Stander Symposium Projects

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  Possible pharmacologic glioma treatment in Drosophila model

  Jenea Imani Adams, Kaitlyn M Alleman, Luke Alan Bressler, Karishma Sanjay Gangwani, Kathleen Theresa McCaslin, Katie Katherine Parker, Kirti Snigdha, Claire C Sullivan

  Glioma is a lethal brain cancer, and current treatment strategies have limited effects by extending life only by a few months. Thus, efforts should be made to discover better inhibitors of glioma growth. Ideally such inhibitors will suppress the progression of glioma by (a) inhibiting the underlying molecular pathways activated in glioma, or (b) prevent rapid proliferation of the glia and other cells that encompass the glioma tumor. We have developed a glioma model by co-activating PI3K and Ras/MAPK specifically in the Drosophila CNS glia. The Drosophila glioma cause the larval brain to appear enlarged due to rapid increase in the stem cells and their glial and neural progeny. These tumors cause the larvae to enter a prolonged larval phase, and eventually kill the organism. We are conducting a chemical screen using Tyrosine kinase inhibitors (Selleck Biochem.) in which we feed early third instar (72h old) larvae 10 or 300uM chemicals in DMSO and then see effects on glioma growth, and survival in mature third instar stage (120h old). Using these metrics, here we present data from our screen pertaining to drugs from rows A, B, C, and D of our library. Once we identify potential glioma inhibitors in the primary screens, we will validate them in secondary screens.

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  Poverty and Education

  Alexandra Gisela Delgrande, Ryan Earl Evensen-Hein

  Poverty affects at-risk students’ academic opportunity through its effects on academic achievement, motivation, development, and education quality. Impoverished at-risk students’ academic achievement is affected by their inability to acquire basic needs. This can be shown by these students’ graduation rates, math scores, and retention rates. There is evidence of poverty having a negative effect on graduation rates, retention rates, and test scores. These students’ can appear less motivated or less engaged in the classroom potentially due to their focus on higher priorities. How could you expect a student to worry about a math test when they do not know how they are getting dinner that night? Since these students are unable to acquire their basic needs, they can also encounter developmental problems. These developmental issues refer to social, emotional, and cognitive development as well as can lead to malnutrition and preterm birth. These developmental setbacks hinder these students’ ability to further develop in school. Another obstacle impoverished students can face is poor education quality. Oftentimes, inexperienced or ineffective educators are assigned to schools with higher impoverished student populations. This unfortunate fact, as well as underfunded districts, and the lack of basic school supplies, further disadvantage impoverished at-risk students. Impoverished at-risk students are put at a disadvantage through poverty’s effects on academic achievement, motivation, retention, development, and education quality.

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  Prenatal Care in Latin America

  Siobhan Kathleen Kenny, Molly Anne Quinn

  Each year, 529, 000 women worldwide die from complications during pregnancy and childbirth, of these 529,000 deaths 22,000 are from Latin America and Caribbean regions (Lubbock & Stephenson, 2008). Nicaragua, one of Latin America’s poorest countries, has a high maternal death rate due to lack of access to services, high fertility rate among a young reproductive age group, complications from unsafe abortions, postpartum hemorrhage, hypertension, and sepsis (Lubbock & Stephenson, 2008). Unlike Nicaragua, Cuba, a fellow Latin American country, has strict policies and procedures for prenatal care. Cuba’s use of the polyclinic, a multidisciplinary professional team that works closely with mothers and children in the community, allows for expecting mothers to have access to basic medical care, such as universal screenings and annual checkups, as well as access to medical educational materials and other necessary preventative care. A preventative approach to prenatal care includes prioritizing and tracking high risk pregnancies, and setting national standards that make the life expectancy at birth on par with western nations (Bragg et. al, 2012). As a result of Cuba’s approach, their maternal mortality rate is on the decline while Nicaragua’s’ in on the rise. The purpose of this poster is to describe the prenatal care disparities between Latin American countries, and offer some strategies to combat this problem.

