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https://www.readbyqxmd.com/read/28535250/evidence-for-the-deregulation-of-protein-turnover-pathways-in-atm-deficient-mouse-cerebellum-an-organotypic-study
#1
Catherine D Kim, Ryan E Reed, Meredith A Juncker, Zhide Fang, Shyamal D Desai
Interferon-stimulated gene 15 (ISG15), an antagonist of the ubiquitin pathway, is elevated in cells and brain tissues obtained from ataxia telangiectasia (A-T) patients. Previous studies reveal that an elevated ISG15 pathway inhibits ubiquitin-dependent protein degradation, leading to activation of basal autophagy as a compensatory mechanism for protein turnover in A-T cells. Also, genotoxic stress (ultraviolet [UV] radiation) deregulates autophagy and induces aberrant degradation of ubiquitylated proteins in A-T cells...
May 23, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28532450/lps-induced-systemic-inflammation-reveals-an-immunomodulatory-role-for-the-prion-protein-at-the-blood-brain-interface
#2
Ø Salvesen, M R Reiten, A Espenes, M K Bakkebø, M A Tranulis, C Ersdal
BACKGROUND: The cellular prion protein (PrP(C)) is an evolutionary conserved protein abundantly expressed not only in the central nervous system but also peripherally including the immune system. A line of Norwegian dairy goats naturally devoid of PrP(C) (PRNP (Ter/Ter)) provides a novel model for studying PrP(C) physiology. METHODS: In order to explore putative roles for PrP(C) in acute inflammatory responses, we performed a lipopolysaccharide (LPS, Escherichia coli O26:B6) challenge of 16 goats (8 PRNP (+/+) and 8 PRNP (Ter/Ter)) and included 10 saline-treated controls (5 of each PRNP genotype)...
May 22, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28527896/molecular-characterization-and-expression-analyses-of-the-solea-senegalensis-interferon-stimulated-gene-15-isg15-following-nnv-infections
#3
Daniel Álvarez-Torres, Ana María Podadera, M Carmen Alonso, Isabel Bandín, Julia Béjar, Esther García-Rosado
Interferons are essential in fish resistance to viral infections. They induce interferon-stimulated genes, such as isg15. In this study, the Senegalese sole isg15 gene (ssisg15) has been characterized. As other isg15, ssisg15 contains a 402-bp intron sited in the 5'-UTR, and the full length cDNA is 1492-bp, including a 480-bp ORF. The expression analyses revealed basal levels of isg15 transcripts, and a clear induction after poly I:C injection, that reached maximum values in brain, head kidney and gills. The ssisg15 induction patterns were similar in RGNNV- and SJNNV-inoculated fish, whereas the reassortant (RG/SJ) isolate, which has higher replication fitness, triggered delayed but higher transcript levels...
May 17, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28521627/disseminated-bacillus-calmette-gu%C3%A3-rin-osteomyelitis-in-twin-sisters-related-to-stat1-gene-deficiency
#4
Sabah Boudjemaa, Linda Dainese, Sébastien Héritier, Caroline Masserot, Samia Hachemane, Jean-Laurent Casanova, Aurore Coulomb, Jacinta Bustamante
Mendelian susceptibility to mycobacterial disease is a rare syndrome characterized by severe clinical infections usually caused by weakly virulent mycobacterial species such as Bacillus Calmette-Guérin vaccines and environmental nontuberculous mycobacteria or more virulent mycobacteria as mycobacterium tuberculosis. Since 1996, 9 genes including 7 autosomal ( STAT1, IFNGR1, IFNGR2, IL12B, IL12RB1, ISG15, and IRF8) and 2 X-linked genes ( NEMO and CYBB) have been identified. Allelic heterogeneity leaded to recognize about 18 genetic diseases with variable clinical phenotypes, but sharing a same physiological mechanism represented by a defect in human IL-12-dependant-INF-γ-mediated immunity...
