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https://www.readbyqxmd.com/read/28226265/alterations-of-ubiquitin-related-proteins-in-the-pathology-and-development-of-schizophrenia-evidence-from-human-and-animal-studies
#1
Jessica L Andrews, Frederic J Goodfellow, Natalie Matosin, Mollie K Snelling, Kelly A Newell, Xu-Feng Huang, Francesca Fernandez-Enright
Gene expression analyses in post-mortem schizophrenia brains suggest that a number of ubiquitin proteasome system (UPS) genes are associated with schizophrenia; however the status of UPS proteins in the schizophrenia brain is largely unknown. Ubiquitin related proteins are inherently involved in memory, neuronal survival and morphology, which are processes implicated in neurodevelopmental disorders such as schizophrenia. We examined levels of five UPS proteins (Protein Inhibitor of Activated STAT2 [PIAS2], F-Box and Leucine rich repeat protein 21 [FBXL21], Mouse Double Minute 2 homolog [MDM2], Ubiquitin Carboxyl-Terminal Hydrolase-L1 [UCHL1] and Ubiquitin Conjugating Enzyme E2D1 [UBE2D1]) involved in these neuronal processes, within the dorsolateral prefrontal cortex of post-mortem schizophrenia subjects and matched controls (n = 30/group), in addition to across neurodevelopmental time-points (juvenile, adolescent and adult stages of life), utilizing a well-established neurodevelopmental phencyclidine (PCP) animal model of schizophrenia...
January 18, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28213522/type-i-interferon-regulated-gene-expression-and-signaling-in-murine-mixed-glial-cells-lacking-signal-transducers-and-activators-of-transcription-1-or-2-or-interferon-regulatory-factor-9
#2
Wen Li, Markus J Hofer, Pattama Songkhunawej, So Ri Jung, Dale Hancock, Gareth Denyer, Iain L Campbell
Type I interferons (IFN-I) are critical in antimicrobial and antitumor defense. Although IFN-I signal via the interferon-stimulated gene factor 3 (ISGF3) complex consisting of STAT1, STAT2 and IRF9, IFN-I can mediate significant biological effects via ISGF3-independent pathways. For example, absence of STAT1, STAT2 or IRF9 exacerbates neurological disease in transgenic mice with CNS-production of IFN-Ι. Here we determined the role of IFN-I-driven, ISGF3-independent signaling in regulating global gene expression in STAT1, STAT2 or IRF9-deficient murine mixed glial cell cultures (MGCs)...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28199372/endometrial-factors-similarly-induced-by-ifnt2-and-ifntc1-through-transcription-factor-foxs1
#3
Kazuya Kusama, Rulan Bai, Keigo Nakamura, Sayaka Okada, Jiro Yasuda, Kazuhiko Imakawa
In ruminants, Interferon tau (IFNT) is the pregnancy recognition protein produced by the mononuclear trophectoderm of the conceptus, and is secreted into the uterine lumen during the peri-attachment period. In our previous study, the high-throughput RNA sequencing (RNA-seq) data obtained from bovine conceptuses during the peri-attachment period identified two IFNT mRNAs, IFNT2 and IFNTc1. However, how each of these IFNT variants regulates endometrial gene expression has not been characterized. Using RNA-seq analysis, we evaluated how IFNT2 and IFNTc1 affected transcript expression in primary bovine endometrial epithelial cells (EECs)...
2017: PloS One
https://www.readbyqxmd.com/read/28184222/canonical-and-non-canonical-aspects-of-jak-stat-signaling-lessons-from-interferons-for-cytokine-responses
#4
REVIEW
Andrea Majoros, Ekaterini Platanitis, Elisabeth Kernbauer-Hölzl, Felix Rosebrock, Mathias Müller, Thomas Decker
Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signal transduction mediates cytokine responses. Canonical signaling is based on STAT tyrosine phosphorylation by activated JAKs. Downstream of interferon (IFN) receptors, activated JAKs cause the formation of the transcription factors IFN-stimulated gene factor 3 (ISGF3), a heterotrimer of STAT1, STAT2 and interferon regulatory factor 9 (IRF9) subunits, and gamma interferon-activated factor (GAF), a STAT1 homodimer. In recent years, several deviations from this paradigm were reported...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28165510/stat2-is-an-essential-adaptor-in-usp18-mediated-suppression-of-type-i-interferon-signaling
#5
Kei-Ichiro Arimoto, Sara Löchte, Samuel A Stoner, Christoph Burkart, Yue Zhang, Sayuri Miyauchi, Stephan Wilmes, Jun-Bao Fan, Jürgen J Heinisch, Zhi Li, Ming Yan, Sandra Pellegrini, Frédéric Colland, Jacob Piehler, Dong-Er Zhang
Type I interferons (IFNs) are multifunctional cytokines that regulate immune responses and cellular functions but also can have detrimental effects on human health. A tight regulatory network therefore controls IFN signaling, which in turn may interfere with medical interventions. The JAK-STAT signaling pathway transmits the IFN extracellular signal to the nucleus, thus resulting in alterations in gene expression. STAT2 is a well-known essential and specific positive effector of type I IFN signaling. Here, we report that STAT2 is also a previously unrecognized, crucial component of the USP18-mediated negative-feedback control in both human and mouse cells...
