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Michael John Patton, Stuart McCorrister, Chris Grant, Garrett Westmacott, Robert Fariss, Pingzhao Hu, Kaiqiong Zhao, Mary Blake, Bill Whitmire, Chunfu Yang, Harlan D Caldwell, Grant McClarty
: The chlamydial protease-like activity factor (CPAF) is hypothesized to be an important secreted virulence factor; however, challenges in denaturing its proteolytic activity have hampered attempts to identify its legitimate targets. Here, we use a genetic and proteomic approach to identify authentic CPAF targets. Human epithelial cells infected with CPAF-sufficient and CPAF-deficient chlamydiae were lysed using known CPAF-denaturing conditions. Their protein profiles were analyzed using isobaric mass tags and liquid chromatography-tandem mass spectrometry...
September 27, 2016: MBio
Mohammad Ehsanul Karim, John Petkau, Paul Gustafson, Robert W Platt, Helen Tremlett
In longitudinal studies, if the time-dependent covariates are affected by the past treatment, time-dependent confounding may be present. For a time-to-event response, marginal structural Cox models are frequently used to deal with such confounding. To avoid some of the problems of fitting marginal structural Cox model, the sequential Cox approach has been suggested as an alternative. Although the estimation mechanisms are different, both approaches claim to estimate the causal effect of treatment by appropriately adjusting for time-dependent confounding...
September 21, 2016: Statistical Methods in Medical Research
X Shi, X Zhang, L Wang, W Li, B Jiang, R Deng, A Wang, G Zhang
Porcine reproductive and respiratory syndrome virus (PRRSV) causes one of the most economically devastating and pandemic porcine diseases. Previous study has shown that MARC-145 cells pretreated with recombinant IFN-β (rIFN-β) couldn't develop cytopathic effect (CPE) of PRRSV. However, up to date, it is not clear whether MARC-145 cells post-treated with rIFN-β could develop CPE of PRRSV. The present work showed that the MARC-145 cells didn't develop the CPE at 120 hr post-infection (p.i.) with low-dose of PRRSV when the cells were pre-treated with rIFN-β (Group 1), post-treated with rIFN-β at 4 hr p...
2016: Acta Virologica
Mehmet Fatih Yetkin, Meral Mirza, Halil Dönmez
The aim of this study is to compare the white matter of multiple sclerosis (MS) patients with healthy controls and to monitor the response to the treatment with magnetic resonance spectroscopy (MRS).Fifteen healthy controls and 36 recently diagnosed MS patients never treated with interferon β were included in this study. In the patient group, MRS was performed before treatment, at 6th and 12th month after the initiation of treatment and once in control group. Patient group was divided into 3 interferon groups randomly...
September 2016: Medicine (Baltimore)
Yonglin Zhao, Yahui Zhao, Ming Zhang, Junjie Zhao, Xudong Ma, Tingqin Huang, Honggang Pang, Jiaxi Li, Jinning Song
Increasing evidence suggests that secondary injury after diffuse axonal injury (DAI) damages more axons than the initial insult, but the underlying mechanisms of this phenomenon are not fully understood. Recent studies show that toll-like receptor 4 (TLR4) plays a critical role in promoting adaptive immune responses and have been shown to be associated with brain damage. The purpose of this study was to investigate the role of the TLR4 signalling pathway in secondary axonal injury in the cortices of DAI rats...
2016: Mediators of Inflammation
Mohammad Ehsanul Karim, Paul Gustafson, John Petkau, Helen Tremlett
In time-to-event analyses of observational studies of drug effectiveness, incorrect handling of the period between cohort entry and first treatment exposure during follow-up may result in immortal time bias. This bias can be eliminated by acknowledging a change in treatment exposure status with time-dependent analyses, such as fitting a time-dependent Cox model. The prescription time-distribution matching (PTDM) method has been proposed as a simpler approach for controlling immortal time bias. Using simulation studies and theoretical quantification of bias, we compared the performance of the PTDM approach with that of the time-dependent Cox model in the presence of immortal time...
August 15, 2016: American Journal of Epidemiology
Jeffrey A Tomalka, Tristan J de Jesus, Parameswaran Ramakrishnan
Recognition of pathogens by Toll-like receptors (TLR) activate multiple signaling cascades and expression of genes tailored to mount a primary immune response, inflammation, cell survival and apoptosis. Although TLR-induced activation of pathways, such as nuclear factor kappaB (NF-κB) and mitogen-activated protein kinases (MAPK), has been well studied, molecular entities controlling quantitative regulation of these pathways during an immune response remain poorly defined. We identified Sam68 as a novel regulator of TLR-induced NF-κB and MAPK activation...
