IUPUI Research Day 2016

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A program describing the Research Day 2016 events and posters is available from: http://hdl.handle.net/1805/9288.

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    Tweets, Hashtags, & Likes: How is Social Media Use Related to Empathy?
    (Office of the Vice Chancellor for Research, 2016-04-08) Zarins, Sasha; Le, Ava; Mahurin, Emily; McFerran, Michael; Konrath, Sara H.
    Empathy is the tendency to perceive and interpret others’ perspectives and feel care and concern for them (Davis, 1983; Hoffman, 1977). However, empathy has been declining in American college students in recent years (Konrath, O’Brien, Hsing, 2011) and many scholars blame new technology and social media (see Konrath, 2012 for a review). Over the course of 3 separate studies, we investigated the relationships between social media usage and empathy. Study 1 found that among online adults Empathic Concern (emotional empathy) was related to less frequent Twitter use, β=-.07, p=.04, and Perspective Taking (cognitive empathy) was related to less frequent Facebook use, β=-.07, p=.05. However, Fantasy and Personal Distress were both associated with more frequent use of Twitter and Facebook, βs=.06-.11, ps=<.04. Study 2 found that among students, dispositional personal distress is associated with more daily tweeting, β=.60, p=.009, but fewer Facebook status updates, β=-.39, p=.007. Finally, Study 3 found that among teens, those higher in empathic concern were more likely to feel connected to their friends and family when using Facebook, β=.47, p=.03. These studies reveal that empathy is related to both the frequency of social media usage and the emotional connections experienced through social media. These results can be used to help better understand and navigate this fairly new media terrain. Our studies take a more comprehensive look at the relationship between empathy and social media use by measuring not only frequency of use but emotional connection on different social media platforms.
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    Identifying Metabolic Pathways Producing Alkamides in Echinacea purpurea
    (Office of the Vice Chancellor for Research, 2016-04-08) Williams, Jermell; Teitgen, Alicen; Minto, Robert
    Echinacea purpurea is a widely used herbal supplement that is frequently taken to relieve cold symptoms. Alkamides are a secondary metabolite found throughout the Echinacea genus that contain fatty acid chains incorporated into amides and are believed to be the bioactive agent in Echinacea. Our goal is to identify and understand the specific metabolic processes by which E. purpurea produces alkamides. In our experiment, Echinacea seedlings were grown to where the first true leaf emerged and unfurled which is when alkamide production is known to be most active. Alkamides were then extracted and taken to the GC/MS and LC/MS for analysis. Extracted alkamides were analyzed by triplequadrupole chromatography to investigate 13C labeling by glucose. Solid phase extractions were also performed to better observe fragmentation patterns. Fatty acids were also extracted to determine if fatty acids and alkamides were affected the same way by light or the lack of light, which would indicate that they are being synthesized in the same place. It was determined that neither compound experienced a synthesis decrease in the dark significant enough to support a model where acyl chains are newly created in the chloroplasts. Therefore alkamides are more likely to be made in the mitochondria. We are currently in the process of examining the spectra in order to determine the structures of the alkamides as well as any metabolic relationships.
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    Improving bone properties and fracture susceptibility: experimental models of genetic manipulation, pharmacologic intervention, and cellular perturbation reveal new approaches for improving bone health
    (Office of the Vice Chancellor for Research, 2016-04-08) Witcher, Phillip C.; Lee, Joowon; Assaf, Noor; Mertz, Susan; Singh, Karan; Thompson, William R.; Robling, Alexander G.
