources used to grow the fungus garden. From this experiment, I concluded that colony growth is primarily carbohydrate-limited.
ContributorsClark, Rebecca, 1981- (Author) / Fewell, Jennifer H (Thesis advisor) / Mueller, Ulrich (Committee member) / Liebig, Juergen (Committee member) / Elser, James (Committee member) / Harrison, Jon (Committee member) / Arizona State University (Publisher)
Created2011
Description
The repression of reproductive competition and the enforcement of altruism are key components to the success of animal societies. Eusocial insects are defined by having a reproductive division of labor, in which reproduction is relegated to one or few individuals while the rest of the group members maintain the colony and help raise offspring. However, workers have retained the ability to reproduce in most insect societies. In the social Hymenoptera, due to haplodiploidy, workers can lay unfertilized male destined eggs without mating. Potential conflict between workers and queens can arise over male production, and policing behaviors performed by nestmate workers and queens are a means of repressing worker reproduction. This work describes the means and results of the regulation of worker reproduction in the ant species Aphaenogaster cockerelli. Through manipulative laboratory studies on mature colonies, the lack of egg policing and the presence of physical policing by both workers and queens of this species are described. Through chemical analysis and artificial chemical treatments, the role of cuticular hydrocarbons as indicators of fertility status and the informational basis of policing in this species is demonstrated. An additional queen-specific chemical signal in the Dufour's gland is discovered to be used to direct nestmate aggression towards reproductive competitors. Finally, the level of actual worker-derived males in field colonies is measured. Together, these studies demonstrate the effectiveness of policing behaviors on the suppression of worker reproduction in a social insect species, and provide an example of how punishment and the threat of punishment is a powerful force in maintaining cooperative societies.
ContributorsSmith, Adrian A. (Author) / Liebig, Juergen (Thesis advisor) / Hoelldobler, Bert (Thesis advisor) / Gadau, Juergen (Committee member) / Johnson, Robert A. (Committee member) / Pratt, Stephen (Committee member) / Arizona State University (Publisher)
Created2011
Description
Of all the signals and cues that orchestrate the activities of a social insect colony, the reproductives' fertility pheromones are perhaps the most fundamental. These pheromones regulate reproductive division of labor, a defining characteristic of eusociality. Despite their critical role, reproductive fertility pheromones are not evenly expressed across the development of a social insect colony and may even be absent in the earliest colony stages. In the ant Camponotus floridanus, queens of incipient colonies do not produce the cuticular hydrocarbons that serve as fertility and egg-marking signals in this species. My dissertation investigates the consequences of the dramatic change in the quantity of these pheromones that occurs as the colony grows. C. floridanus workers from large, established colonies use egg surface hydrocarbons to discriminate among eggs. Eggs with surface hydrocarbons typical of eggs laid by established queens are nurtured, whereas eggs lacking these signals (i.e., eggs laid by workers and incipient queens) are destroyed. I characterized how workers from incipient colonies responded to eggs lacking queen fertility hydrocarbons. I found that established-queen-laid eggs, incipient-queen-laid eggs, and worker-laid eggs were not destroyed by workers at this colony stage. Destruction of worker-laid eggs is a form of policing, and theoretical models predict that policing should be strongest in incipient colonies. Since there was no evidence of policing by egg-eating in incipient C. floridanus colonies, I searched for evidence of another policing mechanism at this colony stage. Finding none, I discuss reasons why policing behavior may not be expressed in incipient colonies. I then considered the mechanism that accounts for the change in workers' response to eggs. By manipulating ants' egg experience and testing their egg-policing decisions, I found that ants use a combination of learned and innate criteria to discriminate between targets of care and destruction. Finally, I investigated how the increasing strength of queen-fertility hydrocarbons affects nestmate recognition, which also relies on cuticular hydrocarbons. I found that queens with strong fertility hydrocarbons can be transferred between established colonies without aggression, but they cannot be introduced into incipient colonies. Queens from incipient colonies cannot be transferred into incipient or established colonies.