June 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28492391/hepatitis-c-virus-drives-increased-type-i-interferon-associated-impairments-associated-with-fibrosis-severity-in-antiretroviral-treatment-treated-hiv-1-hepatitis-c-virus-coinfected-individuals
#5
Morgane Griesbeck, Marc-Antoine Valantin, Karine Lacombe, Assia Samri-Hassimi, Julie Bottero, Catherine Blanc, Zineb Sbihi, Rima Zoorob, Christine Katlama, Marguerite Guiguet, Marcus Altfeld, Brigitte Autran
BACKGROUND: Viral coinfections might contribute to the increased immune activation and inflammation that persist in antiretroviral treatment (ART)-treated HIV-1 patients. We investigated whether the hepatitis C virus (HCV) coinfection contributes to such alterations by impairing the plasmacytoid dendritic cell (pDC) IFNα/TLR7 pathway in a highly homogeneous group of ART-treated HIV-1-HCV-coinfected patients. METHODS: Twenty-nine HIV-1-infected patients with fully suppressive ART were included, 15 of whom being HCV-coinfected with mild-to-moderate fibrosis and matched for their HIV-1 disease, and 13 control healthy donors...
June 1, 2017: AIDS
https://www.readbyqxmd.com/read/28467275/beyond-isglylation-functions-of-free-intracellular-and-extracellular-isg15
#6
Paula Fernandes Dos Santos, Daniel Santos Mansur
ISG15 is a ubiquitin-like type I IFN-stimulated protein of 15 kDa and is one of the most prominently expressed proteins in viral infections. ISG15 is widely known to be involved in a process called ISGylation, where it binds to over 150 targets from a variety of classes of proteins including central immune signaling pathways such as those mediated by NFκB, JNK, and IRF-3. However, ISG15 also exists in a free form that can act intra- or extracellularly. In vitro and in vivo evidences suggest that free ISG15 play different roles in several cellular processes, from cancer and defense against viral infections to activation of immune cells such as lymphocytes, monocytes, and NK cells...
May 3, 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28438633/structural-insights-into-the-interaction-of-coronavirus-papain-like-proteases-and-interferon-stimulated-gene-product-15-from-different-species
#7
Courtney M Daczkowski, John V Dzimianski, Jozlyn R Clasman, Octavia Goodwin, Andrew D Mesecar, Scott D Pegan
Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) encode multifunctional papain-like proteases (PLPs) that have the ability to process the viral polyprotein to facilitate RNA replication and antagonize the host innate immune response. The latter function involves reversing the post-translational modification of cellular proteins conjugated with either ubiquitin (Ub) or Ub-like interferon-stimulated gene product 15 (ISG15). Ub is known to be highly conserved among eukaryotes, but surprisingly, ISG15 is highly divergent among animals...
April 21, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28423001/pre-hatching-embryo-dependent-and-independent-programming-of-endometrial-function-in-cattle
#8
Mariana Sponchiado, Nathália Souza Gomes, Patrícia Kubo Fontes, Thiago Martins, Maite Del Collado, Athos de Assumpção Pastore, Guilherme Pugliesi, Marcelo Fábio Gouveia Nogueira, Mario Binelli
The bovine pre-implantation embryo secretes bioactive molecules from early development stages, but effects on endometrial function are reported to start only after elongation. Here, we interrogated spatially defined regions of the endometrium transcriptome for responses to a day 7 embryo in vivo. We hypothesize that exposure to an embryo changes the abundance of specific transcripts in the cranial region of the pregnant uterine horn. Endometrium was collected from the uterotubal junction (UTJ), anterior (IA), medial (IM) and posterior (IP) regions of the uterine horn ipsilateral to the CL 7 days after estrus from sham-inseminated (Con) or artificially inseminated, confirmed pregnant (Preg) cows...
