IUPUI Research Day 2015

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https://hdl.handle.net/1805/6250

A program book describing the Research Day 2015 events and posters is available from: http://hdl.handle.net/1805/9289.

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The Health of the Serbian Roma/Gypsies: A Research Report
(Office of the Vice Chancellor for Research, 2015-04-17) Biviji-Sharma, Rizwana; Cvorovic, Jelena; Coe, Kathryn
The Balkan region is densely populated by Roma, a socially disadvantaged, stigmatized and relatively reproductively isolated ethnic group. Health data from across Europe show that being a Roma is associated with much poorer health status than is seen in the majority populations or among other ethnic minority groups. These data may not be accurate as the number of Roma was grossly underestimated. Almost nothing is known about the health of Serbian Roma. In this presentation we describe the results of a 2014 study of Serbian Roma women living in two settlements in the northern province of Serbia, with a focus placed on investigating health history of the females and their close kin. We focused on health concerns and on behaviors that are protective or that increase risk for chronic diseases (e.g., cancer, diabetes, and cardiovascular diseases). A special focus placed on reproductive histories.
Delayed effects of acute radiation exposure (DEARE) in a murine model of the hematopoietic acute radiation syndrome: Multiple-organ injury consequent to total body irradiation
(Office of the Vice Chancellor for Research, 2015-04-17) Quickery, Ariel; Unthank, Joseph L.; Miller, Steven J.; Orschell, Christie M.
Introduction. Victims of radiation exposure from terrorist activity, radiation accidents or radiologic warfare will face a variety of acute and chronic organ injuries requiring multi-faceted approaches to treatment. The hematopoietic system is the most sensitive tissue to radiation damage, resulting in the hematopoietic acute radiation syndrome (H-ARS) after exposures of 2-10 Gy in mice. If untreated, H-ARS results in death within weeks from opportunistic infection and/or hemorrhage due to loss of neutrophils and platelets, respectively. However, survivors of ARS are plagued months to years later in life by delayed effects of acute radiation exposure (DEARE), a myriad of chronic illnesses affecting multiple organ systems believed to be due to persistent systemic oxidative stress, inflammation, fibrosis and loss of stem cell self-renewal. Fibrosis and collagen deposition disrupt both normal tissue structure and function and are common to organs with late radiation injury including the kidney and heart after radiation doses >15Gy, but have not been shown to exist after doses as low as those used in the H-ARS model (8Gy). The goal of this study was to determine the extent, if any, of heart and kidney DEARE in survivors of H-ARS. Methods. Mice (male and female C57BL/6) received total body irradiation (TBI; LD50/30 to LD70/30) and kidney and heart were harvested at 9 and 21 months from the H-ARS survivor mice. Tissues were fixed in neutral buffered formalin, paraffin embedded and sectioned, then stained with hematoxylin/eosin (H&E), trichrome, or picosirius red. Serum was collected at 4.3, 9, and 21 months post-TBI and analyzed for blood urea nitrogen (BUN) as an indicator of kidney function. Total RNA was purified from heart and relative changes in NADPH oxidase 2 (Nox2) mRNA expression were assessed by quantitative real-time PCR. Results/Significance. Compared to age-matched non-irradiated controls (NI), renal pathology at 9 months post-TBI was manifest primarily as enlargement of Bowman’s capsule and glomerosclerosis along with limited interstitial fibrosis. By 21 months there was progression of these pathologies as well as extensive interstitial fibrosis, tubular atrophy, cysts, and atubular glomeruli, all of which were more pronounced in TBI mice compared to NI. Consistent with the renal pathology, BUN in TBI mice was significantly increased at 9 and 21 months post-TBI vs. 4.3 months, but normal in NI mice at all time points. In the heart, pericardial, perivascular and interstitial fibrosis were observed at 9 months with increased severity at 21 months post-TBI compared to NI. The perivascular fibrosis was associated with increased medial layer collagen and apparent loss of vascular smooth muscle cells. Nox2 mRNA in heart was increased at 9 and 21 months post-TBI, indicating an increase in oxidant stress. To our knowledge, such striking heart and kidney damage has not been documented after radiation doses as low as those in our H-ARS model (~8Gy) and indicate that DEARE is a concern for individuals exposed to radiation doses previously thought to not elicit late effects.
