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https://www.readbyqxmd.com/read/28432927/type-2-bvdv-n-pro-suppresses-ifn-1-pathway-signaling-in-bovine-cells-and-augments-brsv-replication
#1
Abdulrahman A Alkheraif, Christina L Topliff, Jay Reddy, Chandirasegaran Massilamany, Ruben O Donis, Gregor Meyers, Kent M Eskridge, Clayton L Kelling
Bovine viral diarrhea virus (BVDV) infection induces immunosuppression and in conjunction with bovine respiratory syncytial virus (BRSV) contributes to the bovine respiratory disease complex. Bovine turbinate cells were single or co-infected with type 2 BVDV wild-type (BVDV2-wt), its dysfunctional N(pro) mutant (BVDV2-E), and/or BRSV. BVDV2-E significantly up-regulated PKR, IRF-7, TBK-1, IRF-3, and IFN-β mRNAs based on real-time Q-RT-PCR. BRSV-infected cells expressed significantly up-regulated PKR, IRF-3, IRF-7, and IFN-β mRNAs, whereas BVDV2-wt, but not BVDV2-E, abolished this up-regulation in co-infection...
April 19, 2017: Virology
https://www.readbyqxmd.com/read/28431938/selective-inhibition-of-ezh2-by-a-small-molecule-inhibitor-regulates-microglial-gene-expression-essential-for-inflammation
#2
Sarder Arifuzzaman, Amitabh Das, Sun Hwa Kim, Taeho Yoon, Young Seek Lee, Kyoung Hwa Jung, Young Gyu Chai
Multiple studies have documented that Enhancer of zeste homolog 2 (EZH2) could play a role in inflammation and a wide range of malignancies; however, the underlying mechanisms remain largely unaddressed. Microglial activation is a key process in the production and release of numerous pro-inflammatory mediators that play important roles in inflammation and neurodegeneration in the central nervous system (CNS). Therefore, our aim was to investigate whether inhibition of EZH2 with the selective small molecule inhibitor EPZ-6438 protects against neonatal microglial activation...
April 18, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28426872/importance-and-difficulties-of-pursuing-rtms-research-in-acute-stroke
#3
James R Carey, Diane M Chappuis, Marsha J Finkelstein, Kate L Frost, Lynette K Leuty, Allison L McNulty, Lars I E Oddsson, Erin M Seifert, Teresa J Kimberley
Although much research has been done on repetitive transcranial magnetic stimulation (rTMS) in chronic stroke, only sparse research has been done in acute stroke despite the particularly rich potential for neuroplasticity in this stage. We attempted a preliminary clinical trial in one active, high-quality inpatient rehabilitation facility (IRF) in the -United States. But after enrolling only 4 patients in the grant period, the study was stopped because of low enrollment. The purpose of this paper is to offer a perspective describing the important physiologic rationale for including rTMS in the early phase of stroke, the reasons for our poor patient enrollment in our attempted study, and recommendations to help future studies succeed...
March 1, 2017: Physical Therapy
https://www.readbyqxmd.com/read/28424659/online-measurement-of-microembolic-signal-burden-by-transcranial-doppler-during-catheter-ablation-for-atrial-fibrillation-results-of-a-multicenter-trial
#4
Christian von Bary, Thomas Deneke, Thomas Arentz, Anja Schade, Heiko Lehrmann, Sabine Fredersdorf, Dobri Baldaranov, Lars Maier, Felix Schlachetzki
INTRODUCTION: Left atrial pulmonary vein isolation (PVI) is an accepted treatment option for patients with symptomatic atrial fibrillation (AF). This procedure can be complicated by stroke or silent cerebral embolism. Online measurement of microembolic signals (MESs) by transcranial Doppler (TCD) may be useful for characterizing thromboembolic burden during PVI. In this prospective multicenter trial, we investigated the burden, characteristics, and composition of MES during left atrial catheter ablation using a variety of catheter technologies...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28409338/fluorine-18-labeling-of-the-her2-targeting-single-domain-antibody-2rs15d-using-a-residualizing-label-and-preclinical-evaluation
#5
Zhengyuan Zhou, Ganesan Vaidyanathan, Darryl McDougald, Choong Mo Kang, Irina Balyasnikova, Nick Devoogdt, Angeline N Ta, Brian R McNaughton, Michael R Zalutsky
PURPOSE: Our previous studies with F-18-labeled anti-HER2 single-domain antibodies (sdAbs) utilized 5F7, which binds to the same epitope on HER2 as trastuzumab, complicating its use for positron emission tomography (PET) imaging of patients undergoing trastuzumab therapy. On the other hand, sdAb 2Rs15d binds to a different epitope on HER2 and thus might be a preferable vector for imaging in these patients. The aim of this study was to evaluate the tumor targeting of F-18 -labeled 2Rs15d in HER2-expressing breast carcinoma cells and xenografts...