    Bone, a crucial support structure in the human body, is often taken for granted for its lightweight properties and unparalleled strength. Skeletal fracture is a major clinical condition affecting millions of Americans, which results from abnormal aging, hormonal imbalance, genetic conditions, and lifestyle choices (e.g., exercise). Because fractures are caused by a number of different factors, reducing fracture incidence requires a multifactorial approach to unraveling the underlying biology of bone metabolism, in order to discover new ways to improve bone properties and prevent fractures. We have taken such an approach by conducting (1) genetic manipulation experiments in mice, where genes predicted to be involved in bone mass regulation were mutated; (2) pharmacologic experiments to quantify the dose-response effect of an agent that inhibits bone loss, and (3) cell culture experiments, aimed at revealing molecular pathways activated by mechanical stimulation. METHODS: Mice with mutations in two genes, likely to regulate bone mass (SOST, DKK1) were generated and subjected to in vivo dual energy x-ray absorptiometry (DEXA) scans at 6-wk old. Whole body scans were analyzed for bone mineral density (BMD) using Lunar Piximus II v2.10 software. Mice (6-wk) were also dosed (0, 1, 10, 100, or 1000 mg/kg) with daily alendronate HCl, a bisphosphonate that inhibits osteoclast activity. Six wks later, the mice were sacrificed, and the femurs were dissected and sectioned for histological analysis of bone formation parameters, including mineralizing surface (MS/BS), mineral apposition rate (MAR), and bone formation rate (BFR/BS). To understand the cellular signaling events in response to mechanical loading, bone marrow mesenchymal stem cells (MSCs) were treated with 10, 20, 30, or 40μM PF7408671, an S6 kinase inhibitor. Cells then were subject to 100 cycles of biaxial mechanical strain (2%, 10 cycles/min). Protein lysates were separated by electrophoresis and probed for phosphorylation of Rictor and Akt by Western blot. RESULTS: Mice harboring mutations in either the SOST gene or the DKK1gene exhibited significantly increased BMD compared to wild-type control mice, though the SOST mutation had a stronger effect on BMD than DKK1. Mice with compound mutations (SOST and DKK1 mutations) had significantly greater BMD than mice with either single mutation, suggesting that inhibition of SOST and DKK1 might be an effective means to increase bone mass in patients susceptible to fracture. Mice treated with high-dose alendronate (100 or 1,000 mg/kg) exhibited significant decreases in bone formation parameters (MS/BS, MAR, and BFR/BS) compared to untreated (0 mg) mice, suggesting that while this compound might be beneficial for inhibiting bone loss, it also inhibits bone formation. The signaling hub, mTORC2, is a critical regulator of mechanical force in MSC progenitors. Our data demonstrate that S6 kinase is an upstream activator of mTORC2 in response to mechanical strain. CONCLUSION: Our experiments suggest that genetic manipulation of mice reveal viable protein targets (e.g., SOST, DKK1) that could ultimately be manipulated pharmacologically to improve bone mass. We also found that an FDA-approved class of drugs inhibits bone formation even at very low doses, suggesting that additional pro-anabolic compounds might benefit patients taking bisphosphonates. On a cell signaling level, we found that the mTORC2 pathway shows considerable promise for pharmacologic manipulation to simulate the effects of exercise. Taken together, these experiments highlight the utility of a broad approach to solving bone metabolism challenges that can affect fracture susceptibility.
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    Denial of Uniquely Human Characteristics for Voluntarily Childfree Individuals: Does Violating Social Norms Lead to Dehumanization?
    (Office of the Vice Chancellor for Research, 2016-04-08) Whitaker, Julia; Ashburn-Nardo, Leslie
    Nationally representative data consistently show that an increasing number of individuals are choosing not to have children (Time, 2013). Despite this trend, people who opt out of parenthood experience negativity (Berdahl & Moon, 2013). A recent study furthermore revealed that this negativity was driven by moral outrage (AshburnNardo, in press). Research on dehumanization includes moral sensibility as a characteristic of being human (Haslam, 2006). If those who forgo parenthood elicit moral outrage, it is possible that they are also seen as being less than human. The present research investigates the potential for dehumanization to occur in the form of denying uniquely human characteristics to voluntarily childfree individuals. In a between-subjects experiment, N participants were randomly assigned to evaluate a male vs. female married target who had chosen to have 0 vs. 2 children. They were then asked to rate the likelihood that the target was capable of experiencing uniquely human emotions (e.g., admiration, despair), as well as the likelihood that essential human traits (e.g., warm, irresponsible) and characteristics (e.g., rational, culturally refined) described the target. Statistical analyses are currently underway and are expected to reveal that, relative to targets who have children, targets that chose not to have children will be rated significantly less likely to experience uniquely human secondary emotions, to have complex cognitions and to have uniquely human traits. Target gender will be explored as a potential moderator of these effects. Historically, dehumanization has led to dangerous outcomes for targets. The present findings could suggest that a significant and growing portion of the population could be subject to discrimination in social and workplace situations.
