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Genetic Association Studies Of Copy-Number Variation: Should Assignment Of Copy Number States Precede Testing?, Patrick Breheny, Prabhakar Chalise, Anthony Batzler, Liewei Wang, Brooke L. Fridley

Biostatistics Faculty Publications

Recently, structural variation in the genome has been implicated in many complex diseases. Using genomewide single nucleotide polymorphism (SNP) arrays, researchers are able to investigate the impact not only of SNP variation, but also of copy-number variants (CNVs) on the phenotype. The most common analytic approach involves estimating, at the level of the individual genome, the underlying number of copies present at each location. Once this is completed, tests are performed to determine the association between copy number state and phenotype. An alternative approach is to carry out association testing first, between phenotype and raw intensities from the SNP array …

Proceedings - Wright State University Boonshoft School Of Medicine Fourth Annual Medical Student Research Symposium: Celebrating Medical Student Scholarship, Office Of Research Affairs, Boonshoft School Of Medicine

Medical Student Research Symposium Proceedings

The student abstract booklet is a compilation of abstracts from students' oral and poster presentations at Wright State University's Fourth Annual Boonshoft School of Medicine Medical Student Research Symposium held on April 5, 2012.

Modulation Of Gsk-3Β Activity In Venezuelan Equine Encephalitis Virus Infection, Kylene Kehn-Hall, Aarthi Narayanan, Lindsay Lundberg, Gavin Sampey, Chelsea Pinkham, Irene Guendel, Rachel Van Duyne, Svetlana Senina, Kimberly L. Schultz, Eric Stavale, M. Javad Aman, Charles Bailey, Fatah Kashanchi

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Alphaviruses, including Venezuelan Equine Encephalitis Virus (VEEV), cause disease in both equine and humans that exhibit overt encephalitis in a significant percentage of cases. Features of the host immune response and tissue-specific responses may contribute to fatal outcomes as well as the development of encephalitis. It has previously been shown that VEEV infection of mice induces transcription of pro-inflammatory cytokines genes (e.g., IFN-γ, IL-6, IL-12, iNOS and TNF-α) within 6 h. GSK-3β is a host protein that is known to modulate pro-inflammatory gene expression and has been a therapeutic target in neurodegenerative disorders such as Alzheimer's. Hence inhibition of GSK-3β …

Encoding Of Sensory Prediction Errors In The Human Cerebellum., John Schlerf, Richard B Ivry, Jörn Diedrichsen

Brain and Mind Institute Researchers' Publications

A central tenet of motor neuroscience is that the cerebellum learns from sensory prediction errors. Surprisingly, neuroimaging studies have not revealed definitive signatures of error processing in the cerebellum. Furthermore, neurophysiologic studies suggest an asymmetry, such that the cerebellum may encode errors arising from unexpected sensory events, but not errors reflecting the omission of expected stimuli. We conducted an imaging study to compare the cerebellar response to these two types of errors. Participants made fast out-and-back reaching movements, aiming either for an object that delivered a force pulse if intersected or for a gap between two objects, either of which …

Overexpression Of Serum Response Factor In Astrocytes Improves Neuronal Plasticity In A Model Of Fetal Alcohol Spectrum Disorders, Arco P. Paul

Theses and Dissertations

Neuronal plasticity deficits underlie many of the neurobehavioral problems seen in Fetal Alcohol Spectrum Disorders (FASD). Recently, we showed that third trimester alcohol exposure lead to a persistent disruption in ocular dominance (OD) plasticity. For instance, few days of monocular deprivation results in a robust reduction of cortical regions responsive to the deprived eye in normal animals, but not in ferrets exposed early to alcohol. This plasticity deficit can be reversed if alcohol-exposed animals are treated with a phosphodiesterase type 1 (PDE1) inhibitor during the period of monocular deprivation. PDE1 inhibition can increase cAMP and cGMP levels, activating transcription factors …

