Digital Commons Network^™

Sustaining The Rheumatology Research Enterprise, A. Davidson, D. Polsky

Journal Articles

No abstract provided.

Tyk2 Protein-Coding Variants Protect Against Rheumatoid Arthritis And Autoimmunity, With No Evidence Of Major Pleiotropic Effects On Non-Autoimmune Complex Traits, D. Diogo, L. Bastarache, K. P. Liao, R. R. Graham, R. S. Fulton, J. D. Greenberg, S. Eyre, A. Lee, P. K. Gregersen, R. M. Plenge, +44 Additional Authors

Journal Articles

Despite the success of genome-wide association studies (GWAS) in detecting a large number of loci for complex phenotypes such as rheumatoid arthritis (RA) susceptibility, the lack of information on the causal genes leaves important challenges to interpret GWAS results in the context of the disease biology. Here, we genetically fine-map the RA risk locus at 19p13 to define causal variants, and explore the pleiotropic effects of these same variants in other complex traits. First, we combined Immunochip dense genotyping (n = 23,092 case/control samples), Exomechip genotyping (n = 18,409 case/control samples) and targeted exon-sequencing (n = 2,236 case/controls samples) to …

Widespread Non-Additive And Interaction Effects Within Hla Loci Modulate The Risk Of Autoimmune Diseases, T. Lencz, A. J. Deutsch, B. Han, X. Hu, Y. Okada, S. Eyre, M. Knapp, A. Zhernakova, P. K. Gregersen, S. Raychaudhuri, +27 Additional Authors

Journal Articles

Human leukocyte antigen (HLA) genes confer substantial risk for autoimmune diseases on a log-additive scale. Here we speculated that differences in autoantigen-binding repertoires between a heterozygote's two expressed HLA variants might result in additional non-additive risk effects. We tested the non-additive disease contributions of classical HLA alleles in patients and matched controls for five common autoimmune diseases: rheumatoid arthritis (ncases = 5,337), type 1 diabetes (T1D; ncases = 5,567), psoriasis vulgaris (ncases = 3,089), idiopathic achalasia (ncases = 727) and celiac disease (ncases = 11,115). In four of the five diseases, we observed highly significant, non-additive dominance effects (rheumatoid arthritis, …

Pioglitazone In Early Parkinson's Disease: A Phase 2, Multicentre, Double-Blind, Randomised Trial, T. Simuni, K. Kieburtz, B. Tilley, J. J. Elm, B. Ravina, D. Babcock, M. Emborg, Andrew Feigin, R. Zweig, Parkinson Ninds Exploratory Trials, +38 Additinal Authoris

Journal Articles

Background A systematic assessment of potential disease-modifying compounds for Parkinson's disease concluded that pioglitazone could hold promise for the treatment of patients with this disease. We assessed the effect of pioglitazone on the progression of Parkinson's disease in a multicentre, double-blind, placebo-controlled, futility clinical trial. Methods Participants with the diagnosis of early Parkinson's disease on a stable regimen of 1 mg/day rasagiline or 10 mg/day selegiline were randomly assigned (1:1:1) to 15 mg/day pioglitazone, 45 mg/day pioglitazone, or placebo. Investigators were masked to the treatment assignment. Only the statistical centre and the central pharmacy knew the treatment name associated with …

The Carcinogenic Liver Fluke Opisthorchis Viverrini Is A Reservoir For Species Of Helicobacter., Raksawan Deenonpoe, Chariya Chomvarin, Chawalit Pairojkul, Yaowalux Chamgramol, Alex Loukas, Paul J. Brindley, Banchob Sripa

Microbiology, Immunology, and Tropical Medicine Faculty Publications

There has been a strong, positive correlation between opisthorchiasis-associated cholangiocarcinoma and infection with Helicobacter. Here a rodent model of human infection with Opisthorchis viverrini was utilized to further investigate relationships of apparent co-infections with O. viverrini and H. pylori. A total of 150 hamsters were assigned to five groups: i) Control hamsters not infected with O. viverrini; ii) O. viverrini-infected hamsters; iii) non-O. viverrini infected hamsters treated with antibiotics (ABx); iv) O. viverrini-infected hamsters treated with ABx; and v) O. viverrini-infected hamsters treated both with ABx and praziquantel (PZQ). Stomach, gallbladder, liver, colonic tissue, colorectal feces and O. viverrini worms …

