Stander Symposium Projects

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  The Promise of Justice: Are Public and Private Defense Equal?

  Alicia A Linzmeier

  This thesis will attempt to uncover whether or not public defense lawyers and private defense lawyers achieve the same or similar results for their clients facing serious felony charges in southwestern Ohio. The outcomes of interest are conviction rates, guilty plea rates, incarceration rates, and sentence lengths. Though people facing equally serious charges should receive roughly equal outcomes, this is not always the case. Existing literature suggests that some of the differences could be dependent on the type of lawyer that a defendant has, or whether or not he or she can afford to pay for his or her own representation. Other variables that could have an influence, such as age, gender, race, and number of prior felony convictions, will be controlled for in order to isolate the impact that representation has. This thesis examines whether the differences in outcome manifest themselves in three counties in southwestern Ohio by studying unclassified and first degree felony cases that have been filed since January 1, 2000.

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  The RASSO - A Robotic Assistant for Surgical LaparoScopic Operations

  Sean Patrick Duffin

  The Rasso robot is a biomimetic robot expected to be used in place of standard laproscopic surgery. Being inserted through a 3-4 cm incision, the robot is designed to navigate along the top of the abdominal wall. This is made possible due to the stomach being inflated by a gas throughout the surgery. The Robot, having pads attached to its legs that mimic a gecko's limbs, allow for the robot to adhere itself upside down to the wall of the inflated stomach. The micro-structure of this material allows for adhesion to a wet surface just as a gecko's would. Utilizing a peeling motion to detract the legs, the robot is capable of moving across the surface without dropping towards the surgical area. It is hoped that eventually laproscopic tools can be attached to the robot that will allow this surgery to be performed remotely. My contribution specifically involves the introduction of a new kinematic design that allows for improved movement along the abdominal wall. Within that redesign I also am working towards improving the necessary peeling motion of the gecko-like material so as to minimize reactionary forces acting on the robot.

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  The Regulatory Role of Pravastatin™ in the Venous Shear Stress Dependent Induction of Aquaporin 1 Protein Expression in Human Umbilical Vein Endothelial Cells in vitro.

  Raphael J Crum

  Background: Aquaporins (AQPs) are transmembrane water channels that facilitate osmotically-driven water flux. AQP1 is expressed in vascular endothelium. AQP1 protein abundance is enhanced in cultured human umbilical vein endothelial cells (HUVECs) in response to fluid shear stress. The cholesterol-lowering statin drugs have been shown to regulate the expression of specific AQPs by altering their abundance and/or subcellular localization. Therefore, it is hypothesized that AQP1 may function as a component of the mechanosensory complex in endothelial cells, and therefore, is subject to shear-stress induced gene regulation and modulation of expression by statins. Methods: HUVECs were cultured under static (0 dynes/cm2) and venous fluid shear stress (6 dynes/cm2) in the presence or absence of 5 µM Pravastatin™. Fluorescent immunocytochemistry was used to detect AQP1 protein expression. Images were captured using confocal laser scanning microscopy. Mean fluorescent intensity (in arbitrary units) of AQP1immunofluorescence was determined using ImageJ software, and normalized to control conditions (time zero, static culture with no Pravastatin™). 25-30 cells from two independent experiments were analyzed for each experimental condition. Results: AQP1 immunofluorescence increased 1.3-fold (p<0.05) after 24 hours, and 1.7-fold (p<0.05) after 48 hours in cells cultured under venous fluid shear as comparted to the control. This shear stress-induced expression was blocked by incubation with Pravastatin™ (p>0.05; control vs. venous shear with Pravastatin™). Pravastatin™ had no effect on AQP1 immunofluorescence in static cultures (p>0.05 vs. control). These data indicate that Pravastatin™ prevents shear stress induction of AQP1 in cultured HUVECs. Conclusions: The results presented show that the shear stress induction of AQP1 protein expression is prevented by Pravastatin™. These results further demonstrate a possible tissue-independent function of statin drugs in regulating the expression of AQPs in general and specifically a potential cardioprotective benefit of statins, independent of their cholesterol-lowering function, related to the regulation of AQP1 in vascular endothelial cells.