2017: PloS One
https://www.readbyqxmd.com/read/28387595/interferon-stimulated-gene-expression-as-a-preferred-biomarker-for-disease-activity-in-aicardi-gouti%C3%A3-res-syndrome
#9
Ben X Wang, Stephanie A Grover, Peter Kannu, Grace Yoon, Ronald M Laxer, E Ann Yeh, Eleanor N Fish
Aicardi-Goutières syndrome (AGS) is an early-onset, genetic disease characterized by recurrent fever, multifocal lesions of the brain, and systemic autoimmunity. We report on 3 AGS patients, 2 siblings with an RNASEH2A gene mutation and 1 patient with a SAMHD1 gene mutation. Serial analysis of peripheral blood from all 3 AGS patients showed consistently elevated expression of the interferon-stimulated genes (ISGs): ISG15, RSAD2, and IFI27, not observed in unaffected family members. Enumeration of circulating white blood cells and platelets and examination of C-reactive protein showed no significant deviation from the normal range for Patient 2 with the RNASEH2A mutation and Patient 3 with the SAMHD1 mutation, even when Patient 2 had magnetic resonance imaging abnormalities and ongoing febrile episodes...
April 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28373872/type-i-interferon-gene-response-is-increased-in-early-and-established-rheumatoid-arthritis-and-correlates-with-autoantibody-production
#10
Julio E Castañeda-Delgado, Yadira Bastián-Hernandez, Noe Macias-Segura, David Santiago-Algarra, Jose D Castillo-Ortiz, Ana L Alemán-Navarro, Pedro Martínez-Tejada, Leonor Enciso-Moreno, Yolanda Garcia-De Lira, Diana Olguín-Calderón, Leendert A Trouw, Cesar Ramos-Remus, Jose A Enciso-Moreno
BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory debilitating disease that affects the joints in the early and productive phases of an individual's life. Several cytokines have been linked to the disease pathogenesis and are known to contribute to the inflammatory state characteristic of RA. The participation of type I interferon (IFN) in the pathogenesis of the disease has been already described as well as the identity of the genes that are regulated by this molecule, which are collectively known as the type I IFN signature...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28362325/possible-roles-of-cc-and-cxc-chemokines-in-regulating-bovine-endometrial-function-during-early-pregnancy
#11
Ryosuke Sakumoto, Ken-Go Hayashi, Shiori Fujii, Hiroko Kanahara, Misa Hosoe, Tadashi Furusawa, Keiichiro Kizaki
The aim of the present study was to determine the possible roles of chemokines in regulating bovine endometrial function during early pregnancy. The expression of six chemokines, including CCL2, CCL8, CCL11, CCL14, CCL16, and CXCL10, was higher in the endometrium at 15 and 18 days of pregnancy than at the same days in non-pregnant animals. Immunohistochemical staining showed that chemokine receptors (CCR1, CCR2, CCR3, and CXCR3) were expressed in the epithelial cells and glandular epithelial cells of the bovine endometrium as well as in the fetal trophoblast obtained from a cow on day 18 of pregnancy...
March 31, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28348873/molecular-and-biochemical-characterization-of-the-ns1-protein-of-non-cultured-influenza-b-virus-strains-circulating-in-singapore
#12
Muhammad Raihan Jumat, Puisan Wong, Raphael Tze Chuen Lee, Sebastian Maurer-Stroh, Boon Huan Tan, Richard J Sugrue
In this study we compared the NS1 protein of Influenza B/Lee/40 and several non-cultured Influenza B virus clinical strains detected in Singapore. In B/Lee/40 virus-infected cells and in cells expressing the recombinant B/Lee/40 NS1 protein a full-length 35 kDa NS1 protein and a 23 kDa NS1 protein species (p23) were detected. Mutational analysis of the NS1 gene indicated that p23 was generated by a novel cleavage event within the linker domain between an aspartic acid and proline at amino acid residues at positions 92 and 93 respectively (DP92-93), and that p23 contained the first 92 amino acids of the NS1 protein...