July 4, 2016: Cellular & Molecular Immunology
Luwanika Mlera, Jennifer Lam, Danielle K Offerdahl, Craig Martens, Daniel Sturdevant, Charles V Turner, Stephen F Porcella, Marshall E Bloom
UNLABELLED: Tick-borne flaviviruses (TBFVs) cause febrile illnesses, which may progress to severe encephalitis and/or death in humans globally. Most people who recover from severe acute disease suffer from debilitating neurological sequelae, which may be due to viral persistence, infection-induced neurological cell damage, host response, or some combination of these. Acute TBFV infection of human embryonic kidney (HEK) 293T cells in vitro results in the death of >95% of infected cells by day 5...
2016: MBio
Douglas R Wilcox, Stephen S Folmsbee, William J Muller, Richard Longnecker
UNLABELLED: Newborns are significantly more susceptible to severe viral encephalitis than adults, with differences in the host response to infection implicated as a major factor. However, the specific host signaling pathways responsible for differences in susceptibility and neurologic morbidity have remained unknown. In a murine model of HSV encephalitis, we demonstrated that the choroid plexus (CP) is susceptible to herpes simplex virus 1 (HSV-1) early in infection of the newborn but not the adult brain...
2016: MBio
Miguel A Martín-Acebes, Ana-Belén Blázquez, Rodrigo Cañas-Arranz, Ángela Vázquez-Calvo, Teresa Merino-Ramos, Estela Escribano-Romero, Francisco Sobrino, Juan-Carlos Saiz
Usutu virus (USUV) is a mosquito-borne flavivirus whose circulation had been confined to Africa since it was first detected in 1959. However, in the last decade USUV has emerged in Europe causing episodes of avian mortality and sporadic severe neuroinvasive infections in humans. Remarkably, adult laboratory mice exhibit limited susceptibility to USUV infection, which has impaired the analysis of the immune responses, thus complicating the evaluation of virus-host interactions and of vaccine candidates against this pathogen...
April 19, 2016: Vaccine
Yi Wang, Li Liu
UNLABELLED: Most of the intracellular pattern recognition receptors (PRRs) reside in either the endolysosome or the cytoplasm to sense pathogen-derived RNAs, DNAs, or synthetic analogs of double-stranded RNA (dsRNA), such as poly(I:C). However, it remains elusive whether or not a pathogen-derived protein can function as a cytosolic pathogen-associated molecular pattern (PAMP). In this study, we demonstrate that delivering the membrane gene of severe acute respiratory syndrome coronavirus (SARS-CoV) into HEK293T, HEK293ET, and immobilized murine bone marrow-derived macrophage (J2-Mφ) cells significantly upregulates beta interferon (IFN-β) production...
2016: MBio
Ren Song, Orkide O Koyuncu, Todd M Greco, Benjamin A Diner, Ileana M Cristea, Lynn W Enquist
UNLABELLED: Infection by alphaherpesviruses, including herpes simplex virus (HSV) and pseudorabies virus (PRV), typically begins at epithelial surfaces and continues into the peripheral nervous system (PNS). Inflammatory responses are induced at the infected peripheral site prior to invasion of the PNS. When the peripheral tissue is first infected, only the innervating axons are exposed to this inflammatory milieu, which includes the interferons (IFNs). The fundamental question is how do PNS cell bodies respond to these distant, potentially damaging events experienced by axons...
2016: MBio
Samaneh Enayati, Soroush Seifirad, Parvin Amiri, Milad Abolhalaj, Mahsa Mohammad-Amoli
BACKGROUND: Several inflammatory mediators have been proposed to contribute to the pathogenesis of atherosclerosis. The aim of this study was to evaluate the quantitative expression of pro-inflammatory cytokines in un-stimulated peripheral blood mononuclear cell of patients with coronary artery disease (CAD). METHODS: Interleukin-1 beta (IL-1β), tumor necrosis factor-alpha, and interferon-gamma (IFN-γ) gene expression were evaluated in angiography confirmed patients with and without CAD in a case-control study using quantitative real-time polymerase chain reaction...
September 2015: ARYA Atherosclerosis
Yang Yang, Fei Ye, Na Zhu, Wenling Wang, Yao Deng, Zhengdong Zhao, Wenjie Tan
Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel and highly pathogenic human coronavirus and has quickly spread to other countries in the Middle East, Europe, North Africa and Asia since 2012. Previous studies have shown that MERS-CoV ORF4b antagonizes the early antiviral alpha/beta interferon (IFN-α/β) response, which may significantly contribute to MERS-CoV pathogenesis; however, the underlying mechanism is poorly understood. Here, we found that ORF4b in the cytoplasm could specifically bind to TANK binding kinase 1 (TBK1) and IκB kinase epsilon (IKKε), suppress the molecular interaction between mitochondrial antiviral signaling protein (MAVS) and IKKε, and inhibit IFN regulatory factor 3 (IRF3) phosphorylation and subsequent IFN-β production...