The First 4 Weeks Postpartum: The Mother’s Breastfeeding Concerns and Support
(Office of the Vice Chancellor for Research, 2015-04-17) Rosales, Stacy A.; Shieh, Carol; Bakas, Tamilyn; Busby, Katie
Objective: The first four weeks postpartum are critical for establishing successful breastfeeding because many women wean or stop exclusive breastfeeding during this time. This study explored the breastfeeding concerns of mothers during the first 4 weeks postpartum and the support sought for those concerns. Design: A qualitative approach was used. Participants: Four mothers, recruited from central Indiana in 2014 through social media or word of mouth participated in the study. Inclusion criteria were women in their first four to six weeks postpartum, delivered full term healthy babies and were discharged from the hospital breastfeeding. Methods: Semi-structured telephone interviews were conducted and data were analyzed using content analysis. Interview transcripts were first coded. Codes with similar meaning were grouped into categories. Categories sharing similar features were again collapsed into common themes. Results: Concerns identified by mothers fell into the themes: Infant breastfeeding difficulties (latch), breast complications related to breastfeeding (pain and nipple trauma), and maternal concerns related to milk production (infant milk intake and milk supply). Four common themes of support were identified that mothers utilized to alleviate concerns: Professional support, informational support, peer support, and family support. Conclusions: Mothers identified concerns related to themselves and their infants with respect to breastfeeding in the first four weeks postpartum. These concerns indicate the women’s struggle with establishing a successful breastfeeding pattern and one that is compromised by infant latch difficulty, nipple pain and inadequate milk production. Support was sought at multiple levels from health care professionals to social media. The findings suggest that support from health care professionals who provide valuable information is important. However, postpartum women also utilize other support methods when encountering breastfeeding concerns in the first four weeks postpartum. When developing interventions to assist postpartum women with establishing breastfeeding outside of the hospital setting, nurses need to consider using social media and social networks as resources for breastfeeding information and support.
Evaluation of osteoclastogenesis in the Ts65Dn Down Syndrome Mouse Model
(Office of the Vice Chancellor for Research, 2015-04-17) Abeysekera, Irushi S.; Raje, Kimaya; Roper, Randall J.
Down Syndrome (DS) affects ~1 in 700 live births and is caused by trisomy of human chromosome 21 (Hsa21). DS is characterized by a wide spectrum of phenotypes including cognitive and skeletal abnormalities that affect all individuals with DS. To study these phenotypes, we utilize the Ts65Dn mouse model, which contains three copies of approximately half the gene orthologous found on Hsa21 and exhibits similar phenotypes as found in humans with DS. Individuals with DS and Ts65Dn mice have deficits in bone mineral density (BMD), bone architecture, and bone strength. Three copies of DYRK1A, a serine-threonine kinase encoded on Hsa21, has been linked to deficiencies in bone homeostasis in DS mouse models and individuals with DS. DYRK1A is thought to act via NFATc1, a master regulator of osteoclastogenesis. Epigallocatechin-3-gallate (EGCG), a polyphenol found in high concentrations in green tea, is a known inhibitor of DYRK1A activity. We propose that the DS bone phenotype arises from an increase in osteoclastogenesis and/or maturation which results in increased bone resorption and disrupted bone homeostasis. We hypothesize that treatment of the mice during adolescence with 100 mg/kg/day EGCG would result in normalization of osteoclast numbers in trisomic mice to that of the controls. Osteoclast precursors from femur and spleen were isolated from 8-10 week old mice treated with 100 mg/kg/day EGCG or water from three weeks of age onwards. The cells were grown in the presence of M-CSF & RANK-L to promote osteoclast differentiation. Following 3 weeks in culture, the cells were fixed, TRAP stained, and multinucleated osteoclasts from control and Ts65Dn treated and untreated mice were counted. Mentor: Randall Roper, Department of Biology, IUPUI School of Science, Indianapolis, IN
Targeting the Role of Tyrosine in Amot Protein-lipid Binding Events
(Office of the Vice Chancellor for Research, 2015-04-17) Abufares, Nawara A.; Kimble-Hill, Ann C.