Genetic Polymorphism In A Vegf-Independent Angiogenesis Gene Angpt1 And Overall Survival Of Colorectal Cancer Patients After Surgical Resection, Jingyao Dai, Shaogui Wan, Feng Zhou, Ronald E. Myers, Xu Guo, Bingshan Li, Xiaoying Fu, Juan P. Palazzo, Kefeng Dou, Hushan Yang, Jinliang Xing

Kimmel Cancer Center Faculty Papers

Background

The VEGF-independent angiogenic signaling plays an important role in the development of colorectal cancer (CRC). However, its implication in the clinical outcome of CRC has not been reported. This study aimed to investigate the association between genetic variations in several major VEGF-independent signaling pathway genes and the overall survival of CRC patients.

Methods

Seven single nucleotide polymorphisms (SNPs) in four important VEGF-independent angiogenic genes (ANGPT1, AMOT, DLL4 and ENG) were genotyped in a Chinese population with 408 CRC patients.

Results

One SNP, rs1954727 in ANGPT1, was significantly associated with CRC overall survival. Compared to …

Mussel Inspired Protein-Mediated Surface Modification To Electrospun Fibers And Their Potential Biomedical Applications, Jingwei Xie, Praveesuda Lorwattanapongsa Michael, Shaoping Zhong, Bing Ma, Matthew R. Macewan, Chwee Teck Lim

MIIR Faculty Research

Mussel inspired proteins have been demonstrated to serve as a versatile biologic adhesive with numerous applications. The present study illustrates the use of such Mussel inspired proteins (polydopamine) in the fabrication of functionalized bio-inspired nanomaterials capable of both improving cell response and sustained delivery of model probes. X-ray photoelectron spectroscopy analysis confirmed the ability of dopamine to polymerize on the surface of plasma-treated, electrospun poly(ε-caprolactone) (PCL) fiber mats to form polydopamine coating. Transmission electron microscopy images demonstrated that self-polymerization of dopamine was induced by pH shift and that the thickness of polydopamine coating was readily modulated by adjusting the concentration …

Regulation Of Iron-Related Molecules In The Rat Hippocampus: Sex- And Age-Associated Differences, Srinivasarao Thulluri, Miaozong Wu, Eric R. Blough, Nandini D.P.K. Manne, Ashley B. Litchfield, Bin Wang

MIIR Faculty Research

Iron accumulation, especially that of free oxidized ferrous iron, has been shown to induce tissue oxidative damage and contribute to brain aging and the development of neurodegenerative disease. Here we examine whether sex and advanced age affect the expression of iron-related molecules that participate in regulating free iron levels (heme oxygenase I (HOI), iron-regulatory protein I (IRPI), and ferritin heavy chain (FTH)) and whether changes in the expression of these molecules are associated with differences in the expression of alpha-synuclein (ASN) which is thought to be a critical regulator in the pathogenesis of neurodegeneration. Using a well-established aging animal model, …

Chronic Paracetamol Treatment Influences Indices Of Reactive Oxygen Species Accumulation In The Aging Fischer 344 X Brown Norway Rat Aorta, Kevin M. Rice, Sarath Meduru, Sunil K. Kakarla, Anjaiah Katta, Sriram P. Mupparaju, Brent Kidd, Lynne J. Goebel, Eric R. Blough

MIIR Faculty Research

Previous reports have demonstrated that increased levels of reactive oxygen species (ROS) and alterations in cell signaling characterize aging in the Fischer 344 X Brown Norway (FBN) rat aorta. Other work has suggested that increases in ROS may be related to vascular wall thickening and the development of hypertension. Paracetamol (acetaminophen) is a potent antioxidant that has been found to diminish free radicals in ischemia-reperfusion studies. However, it remains unclear whether chronic paracetamol administration influences signaling or ROS accumulation in the aging aorta. FBN rats (27 months old; n=8) were subjected to 6 months of treatment with a therapeutic dose …

Genetic Manipulation Of Schistosomes - Progress With Integration Competent Vectors, Sutas Suttiprapa, Gabriel Rinaldi, Paul J. Brindley

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Draft genome sequences for Schistosoma japonicum and S. mansoni are now available. The schistosome genome encodes ∼13 000 protein-encoding genes for which the functions of few are well understood. Nonetheless, the new genes represent potential intervention targets, and molecular tools are being developed to determine their importance. Over the past 15 years, noteworthy progress has been achieved towards development of tools for gene manipulation and transgenesis of schistosomes. A brief history of genetic manipulation is presented, along with a review of the field with emphasis on reports of integration of transgenes into schistosome chromosomes.

