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https://www.readbyqxmd.com/read/28928438/zyxin-stabilizes-rig-i-and-mavs-interactions-and-promotes-type-i-interferon-response
#1
Takahisa Kouwaki, Masaaki Okamoto, Hirotake Tsukamoto, Yoshimi Fukushima, Misako Matsumoto, Tsukasa Seya, Hiroyuki Oshiumi
RIG-I and MDA5 are cytoplasmic viral RNA sensors that belong to the RIG-I-like receptors (RLRs), which induce antiviral innate immune responses, including the production of type I interferon and other pro-inflammatory cytokines. After recognition of viral RNA, the N-terminal caspase activation and recruitment domains (CARDs) of RIG-I and MDA5 bind to a CARD in the MAVS adaptor molecule, resulting in MAVS oligomerization and downstream signaling. To reveal the molecular mechanism of MAVS-dependent signaling, we performed a yeast two-hybrid screening and identified zyxin as a protein that binds to MAVS...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28917493/usefulness-of-myocardial-annular-velocity-change-during-mental-stress-to-predict-cardiovascular-outcome-in-patients-with-coronary-artery-disease-from-the-responses-of-mental-stress-induced-myocardial-ischemia-to-escitalopram-treatment-trial
#2
Fawaz Alenezi, Beverly H Brummett, Stephen H Boyle, Zainab Samad, Michael A Babyak, Nabil Alzaeim, Jennifer Wilson, Minna M D Romano, Julia L Sun, Mads Ersboll, Christopher M O'Connor, Eric J Velazquez, Wei Jiang
Mental stress-induced myocardial ischemia is common and a prognostic factor of adverse cardiovascular outcomes in patients with coronary artery disease (CAD). The present study aimed at examining associations between mental stress-induced myocardial annular velocity (MAV) and cardiovascular outcome in patients with CAD. MAV, specifically, diastolic early (e'), diastolic late (a'), and systolic (s') velocities were obtained at rest and during mental stress testing in 224 patients with clinically stable CAD. Using Cox regression models, age, sex, and baseline-adjusted mental stress-induced MAV measures were examined as predictors of a priori defined composite event term that comprised all-cause mortality and/or nonfatal cardiovascular events, resulting in an unplanned hospitalization (major adverse cardiovascular events [MACE])...
July 29, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28874382/evaluation-of-the-innate-immune-modulator-acitretin-as-a-strategy-to-clear-the-hiv-reservoir
#3
Edurne Garcia-Vidal, Marc Castellví, Maria Pujantell, Roger Badia, Antoni Jou, Lucia Gomez, Teresa Puig, Bonaventura Clotet, Ester Ballana, Eva Riveira-Muñoz, José A Esté
The persistence of HIV despite suppressive antiretroviral therapy is a major roadblock to HIV eradication. Current strategies focused on inducing the expression of latent HIV fail to clear the persistent reservoir, prompting the development of new approaches for killing HIV+ cells. Recently, acitretin has been proposed as a pharmacological innate cellular-defense network enhancer that led to virus reactivation and preferential death of infected cells. We have evaluated the capacity of acitretin to reactivate and/or facilitate immune-mediated clearance of HIV+ cells...
September 5, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28862728/value-of-triphasic-mdct-in-the-differentiation-of-small-renal-cell-carcinoma-and-oncocytoma
#4
Michele Scialpi, Eugenio Martorana, Valeria Rondoni, Ahmed Eissa, Ahmed El Sherbiny, Luigi Bevilacqua, Luis H Ros, Irene Escartín Martínez, Michele Milizia, Lucia Manganaro, Maria Antonietta Mazzei, Alfredo D'Andrea, Giampaolo Bianchi
INTRODUCTION: Although differentiation between benign and malignant small renal tumors (≤4 cm) is still difficult, it is a demand for decision making and determining the treatment strategy. Our aim is to evaluate the role of multidetector row computed tomography (MDCT) in the differentiation of small renal clear cell carcinoma (RCC) and renal oncocytoma (RO). METHODS: We reviewed triphasic computed tomographic (CT) scans performed in 43 patients diagnosed with RCC (n = 23) and RO (n = 21)...