ContributorsMoore, Dani (Author) / Liebig, Juergen (Thesis advisor) / Gadau, Juergen (Committee member) / Pratt, Stephen (Committee member) / Smith, Brian (Committee member) / Rutowski, Ronald (Committee member) / Arizona State University (Publisher)
Created2012
Description
A notable feature of advanced eusocial insect groups is a division of labor within the sterile worker caste. However, the physiological aspects underlying the differentiation of behavioral phenotypes are poorly understood in one of the most successful social taxa, the ants. By starting to understand the foundations on which social behaviors are built, it also becomes possible to better evaluate hypothetical explanations regarding the mechanisms behind the evolution of insect eusociality, such as the argument that the reproductive regulatory infrastructure of solitary ancestors was co-opted and modified to produce distinct castes. This dissertation provides new information regarding the internal factors that could underlie the division of labor observed in both founding queens and workers of Pogonomyrmex californicus ants, and shows that changes in task performance are correlated with differences in reproductive physiology in both castes. In queens and workers, foraging behavior is linked to elevated levels of the reproductively-associated juvenile hormone (JH), and, in workers, this behavioral change is accompanied by depressed levels of ecdysteroid hormones. In both castes, the transition to foraging is also associated with reduced ovarian activity. Further investigation shows that queens remain behaviorally plastic, even after worker emergence, but the association between JH and behavioral bias remains the same, suggesting that this hormone is an important component of behavioral development in these ants. In addition to these reproductive factors, treatment with an inhibitor of the nutrient-sensing pathway Target of Rapamycin (TOR) also causes queens to become biased towards foraging, suggesting an additional sensory component that could play an important role in division of labor. Overall, this work provides novel identification of the possible regulators behind ant division of labor, and suggests how reproductive physiology could play an important role in the evolution and regulation of non-reproductive social behaviors.
ContributorsDolezal, Adam G (Author) / Amdam, Gro V (Thesis advisor) / Brent, Colin S. (Committee member) / Gadau, Juergen (Committee member) / Hoelldobler, Bert (Committee member) / Liebig, Juergen (Committee member) / Arizona State University (Publisher)
Created2012
Description
Cancer claims hundreds of thousands of lives every year in US alone. Finding ways for early detection of cancer onset is crucial for better management and treatment of cancer. Thus, biomarkers especially protein biomarkers, being the functional units which reflect dynamic physiological changes, need to be discovered. Though important, there are only a few approved protein cancer biomarkers till date. To accelerate this process, fast, comprehensive and affordable assays are required which can be applied to large population studies. For this, these assays should be able to comprehensively characterize and explore the molecular diversity of nominally "single" proteins across populations. This information is usually unavailable with commonly used immunoassays such as ELISA (enzyme linked immunosorbent assay) which either ignore protein microheterogeneity, or are confounded by it. To this end, mass spectrometric immuno assays (MSIA) for three different human plasma proteins have been developed. These proteins viz. IGF-1, hemopexin and tetranectin have been found in reported literature to show correlations with many diseases along with several carcinomas. Developed assays were used to extract entire proteins from plasma samples and subsequently analyzed on mass spectrometric platforms. Matrix assisted laser desorption ionization (MALDI) and electrospray ionization (ESI) mass spectrometric techniques where used due to their availability and suitability for the analysis. This resulted in visibility of different structural forms of these proteins showing their structural micro-heterogeneity which is invisible to commonly used immunoassays. These assays are fast, comprehensive and can be applied in large sample studies to analyze proteins for biomarker discovery.
ContributorsRai, Samita (Author) / Nelson, Randall (Thesis advisor) / Hayes, Mark (Thesis advisor) / Borges, Chad (Committee member) / Ros, Alexandra (Committee member) / Arizona State University (Publisher)
Created2012
Description
ABSTRACT Communication is vital in the context of everyday life for all organisms, but particularly so in social insects, such as Z. nevadensis. The overall lifestyle and need for altruistic acts of individuals within a colony depends primarily on intracolony chemical communication, with a focus on odorants. The perception of these odorants is made possible by the chemoreceptive functions of sensilla basiconica and sensilla trichoid which exist on the antennal structure. The present study consists of both a morphological analysis and electrophysiological experiment concerning sensilla basiconica. It attempts to characterize the function of neurons present in sensilla basiconica through single sensillum recordings and contributes to existing literature by determining if a social insect, such as the dampwood termite, is able to perceive a wide spectrum of odorants despite having significantly fewer olfactory receptors than most other social insect species. Results indicated that sensilla basiconica presence significantly out-paced that of sensilla trichoid and sensilla chaetica combined, on all flagellomeres. Analysis demonstrated significant responses to all general odorants and several cuticular hydrocarbons. Combined with the knowledge of fewer olfactory receptors present in this species and their lifestyle, results may indicate a positive association between the the social complexity of an insect's lifestyle and the number of ORs the individuals within that colony possess.