August 2016: Microbial Genomics
https://www.readbyqxmd.com/read/28329286/short-course-tlr9-agonist-treatment-impacts-innate-immunity-and-plasma-viremia-in-individuals-with-hiv-infection
#13
Line Vibholm, Mariane H Schleimann, Jesper F Højen, Thomas Benfield, Rasmus Offersen, Katrine Rasmussen, Rikke Olesen, Anders Dige, Jørgen Agnholt, Judith Grau, Maria Buzon, Burghardt Wittig, Mathias Lichterfeld, Andreas Munk Petersen, Xutao Deng, Mohammed Abdel-Mohsen, Satish K Pillai, Sofie Rutsaert, Wim Trypsteen, Ward De Spiegelaere, Linos Vandekerchove, Lars Østergaard, Thomas A Rasmussen, Paul W Denton, Martin Tolstrup, Ole S Søgaard
Background: Treatment with latency reversing agents (LRA) enhances HIV-1 transcription in vivo but only leads to modest reductions in the size of the reservoir, possibly due to insufficient immune-mediated elimination of infected cells. We hypothesized that a single drug molecule - a novel toll-like receptor 9 (TLR9) agonist, MGN1703 - could function as an enhancer of innate immunity and an LRA in vivo. Methods: We conducted a single-arm, open-label study, where 15 virologically suppressed HIV-1 infected individuals on antiretroviral therapy received 60 mg MGN1703 s...
March 9, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28328794/hcv-drives-increased-type-i-ifn-associated-impairments-associated-to-fibrosis-severity-in-art-treated-hiv-1-hcv-coinfected-individuals
#14
Morgane Griesbeck, Marc-Antoine Valantin, Karine Lacombe, Assia Samri-Hassimi, Julie Bottero, Catherine Blanc, Zineb Sbihi, Rima Zoorob, Christine Katlama, Marguerite Guiguet, Marcus Altfeld, Brigitte Autran
BACKGROUND: Viral coinfections might contribute to the increased immune activation and inflammation that persist in ART-treated HIV-1 patients. We investigated whether the HCV co-infection contributes to such alterations by impairing the pDC IFNα/TLR7 pathway in a highly homogeneous group of ART-treated HIV-1-HCV co-infected patients. METHODS: Twenty nine HIV-1-infected patients with fully suppressive ART were included, fifteen of whom being HCV co-infected with mild to moderate fibrosis and matched for their HIV-1 disease, and thirteen control healthy donors...
March 21, 2017: AIDS
https://www.readbyqxmd.com/read/28287327/mechanism-of-cell-intrinsic-adaptation-to-adams-oliver-syndrome-gene-dock6-disruption-highlights-ubiquitin-like-modifier-isg15-as-a-regulator-of-rho-gtpases
#15
Berati Cerikan, Elmar Schiebel
DOCK6 is a RAC1/CDC42 guanine nucleotide exchange factor, however, little is known about its function and sub-cellular localization. DOCK6 regulates the balance between RAC1 and RHOA activity during cell adhesion and is important for CDC42-dependent mitotic chromosome alignment. Surprisingly, a cell intrinsic adaptation mechanism compensates for errors in these DOCK6 functions that arise as a consequence of prolonged DOCK6 depletion or complete removal in DOCK6 knockout cells. Down-regulation of the ubiquitin-like modifier ISG15 accounts for this adaptation...
February 23, 2017: Small GTPases
https://www.readbyqxmd.com/read/28285335/cell-type-dependent-regulation-of-free-isg15-levels-and-isgylation
#16
Angeles C Tecalco Cruz, Karen Mejía-Barreto
Interferon-stimulated gene 15 (ISG15) is an ubiquitin-like protein, which can either be found as a free protein or covalently-bound to target proteins via ISGylation. The functions of free and conjugated ISG15 are ambiguous in tumorigenesis owing to its roles as an oncogene and a tumour suppressor gene. This dual role for ISG15 could be a result of the cancer cell type and the cellular context. Here, we report that ISG15 expression is upregulated in different cancer cells compared to normal cells. Furthermore, we found higher endogenous, free ISG15 protein levels in MCF7 breast cancer cells than in other cells, suggesting that non-conjugated ISG15 levels are cell type-specific...