February 6, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28164560/the-study-of-immune-response-in-pbmc-of-chb-patients-treated-with-ifn-%C3%AE-and-3-tc-in-vitro
#6
Hao Zhang, Zi-Shu Guan, Shi-He Guan, Kai Yang, Ying Pan, Yuan-Yuan Wu, Ai-Hua Wang, Bei-Bei Sun, Jie Hou, Xuan-Xuan Mu, Yu-Feng Gao, Wei-Sheng Cheng
BACKGROUND: The primary aim of this study is to measure the JAK-STAT signaling in HBV infected peripheral blood mononuclear cells (PBMCs) stimulated by IFN-α and 3-TC and explore the influence of HBV to the JAKSTAT signaling pathways. METHODS: PBMCs were separated from healthy volunteers and patients who had not received any treatment with chronic hepatitis B. PBMCs were divided into the control group, IFN-α stimulation group, Lamivudine stimulation group, and combined treatment group...
December 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28152048/zika-virus-antagonizes-type-i-interferon-responses-during-infection-of-human-dendritic-cells
#7
James R Bowen, Kendra M Quicke, Mohan S Maddur, Justin T O'Neal, Circe E McDonald, Nadia B Fedorova, Vinita Puri, Reed S Shabman, Bali Pulendran, Mehul S Suthar
Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that is causally linked to severe neonatal birth defects, including microcephaly, and is associated with Guillain-Barre syndrome in adults. Dendritic cells (DCs) are an important cell type during infection by multiple mosquito-borne flaviviruses, including dengue virus, West Nile virus, Japanese encephalitis virus, and yellow fever virus. Despite this, the interplay between ZIKV and DCs remains poorly defined. Here, we found human DCs supported productive infection by a contemporary Puerto Rican isolate with considerable variability in viral replication, but not viral binding, between DCs from different donors...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28104302/stat5-drives-abnormal-proliferation-in-autosomal-dominant-polycystic-kidney-disease
#8
Maria Fragiadaki, Morgane Lannoy, Madeleine Themanns, Barbara Maurer, Wouter N Leonhard, Dorien J M Peters, Richard Moriggl, Albert C M Ong
Autosomal dominant polycystic kidney disease (ADPKD) leads to renal failure. The hallmark of ADPKD is increased epithelial proliferation, which has been proposed to be due to atypical signaling including abnormal JAK-STAT activity. However, the relative contribution of JAK-STAT family members in promoting proliferation in ADPKD is unknown. Here, we present siRNA JAK-STAT-focused screens discovering a previously unknown proliferative role for multiple JAK-STAT components (including STAT1, STAT2, STAT4, STAT5a, and STAT5b)...
January 16, 2017: Kidney International
https://www.readbyqxmd.com/read/28103257/activation-of-the-jak-stat-signaling-pathway-after-in-vitro-stimulation-with-ifn%C3%A3-in-multiple-sclerosis-patients-according-to-the-therapeutic-response-to-ifn%C3%A3
#9
Isaac Hurtado-Guerrero, Maria Jesús Pinto-Medel, Patricia Urbaneja, Jose Luis Rodriguez-Bada, Antonio León, Miguel Guerrero, Óscar Fernández, Laura Leyva, Begoña Oliver-Martos
Interferon beta (IFNß) is a common treatment used for multiple sclerosis (MS) which acts through the activation of the JAK-STAT pathway. However, this therapy is not always effective and currently there are no reliable biomarkers to predict therapeutic response. We postulate that the heterogeneity in the response to IFNß therapy could be related to differential activation patterns of the JAK-STAT signaling pathway. Our aim was to evaluate the basal levels and the short term activation of this pathway after IFNß stimulation in untreated and IFNß treated patients, as well as according to therapeutic response...
