«Strengthening the Nation through Diversity, Innovation & Leadership in STEM San Antonio,Texas · October 3-6, 2013 Get Connected! Connect with the ...»
University of Texas Health Science Center at San Antonio, San Antonio, TX, 2TheUniversity of Texas Southwestern 1 Medical Center, Dallas, TX, 3University of Mississippi Medical Center, Jackson, MS, 4St. Jude Children’s Research Hospital, Memphis, TN.
Streptococcus pneumoniae (the pneumococcus) accounts for approximately 40% of all cases of community-acquired pneumonia and is a leading cause of bacteremia and sepsis. Individuals hospitalized for invasive pneumococcal disease (IPD) are at an increased risk for sudden death as a result of adverse cardiac events, in particular new or worsened congestive heart failure. Herein we describe the novel observation of cardiac lesions formed within the ventricles of septic mice. Lesion formation was positively correlated with bacterial burden in the blood as well as serum levels of troponin, a clinical marker for cardiac damage. Lesion formation was also concomitant with changes in electrophysiology as measured by limb-lead ECG, which indicated a progressive loss of cardiac contractility.
Lesions increased in number and size during the infection, becoming first detectable at 24 hours post-intravenous challenge, and had a marked absence of infiltrated immune cells, which stands in stark contrast to abscesses typically seen formed by other Gram-positive bacteria. Pneumococci could be visualized within the lesions, and, using immunohistochemistry, we detected the toxin pneumolysin at sites where apoptosis was occurring. Notably, lesions were confined to the heart and occurred following both intratracheal and intravenous challenge. We conclude that mice with severe invasive pneumococcal disease develop altered cardiac electrophysiology that is associated with the presence of lesions. These lesions may explain the high incidence of adverse cardiac events during severe disease.
Studies are ongoing to characterize the mechanism underlying lesion formation, and how this is related to adverse cardiac events in humans with IPD.
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SERRATIA MARCESCENS PNEUMONIANorberto Gonzalez Juarbe, Chris Mares, Rose Seoanes, Molly Bergman.
The University of Texas Health Science Center at San Antonio, San Antonio, TX.
Serratia marcescens, a Gram-negative bacteria, is the most common Serratia species isolated in human infections.
As a ubiquitous, opportunistic bacterium, this organism is an important emerging pathogen possessing multiple antibiotic-resistance mechanisms and ease of transmission in hospitals. Although S. marcescens-caused pneumonia and lung abscesses have been documented, little is known about how the pathogen colonizes and causes disease in the respiratory tract and how the host resolves infection. We propose that both bacterial and host factors contribute to the pathogenesis and resolution of S. marcescens infection. To test this hypothesis, we developed a mouse model of lung infection following intratracheal inoculation. Bacterial burden experiments revealed that the CFU in Graduate
inflammation measured by organ weight after infection was significantly elevated compared to the PBS-treated mice.
Bronchoalveolar lavage fluid from 12, 24, 48, and 72 hours showed an increase of polymorphonuclear leukocytes that peak at 24 hours and then diminish at 48 and 72 hours. A deeper analysis of the immune response revealed that inflammatory cytokines and neutrophil chemokine levels rapidly increase after inoculation. Moreover, we found that neutrophil-depleted mice were susceptible to virulent S. marcescens infection, succumbing within 12 hours postinoculation with a nonlethal dose. These results reveal the importance of a fast and efficient innate immune response to contain this pathogen and suggest that colonization of the lungs is key to Serratia marcescens mortality.
299 GRADUATE POSTER ABSTRACTS
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PNEUMOCOCCAL SERINE-RICH REPEAT PROTEIN INHIBITS COMPLEMENT DEPOSITION AND
OPSONOPHAGOCYTOSIS BY MACROPHAGESRyan Gilley1, Carlos Sanchez1, Catherine Hyams2, Jeremy Brown2, Carlos Orihuela1.
The University of Texas Health Science Center at San Antonio, San Antonio, TX, 2University College Medical School, 1 London, GB.