April 13, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28404737/reprogramming-interferon-regulatory-factor-signaling-in-cardiometabolic-diseases
#6
REVIEW
Yaxing Zhang, Hongliang Li
Interferon regulatory factors (IRFs) are evolutionarily conserved proteins expressed not only in immune cells but also in other tissues and organs outside the immune system. In this review, we discuss mechanisms responsible for IRF-mediated innate immune responses and the function and mechanism of IRFs in cardiometabolic diseases. We focus on the role of IRFs in innate immunity and cardiometabolic homeostasis, and highlight reprogrammed IRF signaling.
May 2017: Physiology
https://www.readbyqxmd.com/read/28386100/petri-net-computational-modelling-of-langerhans-cell-interferon-regulatory-factor-network-predicts-their-role-in-t-cell-activation
#7
Marta E Polak, Chuin Ying Ung, Joanna Masapust, Tom C Freeman, Michael R Ardern-Jones
Langerhans cells (LCs) are able to orchestrate adaptive immune responses in the skin by interpreting the microenvironmental context in which they encounter foreign substances, but the regulatory basis for this has not been established. Utilising systems immunology approaches combining in silico modelling of a reconstructed gene regulatory network (GRN) with in vitro validation of the predictions, we sought to determine the mechanisms of regulation of immune responses in human primary LCs. The key role of Interferon regulatory factors (IRFs) as controllers of the human Langerhans cell response to epidermal cytokines was revealed by whole transcriptome analysis...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28368145/response-bias-and-the-personality-inventory-for-dsm-5-contrasting-self-and-informant-report
#8
Lena C Quilty, Nicole Cosentino, R Michael Bagby
Previous research has raised concerns that scores derived from the Personality Inventory for DSM-5 (PID-5; American Psychiatric Association, 2013; Krueger, Derringer, Markon, Watson, & Skodol, 2012) may be compromised by response styles such as underreporting or overreporting. The informant-report form of the PID-5 (PID-5-IRF; Markon, Quilty, Bagby, & Krueger, 2013) has been recommended for use when response bias is an assessment concern. The purpose of the current investigation was to evaluate PID-5 and PID-5-IRF scale score elevations across participants exhibiting signs of overreporting or underreporting...
April 3, 2017: Personality Disorders
https://www.readbyqxmd.com/read/28367002/tsg-6-downregulates-ifn-alpha-and-tnf-alpha-expression-by-suppressing-irf7-phosphorylation-in-human-plasmacytoid-dendritic-cells
#9
L Kui, G C Chan, P P W Lee
Proinflammatory cytokines such as TNF-α and type I interferons (IFN) are pathogenic signatures of systemic lupus erythematosus, and plasmacytoid dendritic cells (pDCs) play a major role by predominantly producing IFN-α. Given the rise of importance in identifying tumor necrosis stimulated gene 6 (TSG-6) as a key anti-inflammatory regulator, we investigate its function and its ability to counteract proinflammatory cytokine secretion by pDCs in vitro. CpG-A and R837 induced significant endogenous TSG-6 expression in the pDC cell-line GEN2...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28363701/measuring-inpatient-rehabilitation-facility-quality-of-care-discharge-self-care-functional-status-quality-measure
#10
Poonam Pardasaney, Anne Deutsch, Jeniffer Iriondo-Perez, Melvin Ingber, Tara McMullen
OBJECTIVE: This paper describes the calculation and psychometric properties of the discharge self-care functional status quality measure implemented in the Centers for Medicare & Medicaid Services' (CMS) Inpatient Rehabilitation Facility (IRF) Quality Reporting Program (QRP) on October 1, 2016. DESIGN: Medicare fee-for-service (FFS) patients from 38 IRFs that participated in CMS' Post-Acute Care Payment Reform Demonstration were included in this cohort study. Data came from the Continuity Assessment Record and Evaluation (CARE) Item Set, IRF-Patient Assessment Instrument (IRF-PAI), and Medicare claims...
