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Tracking The Progression Of Defects At The Neuromuscular Junction In Huntington's Disease, Katherine A. Trittschuh Jan 2023

Tracking The Progression Of Defects At The Neuromuscular Junction In Huntington's Disease, Katherine A. Trittschuh

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Huntington’s disease (HD) is a genetic disorder associated with progressive cognitive and motor decline. Recent studies in HD models suggest primary peripheral pathologies arise independent of changes in the central nervous system. Our lab found defects in skeletal muscle occurring early in the progression of disease in transgenic R6/2 HD mice, resulting in membrane hyperexcitability. Additionally, there is evidence of decreased quantal content in late-stage R6/2 mice. Here, we investigate pre-synaptic and post-synaptic function at single neuromuscular junctions (NMJ) to make direct comparisons of disease progression in the muscle membrane and motor nerve terminal. We hypothesize that muscle membrane defects …


Tracking The Progression Of Defects At The Neuromuscular Junction In Huntington's Disease, Katherine A. Trittschuh Jan 2023

Tracking The Progression Of Defects At The Neuromuscular Junction In Huntington's Disease, Katherine A. Trittschuh

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Huntington’s disease (HD) is a genetic disorder associated with progressive cognitive and motor decline. Recent studies in HD models suggest primary peripheral pathologies arise independent of changes in the central nervous system. Our lab found defects in skeletal muscle occurring early in the progression of disease in transgenic R6/2 HD mice, resulting in membrane hyperexcitability. Additionally, there is evidence of decreased quantal content in late-stage R6/2 mice. Here, we investigate pre-synaptic and post-synaptic function at single neuromuscular junctions (NMJ) to make direct comparisons of disease progression in the muscle membrane and motor nerve terminal. We hypothesize that muscle membrane defects …


The Impact Of Study Strategies On Academic Performance For Medical Students At Wright State University, Markia Black Jan 2023

The Impact Of Study Strategies On Academic Performance For Medical Students At Wright State University, Markia Black

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Studying plays an important role in the academic success of medical students. It is likely that ineffective study skills result in poor performances on required standardized exams. There is a concern for the lack of empirical data related to what study strategies are the most productive for medical students to practice. My goal is to 1) identify what study strategies students use in their pre-clinical years of medical school, 2) determine if these strategies impact students’ performance on Comprehensive Basic Science Exams and Step 1 exam, and 3) identify study methods that best support student achievement in the pre-clinical phase …


Microplastics In Wetlands Of West Central Ohio : Concentration And Distribution, Mitchell Link Jan 2023

Microplastics In Wetlands Of West Central Ohio : Concentration And Distribution, Mitchell Link

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Wetlands provide many valuable ecosystem services; however, an emerging global contaminant—microplastic (< 5 mm)—may be degrading this important resource. Few studies have extensively surveyed microplastic distribution in wetlands over a broad spatial area. Therefore, the goal of this study is to identify where microplastics are accumulating in wetlands, and whether there is any correlation between microplastic concentration and wetland quality. Soil samples were collected from 30 wetlands in west–central Ohio. Samples were physically separated, density separated, and digested. Average microplastic concentrations were 637 ± 494 items per kg soil per wetland. Higher quality wetlands are accumulating larger concentrations of microplastics. This relationship seems to be driven by greater accumulation of microplastics in forested wetlands than in wetlands surrounded by agriculture. There is no clear distribution pattern of microplastics within wetlands. These results provide insight into the role that wetlands have in association with microplastic accumulation.


To What Extent Do Non-Native Shrubs Support Higher Trophic Levels?, Ari Zakroff Jan 2023

To What Extent Do Non-Native Shrubs Support Higher Trophic Levels?, Ari Zakroff

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Invasive species threaten ecosystems and economies. Globally, biological invasions are estimated to have cost over $2.1 trillion since 1970. In Eastern North American woodlands, invasive plants are rapidly displacing natives. This is concerning, because invasive plants may not support the diverse and abundant arthropod communities essential to ecosystem function. Despite the conceptual understanding of invasive shrubs’ potential to transform forest communities, scant research has focused on the effect of invasive plants on higher trophic levels here in Ohio. To address this gap, I examined the diversity and abundance of arthropod communities, caterpillar performance, and caterpillar predation on two invasive shrubs, …


Environmental Toxicants And Human B Cells: Insights From Crispr Editing And Genomic Sequencing, Clayton Allex-Buckner Jan 2023