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  Pretrial Publicity and Juror Decision-Making: Effects of Inadmissible Confession Evidence and Coverage of Its Exclusion from Trial

  Rebecca S Rhein

  The courts have long been concerned that exposure to media coverage regarding a case making its way through the judicial process (i.e., pretrial publicity [PTP]) may influence jurors’ decision-making in court. Indeed, empirical research over the past two decades has shown that PTP can influence juror decisions. PTP often contains descriptions of evidence or factors that are ultimately deemed inadmissible at trial (e.g., confession evidence), but no research to date has examined what occurs when confessions are reported to the public but later deemed inadmissible. We examined these issues using a 2 (Interrogation Quality: High vs. Low) x3 (Exclusion: Technicality vs. Cause vs. Not Specified) +1 (No Confession PTP Control) +1 (No PTP Control) mock juror experiment. Undergraduate students were randomly assigned to read various forms of pretrial publicity. In a second session conducted two days later, participants read a trial transcript that omitted any mention of the critical evidence contained in some versions of the PTP. Participants evaluated the evidence and rendered a verdict. Participants who were exposed to pretrial publicity were nonsignificantly more likely to find the defendant not guilty than those who received no pretrial publicity. When participants were not told the reason for the exclusion of the confession, they were more likely to convict the defendant. This may reflect a tendency of jurors to fail to disregard inadmissible evidence unless convinced of a rationale for its exclusion.

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  Propionate Perturbation of Listeria monocytogenes Growth and Listeriolysin O Production is Modulated by Anaerobicity

  Jack Clifford Weis

  Propionate is a common food preservative and one of the major short chain fatty acids in the human intestines. Therefore, exposure to propionate is a frequent event for foodborne pathogens and likely takes place under suboxic conditions. However, it is not clear whether the absence of oxygen affects how pathogens respond to propionate. In this study, we investigated how propionate exposure affects Listeria monocytogenes growth and virulence factor production under aerobic or anaerobic conditions. Under anaerobic conditions, propionate supplementations had no effect on planktonic growth but resulted in decreased adherent growth. In contrast, under aerobic conditions, propionate supplementations resulted in a pH-dependent inhibition of planktonic growth and increased adherent growth. The effects of propionate on planktonic growth are also temperature-sensitive. At room temperature, propionate supplementation resulted in decreased doubling times under aerobic but not anaerobic conditions. To begin to investigate the effects of oxygen on L. monocytogenes response to propionate, we further noted that supernatant from cultures grown with propionate contained an increased amount of acetoin under aerobic conditions and a decreased amount of ethanol under both aerobic and anaerobic conditions. Moreover, L. monocytogenes grown with propionate exhibited an increased proportion of odd number straight chain fatty acids in a manner that was more pronounced under anaerobic conditions. Finally, aerobic suppression of listeriolysin O (LLO) production and anaerobic induction of LLO production were observed in L. monocytogenes grown with propionate. These results clearly demonstrate for the first time that L. monocytogenes exposure to propionate resulted a variety of physiological and pathogenic responses. Moreover, the presence or absence of oxygen plays a critical role in shaping L. monocytogenes responses to propionate that can potentially impact bacterial survival in the environment and subsequent interactions within host cells.

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  Pseudomonas aeruginosa biofilm and the properties of polysaccharide associated antibiotic resistance

  Celeste Claire Bergman

  High density growth of bacteria tend to form biofilms by excreting an extracellular matrix. This matrix is composed of adhesive components such as polysaccharides. The polysaccharides serve as cell-to-cell attachments and a selective filter for which outside material must pass. By forming the biofilm, the bacteria create a defense mechanism against antibiotic attacks and other abrasive environmental factors. Pseudomonas aeruginosa is a biofilm forming bacteria with known antibiotic resistance. Four strains were tested, ΔwspF, ΔwspF Δpel, ΔwspF Δpsl, and ΔwspF Δpel Δpsl. Each strain produced differing amounts of the polysaccharides PEL and PSL. The antibiotics gentamicin and ciprofloxacin were used to test antibiotic tolerance of the differing polysaccharides. The results showed that PSL provided antibiotic tolerance against gentamicin but was susceptible to ciprofloxacin. PEL provided antibiotic tolerance to ciprofloxacin but was susceptible to gentamicin.

