IUPUI Research Day 2013

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https://hdl.handle.net/1805/4887

A program book describing the Research Day 2013 events and posters is available from: http://hdl.handle.net/1805/4914.

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Exercise Completed When Young Provides Lifelong Benefit to Cortical Bone Structure and Estimated Strength
(Office of the Vice Chancellor for Research, 2013-04-05) Warden, Stuart J.; Roosa, Sara Mantila; Hurd, Andrea L.; Fuchs, Robyn K.
Exercise induces greatest bone gains during growth, yet reduced bone strength is an age-related phenomenon. This raises the question of whether exercise-induced bone changes when young persist into adulthood. The current studies used Major/Minor League Baseball (MLB/MiLB) players to explore whether exercise-induced gains in humeral bone structure and strength accrued when young persist lifelong. MLB/MiLB players are a unique model as the unilateral upper extremity loading associated with throwing enables the contralateral side to serve as an internal control site and former MLB/MiLB players were consistently exposed to extreme loading reducing secular variations in exercise levels between generations. Dominant-to-nondominant (D-to-ND) differences in humeral cross-sectional properties in MLB/MiLB players were normalized to matched controls to correct for side-to-side differences due to elevated habitual loading associated with arm dominance. Exercise when young induced significant skeletal benefits, with active MLB/MiLB players having nearly double the estimated ability to resist torsion (polar moment of inertia, IP) in the humerus of their dominant arm. The cortical bone mass and area benefits of exercise observed in active MLB/MiLB players were lost in former MLB players following 40-49 years of detraining as a result of elevated medullary expansion and endocortical trabecularization. However, 42% of the total bone area benefit persisted following 50+ years of detraining and contributed to the maintenance of 24% of the benefit on IP. In MLB players who continued to exercise during aging, medullary expansion and endocortical trabecularization were reduced and there was maintenance of the cortical bone mass and area benefits of exercise. These cumulative data indicate: 1) the extreme plasticity of the growing skeleton to exercise; 2) that exercise when young has lifelong benefits on cortical bone size and estimated strength, but not bone mass, and; 3) exercise continued during aging maintains the bone mass benefits of exercise.
Regulation of EVI5, VEGF and P53bp2 during Amphibian Limb Regeneration
(Office of the Vice Chancellor for Research, 2013-04-05) Elkhatib, Wiaam
Understanding limb regeneration on a molecular level could lead to new methods of healing for humans, therefore revolutionizing current medical treatments. The axolotl salamander possesses capabilities of limb regeneration that are lost in the Xenopus laevis froglet. The hypothesized reason is that elevated levels of EVI5 (ecotropic viral integration site 5) binding protein allow the axolotl to regenerate by delaying the mitosis of dedifferentiated cells until they have established a blastema. VEGF (vascular endothelial growth factor) and P53bp2 (tumor protein 53 binding protein 2) genes also take part in this process by stimulating blood vessel formation and regulating apoptosis and cell growth in regenerated tissue. The objective of this study is to clone EVI5, VEGF, and P53BP2 cDNA that can be used to detect their mRNA transcripts during limb regeneration in the axolotl and Xenopus laevis. To accomplish this, RNA is extracted from axolotl and Xenopus laevis limb tissue using an RNeasy kit. Total RNA concentration is then measured spectrophotometrically. RT-PCR (reverse transcription polymerase chain reaction) is used to clone the cDNAs, which are identified by Agarose gel electrophoresis and later sequenced for verification. It took half a year to get high enough RNA concentrations from both species’ tissues and then clone the three genes. The EVI5 band size was determined to be about 200bps, VEGF about 370bps, and P53bp2 about 500bps using the Agarose gel electrophoresis, signifying successful gene cloning. The long-term goal is to determine the role these genes play in limb regeneration with the aim of applying that knowledge to new medical treatments.
Ethanol-induced Retinal Defects are Rescued by Retinoic Acid Supplement in Developing Zebrafish Embryos
(Office of the Vice Chancellor for Research, 2013-04-05) Muralidharan, Pooja; Sarmah, Swapnalee; Marrs, James A.