Amot proteins have been shown to control cell proliferation and differentiation and can selectively bind with high affinity to phosphoinositol containing membranes. This binding event is linked to endocytosis, changes in cellular polarity, and apical membrane sequestration of nuclear transcription factors associated with development of cancer phenotypes. Although the lipid selectivity of the protein has been well characterized, the mechanisms involved in the Amot coiled-coil homology domain (ACCH) binding these membranes are not yet known. The fluorescence properties of the ACCH domain were used to characterize the binding event, however it became clear each of the five native tyrosines proximity to membrane might differ based on fluorescence resonance energy transfer experiments with fluorescently tagged lipids. A variety of short peptides correlating to the amino acid sequence of Amot surrounding these tyrosines were assayed and observed in different membrane mimicking environments to determine if each tyrosine had the ability to bury into the hydrophobic region of the membrane (alcohol study), or simply interacted with the hydrophilic head groups (liposome study). Interactions were characterized by shifts in absorbance, excitation and emission scans peaks. A characterization of these shifts with respect to what is seen with the various tyrosine-phenalanine mutants will further our understanding of whether each tyrosine is buried within the protein or interacts with the membrane. Mentor: Ann Kimble-Hill, Department of Biochemistry, IU School of Medicine
A conceptual model of mental illness stigma constructs
(Office of the Vice Chancellor for Research, 2015-04-17) Adams, Erin L.; Salyers, Michelle P.
Mental illness (MI) stigma negatively impacts a range of psychosocial and functional outcomes, and has yielded a significant volume of empirical literature. In a recent meta-analysis of 256 studies of mental health providers’ stigma towards their own patients, over 90 named stigma instruments were identified and 85 publications created their own instrument to be used in a single study. The exceptional number of stigma instruments in the literature raises questions about the conceptualization of stigma and limits the conclusions that can be drawn across studies. Current literature broadly conceptualizes stigma towards MI as consisting of stereotypes (beliefs), prejudice (emotions), and discrimination (actions). The current analysis expands this framework by categorizing each instrument into primary, secondary, and tertiary stigma categories to produce a model displaying the variety of constructs being assessed (briefly outlined below). Understanding the diversity of these constructs may allow for a nuanced interpretation of existing literature, and may spark discussion as to the centrality of certain constructs within MI stigma. Understanding the current stigma measurement landscape may allow for a reduction in the number of instruments currently in use, enhancing consistency and interpretability of empirical results. Stereotype instruments assess beliefs about the abilities or fundamental qualities of individuals with MI. Four secondary categories emerged. Negative Attributes measures undesirable personal characteristics of individuals with MI and contains four tertiary categories: dangerousness, personal control (i.e., MI symptoms are volitional), moral failing (i.e., symptoms are due to a weakness in character), and resistance to treatment. Prognosis measures beliefs about outcomes and future functioning of individuals with MI within two tertiary categories: optimism for treatment outcome and stability. Present Functioning requires respondents to estimate patients’ likely social integration and quality of life. Competence assesses beliefs about general intelligence, talents, and abilities of individuals with MI. Prejudice instruments assess emotion-based reactions to those with MI. The two secondary categories that emerged were Emotional Reactions and Beliefs about Managing Mental Illness. Emotional Reactions includes the tertiary categories of empathy, negative emotions (i.e., fear, disgust, anger), and professional burnout. Beliefs about Managing Mental Illness measures emotional- and value-based approaches to societal management of individuals with MI and contained four tertiary categories. Authoritarianism emphasizes individuals with MI are inferior and should be handled in a restrictive or coercive manner. Benevolence encompasses paternalistic pity and the belief that individuals with MI must be cared for like children. The prosocial view espouses a Community Mental Health Ideology, in that individuals with MI are just like anyone else and treatment should be integrated into the community and society. Finally, some instruments assess whether it is worthwhile to treat MI. Discrimination instruments assess intent or desire to treat individuals with MI differently from others. The three secondary categories that emerged were Social Distance, Willingness to Treat, and Civil Rights. Social Distance describes the desire to limit social contact with individuals with MI, while Willingness to Treat assesses whether mental health professionals are willing to care for individuals with MI. Civil Rights instruments assess restriction of patients’ human rights within four tertiary categories, including whether individuals with MI should be allowed to: engage in common social roles (e.g. parent, spouse, citizen, employee); participate in their own care; and refuse treatment. These instruments also assess whether patients should be forcibly restrained or secluded. Instruments with items that fell into at least two primary stigma categories and assessed a range of emotions, intended behavior, and beliefs about MI were categorized as General stigma.