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  Quaternion Neural Networks for Sequence Classification

  Cameron E Long

  Recently the field of deep learning has made significant advancement, included in this category is the subject of sequence classification. Recent research has shown that traditional sequence processing deep learning architectures such as the Long Short-Term Memory cell (LSTM) or the Gated Recurrent Unit (GRU) can be replaced by Dilated Fully Convolutional Networks called a Temporal Convolutional Network (TCN). Other research has shown that by representing deep networks with complex and quaternion numbers, the networks tend to show improved convergence while using significantly less learned parameters. We combine these two observations to create a Quaternion Temporal Convolution Network (QTCN), and show its performance on sequential classification tasks.

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  Rapid Miocene Extensional Unroofing of the Southwestern East Humboldt Range Metamorphic Core Complex, Nevada

  Alex Jakob Carte

  The Ruby Mountains and East Humboldt Range of northeastern Nevada expose exceptionally high grade metamorphosed rocks, the tectonic history of which has been hotly debated for decades. To resolve this debate, we collected a WNW-trending transect spanning 20 km of muscovite, biotite, and/or potassium-feldspar bearing samples for dating by the 40Ar/39Ar method. This method allows us to model the timing and progression of cooling, and therefore the uplift history of these rocks. The results from the southernmost transect indicate an early phase of cooling prior to 35Ma (See companion presentation by J. Jeruc). Here, I present results from the western flank of the range that record a later phase in the cooling history. A series of five samples from this transect imply that cooling below 200°C began prior to 30 Ma. The samples then cooled slowly until about 20-24Ma, when they experienced a reheating event to above 250°C. Following reheating, the samples cooled rapidly to below 100°C between 20 and 14Ma, with cooling occuring progressively later towards the WNW. The termination of cooling at 14 Ma is in excellent agreement with fault gouge dating results reported by Haines and van der Pluijm (2010). The progression of cooling ages implies that unroofing proceeded at a rate of 1.8 - 2.4 km/m.y. Although some researchers suggest that the chief trigger of this phase of extension was the drifting of western North America over the Yellowstone hotspot, these results indicate that the onset of extension predated hotspot related volcanism by at least 3 m.y.

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  Rational Bargaining Strategies

  Chloe Lynne Beckett

  Ariel Rubinstein proved a perfect equilibrium partition exists in a bargaining model. His results come from a game in which two players must agree on a contract that states how to partition a pie of size one. Several statements regarding the players’ preferences are assumed. To begin, one player makes an offer and the other player accepts the offer or rejects the offer with another proposal. The Perfect Equilibrium Partitions (PEP) are described in all the models satisfying the assumptions. Solutions to the above scenario using fixed bargaining cost and then fixed discounting factors will be displayed during the presentation.

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  Real-time 3D Scene Reconstruction with Surface Optimization

  Ruixu Liu

  A real-time 3D scene reconstruction system with surface optimization is proposed. The dense 3D point cloud model is created by utilizing rotation and orientation invariant feature matching along with loop-closure detection algorithm on RGB-D images in a mobile robot. The high resolution and smooth mesh model is implemented on a GPU based computer through wireless communication.

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  Real World Comparison of Modern Power v. Alternative "Green" Energy

  Davis R.C. Davis, Aaron Joseph Eversole, Daniel Thomas Vezdos

  Currently in the modern world we are faced with greater and greater evidence of the shortcomings in the conservation and protection of our shared earth. No place is this more evident than our reliance on the modern power cycle. In an effort to better understand the modern power cycle and the facts, both negative and positive, of “green” replacements we analyzed cradle to grave economic, environmental, and political impacts of said areas. All in an effort to finally settle the case of modern power v. alternative “green” energy.

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  Reducing Thermal Limitations of Flexible Electronics with Printed Architected Substrates

