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https://www.readbyqxmd.com/read/29053745/impact-of-the-structural-integrity-of-the-three-way-junction-of-adenovirus-vai-rna-on-pkr-inhibition
#1
Edis Dzananovic, Astha, Grzegorz Chojnowski, Soumya Deo, Evan P Booy, Pauline Padilla-Meier, Kevin McEleney, Janusz M Bujnicki, Trushar R Patel, Sean A McKenna
Highly structured RNA derived from viral genomes is a key cellular indicator of viral infection. In response, cells produce the interferon inducible RNA-dependent protein kinase (PKR) that, when bound to viral dsRNA, phosphorylates eukaryotic initiation factor 2α and attenuates viral protein translation. Adenovirus can evade this line of defence through transcription of a non-coding RNA, VAI, an inhibitor of PKR. VAI consists of three base-paired regions that meet at a three-way junction; an apical stem responsible for the interaction with PKR, a central stem required for inhibition, and a terminal stem...
2017: PloS One
https://www.readbyqxmd.com/read/29053414/perk-phosphorylated-eif2%C3%AE-pathway-suppresses-tumor-metastasis-through-downregulating-expression-of-programmed-death-ligand-1-and-cxcl5-in-triple-negative-breast-cancer
#2
Weiwei Zou, Yu Bai, Xilong Wang, Kai Cheng, Hongguang Sun, Guoqiang Zhang, Xiaohong Wang, Zhenlin Yang
Endoplasmic reticulum (ER) stress has been reported to be associated with metastasis in many malignant tumors. PKR-like ER kinase-phosphorylated eukaryotic translation initiation factor 2α (PERK-p-eIF2α) pathway is one of the three main signal pathways in ER stress, however, its mechanism in regulating breast cancer (BC) relapse or metastasis was still not completely understood. Besides, drug resistance was an important factor influencing the effect of tumor treatment and whether PERK-p-eIF2α pathway was involved in the drug resistance to BC treatment also needs to be explored...
October 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/29045748/conserved-asymmetry-underpins-homodimerization-of-dicer-associated-double-stranded-rna-binding-proteins
#3
Alex Heyam, Claire E Coupland, Clément Dégut, Ruth A Haley, Nicola J Baxter, Leonhard Jakob, Pedro M Aguiar, Gunter Meister, Michael P Williamson, Dimitris Lagos, Michael J Plevin
Double-stranded RNA-binding domains (dsRBDs) are commonly found in modular proteins that interact with RNA. Two varieties of dsRBD exist: canonical Type A dsRBDs interact with dsRNA, while non-canonical Type B dsRBDs lack RNA-binding residues and instead interact with other proteins. In higher eukaryotes, the microRNA biogenesis enzyme Dicer forms a 1:1 association with a dsRNA-binding protein (dsRBP). Human Dicer associates with HIV TAR RNA-binding protein (TRBP) or protein activator of PKR (PACT), while Drosophila Dicer-1 associates with Loquacious (Loqs)...
October 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29039478/phosphorylation-of-eif2%C3%AE-suppresses-cisplatin-induced-p53-activation-and-apoptosis-by-attenuating-oxidative-stress-via-atf4-mediated-ho-1-expression-in-human-renal-proximal-tubular-cells
#4
Sung-Min Ju, Yong-Seok Jo, Yoo-Min Jeon, Hyun-Ock Pae, Dae-Gill Kang, Ho-Sub Lee, Jun-Sang Bae, Byung-Hun Jeon
Cisplatin is one of the most widely used chemotherapeutic agents for the treatment of human cancers. However, the nephrotoxicity of cisplatin limits its use as a therapeutic agent. It has been suggested that oxidative stress and p53 activation play important roles in cisplatin-induced nephrotoxicity. It has been demonstrated that the eukaryotic translation initiation factor 2α (eIF2α) may protect HK-2 human renal proximal tubular cells against cisplatin-induced apoptosis through inhibition of reactive oxygen species (ROS)‑mediated p53 activation...
October 10, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29036202/toxoplasma-gondii-induces-fak-src-stat3-signaling-during-infection-of-host-cells-that-prevents-parasite-targeting-by-autophagy
#5
Jose-Andres C Portillo, Luis Muniz-Feliciano, Yalitza Lopez Corcino, So Jung Lee, Jennifer Van Grol, Sarah J Parsons, William P Schiemman, Carlos S Subauste
Targeting of Toxoplasma gondii by autophagy is an effective mechanism by which host cells kill the protozoan. Thus, the parasite must avoid autophagic targeting to survive. Here we show that the mammalian cytoplasmic molecule Focal Adhesion Kinase (FAK) becomes activated during invasion of host cells. Activated FAK appears to accompany the formation of the moving junction (as assessed by expression the parasite protein RON4). FAK activation was inhibited by approaches that impaired β1 and β3 integrin signaling...
