Matching Items (82)
Description
Alzheimer’s disease (AD) is a progressive cognitive and behavior disorder that is characterized by the deposition of extracellular Aβ plaques, intracellular neurofibrillary tangles, and neuroinflammation. Aβ is generated by cleavage of the amyloid precursor protein (APP) by β-secretase (BACE1) and, subsequently, y- secretase. In recent years, there has been an increasing interest in studying and understanding inflammation as a therapeutic target for AD. Inflammation manifests in the brain in the form of activated microglia and astrocytes. These cells are able to release high levels of inflammatory cytokines such as Tumor Necrosis Factor-α (TNF-α). TNF-α is a major cytokine, which is involved in early inflammatory events and plays a role in the progression of AD pathology. There are currently no treatments that target chronic neuroinflammation. However, previous work in our laboratory with transgenic mice modeling AD suggested that the anti-cancer drug lenalidomide could lower neuroinflammation and slow AD progression, though the cellular and molecular mechanisms are yet to be elucidated. Here we hypothesized that lenalidomide can modulate TNF-α production in microglia and decrease amyloidogenesis. Using immortal cell lines mimicking several brain cell types, we discovered that lenalidomide is likely to decrease inflammation by modulating microglia cells rather than neurons or astrocytes. In addition, the drug may prevent the overexpression of BACE1 upon inflammation, thus blocking the overproduction of Aβ. If confirmed, these results could lead to a better understanding of how inflammation regulates Aβ synthesis and provide novel cellular and molecular therapeutic targets to control the progression AD.
ContributorsGujju, Manasa (Author) / DeCourt, Boris (Thesis director) / Olive, M. Foster (Committee member) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Nicotine addiction remains a prevalent public health issue, and the FDA has released a statement outlining the systematic reduction of nicotine to non-zero levels in the coming years. Current research has not yet established the effects of abrupt nicotine dose reduction on vulnerability to relapse, nor has abrupt nicotine dose reduction been evaluated in terms of behavioral economic characteristics of demand and elasticity been evaluated for reduced doses of nicotine. Using a rat model, we first evaluated the comparability of between- and within-session protocols for establishing characteristics of demand and elasticity for nicotine to shorten experimental timelines for this study and future studies. We then tested environmental enrichment and sex as factors of elasticity of demand for nicotine. Using a rat model of relapse to cues, we also examined the effects of nicotine dose-reduction on vulnerability to relapse. We found differences in maximum consumption and demand between the between- and within-session protocols, as well as sex differences in elasticity of demand on the within-session protocol where male demand was more elastic than female demand. Additionally, we found that enrichment significantly increased elasticity of demand for nicotine for both males and females. Finally, preliminary analyses revealed that nicotine dose reduction yields more inelastic demand and higher maximum consumption, and these outcomes predict increased time to extinction of the association between nicotine and contingent cues, and increased rates of relapse. These studies highlight the usefulness and validity of within-session protocols, and also illustrate the necessity for rigorous testing of forced dose reduction on nicotine vulnerability.
ContributorsCabrera-Brown, Gabriella Paula (Author) / Gipson-Reichardt, Cassandra (Thesis director) / Olive, M. Foster (Committee member) / Davis, Mary (Committee member) / Sanford School of Social and Family Dynamics (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
Description
Cases of heroin use and overdose are on the rise in the United States which has created what some call a public health crisis. Previous studies have investigated the beneficial effect of social interaction recovering addicts, and in animal models of addiction, social interaction can prevent or reverse the conditioned rewarding effects of cocaine. This study sought to determine if social interaction would prevent or diminish a conditioned preference for a heroin-paired context. Following establishment of baseline place preference, adult male Sprague-Dawley rats underwent once daily conditioning with either saline, heroin (1 mg/kg), or the animal's cage-mate for a total of 8 conditioning sessions. Assessment of post-conditioning place preference revealed that both the heroin injections and the presence of the cage-mate produced a place preference . In contrast to the findings of previous studies using cocaine as the conditioning drug, it was determined that rats preferred the heroin-paired context over that paired with the cage-mate.. These findings suggest that the protective effects of social interaction found in prior studies using cocaine as the conditioning drug may not extend to opiates, perhaps a result of stronger contextual conditioning and/or rewarding effects of this class of abused drugs.