Interaction of synchronized dynamics in cortical and subcortical circuits in Parkinson’s disease
(Office of the Vice Chancellor for Research, 2015-04-17) Ahn, Sungwoo; Zauber, S. Elizabeth; Worth, Robert M.; Witt, Thomas; Rubchinsky, Leonid L.
Parkinson’s disease pathophysiology is marked by increased oscillatory and synchronous activity in the beta frequency band in cortical and basal ganglia circuits. This study explores the functional connections between synchronized dynamics of cortical areas and dynamics of subcortical areas in Parkinson’s disease. We simultaneously recorded neuronal units (spikes) and local field potentials (LFP) from subthalamic nucleus (STN), and electroencephalograms (EEGs) from the scalp in parkinsonian patients and analyzed the correlation between the time-courses of the spike-LFP synchronization and inter-electrode EEG synchronization. We found the (noninvasively obtained) time-course of the synchrony strength between EEG electrodes and the (invasively obtained) time-course of the synchrony between spiking unit and LFP in STN to be weakly, but significantly correlated with each other. This correlation is largest for the bilateral motor EEG synchronization followed by bilateral frontal EEG synchronization. Our observations suggest that there may be multiple functional modes by which the cortical and basal ganglia circuits interact with each other in Parkinson’s disease: not only synchronization may be observed between some areas in cortex and the basal ganglia, but also synchronization within cortex and within basal ganglia may be related, suggesting potentially more global way of functional interaction. More coherent dynamics in one brain region may modulate or activate the dynamics of another brain region in a more powerful way causing correlations between changes in synchrony strength in both regions.
Analysis of Heart Rate Variability in Male and Female Rats
(Office of the Vice Chancellor for Research, 2015-04-17) Ajayi, Tolulope O.; Santa Cruz Chavez, Grace; Schild, John H.
Heart disease is the leading cause of death in the United States. Quantitative measures of cardiovascular function are often essential to effective clinical interventions. The QRS complex is one such measure widely used by cardiologists. These analyses can involve subtle changes in the magnitude and time course of the QRS complex, to differences in the timing between successive heart beats. Electrocardiograms (ECG) are continuous recordings of the QRS complex at various locations across the body surface and provide a comprehensive measurement of the electrical activity of the heart. Knowledge obtained from investigating ECG signal characteristics can help the cardiologist diagnose possible health or cardiac abnormalities such as arrhythmias and can provide objective measures of heart health following injury such as myocardial infarction. Heart rate variability (HRV) can also serve as a reliable indicator of heart health and has been shown to be a strong indicator of mortality and morbidity following myocardial infarction. Unfortunately, very little is known concerning the neurophysiological mechanisms underlying HRV beyond the broader impact of the autonomic nervous system and associated neurocirculatory reflexes. In this research project, we first implemented several established methods for quantifying HRV in male and female rats such as calculating the power spectral density of a long time series of HRV measures, and calculating the standard deviation of the averages of all beat-to-beat intervals in the recording. These measures compared well to those in the literature supporting the accuracy and reliability of the Matlab scripts created to process these data. Simultaneous recordings of the QRS complex and femoral arterial pressure (BP) provided the opportunity to determine how well BP recordings could be used to quantify HRV. In addition, HRV measurements were compared across populations of male and normal, cycling (OVI) and ovariectomized (OVX) female rats in order to determine if HRV is sexually dimorphic. Mentors: John H. Schild, Grace Santa Cruz Chavez, Department of Biomedical Engineering, Purdue School of Engineering and Technology, IUPUI, Indianapolis, IN