Environmental Toxicants And Human B Cells: Insights From Crispr Editing And Genomic Sequencing, Clayton Allex-Buckner

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The human immunoglobulin heavy chain gene locus (IGH) has two 3 prime regulatory regions (3’IGHRR), each containing three enhancers (hs3, hs1.2, hs4). In animal models, the 3’IghRR regulates IgH expression and class switch recombination (CSR) to different Ig isotypes. The 3’IGHRR hs1.2 enhancer in humans is polymorphic in that an invariant sequence (IS) can be repeated one to four times in tandem. The hs1.2 polymorphism is of interest due to its association with several human autoimmune disorders and its potential sensitivity to exogenous substances such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin). In mouse models, TCDD inhibits the hs1.2 enhancer and 3’IghRR …


To Determine The Role Of The Platelet Activating Factor - Receptor In Folfirinox Therapy-Mediated Microvesicles Particle Generation, Krishna Awasthi Jan 2023

To Determine The Role Of The Platelet Activating Factor - Receptor In Folfirinox Therapy-Mediated Microvesicles Particle Generation, Krishna Awasthi

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Given that Pancreatic cancer continues to be one of the primary causes of cancer-related death and that existing treatment options have a poor success rate, it is important to investigate the role of potential factor(s) involved in pancreatic cancer growth or diminishing the effectiveness of chemotherapeutic agents. An alternative regimen for pancreatic cancer treatment called FOLFIRINOX has shown to increase the survival rate and improve Eastern Cooperative Oncology Group (ECOG) performance status score among the pancreatic cancer patients. However, FOLFIRINOX therapy is associated with several side effects. Through mechanisms involving the secretion of microvesicle particles (MVP), studies, including ours have …


Regulation Of Cathepsin L Expression And Activity By Cell Confluence And The Circadian Clock, Prashant Gaikwad Jan 2023

Regulation Of Cathepsin L Expression And Activity By Cell Confluence And The Circadian Clock, Prashant Gaikwad

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Cathepsin L is a lysosomal cysteine protease that is encoded by the CTSL gene in humans. Previous results have shown that CTSL expression and activity towards the DNA repair protein XPA are elevated in lysates of confluent/quiescent HaCaT keratinocytes. Because other nuclear proteins, including 53BP1 and histone H3, have also been reported to be CTSL substrates under conditions of cell differentiation, senescence, or quiescence, CTSL expression and activity (cleavage) of multiple nuclear proteins was examined in lysates from HaCaT cells and other cell lines at various days after plating and cell confluency. Our study found that adding CTSL inhibitors to …


Regulation Of Erk3 By Kras Signalling And Its Role In The Growth Of Lung Adenocarcinoma (Luad) Cells, Shreya Akunapuram Jan 2023

Regulation Of Erk3 By Kras Signalling And Its Role In The Growth Of Lung Adenocarcinoma (Luad) Cells, Shreya Akunapuram

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Extracellular signal related kinase 3 (ERK3) is one of the atypical mitogen activated protein kinases (MAPK). It is expressed ubiquitously and plays a role in a variety of cellular processes, including cell growth and differentiation. ERK3’s role in promoting migration and invasion in various cancers has been well established. ERK3 is upregulated in non-small cell lung cancers (NSCLCs) and has been shown to promote NSCLC tumor growth and progression. However, the regulation of ERK3 in lung cancers remains largely unclear. A recent study indicates that ERK3 phosphorylation at S189, an indicator of ERK3 activity, is upregulated by KRAS in NSCLCs. …


Female Middle Aged Rats Showed Increased Recovery From A Focal Demyelination With Drug Combination : Changes In Dcx And Nfkb Suggest Increased Oligodendrocytes Production, Andrew James Smith Jan 2023

Female Middle Aged Rats Showed Increased Recovery From A Focal Demyelination With Drug Combination : Changes In Dcx And Nfkb Suggest Increased Oligodendrocytes Production, Andrew James Smith

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Neurodegenerative diseases such as multiple sclerosis affect millions of people around the globe, and promising treatments to counter its progress have been studied extensively. In our study, we used Dawley rats and tested them using the Montoya Staircase test to evaluate their ability to use their forelimbs. After training, surgery was performed using lysolecithin to induce focal demyelination on the rats. After the surgery a drug combination of fluoxetine, ibuprofen, and ascorbic acid was used on injured rats and they were then retested on the Montoya Staircase test. They were then sacrificed and were stained for doublecortin (DCX) and nuclear …


