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Egr3 is an immediate early gene transcription factor that shows genetic association with schizophrenia, and is found in decreased levels in the brains of schizophrenia patients. Schizophrenia patients also exhibit cognitive and memory deficits, both of which Egr3 has been shown to play a crucial role in. Additionally, high levels

Egr3 is an immediate early gene transcription factor that shows genetic association with schizophrenia, and is found in decreased levels in the brains of schizophrenia patients. Schizophrenia patients also exhibit cognitive and memory deficits, both of which Egr3 has been shown to play a crucial role in. Additionally, high levels of DNA damage are found in the brains of schizophrenia patients. A recent study has shown that DNA damage occurs as a result of normal physiological activity in neurons and is required for induction of gene expression of a subset of early response genes. Also, failure to repair this damage can lead to gene expression in a constitutive switched on state. Egr3 knockout (Egr3-/-) mice show deficits in hippocampal synaptic plasticity and memory. We were interested in characterizing downstream targets of EGR3 in the hippocampus. To determine these targets, electroconvulsive seizure (ECS) was carried out in Egr3 -/- versus wild type (WT) mice, and a microarray study was first done in our lab. ECS maximally stimulates Egr3 expression and we hypothesized that there would be gene targets that are differentially expressed between Egr3 -/- and WT mice that had been subjected to ECS. Two separate analyses of the microarray yielded 65 common genes that were determined as being differentially expressed between WT and Egr3 -/- mice after ECS. Further Ingenuity Pathway Analysis of these 65 genes indicated the Gadd45 signaling pathway to be the top canonical pathway, with the top four pathways all being associated with DNA damage or DNA repair. A literature survey was conducted for these 65 genes and their associated pathways, and 12 of the 65 genes were found to be involved in DNA damage response and/or DNA repair. Validation of differential expression was then conducted for each of the 12 genes, in both the original male cohort used for microarray studies and an additional female cohort of mice. 7 of these genes validated through quantitative real time PCR (qRT-PCR) in the original male cohort used for the microarray study, and 4 validated in both the original male cohort and an independent female cohort. Bioinformatics analysis yielded predicted EGR3 binding sites in promoters of these 12 genes, validating their role as potential transcription targets of EGR3. These data reveal EGR3 to be a novel regulator of DNA repair. Further studies will be needed to characterize the role of Egr3 in repairing DNA damage.
ContributorsBarkatullah, Arhem Fatima (Author) / Newbern, Jason (Thesis director) / Gallitano, Amelia (Committee member) / Marballi, Ketan (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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"No civil discourse, no cooperation; misinformation, mistruth." These were the words of former Facebook Vice President Chamath Palihapitiya who publicly expressed his regret in a 2017 interview over his role in co-creating Facebook. Palihapitiya shared that social media is ripping apart the social fabric of society and he also sounded

"No civil discourse, no cooperation; misinformation, mistruth." These were the words of former Facebook Vice President Chamath Palihapitiya who publicly expressed his regret in a 2017 interview over his role in co-creating Facebook. Palihapitiya shared that social media is ripping apart the social fabric of society and he also sounded the alarm regarding social media’s unavoidable global impact. He is only one of social media’s countless critics. The more disturbing issue resides in the empirical evidence supporting such notions. At least 95% of adolescents own a smartphone and spend an average time of two to four hours a day on social media. Moreover, 91% of 16-24-year-olds use social media, yet youth rate Instagram, Facebook, and Twitter as the worst social media platforms. However, the social, clinical, and neurodevelopment ramifications of using social media regularly are only beginning to emerge in research. Early research findings show that social media platforms trigger anxiety, depression, low self-esteem, and other negative mental health effects. These negative mental health symptoms are commonly reported by individuals from of 18-25-years old, a unique period of human development known as emerging adulthood. Although emerging adulthood is characterized by identity exploration, unbounded optimism, and freedom from most responsibilities, it also serves as a high-risk period for the onset of most psychological disorders. Despite social media’s adverse impacts, it retains its utility as it facilitates identity exploration and virtual socialization for emerging adults. Investigating the “user-centered” design and neuroscience underlying social media platforms can help reveal, and potentially mitigate, the onset of negative mental health consequences among emerging adults. Effectively deconstructing the Facebook, Twitter, and Instagram (i.e., hereafter referred to as “The Big Three”) will require an extensive analysis into common features across platforms. A few examples of these design features include: like and reaction counters, perpetual news feeds, and omnipresent banners and notifications surrounding the user’s viewport. Such social media features are inherently designed to stimulate specific neurotransmitters and hormones such as dopamine, serotonin, and cortisol. Identifying such predacious social media features that unknowingly manipulate and highjack emerging adults’ brain chemistry will serve as a first step in mitigating the negative mental health effects of today’s social media platforms. A second concrete step will involve altering or eliminating said features by creating a social media platform that supports and even enhances mental well-being.

ContributorsGupta, Anay (Author) / Flores, Valerie (Thesis director) / Carrasquilla, Christina (Committee member) / Barnett, Jessica (Committee member) / The Sidney Poitier New American Film School (Contributor) / Computer Science and Engineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description
The Barrett Honors College website contains a lot of information that isn’t easily accessible by Honors Students. Many honors students have trouble finding the correct information they need. Important information is scattered all over the website making it difficult for honors students to find and understand the information they need.