ContributorsMarble, Krista Lillian (Author) / Olive, M. Foster (Thesis director) / Tomek, Seven (Committee member) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
Description
The RAS/MAPK (RAS/Mitogen Activated Protein Kinase) pathway is a highly conserved, canonical signaling cascade that is highly involved in cellular growth and proliferation as well as cell migration. As such, it plays an important role in development, specifically in development of the nervous system. Activation of ERK is indispensable for the differentiation of Embryonic Stem Cells (ESC) into neuronal precursors (Li z et al, 2006). ERK signaling has also shown to mediate Schwann cell myelination of the peripheral nervous system (PNS) as well as oligodendrocyte proliferation (Newbern et al, 2011). The class of developmental disorders that result in the dysregulation of RAS signaling are known as RASopathies. The molecular and cell-specific consequences of these various pathway mutations remain to be elucidated. While there is evidence for altered DNA transcription in RASopathies, there is little work examining the effects of the RASopathy-linked mutations on protein translation and post-translational modifications in vivo. RASopathies have phenotypic and molecular similarities to other disorders such as Fragile X Syndrome (FXS) and Tuberous Sclerosis (TSC) that show evidence of aberrant protein synthesis and affect related pathways. There are also well-defined downstream RAS pathway elements involved in translation. Additionally, aberrant corticospinal axon outgrowth has been observed in disease models of RASopathies (Xing et al, 2016). For these reasons, this present study examines a subset of proteins involved in translation and translational regulation in the context of RASopathy disease states. Results indicate that in both of the tested RASopathy model systems, there is altered mTOR expression. Additionally the loss of function model showed a decrease in rps6 activation. This data supports a role for the selective dysregulation of translational control elements in RASopathy models. This data also indicates that the primary candidate mechanism for control of altered translation in these modes is through the altered expression of mTOR.
ContributorsHilbert, Alexander Robert (Author) / Newbern, Jason (Thesis director) / Olive, M. Foster (Committee member) / Bjorklund, Reed (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
This study examined perception of K12 schooling systems as experienced by a randomsample of adults in Phoenix, AZ. It explored whether the values purported as key factors
in the American K12 schooling system - as presented in academic literature - were compatible with the lives, interests and goals of ‘users’, student-participants. In addition, it offered opportunity for post-K12 student-participants to share their views on the purposes, goals, and outcomes they held to be important. The sample consisted of 139 post-K12 stu-
dents/individuals residing in Phoenix, AZ. Mean age of student-participants was 29. Results indicated a mismatch between purported K12 schooling goals and important outcomes embedded in the system and values held by the K12 student-participants. The participants in this research generally perceived K12 schooling as valuable, both to themselves and to society at large, but stressed that the deficiencies they perceived in the system were particular to delivery platforms as they relate to the learning styles of students and belonging. Future life skills and success - in and after K12 schooling - whether related to college or not were also of importance. Results revealed that the initial hypothesis of income, age, and ethnicity as
key factors in satisfaction with K12 schooling was not borne-out. Rather it revealed that a sense of belonging and the suitability of learning platforms to the individual learning styles of students were of greatest significance.
ContributorsParker-Anderies, Margaret (Author) / Janssen, Marco (Thesis advisor) / Garcia, David (Committee member) / Mishra, Punya (Committee member) / Arizona State University (Publisher)
Created2022
Description
One of the identified health risk areas for human spaceflight is infectious disease, particularly involving environmental microorganisms already found on the International Space Station (ISS). In particular, bacteria belonging to the Burkholderia cepacia complex (Bcc) which can cause human disease in those who are immunocompromised, have been identified in the ISS water supply. This present study characterized the effect of spaceflight analog culture conditions on Bcc to certain physiological stresses (acid and thermal as well as intracellular survival in U927 human macrophage cells). The NASA-designed Rotating Wall Vessel (RWV) bioreactor was used as the spaceflight analogue culture system in these studies to grow Bcc bacterial cells under Low Shear Modeled Microgravity (LSMMG) conditions. Results show that LSMMG culture increased the resistance of Bcc to both acid and thermal stressors, but did not alter phagocytic uptake in 2-D monolayers of human monocytes.