August 11, 2017: Urologia
https://www.readbyqxmd.com/read/28846086/the-rna-helicase-ddx46-inhibits-innate-immunity-by-entrapping-m-6-a-demethylated-antiviral-transcripts-in-the-nucleus
#5
Qingliang Zheng, Jin Hou, Ye Zhou, Zhenyang Li, Xuetao Cao
DEAD-box (DDX) helicases are vital for the recognition of RNA and metabolism and are critical for the initiation of antiviral innate immunity. Modification of RNA is involved in many biological processes; however, its role in antiviral innate immunity has remained unclear. Here we found that nuclear DDX member DDX46 inhibited the production of type I interferons after viral infection. DDX46 bound Mavs, Traf3 and Traf6 transcripts (which encode signaling molecules involved in antiviral responses) via their conserved CCGGUU element...
October 2017: Nature Immunology
https://www.readbyqxmd.com/read/28837698/differences-in-pathogenicity-of-three-animal-isolates-of-mycobacterium-species-in-a-mouse-model
#6
Haodi Dong, Yue Lv, Srinand Sreevatsan, Deming Zhao, Xiangmei Zhou
Animal mycobacterioses are among the most important zoonoses worldwide. These are generally caused by either Mycobacterium tuberculosis (MTB), M. bovis (MBO) or M. avium (MAV). To test the hypothesis that different species of pathogenic mycobacteria isolated from varied anatomic locations or animal species differ in virulence and pathogenicity, we performed experiments with three mycobacteria strains (NTSE-3(MTB), NTSE-4(MBO) and NTSE-5 (MAV)) obtained from animal species. Spoligotyping analysis was used to confirm both MTB and MBO strains while the MAV strain was confirmed by 16s rDNA sequencing...
2017: PloS One
https://www.readbyqxmd.com/read/28822807/spontaneous-activation-of-a-mavs-dependent-antiviral-signaling-pathway-determines-high-basal-interferon-%C3%AE-expression-in-cardiac-myocytes
#7
Efraín E Rivera-Serrano, Nicole DeAngelis, Barbara Sherry
Viral myocarditis is a leading cause of sudden death in young adults as the limited turnover of cardiac myocytes renders the heart particularly vulnerable to viral damage. Viruses induce an antiviral type I interferon (IFN-α/β) response in essentially all cell types, providing an immediate innate protection. Cardiac myocytes express high basal levels of IFN-β to help pre-arm them against viral infections, however the mechanism underlying this expression remains unclear. Using primary cultures of murine cardiac and skeletal muscle cells, we demonstrate here that the mitochondrial antiviral signaling (MAVS) pathway is spontaneously activated in unstimulated cardiac myocytes but not cardiac fibroblasts or skeletal muscle cells...
October 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28818792/regulation-of-type-i-interferon-responses-by-mitochondria-derived-reactive-oxygen-species-in-plasmacytoid-dendritic-cells
#8
Zsofia Agod, Tünde Fekete, Marietta M Budai, Aliz Varga, Attila Szabo, Hyelim Moon, Istvan Boldogh, Tamas Biro, Arpad Lanyi, Attila Bacsi, Kitti Pazmandi
Mitochondrial reactive oxygen species (mtROS) generated continuously under physiological conditions have recently emerged as critical players in the regulation of immune signaling pathways. In this study we have investigated the regulation of antiviral signaling by increased mtROS production in plasmacytoid dendritic cells (pDCs), which, as major producers of type I interferons (IFN), are the key coordinators of antiviral immunity. The early phase of type I IFN production in pDCs is mediated by endosomal Toll-like receptors (TLRs), whereas the late phase of IFN response can also be triggered by cytosolic retinoic acid-inducible gene-I (RIG-I), expression of which is induced upon TLR stimulation...
