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- All Subjects: Cancer
- Creators: Barrett, The Honors College
- Member of: Barrett, The Honors College Thesis/Creative Project Collection
- Resource Type: Text
Description
Glioblastoma multiforme is associated with a very low survival rate and is recognized as the most vicious form of intracranial cancer. The Akt gene pathway has three different isoforms, each of which has a different role in the tumors of GBM. Preliminary data suggests that Akt3 may work to decrease tumorigenicity. A produced image that visualizes the subcellular localization of Akt3 led the author to believe that Akt3 may reduce tumorigenicity by decreasing genomic instability caused by the cancer. To explore this, flow cytometry was performed on GBM cell lines with Akt3v1 over-expression, Akt3v2 over-expression, and a control glioma cell line.
ContributorsGhorayeb, Antoine (Author) / Neisewander, Janet (Thesis director) / Diehnelt, Chris (Committee member) / Moussallem, Suzan (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2012-12
Description
The primary channel responsible for cold thermo-transduction in mammals is the transient receptor potential melastatin 8 (TRPM8) channel. TRPM8 is a polymodal, nonselective cation channel with an activation that is dependent on a variety of signals, including the membrane potential, calcium concentration, temperature, and ligands such as menthol. Mathematical modeling provides valuable insight into biochemical phenomena, such as the activity of these channels, which are difficult to observe experimentally. Here, we propose a TRPM8 gating model, represented as a system of ordinary differential equations with menthol, calcium, voltage, and temperature dependencies. We use voltage-clamp data from transfected HEK293 cells in the presence of menthol to create a menthol-dependent voltage shift of activation. We fit the parameters of the TRPM8 gating model to replicate experimental TRPM8 transfected HEK293 cell voltage clamp electrophysiology data using a genetic algorithm. Using k-means clustering, we note eight clusters within 110 total parameter sets consisting of parameter solutions that provide a good fit to the experimental data. We then replicate novel fixed-voltage temperature ramp and fixed-temperature voltage ramp experimental data, demonstrating that our model can replicate the dynamic behaviors of TRPM8. With this TRPM8 gating model, we analyze the various parameter sets obtained from the genetic algorithm and find that different parameter combinations of calcium decay, calcium voltage shift of activation, and temperature sensitivity are able to match static voltage clamp data although differ in their effects on hysteresis and maximal current within prolonged temperature ramp simulations.
ContributorsDudebout, Eric (Author) / Crook, Sharon (Thesis director) / Van Horn, Wade (Committee member) / Barrett, The Honors College (Contributor) / School of Molecular Sciences (Contributor)
Created2024-05
Description
Alzheimer’s disease (AD) is characterized by memory decline and dementia, and conclusively diagnosed postmortem from tangles and plaques. Plaques come from β-amyloid protein (Aβ), which damages the brain, especially the hippocampus, a structure vital for memory formation. However, whether plaques and tangles cause or result from AD is unclear. Our goal was to use a preclinical AD model to identify the early stages of cognitive dysfunction before AD becomes severe to enhance targeted interventions. We used a transgenic mouse (APP/PS1) that slowly develops plaques, with minimal expression around 5-6 months (young adult) with more expression by 12 months (middle-age). Our aim was to determine whether young adult mice would show cognitive symptomatology that could be used as a future metric for targeted treatment before AD advances further. We had three independent variables: Sex (Male, Female), Age (5-6, 8-10 months) and Genotype (APP/PS1, wildtype, WT). We used behavioral assays to assess spatial memory (hippocampal function), working memory (prefrontal cortex function), and anxiety (amygdala function). For my honor’s thesis, I focused on using the Morris Water Maze (MWM) to assess hippocampal function and the Open Field (OF) to assess anxiety and locomotion. In MWM, all groups were given four trials/day for four days with a probe trial to assess strategy immediately after the last trial on day 4. All groups swam shorter distances across days to show they were learning and revealed sex differences. The APP/PS1 males (young and old) learned the task more slowly than their WT male counterparts, but were using spatial strategies as demonstrated by the probe trial. For the females, all groups learned the task similarly, but the probe trial revealed that the APP/PS1 females (young and old) were using non-spatial strategies. Moreover, the males significantly swam shorter distances than the females, learning faster. The use of the visible platform task confirmed that the mice were capable of performing the swim task. For the OF, mice were placed in a square arena and given 10 minutes to explore and found sex differences in anxiety profile. All the female mice expressed similar anxiety profiles, whereas the APP/PS1 males had higher anxiety profiles than their WT males counterparts. These results revealed that there were sex-specific differences in cognition and anxiety profiles in the APP/PS1 mouse model. This indicates that individual characteristics are important to consider when using tailored interventions. In summary, these findings emphasize the potential for early detection and targeted treatment strategies to help mitigate AD progression.