Fetal Alcohol Spectrum Disorder (FASD) is caused by prenatal alcohol exposure, producing a spectrum of defects including facial abnormalities, sensory (visual and auditory) deficits, impaired fine motor skills and learning deficits including mental retardation. Our laboratory has used a zebrafish model for FASD that exposes embryos to ethanol during early development (midblastula transition through somitogenesis). Children diagnosed with FASD frequently show severe eye defects ranging from small eyes, underdeveloped optic nerve, and cataract. Zebrafish embryos exposed to ethanol showed defects similar to human eye birth defects. Presence of ethanol affected the differentiation of many retinal cell types including, retinal ganglion cells and photoreceptors. We hypothesize that ethanol may affect retinal patterning by competing with Retinaldehyde dehydrogenase (Raldh), reducing retinoic acid (RA) synthesis and signaling. Co-treatment of embryos with ethanol and 10-9 M RA could rescue the photoreceptor and retinal ganglion cell differentiation defects in the retina. RA plays a crucial role in the dorso-ventral patterning of the retina, and the enzymes involved in RA biosynthesis are expressed in the ventral retina during mid-somitogenesis stage. Our experiments showed that ethanol exposure during that critical time window when Raldh is expressed in the ventral retina causes severe defects in retinal cell specification. No defects were induced by ethanol exposure at the earlier stages. Presence of RA during photoreceptor differentiation could rescue ethanol-induced photoreceptor differentiation defects. Future work will dissect molecular mechanisms underlying ethanol defects, including retinoic acid-mediated eye development mechanisms. Determining the effects of ethanol exposure on retinal morphogenesis and differentiation will help identify potential therapeutic targets for ocular defects in this regrettably frequent birth defect syndrome.
THE INDIANA CENTER FOR BREAST CANCER RESEARCH: PROGRESS REPORT
(Office of the Vice Chancellor for Research, 2013-04-05) Nakshatri, Harikrishna; Sledge, George W., Jr.; Badve, Sunil; Bales, Casey; Gilley, David P.; Goswami, Chirayu; Wells, Clark D.; Guise, Theresa; Ziner, Kim W.
The mission of IUPUI breast cancer center is to address prevention, early detection, and treatment of breast cancer through translational projects, supportive cores, and synergistic programs. This poster details our efforts improve resources for breast cancer research and efforts to develop multi-PI investigator proposals. The Signature Center Initiative has developed two web resources: the Breast Cancer Prognostics Database (BCDB) to study prognostic implications of genes of interest in publically available breast cancer databases and PROGmiR, a microRNA database. The BCDB can be used to study overall, recurrence free and metastasis free survival in large patient series. PROGmiR allows investigators to study the prognostic importance of microRNAs. PROGmiR has recently been published and has been accessed by investigators from several countries. The signature center has also devoted considerable efforts in developing tumor tissue resource. Tissue Bank includes a total sample of N = 500 cases with 30% non-Caucasian cases from Wishard Memorial Hospital. Currently 237 cases have been assembled into a Tissue Microarray with clinical and follow up data. The breast cancer center has funded three pilot projects. Drs. Clark Wells, S. Badve, and G. Sandusky are collaborating on the project: “Histologic Analysis of the Protein Levels of Amot130, AmotL1 and YAP in Normal, Hyperplastic and Invasive Breast Cancer Tissues”. This project is investigating localized protein expression in paraffin-embedded tissues to associate expression levels with disease subtype and patient outcome. Dr. David Gilley and his group are collaborating on the project: “Luminal mammary progenitors are a unique site of telomere dysfunction”. This project is investigating the relationship between telomere dysfunction and breast cancer tumorigenesis. In the third project, Dr. Theresa Guise will be investigating the mechanisms of cancer-associated cachexia. Several multi-PI proposals are under preparation and one proposal with Drs. Nakshatri and Kathy Miller as PIs is currently under review.