The Barrett Honors College website contains a lot of information that isn’t easily accessible by Honors Students. Many honors students have trouble finding the correct information they need. Important information is scattered all over the website making it difficult for honors students to find and understand the information they need. One example of this is the requirements for Lower and Upper Division credit. This website displays the upper and lower division credit needed for a student to graduate from the honors college via a noninteractive flowchart. Many high school seniors find it difficult to understand the mundane flowchart outlining the required honors credit that is required for graduating from Barrett at Arizona State University. Also, it is confusing for many transfer students with unique circumstances to determine the necessary requirements for them to graduate as a Barrett student.
These difficult flowcharts and confusing websites have a huge impact on a student’s ability to adequately receive the information they need and, in the end, can have a negative impact on their ultimate decision when deciding if Barrett is right for them. A better user experience can be a more effective way of displaying information to students. A better design that allows to user more interaction would allow for the user to better understand the information they are presented. Instead of a monotone flowchart displaying the requirements necessary to graduate with honors status, A web application where a user can input their information and get an output of the necessary requirements tailored to the unique circumstance would be more informative, useful, and easier to use. The web app would take information such as a student’s year, whether it be an incoming freshman or transfer student, and their current and previous course credit to determine the specific number of honors credits, The Human Event courses, and Thesis project required for this user to complete the requirements for Barrett Honors College. This application would give the user a better understanding of what is required of them and in turn lead to a better user experience.
ContributorsGandhe, Nikhil (Author) / Menees, Jodi (Thesis director) / Barnett, Jessica (Committee member) / Davis, Jonathan (Committee member) / Computer Science and Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
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Description
Immediate early genes (IEGs) are rapidly activated in response to an environmental stimulus, and most code for transcription factors that mediate processes of synaptic plasticity, learning, and memory. EGR3, an immediate early gene transcription factor, is a mediator of biological processes that are disrupted in patients with schizophrenia (SCZ). A

Immediate early genes (IEGs) are rapidly activated in response to an environmental stimulus, and most code for transcription factors that mediate processes of synaptic plasticity, learning, and memory. EGR3, an immediate early gene transcription factor, is a mediator of biological processes that are disrupted in patients with schizophrenia (SCZ). A microarray experiment conducted by our lab revealed that Egr3 also regulates genes involved in DNA damage response. A recent study revealed that physiological neuronal activity results in the formation of DNA double-stranded breaks (DSBs) in the promoters of IEGs. Additionally, they showed that these DSBs are essential for inducing the expression of IEGs, and failure to repair these DSBs results in the persistent expression of IEGs. We hypothesize that Egr3 plays a role in repairing activity- induced DNA DSBs, and mice lacking Egr3 should have an abnormal accumulation of these DSBs. Before proceeding with that experiment, we conducted a preliminary investigation to determine if electroconvulsive stimulation (ECS) is a reliable method of inducing activity- dependent DNA damage, and to measure this DNA damage in three subregions of the hippocampus: CA1, CA3, and dentate gyrus (DG). We asked the question, are levels of DNA DSBs different between these hippocampal subregions in animals at baseline and following electroconvulsive stimulation (ECS)? To answer this question, we quantified γ-H2AX, a biomarker of DNA DSBs, in the hippocampal subregions of wildtype mice. Due to technical errors and small sample size, we were unable to substantiate our preliminary findings. Despite these shortcomings, our experimental design can be modified in future studies that investigate the role of Egr3 in activity-induced DNA damage repair.
ContributorsKhoshaba, Rami Samuel (Author) / Newbern, Jason (Thesis director) / Gallitano, Amelia (Committee member) / Marballi, Ketan (Committee member) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
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Description
Damage to DNA can affect the genes it encodes; if this damage is not repaired, abnormal proteins may be produced and cellular functions may be disturbed. DNA damage has been implicated in the initiation and progression of a variety of diseases. Conversely, DNA damage has also been discovered to contribute

Damage to DNA can affect the genes it encodes; if this damage is not repaired, abnormal proteins may be produced and cellular functions may be disturbed. DNA damage has been implicated in the initiation and progression of a variety of diseases. Conversely, DNA damage has also been discovered to contribute to beneficial biological processes. Madabhushi and colleagues (2015) determined that activity-dependent DNA double strand breaks (DSBs) in the promoter region of immediate early genes (IEGs) induced their expression. EGR3 is an IEG transcription factor which regulates the expression of growth factors and synaptic plasticity-associated genes. In a previously conducted microarray experiment, it was revealed that EGR3 regulates the expression of genes associated with DNA repair such as Cenpa and Nr4a2. These findings inspired us to investigate if EGR3 affects DNA repair in vivo. Before conducting this experiment, we sought to standardize and optimize a method of inducing DNA damage in the hippocampus. Electroconvulsive stimulation (ECS) is utilized to induce neuronal activity. Since neuronal activity leads to the formation of DNA DSBs, we theorized that ECS could be used to induce DNA DSBs in the hippocampus. We predicted that mice that receive ECS would have more DNA DSBs than those that receive the sham treatment. Gamma H2AX, a biomarker for DNA damage, was utilized to quantify DNA DSBs. Gamma H2AX expression in the dentate gyrus, CA1 and CA3 regions of the hippocampus was compared between mice that received the sham treatment and mice that received ECS. Mice that received ECS were sacrificed either 1 or 2 hours post-administration, constituting treatment conditions of 1 hr post-ECS and 2 hrs post-ECS. Our results suggest that ECS has a statistically significant effect exclusively in the CA1 region of the hippocampus. However, our analyses may have been limited due to sample size. A power analysis was conducted, and the results suggest that a sample size of n=4 mice will be sufficient to detect significant differences across treatments in all three regions of the hippocampus. Ultimately, future studies with an increased sample size will need to be conducted to conclusively assess the use of ECS to induce DNA damage within the hippocampus.
ContributorsAden, Aisha Abubakar (Author) / Newbern, Jason (Thesis director) / Gallitano, Amelia (Thesis director) / Marballi, Ketan (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05