The Association Between Sleep Loss And Women’S Wellness Decisions, Gudeta D. Fufaa, Amber S. Linde

Walden Faculty and Staff Publications

Sleep loss is an important determinant of health status owing to its relationships with molecular, immune, and neural changes; these changes, in turn, are important etiological mechanisms for the development of cardiovascular, metabolic diseases and increased risk of accident related injuries. While the association between sleep loss and risk of weight gain is established, studies on the association between sleep loss and nutrition and physical activity are limited. The purpose of this research was to determine if there are significant associations between reported sleep variations and nutrition and physical activity level while recognizing the association between body mass index (BMI) …

Respiratory Particle Deposition Probability Due To Sedimentation With Variable Gravity And Electrostatic Forces, Ioannis Haranas, Ioannis Gkigkitzis, George D. Zouganelis, Maria K. Haranas, Samantha Kirk

Physics and Computer Science Faculty Publications

In this paper, we study the effects of the acceleration gravity on the sedimentation deposition probability, as well as the aerosol deposition rate on the surface of the Earth and Mars, but also aboard a spacecraft in orbit around Earth and Mars as well for particles with density ρ_p = 1300 kg/m³, diameters d_p = 1, 3, 5 µm and residence times t = 0.0272, 0.2 s respectively. For particles of diameter 1 µm we find that, on the surface of Earth and Mars the deposition probabilities are higher at the poles when compared to the …

Immunological Function Of Blimp-1 In Dendritic Cells And Relevance To Autoimmune Diseases, S. J. Kim

Journal Articles

Previous studies have identified the immunological functions of transcription factor B lymphocyte-induced maturation protein-1 (Blimp-1) in various adaptive immune cell types such as T and B lymphocytes. More recently, it has been shown that Blimp-1 extends its functional roles to dendritic cells (DCs) and macrophages, two cell types belonging to the innate immune system. The protein acts as a direct and indirect regulator of target genes by recruiting chromatin modification factors and by regulating microRNA expression, respectively. In DCs, Blimp-1 has been identified as one of the components involved in antigen presentation. Genome-wide association studies identified polymorphisms associated with multiple …

A Stationary Wavelet Entropy-Based Clustering Approach Accurately Predicts Gene Expression, N. Nguyen, A. Vo, I. Choi, K. J. Won

Journal Articles

Studying epigenetic landscapes is important to understand the condition for gene regulation. Clustering is a useful approach to study epigenetic landscapes by grouping genes based on their epigenetic conditions. However, classical clustering approaches that often use a representative value of the signals in a fixed-sized window do not fully use the information written in the epigenetic landscapes. Clustering approaches to maximize the information of the epigenetic signals are necessary for better understanding gene regulatory environments. For effective clustering of multidimensional epigenetic signals, we developed a method called Dewer, which uses the entropy of stationary wavelet of epigenetic signals inside enriched …

Studies On Ageing And The Severity Of Radiographic Joint Damage In Rheumatoid Arthritis, L. Mangnus, H. W. Van Steenbergen, E. Lindqvist, E. Brouwer, M. Reijnierse, T. W. Huizinga, P. K. Gregersen, E. Berglin, S. Rantapaa-Dahlqvist, A. H. Van Der Helm-Van Mil, +1 Additional Author

Journal Articles

INTRODUCTION: The western population is ageing. It is unknown whether age at diagnosis affects the severity of Rheumatoid Arthritis (RA), we therefore performed the present study. METHOD: 1,875 RA-patients (7,219 radiographs) included in five European and North-American cohorts (Leiden-EAC, Wichita, Umea, Groningen and Lund) were studied on associations between age at diagnosis and joint damage severity. In 698 Leiden RA-patients with 7-years follow-up it was explored if symptom duration, anti-citrullinated-peptide-antibodies (ACPA), swollen joint count (SJC) and C-reactive-protein (CRP) mediated the association of age with joint damage. Fifty-six other RA-patients of the EAC-cohort underwent baseline MRIs of wrist, MCP and MTP-joints; …