Barriers, Facilitators, and Suggestive HIV Interventions for Women: Preliminary Data from a Secondary Analysis
(Office of the Vice Chancellor for Research, 2013-04-05) Schmitt, Herman C.; Burrage, Joe
The Centers for Disease Control and Prevention report that women account for almost ten thousand of those newly diagnosed with HIV annually. Within this group, Latina, non-Latina white and non-Latina black women are particularly affected. The purpose of this secondary analysis was to analyze existing de-identified data for barriers and facilitators for HIV testing and willingness to participate in a vaccine if available. The data were 30 de-identified transcripts of one hour interviews obtained from three groups of women (10 Latinas, 10 non-Latina white, and 10 non- Latina black) during the initial phase of a parent study, “HIV Testing and Women’s Attitudes on HIV Vaccine Trials”: G. Zimet, PI. A semi-structured interview guide had been used to guide the interviews. This sub analysis was conducted with removal of ethnic classification to reduce bias during qualitative review. Three predominant categories of fear, time, and cost emerged from all interviews regardless of ethnicity. Less prominent categories of gender, education, trust, motherhood, discrimination, loss of integrity, invincibility, safety, age, testing accuracy, confidentiality, indifference, pride, lifestyle, divine justice, and stress varied among the three groups. These categories will provide the basis for further analysis to determine subthemes and themes, and if there are themes unique to any of the three groups.
Axolotl Xenografts Improve Regeneration of Xenopus Hind Limbs
(Office of the Vice Chancellor for Research, 2013-04-05) Chen, Xiaoping; Stocum, David L.
Axolotls regenerate perfect copies of amputated limbs, whereas Xenopus froglet limbs regenerate only a spike of cartilage. We asked whether axolotl muscle and cartilage xenografted from normal or GFP-labeled limbs to amputated froglet limbs, with or without treatment with cyclosporin A (CSA) and/or retinoic acid (RA), would improve Xenopus limb regeneration via the release of regeneration-promoting factors into the host limb tissue. The grafted froglet limbs were allowed to regenerate for three months to two years. We detected initial symptoms of graft vs. host disease with or without CSA treatment that subsequently disappeared. The grafted limbs first formed a spike that subsequently grew wider at the tip and after three months began to separate into 2-5 digit-like structures that continued to grow. CSA and low-dose RA treatment decreased the time at which digit formation could be detected but were not necessary for digit formation. The digit pattern was not asymmetric, thus individual digits were not identifiable. Immature muscle was detected in the regenerated limbs by trichrome and MF-20 antibody staining, and nerve fibers were detected by Luxol Fast Blue staining. In one limb with a GFP graft, a few axolotl cells were detected around the base of the digits that may have stimulated digit separation. Although the mechanism of digit formation remains obscure, we conclude that factors released by degraded axolotl tissue or surviving axolotl cells can stimulate complex tissue regeneration and initiate the first step of digital anterior-posterior pattern formation in regenerating Xenopus hind limbs. These results have significance for the possibility of stimulating the regeneration of complex mammalian structures that have been injured by trauma or disease.
Institute for American Thought
(Office of the Vice Chancellor for Research, 2013-04-05) IUPUI (Campus). Institute for American Thought
This poster will have images of recent volumes published by the critical editions being edited by the Institute for American Thought. Information will tell how long the critical editions have been in existence, how much funding has been received. The five critical editions of the Institute along with its two academic programs will be mentioned.
Paced Respiration for Vasomotor and Other Menopausal Symptoms: A Randomized, Controlled Trial
(Office of the Vice Chancellor for Research, 2013-04-05) Carpenter, Janet S.; Burns, Debra S.; Wu, Jingwei; Otte, Julie L.; Yu, Menggang
Background: Paced respiration has been internationally recommended for vasomotor symptoms (e.g., hot flashes, night sweats) despite limited empirical evidence. Objective: To evaluate efficacy of a paced respiration intervention against breathing control and usual care control for vasomotor and other menopausal symptoms. Design: A 16-week, 3-group, partially blinded, controlled trial with 2:2:1 randomization and stratification by group (breast cancer, no cancer) was conducted in a Midwestern city and surrounding area. Participants: 218 randomized women (96 breast cancer survivors, 122 menopausal women without cancer) were recruited through community mailings and registries (29% minority). Interventions: Training, home practice support, and instructions to use the breathing at the time of each hot flash were delivered via compact disc with printed booklet (paced respiration intervention) or digital videodisc with printed booklet (fast shallow breathing control). Usual care control received a letter regarding group assignment. Main Measures: Outcomes included hot flash frequency, severity, and bother (primary), hot flash interference in daily life, perceived control over hot flashes, and mood and sleep disturbances (secondary). Intervention performance, adherence, and adverse events were assessed. Key Results: There were no significant group differences for primary outcomes at 8- or 16-weeks post-randomization. Most intervention participants did not achieve 50% reduction in vasomotor symptoms despite demonstrated ability to correctly do paced respiration and daily practice. Statistically significant differences in secondary outcomes at 8- and 16-weeks were small, not likely to be clinically relevant, and as likely to favor intervention as breathing control. Conclusions: Paced respiration is unlikely to provide clinical benefit for vasomotor or other menopausal symptoms in breast cancer survivors or menopausal women without cancer.