Periodic Paralysis : Pursuing A Protocol, Kirsten Denman Jan 2023

Periodic Paralysis : Pursuing A Protocol, Kirsten Denman

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Hypokalemic Periodic Paralysis is an autosomal dominant disease of skeletal muscle in which patients experience episodes of weakness. There is currently no highly effective therapy. A mouse model has been created to study the disease to better understand the physiological changes leading to weakness and to develop novel treatments. However, the work done with the mouse model has used ever-changing protocols and the data produced have been insufficient to answer key questions and bring treatments closer to clinical trials. I evaluated factors of temperature, insulin, potassium concentrations, and length of protocol or exercise, to develop a protocol that reproducibly triggers …


Heightened Levels Of Microvesicle Particles Resulting From Combination Of Ethanol And Thermal Burn Injury, Chad Alan Brewer Jan 2022

Heightened Levels Of Microvesicle Particles Resulting From Combination Of Ethanol And Thermal Burn Injury, Chad Alan Brewer

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Ethanol (EtOH), in combination with thermal burn injury, is a clinically significant problem resulting in an increase in morbidity and mortality due to acute multi-organ toxicity from excess systemic cytokine release. This intoxicated thermal burn affects close to 50% of the total numbers of hospital-admitted burn patients and currently has no standard treatment. However, using in vitro cellular and in vivo murine models, our group has provided data implicating the augmented production of the lipid mediator Platelet-activating factor (PAF) in keratinocytes in response to intoxicated thermal burn injury in the subsequent pathology. Of importance, our group has demonstrated that activation …


Microglia Distribution In The Lateral Ventricles Following Treatment Of Lysolecithin Model Of Multiple Sclerosis, Spencer James Wilson Jan 2022

Microglia Distribution In The Lateral Ventricles Following Treatment Of Lysolecithin Model Of Multiple Sclerosis, Spencer James Wilson

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Multiple sclerosis (MS) affects an estimated one million people in the US alone (Wallin et al., 2019). We modeled MS in rats using lysolecithin injection into the corpus callosum to diminish motor function unilaterally through demyelination, meanwhile treating the injury with Fluoxetine, Ibuprofen, and ascorbic acid (FIAA) to increase neurogenesis and oligodendrogenesis. Motor function was assessed using the Montoya Staircase test pre- and post-surgery. Motor capabilities recovered in the contralateral limb, but not in the ipsilateral, and recovery was not significantly affected by treatment. We identified microglia by CX3CR1 and examined its distribution in the adult neurogenic niche, the SVZ …


Replication Stress Induced By The Ribonucleotide Reductase Inhibitors Guanazole, Triapine, And Gemcitabine In Fission Yeast, Mashael Yahya A Alyahya Jan 2022

Replication Stress Induced By The Ribonucleotide Reductase Inhibitors Guanazole, Triapine, And Gemcitabine In Fission Yeast, Mashael Yahya A Alyahya

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Replication stress can be produced by various exogenous or endogenous factors that perturb the movement of replication forks. To overcome the stress, the cells provoke the DNA replication checkpoint to mobilize several pathways to protect the forks, maintain genome integrity, and promote cell survival. Defects in the replication checkpoint cause forks collapse, leading to chromosomal DNA damage or cell death. Although the replication checkpoint is crucial for genome integrity in all eukaryotes, the underlying mechanisms remains to be fully understood. To investigate the mechanisms of DRC, hydroxyurea (HU), an established inhibitor of ribonucleotide reductase (RNR), has been widely used in …


The Impact Of Sentiment And Misinformation Cycling Through The Social Media Platform, Twitter, During The Initial Phase Of The Covid-19 Vaccine Rollout, Emily Grace Burwell Jan 2022

The Impact Of Sentiment And Misinformation Cycling Through The Social Media Platform, Twitter, During The Initial Phase Of The Covid-19 Vaccine Rollout, Emily Grace Burwell

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This study assesses the underlying topics, sentiment, and types of information regarding COVID-19 vaccines on Twitter during the initiation of the vaccine rollout. Tweets about the COVID-19 vaccine were collected and the relevant tweets were then filtered out using a relevancy classifier. Latent Dirichlet Allocation (LDA) was used to uncover topics of discussion within the relevant tweets. The NRC lexicon was used to assess positive and negative sentiment within tweets. The type of information (information, misinformation, opinion, or question) in tweets was evaluated. The relevancy classifier resulted in a dataset of 210,657 relevant tweets. Eight topics provided the best representation …


Impaired Β-Cell Neogenesis In A Mouse Model Of Metabolic Syndrome, Modhi Abdullah Alshammari Jan 2022