Child And Adolescent Psychiatrists' Reported Monitoring Behaviors For Second-Generation Antipsychotics, A. M. Rodday, S. K. Parsons, C. Mankiw, C. U. Correll, A. S. Robb, B. T. Zima, T. S. Saunders, L. K. Leslie

Journal Articles

Objective: The number of children and adolescents (hereafter referred to as "children") who have been prescribed second-generation antipsychotics (SGAs) has increased over the last decade, but little is known about monitoring practices in pediatric patients who are vulnerable to adverse effects. We examined factors associated with psychiatrists' self-reported monitoring of children who were prescribed SGAs. Methods: A survey was mailed to a national, randomly selected sample of 1600 child and adolescent psychiatrists from the American Medical Association mailing list. Using logistic regression, we tested whether psychiatrist characteristics, attitudes, and practice characteristics were associated with monitoring (baseline and/or periodic) the following: …

Redox Regulation Of Nlrp3 Inflammasomes: Ros As Trigger Or Effector?, Justine M. Abais, Min Xia, Yang Zhang, Krishna M. Boini, Pin-Lan Li

Pharmacology and Toxicology Publications

Significance: Inflammasomes are multiprotein complexes localized within the cytoplasm of the cell that are responsible for the maturation of proinflammatory cytokines such as interleukin-1β (IL-1β) and IL-18, and the activation of a highly inflammatory form of cell death, pyroptosis. In response to infection or cellular stress, inflammasomes are assembled, activated, and involved in host defense and pathophysiology of diseases. Clarification of the molecular mechanisms leading to the activation of this intracellular inflammatory machinery may provide new insights into the concept of inflammation as the root of and route to human diseases. Recent Advances: The activation of inflammasomes, specifically the most …

Stromal Monocarboxylate Transporter Mct4 Is A Poor Prognostic Factor In Squamous Cell Carcinoma, Mehri Mollaee, Md, P. Cotzia, Patrick Tassone, Md, Adam J. Luginbuhl, Md, Ubaldo E. Martinez-Outshoorn, Md, Tingting Zhan, Joseph M. Curry, Md, Madalina Tuluc, Md

Department of Pathology, Anatomy, and Cell Biology Resident's Posters

ABSTRACT

Introduction:

Monocarboxylate transporter 4 (MCT4) is the main exporter of lactate out of cells. It is also a critical component in the glycolytic metabolism of cancer cells. In this study, stromal MCT4 in oral SCC was correlated with risk of recurrence (ROR), extent of primary tumor (pT) and nodal metastasis (pN), perineural invasion (PNI), lymphovascular invasion (LVI), HPV status, extracapsular extension (ECE) and positive margin.

Methods:

Clinical data were collected for 86 consecutive patients with oral HNSCC. Tissue microarrays (TMA) were constructed from paraffin blocks of resection specimens and stained for MCT4. Immunohistochemistry (IHC) staining was assessed and quantified …

Workflow Modifications And Addition Of Maldi-Tof Technology Significantly Improved Turn-Around-Time To Identification Of Common Urine Pathogens, Dimath Alyemni, Md, Christine M. Lam, Amity L. Roberts, Phd, D(Abmm)

Department of Pathology, Anatomy, and Cell Biology Resident's Posters

Background:

In order to improve the identification of common aerobic urine cultures as well as antimicrobial susceptibility testing (AST) setup at an Academic Medical Center, work-flow modifications and MALDI-TOF technology were incorporated. Previously, the majority of species identification was achieved with conventional identification/antimicrobial susceptibility combo panels. All urine cultures, regardless of laboratory receipt time, were previously read once per day on 1st shift.