Increased Ischemic Cardiac Deaths in Central Indiana in Summer Months Compared to Winter Months
(Office of the Vice Chancellor for Research, 2013-04-05) Cook, Shannon; Lloyd, Frank, Jr.; Ballew, Alfie; Sandusky, George E.
Cardiovascular diseases have been the leading cause of death in the United States for several decades. Despite sustained declines in the mortality rates from these diseases, the magnitude of the disease is still staggering. One large recent study, using data on hundreds of heart attacks documented in the National Registry of Myocardial Infarction, found that 53 percent more cases in winter than in summer. The primary culprit, many believe, is temperature. Cold weather narrows coronary arteries and raises blood pressure, stressing the heart. Physical strain and ruptured plaques caused by shoveling snow are also commonly cited. But in a recent study, two researchers, found that the risk increases even in warm climates. Analyzing death certificates in seven regions with different climates, Los Angeles, Texas, Arizona, Pennsylvania, Massachusetts and others found that cardiovascular deaths rose up to 36 percent between summer and winter, regardless of climate and temperatures In this study we evaluated the incidence of ischemic cardiomyopathy in the Central Indiana area in the winter months compared to the summer months for the years 1998 to 2002. Approximately 5325 deaths were seen in the Marion County Morgue in central Indiana in this time period. There were 609 ischemic cardiac deaths seen in the summer (March 15th through October 15th) compared to 434 ischemic cardiac deaths seen in the winter (October 15th through March 15th). The deaths by years in the summer were 129, 131, 92, 127, and 130 and in the winter were 95, 96, 90, 96, and 57 respectively. In conclusion, this study was consistent with the outcome as the previous study done in multiple northern and southern cities in the country.
Wnt Signaling in Zebrafish Fin Regeneration: Chemical Biology Using GSK3b Inhibitors
(Office of the Vice Chancellor for Research, 2013-04-05) Curtis, Courtney; Sarmah, Swapnalee; Collins, Kayla; Chu, Shaoyou; Sato, Mas; Sanchez-Felix, Manuel; Marrs, James A.
Bone growth can be impaired due to disease, such as osteoporosis, and Wnt signaling pathways regulate bone growth. The parathyroid hormone (PTH) is therapeutic for anabolic bone growth (bone building), which activates Wnt signaling, leading to bone growth. GSK3b (glycogen synthetase kinase 3 beta) protein inhibitors activate Wnt signaling, including in bone growth models. Our study utilized a zebrafish model system to study Wnt activated fin regeneration and bone growth. Wnt signaling is the first genetically identified step in fin regeneration, and bony rays are the main differentiated cell type in fins. Thus, zebrafish fin regeneration may be a useful model to study Wnt signaling mediated bone growth. Fin regeneration experiments were conducted using various concentrations of GSK3b inhibitor compound for different treatment periods and regenerative outgrowth was measured at 4 and 7 days post amputation. Experiments revealed continuous low concentration (5-6 nM) treatment to be most effective at increasing regeneration. Higher concentrations inhibited fin growth, perhaps by excessive stimulation of differentiation programs. In situ hybridization experiments were performed to examine effects of Gsk3b inhibitor on Wnt responsive gene expression. Initial experiments show temporal and spatial changes on individual gene markers following GSK3b inhibitor treatment. Additionally, confocal microscopy and immunofluorescence labeling data indicated that the Wnt signaling intracellular signal transducer, betacatenin, accumulates throughout Gsk3b inhibitor treated tissues. Finally, experiments are underway to quantify phosphohistone-3 staining in regenerating tissue to measure effects of Gsk3b inhibitor on cell proliferation. Together, these data indicate that bone growth in zebrafish fin regeneration is improved by activating Wnt signaling. Zebrafish Wnt signaling experiments provide good model to study bone growth and bone repair mechanisms, and may provide an efficient drug discovery platform.

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