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  The Relationship between Divorce, Parenting, and Childhood Outcomes

  Lisa E Stone

  Recent research has focused on how divorce can potentially cause and contribute to adjustment problems in children, such as behavioral and emotional problems (Donahue, et. al, 2010; Hetherington & Stanley-Hagan, 1999; Price & Kunz, 2003). Multiple factors can mediate and moderate the relationship between divorce and negative outcomes, causing certain children to be more susceptible to the effects of divorce than others. Parenting can change drastically after divorce, such as decreased amount and quality of time spent with parents. Researchers suggest that this change in parenting can mediate the relationship between divorce and negative child adjustment, with negative parenting characteristics increasing the likelihood of negative adjustment (Forehand, Thomas, Wierson, Brody, & Fauber, 1990; Martinez & Forgatch, 1999; Lansford, 2009). The present study examined how parenting is related to the relationship between divorce and juvenile delinquency and the relationship between divorce and depression. It was hypothesized that parenting, as measured by maternal emotional support, would mediate the effects of divorce on both delinquency and depression. Data came from an extensive, nationally representative longitudinal study, consisting of both mothers and their offspring, totaling approximately 11,500 participants. Analyses explored both the direct relationship between divorce and delinquency/depression and the indirect relationship between divorce, parenting, and delinquency/depression. Results indicated that divorce predicts lower levels of maternal emotional support, which predicts higher levels of delinquency. Results also indicated that there is a direct relationship between divorce and delinquency, meaning that parenting only accounted for a portion of the effects of divorce on delinquency. Results also showed that there was not a mediated relationship between divorce, maternal emotional support, and depression, meaning that divorce and parenting did not predict levels of depression. It is important to identify what factors moderate and mediate the effects of divorce because identification of the factors can lead to potential positive interventions.

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  The Relationship Between Parental Communications About Race and Their Children’s Racial Identity

  Briana J Moore

  While racial and ethnic identity (REI) has been studied extensively among older children and adults, we know little about its emergence in early childhood. Using measurements developed for this study, we investigate REI among kindergartners as well as its relationship with cross-race inclusion. In addition, we examine the contribution of parental communications (e.g., preparation for bias, ethnic pride, and egalitarianism) toward the development of REI. We determined African-American children’s individual preferences for 6 different leisure activities (e.g., playing a musical instrument, playing a video game, etc.), establishing a rank order for each child. Subsequently, pairs of photographs were presented, each pair depicting two activities. Children were asked to pick the activity that would be “most fun.” While one photo depicted a Black child engaged in one activity, the other depicted a White child engaged in a different activity. Based upon each child’s baseline order of preferences, any unexpected choice was noted as a shift toward the “same-race” or “cross-race” model. A REI score is defined as the number of same-race minus cross-race shifts. REI scores were compared with scores obtained from two other tasks. The “Racial Inclusion Task” requires each child to select 4 children who they would like to invite to their birthday party. One-half of the potential choices are Black, while the remaining half are White. The “Activity Preference Task” requires children to rate how much fun it would be to participate in a variety of activities (e.g., a tug-of-war game). Each activity was depicted by a photograph of Black children or of White children. We predicted that parental communications involving ethnic pride would be related to REI scores, cross-race inclusion, and activities depicted by cross-race models. Implications of our findings for the development of positive racial identities and the encouragement of inclusive attitudes are discussed.