Streptococcus pneumoniae is an important human pathogen and is the leading cause of community-acquired pneumonia throughout the world; this is despite the availability of multiple effective vaccines. Although S. pneumoniae is primarily a commensal of the human nasopharynx, it is an opportunistic pathogen and has the capacity to cause invasive pneumococcal disease. Pneumococcal serine-rich repeat protein (PsrP) is a member of the serine-rich repeat protein family found exclusively in Gram-positive bacteria and is a key virulence factor that facilitates S.
pneumoniae adhesion to lung epithelial cells by binding to keratin 10. Our lab has recently determined that PsrP also protects the bacteria against opsonophagocytosis. Western blot and FACS analysis showed that mutants deficient in PsrP (Ωpsrp) had greater amounts of detectable C3b on their surface than wild-type bacteria. FACS data also suggest macrophages take up fewer pneumococci when PsrP is present. Ongoing studies are focused on determining which complement pathway is deterred by the presence of PsrP. Planned studies include treating serum with EGTA, which preferentially chelates Ca2+, thereby inhibiting the classical cascade but leaving the alternative cascade intact.
Additionally, depleting serum of key complement components like C4 or Factor H will selectively inhibit one pathway.
Collectively, these experiments will determine which complement pathway is inhibited by the presence of PsrP.
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DIFFERENCES IN NATURAL HEALTH PRODUCT USE AMONG SAUDI ARABIAN STUDENTS: USA VS. SAUDIARABIA Samiah Alqahtani1, Ahmad Aboshaiqah2, Ali Almajwal2, Dina Haque1, Maria Pontes Ferreira1.
Wayne State University, Detroit, MI, 2King Saud University, Riyadh, SA.
1 We test hypotheses regarding Saudi student use of natural health products (NHP) for health maintenance (HealthM).
We hypothesize that there are geoethnic and gender differences in NHP use. We also seek to identify the top 10 NHPs used for HealthM by Saudi students and to determine predictor variables for student use of the top ten NHPs for HealthM. Students from King Saud University (n = 500: 250 males and 250 females) and Wayne State University (n = 500; 250 males and 250 females) will participate in a cross-sectional online survey of NHP use. χ² and Fisher exact tests will analyze group differences and determine the top ten NHPs used for HealthM. Multiple logistic regression analyses will determine predictor variables for the top ten NHPs used for HealthM. Data will be analyzed by SPSS software 20. The critical alpha level will be set at 0.05 a priori. We expect Saudi students (Saudi Arabia) use different NHPs for HealthM than US-Saudi students. We also expect to find greater use of NHP for HealthM among female students, regardless of country. We will identify the top ten NHPs used for HealthM. Gender, tobacco status, age, and geoethnicity are expected predictor variables for student use of the top ten NHPs for HealthM. These anticipated novel findings of under-studied groups should clarify medicinal plants commonly used by Saudi Arabian male and female students (US vs. Saudi Arabia). Future directions include the establishment of the evidence-based efficacy of popular NHPs used by Saudi students.
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ASSESSING THE IMPACT OF ELDERS ON STUDENT INTEREST IN STEMSarah Alkholy1, Priscila Angeles Rojas1, Tanya Dahms2, Maria Pontes Ferreira1, Fidji Gendron3 Wayne State University, Detroit, MI, 2University of Regina, Regina, SK, CA, 3First Nations University of Canada, 1 Regina, SK, CA.
Minorities are underrepresented in postsecondary education, have high attrition rates, and are poorly represented in STEM fields. Academic performance improves when cultural relevance and support and are provided. The interface of Western science and Indigenous science provides an opportunity for bridging this divide. We hypothesize that the presence of Indigenous science Elder educators alongside Western science educators in an online STEM course is associated with cultural relevance/supportiveness of the course, student learning outcomes, student interest in
300 GRADUATE POSTER ABSTRACTS
STEM, and perceived merit of Indigenous science educators in postsecondary STEM education. We conducted a longitudinal study of an interdisciplinary, multi-institutional, cross-cultural online STEM course in spring 2013 offered at mainstream and Tribal universities. Precourse and postcourse surveys were administered to participating students. Learning outcomes were measured by quizzes. The outcome measures of interest per the hypotheses were assessed. Group differences will be tested by ANOVA, and predictor variables determined by regression (SPSS software). We expect to find differences between the with-Elders group and the without-Elders group of students;
specifically, the presence of Elders in an online STEM course will improve course cultural relevance, student learning outcomes, student interest in STEM, and perception of the merit of Elders in postsecondary STEM education. We anticipate that Elders can be involved in novel pedagogical approaches and delivery modalities to reach Aboriginal students, such as live and distance delivery of health-related courses. These findings can influence STEM education policy toward an increased Native retention in STEM while benefiting all students.