March 11, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28284594/orally-administered-live-attenuated-salmonella-typhimurium-protects-mice-against-lethal-infection-with-h1n1-influenza-virus
#17
Nitin Machindra Kamble, Irshad Ahmed Hajam, John Hwa Lee
Pre-stimulation of toll-like receptors (TLRs) by agonists has been shown to increase protection against influenza virus infection. In this study, we evaluated the protective response generated against influenza A/Puerto Rico/8/1934 (PR8; H1N1) virus by oral and nasal administration of live attenuated Salmonella enterica serovar Typhimurium, JOL911 strain, in mice. Oral and nasal inoculation of JOL911 significantly increased the mRNA copy number of TLR-2, TLR4 and TLR5, and downstream type I interferon (IFN) molecules, IFN-α and IFN-β, both in peripheral blood mononuclear cells (PBMCs) and in lung tissue...
March 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28279792/transcriptome-data-analysis-of-grass-carp-ctenopharyngodon-idella-infected-by-reovirus-provides-insights-into-two-immune-related-genes
#18
Zao Dai, Jicheng Li, Chengyu Hu, Fang Wang, Binhua Wang, Xiao Shi, Qunhao Hou, Waigen Huang, Gang Lin
Grass carp (Ctenopharyngodon idella) was one of the economically important freshwater fish in China. However, hemorrhagic disease caused by grass carp reovirus (GCRV) results in a tremendous loss in the process of grass carp cultivation. Transcriptome analysis could provide a comprehensive understanding of the molecular mechanisms involved in specific biological processes and diseases for the resistance to reovirus infection of grass carp. In this study, the raw data from NCBI (accession number: SRA099702) were analyzed, in which, 50 significant differentially expressed genes by routine transcriptome analysis and 84 notably differentially expressed genes by co-expression network method...
May 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28254416/molecular-characterization-and-biological-activity-of-bovine-interferon-omega3
#19
Dong An, Yongli Guo, Jun Bao, Xiuxin Luo, Ying Liu, Bo Ma, Mingchun Gao, Junwei Wang
Bovine interferon-omega3 (BoIFN-ω3) gene was amplified from bovine liver genomic DNA, which encodes a 195-amino acid protein containing a 23-amino acid signal peptide. Analysis of the molecular characteristics revealed that BoIFN-ω3 evolving from IFN-ω, contained four cysteine residues and five alpha helices, showing that BoIFN-ω3 presented the typical molecular characteristics of type I interferon. BoIFN-ω3 exhibited antiviral and antiproliferative activities, which exerted a protective effect against VSV in several mammalian cell lines, as well as against BEV, IBRV, and BVDV in MDBK cell...
February 10, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28242811/deubiquitinase-usp18-loss-mislocalizes-and-destabilizes-kras-in-lung-cancer
#20
Lisa Maria Mustachio, Yun Lu, Laura J Tafe, Vincent Memoli, Jaime Rodriguez-Canales, Barbara Mino, Pamela Andrea Villalobos, Ignacio Wistuba, Hiroyuki Katayama, Samir M Hanash, Jason Roszik, Masanori Kawakami, Kwang-Jin Cho, John F Hancock, Fadzai Chinyengetere, Shanhu Hu, Xi Liu, Sarah J Freemantle, Ethan Dmitrovsky
KRAS is frequently mutated in lung cancers and is associated with aggressive biology and chemotherapy resistance. Therefore, innovative approaches are needed to treat these lung cancers. Prior work implicated the IFN-stimulated gene 15 (ISG15) deubiquitinase (DUB) USP18 as having antineoplastic activity by regulating lung cancer growth and oncoprotein stability. This study demonstrates that USP18 affects the stability of the KRAS oncoprotein. Interestingly, loss of USP18 reduced KRAS expression, and engineered gain of USP18 expression increased KRAS protein levels in lung cancer cells...
February 27, 2017: Molecular Cancer Research: MCR
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