Five-Year Longitudinal Assessment Of The Downstream Impact On Schistosomiasis Transmission Following Closure Of The Three Gorges Dam., Darren J. Gray, Aaron P. Thrift, Gail M. Williams, Feng Zheng, Yue-Sheng Li, Jiagang Guo, Honggen Chen, Tianping Wang, Xin J. Xu, Rong Zhu, Hongqing Zhu, Chun Li Cao, Dan D. Lin, Zhen Y. Zhao, Robert S. Li, George M. Davis, Donald P. Mcmanus

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Schistosoma japonicum is a major public health concern in the Peoples' Republic of China (PRC), with about 800,000 people infected and another 50 million living in areas at risk of infection. Based on ecological, environmental, population genetic and molecular factors, schistosomiasis transmission in PRC can be categorised into four discrete ecosystems or transmission modes. It is predicted that, long-term, the Three Gorges Dam (TGD) will impact upon the transmission of schistosomiasis in the PRC, with varying degree across the four transmission modes.

Methodology/Principal Findings

We undertook longitudinal surveillance from 2002 to 2006 in sentinel villages of the three transmission …

Resource Availability, Mortality And Fertility: A Path Analytic Approach To Global Life History Variation, Mark A. Caudell, Robert J. Quinlan

Human Biology Open Access Pre-Prints

Humans exhibit considerable diversity in timing and rate of reproduction. Life history theory suggests that ecological cues of resource richness and survival probabilities shape human phenotypes across populations. Populations experiencing high extrinsic mortality due to uncertainty in resources should exhibit faster life histories. Here we use a path analytic approach informed by life history theory to model the multiple pathways between resources, mortality rates, and reproductive behavior in 191 countries. Resources that account for the most variance in population mortality rates are predicted to explain the most variance in total fertility rates. Results indicate that resources (e.g., calories, sanitation, education, …

Provision Of Pandemic Disease Information By Health Sciences Librarians: A Multisite Comparative Case Series., Robin Featherstone, Gabriel Boldt, Nazi Torabi, Shauna-Lee Konrad

Western Libraries Publications

Objective: The research provides an understanding of pandemic information needs and informs professional development initiatives for librarians in disaster medicine. Methods: Utilizing a multisite, comparative case series design, the researchers conducted semi-structured interviews and examined supplementary materials in the form of organizational documents, correspondence, and websites to create a complete picture of each case. The rigor of the case series was ensured through data and investigator triangulation. Interview transcripts were coded using NVivo to identify common themes and points of comparison. Results: Comparison of the four cases revealed a distinct difference between “client-initiated” and “librarian-initiated” provision of pandemic information. Librarian-initiated …

Quantitative Pulmonary Imaging Using Computed Tomography And Magnetic Resonance Imaging, George R Washko, Grace Parraga, Harvey O Coxson

Medical Biophysics Publications

Measurements of lung function, including spirometry and body plethesmography, are easy to perform and are the current clinical standard for assessing disease severity. However, these lung functional techniques do not adequately explain the observed variability in clinical manifestations of disease and offer little insight into the relationship of lung structure and function. Lung imaging and the image-based assessment of lung disease has matured to the extent that it is common for clinical, epidemiologic and genetic investigation to have a component dedicated to image analysis. There are several exciting imaging modalities currently being used for the non-invasive study of lung anatomy …