July 29, 2017: Redox Biology
https://www.readbyqxmd.com/read/28814035/decoding-of-individual-finger-movements-from-surface-emg-signals-using-vector-autoregressive-hierarchical-hidden-markov-models-varhhmm
#9
Nebojsa Malesevic, Dimitrije Markovic, Gunter Kanitz, Marco Controzzi, Christian Cipriani, Christian Antfolk
In this paper we present a novel method for predicting individual fingers movements from surface electromyography (EMG). The method is intended for real-time dexterous control of a multifunctional prosthetic hand device. The EMG data was recorded using 16 single-ended channels positioned on the forearm of healthy participants. Synchronously with the EMG recording, the subjects performed consecutive finger movements based on the visual cues. Our algorithm could be described in following steps: extracting mean average value (MAV) of the EMG to be used as the feature for classification, piece-wise linear modeling of EMG feature dynamics, implementation of hierarchical hidden Markov models (HHMM) to capture transitions between linear models, and implementation of Bayesian inference as the classifier...
July 2017: IEEE ... International Conference on Rehabilitation Robotics: [proceedings]
https://www.readbyqxmd.com/read/28811654/characterization-of-the-mollusc-rig-i-mavs-pathway-reveals-an-archaic-antiviral-signalling-framework-in-invertebrates
#10
Baoyu Huang, Linlin Zhang, Yishuai Du, Fei Xu, Li Li, Guofan Zhang
Despite the mitochondrial antiviral signalling protein (MAVS)-dependent RIG-I-like receptor (RLR) signalling pathway in the cytosol plays an indispensable role in the antiviral immunity of the host, surprising little is known in invertebrates. Here we characterized the major members of RLR pathway and investigated their signal transduction a Molluscs. We show that genes involved in RLR pathway were significantly induced during virus challenge, including CgRIG-I-1, CgMAVS, CgTRAF6 (TNF receptor-associated factor 6), and CgIRFs (interferon regulatory factors...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808966/methods-to-visualize-mavs-subcellular-localization
#11
Christine Vazquez, Dia C Beachboard, Stacy M Horner
The mitochondrial antiviral signaling (MAVS) protein is a central adaptor protein required for antiviral innate immune signaling. To facilitate its roles in innate immunity, MAVS localizes to multiple intracellular membranous compartments, including the mitochondria, the mitochondrial-associated ER membrane (MAM), and peroxisomes. Studies of MAVS function therefore often require an analysis of MAVS localization. To detect MAVS protein on intracellular membranes, biochemical fractionation to isolate MAMs, mitochondria, or peroxisomes can be used...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28806745/persistent-mycobacteria-evade-an-antibacterial-program-mediated-by-phagolysosomal-tlr7-8-myd88-in-human-primary-macrophages
#12
Alexandre Gidon, Signe Elisabeth Åsberg, Claire Louet, Liv Ryan, Markus Haug, Trude Helen Flo
Pathogenic mycobacteria reside in macrophages where they avoid lysosomal targeting and degradation through poorly understood mechanisms proposed to involve arrest of phagosomal maturation at an early endosomal stage. A clear understanding of how this relates to host defenses elicited from various intracellular compartments is also missing and can only be studied using techniques allowing single cell and subcellular analyses. Using confocal imaging of human primary macrophages infected with Mycobacterium avium (Mav) we show evidence that Mav phagosomes are not arrested at an early endosomal stage, but mature to a (LAMP1+/LAMP2+/CD63+) late endosomal/phagolysosomal stage where inflammatory signaling and Mav growth restriction is initiated through a mechanism involving Toll-like receptors (TLR) 7 and 8, the adaptor MyD88 and transcription factors NF-κB and IRF-1...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28783846/cardiorespiratory-responses-to-continuous-and-intermittent-exercises-in-children
#13
Georges Baquet, François-Xavier Gamelin, Julien Aucouturier, Serge Berthoin
The aim of the study was to characterize aerobic responses to high intensity intermittent (HIIE) and continuous (CE) exercises in prepubertal children. 26 children aged 8 to 11-year-old took part in a preliminary session to determine peakVO2 and Maximal Aerobic Velocity (MAV). In 5 subsequent experimental visits, the participants completed 2 CE and 3 HIIE sessions in a randomized order. HIIE consisted of short intermittent 10-s and 20-s running bouts at 100 to 130% MAV, interspersed with recovery periods of equal duration (S-HIIE1 and S-HIIE2 respectively) and 5-s of sprinting and jumping at maximal intensity with 15-s recovery periods (S-HIIE3)...