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  The Role of M1BP in Eye Development of Drosophila melanogaster

  Neha Gogia, Ankita Sarkar, Evan J Wypasek

  Many genes in the Drosophila melanogaster have Pol II paused at the promoter proximal region, because the binding of either the GAGA factor or the Motif 1 binding protein (M1BP). M1BP resides on chromosome 2 of Drosophila melanogaster and directs a distinct transcriptional mechanism evolved from the TATA box. M1BP is highly conserved across the species and encodes a 55kDa protein containing five C2H2 zinc-fingers domains. A battery of highly conserved genes regulates drosophila eye development. Based on high throughput studies, it has been suggested that M1BP may regulate gene expression during Drosophila eye development, but its exact role is unknown. Our aim is to study the role of M1BP during eye development. We have used Green Fluorescent Protein (GFP) marker to identify intended regions to be expressed. This GFP marker has expressed the dorsal, ventral, morphogenetic furrow and the entire eye. This aim is further focused with absence of M1BP being produced in the stock fly and then focusing on the phenotype and genotype when crossed with another set of flies that have a suppression in development of some aspect of the eye. We found that absence of M1BP function in dorsal and ventral eye margins results in the suppression of eye fate. This suppression of eye fate was found when both the dorsal and ventral margins were expressed, along with a suppression of eye fate when the dorsal and ventral regions were expressed separately. The absence of M1BP also led to the suppression of the gene from the complete eye, giving us a head loss phenotype. This head loss phenotype shows the destruction and absence of photoreceptors in the developmental stages of the eye.

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  The role of micronutrients: because what we put into the soil actually matters to plants

  Kiersten P Angelos, Carly Christine Delois, Madison J Dembinski, Amanda N Finke, Kaitlin M Gawkins, Shania E Hurst, Madeline R Norman, Ryan W Reihart, Mackenzie E Ryan

  A critical need exists to understand what affects plant communities in coastal tallgrass ecosystems that are considered endangered ecosystems. We conducted an experiment in a coastal tall grass prairie in Texas that manipulated the amount of macronutrients (nitrogen and phosphorus) and micronutrients (calcium, sodium and potassium) in all possible combinations on a large scale. We estimated percent cover of every plant species in 4 pooled quadrats in all plots. Plant biomass was estimated by vegetation clipping. We found that when macronutrients were abundant then micronutrients had more profound effects on plant biomass and species richness, and some species seem co-limited by macro- and micronutrients. This data should be used to determine how to restore and treat coastal tallgrass prairies to understand their potential restoration.

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  The Role of Quality in S&P 500 Stock Returns: An Empirical Analysis 2007-2015

  Sam William Verrilli

  In this study, high quality stocks are defined as stocks with high returns on equity (ROE). Low quality stocks have low ROEs. The first hypothesis to be tested is that high ROE stocks outperform low ROE stocks over long periods of time (the persistence factor). A second hypothesis to be tested is that high ROE stocks outperform low ROE stocks in periods of market downturns and high volatility. A third hypothesis to be tested is that low ROE stocks outperform during market rebound periods. S&P 500 stocks are used in the analysis and the S&P 500 SPDR ETF (SPY) is used as a performance benchmark.

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  The Role of Safety and Leverage in S&P 500 Stock Returns: An Empirical Analysis, 2007-2015

  Kevin Michael Wargo

  In this study I use debt-to-equity as both a measure of safety and leverage. Low debt-to-equity stocks provide a measure of safety while high debt-to-equity stocks offer leverage. Using S&P 500 stocks ranked from low to high debt-to-equity I test the following hypotheses: (1) Low debt-to-equity portfolios outperform high debt-to-equity portfolios over long periods of time (i.e. persistence), (2) In periods of market growth, high debt-to-equity portfolios outperform low debt-to-equity portfolios, and (3) In market downturns, low debt-to-equity portfolios outperform high debt-to-equity portfolios.

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  The Social and Mental Health Factors Impacting Academic Achievement

  Sarah E Rolfsen, Stephanie Sheikh

  This presentation will explore how students develop socially and the impact that concussions may have on student learning. Specifically, Identifying the effect educational practices have on student social development and influences the academic progress of students with concussions.

