Matching Items (194)
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
The use of synthetic cathinones or "bath salts" has risen dramatically in recent years with one of the most popular being Methylendioxypyrovalerone (MDPV). Following the temporary legislative ban on the sale and distribution of this compound , a multitude of other cathinone derivatives have been synthesized. The current study seeks to compare the abuse potential of MDPV with one of the emergent synthetic cathinones 4-methylethcathinone (4-MEC), based on their respective ability to lower current thresholds in an intracranial self-stimulation (ICSS) paradigm. Following acute administration (0.1, 0.5, 1 and 2 mg/kg i.p.) MDPV was found to significantly lower ICSS thresholds at all doses tested (F4,35=11.549, p<0.001). However, following acute administration (0.3,1,3,10,30 mg/kg i.p) 4-MEC produced no significant ICSS threshold depression (F5,135= 0.622, p = 0.684). Together these findings suggest that while MDPV may possess significant abuse potential, other synthetic cathinones such as 4-MEC may have a drastically reduced potential for abuse.
ContributorsWegner, Scott Andrew (Author) / Olive, M. Foster (Thesis director) / Presson, Clark (Committee member) / Sanabria, Federico (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / Department of Psychology (Contributor)
Created2013-05
Description
Chronic restraint stress impairs hippocampal-mediated spatial learning and memory, which improves following a post-stress recovery period. Here, we investigated whether brain derived neurotrophic factor (BDNF), a protein important for hippocampal function, would alter the recovery from chronic stress-induced spatial memory deficits. Adult male Sprague-Dawley rats were infused into the hippocampus with adeno- associated viral vectors containing the coding sequence for short interfering (si)RNA directed against BDNF or a scrambled sequence (Scr), with both containing the coding information for green fluorescent protein to aid in anatomical localization. Rats were then chronically restrained (wire mesh, 6h/d/21d) and assessed for spatial learning and memory using a radial arm water maze (RAWM) either immediately after stressor cessation (Str-Imm) or following a 21-day post-stress recovery period (Str-Rec). All groups learned the RAWM task similarly, but differed on the memory retention trial. Rats in the Str-Imm group, regardless of viral vector contents, committed more errors in the spatial reference memory domain than did non-stressed controls. Importantly, the typical improvement in spatial memory following recovery from chronic stress was blocked with the siRNA against BDNF, as Str-Rec-siRNA performed worse on the RAWM compared to the non-stressed controls or Str-Rec-Scr. These effects were specific for the reference memory domain as repeated entry errors that reflect spatial working memory were unaffected by stress condition or viral vector contents. These results demonstrate that hippocampal BDNF is necessary for the recovery from stress-induced hippocampal dependent spatial memory deficits in the reference memory domain.
ContributorsOrtiz, J. Bryce (Author) / Conrad, Cheryl D. (Thesis advisor) / Olive, M. Foster (Committee member) / Taylor, Sara (Committee member) / Bimonte-Nelson, Heather A. (Committee member) / Arizona State University (Publisher)
Created2013
Description
The brain is a fundamental target of the stress response that promotes adaptation and survival but the repeated activation of the stress response has the potential alter cognition, emotion, and motivation, key functions of the limbic system. Three structures of the limbic system in particular, the hippocampus, medial prefrontal cortex (mPFC), and amygdala, are of special interest due to documented structural changes and their implication in post-traumatic stress disorder (PTSD). One of many notable chronic stress-induced changes include dendritic arbor restructuring, which reflect plasticity patterns in parallel with the direction of alterations observed in functional imaging studies in PTSD patients. For instance, chronic stress produces dendritic retraction in the hippocampus and mPFC, but dendritic hypertrophy in the amygdala, consistent with functional imaging in patients with PTSD. Some have hypothesized that these limbic region's modifications contribute to one's susceptibility to develop PTSD following a traumatic event. Consequently, we used a familiar chronic stress procedure in a rat model to create a vulnerable brain that might develop traits consistent with PTSD when presented with a challenge. In adult male rats, chronic stress by wire mesh restraint (6h/d/21d) was followed by a variety of behavioral tasks including radial arm water maze (RAWM), fear conditioning and extinction, and fear memory reconsolidation to determine chronic stress effects on behaviors mediated by these limbic structures. In chapter 2, we corroborated past findings that chronic stress caused hippocampal CA3 dendritic retraction. Importantly, we present new findings that CA3 dendritic retraction corresponded with poor spatial memory in the RAWM and that these outcomes reversed after a recovery period. In chapter 3, we also showed that chronic stress impaired mPFC-mediated extinction memory, findings that others have reported. Using carefully assessed behavior, we present new findings that chronic stress impacted nonassociative fear by enhancing contextual fear during extinction that generalized to a new context. Moreover, the generalization behavior corresponded with enhanced functional activation in the hippocampus and amygdala during fear extinction memory retrieval. In chapter 5, we showed for the first time that chronic stress enhanced amygdala functional activation during fear memory retrieval, i.e., reactivation. Moreover, these enhanced fear memories were resistant to protein synthesis interference to disrupt a previously formed memory, called reconsolidation in a novel attempt to weaken chronic stress enhanced traumatic memory. Collectively, these studies demonstrated the plastic and dynamic effects of chronic stress on limbic neurocircuitry implicated in PTSD. We showed that chronic stress created a structural and functional imbalance across the hippocampus, mPFC, and amygdala, which lead to a PTSD-like phenotype with persistent and exaggerated fear following fear conditioning. These behavioral disruptions in conjunction with morphological and functional imaging data reflect a chronic stress-induced imbalance between hippocampal and mPFC regulation in favor of amygdala function overdrive, and supports a novel approach for traumatic memory processing in PTSD.