ContributorsVu, Christian-Alexander (Author) / Nickerson, Cheryl (Thesis director) / Barrila, Jennifer (Committee member) / Ott, Mark (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2023-05
Description
The consumption of food, energy, and water (FEW) resources in U.S. households is very carbon-intensive. However, these negative climate change impacts are often invisible due to insufficient awareness and knowledge. Serious games (SGs) can potentially address this issue through an experiential and rigorous approach to simulate household actions and impacts in a playful but realistic setting. This dissertation focuses on: (a) the design and testing of an SG called HomeRUN (Role-play for Understanding Nexus); (b) the effectiveness of gameplay in advancing player knowledge about the upfront costs, financial returns, and greenhouse gas (GHG) emissions of various household decisions; and (c) the effectiveness of intervention messages in increasing FEW conservation to reduce household GHG emissions. The results of gameplay sessions played by 150 university students show that HomeRUN is fun to play, creates a flow experience, and results in experiential learning. The majority of players agreed that the game experience will continue over time to influence their future consumption behaviors to conserve FEW resources. Female players tended to gain more knowledge about financial aspects of interventions, whereas male players were more likely to increase their understandings of GHG emissions and resource consumption after playing HomeRUN. Social comparison intervention messages about energy and food consumption led to the highest reductions in household carbon emissions. The messages associated with each FEW resource tended to be most likely to lead to FEW conservation actions with the game that most closely corresponded to the particular FEW resource addressed in the message. This dissertation advances understandings about the design and use of SGs to foster learning and promote sustainable household FEW consumption.
ContributorsHanif, Muhammad Adnan (Author) / Agusdinata, Datu Buyung (Thesis advisor) / Halvorsen, Kathleen (Committee member) / Janssen, Marco (Committee member) / Arizona State University (Publisher)
Created2021
Description
Copper demand is surging in the U.S. and around the world as countries embrace new forms of energy to combat climate change. But copper mining – while a key strategy to address supply shortages – can serve as a vehicle for injustice by imposing socio-ecological burdens for nearby communities. Due to the growing demand for copper with resulting justice issues, more research is needed to evaluate governance for the mining sector using an environmental justice lens. The National Environmental Policy Act (NEPA) is a key environmental regulation that governs mining in the U.S. Therefore, I used a qualitative case study approach to examine how NEPA requirements shape engagement in public comment opportunities. I selected the Resolution Copper Mine as a case study because of its potential to support the energy transition but pose a significant dilemma for justice: the mine is anticipated to generate 25 percent of the U.S. copper demand each year but disturb lands that hold spiritual significance for Native American Tribes. I used the Institutional Analysis and Development (IAD) framework to analyze institutional dynamics and evaluate the NEPA process for public participation using a procedural justice lens. Drawing on interview data and document analysis, the results show that process rules such as a land exchange bill and the lengths of comment opportunities were among the key barriers for participation. Socioeconomic conditions of communities including access to social resources (i.e. access to internet and technical assistance) and institutional trust posed further barriers for participation. Hence, this study suggests that federal decision-makers should aim to better integrate procedural justice into the NEPA process.