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  The Social Media Campus Intervention

  Alexander J Beattie

  Social media is a form of documentative communication that is used by people to express and evoke emotions, actions, thoughts, visuals, and messages of various depths in their experiences and through various stages of life. Told like a story of an individual, social media conveys incredibly personal struggles, extravagant nights out, celebrations, and overcoming life obstacles only few could imagine during their lifetime. Social media in higher education can be like attempting a very risky walk on a tightrope of immeasurable height, especially when there is no awareness showcasing “the life,” peer pressure, and/or possible implications on their future, such as employment. While some students believe they have the level of awareness necessary in relation to displaying appropriate social media practices, others disregard the rules and/or use alternative and multiple forms of deception to express what they really want to convey to certain audiences. If reflection, critical thinking, and evaluation regarding the appropriateness and impact that a social media post can have on a student’s future are absent, students risk losing everything they have worked for in the hopes of achieving better opportunities.

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  The Sound of Silence: An Introduction to the Use of Acoustics in Tracking Climate Change

  Kaleigh J Barkaszi

  Climate change is occurring, the planet is warming, and anthropogenic activities are to blame for the environmental degradation. Tracking climate change is a long process, taking years before changes are noticeable and it becomes too late to mitigate or preserve the habitat. An emerging field of soundscape ecology presents the opportunity and ability to observe climate change effects before irreparable damage is done. Using acoustics to monitor ecosystems also provides an understanding of species behavior, weather patterns, and the effects of greenhouse gas emissions, to name a few. Biological organisms rely on sound to send and receive vital information regarding the area around them. As anthropogenic activities continue and increase warming events, the acoustic environment changes which many species may be unable to adapt to. Little research has been done using acoustics to track and measure effects of climate change, and even less have been conducted in the Arctic. The Arctic is still a relatively pristine environment, yet with global climatic warming, changes are predicted to occur rapidly and significantly. This paper introduces the complex interactions and responses triggered by climate change events. Using acoustics can provide a perspective on climate change effects before they are drastically observed. Recordings made in the north of Iceland were used to examine the effectiveness of acoustic monitoring. Terrestrial and underwater recordings were made to evaluate ambient noise levels and predict how climate change will affect the ambient noise of an environment. The results of the project demonstrate how acoustics can be used as a tool to track climate change effects over long periods of time.

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  The Stone-Weierstrass Approximation Theorem and Applications

  Melissa E Fox, Emma Laura Whitney

  Abstract: We outline the proof of the celebrated Stone-Weierstrass Theorem and give two applications. It is known that the polynomials are dense on C[a,b], the space of continuous functions defined on a closed bounded interval [a,b]; that is, given a continuous function and a tolerance for that function, a polynomial can be found within the tolerance of the function. We show that in the space C(M), where M is compact, if we consider the subalgebra A of C(M) that contains the constant functions and separates points of C(M), then A is dense in C(M). Then it follows that the piecewise linear functions and the trigonometric polynomials are dense in the space of continuous functions on compact domains.

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  Transcriptional regulation of dronc by the Hippo pathway.

  Karishma S Gangwani, Kirti Snigdha

  The growth regulatory Hippo pathway maintains tissue homeostasis by tightly regulating cell proliferation and cell death. This key pathway is conserved between humans and fruit flies (Drosophila melanogaster), and misexpression of this pathway is linked to cancer. The core components of the pathway include two kinases Hippo (Hpo) and its target Warts (Wts) and the transcriptional co-activator Yorkie (Yki). When the pathway is active, Hippo (Hpo) along with Wts bring about phosphorylation of Yki which leads to cell death. Yki acts in an activator complex by associating with Scalloped (Sd) to regulate target genes. Inactivation of hpo leads to overgrowth due to activation of cell cycle and cell proliferation genes such as Cyclin E, A, B, D, and diap1; and downregulation of caspases of the apoptotic pathway like dronc and drice which ensures that cells/tissues overproliferate on pathway downregulation. These Yki mediated regulatory interactions are thought to promote tumor growth. Previous work from our lab has shown that the Hippo pathway transcriptionally downregulates dronc- this is an important but underexplored aspect of Hippo signaling as till date dronc is the only negatively regulated transcriptional target of the Hippo pathway. To induce cell death, Dronc activates caspase-3 (Drice) that leads to formation of the apoptosome complex. When Yki levels are low inside the nucleus there is an increase of Dronc expression and vice versa, however, it is unknown if Yki directly regulates dronc expression during Hippo signaling. We hypothesize that Yki functions both as an activator and a repressor simultaneously. To test this, we will express transgenic constructs expressing different sequences of the Dronc promoter to find which sequences are required for Yki mediated dronc repression. We are also investigating the transcription factors/repressors that may associate with Yki to mediate its repressive activity. Here we present our findings from these studies.