Single-Chain Vαvβ T Cell Receptors Function Without Mispairing With Endogenous Tcr Chains1, David H. Aggen, Adam S. Chervin, Thomas M. Schmitt, Boris Engels, Jennifer D. Stone, Sarah A. Richman, Kurt H. Piepenbrink, Brian M. Baker, Philip D. Greenberg, Hans Schreiber, David M. Kranz

Food for Health: Publications

Transduction of exogenous T cell receptor (TCR) genes into patients’ activated peripheral blood T cells is a potent strategy to generate large numbers of specific T cells for adoptive therapy of cancer and viral diseases. However, the remarkable clinical promise of this powerful approach is still being overshadowed by a serious potential consequence: mispairing of the exogenous TCR chains with endogenous TCR chains. These “mixed” heterodimers can generate new specificities that result in graft-versus-host reactions. Engineering TCR constant regions of the exogenous chains with a cysteine promotes proper pairing and reduces the mispairing, but, as we show here, does not …

Tailoring The Immune Response By Targeting C-Type Lectin Receptors On Alveolar Macrophages Using “Pathogen-Like” Amphiphilic Polyanhydride Nanoparticles, Ana V. Chavez-Santicoy, Rajarshi Roychoudhury, Nicola L.B. Pohl, Michael J. Wannemeuhler, Balaji Narasimhan, Amanda E. Ramer-Tait

Amanda Ramer-Tait Publications

C-type lectin receptors (CLRs) offer unique advantages for tailoring immune responses. Engagement of CLRs regulates antigen presenting cell (APC) activation and promotes delivery of antigens to specific intracellular compartments inside APCs for efficient processing and presentation. In these studies, we have designed an approach for targeted antigen delivery by decorating the surface of polyanhydride nanoparticles with specific carbohydrates to provide pathogen-like properties. Two conserved carbohydrate structures often found on the surface of respiratory pathogens, galactose and di-mannose, were used to functionalize the surface of polyanhydride nanoparticles and target CLRs on alveolar macrophages (AMϕ), a principle respiratory tract APC. Co-culture of …

Genome-Wide Patterns Of Arabidopsis Gene Expression In Nature, Christina L. Richards, Ulises Rosas, Joshua A. Banta, Naeha Bhambra, Michael D. Purugganan

Integrative Biology Faculty and Staff Publications

Organisms in the wild are subject to multiple, fluctuating environmental factors, and it is in complex natural environments that genetic regulatory networks actually function and evolve. We assessed genome-wide gene expression patterns in the wild in two natural accessions of the model plant Arabidopsis thaliana and examined the nature of transcriptional variation throughout its life cycle and gene expression correlations with natural environmental fluctuations. We grew plants in a natural field environment and measured genome-wide time-series gene expression from the plant shoot every three days, spanning the seedling to reproductive stages. We find that 15,352 genes were expressed in the …

Pharmacists And Pharmacogenomics: An Evaluation Of Knowledge, Beliefs, Attitudes And Practices, Laressa Bethishou, Angela Chen, Chrissie Chew, Richard Dang, Courtney Greenber, Rebecca Ashlee Klevens, Vlada Treynker, Andrew Warnock, Melissa Durham, Jeffery A. Goad, Edith Mirzaian

Pharmacy Faculty Articles and Research

"Pharmacogenomics is the term used to describe the rapidly advancing study on how genetic makeup can impact drug therapy. In specialized clinical situations, such as the use of irinotecan in colon cancer or abacavir in HIV infections, it is now possible to identify specific genotypes that correlate strongly with a patient's therapeutic outcome, with implications on both efficacy and side effects. On a broader scale, a systematic review published by the Journal of the American Medical Association on the top 27 adverse reaction-causing drugs found that a majority of the adverse effects have a genetic component, suggesting that an analysis …

Ventilator Associated Pneumonia Prevention In The Traumatically Injured Patient: Beyond The Bundle!, Cindy Umbrell Msn,Rn,Cns,Ccrn, Kenneth Miller Med, Rrt-Nps

Patient Care Services / Nursing

No abstract provided.