The Development of a Wireless Control System for Integration on Drones
(Office of the Vice Chancellor for Research, 2015-04-17) Allen, Tim; Tovar, Andrés
The use of remotely controlled drones has proven to assists humans in day to day life. Whether it be by keeping our military personnel safe, defusing bombs, or exploring parts of space humans have not yet reached. The purpose of this project was to develop a control system that can be used on a drone. The control system allows a user to control a radio controlled vehicle up to 300 yards away. It contains a wireless video feedback system so that the user can still control the vehicle even when it is out of the user’s line of sight. The user controls the vehicle with a custom made software package that includes a graphical user interface. The software takes commands from the user and transmits them through the serial port to an xBee module. The xBee module on the vehicle receives the information and transmits it to the microcontroller on the vehicle. The microcontroller then executes necessary commands and sends any feedback required. The software package includes controls for the steering, throttle, and camera control. The outcome of this project is a control system that can be incorporated in to future drone projects. The software is fully documented to make customizing it to individual projects simple. The circuitry on the receiving end of the control system contains serial ports to make it possible to integrate any other peripheral technology in to the existing control system. The end result of this project is a working prototype that will allow future students to build off of. This will expedite further research of drones at IUPUI. Mentor: Andres Tovar, Department of Mechanical Engineering, Purdue School of Engineering and Technology
The Role of Transforming Growth Factorβ (TGF-β)-activated Kinase 1 (TAK1) in Retinal Development
(Office of the Vice Chancellor for Research, 2015-04-17) Altara, Ira; Tiwari, Sarika; Belecky-Adams, Teri
Purpose: The formation of the retina is dependent on multiple transcription factors being expressed in the correct time and place. Transforming growth factor-β-activated kinase1 (TAK1), a serine threonine kinase, has been increasingly associated with regulation of proliferation, differentiation and apoptosis of many cell types both within and outside of the central nervous system. However, little is known about its role in development of the retina. Previous results from our lab have indicated that TAK1 is expressed throughout the developing retina; however activated TAK1 is found predominantly in the dividing progenitors of the early developing chick retina. Retinas injected with TAK1 inhibitor appeared to have an increase in progenitor population and a decrease in differentiating retinal ganglion cells. The present study evaluated the potential role of TAK1 in inducing apoptosis in the developing chick retina. Methods: Embryonic day 3(E3) chick retina were injected with vehicle and 1.0 M or 2.0 M concentration (5Z)-7-Oxozeaenol, an irreversible inhibitor of TAK1. 24 hours post inhibition the tissue was harvested. Immunohistochemistry (IHC) was performed to analyze the levels of cleaved caspase 3 expression, a protein activated during apoptosis. Nuclei stained with DAPI were used to quantify the number of cells expressing the caspase3. Lipopolysaccharide (LPS) treated adult, postnatal 30 (P30), mouse retina was used as a positive control for our IHC. Results: No difference in the level of cleaved (activated) caspase 3 immunolabel was found in vehicle-, 1.0 and 2.0 M inhibitor-injected retinas. Conclusion: Lack of cleaved caspase 3 immunolabel in TAK1-inhibited retinas indicates that TAK1 may not be playing any role in inducing cell death through apoptosis in the developing chick retina used in our study. These preliminary results suggest further research should be done to better understand its role in retinal development. Mentors: Teri Belecky-Adams and Sarika Tiwari, Center for Regenerative Biology and Medicine, IUPUI, Department of Biology, IUPUI

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