OTHER BIOLOGICAL SCIENCES
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IDENTIFYING BIOMARKERS FOR MONITORING DISEASE PROGRESSION IN EXPERIMENTAL AUTOIMMUNE
ENCEPHALOMYELITIS BY M2 PROTEOMICSErica Saenz-Trevino, Niannian Ji, Itay Raphael, William E. Haskins, Thomas Forsthuber.
University of Texas at San Antonio, San Antonio, TX.
Multiple sclerosis (MS) is the most common debilitating, progressive neurological disorder which afflicts over 400,000 Americans. Currently, determining clinical and subclinical progression for MS patients has been an obstacle for MS therapy due to the lack of specific and sensitive laboratory tests. Recently, our lab has developed a technique called microwave & magnetic (M2) proteomics, which is a rapid, quantitative approach ideal for identifying putative protein biomarkers and therapeutic targets of experimental autoimmune encephalomyelitis (EAE), a commonly used animal model for MS research. Notably, we identified a number of putative-biomarkers that correlated with different stages of relapsing-remitting EAE. The objective of our research is to identify protein biomarkers correlated to disease progression using the progressive EAE disease model in nonobese, diabetic (NOD) mice. We hypothesize that during the disease some key central nervous system (CNS) disease specific proteins will be released into blood and/ or cerebrospinal fluid (CSF) and the identification of these proteins can be used to determine disease progression.
In this study, we will induce progressive EAE disease in NOD mice, monitor clinical symptoms, and analyze the CNS proteome changes at representative time points of the disease using M2 proteomics. After identifying putative CNSspecific proteins for disease progression, we will use M2 proteomics and other quantitative measurements (e.g., ELISA) to identify candidate protein biomarkers indicative for EAE progression in the blood and/or CSF. This research will provide a proof-of-principle for the development of novel prognostic tests in MS patients. (Partially supported by NSF LSAMP-BD 1249284.)
Triple-negative breast cancer (TNBC) has a poor prognosis and high metastatic rate. Receptor activator of nuclear factor kappa-B (RANK), a promoter of bone metastasis, may contribute to the enrichment of cancer stem cells (CSCs). CSCs are enriched with the epithelial-to-mesenchymal (EMT) phenotype. It is unknown whether RANK is a clinically relevant target in TNBC. We hypothesized that RANK promotes tumorigenicity and metastasis of TNBC via the regulation of EMT and enrichment of CSCs. We analyzed RANK mRNA expression levels, obtained by Affymetrix gene chip array, in ER+/HER2- breast tumors (n = 22) and ER-/HER2- primary breast tumors (n = 18) including TNBC tumors and found RANK expression to be higher in the ER-/HER2- breast tumors compared with the ER+/HER2- breast tumors (P = 0.034). We stably transfected human TNBC cell line MDA-MB-231 with scrambled shRNA, RANK shRNA, clone 1, or clone 2 to examine whether RANK regulates migration and invasion, EMT, and CSC-like phenotype. RANK knockdown in MDA-MB-231 inhibited migration (P = 0.0005) and invasion (P = 0.0006) and reduced mammospheres (P = 0.0188). In 3D matrigel, we observed signficant inhibition of EMT-like phenotype in MDA-MB-231 RANK shRNA
301 GRADUATE POSTER ABSTRACTS
(P 0.05), and downregulation of EMT markers, vimentin, and snail shown by qRT PCR analysis. We concluded RANK is a regulator of EMT and CSC-like phenotype in TNBC cells. We plan to investigate the effects of RANK inhibition on EMT, CSC enrichment, and metastasis in vivo using TNBC xenograft and metastatic mouse models. The significance of this work is that finding a therapeutic target for TNBC will reduce the mortality of this deadly disease.
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DETERGENT STABILITY SCREENING OF VOLTAGE-GATED PROTON CHANNELAmruta Agharkar, Eric B. Gonzales.
University of North Texas Health Science Center, Fort Worth, TX.