ContributorsMontero, Martina Anne (Author) / Conrad, Cheryl (Thesis director) / Gewirtz, Jonathan (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor)
Created2024-05
Description
Immediate early genes (IEGs) are the first set of genes to be transcribed in a cell in response to stimuli; their expression is quick and is not protein synthesis dependent. Neurons are activated in response to external stimuli, causing a rapid increase in IEG expression in the brain. IEG proteins go on to affect fundamental neurobiological processes that are known to be dysfunctional in patients with psychiatric disorders, and therefore IEGs have been connected to the pathogenesis of schizophrenia. Early growth response (Egr) genes are immediate early gene transcription factors (IEG-TFs) that are expressed in response to an altered environment. The IEG-TFs, early growth response 1 (EGR1) and early growth response 3 (EGR3) are necessary for processes such as memory and synaptic plasticity; lack of function in these genes causes dysfunction or disruption of these processes. We wanted to observe if increasing the function of Egrs by overexpressing them will lead to improved memory. To help further understand how behavior is affected by the overexpression (O/E) of Egr1 in response to stimuli, the AAV-ESARE-Egr1 virus was developed to be injected in the hippocampus of mice. In the hippocampus of wild-type (WT) mice, cells that are active endogenously express Egr1. The virus was created using the synaptic activity-response element (SARE), an element discovered on the promoter of the IEG activity-regulated cytoskeleton-associated (Arc) gene by our collaborators in Japan. Using an “enhanced” form of SARE (ESARE), our newly created virus acts to overexpress Egr1 only in response to activity in the hippocampus; we can then observe if the behavioral processes associated with Egr1 will improve. First, this project aims to validate that the AAV-ESARE-Egr1 virus is increasing Egr1 expression in the active hippocampal dentate gyrus (DG) granule cells of WT mice, and only in response to activity. The activity is in the form of a physiological stimulus, environmental enrichment (EE) and a non-physiological stimulus, electroconvulsive seizures (ECS). After confirming these characteristics of AAV-ESARE-Egr1 we can then use it to observe if EGR1 O/E improves the memory of mice.
ContributorsWallace, Sophie (Author) / Lewis, Candace (Thesis director) / Gallitano, Amelia (Committee member) / Barrett, The Honors College (Contributor) / College of Integrative Sciences and Arts (Contributor)
Created2024-05
Description
Objective: Previous studies have expressed that individuals with dyslexia may be hypersensitive to stimuli when compared to typical individuals, creating the neural noise hypothesis. This study uses electroencephalogram (EEG) to look at participants' mismatch negativity (MMN) response to the distinctive English phoneme /æ/ and an allophone of the phoneme /æ/, measuring their reaction to the variation between these two sounds.
Methods: Twenty-two adults, fourteen with dyslexia and 8 controls partook in an auditory oddball EEG experiment measuring MMN with the amplitudes and latencies being collected.
Results: Five participants demonstrated a large MMN response, four of which were in the dyslexic group. These participants’ results indicate an increased sensitivity to phonetic differences.
Significance: Understanding how some individuals with dyslexia process phonetic differences may be key to comprehending how a dyslexic subtype takes in auditory information.
ContributorsOvaska, Madeline (Author) / Peter, Beate (Thesis director) / Daliri, Ayoub (Committee member) / Kim, Yookyung (Committee member) / Barrett, The Honors College (Contributor) / College of Integrative Sciences and Arts (Contributor) / Department of Psychology (Contributor)
Created2024-05