October 16, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29022489/adar1-expression-is-associated-with-tumour-infiltrating-lymphocytes-in-triple-negative-breast-cancer
#6
In Hye Song, Young-Ae Kim, Sun-Hee Heo, In Ah Park, Miseon Lee, Won Seon Bang, Hye Seon Park, Gyungyub Gong, Hee Jin Lee
Tumours with a high mutation burden exhibit considerable neoantigens and tumour-infiltrating lymphocytes. RNA editing by ADAR1 is a source of changes in epitope. However, ADAR1 expression in cancer cells and tumour-infiltrating lymphocyte levels in triple-negative breast cancer have not been well evaluated. We immunohistochemically examined ADAR1 expression in 681 triple-negative breast cancer patients and analysed their clinicopathological characteristics. We also analysed basal-like tumours using The Cancer Genome Atlas data...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29022337/asymmetric-syntheses-of-3-deoxy-3-aminosphingoid-bases-approaches-based-on-parallel-kinetic-resolution-and-double-asymmetric-induction
#7
Kristína Csatayová, Stephen G Davies, Ai M Fletcher, Thomas R Fowler, Matthew S Kennedy, Paul M Roberts, James E Thomson
The asymmetric syntheses of a range of N- and O-protected 3-deoxy-3-aminosphingoid bases have been achieved using two complementary approaches. DL-Serine was converted to a racemic N,N-dibenzyl-protected γ-amino-α,β-unsaturated ester which was resolved using a parallel kinetic resolution (PKR) strategy upon reaction with a pseudoenantiomeric mixture of lithium (R)-N-benzyl-N-(α-methylbenzyl)amide and lithium (S)-N-3,4-dimethoxybenzyl-N-(α-methylbenzyl)amide, giving the corresponding enantio- and diastereoisomerically pure β,γ-diamino esters...
October 12, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28990932/uromodulin-p-cys147trp-mutation-drives-kidney-disease-by-activating-er-stress-and-apoptosis
#8
Bryce G Johnson, Lan T Dang, Graham Marsh, Allie M Roach, Zebulon G Levine, Anthony Monti, Deepak Reyon, Lionel Feigenbaum, Jeremy S Duffield
Uromodulin-associated kidney disease (UAKD) is caused by mutations in the uromodulin (UMOD) gene that result in a misfolded form of UMOD protein, which is normally secreted by nephrons. In UAKD patients, mutant UMOD is poorly secreted and accumulates in the ER of distal kidney epithelium, but its role in disease progression is largely unknown. Here, we modeled UMOD accumulation in mice by expressing the murine equivalent of the human UMOD p.Cys148Trp point mutation (UmodC147W/+ mice). Like affected humans, these UmodC147W/+ mice developed spontaneous and progressive kidney disease with organ failure over 24 weeks...
October 9, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28986216/innate-immune-responses-against-rock-bream-iridovirus-rbiv-infection-in-rock-bream-oplegnathus-fasciatus-following-poly-i-c-administration
#9
Myung-Hwa Jung, Sung-Ju Jung
Poly (I:C) showed promise as an immunoprotective agents in rock bream against rock bream iridovirus (RBIV) infection. In this study, we evaluated the time-dependent virus replication pattern and antiviral immune responses in RBIV-infected rock bream with and without poly (I:C) administration. In the poly (I:C)+virus-injected group, virus copy numbers were more than 18.9-, 24.0- and 479.2-fold lower than in the virus only injected group at 4 (4.73 × 10(4) and 8.95 × 10(5)/μl, respectively), 7 (3.67 × 10(5) and 8...
October 4, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28982375/pkr-involvement-in-alzheimer-s-disease
#10
REVIEW
Jacques Hugon, François Mouton-Liger, Julien Dumurgier, Claire Paquet
BACKGROUND: Brain lesions in Alzheimer's disease (AD) are characterized by Aβ accumulation, neurofibrillary tangles, and synaptic and neuronal vanishing. According to the amyloid cascade hypothesis, Aβ1-42 oligomers could trigger a neurotoxic cascade with kinase activation that leads to tau phosphorylation and neurodegeneration. Detrimental pathways that are associated with kinase activation could also be linked to the triggering of direct neuronal death, the production of free radicals, and neuroinflammation...