Impaired Β-Cell Neogenesis In A Mouse Model Of Metabolic Syndrome, Modhi Abdullah Alshammari

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Pancreatic islet β-cell plays an essential role in insulin release and hence glucose homeostasis. The maintenance of glucose homeostasis depends on β-cell ability to cope with enough insulin to fulfill metabolic and physiological demands. Adequate insulin release is the result of highly complex and dynamic interplays between acute changes in β- cell electrical activity, exocytosis and chronic adaptations in cellular function, volume, mass and proliferation. All of this appears modulated, to some extent, by the functional presence of Slc12a2 symporters, also known as Na+K+2Cl– cotransporter-1 (Nkcc1), which accumulates intracellular Cl– above its electrochemical equilibrium. Recent studies from our laboratory showed …


Exploring The Host Range, Impacts, And Distribution Of Black Rot Disease On Alliaria Petiolata, Gabriela Ivette Harney-Davila Jan 2022

Exploring The Host Range, Impacts, And Distribution Of Black Rot Disease On Alliaria Petiolata, Gabriela Ivette Harney-Davila

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Garlic mustard is an invasive Eurasian biennial spreading in deciduous forests of North America. Garlic mustard plants in Ohio can be infected with a strain of Xanthomonas campestris, the causal agent of black rot disease in brassicas. I examined variation in susceptibility to X. campestris among garlic mustard populations, several native wild species, and agricultural crop varieties. Twenty-four garlic mustard populations were universally susceptible to X. campestris, though disease severity varied. Cardamine concatenata and Cardamine diphylla were susceptible but can phenologically escape infection in the field. Of the 14 agricultural crops tested, three cultivars (Raphanus sativus, Brassica rapa var. Rapa …


Evaluation Of A Monosynaptic Spinal Circuit In Multiple Mouse Models Of Amyotrophic Lateral Sclerosis, Maura A. Curran Jan 2022

Evaluation Of A Monosynaptic Spinal Circuit In Multiple Mouse Models Of Amyotrophic Lateral Sclerosis, Maura A. Curran

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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. To date, there are no significant disease-modifying treatments, and one limiting factor in treatment is the amount of time it takes for a patient to receive a diagnosis of ALS. This study examined multiple mouse models before symptom onset to help identify early changes in a reflex circuit of ALS mice. Dorsal root stimulation of the sacral spinal cord in multiple models ALS mouse models showed changes in the resulting ventral root compound action potential amplitude, latency, and ability to maintain synaptic depression. These data also suggest that a mouse model …


Community-Level Effects Of A Widescale Reduction In White-Tailed Deer (Odocoileus Virginianus) Density, Mariah Slaughter Jan 2022

Community-Level Effects Of A Widescale Reduction In White-Tailed Deer (Odocoileus Virginianus) Density, Mariah Slaughter

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The prolonged overabundance of white-tailed deer (Odocoileus virginianus) throughout the deciduous forests of eastern North America has resulted in widespread changes in the understory community. Studies have demonstrated that the exclusion of deer can allow some aspects of the understory to recover, but there are strong time-lags for deer-preferred species. Additionally, these exclosures only test the presence/absence of deer, which is not a feasible management option or desirable as deer are a part of the community. Here I evaluate how large-scale deer density manipulations within the Kinzua Quality Deer Cooperative of Pennsylvania affected understory vegetation communities. Using data from six …


Instability And Extrachromosomal Circular Dna Formation At Microsatellites And Unstable Dna Sequences, Matilyn M. Shanahan Jan 2022

Instability And Extrachromosomal Circular Dna Formation At Microsatellites And Unstable Dna Sequences, Matilyn M. Shanahan

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We have previously documented our evidence of genetic instabilities at the (Pu/Py)78 and (ATTCT)47 sequences and our reasoning for identifying break-induced replication (BIR) as the mode of repair responsible for the mutations in the DNA flanking the unstable inserts. Now, as our lab investigates the protein mechanisms at play in the BIR pathway taking place at these sites, we are also expanding our knowledge of how this mechanism extends into the pathways responsible for forming extrachromosomal circular DNA (eccDNA) molecules. We have documented the phenomena posed as the driving factors for eccDNA formation in our systems containing (Pu/Py)78 and (ATTCT)47. …


Genomic Instability At A Polypurine/Polypyrimidine Repeat Sequence, Nathen S. Zavada Jan 2022

