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Description
Following a traumatic brain injury (TBI) 5-50% of patients will develop post traumatic epilepsy (PTE). Pediatric patients are most susceptible with the highest incidence of PTE. Currently, we cannot prevent the development of PTE and knowledge of basic mechanisms are unknown. This has led to several shortcomings to the treatment of PTE, one of which is the use of anticonvulsant medication to the population of TBI patients that are not likely to develop PTE. The complication of identifying the two populations has been hindered by the ability to find a marker to the pathogenesis of PTE. The central hypothesis of this dissertation is that following TBI, the cortex undergoes distinct cellular and synaptic reorganization that facilitates cortical excitability and promotes seizure development. Chapter 2 of this dissertation details excitatory and inhibitory changes in the rat cortex after severe TBI. This dissertation aims to identify cortical changes to a single cell level after severe TBI using whole cell patch clamp and electroencephalogram electrophysiology. The work of this dissertation concluded that excitatory and inhibitory synaptic activity in cortical controlled impact (CCI) animals showed the development of distinct burst discharges that were not present in control animals. The results suggest that CCI induces early "silent" seizures that are detectable on EEG and correlate with changes to the synaptic excitability in the cortex. The synaptic changes and development of burst discharges may play an important role in synchronizing the network and promoting the development of PTE.
ContributorsNichols, Joshua (Author) / Anderson, Trent (Thesis advisor) / Neisewander, Janet (Thesis advisor) / Newbern, Jason (Committee member) / Arizona State University (Publisher)
Created2014
Description
The ability to detect and appropriately respond to chemical stimuli is important for many organisms, ranging from bacteria to multicellular animals. Responses to these stimuli can be plastic over multiple time scales. In the short-term, the synaptic strengths of neurons embedded in neural circuits can be modified and result in various forms of learning. In the long-term, the overall developmental trajectory of the olfactory network can be altered and synaptic strengths can be modified on a broad scale as a direct result of long-term (chronic) stimulus experience. Over evolutionary time the olfactory system can impose selection pressures that affect the odorants used in communication networks. On short time scales, I measured the effects of repeated alarm pheromone exposure on the colony-level defense behaviors in a social bee. I found that the responses to the alarm pheromone were plastic. This suggests that there may be mechanisms that affect individual plasticity to pheromones and regulate how these individuals act in groups to coordinate nest defense. On longer time scales, I measured the behavioral and neural affects of bees given a single chronic odor experience versus bees that had a natural, more diverse olfactory experience. The central brains of bees with a deprived odor experience responded more similarly to odorants in imaging studies, and did not develop a fully mature olfactory network. Additionally, these immature networks showed behavioral deficits when recalling odor mixture components. Over evolutionary time, signals need to engage the attention of and be easily recognized by bees. I measured responses of bees to a floral mixture and its constituent monomolecular components. I found that natural floral mixtures engage the orientation of bees’ antennae more strongly than single-component odorants and also provide more consistent central brain responses between stimulations. Together, these studies highlight the importance of olfactory experience on different scales and how the nervous system might impose pressures to select the stimuli used as signals in communication networks.
ContributorsJernigan, Christopher (Author) / Smith, Brian H. (Thesis advisor) / Newbern, Jason (Committee member) / Harrisoin, Jon (Committee member) / Rutowski, Ronald (Committee member) / Pratt, Stephen (Committee member) / Arizona State University (Publisher)
Created2018
Description
Parkinson’s disease (PD) is a progressive neurodegenerative disorder, diagnosed late in
the disease by a series of motor deficits that manifest over years or decades. It is characterized by degeneration of mid-brain dopaminergic neurons with a high prevalence of dementia associated with the spread of pathology to cortical regions. Patients exhibiting symptoms have already undergone significant neuronal loss without chance for recovery. Analysis of disease specific changes in gene expression directly from human patients can uncover invaluable clues about a still unknown etiology, the potential of which grows exponentially as additional gene regulatory measures are questioned. Epigenetic mechanisms are emerging as important components of neurodegeneration, including PD; the extent to which methylation changes correlate with disease progression has not yet been reported. This collection of work aims to define multiple layers of PD that will work toward developing biomarkers that not only could improve diagnostic accuracy, but also push the boundaries of the disease detection timeline. I examined changes in gene expression, alternative splicing of those gene products, and the regulatory mechanism of DNA methylation in the Parkinson’s disease system, as well as the pathologically related Alzheimer’s disease (AD). I first used RNA sequencing (RNAseq) to evaluate differential gene expression and alternative splicing in the posterior cingulate cortex of patients with PD and PD with dementia (PDD). Next, I performed a longitudinal genome-wide methylation study surveying ~850K CpG methylation sites in whole blood from 189 PD patients and 191 control individuals obtained at both a baseline and at a follow-up visit after 2 years. I also considered how symptom management medications could affect the regulatory mechanism of DNA methylation. In the last chapter of this work, I intersected RNAseq and DNA methylation array datasets from whole blood patient samples for integrated differential analyses of both PD and AD. Changes in gene expression and DNA methylation reveal clear patterns of pathway dysregulation that can be seen across brain and blood, from one study to the next. I present a thorough survey of molecular changes occurring within the idiopathic Parkinson’s disease patient and propose candidate targets for potential molecular biomarkers.