ContributorsLewis, Sydney (Author) / Kellner, Elke (Thesis director) / Janssen, Marco (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2024-05
Description
Anthropogenic land use has irrevocably transformed the natural systems on which humankind relies. Understanding where, why, and how social and economic processes drive globally-important land-use changes, from deforestation to urbanization, has advanced substantially. Illicit and clandestine activities--behavior that is intentionally secret because it breaks formal laws or violates informal norms--are poorly understood, however, despite the recognition of their significant role in land change. This dissertation fills this lacuna by studying illicit and clandestine activity and quantifying its influence on land-use patterns through examining informal urbanization in Mexico City and deforestation Central America. The first chapter introduces the topic, presenting a framework to examine illicit transactions in land systems. The second chapter uses data from interviews with actors involved with land development in Mexico City, demonstrating how economic and political payoffs explain the persistence of four types of informal urban expansion. The third chapter examines how electoral politics influence informal urban expansion and land titling in Mexico City using panel regression. Results show land title distribution increases just before elections, and more titles are extended to loyal voters of the dominant party in power. Urban expansion increases with electoral competition in local elections for borough chiefs and legislators. The fourth chapter tests and confirms the hypothesis that narcotrafficking has a causal effect on forest loss in Central America from 2001-2016 using two proxies of narcoactivity: drug seizures and events from media reports. The fifth chapter explores the spatial signature and pattern of informal urban development. It uses a typology of urban informality identified in chapter two to hypothesize and demonstrate distinct urban expansion patterns from satellite imagery. The sixth and final chapter summarizes the role of illicit and clandestine activity in shaping deforestation and urban expansion through illegal economies, electoral politics, and other informal transactions. Measures of illicit and clandestine activity should--and could--be incorporated into land change models to account for a wider range of relevant causes. This dissertation shines a new light on the previously hidden processes behind ever-easier to detect land-use patterns as earth observing satellites increase spatial and temporal resolution.
ContributorsTellman, Elizabeth (Author) / Turner II, Billie L (Thesis advisor) / Eakin, Hallie (Thesis advisor) / Janssen, Marco (Committee member) / Alba, Felipe de (Committee member) / Jain, Meha (Committee member) / Arizona State University (Publisher)
Created2019
Description
Salmonella enterica serovar Typhimurium (S. Typhimurium) is a Gram-negative enteric pathogen that causes self-limiting gastroenteritis in healthy individuals and can cause systemic infections in those who are immunocompromised. During its natural lifecycle, S. Typhimurium encounters a wide variety of stresses it must sense and respond to in a dynamic and coordinated fashion to induce resistance and ensure survival. Salmonella is subjected to a series of stresses that include temperature shifts, pH variability, detergent-like bile salts, oxidative environments and changes in fluid shear levels. Previously, our lab showed that cultures of S. Typhimurium grown under physiological low fluid shear (LFS) conditions similar to those encountered in the intestinal tract during infection uniquely regulates the virulence, gene expression and pathogenesis-related stress responses of this pathogen during log phase. Interestingly, the log phase Salmonella mechanosensitive responses to LFS were independent of the master stress response sigma factor, RpoS, departing from our conventional understanding of RpoS regulation. Since RpoS is a growth phase dependent regulator with increased stability in stationary phase, the current study investigated the role of RpoS in mediating pathogenesis-related stress responses in stationary phase S. Typhimurium grown under LFS and control conditions. Specifically, stationary phase responses to acid, thermal, bile and oxidative stress were assayed. To our knowledge the results from the current study demonstrate the first report that the mechanical force of LFS globally alters the S. Typhimurium χ3339 stationary phase stress response independently of RpoS to acid and bile stressors but dependently on RpoS to oxidative and thermal stress. This indicates that fluid shear-dependent differences in acid and bile stress responses are regulated by alternative pathway(s) in S. Typhimurium, were the oxidative and thermal stress responses are regulated through RpoS in LFS conditions. Results from this study further highlight how bacterial mechanosensation may be important in promoting niche recognition and adaptation in the mammalian host during infection, and may lead to characterization of previously unidentified pathogenesis strategies.
ContributorsCrenshaw, Keith (Author) / Nickerson, Cheryl A. (Thesis advisor) / Barrila, Jennifer (Thesis advisor) / Ott, C. (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2016