Cosmetic Neurology: Enhancement Of The Mind And Attention Deficit Hyperactive Disorder Medication Abuse Among College Students, Mary M. Huff

Senior Honors Theses

Cosmetic neurology is becoming increasingly popular, and it is not just sleep deprived, over worked college students who are interested. People are beginning to seek off-label prescriptions for medications that are typically used to treat disorders such as attention deficit hyperactive disorder (ADHD) or narcolepsy, while researchers are trying to create drugs used solely for mind enhancement purposes. Along with these drugs come many legal and ethical quandaries relating to the regulation of current use as well as the what ifs of future possibilities. A survey was conducted among college students regarding the diagnosis of ADHD, the abuse of ADHD …

Molecular Staging Individualizing Cancer Management, Alex Mejia, Stephanie Schulz, Terry Hyslop, David S. Weinberg, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Although the most important prognostic and predictive marker in colorectal cancer is tumor cells in lymph nodes, ∼30% of patients who are node-negative die from occult metastases. Molecular staging employing specific markers and sensitive detection technologies has emerged as a powerful platform to assess prognosis in node-negative colon cancer. Integrating molecular staging into algorithms that individualize patient management will require validation and the definition of relationships between occult tumor cells, prognosis, and responses to chemotherapy. J. Surg. Oncol. 2012; 105:468-474. © 2012 Wiley Periodicals, Inc.

Copyright © 2012 Wiley Periodicals, Inc.

Essential Role Of Caveolin-3 In Adiponectin Signalsome Formation And Adiponectin Cardioprotection., Yajing Wang, Xiaoliang Wang, Jean-François Jasmin, Wayne Bond Lau, Rong Li, Yuexin Yuan, Wei Yi, Kurt Chuprun, Michael P. Lisanti, Walter J Koch, Erhe Gao, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

OBJECTIVE: Adiponectin (APN) system malfunction is causatively related to increased cardiovascular morbidity/mortality in diabetic patients. The aim of the current study was to investigate molecular mechanisms responsible for APN transmembrane signaling and cardioprotection.

METHODS AND RESULTS: Compared with wild-type mice, caveolin-3 knockout (Cav-3KO) mice exhibited modestly increased myocardial ischemia/reperfusion injury (increased infarct size, apoptosis, and poorer cardiac function recovery; P

CONCLUSIONS: Taken together, these results demonstrated for the first time that Cav-3 plays an essential role in APN transmembrane signaling and APN anti-ischemic/cardioprotective actions.

P53 Expression In Oropharyngeal Squamous Cell Carcinoma In Increased In Hpv Positive Smokers, Madalina Tuluc, Voichita Bar-Ad, Zi-Xuan Wang, Joseph Curry

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background and Objectives

High risk HPV is associated with oropharyngeal SCC (OSCC) and is responsible for the increasing incidence of this cancer type among younger patients.

Patients with HPV positive oropharyngeal SCC have a better prognosis when compared with HPV negative, tobacco induced SCC.

HPV E6 inactivates p53 leading to low expression of p53; tobacco induced oropharyngeal SCC is characterized by p53 overexpression, resistance to treatment and poor prognosis. However, in many cases of HPV OSCC, there is a history of current or remote smoking, making this disease a multifactorial process. We expect that smoking will influence the level of …

Gene Patents No More? Deciphering The Meaning Of Prometheus, Fazal Khan, Lindsay Kessler

Scholarly Works

When Congress enacted the United States Patent Act in 1952, it specified that patentable subject matter included anything “under the sun that is made by man.” Three decades ago the United States Patent and Trademark Office (USPTO) issued the first gene patent and ushered in a brave new gold rush. Some genes are associated with specific diseases, so being able to identify these sequences is an essential first step for developing genomic diagnostic tests and therapies. The problem with gene patents is that they allow modern-day prospectors to cordon off access to naturally occurring DNA sequences and exclude others from …

Expression Of Stem Cell Marker Aldh1 In Cervical Intraepithelial Neoplasia, Ping Gong, Juan Palazzo, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Conclusions:

Cervical dysplasia show positive staining for ALDH1 compared to normal cervical mucosa.