March 28, 2017: Archives of Physical Medicine and Rehabilitation
https://www.readbyqxmd.com/read/28362432/regulation-of-transcriptional-activators-by-dna-binding-domain-ubiquitination
#11
Vivien Landré, Bhindu Revi, Maria Gil Mir, Chandra Verma, Ted R Hupp, Nick Gilbert, Kathryn L Ball
Ubiquitin is a key component of the regulatory network that maintains gene expression in eukaryotes, yet the molecular mechanism(s) by which non-degradative ubiquitination modulates transcriptional activator (TA) function is unknown. Here endogenous p53, a stress-activated transcription factor required to maintain health, is stably monoubiquitinated, following pathway activation by IR or Nutlin-3 and localized to the nucleus where it becomes tightly associated with chromatin. Comparative structure-function analysis and in silico modelling demonstrate a direct role for DNA-binding domain (DBD) monoubiquitination in TA activation...
March 31, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28356386/the-granulocyte-progenitor-stage-is-a-key-target-of-irf8-mediated-regulation-of-myeloid-derived-suppressor-cell-production
#12
Colleen S Netherby, Michelle N Messmer, Lauren Burkard-Mandel, Sean Colligan, Austin Miller, Eduardo Cortes Gomez, Jianmin Wang, Michael J Nemeth, Scott I Abrams
Alterations in myelopoiesis are common across various tumor types, resulting in immature populations termed myeloid-derived suppressor cells (MDSCs). MDSC burden correlates with poorer clinical outcomes, credited to their ability to suppress antitumor immunity. MDSCs consist of two major subsets, monocytic and polymorphonuclear (PMN). Intriguingly, the latter subset predominates in many patients and tumor models, although the mechanisms favoring PMN-MDSC responses remain poorly understood. Ordinarily, lineage-restricted transcription factors regulate myelopoiesis that collectively dictate cell fate...
March 29, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28336364/mechanisms-and-roles-by-which-irf-3-mediates-the-regulation-of-ormdl3-transcription-in-respiratory-syncytial-virus-infection
#13
Xiao-Hua Wang, Jin Shu, Chun-Ming Jiang, Li-Li Zhuang, Wei-Xia Yang, Hui-Weng Zhang, Lu-Lu Wang, Lin Li, Xiao-Qing Chen, Rui Jin, Guo-Ping Zhou
Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis in infancy, which is a major risk factor for recurrent wheezing and asthma. Orosomucoid 1-like protein 3 (ORMDL3) has been reported to associate with virus-triggered recurrent wheezing and asthma in children. However, little is known about how ORMDL3 is involved into RSV infection. In this study, we showed that the mRNA expression of ORMDL3 is significantly increased in the peripheral blood lymphocytes of infants with RSV-induced bronchiolitis compared with uninfected controls, also increased in bronchial epithelial cells and lung fibroblasts following RSV infection in vitro...
March 20, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28331615/nuclear-irf-1-expression-as-a-mechanism-to-assess-capability-to-express-pd-l1-and-response-to-pd-1-therapy-in-metastatic-melanoma
#14
James W Smithy, Lauren M Moore, Vasiliki Pelekanou, Jamaal Rehman, Patricia Gaule, Pok Fai Wong, Veronique M Neumeister, Mario Sznol, Harriet M Kluger, David L Rimm
BACKGROUND: Predictive biomarkers for antibodies against programmed death 1 (PD-1) remain a major unmet need in metastatic melanoma. Specifically, response is seen in tumors that do not express programmed death ligand 1 (PD-L1), highlighting the need for a more sensitive biomarker. We hypothesize that capacity to express PD-L1, as assessed by an assay for a PD-L1 transcription factor, interferon regulatory factor 1 (IRF-1), may better distinguish patients likely to benefit from anti-PD-1 immunotherapy...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28318807/microrna-302d-targets-irf9-to-regulate-the-ifn-induced-gene-expression-in-sle
#15
Siobhán Smith, Thilini Fernando, Pei Wen Wu, Jane Seo, Joan Ní Gabhann, Olga Piskareva, Eoghan McCarthy, Donough Howard, Paul O'Connell, Richard Conway, Phil Gallagher, Eamonn Molloy, Raymond L Stallings, Grainne Kearns, Lindsy Forbess, Mariko Ishimori, Swamy Venuturupalli, Daniel Wallace, Michael Weisman, Caroline A Jefferies
Systemic lupus erythematosus (SLE) is a complex disease targeting multiple organs as a result of overactivation of the type I interferon (IFN) system, a feature currently being targeted by multiple biologic therapies against IFN-α. We have identified an estrogen-regulated microRNA, miR-302d, whose expression is decreased in SLE patient monocytes and identify its target as interferon regulatory factor (IRF)-9, a critical component of the transcriptional complex that regulates expression of interferon-stimulated genes (ISGs)...