ContributorsHoffman, Ann (Author) / Conrad, Cheryl D. (Thesis advisor) / Olive, M. Foster (Committee member) / Hammer, Jr., Ronald P. (Committee member) / Sanabria, Federico (Committee member) / Arizona State University (Publisher)
Created2013
Description
For over a century, researchers have been investigating collective cognition, in which a group of individuals together process information and act as a single cognitive unit. However, I still know little about circumstances under which groups achieve better (or worse) decisions than individuals. My dissertation research directly addressed this longstanding question, using the house-hunting ant Temnothorax rugatulus as a model system. Here I applied concepts and methods developed in psychology not only to individuals but also to colonies in order to investigate differences of their cognitive abilities. This approach is inspired by the superorganism concept, which sees a tightly integrated insect society as the analog of a single organism. I combined experimental manipulations and models to elucidate the emergent processes of collective cognition. My studies show that groups can achieve superior cognition by sharing the burden of option assessment among members and by integrating information from members using positive feedback. However, the same positive feedback can lock the group into a suboptimal choice in certain circumstances. Although ants are obligately social, my results show that they can be isolated and individually tested on cognitive tasks. In the future, this novel approach will help the field of animal behavior move towards better understanding of collective cognition.
ContributorsSasaki, Takao (Author) / Pratt, Stephen C (Thesis advisor) / Amazeen, Polemnia (Committee member) / Liebig, Jürgen (Committee member) / Janssen, Marco (Committee member) / Fewell, Jennifer (Committee member) / Hölldobler, Bert (Committee member) / Arizona State University (Publisher)
Created2013
Description
Consideration of both biological and human-use dynamics in coupled social-ecological systems is essential for the success of interventions such as marine reserves. As purely human institutions, marine reserves have no direct effects on ecological systems. Consequently, the success of a marine reserve depends on managers` ability to alter human behavior in the direction and magnitude that supports reserve objectives. Further, a marine reserve is just one component in a larger coupled social-ecological system. The social, economic, political, and biological landscape all determine the social acceptability of a reserve, conflicts that arise, how the reserve interacts with existing fisheries management, accuracy of reserve monitoring, and whether the reserve is ultimately able to meet conservation and fishery enhancement goals. Just as the social-ecological landscape is critical at all stages for marine reserve, from initial establishment to maintenance, the reserve in turn interacts with biological and human use dynamics beyond its borders. Those interactions can lead to the failure of a reserve to meet management goals, or compromise management goals outside the reserve. I use a bio-economic model of a fishery in a spatially patchy environment to demonstrate how the pre-reserve fisheries management strategy determines the pattern of fishing effort displacement once the reserve is established, and discuss the social, political, and biological consequences of different patterns for the reserve and the fishery. Using a stochastic bio-economic model, I demonstrate how biological and human use connectivity can confound the accurate detection of reserve effects by violating assumptions in the quasi-experimental framework. Finally, I examine data on recreational fishing site selection to investigate changes in response to the announcement of enforcement of a marine reserve in the Gulf of California, Mexico. I generate a scale of fines that would fully or partially protect the reserve, providing a data-driven way for managers to balance biological and socio-economic goals. I suggest that natural resource managers consider human use dynamics with the same frequency, rigor, and tools as they do biological stocks.