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    Selective Plane Illumination Microscopy, A New Imaging Modality Available at the Indiana Center for Biological Microscopy
    (Office of the Vice Chancellor for Research, 2016-04-08) Winfree, Seth; Smith, Nathaniel; Dunn, Ken; Kamocka, Malgorzata; Molitoris, Bruce
    Microscopy is a primary tool for studying 3D tissue models. Microscopy provides the only means of distinguishing the behaviors of individual cells in a heterogeneous context that obscures biochemical assays. SPIM (Selective Plane Illumination Microscopy) is new approach that is ideally suited to the unique problems involved in high-resolution imaging of 3D tissue models. In the simplest form of SPIM, a cylindrical lens is used to generate a thin lightsheet (1-10 microns) that illuminates a sample. An imaging objective lens, placed orthogonal to this lightsheet is used to collect an image of fluorescence that is selectively excited in this single illuminated plane. The sample is then rotated, and the process is repeated until a multiview dataset of the entire sample is collected. These cross-section images are then assembled to give a complete 3D image of the sample. This approach offers several advantages over conventional methods of imaging thick tissues. First, SPIM provides superior axial resolution for large field-of-view images, deconvolved SPIM volumes have isotropic 3D resolution. Second, SPIM is a “gentle” imaging approach and is better suited to imaging living tissues than either confocal or multiphoton microscopy, supporting studies of cell migration, development, signaling and physiology. Third, imaging speeds can be 30 to 200 fold faster than scanning confocal or multiphoton systems, enabling resolution of dynamic events, and rapid collection of large image datasets. We describe the assembly and customization of an OpenSPIM based lightsheet microscope (IU OpenSPIM) as a platform for developing new imaging technologies. To this end we have implemented software and hardware for multi-channel laser control and temperature and perfusion control. We present examples of highresolution, live and high speed imaging, demonstrating these capabilities. The IU OpenSPIM is a centerpiece in the development of new software for 3D tissue cytometry and a novel screening platform.
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    International Factors Impacting Corporate Social Responsibility at STEM Organizations
    (Office of the Vice Chancellor for Research, 2016-04-08) Whinery, Tiffany E.
    Corporate Social Responsibility (CSR) has gained significant attention over the past decade and continues to grow as a rising global effort in STEM organizations across multiple industries. Many countries have a longstanding history of practicing CSR and have adopted or adapted the Western model of corporate volunteerism. However, little research has been conducted to determine cultural factors that impact this practice such as volunteer motivation, satisfaction, and project types. This study explores the CSR efforts of, Eli Lilly and Company (Lilly), whose annual day of service provides employees across the globe the opportunity to serve various organizations and their communities through diverse projects. This research aims to determine the influence of culture dimensions and societal norms on multiple aspects of Lilly’s volunteer efforts such as the acceptance of the practice and perspectives of volunteers.
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    Testing Therapeutic Candidates in a Mouse Model of Polycystic Kidney Disease
    (Office of the Vice Chancellor for Research, 2016-04-08) McConkey, Shannon; Yang, Jenny; Bacallao, Robert; Berbari, Nicolas F.
    Approximately 1 in 500 middle aged people in the United States will be diagnosed with Polycystic Kidney Disease (PKD), an inherited genetic disorder that results in extreme cysts on the kidneys. PKD eventually leads to end-stage kidney failure and current treatments are limited to dialysis or transplantation. Thus, a pharmacological approach to prevent, delay, or slow the progression of PKD would revolutionize treatment and improve mortality. Interestingly, many proteins associated with PKD have been found in and around the primary cilia of renal epithelial cells. Cilia are small microtubule-based cellular appendages found on the surface of most cell types in the human body and are broadly classified as either “motile” or “primary” (immotile). Primary cilia are known to be mechano- and environmental sensors, and play a critical role in cell-to-cell communication. The aim of this proposed research is to use potential therapeutics identified in silico and in vitro in animal models of PKD to determine if the compound can delay or prevent cystogenesis. Here we test Sildenafil citrate (Viagra) in an animal model of rapidly progressing cyst formation for its ability to ameliorate the phenotype. Further research directed at understanding the cilia, cell-cycle, and cilia-mediated signalling activity will hopefully provide important insights into the mechanisms of renal cyst pathogenesis and lead to better approaches for therapeutic intervention for PKD.