  Katherine Morris Burzynski

  Consumers and military personnel alike are demanding ubiquitous electronic devices which require enhanced flexibility and conformality of electronic materials and packaging, while maintaining device performance. Whether it be high-power devices for faster data speeds, such as fifth generation wireless communication technology or wearable sensors to facilitate the Internet of Things, the age of flexible, high performance electronic devices has begun. Managing the heat from flexible electronics is a fundamental challenge. Even on rigid substrates with significantly higher thermal conductivity than polymeric substrates, the full potential of semiconducting materials is often thermally limited. The flexible gallium nitride (GaN) transistors employed in this work are conventionally processed devices that can be released from their growth substrate and transferred to a variety of rigid and flexible substrates. Characterization of the GaN device behavior on the as-grown sapphire wafers provide a baseline for evaluation of engineered substrates. Thermal imaging of devices in operation reveals that the current passing through an as-grown GaN transistor reaches the target operating temperature at approximately five times the power of the same device transferred to a flexible substrate. Printable, thermally conductive nanocomposites integrating 1D, 2D, and 3D forms of carbon in a flexible polymer matrix, as well as metal nanoparticles, were developed to maximize heat transfer from electronic devices. The thermal conductivity of the candidate substrate materials was measured experimentally to have more than a 900 percent increase in thermal conductivity (from 0.2 to 1.7 W/mK), while maintaining desirable mechanical properties. The performance of devices transferred to these novel flexible composite substrates was characterized and used in computational simulations to predict flexible substrate architectures that effectively promote point-to-volume heat transfer to further improve device performance. Additive manufacturing for engineered architectures of the flexible, thermally conductive substrate materials was demonstrated to substantially reduce the thermal limitation of high-power flexible electronics.

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  Regression Analysis of United States Airfare

  Sarah Marie Hartness

  Millions of flights depart in the United States every year. Using a 10% sample of all flights tracked by the Bureau of Transportation Statistics, we will study how much it costs on average to fly domestically and its distribution. We will also take the four most popular states to fly out of (California, Florida, Texas, and New York) and compare the costs people are paying to fly from these states and whether or not people are flying round trip from these states. Regression analysis will be used to study the relationship between several variables (for example, the number of passengers and the distance) and the cost of the flights. Finally, we will look at when people are flying most often. It is expected to be in the last quarter of the year due to the holiday season.

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  Relatedness and Well-being in the Digital Age

  Christopher Theodore Jurgens

  Research on online socialization and well-being has found positive as well as inverse relations. The present study (N = 200 Mechanical Turk participants) investigates online relatedness to others, which we expect to correlate positively with well-being and to be greater for users on forum platforms than for social networking sites (SNS) like Facebook. We also investigate well-being differences between online socialization platforms, which we expect to be higher for forum usage than for SNS usage. Finally, we examine mediating and moderating effects of online relatedness, such that (1) online forum relatedness mediates the relation between forum use and well-being and (2) participants with low SNS relatedness and high SNS usage report especially low levels of well-being than do participants with high SNS relatedness regardless of SNS usage.

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  Religiosity and Political Participation

  George Joseph Bommer, Claudia Nicole Dominique, Bea Mercedes Santos

  Religiosity can be described as the extent to which an individual is committed to their values, beliefs, and practices of, or related to, their faith. A person’s religiosity can impact many aspects of daily life, including their identity and attitudes towards politics. The relationship between religion and politics has been the focus of much research, with many studies examining the relationship between religiosity and political affiliation, or the political party with which a person most identifies. Data from the 2018 midterm elections (Pew, 2018) found that the candidate a person voted for was largely influenced by their religious affiliation, such that more religious people, in general, were more likely to vote for Republican candidates while less religious people were more likely to vote for Democratic candidates. Recently, however, studies have shifted their attention to the association between religiosity and politically-related civic engagement. While previous research finds that religiosity impacts who a person votes for, it does not speak to whether voting in elections, in general, differs by a person's religiosity. The current research seeks to contribute to this line of research by focusing on the extent to which an individual’s religiosity is associated with their political behavior, specifically whether they register to vote and whether they vote (if eligible and registered).

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  Resolution Exploration using Two-Dimensional Deep Learning Architectures

  Brandon Montel Payne

  The main objective of this research project is image resolution exploration for employing two-dimensional deep learning architectures and algorithms. This is to aid in military surveillance in either drones or ground robots that are used for collecting information to detect threat objects. The goal of the proposed research is to make the autonomous system be able to recognize certain objects in the field by using 2D machine learning resources, and to determine the resolution requirement in the imagery.

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  Resolution exploration using Two-Dimensional Deep Learning Architectures for Infrared Data Captures

  Jonathan Paul Schierl

  This project investigates the effectiveness of deep learning architecture as a means of object detection. To determine the accuracy of the developed algorithm, two-dimensional short-wave infrared aerial captures will be used as training data. By analyzing the accuracy of detection rates with varying resolutions, a baseline image quality for accurate detection will begin to emerge.