the disease by a series of motor deficits that manifest over years or decades. It is characterized by degeneration of mid-brain dopaminergic neurons with a high prevalence of dementia associated with the spread of pathology to cortical regions. Patients exhibiting symptoms have already undergone significant neuronal loss without chance for recovery. Analysis of disease specific changes in gene expression directly from human patients can uncover invaluable clues about a still unknown etiology, the potential of which grows exponentially as additional gene regulatory measures are questioned. Epigenetic mechanisms are emerging as important components of neurodegeneration, including PD; the extent to which methylation changes correlate with disease progression has not yet been reported. This collection of work aims to define multiple layers of PD that will work toward developing biomarkers that not only could improve diagnostic accuracy, but also push the boundaries of the disease detection timeline. I examined changes in gene expression, alternative splicing of those gene products, and the regulatory mechanism of DNA methylation in the Parkinson’s disease system, as well as the pathologically related Alzheimer’s disease (AD). I first used RNA sequencing (RNAseq) to evaluate differential gene expression and alternative splicing in the posterior cingulate cortex of patients with PD and PD with dementia (PDD). Next, I performed a longitudinal genome-wide methylation study surveying ~850K CpG methylation sites in whole blood from 189 PD patients and 191 control individuals obtained at both a baseline and at a follow-up visit after 2 years. I also considered how symptom management medications could affect the regulatory mechanism of DNA methylation. In the last chapter of this work, I intersected RNAseq and DNA methylation array datasets from whole blood patient samples for integrated differential analyses of both PD and AD. Changes in gene expression and DNA methylation reveal clear patterns of pathway dysregulation that can be seen across brain and blood, from one study to the next. I present a thorough survey of molecular changes occurring within the idiopathic Parkinson’s disease patient and propose candidate targets for potential molecular biomarkers.
ContributorsHenderson, Adrienne Rose (Author) / Huentelman, Matthew J (Thesis advisor) / Newbern, Jason (Thesis advisor) / Dunckley, Travis L (Committee member) / Jensen, Kendall (Committee member) / Wilson, Melissa (Committee member) / Arizona State University (Publisher)
Created2019
Description
Multicellular organisms use precise gene regulation, executed throughout development, to build and sustain various cell and tissue types. Post-transcriptional gene regulation is essential for metazoan development and acts on mRNA to determine its localization, stability, and translation. MicroRNAs (miRNAs) and RNA binding proteins (RBPs) are the principal effectors of post-transcriptional gene regulation and act by targeting the 3'untranslated regions (3'UTRs) of mRNA. MiRNAs are small non-coding RNAs that have the potential to regulate hundreds to thousands of genes and are dysregulated in many prevalent human diseases such as diabetes, Alzheimer's disease, Duchenne muscular dystrophy, and cancer. However, the precise contribution of miRNAs to the pathology of these diseases is not known.
MiRNA-based gene regulation occurs in a tissue-specific manner and is implemented by an interplay of poorly understood and complex mechanisms, which control both the presence of the miRNAs and their targets. As a consequence, the precise contributions of miRNAs to gene regulation are not well known. The research presented in this thesis systematically explores the targets and effects of miRNA-based gene regulation in cell lines and tissues.
I hypothesize that miRNAs have distinct tissue-specific roles that contribute to the gene expression differences seen across tissues. To address this hypothesis and expand our understanding of miRNA-based gene regulation, 1) I developed the human 3'UTRome v1, a resource for studying post-transcriptional gene regulation. Using this resource, I explored the targets of two cancer-associated miRNAs miR-221 and let-7c. I identified novel targets of both these miRNAs, which present potential mechanisms by which they contribute to cancer. 2) Identified in vivo, tissue-specific targets in the intestine and body muscle of the model organism Caenorhabditis elegans. The results from this study revealed that miRNAs regulate tissue homeostasis, and that alternative polyadenylation and miRNA expression patterns modulate miRNA targeting at the tissue-specific level. 3) Explored the functional relevance of miRNA targeting to tissue-specific gene expression, where I found that miRNAs contribute to the biogenesis of mRNAs, through alternative splicing, by regulating tissue-specific expression of splicing factors. These results expand our understanding of the mechanisms that guide miRNA targeting and its effects on tissue-specific gene expression.
