Novel type I interferon IL-28A suppresses hepatitis C viral RNA replication

Interferon alpha (IFN-α)-based therapy is the currently approved treatment for chronic hepatitis C viral infection. The sustained antiviral response rate is approximately 50% for genotype-1 infection. The major challenge to the HCV community is to improve antiviral efficacy and to reduce the side effects typically seen in IFNα-based therapy. One of the strategies is to identify new interferons, which may have better efficacy and less undesirable side effects. In this report, we examined the role of IL-28A (IFN λ2), a novel type I IFN, in suppression of human hepatitis C viral RNA replication. We have cloned both the human genomic DNA and cDNA of IL-28A, and evaluated their biological activity using HCV RNA replicon cell culture system. The results show that IL-28A effectively inhibits HCV subgenomic RNA replication in a dose-dependent manner. Treatment of human hepatoma cells with IL-28A activates the JAK-STAT signaling pathway and induces the expression of some interferon-stimulated genes (ISGs), such as 6–16 and 1–8U. We also demonstrate that IL-28A induces expression of HLA class I antigens in human hepatoma cells. Moreover, IL-28A appears to specifically suppress HCV IRES-mediated translation. Although IL-28A receptor shares one subunit with the IL-10 receptor, IL-10 treatment has no detectable effect on IL-28A-induced antiviral activity. Interestingly, IL-28A can synergistically enhance IFNα antiviral efficacy. Our results suggest that IL-28A antiviral activity is associated with the activation of the JAK-STAT signaling pathway and expression of ISGs. The effectiveness of IL-28A antiviral activity and its synergistic effect on IFN-α indicate that IL-28A may be potentially used to treat HCV chronic infection

Decision support for target country selection of future generation sovereign wealth funds: Hedging the country industry risk

AbstractThis paper addresses the challenging problem of selecting target country for future Sovereign Wealth Funds’ (SWFs) asset allocation to hedge the industry risk, which is rarely studied in the field. The target country selection includes which country and how much to invest to obtain the return objective and minimize the risk of these funds. In terms of the industrial perspective, the home country as the investor should consider SWF as part of its budget to make decision in long term. In order to control the risk, this paper measures the similarity between the home and the recipient country of SWF investment. The industrial risk of SWFs’ recipient country is also taken into consideration which is measured by concentration ratio. Based on an analytical process of target country selection, the paper finds that Kazakhstan, India, Australia, Greece, Spain, United States, Austria, Portugal, Peru, Netherlands are the top 10 countries that China should consider as its investment priorities

Phylogenetic, Expression, and Bioinformatic Analysis of the ABC1

We studied 17 ABC1 genes in Populus trichocarpa, all of which contained an ABC1 domain consisting of about 120 amino acid residues. Most of the ABC1 gene products were located in the mitochondria or chloroplasts. All had a conserved VAVK-like motif and a DFG motif. Phylogenetic analysis grouped the genes into three subgroups. In addition, the chromosomal locations of the genes on the 19 Populus chromosomes were determined. Gene structure was studied through exon/intron organization and the MEME motif finder, while heatmap was used to study the expression diversity using EST libraries. According to the heatmap, PtrABC1P14 was highlighted because of the high expression in tension wood which related to secondary cell wall formation and cellulose synthesis, thus making a contribution to follow-up experiment in wood formation. Promoter cis-element analysis indicated that almost all of the ABC1 genes contained one or two cis-elements related to ABA signal transduction pathway and drought stress. Quantitative real-time PCR was carried out to evaluate the expression of all of the genes under abiotic stress conditions (ABA, CdCl2, high temperature, high salinity, and drought); the results showed that some of the genes were affected by these stresses and confirmed the results of promoter cis-element analysis

Flammability characteristics of chemical treated woven hemp fabric

Woven hemp fabric was treated with sodium hydroxide, commercial flame retardant chemical, and combination of both to increase its fire-retardant properties. Treatments of fire-retardant changed the properties of woven hemp fabric such as increased its fabric shrinkage and density of fibres which ranges from 0.67 to 5% and 1.43 to 1.53 g/cm3 respectively. After the treatment, the fire retardancy of the fabric increased tremendously which was observed by the burning, thermogravimetry and limiting oxygen index tests. Some of the samples were not burnt when exposed to flame source and the burning rate needed to be measured under exaggeration of flame at longer time. The limiting oxygen index value increased from 18.6 to 51 after the treatments which explained the scenario happened in the burning tests. Nevertheless, its mechanical properties decreased slightly that ranges from 18 to 32% and 23 to 39% for warp and weft respectively compared to untreated fibre

Innate Host Response in Primary Human Hepatocytes with Hepatitis C Virus Infection

The interaction between hepatitis C virus (HCV) and innate antiviral defense systems in primary human hepatocytes is not well understood. The objective of this study is to examine how primary human hepatocytes response to HCV infection.An infectious HCV isolate JFH1 was used to infect isolated primary human hepatocytes. HCV RNA or NS5A protein in the cells was detected by real-time PCR or immunofluorescence staining respectively. Apoptosis was examined with flow cytometry. Mechanisms of HCV-induced IFN-β expression and apoptosis were determined.Primary human hepatocytes were susceptible to JFH1 virus and released infectious virus. IFN-α inhibited viral RNA replication in the cells. IFN-β and interferon-stimulated genes were induced in the cells during acute infection. HCV infection induced apoptosis of primary human hepatocytes through the TRAIL-mediated pathway. Silencing RIG-I expression in primary human hepatocytes inhibited IFN-β and TRAIL expression and blocked apoptosis of the cells, which facilitated viral RNA replication in the cells. Moreover, HCV NS34A protein inhibited viral induced IFN-β expression in primary human hepatocytes.Innate host response is intact in HCV-infected primary human hepatocytes. RIG-I plays a key role in the induction of IFN and TRAIL by viruses and apoptosis of primary human hepatocytes via activation of the TRAIL-mediated pathway. HCV NS34A protein appears to be capable of disrupting the innate antiviral host responses in primary human hepatocytes. Our study provides a novel mechanism by which primary human hepatocytes respond to natural HCV infection

Three Gorges Dam: Friend or Foe of Riverine Greenhouse Gases?