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  Resolving the Molecular Mechanisms by Which DNA Mutations Alter the Function of a Genetic Switch

  Michael Weinstein

  Animal genomes likely possesses anywhere from tens of thousands to more than a million mutations that are genetic baggage from DNA replication mistakes or “mutations” that occurred in the past. Each mutation can either improve, reduce, or have no effect on fitness. Moreover, the effects of such mutations can depend on the presence or absence of other mutations, so called epistatic interactions. A goal of evolutionary-developmental biology research is to identify the mutations responsible for the evolution of form and function, and to understand the molecular mechanisms of their effects. This goal remains out of reach, as the effects of mutations and epistatic interactions are difficult to predict without knowing the function of the DNA sequence they reside in. This difficulty is heightened for mutations occurring in cis-regulatory element sequences that act as switches to control gene transcription. We are using a fruit fly model to test hypotheses about the molecular mechanisms by which mutations alter a genetic switch’s activity, and whether these function-altering mutations are subjected to the tyranny of epistatic interactions. Specifically, we are investigating the Drosophila melanogaster dimorphic element that is a transcription-regulating switch for the bric-à-brac genes. Three mutations in the dimorphic element were identified that individually alter the level of bric-à-brac transcription. The presence or absence of epistatic interactions will be determined by measuring the activity of dimorphic elements from related species that have been engineered to possess the Drosophila melanogaster mutations. I will also test the hypothesis that these mutations impart their effects by creating or destroying binding sites for proteins known as transcription factors. The results will provide a sorely needed example where an understanding of molecular mechanisms bridges the gap between a cis-regulatory element’s DNA sequence and it’s in vivo function.

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  Revising a Document About Sugar and the Body for UD Intensive English Program Students

  Nicholas Bianco, Patrick William O'Brien, Katie Marie Perry, Janeta Y Yancheva

  Having adequate health literacy is important in order for someone to be able to understand medical information that is presented to them. On UD’s campus, a large number of international students speak English as their second language. For this project, we worked with the Intensive English Program (IEP) students to create a brochure about sugar and the body that is more understandable and usable for their literacy level. We met with the IEP students at the beginning of the project to see what they already understood and what they wanted to learn more about. While the average American reading level is 8th grade, the IEP students in this course read at approximately a 3rd-4th-grade level. The goal of our project was to modify an existing document to make it readable and usable for the IEP students. The document we chose came from betterhealth.vic.gov.au. We first analyzed the four domains of health literacy by performing a Health Literacy Load Analysis in order to improve the readability in our final brochure. We field tested the draft with the IEP students once more before finalizing the brochure to gain feedback on their understanding of the material. The completion of the final document was followed with a SMOG and Word test and determined that the reading level was reduced significantly. This project showed us that it is possible to reduce a health document to a lower reading level in order to more effectively communicate health information.

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  Risk in Fraternity and Sorority Life: the Policies, Experiences, and Opinions of the Students

  Ally Katherine Michalski

  At times it seems as if the word risk is synonymous with fraternity and sorority life. Are there more problems involving students in Greek organizations or does the media make it seem that way? Are female students in sororities more likely to feel unsafe or be subjected to dangerous behavior? Do men and women in fraternities and sororities get lower grades? The purpose of this study was to find out what kind of risk, if any, students in fraternities and sororities feel exist on their campus or nationally. This research was conducted with the intent to learn from students and understand what experiences they have had while participating in Greek-letter organizations. Interviews were conducted with current undergraduate students from two different institutions to find out their thoughts and opinions about risk and their experiences thus far as members of their organizations. The questions were created based off of three topics that were recurrent while preparing to conduct interviews, alcohol consumption, sexual encounters, and individual student development and academics. The conclusions of this research come from time spent with various students from their different respective councils. It shows that while they may have chosen different organizations based on values and needs, many of their experiences when it comes to risk, and as a whole, have been similar.