MiRNA-based gene regulation occurs in a tissue-specific manner and is implemented by an interplay of poorly understood and complex mechanisms, which control both the presence of the miRNAs and their targets. As a consequence, the precise contributions of miRNAs to gene regulation are not well known. The research presented in this thesis systematically explores the targets and effects of miRNA-based gene regulation in cell lines and tissues.
I hypothesize that miRNAs have distinct tissue-specific roles that contribute to the gene expression differences seen across tissues. To address this hypothesis and expand our understanding of miRNA-based gene regulation, 1) I developed the human 3'UTRome v1, a resource for studying post-transcriptional gene regulation. Using this resource, I explored the targets of two cancer-associated miRNAs miR-221 and let-7c. I identified novel targets of both these miRNAs, which present potential mechanisms by which they contribute to cancer. 2) Identified in vivo, tissue-specific targets in the intestine and body muscle of the model organism Caenorhabditis elegans. The results from this study revealed that miRNAs regulate tissue homeostasis, and that alternative polyadenylation and miRNA expression patterns modulate miRNA targeting at the tissue-specific level. 3) Explored the functional relevance of miRNA targeting to tissue-specific gene expression, where I found that miRNAs contribute to the biogenesis of mRNAs, through alternative splicing, by regulating tissue-specific expression of splicing factors. These results expand our understanding of the mechanisms that guide miRNA targeting and its effects on tissue-specific gene expression.
ContributorsKotagama, Kasuen Indrajith Bandara (Author) / Mangone, Marco (Thesis advisor) / LaBaer, Joshua (Committee member) / Newbern, Jason (Committee member) / Rawls, Alan (Committee member) / Arizona State University (Publisher)
Created2019
Description
The inherent risk in testing drugs has been hotly debated since the government first started regulating the drug industry in the early 1900s. Who can assume the risks associated with trying new pharmaceuticals is unclear when looked at through society's lens. In the mid twentieth century, the US Food and Drug Administration (FDA) published several guidance documents encouraging researchers to exclude women from early clinical drug research. The motivation to publish those documents and the subsequent guidance documents in which the FDA and other regulatory offices established their standpoints on women in drug research may have been connected to current events at the time. The problem of whether women should be involved in drug research is a question of who can assume risk and who is responsible for disseminating what specific kinds of information. The problem tends to be framed as one that juxtaposes the health of women and fetuses and sets their health as in opposition. That opposition, coupled with the inherent uncertainty in testing drugs, provides for a complex set of issues surrounding consent and access to information.
ContributorsMeek, Caroline Jane (Author) / Maienschein, Jane (Thesis director) / Brian, Jennifer (Committee member) / School of Life Sciences (Contributor) / Sanford School of Social and Family Dynamics (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
This study asks the question: does gender-based discrimination exists within Arizona State University's Army Reserve Officer Training Corps (ROTC), and if so, what are the effects of such discrimination? Within this study, discrimination is defined as: the treatment or consideration of, or making a distinction in favor of or against, a person or thing based on the group, class, or category to which that person or thing belongs, rather than on individual merit. The researcher predicted that this study would show that gender-based discrimination operates within the masculine military culture of Army ROTC at ASU, resulting from women's hyper-visibility and evidenced by their lack of positive recognition and disbelief in having a voice in the program. These expectations were based on background research claiming that the token status of women in military roles causes them to be more heavily scrutinized, and they consequentially try to attain success by adapting to the masculine military culture by which they are constantly measured. For the purposes of this study, success is defined as: the attainment of wealth, favor, or eminence . This study relies on exploratory interviews and an online survey conducted with male and female Army ROTC cadets of all grade levels at Arizona State University. The interviews and survey collected demographic information and perspectives on individual experiences to establish an understanding of privilege and marginalization within the program. These results do support the prediction that women in Army ROTC at ASU face discrimination based on their unique visibility and lack of positive recognition and voice in the program. Likewise, the survey results indicate that race also has a significant impact on one's experience in Army ROTC, which is discussed later in this study in regard to needs for future research. ASU Army ROTC includes approximately 100 cadets, and approximately 30-40 of those cadets participated in this study. Additionally, the University of Arizona and the Northern Arizona University Army ROTC programs were invited to participate in this study and declined to do so, which would have offered a greater sample population. Nonetheless, the results of this research will be useful for analysis and further discussion of gender-equality in Army ROTC at Arizona State University.