ContributorsFujitani, Marie (Author) / Abbott, Joshua (Thesis advisor) / Fenichel, Eli (Thesis advisor) / Gerber, Leah (Committee member) / Anderies, John (Committee member) / Arizona State University (Publisher)
Created2014
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
The spread of invasive species may be greatly affected by human responses to prior species spread, but models and estimation methods seldom explicitly consider human responses. I investigate the effects of management responses on estimates of invasive species spread rates. To do this, I create an agent-based simulation model of an insect invasion across a county-level citrus landscape. My model provides an approximation of a complex spatial environment while allowing the "truth" to be known. The modeled environment consists of citrus orchards with insect pests dispersing among them. Insects move across the simulation environment infesting orchards, while orchard managers respond by administering insecticide according to analyst-selected behavior profiles and management responses may depend on prior invasion states. Dispersal data is generated in each simulation and used to calculate spread rate via a set of estimators selected for their predominance in the empirical literature. Spread rate is a mechanistic, emergent phenomenon measured at the population level caused by a suite of latent biological, environmental, and anthropogenic. I test the effectiveness of orchard behavior profiles on invasion suppression and evaluate the robustness of the estimators given orchard responses. I find that allowing growers to use future expectations of spread in management decisions leads to reduced spread rates. Acting in a preventative manner by applying insecticide before insects are actually present, orchards are able to lower spread rates more than by reactive behavior alone. Spread rates are highly sensitive to spatial configuration. Spatial configuration is hardly a random process, consisting of many latent factors often not accounted for in spread rate estimation. Not considering these factors may lead to an omitted variables bias and skew estimation results. The ability of spread rate estimators to predict future spread varies considerably between estimators, and with spatial configuration, invader biological parameters, and orchard behavior profile. The model suggests that understanding the latent factors inherent to dispersal is important for selecting phenomenological models of spread and interpreting estimation results. This indicates a need for caution when evaluating spread. Although standard practice, current empirical estimators may both over- and underestimate spread rate in the simulation.
ContributorsShanafelt, David William (Author) / Fenichel, Eli P (Thesis advisor) / Richards, Timothy (Committee member) / Janssen, Marco (Committee member) / Arizona State University (Publisher)
Created2012
Description
Some of the most talented, innovative, and experimental artists are students, but they are often discouraged by the price of higher education and lack of scholarship or funding opportunities. Additionally, the art industry has become stagnant. Traditional brick-and-mortar galleries are not willing to represent young, unknown artists. Their overhead is simply too high for risky choices.
The Student Art Project is art patronage for the 21st century—a curated online gallery featuring exceptional student artists. The Student Art Project is a highly curated experience for buyers. Only five artists are featured each month. Buyers are not bombarded with thousands of different products and separate artists “shops”. They can read artists bios and find art they connect with.
Student artists apply through an online form. Once accepted to the program, artists receive a $200 materials stipend to create an exclusive collection of 5-10 pieces. Original artwork and limited edition prints are sold through our website. These collections can potentially fund an entire year of college tuition, a life-changing amount for many students.
Brick-and-mortar galleries typically take 40-60% of the retail price of artwork. The Student Art Project will only take 30%, which we will use to reinvest in future artists. Other art websites, like Etsy, require the artists to ship, invoice, and communicate with customers. For students, this means less time spent in the classroom and less time developing their craft. The Student Art Project handles all business functions for our artists, allowing them to concentrate on what really matters, their education.
The Student Art Project is art patronage for the 21st century—a curated online gallery featuring exceptional student artists. The Student Art Project is a highly curated experience for buyers. Only five artists are featured each month. Buyers are not bombarded with thousands of different products and separate artists “shops”. They can read artists bios and find art they connect with.
Student artists apply through an online form. Once accepted to the program, artists receive a $200 materials stipend to create an exclusive collection of 5-10 pieces. Original artwork and limited edition prints are sold through our website. These collections can potentially fund an entire year of college tuition, a life-changing amount for many students.
Brick-and-mortar galleries typically take 40-60% of the retail price of artwork. The Student Art Project will only take 30%, which we will use to reinvest in future artists. Other art websites, like Etsy, require the artists to ship, invoice, and communicate with customers. For students, this means less time spent in the classroom and less time developing their craft. The Student Art Project handles all business functions for our artists, allowing them to concentrate on what really matters, their education.
