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https://www.readbyqxmd.com/read/27885721/physicochemical-and-electronic-properties-of-cationic-6-helicenes-from-chemical-and-electrochemical-stabilities-to-far-red-polarized-luminescence
#1
Johann Bosson, Geraldine M Labrador, Simon Pascal, François-Alexandre Miannay, Oleksandr Yushchenko, Haidong Li, Laurent Bouffier, Neso Sojic, Roberto C Tovar, Gilles Muller, Denis Jacquemin, Adèle D Laurent, Boris Le Guennic, Eric Vauthey, Jérôme Lacour
The physicochemical properties of cationic dioxa (1), azaoxa (2), and diaza (3) [6]helicenes demonstrate a much higher chemical stability of the diaza adduct 3 (pKR+ =20.4, Ered1/2 =-0.72 V) compared to its azaoxa 2 (pKR+ =15.2, Ered1/2 =-0.45 V) and dioxa 1 (pKR+ =8.8, Ered1/2 =-0.12 V) analogues. The fluorescence of these cationic chromophores is established, and ranges from the orange to the far-red regions. From 1 to 3, a bathochromic shift of the lowest energy transitions (up to 614 nm in acetonitrile) and an enhancement of the fluorescence quantum yields and lifetimes (up to 31 % and 9...
November 25, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27867349/baclofen-protects-primary-rat-retinal-ganglion-cells-from-chemical-hypoxia-induced-apoptosis-through-the-akt-and-perk-pathways
#2
Pingping Fu, Qiang Wu, Jianyan Hu, Tingting Li, Fengjuan Gao
Retinal ganglion cells (RGCs) consume large quantities of energy to convert light information into a neuronal signal, which makes them highly susceptible to hypoxic injury. This study aimed to investigate the potential protection by baclofen, a GABAB receptor agonist of RGCs against hypoxia-induced apoptosis. Cobalt chloride (CoCl2) was applied to mimic hypoxia. Primary rat RGCs were subjected to CoCl2 with or without baclofen treatment, and RNA interference techniques were used to knock down the GABAB2 gene in the primary RGCs...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27837013/partial-reconstitution-of-the-rnai-response-in-human-cells-using-drosophila-gene-products
#3
Edward M Kennedy, Anand V R Kornepati, Hal P Bogerd, Bryan R Cullen
While mammalian somatic cells are incapable of mounting an effective RNA interference (RNAi) response to viral infections, plants and invertebrates are able to generate high levels of viral short interfering RNAs (siRNAs) that can control many infections. In Drosophila, the RNAi response is mediated by the Dicer 2 enzyme (dDcr2) acting in concert with two co-factors called Loqs-PD and R2D2. To examine whether a functional RNAi response could be mounted in human somatic cells, we expressed dDcr2, in the presence or absence of Loqs-PD and/or R2D2, in a previously described human cell line, NoDice/ΔPKR, that lacks functional forms of human Dicer (hDcr) and PKR...
November 11, 2016: RNA
https://www.readbyqxmd.com/read/27833096/immunoproteasome-induction-is-suppressed-in-hepatitis-c-virus-infected-cells-in-a-protein-kinase-r-dependent-manner
#4
In Soo Oh, Kathrin Textoris-Taube, Pil Soo Sung, Wonseok Kang, Xenia Gorny, Thilo Kähne, Seon-Hui Hong, Young Joon Choi, Clemens Cammann, Michael Naumann, Jong Hoon Kim, Su-Hyung Park, Ook Joon Yoo, Peter M Kloetzel, Ulrike Seifert, Eui-Cheol Shin
By changing the relative abundance of generated antigenic peptides through alterations in the proteolytic activity, interferon (IFN)-γ-induced immunoproteasomes influence the outcome of CD8(+) cytotoxic T lymphocyte responses. In the present study, we investigated the effects of hepatitis C virus (HCV) infection on IFN-γ-induced immunoproteasome expression using a HCV infection cell culture system. We found that, although IFN-γ induced the transcriptional expression of mRNAs encoding the β1i/LMP2, β2i/MECL-1 and β5i/LMP7 immunoproteasome subunits, the formation of immunoproteasomes was significantly suppressed in HCV-infected cells...