ContributorsMcGlone, Taylor (Author) / Liebig, Juergen (Thesis director) / Ghaninia, Majid (Committee member) / Barrett, The Honors College (Contributor)
Created2015-05
Description
Self-maintenance behaviors, like preening in birds, can have important effects on fitness in many animals. Birds produce preen oil, which is a mixture of volatile and non-volatile compounds, that is spread through their feathers during grooming and influences feather integrity, waterproofing, and coloration. As urban areas grow and present conditions that may demand increased feather self-maintenance (e.g. due to soiling, pollution, elevated UV exposure due to natural habitat alterations), it is important to examine how preening and preen oil may be affected by this process. I assessed variation in preen oil composition in house finches (Haemorhous mexicanus) as a function of sex, urbanization, and plumage hue, a sexually selected indicator of male quality. Preen oil samples from birds captured at urban and rural sites were analyzed using gas chromatography-mass spectrometry. We detected 18 major peaks, which we tentatively identified as esters, and found that, although there were no sex or urban-rural differences in preen oil constituents, there was a significant interactive effect of sex and urbanization, with rural females and urban males having higher amounts of some components. This suggests that factors that vary with sex or urbanization, such as the timing of seasonal cycles, are affecting preen oil composition. There were no significant relationships between coloration and preen oil composition, suggesting that preen oil composition does not vary with male quality.
ContributorsBrooks, Ellen Elizabeth (Author) / McGraw, Kevin (Thesis director) / Liebig, Juergen (Committee member) / Weaver, Melinda (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Bacteria play a vital role in the world ecosystem, more importantly human health and disease. The capability to differentiate and identify these microorganisms serves as an important research objective. In past years, separations-based approaches have served as a way to observe and identify bacteria based on their characteristics. Gradient insulator dielectrophoresis (g-iDEP) provides benefits in identifying serotypes of a single species with precise separation. Separation of Staphylococcus epidermidis in a single g-iDEP microchannel is conducted exploiting their electrophoretic and electrokinetic properties. The cells were captured and concentrated at gates with interacting forces within the microchannel to clearly distinguish between the two strains. These results provide support for g-iDEP serving as a separating method and, furthermore, future clinical applications.
ContributorsDavis, Paige Elizabeth (Author) / Hayes, Mark (Thesis director) / Borges, Chad (Committee member) / Jones, Paul (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor)
Created2015-05
Description
Background: High risk types of human papillomavirus (HPV) are known to cause cancer, including cervical (99%) and oropharyngeal cancer (70%). HPV type 16 is the most common subtype. Three antigens that are critical for integration or tumor progression are E2, E6 and E7. In this study, we developed a systematic approach to identify naturally-processed HPV16-derived HLA class I epitopes for immunotherapy development. Methods: K562 cells, which lack HLA expression, were transduced with each HPV16 antigen using lentivirus and supertransfected with HLA-A2 by nucleofection. Stable cell lines expressing each antigen were selected for and maintained throughout the investigation. In order to establish a Gateway-compatible vector for robust transient gene expression, a Gateway recombination expression cloning cassette was inserted into the commercial Lonza pMAX GFP backbone, which has been experimentally shown to display high transfection expression efficiency. GFP was cloned into the vector and plain K562 cells were transfected with the plasmid by nucleofection. Results: Expression of K562-A2 was tested at various time points by flow cytometry and A2 expression was confirmed. Protein expression was shown for the transduced K562 E7 by Western blot analysis. High transfection efficiency of the pMAX_GFP_Dest vector (up to 97% GFP+ cells) was obtained 48 hours post transfection, comparable to the commercial GFP-plasmid. Conclusion: We have established a rapid system for target viral antigen co-expression with single HLA molecules for analysis of antigen presentation. Using HPV as a model system, our goal is to identify specific antigenic peptide sequences to develop immunotherapeutic treatments for HPV-associated cancers.
ContributorsVarda, Bianca Marie (Author) / Anderson, Karen (Thesis director) / Borges, Chad (Committee member) / Krishna, Sri (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05