ContributorsAllemang, Lindsey Ann (Author) / Wood, Reed (Thesis director) / Switzer, Heather (Committee member) / School of Politics and Global Studies (Contributor) / School of Social Transformation (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Few studies have examined the correlations between individual characteristics and other popular forms of social media other than Facebook. This study explored the ways emerging adults use Instagram and Snapchat and examined the relationships between social media and individual characteristics. A sample of 393 participants were recruited from a large university in the Southwestern United States. The participants completed an online questionnaire that included a newly developed social media measure along with established measures that examined the individual characteristics of social comparison orientation, self-esteem, loneliness, contingent self-worth, narcissism, and life satisfaction. In the present study, more participants reported having an active Instagram account than an active Facebook or Snapchat account. Additionally, a higher number of participants also reported preferring Instagram and Snapchat compared to Facebook. Significant correlations were found between various individual characteristics and three aspects of social media use: overall time spent on social media, whether the individual felt that their time spent on social media was meaningful, and how the individual felt emotionally after comparing themselves to others' photos and posts. Potential explanations and implications of the results are discussed.
ContributorsArndorfer, Sydney (Author) / Field, Ryan (Thesis director) / Sechler, Casey (Committee member) / School of Community Resources and Development (Contributor) / Sanford School of Social and Family Dynamics (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Genocide studies have traditionally focused on the perpetrator’s intent to eradicate a particular identity-based group, using the Holocaust as their model and point of comparison. Although some aspects of the Holocaust were undoubtedly unique, recent scholars have sought to challenge the notion that it was a singular phenomenon. Instead, they draw attention to a recurring pattern of genocidal events throughout history by shifting the focus from intent to structure. One particular branch of scholars seeks to connect the ideology and tactics of imperialism with certain genocidal events. These anti-imperialist genocide scholars concede that their model cannot account for all genocides, but still claim that it creates meaningful connections between genocides committed by Western colonialist powers and those that have occurred in a neoimperialist world order shaped according to Western interests. The latter includes genocides in postcolonial states, which these scholars believe were shaped by the scars of their colonial past, as well as genocides in which imperial hegemons assisted local perpetrators. Imperialist and former colonial powers have contributed meaningfully to all of these kinds of genocides, yet their contributions have largely been ignored due to their own influence on the creation of the current international order. Incorporating the anti-imperialist perspective into the core doctrine of genocide studies may lead to breakthroughs in areas of related policy and practice, such as prevention and accountability.
ContributorsParker, Ashleigh Mae (Author) / Thies, Cameron (Thesis director) / Sivak, Henry (Committee member) / School of Politics and Global Studies (Contributor) / School of Social Transformation (Contributor) / Department of English (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Political polarization is the coalescence of political parties -- and the individuals of which parties are composed -- around opposing ends of the ideological spectrum. Political parties in the United States have always been divided, however, in recent years this division has only intensified. Recently, polarization has also wound its way to the Supreme Court and the nomination processes of justices to the Court. This paper examines how prevalent polarization in the Supreme Court nomination process has become by looking specifically at the failed nomination of Judge Merrick Garland and the confirmations of now-Justices Neil Gorsuch and Brett Kavanaugh. This is accomplished by comparing the ideologies and qualifications of the three most recent nominees to those of previous nominees, as well as analysing the ideological composition of the Senate at the times of the individual nominations.
ContributorsJoss, Jacob (Author) / Hoekstra, Valerie (Thesis director) / Critchlow, Donald (Committee member) / Computer Science and Engineering Program (Contributor) / School of Politics and Global Studies (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
As the U.S. reckons with the reality of sexual assault and harassment in the wake of the #MeToo movement, it is particularly important to consider sexual assault in the military, an institution that is a massive employer and the face of the U.S. abroad. Media coverage is a catalyst for change, and the nature and scope of coverage is indicative of public and political attitudes. This thesis uses both quantitative and qualitative data to analyze characteristics of military sexual assault cases that complicate media coverage and to identify strengths and weaknesses of the media's approach to such stories. On the quantitative side, it takes advantage of nearly 600 case reports of sexual assault from U.S. military bases in Japan that were categorized to identify themes such as disposition outcomes, alcohol involvement and victim participation in investigations. Qualitatively, this thesis includes interviews with military officials, victims' advocates, journalists and other stakeholders that help to create a more holistic understanding of how media cover military sexual assault. Notably, this thesis finds that a lack of public interest in the military, a lack of congruency between military and civilian systems, and a highly complex hierarchy that limits journalists' access to military sources and data all complicate coverage. Drawing from these conclusions, it recommends that the media avoid episodic reporting, focus on personalizing stories in an institutional context, embrace accountability journalism and dedicate resources to pursuing complex investigations. It also acknowledges the important role of non-traditional media in the future of information sharing on the topic of military sexual assault.
ContributorsArmstrong, Mia Anne (Author) / Warner, Carolyn (Thesis director) / Gilger, Kristin (Committee member) / Walter Cronkite School of Journalism and Mass Communication (Contributor) / School of Politics and Global Studies (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05