ALDH1 positive cells distribution parallels the dysplastic cells in cervical dysplasia.

CSC, as detected by ALDH1 expression, may play a role in the progression of cervical intraepithelial neoplasia and carcinogenesis.

Aberrant Expression Of Cd56 On Granulocytes And Monocytes In Myeloproliferative Neoplasm And Myelodysplastic Syndrome, Ping Gong, Md, Fernanco Metrebian, Md, Alina Dulau-Florea, Md, Zi-Xuan Wang, Phd, Renu Bajaj, Phd, Stephen C Peiper, Jerald Z. Gong, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Conclusions:

Aberrant CD56 expression on granulocytes is seen in all aubtypes MPN and high grade MDS. CD56 expression in MPN correlated with bone marrow morphology, BCR/ABL transcript, and bone marrow engraftment study following treatment. Identification of abnormal CD56+ granulocytes and monocytes is helpful in both the initial diagnosis and long-term follow up of patients with MPN and MDS.

Loss Of Retinoblastoma (Rb) Tumor Suppressor Expression In Breast Cancer Correlates With Better Response To Neoadjuvant Chemotherapy, Jeanne Mcfalls, Md, Jessica Kline, Ba, Gordon Schwartz, Md, Mba, Facs, Angieszka Witkiewicz, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Conclusions:

Loss of RB tumor suppressor staining in pre-treatment breast cancer biopsies can be used prior to initiation of neoadjuvant chemotherapy to predict good tumor response. This association between RB loss and good neoadjuvant response holds regardless of ER status and across various chemotherapy regimens. Assessment of RB status in the pre-treatment biopsy could be useful clinical tool to define patients who are most likely to benefit from neoadjuvant chemotherapy.

P16/Rb Correlations In Oropharyngeal Squamous Cell Carcinoma (Oscc), Madalina Tuluc, Voichita Bar-Ad, David Cognetti

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The objective of this study is to explore the patterns of Rb expression in p16 positive and negative OSCC, in relation to patient's smoking history.

The Metastasis Suppressor Kiss1 Lacks Antimetastatic Activity In The C8161.9 Xenograft Model Of Melanoma., Jean-Marc Navenot, Barry Evans, Shinya Oishi, Shohei Setsuda, Nobutaka Fujii, Stephen C Peiper

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The objective of this study was to use the established xenograft model of human melanoma (C8161.9) to test a pharmacological approach to the effect of the metastasis suppressor KISS1. A KISS1 analog was used to inhibit the metastatic development of C8161.9 cells in nude mice. Further experiments were performed to test the validity of the C8161.9 model and test the connection between KISS1 expression and loss of metastatic potential. New clones of C8161.9 cells were obtained, with or without KISS1 expression, and were tested for metastasis formation. The absence of benefit in survival with the KISS1 analog compared with PBS …

Targeting Apoptosis For Optical Imaging Of Infection, Mathew L Thakur, Kaijun Zhang, Bishnuhari Paudyal, Devadhas Devakumar, Maria Y Covarrubias, Changpo Cheng, Brian D Gray, Eric Wickstrom, Koon Y Pak

Department of Radiology Faculty Papers

PURPOSE: Infection is ubiquitous and a major cause of morbidity and mortality. The most reliable method for localizing infection requires radiolabeling autologous white blood cells ex vivo. A compound that can be injected directly into a patient and can selectively image infectious foci will eliminate the drawbacks. The resolution of infection is associated with neutrophil apoptosis and necrosis presenting phosphatidylserine (PS) on the neutrophil outer leaflet. Targeting PS with intravenous administration of a PS-specific, near-infrared (NIR) fluorophore will permit localization of infectious foci by optical imaging.

METHODS: Bacterial infection and sterile inflammation were induced in separate groups (n = 5) …