October 5, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28978012/dicer-protein-levels-elevated-by-mild-hyperthermia-promote-a-pro-survival-phenotype
#11
Anand S Devasthanam, Thomas B Tomasi
Cellular exposure to mild stress (39.5°C - 41.5°C) induces thermotolerance, rendering cells resistant to a subsequent heat shock (>42°C) insult. We found that mild hyperthermia at 39.5°C leads to elevations in dicer, a protein well-known for its role in microRNA processing and for its role in cellular stress responses. However, whether elevated dicer protein levels play a role in sustaining a thermotolerant phenotype has, to our knowledge, not been reported. Here we demonstrate that elevated dicer protein is linked to a thermotolerant phenotype in the cervical carcinoma cell line HeLa and in murine embryonic fibroblasts (MEF), and demonstrate that dicer plays a role in mediating PKR and eIF2α phosphorylation...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28967880/nlrx1-promotes-immediate-irf1-directed-antiviral-responses-by-limiting-dsrna-activated-translational-inhibition-mediated-by-pkr
#12
Hui Feng, Erik M Lenarcic, Daisuke Yamane, Eliane Wauthier, Jinyao Mo, Haitao Guo, David R McGivern, Olga González-López, Ichiro Misumi, Lola M Reid, Jason K Whitmire, Jenny P-Y Ting, Joseph A Duncan, Nathaniel J Moorman, Stanley M Lemon
NLRX1 is unique among the nucleotide-binding-domain and leucine-rich-repeat (NLR) proteins in its mitochondrial localization and ability to negatively regulate antiviral innate immunity dependent on the adaptors MAVS and STING. However, some studies have suggested a positive regulatory role for NLRX1 in inducing antiviral responses. We found that NLRX1 exerted opposing regulatory effects on viral activation of the transcription factors IRF1 and IRF3, which might potentially explain such contradictory results...
October 2, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28963374/protective-effect-of-autophagy-on-endoplasmic-reticulum-stress-induced-apoptosis-of-alveolar-epithelial-cells-in-rat-models-of-copd
#13
Yao Tang, Qi-Hang Cai, Yong-Jian Wang, Shao-Hua Fan, Zi-Feng Zhang, Meng-Qi Xiao, Jin-Yu Zhu, Dong-Mei Wu, Jun Lu, Yuan-Lin Zheng
During this study, we explored the protective effects of autophagy on endoplasmic reticulum stress (ERS)-induced apoptosis belonging to alveolar epithelial cells (AECs) in rat models with chronic obstructive pulmonary disease (COPD). Fifty-six 12-week-old male Sprague-Dawley (SD) rats were randomly assigned into the COPD group (rats exposed to cigarette smoke), the 3-methyladenine (3-MA) intervention group (COPD rats were administrated with 10 mg/kg autophagy inhibitors), the chloroquine (CQ)-intervention group (COPD rats were administrated with 40 mg/kg CQ) and the control group (rats breathed in normal saline)...
September 29, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28959260/systems-approach-reveals-nuclear-factor-erythroid-2-related-factor-2-protein-kinase-r-crosstalk-in-human-cutaneous-leishmaniasis
#14
Áislan de Carvalho Vivarini, Teresa Cristina Calegari-Silva, Alessandra Mattos Saliba, Viviane Sampaio Boaventura, Jaqueline França-Costa, Ricardo Khouri, Tim Dierckx, Karina Luiza Dias-Teixeira, Nicolas Fasel, Aldina Maria Prado Barral, Valéria Matos Borges, Johan Van Weyenbergh, Ulisses Gazos Lopes
Leishmania parasites infect macrophages, causing a wide spectrum of human diseases, from cutaneous to visceral forms. In search of novel therapeutic targets, we performed comprehensive in vitro and ex vivo mapping of the signaling pathways upstream and downstream of antioxidant transcription factor [nuclear factor erythroid 2-related factor 2 (Nrf2)] in cutaneous leishmaniasis (CL), by combining functional assays in human and murine macrophages with a systems biology analysis of in situ (skin biopsies) CL patient samples...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28958921/ifna2-p-ala120thr-impairs-the-inhibitory-activity-of-interferon-%C3%AE-2-against-the-hepatitis-b-virus-through-altering-its-binding-to-the-receptor
#15
Chuming Chen, Xiang Zhu, Wenxiong Xu, Fangji Yang, Genglin Zhang, Lina Wu, Yongyuan Zheng, Zhiliang Gao, Chan Xie, Liang Peng
BACKGROUND: Our previous study found that a rare genetic mutation IFNA2p.Ala120Thr affects the structure of IFN-α2 and contributes to increased host susceptibility to CHB. However, the way in which the single amino acid residue mutation affects IFN-α2 activity is unclear. The purpose of this research was to investigate the effects and mechanisms of IFNA2p.Ala120Thr on IFN-α2 activity. METHODS: Plasmid transfection of BL-21 was used to construct both wild type IFNA2 (wt) and p...