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    The NeoWarm biomedical device: Assessment of feasibility and cultural acceptability, identification of potential barriers and challenges, and stakeholder mapping
    (Office of the Vice Chancellor for Research, 2016-04-08) Watts, Thomasina; Siddiki, Furhan; Savita, Aakash
    Introduction: Across the globe, approximately 4 million newborns die each year; complications from hypothermia underlie many of these deaths. Regions with fewer resources for neonatal care have higher rates of hypothermia­related death. Kangaroo Mother Care (KMC) is the practice of prolonged skin­to­skin contact to prevent hypothermia among small and premature infants. KMC is cost effective, and proven to reduce hypothermia; however, KMC programs are often discontinued or fail to expand. A built prototype of a biomedical device, called NeoWarm, has been developed to augment KMC initiatives. Identification of potential barriers and facilitators to adoption the NeoWarm technology is urgently needed. Methods: In order to assess the feasibility of NeoWarm, and to identify current barriers to implementation of KMC and NeoWarm, a comprehensive literature review was conducted. Key barriers and facilitators to existing KMC programs in sub­Saharan Africa, Asia, and Latin America were identified. Stakeholder mapping and analysis in relation to the NeoWarm device for three “target countries” within each of these global regions was performed. Potential stakeholders were identified and categorically ranked in terms of influence and relevance. Results: Three key barriers to KMC programs were identified. These included: unacceptability among male stakeholders; lack of support from health care providers and insufficient health infrastructure, leading to fears of tuberculosis and other infections spreading in crowded KMC wards. Comprehensive stakeholder mapping for Kenya, India, and Guatemala revealed a complex web of potential influencers and regulatory processes for adoption of NeoWarm technology. Conclusion: The NeoWarm device may support increased acceptance of KMC among male stakeholders and some health care providers; however, the concerns regarding spread of tuberculosis among KMC mother­baby pairs was an unexpected finding, which will significantly inform subsequent NeoWarm development and testing. Stakeholder mapping and analysis revealed many potential NeoWarm partners within each region whom had not been previously identified.
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    Ab initio study of anisotropic mechanical properties of LiCoO2 during lithium intercalation and deintercalation process
    (Office of the Vice Chancellor for Research, 2016-04-08) Wu, Linmin; Zhang, Jing
    The mechanical properties of LixCoO2 under various Li concentrations and associated anisotropy have been systematically studied using the first principles method. During the lithium intercalation process, the Young's modulus, bulk modulus, shear modulus, and ultimate strength increase with increasing lithium concentration. Strong anisotropy of mechanical properties between a-axis and c-axis in LixCoO2 is identified at low lithium concentrations, and the anisotropy decreases with increasing lithium concentration. The observed lithium concentration dependence and anisotropy are explained by analyzing the charge transfer using Bader charge analysis, bond order analysis, and bond strength by investigating partial density of states and charge density difference. With the decrease of Li concentration, the charge depletion in the bonding regions increases, indicating a weaker Co-O bond strength. Additionally, the Young's modulus, bulk modulus, shear modulus, and toughness are obtained by simulating ab initio tensile tests. From the simulated stress-strain curves, LixCoO2 shows the highest toughness, which is in contraction with Pugh criterion prediction based on elastic properties only.
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    The translational regulator dFMRP interacts with epidermal growth factor receptor to regulate apoptosis in Drosophila
    (Office of the Vice Chancellor for Research, 2016-04-08) Zic, Jessica Z.; Sherwood, Jacqueline E.; Tessier, Charles R.
    Posttranscriptional gene regulation is required for all aspects of cellular and tissue development and is a major mechanism underlying many diseases ranging from neurological disorders to cancer. The translational repressor fragile x mental retardation protein (FMRP) is ubiquitously expressed throughout development but is silenced in Fragile X Syndrome, an autism spectrum disorder. Interestingly, high levels of FMRP have recently been identified in human metastatic breast cancer. FMRP overexpression in these patients is directly correlated with increased lung metastasis suggesting a direct role for translational regulation both in cell proliferation and in invasive cell migration. Interestingly, however, FMRP can promote both proliferation and apoptosis. To dissect FMRP’s role in cancer development and progression, we are exploiting the powerful genetic system of Drosophila. Drosophila is an excellent model organism for human diseases associated with FMRP due to the strong evolutionary conservation of the fragile x mental retardation gene 1 which encodes this protein. dFMRP was overexpressed in the Drosophila imaginal wing disc, an epithelial tissue model. Contrary to a role in proliferation, overexpression of dFMRP leads to obvious cell loss in the adult wing and an increase in apoptotic markers. Using a combinatorial genetic screen, we have identified genes which are able to suppress this apoptotic phenotype and thus may be important for FMRP-­‐dependent tumorigenesis. Our focus is now on the epidermal growth factor receptor (EGFR) signaling pathway since blocking this mechanism is able to completely rescue the dFMRP-­‐overexpression wing defects. Clonal analysis reveals that dFMRP overexpressing cells survive their dFMRP-­induced apoptotic programming when co-­‐expressing a dominant negative form of EGFR. Additional clonal analyses are being used to explore the potential significance of this survival on tumor formation and metastasis.