Methods:

The initial workflow modification involved addition of a 2nd shift urine culture reading. Urine specimens received from 8:00 AM to 4:00 PM were read on 1st shift, while urine specimens received from 4:00 PM to 8:00 …

Is Myeloproliferative Neoplasm With Splanchnic Vein Thrombosis A Distinct Clinical Entity?, Upasana Joneja, Md, Jerald Z. Gong, Md, Guldeep Uppal, Md

Department of Pathology, Anatomy, and Cell Biology Resident's Posters

Clinical History:

A 29 year-old previously healthy female presented with sub-acute symptoms of weight loss, right upper quadrant pain and nausea.

CBC results: WBC-11.7, Hb- 12.5, Platelet- 286, MCV- 90, MCV- 26.8, RDW- 18%.

Imaging: Ultrasound and MRI of the abdomen were suggestive of Budd-Chiari syndrome that was supported by a liver biopsy showing features of hepatic outflow obstruction(Figure 1). There was no clinical or radiological evidence of splenomegaly. The hypercoagulable work-up was negative. An underlying Myeloproliferative Neoplasm (MPN) was suspected.

Ascorbic Acid And Ascorbate-2-Phosphate Decrease Hif Activity And Malignant Properties Of Human Melanoma Cells, Sarah Miles, Adam P. Fischer, Sandeep J. Joshi, Richard M. Niles

Biochemistry and Microbiology

Background: Hypoxia inducible factor-1 alpha (HIF-1α) is thought to play a role in melanoma carcinogenesis. Posttranslational regulation of HIF-1α is dependent on Prolyl hydroxylase (PHD 1–3) and Factor Inhibiting HIF (FIH) hydroxylase enzymes, which require ascorbic acid as a co-factor for optimal function. Depleted intra-tumoral ascorbic acid may thus play a role in the loss of HIF-1α regulation in melanoma. These studies assess the ability of ascorbic acid to reduce HIF-1α protein and transcriptional activity in metastatic melanoma and reduce its invasive potential.

Methods: HIF-1α protein was evaluated by western blot, while transcriptional activity was measured by HIF-1 HRE-luciferase reporter …

Assessment Of Artificial Mirna Architectures For Higher Knockdown Efficiencies Without The Undesired Effects In Mice., Hiromi Miura, Hidetoshi Inoko, Masafumi Tanaka, Hirofumi Nakaoka, Minoru Kimura, Channabasavaiah B. Gurumurthy, Masahiro Sato, Masato Ohtsuka

Journal Articles: Genetics, Cell Biology & Anatomy

RNAi-based strategies have been used for hypomorphic analyses. However, there are technical challenges to achieve robust, reproducible knockdown effect. Here we examined the artificial microRNA (amiRNA) architectures that could provide higher knockdown efficiencies. Using transient and stable transfection assays in cells, we found that simple amiRNA-expression cassettes, that did not contain a marker gene (-MG), displayed higher amiRNA expression and more efficient knockdown than those that contained a marker gene (+MG). Further, we tested this phenomenon in vivo, by analyzing amiRNA-expressing mice that were produced by the pronuclear injection-based targeted transgenesis (PITT) method. While we observed significant silencing of the …

High-Field Functional Imaging Of Pitch Processing In Auditory Cortex Of The Cat., Blake E. Butler, Amee J Hall, Stephen G Lomber

Brain and Mind Institute Researchers' Publications

The perception of pitch is a widely studied and hotly debated topic in human hearing. Many of these studies combine functional imaging techniques with stimuli designed to disambiguate the percept of pitch from frequency information present in the stimulus. While useful in identifying potential "pitch centres" in cortex, the existence of truly pitch-responsive neurons requires single neuron-level measures that can only be undertaken in animal models. While a number of animals have been shown to be sensitive to pitch, few studies have addressed the location of cortical generators of pitch percepts in non-human models. The current study uses high-field functional …