September 25, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28952419/nrf2-protects-against-oxidative-stress-induced-by-sio2-nanoparticles
#16
Wei Liu, Tao Hu, Li Zhou, Desheng Wu, Xinfeng Huang, Xiaohu Ren, Yuan Lv, Wenxu Hong, Guanqin Huang, Zequn Lin, Jianjun Liu
AIM: The aim of our study was to explore the role of nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) on the exposure of SiO2 nanoparticles (NPs) and its influence. MATERIALS & METHODS: To understand the mechanism of NP-induced oxidative stress, the involvement of oxidative-stress-responding transcription factors and the Nrf2/antioxidant reactive element (ARE) signaling pathway in the toxicity of SiO2 NPs' exposure was investigated via in vivo and in vitro models...
October 2017: Nanomedicine
https://www.readbyqxmd.com/read/28949374/fibroblast-growth-factor-21-protects-rat-cardiomyocytes-from-endoplasmic-reticulum-stress-by-promoting-the-fibroblast-growth-factor-receptor-1-extracellular-signal%C3%A2-regulated-kinase-1-2-signaling-pathway
#17
Pingping Liang, Lin Zhong, Lei Gong, Jiahui Wang, Yujie Zhu, Weifeng Liu, Jun Yang
Fibroblast growth factor 21 (FGF21), as an endocrine factor, is secreted into circulation by injured cardiomyocytes. Endoplasmic reticulum (ER) stress-induced apoptosis has been proposed as an important pathophysiological mechanism for cardiomyocyte injury. However, whether the enhanced expression of FGF21 in cardiomyocytes is linked to ER stress, and the effect and underlying mechanism of FGF21 on ER stress-induced cardiomyocyte apoptosis remain unclear. In the present study, it was demonstrated that mild ER stress resulted in upregulated expression levels of FGF21 and its main receptors, as a response to cell compensation, at the induction of ≤5 µM tunicamycin (TM)...
September 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28930151/perk-signal-modulated-protein-translation-promotes-the-survivability-of-dengue-2-virus-infected-mosquito-cells-and-extends-viral-replication
#18
Jiun-Nan Hou, Tien-Huang Chen, Yi-Hsuan Chiang, Jing-Yun Peng, Tsong-Han Yang, Chih-Chieh Cheng, Eny Sofiyatun, Cheng-Hsun Chiu, Chuan Chiang-Ni, Wei-June Chen
Survival of mosquitoes from dengue virus (DENV) infection is a prerequisite of viral transmission to the host. This study aimed to see how mosquito cells can survive the infection during prosperous replication of the virus. In C6/36 cells, global protein translation was shut down after infection by DENV type 2 (DENV2). However, it returned to a normal level when infected cells were treated with an inhibitor of the protein kinase RNA (PKR)-like ER kinase (PERK) signaling pathway. Based on a 7-Methylguanosine 5'-triphosphate (m7GTP) pull-down assay, the eukaryotic translation initiation factor 4F (eIF4F) complex was also identified in DENV2-infected cells...
September 20, 2017: Viruses
https://www.readbyqxmd.com/read/28929048/brand-versus-generic-dispensing-trend-for-ciprofloxacin-500-mg-levofloxacin-500-mg-and-moxifloxacin-400-mg-oral-dosage-forms-among-pharmacies-of-karachi-pakistan
#19
Fatima Zehra, Atta Abbas Naqvi, Sumbul Tasneem, Rizwan Ahmad, Niyaz Ahmad, Adnan Zia Shamsi, Naqiya Ali Asghar, Ghufran Ullah Khan
INTRODUCTION: Pakistan spends 0.7% of its gross domestic product on health. The public sector health-care system provides services to 22% of population thus paving the way for a dominant private sector. Patients in Pakistan mostly pay their medical expenses directly, and 64% of the health expenditures are borne by the household. Expenditure on medicine constitutes 43% of the total household expenditure. METHODS: A quantitative cross-sectional study was conducted in Karachi, Pakistan, for a month...
April 2017: International Journal of Pharmaceutical Investigation
https://www.readbyqxmd.com/read/28919326/characterization-of-a-pkr-inhibitor-from-the-pathogenic-ranavirus-ambystoma-tigrinum-virus-using-a-heterologous-vaccinia-virus-system
#20
Trung P Huynh, James K Jancovich, Latha Tripuraneni, Michael C Heck, Jeffrey O Langland, Bertram L Jacobs
Ambystoma tigrinum virus (ATV) (family Iridoviridae, genus Ranavirus) was isolated from diseased tiger salamanders (Ambystoma tigrinum stebbinsi) from the San Rafael Valley in southern Arizona, USA in 1996. Genomic sequencing of ATV, as well as other members of the genus, identified an open reading frame that has homology to the eukaryotic translation initiation factor, eIF2α (ATV eIF2α homologue, vIF2αH). Therefore, we asked if the ATV vIF2αH could also inhibit PKR. To test this hypothesis, the ATV vIF2αH was cloned into vaccinia virus (VACV) in place of the well-characterized VACV PKR inhibitor, E3L...
November 2017: Virology
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