2017: PloS One
https://www.readbyqxmd.com/read/28087227/a-novel-kindred-with-inherited-stat2-deficiency-and-severe-viral-illness
#10
Leen Moens, Lien Van Eyck, Dirk Jochmans, Tania Mitera, Glynis Frans, Xavier Bossuyt, Patrick Matthys, Johan Neyts, Michael Ciancanelli, Shen-Ying Zhang, Rik Gijsbers, Jean-Laurent Casanova, Stephanie Boisson-Dupuis, Isabelle Meyts, Adrian Liston
No abstract text is available yet for this article.
January 5, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28069291/antagonizing-cytokine-mediated-jak-stat-signaling-by-porcine-reproductive-and-respiratory-syndrome-virus
#11
REVIEW
Liping Yang, Yan-Jin Zhang
Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway is activated by myriad cytokines, which are involved in regulation of cell growth, proliferation, differentiation, apoptosis, angiogenesis, immunity and inflammatory response. Because of its significance in immune response, JAK-STAT pathway is often targeted by pathogens, including porcine reproductive and respiratory syndrome virus (PRRSV). PRRSV causes reproductive failure in sows and respiratory disease in pigs of all ages...
December 30, 2016: Veterinary Microbiology
https://www.readbyqxmd.com/read/28062696/prostaglandin-e2-inhibition-of-il-27-production-in-murine-dendritic-cells-a-novel-mechanism-that-involves-irf1
#12
Kirsten M Hooper, Jui-Hung Yen, Weimin Kong, Kate M Rahbari, Ping-Chang Kuo, Ana M Gamero, Doina Ganea
IL-27, a multifunctional cytokine produced by APCs, antagonizes inflammation by affecting conventional dendritic cells (cDC), inducing IL-10, and promoting development of regulatory Tr1 cells. Although the mechanisms involved in IL-27 induction are well studied, much less is known about the factors that negatively impact IL-27 expression. PGE2, a major immunomodulatory prostanoid, acts as a proinflammatory agent in several models of inflammatory/autoimmune disease, promoting primarily Th17 development and function...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28003963/transcriptome-analysis-reveals-common-differential-and-global-gene-expression-profiles-in-bluetongue-virus-serotype-16-btv-16-infected-peripheral-blood-mononuclear-cells-pbmcs-in-sheep-and-goats
#13
Anjali Singh, Minakshi Prasad, Bina Mishra, Siddappa Manjunath, Amit Ranjan Sahu, G Bhuvana Priya, Sajad Ahmad Wani, Aditya Prasad Sahoo, Amit Kumar, Shweta Balodi, Anupama Deora, Shikha Saxena, Ravi Kumar Gandham
Bluetongue is an economically important infectious, arthropod borne viral disease of domestic and wild ruminants, caused by Bluetongue virus (BTV). Sheep are considered the most susceptible hosts, while cattle, buffalo and goats serve as reservoirs. The viral pathogenesis of BTV resulting in presence or absence of clinical disease among different hosts is not clearly understood. In the present study, transcriptome of sheep and goats peripheral blood mononuclear cells infected with BTV-16 was explored. The differentially expressed genes (DEGs) identified were found to be significantly enriched for immune system processes - NFκB signaling, MAPK signaling, Ras signaling, NOD signaling, RIG signaling, TNF signaling, TLR signaling, JAK-STAT signaling and VEGF signaling pathways...
March 2017: Genomics Data
https://www.readbyqxmd.com/read/28003146/injectable-hyaluronic-acid-down-regulates-interferon-signaling-molecules-igfbp3-and-ifit3-in-the-bovine-intervertebral-disc
#14
Zepur Kazezian, Zhen Li, Mauro Alini, Sibylle Grad, Abhay Pandit
: Low back pain which is a major cause of disability for people aged between 20 and 50 years imposes a serious socio-economic burden. The current focus of regenerative medicine is on identifying molecular markers to facilitate the design of targeted therapeutics. Previously, we have demonstrated that expression of the anti-proliferative interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) and pro-apoptotic insulin-like growth factor-binding protein-3 (IGFBP3), are up-regulated as downstream targets of the inflammatory cytokine interferon α (IFNα) signaling pathway in the human annulus fibrosus (AF)...
December 18, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27988795/a-novel-anti-viral-role-for-stat3-in-ifn-%C3%AE-signalling-responses
#15
Rebecca Mahony, Siobhán Gargan, Kim L Roberts, Nollaig Bourke, Sinead E Keating, Andrew G Bowie, Cliona O'Farrelly, Nigel J Stevenson
The cytokine, Interferon (IFN)-α, induces a wide spectrum of anti-viral mediators, via the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. STAT1 and STAT2 are well characterised to upregulate IFN-stimulated gene (ISG) expression; but even though STAT3 is also activated by IFN-α, its role in anti-viral ISG induction is unclear. Several viruses, including Hepatitis C and Mumps, reduce cellular STAT3 protein levels, via the promotion of ubiquitin-mediated proteasomal degradation...