Early Initiation Of Antiretroviral Therapy Can Functionally Control Productive Hiv-1 Infection In Humanized-Blt Mice, Qingsheng Li, For Yue Tso, Guobin Kang, Wuxun Lu, Yue Li, Wenjin Fan, Zhe Yuan, Christopher J. Destache, Charles Wood

Nebraska Center for Virology: Faculty Publications

Background—Recent reports showed that functional control of HIV-1 infection for a prolonged time is possible by early anti-retroviral therapy (ART); however its underlying mechanism needs to be studied with a suitable animal model. Recently, humanized-BLT (bone marrow, liver and thymus) mouse (hu-BLT) was shown to be an excellent model for studying HIV-1 infection. We thus tested the feasibility of studying functional control of HIV-1 infection using hu-BLT mice.

Methods—Animals in three treatment groups (Rx-6h, Rx-24h, Rx-48h) and untreated group were infected with HIV-1, followed by ART initiation at 6, 24 or 48 hours post-infection and continued daily for two weeks. …

The Role Of Dendritic Cell Subsets And Innate Immunity In The Pathogenesis Of Type 1 Diabetes And Other Autoimmune Diseases, Jeffrey D. Price, Kristin V. Tarbell

Nebraska Center for Virology: Faculty Publications

Dendritic cells (DCs) are key antigen-presenting cells that have an important role in autoimmune pathogenesis. DCs control both steady-state T cell tolerance and activation of pathogenic responses. The balance between these two outcomes depends on several factors, including genetic susceptibility, environmental signals that stimulate varied innate responses, and which DC subset is presenting antigen. Although the specific DC phenotype can diverge depending on the tissue location and context, there are four main subsets identified in both mouse and human: conventional cDC1 and cDC2, plasmacytoid DCs, and monocyte-derived DCs. In this review, we will discuss the role of these subsets in …

Cerium Oxide Nanoparticles Attenuate Polymicrobial Sepsis Induced Splenic Damage In Male Sprague Dawley Rats, Venkata Vinay Kumar Bandarupalli

Theses, Dissertations and Capstones

Sepsis is a serious life threatening medical emergency which, if not treated properly, oftentimes results in organ failure and death. Current sepsis treatment protocols are largely centered on the use of antibiotics and supportive care. Recent studies have suggested that antibiotics fail to be effective for sepsis treatment when administered during hypo-dynamic phase of sepsis that is usually characterized by the presence of a cytokine storm. As such, there is an urgent need to develop novel therapeutic drugs that target the inflammatory cytokines that are secreted as a result of increased reactive oxygen species. Cerium oxide nanoparticles (CeO2) have been …

Contribution Of Nrf2 To Atherogenic Phenotype Switching Of Coronary Arterial Smooth Muscle Cells Lacking Cd38 Gene, Ming Xu, Xiao-Xue Li, Lei Wang, Mi Wang, Yang Zhang, Pin-Lan Li

Pharmacology and Toxicology Publications

Background/Aims: Recent studies have indicated that CD38 gene deficiency results in dedifferentiation or transdifferentiation of arterial smooth muscle cells upon atherogenic stimulations. However, the molecular mechanisms mediating this vascular smooth muscle (SMC) phenotypic switching remain unknown. Methods & Results: In the present study, we first characterized the phenotypic change in the primary cultures of coronary arterial myocytes (CAMs) from CD38-/- mice. It was shown that CD38 deficiency decreased the expression of contractile marker calponin, SM22α and α-SMA but increased the expression of SMC dedifferentiation marker, vimentin, which was accompanied by enhanced cell proliferation. This phenotypic change in CD38-/- CAMs was …

Concentration-Dependent Diversification Effects Of Free Cholesterol Loading On Macrophage Viability And Polarization, Xiaoyang Xu, Aolin Zhang, Ningjun Li, Pin-Lan Li, Fan Zhang