2015: Scientific Reports
Yan Li, Young Mee Kim, Jing Zou, Qing-Yin Wang, Shovanlal Gayen, Ying Lei Wong, Le Tian Lee, Xuping Xie, Qiwei Huang, Julien Lescar, Pei-Yong Shi, CongBao Kang
The transmembrane NS4B protein of dengue virus (DENV) is a validated antiviral target that plays important roles in viral replication and invasion of innate immune response. The first 125 amino acids of DENV NS4B are sufficient for inhibition of alpha/beta interferon signaling. Resistance mutations to NS4B inhibitors are all mapped to the first 125 amino acids. In this study, we expressed and purified a protein representing the first 125 amino acids of NS4B (NS4B(1-125)). This recombinant NS4B(1-125) protein was reconstituted into detergent micelles...
December 2015: Biochimica et Biophysica Acta
Emily Dorman, Anuraag R Kansal, Sujata Sarda
OBJECTIVE: Multiple sclerosis (MS) causes significant disability globally and is especially prevalent in Canada. Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) is an orally administered disease-modifying treatment (DMT) for patients with relapsing-remitting MS (RRMS) that is currently on the market in the US, Australia, Canada, and Europe. A budget impact model (BIM) was developed to assess the financial consequences of introducing DMF for treatment of RRMS in Canada...
2015: Journal of Medical Economics
Brandon J Dixon, Cesar Reis, Wing Mann Ho, Jiping Tang, John H Zhang
Neonatal hypoxic ischemic encephalopathy (HIE) is a devastating disease that primarily causes neuronal and white matter injury and is among the leading cause of death among infants. Currently there are no well-established treatments; thus, it is important to understand the pathophysiology of the disease and elucidate complications that are creating a gap between basic science and clinical translation. In the development of neuroprotective strategies and translation of experimental results in HIE, there are many limitations and challenges to master based on an appropriate study design, drug delivery properties, dosage, and use in neonates...
2015: International Journal of Molecular Sciences
Irene Tramacere, Cinzia Del Giovane, Georgia Salanti, Roberto D'Amico, Graziella Filippini
BACKGROUND: Different therapeutic strategies are available for the treatment of people with relapsing-remitting multiple sclerosis (RRMS), including immunomodulators, immunosuppressants and biologics. Although there is consensus that these therapies reduce the frequency of relapses, their relative benefit in delaying new relapses or disability worsening remains unclear due to the limited number of direct comparison trials. OBJECTIVES: To compare the benefit and acceptability of interferon beta-1b, interferon beta-1a (Avonex, Rebif), glatiramer acetate, natalizumab, mitoxantrone, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, pegylated interferon beta-1a, daclizumab, laquinimod, azathioprine and immunoglobulins for the treatment of people with RRMS and to provide a ranking of these treatments according to their benefit and acceptability, defined as the proportion of participants who withdrew due to any adverse event...
2015: Cochrane Database of Systematic Reviews
X Zhou, H Loomis-King, S J Gurczynski, C A Wilke, K E Konopka, C Ptaschinski, S M Coomes, Y Iwakura, L F van Dyk, N W Lukacs, B B Moore
Hematopoietic stem cell transplantation (HSCT) efficacy is limited by numerous pulmonary complications. We developed a model of syngeneic bone marrow transplantion (BMT) followed by infection with murine gamma herpesvirus-68 that results in pneumonitis and fibrosis and mimics human "noninfectious" HSCT complications. BMT mice experience increased early lytic replication, but establish viral latency by 21 days post infection. CD4 T cells in BMT mice are skewed toward interleukin (IL)-17A rather than interferon (IFN)-γ production...
May 2016: Mucosal Immunology
Pietro Iaffaldano, Giuseppe Lucisano, Carlo Pozzilli, Vincenzo Brescia Morra, Angelo Ghezzi, Enrico Millefiorini, Francesco Patti, Alessandra Lugaresi, Giovanni Bosco Zimatore, Maria Giovanna Marrosu, Maria Pia Amato, Antonio Bertolotto, Roberto Bergamaschi, Franco Granella, Gabriella Coniglio, Gioacchino Tedeschi, Patrizia Sola, Giacomo Lus, Maria Teresa Ferrò, Gerardo Iuliano, Francesco Corea, Alessandra Protti, Paola Cavalla, Angelica Guareschi, Mariaemma Rodegher, Damiano Paolicelli, Carla Tortorella, Vito Lepore, Luca Prosperini, Francesco Saccà, Damiano Baroncini, Giancarlo Comi, Maria Trojano
The comparative effectiveness of fingolimod versus interferon beta/glatiramer acetate was assessed in a multicentre, observational, prospectively acquired cohort study including 613 patients with relapsing multiple sclerosis discontinuing natalizumab in the Italian iMedWeb registry. First, after natalizumab suspension, the relapse risk during the untreated wash-out period and during the course of switch therapies was estimated through Poisson regression analyses in separated models. During the wash-out period an increased risk of relapses was found in patients with a higher number of relapses before natalizumab treatment (incidence rate ratio = 1...
November 2015: Brain: a Journal of Neurology
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