November 11, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27826543/endogenous-retrovirus-ev21-dose-not-recombine-with-alv-j-and-induces-the-expression-of-isgs-in-the-host
#5
Min Feng, Yan Tan, Manman Dai, Yuanfang Li, Tingting Xie, Hongmei Li, Meiqing Shi, Xiquan Zhang
Avian leukosis virus subgroup J (ALV-J) infection can cause tumors and immunosuppression. Endogenous viruses integrate into host genomes and can recombine with exogenous avian leukosis virus (ALV). In this study, we analyzed the interaction of endogenous retrovirus 21 (ev21) with the ALV-J in late-feathering Chinese yellow chicken. Two ALV-J strains M180 and K243 were isolated from late-feathering and fast-feathering Chinese yellow chicken flocks, respectively. The env gene of the two strains showed 94.2-94...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27803482/development-of-novel-genetically-engineered-adenoviruses-based-on-functional-analyses-of-adenovirus-encoded-small-rnas
#6
Mitsuhiro Machitani
 The adenovirus (Ad) genome encodes two small noncoding RNAs, VA-RNA I and II, which support Ad replication by antagonizing the antiviral action associated with the Ad-induced activation of double-stranded RNA-dependent protein kinase (PKR). VA-RNAs are also processed in a manner similar to microRNAs (miRNAs), resulting in the production of VA-RNA-derived miRNAs (mivaRNAs). mivaRNAs are incorporated into the RNA-induced silencing complex (RISC) and exhibit posttranscriptional silencing in a manner similar to miRNAs...
2016: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/27801783/cytotoxicity-of-11-epi-sinulariolide-acetate-isolated-from-cultured-soft-corals-on-ha22t-cells-through-the-endoplasmic-reticulum-stress-pathway-and-mitochondrial-dysfunction
#7
Jen-Jie Lin, Robert Y L Wang, Jiing-Chuan Chen, Chien-Chih Chiu, Ming-Hui Liao, Yu-Jen Wu
Natural compounds from soft corals have been increasingly used for their antitumor therapeutic properties. This study examined 11-epi-sinulariolide acetate (11-epi-SA), an active compound isolated from the cultured soft coral Sinularia flexibilis, to determine its potential antitumor effect on four hepatocellular carcinoma cell lines. Cell viability was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and the results demonstrated that 11-epi-SA treatment showed more cytotoxic effect toward HA22T cells...
October 27, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27783669/middle-east-respiratory-coronavirus-accessory-protein-4a-inhibits-pkr-mediated-antiviral-stress-responses
#8
Huib H Rabouw, Martijn A Langereis, Robert C M Knaap, Tim J Dalebout, Javier Canton, Isabel Sola, Luis Enjuanes, Peter J Bredenbeek, Marjolein Kikkert, Raoul J de Groot, Frank J M van Kuppeveld
Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory infections that can be life-threatening. To establish an infection and spread, MERS-CoV, like most other viruses, must navigate through an intricate network of antiviral host responses. Besides the well-known type I interferon (IFN-α/β) response, the protein kinase R (PKR)-mediated stress response is being recognized as an important innate response pathway. Upon detecting viral dsRNA, PKR phosphorylates eIF2α, leading to the inhibition of cellular and viral translation and the formation of stress granules (SGs), which are increasingly recognized as platforms for antiviral signaling pathways...
October 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27780231/a-single-amino-acid-dictates-protein-kinase-r-susceptibility-to-unrelated-viral-antagonists
#9
Kathryn S Carpentier, Nicolle M Esparo, Stephanie J Child, Adam P Geballe
During millions of years of coevolution with their hosts, cytomegaloviruses (CMVs) have succeeded in adapting to overcome host-specific immune defenses, including the protein kinase R (PKR) pathway. Consequently, these adaptations may also contribute to the inability of CMVs to cross species barriers. Here, we provide evidence that the evolutionary arms race between the antiviral factor PKR and its CMV antagonist TRS1 has led to extensive differences in the species-specificity of primate CMV TRS1 proteins. Moreover, we identify a single residue in human PKR that when mutated to the amino acid present in African green monkey (Agm) PKR (F489S) is sufficient to confer resistance to HCMVTRS1...
October 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27770702/modulation-of-hcv-replication-and-translation-by-erbb3-binding-protein1-isoforms
#10
Priya Mishra, Updesh Dixit, Ashutosh K Pandey, Alok Upadhyay, Virendra N Pandey
We recently identified a cell-factor, ErbB3 binding protein 1 (Ebp-1), which specifically interacts with the viral RNA genome and modulates HCV replication and translation. Ebp1 has two isoforms, p48, and p42, that result from differential splicing. We found that both isoforms interact with HCV proteins NS5A and NS5B, as well as cell-factor PKR. The p48 isoform, which localizes in the cytoplasm and nuclei, promoted HCV replication, whereas the shorter p42 isoform, which resides exclusively in the cytoplasm, strongly inhibited HCV replication...