ContributorsDangler, Rebecca Leigh (Author) / Trujillo, Rhett (Thesis director) / Coleman, Sean (Committee member) / Barrett, The Honors College (Contributor) / Herberger Institute for Design and the Arts (Contributor) / Department of Management (Contributor)
Created2015-05
Description
Drought is one of the most pressing issues affecting the future of the standard of living here in Phoenix. With the threat of water rationing and steep price hikes looming on the horizon for water customers in California, the desert southwest, and in drought-stricken communities worldwide, industrial designers are in a prime position to help improve the experience of water conservation so that consumers are willing to start taking conscious steps toward rethinking their relationship with water usage.
In a research group, several designers sought to understand the depth and complexity of this highly politicized issue by interviewing a wide variety of stakeholders, including sustainability experts, landscapers, water company executives, small business owners, reservoir forest rangers, and many more. Data synthesis led to the conclusion that residential water use is a lifestyle issue, and the only real way to conserve involves a significant shift in the collective idea of an “ideal” home—lawns, pools, and overwatered landscaping contribute to 70% of all water use by residences in the Phoenix area. The only real way to conserve involves increasing population density and creating communal green spaces.
DR. DISH is a dishwashing device that is meant to fit into the high-density living spaces that are rapidly being built in the face of the massive exodus of people into the world’s cities. To help busy apartment and condominium dwellers conserve water and time, DR. DISH converts a standard kitchen sink into a small dishwasher, which uses significantly less water than hand-washing dishes or rinsing dishes before putting them into a conventional dishwasher. Using advanced filtration technology and a powerful rinse cycle, a load dishes can be cleaned with about 2 gallons of water. Fully automating the dishwashing process also saves the user time and minimizes unpleasant contact with food residue and grease.
This device is meant to have a significant impact upon the water use of households that do not have a dishwasher, or simply do not use their dishwasher. With a low target price point and myriad convenient features, DR. DISH is a high-tech solution that promises water savings at a time when every effort toward conservation is absolutely critical. As we move toward a new era in determining water rights and imposing mandatory restrictions upon each and every person living in affected areas, creating conservation solutions that will be relevant for the lifestyles of the future is especially important, and the agility of designers in coming up with products that quickly cut consumer water consumption will be a key factor in determining whether humanity will be able to adapt to a new era in our relationship with natural resources.
In a research group, several designers sought to understand the depth and complexity of this highly politicized issue by interviewing a wide variety of stakeholders, including sustainability experts, landscapers, water company executives, small business owners, reservoir forest rangers, and many more. Data synthesis led to the conclusion that residential water use is a lifestyle issue, and the only real way to conserve involves a significant shift in the collective idea of an “ideal” home—lawns, pools, and overwatered landscaping contribute to 70% of all water use by residences in the Phoenix area. The only real way to conserve involves increasing population density and creating communal green spaces.
DR. DISH is a dishwashing device that is meant to fit into the high-density living spaces that are rapidly being built in the face of the massive exodus of people into the world’s cities. To help busy apartment and condominium dwellers conserve water and time, DR. DISH converts a standard kitchen sink into a small dishwasher, which uses significantly less water than hand-washing dishes or rinsing dishes before putting them into a conventional dishwasher. Using advanced filtration technology and a powerful rinse cycle, a load dishes can be cleaned with about 2 gallons of water. Fully automating the dishwashing process also saves the user time and minimizes unpleasant contact with food residue and grease.
This device is meant to have a significant impact upon the water use of households that do not have a dishwasher, or simply do not use their dishwasher. With a low target price point and myriad convenient features, DR. DISH is a high-tech solution that promises water savings at a time when every effort toward conservation is absolutely critical. As we move toward a new era in determining water rights and imposing mandatory restrictions upon each and every person living in affected areas, creating conservation solutions that will be relevant for the lifestyles of the future is especially important, and the agility of designers in coming up with products that quickly cut consumer water consumption will be a key factor in determining whether humanity will be able to adapt to a new era in our relationship with natural resources.
ContributorsMarcinkowski, Margaret Nicole (Author) / Shin, Dosun (Thesis director) / McDermott, Lauren (Committee member) / Barrett, The Honors College (Contributor) / The Design School (Contributor) / Herberger Institute for Design and the Arts (Contributor)
Created2015-05