March 17, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28297677/recombinant-bcg-expressing-esx-1-of-mycobacterium-marinum-combines-low-virulence-with-cytosolic-immune-signaling-and-improved-tb-protection
#16
Matthias I Gröschel, Fadel Sayes, Sung Jae Shin, Wafa Frigui, Alexandre Pawlik, Mickael Orgeur, Robin Canetti, Nadine Honoré, Roxane Simeone, Tjip S van der Werf, Wilbert Bitter, Sang-Nae Cho, Laleh Majlessi, Roland Brosch
Recent insights into the mechanisms by which Mycobacterium tuberculosis, the etiologic agent of human tuberculosis, is recognized by cytosolic nucleotide sensors have opened new avenues for rational vaccine design. The only licensed anti-tuberculosis vaccine, Mycobacterium bovis BCG, provides limited protection. A feature of BCG is the partial deletion of the ESX-1 type VII secretion system, which governs phagosomal rupture and cytosolic pattern recognition, key intracellular phenotypes linked to increased immune signaling...
March 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28288457/interferon-dependent-induction-of-clr-b-during-mouse-cytomegalovirus-infection-protects-bystander-cells-from-natural-killer-cells-via-nkr-p1b-mediated-inhibition
#17
Christina L Kirkham, Oscar A Aguilar, Tao Yu, Miho Tanaka, Aruz Mesci, Kuan-Lun Chu, Jason H Fine, Karen L Mossman, Rod Bremner, David S J Allan, James R Carlyle
Natural killer (NK) cells are innate lymphocytes that aid in self-nonself discrimination by recognizing cells undergoing pathological alterations. The NKR-P1B inhibitory receptor recognizes Clr-b, a self-encoded marker of cell health downregulated during viral infection. Here, we show that Clr-b loss during mouse cytomegalovirus (MCMV) infection is predicated by a loss of Clr-b (Clec2d) promoter activity and nascent transcripts, driven in part by MCMV ie3 (M122) activity. In contrast, uninfected bystander cells near MCMV-infected fibroblasts reciprocally upregulate Clr-b expression due to paracrine type-I interferon (IFN) signaling...
March 14, 2017: Journal of Innate Immunity
https://www.readbyqxmd.com/read/28286505/mda5-induces-a-stronger-interferon-response-than-rig-i-to-gcrv-infection-through-a-mechanism-involving-the-phosphorylation-and-dimerization-of-irf3-and-irf7-in-cik-cells
#18
Quanyuan Wan, Chunrong Yang, Youliang Rao, Zhiwei Liao, Jianguo Su
Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are critical cytosolic sensors that trigger the production of interferons (IFNs). Though their recognition functions are well identified, their unique roles in the downstream signal transduction remain to be elucidated. Herein, we report the differential effect between grass carp (Ctenopharyngodon idella) MDA5 (CiMDA5) and CiRIG-I on the production of various IFNs upon grass carp reovirus (GCRV) infection in C. idella kidney (CIK) cell line...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28283223/interferon-regulatory-factor-signaling-in-autoimmune-disease
#19
REVIEW
Bharati Matta, Su Song, Dan Li, Betsy J Barnes
Interferon regulatory factors (IRFs) play critical roles in pathogen-induced innate immune responses and the subsequent induction of adaptive immune response. Dysregulation of IRF signaling is therefore thought to contribute to autoimmune disease pathogenesis. Indeed, numerous murine in vivo studies have documented protection from or enhanced susceptibility to particular autoimmune diseases in Irf-deficient mice. What has been lacking, however, is replication of these in vivo observations in primary immune cells from patients with autoimmune disease...
March 7, 2017: Cytokine
https://www.readbyqxmd.com/read/28266555/interferon-regulatory-factor-1-activates-autophagy-to-aggravate-hepatic-ischemia-reperfusion-injury-via-the-p38-p62-pathway-in-mice
#20
Yao Yu, Shipeng Li, Zhen Wang, Jindan He, Yijie Ding, Haiming Zhang, Wenli Yu, Yiwei Shi, Zilin Cui, Ximo Wang, Zhiliang Wang, Liying Sun, Rongxin Zhang, Hongyin Du, Zhijun Zhu
Increasing evidence has linked autophagy to a detrimental role in hepatic ischemia- reperfusion (IR) injury (IRI). Here we focus on the role of interferon regulatory factor-1 (IRF-1) in regulating autophagy to aggravate hepatic IRI. We found that IRF-1 was up-regulated during hepatic IRI and was associated with an activation of the autophagic signaling. This increased IRF-1 expression, which was allied with high autophagic activity, amplified liver damage to IR, an effect which was abrogated by IRF-1 depletion...
March 7, 2017: Scientific Reports
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