October 19, 2016: Virology
https://www.readbyqxmd.com/read/27761878/moderate-endoplasmic-reticulum-stress-activates-a-perk-and-p38-dependent-apoptosis
#11
Emily C Lumley, Acadia R Osborn, Jessica E Scott, Amanda G Scholl, Vicki Mercado, Young T McMahan, Zachary G Coffman, Jay L Brewster
The endoplasmic reticulum (ER) has the ability to signal organelle dysfunction via a complex signaling network known as the unfolded protein response (UPR). In this work, hamster fibroblast cells exhibiting moderate levels of ER stress were compared to those exhibiting severe ER stress. Inhibition of N-linked glycosylation was accomplished via a temperature-sensitive mutation in the Dad1 subunit of the oligosaccharyltransferase (OST) complex or by direct inhibition with tunicamycin (Tm). Temperature shift (TS) treatment generated weak activation of ER stress signaling when compared to doses of Tm that are typically used in ER stress studies (500-1000 nM)...
October 20, 2016: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/27749929/rabies-virus-infection-induces-the-formation-of-stress-granules-closely-connected-to-the-viral-factories
#12
Jovan Nikolic, Ahmet Civas, Zoé Lama, Cécile Lagaudrière-Gesbert, Danielle Blondel
Stress granules (SGs) are membrane-less dynamic structures consisting of mRNA and protein aggregates that form rapidly in response to a wide range of environmental cellular stresses and viral infections. They act as storage sites for translationally silenced mRNAs under stress conditions. During viral infection, SG formation results in the modulation of innate antiviral immune responses, and several viruses have the ability to either promote or prevent SG assembly. Here, we show that rabies virus (RABV) induces SG formation in infected cells, as revealed by the detection of SG-marker proteins Ras GTPase-activating protein-binding protein 1 (G3BP1), T-cell intracellular antigen 1 (TIA-1) and poly(A)-binding protein (PABP) in the RNA granules formed during viral infection...
October 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27748164/evaluation-of-human-microtubule-affinity-regulating-kinase-4-inhibitors-fluorescence-binding-studies-enzyme-and-cell-assays
#13
Farha Naz, Neha Sami, Abu Turab Naqvi, Asimul Islam, Faizan Ahmad, Md Imtaiyaz Hassan
Human microtubule affinity-regulating kinase 4 (MARK4) is considered as an encouraging drug target for the design and development of inhibitors to cure several life threatening diseases such as Alzheimer disease, cancer, obesity and type-II diabetes. Recently, we have reported four ligands namely, BX-912, BX-795, PKR-inhibitor and OTSSP167 (hydrochloride) which bind preferentially to the two different constructs of human MARK4 containing kinase domain. To ensure the role of ubiquitin associated (UBA) domain in the ligand binding, we made a newer construct of MARK4 which contain both kinase and UBA domains, named as MARK4-F3...
October 16, 2016: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/27733380/the-unfolded-protein-response-regulates-uterine-myocyte-anti-oxidant-responsiveness-during-pregnancy
#14
Saiprasad Ramnarayanan, Chandrashekara Kyathanahalli, Judith Ingles, Miejung Park-York, Pancharatnam Jeyasuria, Jennifer C Condon
There is considerable evidence that implicates oxidative stress in the pathophysiology of human pregnancy complications. However the role and the mechanism of maintaining an anti-oxidant pro-survival uterine environment during normal pregnancy is largely unresolved. Herein we report the highly active uterine unfolded protein response plays a key role in promoting anti-oxidant activity in the uterine myocyte across gestation. The unfolded protein response senses the accumulation of misfolded proteins in the endoplasmic reticulum (ER) and activates a signaling network that consists of the transmembrane protein kinase eukaryotic translation initiation factor 2 alpha kinase 3/PKR-like-ER kinase (EIF2AK3), which acts to decrease protein translation levels allowing for a lowered need for protein folding during periods of ER stress...
October 12, 2016: Biology of Reproduction
https://www.readbyqxmd.com/read/27725157/multivesicular-body-formation-enhancement-and-exosome-release-during-endoplasmic-reticulum-stress
#15
Soshi Kanemoto, Ryota Nitani, Tatsuhiko Murakami, Masayuki Kaneko, Rie Asada, Koji Matsuhisa, Atsushi Saito, Kazunori Imaizumi
The endoplasmic reticulum (ER) plays a pivotal role in maintaining cellular homeostasis. However, numerous environmental and genetic factors give rise to ER stress by inducing an accumulation of unfolded proteins. Under ER stress conditions, cells initiate the unfolded protein response (UPR). Here, we demonstrate a novel aspect of the UPR by electron microscopy and immunostaining analyses, whereby multivesicular body (MVB) formation was enhanced after ER stress. This MVB formation was influenced by inhibition of ER stress transducers inositol required enzyme 1 (IRE1) and PKR-like ER kinase (PERK)...