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  Role of calcium signaling in Aβ42-mediated neurodegeneration in a Drosophila model of Alzheimer’s disease

  Neha Gogia, Chris Y Kang, Dena M Schaeffer, Catherine Jean Yeates

  Alzheimer’s disease (AD) is a neurodegenerative disease that affects more than five million individuals in the United States alone, where it is the sixth leading cause of death. While there is currently no cure for the disease, it is a highly investigated topic of research. The Drosophila melanogaster eye model is an excellent system to study AD, due to the highly conserved genetic machinery shared between flies and humans. We have developed a transgenic fly model of AD in which we use the GAL4/UAS system to misexpress high levels of human Aβ42 peptides in the differentiating photoreceptor neurons in the fly eye. We use this system to determine whether modulating the function of the calcium signaling pathway can modify Aβ42 mediated neurodegeneration. We used RNAi to knock down six components of the calcium signaling pathway (stim-RNAi, serca-RNAi, orai-RNAi, inx2-RNAi, ip3r-RNAi, and plc 21c-RNAi) in an Aβ42 background in the eye and observed the effects in both eye antennal imaginal discs and adult eyes. Our results showed evidence that knocking down components of the calcium signaling pathway may ameliorate the neurodegeneration mediated by Aβ42. Aberrant calcium signaling has also been implicated in cancer and other neurological diseases besides AD. Our research further implicates intracellular calcium signaling in neurodegenerative disorders such as AD. Further research will determine the molecular mechanisms linking calcium signaling with Aβ42 mediated neurodegeneration.

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  Role of Hippo and Ecdysone Receptor Signaling in regulation of dronc.

  Karishma Sanjay Gangwani

  The Hippo pathway is an evolutionarily conserved pathway that regulates organ size and tissue homeostasis in Drosophila and mammals. The pathway functions by regulating the nuclear availability of transcriptional cofactor Yorkie (Yki), mammalian YAP, which is regulated by the activity of a core kinase cascade comprising the serine threonine kinases Hippo (Hpo) and Warts (Wts) and their accessory proteins. Yki binds with transcription factors like Scalloped (Sd) or Homothorax (Hth) to regulate target genes involved in cell proliferation and survival. Downregulation of the Hpo pathway causes increased cell proliferation and overgrowth, whereas hyperactivation of this pathway leads to cell death due to activation of caspases. Caspase proteins are cysteine aspartic proteases which play essential roles in cellular signaling and development via apoptosis. We showed that the initiator caspase dronc (mammalian Caspase 9) is a transcriptional target of Yki. We found that loss of Hippo signaling leads to downregulation of dronc expression, whereas downregulation of Sd resulted in derepression of dronc expression. We also found that known binding partners of Sd like E2F and Tgi are also involved in regulating dronc expression. Earlier studies have shown that dronc expression is regulated by the Ecdysone receptor (EcR) signaling pathway and mapped a EcR regulatory element on dronc promoter. We found that depletion of EcR or its corepressors like Smrter caused de-repression of dronc expression. Overexpression of Taiman (Tai) a binding partner of EcR and Yki also derepressed dronc expression. We hypothesize that dronc expression is regulated by the Hippo and EcR signaling pathways. Here, we present our work on the regulation of dronc by the Hippo and EcR signaling pathways, and its implications on development.

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  Role of Hippo Signaling in Amyotrophic Lateral Sclerosis (ALS) disease using Drosophila eye model

  Neha Gogia, Abijeet Singh Mehta

  Amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s Disease, is a late-onset neurodegenerative disorder characterized by loss of cortical and spinal motor neurons with no known cure to-date. Mutations in genes including human Fused in Sarcoma (h-FUS), (caz in Drosophila), is a DNA/RNA binding protein, plays a crucial role in regulating nucleocytoplasmic RNA transport, alternative splicing and has known to be associated with causing ALS. It has been shown earlier that targeted misexpression of h-FUS or its mutants R518K and R521C (using GAL4/UAS system), in Drosophila melanogaster (a.k.a fruit fly) eye, causes accumulation of ubiquitinated proteins which enhances ALS mediated neurodegeneration. In order to 1. understand this process better, 2. search for genetic modifier of ALS and 3. to elucidate the mechanism of action by which FUS mediates neurodegeneration, we used this fruit fly eye model of ALS (as genetic machinery is conserved from fruit flies to humans) and, checked the effect of modulating the levels of Hippo (growth regulatory pathway, highly conserved) and c-Jun N-terminal Kinase (JNK) signaling in h-FUS or its mutants R518K, R521C background and checked for their resultant phenotypes in 1. larval eye-antennal imaginal discs and 2. adult fly eyes. Results from our studies confirms that, Hippo (hpo), is a newly identified genetic modifier of ALS mediated neurodegeneration, and that activation of Hippo or JNK pathway in FUS background worsens FUS mediated neurodegeneration while their in-activation significantly rescues FUS mediated neurodegeneration in fly eye. The results were confirmed by checking 1. cell death (TUNEL assay), 2. axonal targeting (functionality of photoreceptor neurons) from the retina to the brain, 3. Q-PCR, Western blot analysis, and 4. by checking how downstream targets of Hippo and JNK pathway gets regulated in these backgrounds. Our data presents a model that upregulation of FUS or its mutants, results in activation of Hippo pathway, which further activates c-Jun N-terminal Kinase (JNK) signaling and causes neurodegeneration/ photoreceptor neuronal cell death which ultimately causes ALS. This study helps in understanding the molecular genetic mechanism behind ALS associated h-FUS mediated neurodegeneration and finding effective, reliable future therapeutic targets that can modify the neurodegenerative behavior of ALS.