Pharmacology and Toxicology Publications

Background/Aims: The accumulation of free cholesterol in atherosclerotic lesions has been well documented in both animals and humans. In studying the relevance of free cholesterol buildup in atherosclerosis, contradictory results have been generated, indicating that free cholesterol produces both pro- and anti-atherosclerosis effects in macrophages. This inconsistency might stem from the examination of only select concentrations of free cholesterol. In the present study, we sought to investigate the implication of excess free cholesterol loading in the pathophysiology of atherosclerosis across a broad concentration range from (in µg/ml) 0 to 60. Methods:Macrophage viability was determined by measuring formazan formation and …

Genetic Modifiers Of Duchenne Muscular Dystrophy And Dilated Cardiomyopathy., Andrea Barp, Luca Bello, Luisa Politano, Paola Melacini, Chiara Calore, Eric P. Hoffman, +16 Additional Authors

Genomics and Precision Medicine Faculty Publications

OBJECTIVE: Dilated cardiomyopathy (DCM) is a major complication and leading cause of death in Duchenne muscular dystrophy (DMD). DCM onset is variable, suggesting modifier effects of genetic or environmental factors. We aimed to determine if polymorphisms previously associated with age at loss of independent ambulation (LoA) in DMD (rs28357094 in the SPP1 promoter, rs10880 and the VTTT/IAAM haplotype in LTBP4) also modify DCM onset.

METHODS: A multicentric cohort of 178 DMD patients was genotyped by TaqMan assays. We performed a time-to-event analysis of DCM onset, with age as time variable, and finding of left ventricular ejection fraction < 50% and/or end diastolic volume > 70 mL/m2 as …

Transcriptional Pathways Associated With Skeletal Muscle Changes After Spinal Cord Injury And Treadmill Locomotor Training., Celine Baligand, Yi-Wen Chen, Fan Ye, Sachchida Nand Pandey, San-Huei Lai, Min Liu, Krista Vandenborne

Genomics and Precision Medicine Faculty Publications

The genetic and molecular events associated with changes in muscle mass and function after SCI and after the implementation of candidate therapeutic approaches are still not completely known. The overall objective of this study was to identify key molecular pathways activated with muscle remodeling after SCI and locomotor training. We implemented treadmill training in a well-characterized rat model of moderate SCI and performed genome wide expression profiling on soleus muscles at multiple time points: 3, 8, and 14 days after SCI. We found that the activity of the protein ubiquitination and mitochondrial function related pathways was altered with SCI and …

Gene Function In Schistosomes: Recent Advances Toward A Cure, Arnon D. Jurburg, Paul J. Brindley

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Voltage-Gated Na+ Channel Activity Increases Colon Cancer Transcriptional Activity And Invasion Via Persistent Mapk Signaling, Carrie D. House, Bi-Dar Wang, Kristin Ceniccola, Russell Williams, May Simaan, Norman H. Lee, +7 Additional Authors

Pharmacology and Physiology Faculty Publications

Functional expression of voltage-gated Na⁺ channels (VGSCs) has been demonstrated in multiple cancer cell types where channel activity induces invasive activity. The signaling mechanisms by which VGSCs promote oncogenesis remain poorly understood. We explored the signal transduction process critical to VGSC-mediated invasion on the basis of reports linking channel activity to gene expression changes in excitable cells. Coincidentally, many genes transcriptionally regulated by the SCN5A isoform in colon cancer have an over-representation of cis-acting sites for transcription factors phosphorylated by ERK1/2 MAPK. We hypothesized that VGSC activity promotes MAPK activation to induce transcriptional changes in invasion-related genes. Using …

Neuroscience, Mindreading, And The Courts: The Example Of Pain, Henry T. Greely

Journal of Health Care Law and Policy

No abstract provided.

Neuronal Migration: How Do You Build A Brain?, Sravya Uppalapati

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Senior biology major Alex Burkard is working in the Walsh Neurodevelopment Laboratory at VCU to help answer the question, ‘How do you build a brain?’ Burkard is researching neuronal migration in Zebrafish and how cellular polarity affects hindbrain development.

Immortal Mortals, Sterling Giles

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Junior Information Systems and Bioinformatics major Michael Kiflezghi focuses his research interests on an organism’s lifespan and gut microbial communities.