October 7, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27718290/pkr-regulates-lps-induced-osteoclast-formation-and-bone-destruction-in-vitro-and-in-vivo
#16
Jumpei Teramachi, Yuji Inagaki, Hiroki Shinohara, Hirohiko Okamura, Di Yang, Kazuhiko Ochiai, Ryoko Baba, Hiroyuki Morimoto, Toshihiko Nagata, Tatsuji Haneji
OBJECTIVE: In the present study, we aimed to clarify the precise mechanism underlying LPS-induced osteoclastogenesis in periodontal disease with a special reference to PKR. MATERIAL AND METHODS: We dissected the role of PKR in LPS-induced osteoclast differentiation and function using primary mouse bone marrow cells and RAW264.7 preosteoclastic cell line. We used a rat experimental periodontitis (PD) model induced by ligature placement with a Porphyromonas gingivalis LPS injection (PD rat), and analyzed the therapeutic effects of C16, a PKR inhibitor, on bone loss in PD rats...
October 8, 2016: Oral Diseases
https://www.readbyqxmd.com/read/27711108/mechanistic-insight-into-the-host-transcription-inhibition-function-of-rift-valley-fever-virus-nss-and-its-importance-in-virulence
#17
Kaori Terasaki, Sydney I Ramirez, Shinji Makino
Rift Valley fever virus (RVFV), a member of the genus Phlebovirus within the family Bunyaviridae, causes periodic outbreaks in livestocks and humans in countries of the African continent and Middle East. RVFV NSs protein, a nonstructural protein, is a major virulence factor that exhibits several important biological properties. These include suppression of general transcription, inhibition of IFN-β promoter induction and degradation of double-stranded RNA-dependent protein kinase R. Although each of these biological functions of NSs are considered important for countering the antiviral response in the host, the individual contributions of these functions towards RVFV virulence remains unclear...
October 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27708647/cherry-valley-ducks-mitochondrial-antiviral-signaling-protein-mediated-signaling-pathway-and-antiviral-activity-research
#18
Ning Li, Tianqi Hong, Rong Li, Yao Wang, Mengjiao Guo, Zongxi Cao, Yumei Cai, Sidang Liu, Tongjie Chai, Liangmeng Wei
Mitochondrial antiviral-signaling protein (MAVS), an adaptor protein of retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs)-mediated signal pathway, is involved in innate immunity. In this study, Cherry Valley duck MAVS (duMAVS) was cloned from the spleen and analyzed. duMAVS was determined to have a caspase activation and recruitment domain at N-terminal, followed by a proline-rich domain and a transmembrane domain at C-terminal. Quantitative real-time PCR indicated that duMAVS was expressed in all tissues tested across a broad expression spectrum...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27707917/identification-of-ifn-stimulated-gene-isg-proteins-that-inhibit-human-parainfluenza-virus-type-3
#19
M A G Rabbani, Michael Ribaudo, Ju-Tao Guo, Sailen Barik
: A major arm of cellular innate immunity is type I interferon (IFN), represented by IFN-α and IFN-β. Type I IFN transcriptionally induces a large number of cellular genes, collectively known as IFN-Stimulated Genes or ISGs, which act as antivirals. The IFIT (interferon-induced proteins with tetratricopeptide repeats)-family proteins constitute a major subclass of ISG, and are characterized by multiple tetratricopeptide repeats (TPRs). Here, we have interrogated IFIT proteins for their ability to inhibit the growth of human parainfluenza virus type 3 (PIV3), a nonsegmented negative-strand RNA virus of the Paramyxoviridae family and major cause of respiratory disease in children...
October 5, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27684051/stable-red-emissive-cationic-dithienotropylium-dyes
#20
Kengo Asai, Aiko Fukazawa, Shigehiro Yamaguchi
A series of thiophene-fused tropylium ions, containing various electron-donating amino groups at the terminal positions, was synthesized. The fusion of the thiophene rings, as well as the presence of the terminal amino groups endows the cationic tropylium ion with excellent stability and high pKR(+) values. X-ray crystallographic analysis of these compounds revealed a pronounced quinoidal character for the amino-substituted dithienotropylium skeletons. These compounds exhibit attractive photophysical properties such as strong absorption in the visible region combined with red fluorescence...
September 29, 2016: Chemistry: a European Journal
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