Genomic Instability At A Polypurine/Polypyrimidine Repeat Sequence, Nathen S. Zavada

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Microsatellite repeat sequences have been shown to induce replication stalling, fork collapse, double-strand breaks (DSBs), and possibly stimulate break-induced replication. In this study we use a dual-fluorescent HeLa model that is designed to monitor recombination at an ectopic site through use of flow cytometry and inverse PCR with a microsatellite in the lagging strand for DNA synthesis. To test the stability of the 78 bp polypurine/pyrimidine repeat from the PDK1 locus, we subjected cells to replication stress drugs designed to induce DSBs and measure break-induced replication (BIR). The study revealed that polypurine repeat cells undergo endogenous stress contributing to instability …


Ahr-Mediated Transcriptional Regulation Of The Human Immunoglobulin Hs1.2 Enhancer, Sydney White Jan 2022

Ahr-Mediated Transcriptional Regulation Of The Human Immunoglobulin Hs1.2 Enhancer, Sydney White

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The 3'IGHRR is thought to be responsible for the transcription of the immunoglobulin heavy chain (IGH) gene locus, which is essential for the production of antibodies. The human 3’IGHRR, which is duplicated in humans, contains the hs3, hs4, and hs1.2 enhancers. Additionally, the hs1.2 enhancer is polymorphic in humans and consists of a 53 bp invariant sequence that can be repeated one to four times. Previous experiments in a mouse and human B-cell line model have shown that the high affinity AhR ligand and environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can induce hs1.2 enhancer activity in an AhR-dependent manner. The AhR is …


Use Of Forelimb Asymmetry In The Analysis Of Cns Recovery From A Demyelination Event, Joseph C. Hinkle Jan 2022

Use Of Forelimb Asymmetry In The Analysis Of Cns Recovery From A Demyelination Event, Joseph C. Hinkle

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Using forelimb asymmetry analysis along with Montoya Staircase methodology we tested how a fluoxetine simvastatin ascorbic acid drug cocktail would affect recovery from a demyelinating event in a rat model, with the hypothesis that if administered then it would help female recovery but hinder male recovery. It was found that a fluoxetine simvastatin and ascorbic acid drug cocktail did not significantly enhance recovery from a demyelination model injury in female rats, and that the same drug cocktail significantly slowed male rat recovery from the same type of injury. It was also apparent that the more effective methodology for investigating this …


Ifn-Γ Increases The Expression Of Sars-Cov-2 Receptors On Vero E6 Cells, Bindu Madhavi Madabattula Jan 2022

Ifn-Γ Increases The Expression Of Sars-Cov-2 Receptors On Vero E6 Cells, Bindu Madhavi Madabattula

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Respiratory epithelial cells are the initial target for SARS-CoV-2 infection. IFN-γ is known to increase the expression of ACE-2, an initial receptor for SARS-CoV-2, on epithelial cells. This study focuses on examining the effect of IFN-γ for ACE-2, TMPRSS2, and neuropilin-1 on Vero E6 cells using two immunofluorescence methods, namely, direct (membrane) fluorescence method and Cytation5 method. Direct fluorescence was determined using an Accu-Scope and ImageJ analysis. Using this method, significance (p<0.023) was observed only for ACE-2 when Vero E6 cells were treated with IFN-γ. Cytation5 fluorescence was determined using a Bio-tek Cytation5 plate reader. The results showed that IFN-γ significantly increased (p<0.001) the expression of ACE-2, neuropilin-1, and TMPRSS2. These results indicate Cytation5 is a more sensitive method for determining the expression of receptors on Vero E6 cells. The elevated levels of SARS-CoV-2 receptors expression resulting from IFN-γ treatment makes the epithelial cells more susceptible targets of SARS-CoV-2 infection. IFN-γ is most likely provided by innate immune cells in the initial COVID-19 infection, consequently contributing to the severity of disease.