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  Trends in Education/Health Care Services Employment and S&P 500 Sector Price Movements: An Empirical Analysis 2009-2016.

  Michael A Capicotto, Bennett A Zynn

  Education and Health Care Services is one of the fastest growing employment sectors in the US. In this study we examine the relationship between it and nine S&P 500 sector ETF's plus SPY, a proxy for the S&P 500 Index. We test the hypothesis that Education and Healthcare employment growth co-varies directly with SPY and the nine sector ETF's. The period of analysis is 2009-2016 with monthly data used to construct the regression equations.

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  Tuckman v. the LGBTQ+ Community: The Impact of Bias-Related Incidents on Group Formation and Leadership Development of LGBTQ+ Identifying, Undergraduate Students at the University of Dayton

  Adam D Booher

  A main component of the successful development of undergraduate students is a healthy combination of academic success and interpersonal development. Interpersonal development relies heavily on undergraduate students' abilities to be involved socially and effectively form groups with their peers. The Tuckman (1965) model of group formation only works when members of the group are operating in a relatively conflict-free environment (Cassidy, 2007). What happens when bias-related conflicts and assumptions become present in the group formation process? This study focuses on bias-related concerns among LGBTQ+ undergraduate students at the University of Dayton and the influence that these concerns have on the students' ability to effectively form groups with their non-marginalized peers. This study is significant because it indicates that student affairs professionals ought to cater group formation to the needs of all the students involved in the process, not just those who identify as the majority in terms of their sexual identity.

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  Two clone system to study cell-cell communication between wild-type and amyloi-beta 42 plaque forming cells in Alzheimer's disease.

  Jordan C Dubbs, Sean A Kelly, Nilan Mani, Ankita Sarkar

  Alzheimer’s is a neurodegenerative disease caused by the miscleavage of the Amyloid precursor protein (APP). When the APP protein is properly cleaved it forms Aβ40 protein, and when it is improperly cleaved it forms the Aβ42 protein that is 2 extra amino acids long. This causes the formation of plaques within the neuron cells and leads to cell death and ultimately large scale changes in the brain tissue. We have designed a genetic system where we have combined strength of FLP/FRT system with the Gal4/UAS –system to target Aβ42 cells in the developing retinal neurons of the developing eye. Misexpression of Aβ42 results in strong neurodegenerative phenotype. Using our newly developed system we are making two types of clones by FLP FRT mediated recombination where one clone of cells is marked by strong presence of GFP reporter and express high levels of Aβ42 whereas the other clone of cells which are marked by the absence GFP are wild-type retinal neurons. The purpose of the Two Clone System is to track the progression of Alzheimer and Wild Type cells within the eye imaginal disc of D. melanogaster. The system was developed to see if the rate of progression of Wild Type cells and Alzheimer's cells would be equal. Furthermore, using markers for various signaling pathways we will test if there is a signal emanating from Aβ42 expressing cells that trigger neurodegeneration. The results from these studies will be presented.

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  Two-Step Synthetic Route to BODIPY Dyes for Solar Cell Applications