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  Role of Lunasin in Alzheimer’s disease

  Steven Gerard Borchers, Prajakta D Deshpande, Neha Gogia

  Alzheimer’s disease (AD), a common form of dementia and age related progressive neurodegenerative disorder, manifests as memory loss and reduced cognitive ability. One of the hallmarks of AD is the 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. Recently, we found that a plant protein Lunasin can ameliorate Aβ42 mediated neurodegeneration in the eye by blocking c-Jun N-terminal kinase (JNK) signaling pathway. It is known that Immune deficiency (IMD) pathway, Nuclear factor-κB (NF-κB) signaling pathway, Toll receptor pathway and JNK pathway crosstalk with each other in neurodegeneration. Here we test the role of IMD and NF-κB pathway in Aβ42 mediated neurodegeneration. Loss of function of Relish (Rel), a member of and NF-κB and its downstream gene- Diptericin rescues the small glazy eye phenotype. Our working model is that Lunasin might down-regulate JNK signalling pathway which in turn downregulates IMD pathway to ameliorate Aβ42 mediated neurodegeneration.

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  Role of Relish/NFkB Apoptosis Pathway in Amyloid-beta 42 mediated neurodegeneration in Alzheimer’s disease

  Steven Gerard Borchers, Prajakta D Deshpande, Neha Gogia

  Alzheimer’s disease (AD), is a neurodegenerative disease which affects mental functions of the patients. This disorder progresses with age and does not have a cure to-date. One of the reasons for the manifestation of AD is the accumulation of amyloid-beta-42 (Aβ42) proteins. In our study, we have used Drosophila as our model organism (as 75% of the genetic machinery is conserved between flies and humans), and have developed a model where when human Aβ42 is misexpressed in the differentiating eye, it triggers cell death in retinal neurons of the eye. We have identified that Lunasin (a soy-based anti-inflammatory protein), can block Aβ42 mediated cell death and thus wanted to test whether NFkB pathway (anti-inflammatory pathway, lead to translation of apoptotic proteins of jun-N Terminal Kinase, JNK pathway), helps lunasin blocking cell death. In order to test this, we developed transgenic flies which can produce human Aβ42 and Aβ42+Lunasin in Drosophila eye and checked the effect of modulating NFkB pathway in this background. Our hypothesis states that manipulating the levels of Relish (component of the Imd-NFkB pathway), could lead to activity variation in JNK pathway in Aβ42+Lunasin flies. To test our hypothesis, we used GAL4/UAS system genetic technique and misexpressed Relish and RelishRNAi in human Aβ42 and Aβ42+Lunasin background and checked for the resultant phenotypes in (1) larval eye discs and (2) adults. Our data shows that downregulation of Relish interferes with Lunasin’s ability to rescue Aβ42 phenotypes and thus leads to eye suppression phenotypes, which suggests that Imd-NFkB pathway plays a positive role in Lunasin’s ability to mitigate the neuronal cell death cause by the accumulation of Aβ42 plaques. These studies have significant bearing on the use of NFkB members as biomarkers or druggable targets and generate new insights into the mechanism by which Aβ42 mediated neurodegeneration cell death can be blocked in future.