December 17, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27929099/stat1-is-essential-for-the-inhibition-of-hepatitis-c-virus-replication-by-interferon-%C3%AE-but-not-by-interferon-%C3%AE
#16
Shota Yamauchi, Kenji Takeuchi, Kazuyasu Chihara, Chisato Honjoh, Yuji Kato, Hatsumi Yoshiki, Hak Hotta, Kiyonao Sada
Interferon-α (IFN-α) and IFN-λ are structurally distinct cytokines that bind to different receptors, but induce expression of similar sets of genes through Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathways. The difference between IFN-α and IFN-λ signaling remains poorly understood. Here, using the CRISPR/Cas9 system, we examine the role of STAT1 and STAT2 in the inhibition of hepatitis C virus (HCV) replication by IFN-α and IFN-λ. Treatment with IFN-α increases expression of IFN-stimulated genes (ISGs) such as double-stranded RNA-activated protein kinase (PKR) and decreases viral RNA and protein levels in HCV-infected Huh-7...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910206/balance-between-il-3-and-type-iinterferons-and-their-interrelationship-with-fasl-dictates-lifespan-and-effector-functions-of-human-basophils
#17
B R Hagmann, A Odermatt, T Kaufmann, C A Dahinden, M Fux
BACKGROUND: In contrast to eosinophils and neutrophils, the regulation of the lifespan of human basophils is poorly defined, with the exception of the potent anti-apoptotic effect of IL-3 that also promotes pro-inflammatory effector functions and phenotypic changes. Type I IFNs (IFN-α, IFN-β), which are well known for their anti-viral activities, have the capacity to inhibit allergic inflammation. OBJECTIVE: To elucidate whether type I IFNs have the potential to abrogate the lifespan and/or effector functions of human basophils...
January 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27907166/vaccinia-virus-protein-c6-inhibits-type-i-ifn-signalling-in-the-nucleus-and-binds-to-the-transactivation-domain-of-stat2
#18
Jennifer H Stuart, Rebecca P Sumner, Yongxu Lu, Joseph S Snowden, Geoffrey L Smith
The type I interferon (IFN) response is a crucial innate immune signalling pathway required for defense against viral infection. Accordingly, the great majority of mammalian viruses possess means to inhibit this important host immune response. Here we show that vaccinia virus (VACV) strain Western Reserve protein C6, is a dual function protein that inhibits the cellular response to type I IFNs in addition to its published function as an inhibitor of IRF-3 activation, thereby restricting type I IFN production from infected cells...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27881648/modeling-severe-fever-with-thrombocytopenia-syndrome-virus-infection-in-golden-syrian-hamsters-importance-of-stat2-in-preventing-disease-and-effective-treatment-with-favipiravir
#19
Brian B Gowen, Jonna B Westover, Jinxin Miao, Arnaud J Van Wettere, Johanna D Rigas, Brady T Hickerson, Kie-Hoon Jung, Rong Li, Bettina L Conrad, Skot Nielson, Yousuke Furuta, Zhongde Wang
: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease endemic in parts of Asia. The etiologic agent, SFTS virus (SFTSV; family Bunyaviridae, genus Phlebovirus) has caused significant morbidity and mortality in China, South Korea, and Japan, with key features of disease being intense fever, thrombocytopenia, and leukopenia. Case fatality rates are estimated to be in the 30% range, and no antivirals or vaccines are approved for use for treatment and prevention of SFTS...
February 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27855377/inhibition-of-stat-pathway-impairs-anti-hepatitis-c-virus-effect-of-interferon-alpha
#20
Lan-Juan Zhao, Sheng-Fei He, Yuan Liu, Ping Zhao, Zhong-Qi Bian, Zhong-Tian Qi
BACKGROUND/AIMS: Signal transducer and activator of transcription (STAT) pathway plays an important role in antiviral efficacy of interferon alpha (IFN-α). IFN-α is the main therapeutic against hepatitis C virus (HCV) infection. We explored effects of IFN-α on HCV replication and antiviral gene expression by targeting STAT. METHODS: In response to IFN-α, STAT status, HCV replication, and antiviral gene expression were analyzed in human hepatoma Huh7.5.1 cells before and after cell culture-derived HCV infection...
2016: Cellular Physiology and Biochemistry
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