  John Connor Quinn

  Dye Sensitized Solar Cells (DSSCs) are beginning to show great promise as an alternative energy source, but the cost and lack of efficiency of most current dyes remains a problem. A series of BODIPY dyes have been synthesized by a two-step synthetic route to provide a solution. A dipyrrin was formed through the reaction of either napthyl[1,2-c]pyrrole or fluorantho[2,3-c]pyrrole with one of several aromatic aldehydes in a solid state reaction. The resulting dipyrrins were reacted with boron trifluoride to give a series of highly conjugated BODIPY dyes. Upon analyzing the photophysical properties of the dyes with UV-VIS and fluorescence spectroscopy, it was found that using the more highly conjugated fluoranthro[2,3-c]pyrrole to form the dipyrrin core results in a favorable red shift of about 50 nm, as compared to more modest shifts as a result of changing the aldehyde. Cyclic voltametry also demonstrated a stabilization of the LUMO energy of the dyes formed from the more highly conjugated pyrrole. All of the dyes display molar absorptivities greater than 100 000 M−1 cm−1 with photoluminescence quantum efficiencies of 0.5–1.0, and the HOMO and LUMO energies of the dyes further illustrate the suitability of these dyes for use in DSSCs.

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  Two-Step Synthetic Route toward Asymmetric and Symmetric Boron Dipyrromethenes: Synthesis, Optical Properties, and Electrochemistry

  Michael A Coladipietro

  A two-step synthetic route toward BODIPY dyes is accomplished by reaction of the readily available naphtho[1,2-c]pyrrole with various aldehydes followed by coordination of BF2. Synthesis of the dipyrromethene is achieved by simply heating the pyrrole and aldehyde at moderate temperatures for less than 30 min. In addition to the absence of solvent this reaction does not require an acid catalyst or an oxidizing agent to achieve the dipyrromethene. Investigation of various aldehydes by this method suggests that the choice of aldehyde plays a role in the formation of either symmetric or asymmetric BODIPYs. The dyes have exceptionally high molar absorptivities (> 100000 m–1 cm–1) in the far visible region of the electromagnetic spectrum with intense emission and high quantum efficiency.

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  UD-Bodipy Fluorophores: A Computational Study

  Anthony M Rose

  Boron-dipyrromethene (BODIPY) compounds are an exciting class of fluorescent molecules. Several variations on this structure exist in the literature and have been studied extensively by experimental as well as computational methods. Unfortunately, these compounds can be expensive to make and many do not contain optimal properties such as absorbance in the near-IR region of 700-1000 nm. Recent efforts in the Swavey laboratory at the University of Dayton (UD) have revealed a new class of these molecules (UD-BODIPY) with quantum efficiencies ~1, making them rare and interesting chromaphores, but still lack the desired absorbance profile. We hypothesize the properties of UD-BODIPY chemicals are related to their structure, but the relationship between structure and activity is not yet fully understood. Several UD-BODIPY’s have been prepared in the laboratory and they all posses an double benzo[e]isoindole core. UD-BODIPYs can be synthesized easily by condensation of different aldehydes to form the more complex fused ring systems. As with any synthesis, it might be faster and more efficient to screen large numbers of UD-BODIPYs in silico before their synthesis is attempted. UD-BODIPY’s will be evaluated through for suitability as fluorescent dyes in biological systems or for use in organic solar cells. We are developing a robust computational method for screening and selecting interesting UD-BODIPY compounds. The goal is to understand the influence of geometry and/or structure changes on the fluorescence performance of these chemicals. We will then use our knowledge to design new UD-BODIPYs.

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  Understanding the Effects of Propionic Acid on Listeria monocytogenes Growth, Survival, and Virulence.

  Elizabeth A Abrams, Kaitlin E Beemiller, Eric Edward Newton, Erica Rinehart, Nathan C Wallace