Expression Of Sars Cov2 Receptors Influenced Upon Cytokine Polarizations (Il-4 And Ifnγ) In Hemangioendothelioma Cells, Chandra Lekha Koopari Jan 2022

Expression Of Sars Cov2 Receptors Influenced Upon Cytokine Polarizations (Il-4 And Ifnγ) In Hemangioendothelioma Cells, Chandra Lekha Koopari

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Endothelial cells are distinct multifunctional cells with essential metabolic and synthetic roles along with their ability to function as selective permeability barrier. Endothelial cells (ECs), the major component of blood vessels, essentially interact directly yet differently with inflammatory cytokines. ECs are well recognized to be polarized cells, but little is known about the potential function of inflammatory mediators. Covid 19 may have long-term health effects on par with chronic illnesses. Vascular inflammatory disease and coagulopathy linked to COVID-19 are exacerbated by endothelial cell (EC) dysfunction. SARS-CoV-2 enters the host cell through the Angiotensin Converting Enzyme 2 (ACE2) receptor and primes …


Chemosensitivity Of Locus Coeruleus Neurons Decreases With Postnatal Development, Yasmeen Samar Jan 2022

Chemosensitivity Of Locus Coeruleus Neurons Decreases With Postnatal Development, Yasmeen Samar

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The locus coeruleus (LC) is a chemosensory area partially responsible for ventilation. Control over ventilation relies on inter-network communication via chemical and electrical synapses and chemosensitivity to CO2/pH. As the LC develops, it’s neural control over ventilation changes. This study investigates the chemosensitivity of the locus coeruleus over the course of development in postnatal rats. We hypothesize that 1) the CO2 sensitivity of LC neurons is highest at birth and declines with development 2) LC neurons are intrinsically chemosensitive and this chemosensitivity does not decrease with development and 3) the presence of gap junctions is highest at the beginning of …


Modeling Als-Associated Matrin-3 Toxicity In Yeast, Widad El-Zein Jan 2022

Modeling Als-Associated Matrin-3 Toxicity In Yeast, Widad El-Zein

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ALS is a neurodegenerative disease characterized by degeneration of upper and lower motor neurons in the brain and spinal cord leading to progressive paralysis and ultimately death. Perturbations in RNA metabolism and RNA binding proteins have emerged as underlying defects in ALS pathogenesis. Matrin-3 is a multifunctional RNA binding protein that has been linked to familial and sporadic ALS. Matrin-3 is normally found in the nucleus, but mutations in the gene cause mislocalization of the protein from the nucleus into the cytoplasm of neuronal cells where it forms protein aggregates. In this study, we show that over-expressing human MATR3 in …


Reconstruction Of Gut Microbiome Via Intermittent Feeding, Kourtney Sprague Jan 2022

Reconstruction Of Gut Microbiome Via Intermittent Feeding, Kourtney Sprague

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The benefits of intermittent fasting have been studied across many facets of health. It is known that physiologically fasting results in a metabolic switch from liver-derived glucose to adipose cell derived ketones to be used as energy and signaling molecules. Fasting down-regulates inflammation, increases expression of antioxidant defenses, and activates pathways for DNA repair and autophagy. While fasting or intermittent feeding effects on host physiology have been identified, the relationship between fasting and gut microbiome is not as well known. In times of gut rest, resident microbes undergo detoxication and motility, and in times of activity, gut microbes undergo DNA …


The Role Of Pi4kb In Cellular Localization Of Small Gtpases, Parisa Sadrpour Jan 2022

The Role Of Pi4kb In Cellular Localization Of Small Gtpases, Parisa Sadrpour

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Constitutively active oncogenic mutant K-Ras is one the principal contributors to human cancers including 90% of pancreatic, 50% of colorectal and 32% of non-small cell lung cancers. However, except for K-Ras G12C oncogenic mutant, which only presents in about 13% of non-small cell lung cancer patients, there is no anti-K-Ras therapy for a considerable subset of K-Ras mutations in human tumors, reflecting challenges for targeting oncogenic K-Ras activity. K-Ras is a membrane-bound small GTPase; when active, it triggers multiple signaling pathways regulating a variety of key cellular functions such as cell growth, proliferation and survival. To initiate these signaling cascades, …


Microsatellites And Their Association With Break Induced Replication, French J. Damewood Iv Jan 2021

Microsatellites And Their Association With Break Induced Replication, French J. Damewood Iv

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To study microsatellites instability and their repair pathways a dual fluorescent (DF2) and selectable (ganciclovir sensitive/ thymidine kinase (TK) expressing) cell system was assayed using replication fork stalling agents hydroxyurea and telomestatin. These cell lines carried ectopically integrated microsatellites derived from the Dystrophia Myotonica Protein Kinase (DMPK) gene ((CTG)102 microsatellite), or an 88 bp polypurine/ polypyrimidine (Pu/Py) repeat from the PKD-1 locus, inserted into a FLP recombinase target site. These microsatellites form non-B DNA structures in -vivo and in-vitro causing replication fork stalling and double strand breaks. DF2 myc (CTG)102 -TK cells treated with hydroxyurea were assayed for mutagenesis of …