September 2017: International Journal of Sports Medicine
https://www.readbyqxmd.com/read/28768867/mechanism-of-interferon-stimulated-gene-induction-in-hiv-1-infected-macrophages
#14
Najla Nasr, Abdullateef A Alshehri, Thomas K Wright, Maryam Shahid, Bonnie M Heiner, Andrew N Harman, Rachel A Botting, Karla J Helbig, Michael R Beard, Kazuo Suzuki, Anthony D Kelleher, Paul Hertzog, Anthony L Cunningham
Viruses manipulate the complex interferon and interferon stimulated gene (ISG) system in different ways. We have previously shown that HIV inhibits type I and III interferons in its key target cells but directly stimulates a subset of >20 ISGs in macrophages and dendritic cells many of which are antiviral. Here we examined the mechanism of induction of ISGs and showed this occurred in two phases. The first phase was transient (0-24hpi) induced mainly by extracellular vesicles, and one of its component proteins HSP90α, contained within the HIV inoculum...
August 2, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28768863/hras-egfr-met-and-ron-are-recurrently-activated-by-provirus-insertion-in-mav-2-retrovirus-induced-liver-tumors
#15
Vladimir Pecenka, Petr Pajer, Vít Karafiat, Petra Kasparova, Jana Dudlova, Michal Dvorak
Myeloblastosis-associated virus-2 (MAV-2) is a highly tumorigenic simple avian retrovirus. Chickens infected in ovo with MAV-2 develop tumors in kidneys, lungs, and liver with a short latency of less then 8 weeks. Here we report the results of molecular analyses of MAV-2-induced liver tumors that fall into three classes: hepatic hemangiosarcomas (HHS), intrahepatic cholangiocarcinomas (ICC), and hepatocellular carcinomas (HCC). Comprehensive inverse PCR-based screening of 92 chicken liver tumors revealed that in ca 86 % of these tumors, MAV-2 provirus had integrated into one of four gene loci: HRAS, EGFR, MET, and RON Insertionally mutated genes correlated with tumor type - HRAS was hit in HHSs, MET in ICCs, RON mostly in ICCs and EGFR mostly in HCC...
August 2, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28768533/progression-of-pathology-in-pink1-deficient-mouse-brain-from-splicing-via-ubiquitination-er-stress-and-mitophagy-changes-to-neuroinflammation
#16
Sylvia Torres-Odio, Jana Key, Hans-Hermann Hoepken, Júlia Canet-Pons, Lucie Valek, Bastian Roller, Michael Walter, Blas Morales-Gordo, David Meierhofer, Patrick N Harter, Michel Mittelbronn, Irmgard Tegeder, Suzana Gispert, Georg Auburger
BACKGROUND: PINK1 deficiency causes the autosomal recessive PARK6 variant of Parkinson's disease. PINK1 activates ubiquitin by phosphorylation and cooperates with the downstream ubiquitin ligase PARKIN, to exert quality control and control autophagic degradation of mitochondria and of misfolded proteins in all cell types. METHODS: Global transcriptome profiling of mouse brain and neuron cultures were assessed in protein-protein interaction diagrams and by pathway enrichment algorithms...