  Listeria monocytogenes is a bacterial pathogen that causes foodborne gastrointestinal illnesses. In the absence of a strong immune system, Listeria can cause fatal infection by breaking the intestinal wall and spreading to other organs. Therefore, prevention of fatal infections relies on blocking Listeria from adhering to the intestinal wall. My work focused on understanding how propionate, a natural intestinal acid in healthy individuals, affects Listeria’s ability to grow and cause disease. We first conducted growth curves in BHI and found that propionate supplementations with concentrations up to 25mM resulted in a small decrease in in vitro growth under both aerobic and anaerobic conditions. In contrast, using hemolytic assays, we found that propionate supplementation resulted in a significant increase in listeriolysin O (LLO) supernatant activity after anaerobic growth, but a significant decrease in LLO supernatant activity after aerobic growth. To further determine the effect of propionate on Listeria pathogenesis, we infected RAW264.7 macrophages with Listeria grown aerobically or anaerobically, with or without propionate supplementations. Our results showed that compared to aerobically grown Listeria, anaerobically grown Listeria exhibited significantly higher intracellular CFUs during early infection time points, but lower intracellular CFUs during later time points. Supplementation of propionate during Listeria in vitro growth did not impact intracellular growth. Finally, we tested the hemolytic ability and intracellular growth of environmental Listeria isolates and saw results mimicking those of our lab strain. Together, our results suggest that Listeria is capable of growth with high levels of propionate but likely adapts to propionate differently depending on the presence or absence of oxygen. Further research is being conducted to test for protective effects of propionate on mammalian cells by treating the cells with propionate prior to infection. We hope to fully understand the extent of influence propionate has on host-pathogen interactions.

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  Understanding the Repopulation of Glioblastoma in Drosophila Melanogaster Model System

  Leah D Bullock, Kirti Snigdha

  Glioblastoma Multiforme (GBM) is the most common form of malignant brain tumors, accounting for about 52% of all primary brain tumors. Patients diagnosed with GBM typically die within a few months after diagnosis. Upon initial diagnosis of GBM, standard treatment consists of surgery, radiation therapy, and chemotherapy. GBM has an unfavorable diagnosis due to the high rates of tumor recurrence. The cause of the repopulation of the tumor after treatment is currently unknown. Therefore there is a need to create a simple model system to study the repopulation of GBM. We have created a simple glioma model in Drosophila melanogaster to study the effects of X-ray radiation on tumor size and repopulation of the tumor. We generated the glioma model by suppressing Pten while overexpressing oncogene RasV12 in glial cells of the fly brain to induce tumor. Flies with genotype UASPten RNAi;UASRasV12; Repo Gal4 UASGFP developed aggressive brain tumors and failed to survive to the adult stage. To model repopulation, we standardized the X-ray dosage. We observed that after exposing the 1st instar larvae to 3.5 gy X-ray, there was a significant reduction in tumor size in the larvae compared to the unexposed samples. This revealed effects of X-ray radiation on tumor; however there was still excess of glial population after X-ray treatment as seen in human gliomas too. Hence we have effectively established a glioma repopulation model. We are now looking into the mechanistic details of why X-ray radiation causes reduction in tumor and why repopulation of tumor cells occurs after treatment. Here we report our recent findings. Since most of the signaling pathways are conserved from flies to mammals, these findings can be utilized in other model systems and in humans and opens new avenues for glioma treatment.

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  Understanding the role of receptor tyrosine kinase in Glioblastoma using Drosophila Melanogaster model system

  Minh T Ho, Kirti Snigdha

  Glioblastoma Multiforme (GBM) is one the most aggressive form and lethal form of brain tumors. Every year thousands of new cases are reported with a very poor prognosis. High lethality of GBM can be attributed to its recurrence after treatment, cause of which is currently unknown. Recent studies have identified few key signaling pathway components which are modified in the GBM. . These transmembrane proteins are apical of several interconnected signaling cascades. Phosphatidylinositol 3-kinase-mammalian target of rapamycin (PI3K/mTOR) signaling is elevated in ~88% of all glioblastoma due to suppression of PTEN. It is predicted that PI3K signaling contributes to therapy resistance in GBM cell lines due to its role in motility and proliferation. Along with the activated RAS from mitogen-activated protein kinase (MAPK) pathway , PI3K-mTOR signaling pathways control cell survival, differentiation, proliferation, metabolism, and motility in response to extracellular cues. Overexpression of activated RAS has been reported in multiple cases of GBM. Growth factor receptors that regulate RAS like Receptor tyrosine kinases are also often overexpressed by mutations in many different cancers, including glioblastoma. We hypothesize that receptor tyrosine kinases (RTK) affect the GBM growth by interacting with PI3K/mTOR and RAS/MAPK pathway and could be a possible target for GBM therapy. Since most of the signaling pathways are conserved from flies to mammals we have created a simple glioma model in Drosophila melanogaster to study this interaction. We generated the glioblastoma model by suppressing Pten while overexpressing oncogene RasV12 in glial cells of the fly brain to induce tumor. Flies with genotype UASPtenRNAi UASRasV12; Repo Gal4 UASGFP developed aggressive brain tumors and failed to survive to the adult stage. We will downregulate receptor tyrosine kinases like ALK and SEV in this glioblastoma model and evaluate its effect on growth and repopulation of glioblastoma. Here we report our recent findings.

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  Understanding the role of Wingless (Wg) signaling pathway in Amyloid-beta 42 (Aβ42) mediated neurodegeneration in Alzheimer’s Disease

  Ankita Sarkar

  Alzheimer’s disease (AD), a common form of dementia and an age related progressive neurodegenerative disorder, manifests as memory loss and reduced cognitive ability. One of the hallmarks of AD is formation of the Amyloid-beta 42 (hereafter Aβ42) plaques, which triggers oxidative stress due to aberrant signaling and finally results in the death of neurons. However, the exact mechanism causing cell death is still not well understood. We misexpressed high levels of human Aβ42 protein in the developing fly retina, which mimics AD like neuropathology. In a forward genetic screen, we identified members of highly conserved Wingless (Wg) signaling pathway as modifiers of the Aβ42 mediated neurodegeneration. Misexpression of negative regulator of Wg like Shaggy kinase (sgg) or a dominant negative form of Drosophila T-cell factor (dTCFDN5) or blocking Wg transport specifically by downregulating Porcupine (using porcupineRNAi) rescued Aβ42 mediated neurodegeneration by reducing the number of dying cells and restoring the axonal targeting from the retina to the brain. In order to determine the role of Wg in early vs late onset of AD, we have modulated our transgenic expression system to activate at different time points and will assess whether Wg is activated in all stages. It is also known that Wg induces cell death in the early eye developmental stage of Drosophila. We therefore want to understand by what mechanism and in which cells the Wg signaling is triggering cell death, whether it’s the Aβ42 misexpressing cells or the neighboring wild type cells. In order to approach this question we have developed a two clone system in our lab to understand the crosstalk between the two cell populations. We have shown that the wild type neighboring cells are undergoing cell death compared to the Aβ42 misexpressed cells. Data from the experiments will be presented.

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  Understanding tumor metastasis in Drosophila Melanogaster model system

  Oscar A Barnes, Kirti Snigdha

  Cancer can be described as the uncontrolled growth of abnormal cells in an organism’s body, which occurs when the normal control systems in the body are malfunctioning. This produces a mass of the continually growing cells called a tumor. However, during tumor progression, the cancer cells through blood vessels migrate from the primary site of origin to secondary site where they affect another organ. This spreading of the cancer cells is called metastasis and makes treatment of cancer so difficult. Hence it is highly necessary to understand how the tumor metastasis happens and what is the role of normal cell in this process. Drosophila melanogaster commonly known as fruit fly has served as a useful model organism because of its well understood genome, availability of genetic tools and many evolutionarily conserved signaling pathways. Our understanding of the mechanisms regulating cell growth, differentiation and development has been considerably advanced by studies in Drosophila. Ras genes are associated with cell proliferation and overexpression of Ras protein leads to benign tumor in developing flies. Studies showed that suppressing cell polarity genes like Scrib induced neoplastic tumors. To model metastatic tumor, we co-activated the oncogene RasV12 and loss of polarity gene ScribRNAi in the wing imaginal disc. We used the UAS-GAL4 system to create the mutation in only few cells that will become invasive while remaining cells are normal in their genetic makeup. We hypothesize that these non-mutated normal cells and mutated cells interact among each other through signaling pathways to promote the tumor metastasis. To evaluate this we study the changes the key signaling pathways and metastatic markers like JNK, MMP1, Eiger through immunohistochemistry. We present our recent findings on this.