August 2, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28747493/role-of-viral-hemorrhagic-septicemia-virus-matrix-m-protein-in-suppressing-host-transcription
#17
Qi Ke, Wade Weaver, Adam Pore, Bartolomeo Gorgoglione, Julia Halo Wildschutte, Peng Xiao, Brian S Shepherd, Allyn Spear, Krishnamurthy Malathi, Carol A Stepien, Vikram N Vakharia, Douglas W Leaman
Viral Hemorrhagic Septicemia virus (VHSV) is a pathogenic fish rhabdovirus found in discrete locales throughout the northern hemisphere. VHSV infection of fish cells leads to upregulation of the host's virus detection response, but the virus quickly suppresses interferon (IFN) production and antiviral genes expression. By systematically screening each of the six VHSV structural and nonstructural genes, we have identified matrix protein (M) as its most potent anti-host protein. VHSV-IVb M alone suppressed mitochondrial antiviral signaling protein (MAVS) and type I IFN-induced gene expression in a dose-dependent manner...
July 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28733470/dendritic-cell-targeted-lentiviral-vector-immunization-uses-pseudotransduction-and-dna-mediated-sting-and-cgas-activation
#18
Jocelyn T Kim, Yarong Liu, Rajan P Kulkarni, Kevin K Lee, Bingbing Dai, Geoffrey Lovely, Yong Ouyang, Pin Wang, Lili Yang, David Baltimore
Dendritic cell (DC) activation and antigen presentation are critical for efficient priming of T cell responses. Here, we study how lentiviral vectors (LVs) deliver antigen and activate DCs to generate T cell immunization in vivo. We report that antigenic proteins delivered in vector particles via pseudotransduction were sufficient to stimulate an antigen-specific immune response. The delivery of the viral genome encoding the antigen increased the magnitude of this response in vivo but was irrelevant in vitro...
July 21, 2017: Science Immunology
https://www.readbyqxmd.com/read/28720183/g-loc-warning-algorithms-based-on-emg-features-of-the-gastrocnemius-muscle
#19
Sungho Kim, Taehwan Cho, Yongkyun Lee, Hyojin Koo, Booyong Choi, Dongsoo Kim
BACKGROUND: G-induced loss of consciousness (G-LOC) is mainly caused by failure to sustain an oxygenated blood supply to the pilot's brain because of the sudden acceleration in the direction of the +Gz axis, and is considered a critical safety issue. The purpose of this study was to develop G-LOC warning algorithms based on monitoring electromyograms (EMG) of the gastrocnemius muscle on the calf. METHODS: EMG data was retrieved from a total of 67 pilots and pilot trainees of the Korean Air Force during high-G training on a human centrifugal simulator...
August 1, 2017: Aerospace Medicine and Human Performance
https://www.readbyqxmd.com/read/28717359/the-c-terminal-effector-domain-of-non-structural-protein-1-of-influenza-a-virus-blocks-ifn-%C3%AE-production-by-targeting-tnf-receptor-associated-factor-3
#20
Wei Qian, Xiaoqin Wei, Kelei Guo, Yongtao Li, Xian Lin, Zhong Zou, Hongbo Zhou, Meilin Jin
Influenza A virus non-structural protein 1 (NS1) antagonizes interferon response through diverse strategies, particularly by inhibiting the activation of interferon regulatory factor 3 (IRF3) and IFN-β transcription. However, the underlying mechanisms used by the NS1 C-terminal effector domain (ED) to inhibit the activation of IFN-β pathway are not well understood. In this study, we used influenza virus subtype of H5N1 to demonstrate that the NS1 C-terminal ED but not the N-terminal RNA-binding domain, binds TNF receptor-associated factor 3 (TRAF3)...
2017: Frontiers in Immunology
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