International audienceDams are often regarded as greenhouse gas (GHG) emitters. However, our study indicated that the world's largest dam, the Three Gorges Dam (TGD), has caused significant drops in annual average emissions of CO$_2$, CH$_4$ and N$_2$O over 4300 km along the Yangtze River, accompanied by remarkable reductions in the annual export of CO$_2$ (79%), CH$_4$ (50%) and N$_2$O (9%) to the sea. Since the commencement of its operation in 2003, the TGD has altered the carbonate equilibrium in the reservoir area, enhanced methanogenesis in the upstream, and restrained methanogenesis and denitrification via modifying anoxic habitats through long-distance scouring in the downstream. These findings suggest that 'large-dam effects' are far beyond our previous understanding spatiotemporally, which highlights the fundamental importance of whole-system budgeting of GHGs under the profound impacts of huge dams

Targeted Delivery of Chemotherapy Agents Using a Liver Cancer-Specific Aptamer

Using antibody/aptamer-drug conjugates can be a promising method for decreasing toxicity, while increasing the efficiency of chemotherapy.In this study, the antitumor agent Doxorubicin (Dox) was incorporated into the modified DNA aptamer TLS11a-GC, which specifically targets LH86, a human hepatocellular carcinoma cell line. Cell viability tests demonstrated that the TLS11a-GC-Dox conjugates exhibited both potency and target specificity. Importantly, intercalating Dox into the modified aptamer inhibited nonspecific uptake of membrane-permeable Dox to the non-target cell line. Since the conjugates are selective for cells that express higher amounts of target proteins, both criteria noted above are met, making TLS11a-GC-Dox conjugates potential candidates for targeted delivery to liver cancer cells.Considering the large number of available aptamers that have specific targets for a wide variety of cancer cells, this novel aptamer-drug intercalation method will have promising implications for chemotherapeutics in general

Characterization of HCV Interactions with Toll-Like Receptors and RIG-I in Liver Cells

The aim of this study was to examine the mechanisms of IFN induction and viral escape. In order to accomplish the goal we compared our new hepatoma cell line LH86, which has intact TLR3 and RIG-I expression and responds to HCV by inducing IFN, with Huh7.5 cells which lack those features.The initial interaction of LH86 cells, Huh7.5 cells or their transfected counter parts (LH86 siRIG-I, siTLR3 or siTLR7 and Huh7.5 RIG-I, TLR3 or TLR7) after infection with HCV (strain JFH-1) was studied by measuring the expression levels of IFNβ, TRAIL, DR4, DR5 and their correlation to viral replication.HCV replicating RNA induces IFN in LH86 cells. The IFN induction system is functional in LH86, and the expression of the RIG-I and TLR3 in LH86 is comparable to the primary hepatocytes. Both proteins appear to play important roles in suppression of viral replication. We found that innate immunity against HCV is associated with the induction of apoptosis by RIG-I through the TRAIL pathway and the establishment of an antiviral state by TLR3. HCV envelope proteins interfere with the expression of TLR3 and RIG-I.These findings correlate with the lower expression level of PRRs in HCV chronic patients and highlight the importance of the PRRs in the initial interaction of the virus and its host cells. This work represents a novel mechanism of viral pathogenesis for HCV and demonstrates the role of PRRs in viral infection

Interleukin-1 Inhibits Hepatitis C Virus Subgenomic RNA Replication by Activation of Extracellular Regulated Kinase Pathway

Interleukin-1 (IL-1) plays an important role in the inflammatory process. Some studies have demonstrated that IL-1 production was impaired in patients with chronic infections of hepatitis C virus (HCV), implying that IL-1 may play a role in viral clearance. Using an HCV subgenomic replicon cell line, we demonstrate that IL-1 can effectively inhibit HCV subgenomic RNA replication and viral protein expression, suggesting that IL-1 has direct antiviral activity. The inhibitory effect is associated with the extracellular regulatory kinase (ERK) activation. In addition, we also show that IL-1 can induce one of the interferon-stimulated genes (ISGs), 1-8U, which exhibits antiviral activity. However, it has no effect on the other ISG, 6-16, suggesting that IL-1 induces novel antiviral pathways within a cell

Two/Quasi-two-dimensional perovskite-based heterostructures: construction, properties and applications

Two-dimensional (2D)/quasi-2D organic-inorganic halide perovskites are regarded as naturally formed multiple quantum wells with inorganic layers isolated by long organic chains, which exhibit layered structure, large exciton binding energy, strong nonlinear optical effect, tunable bandgap via changing the layer number or chemical composition, improved environmental stability, and excellent optoelectronic properties. The extensive choice of long organic chains endows 2D/quasi-2D perovskites with tunable electron-phonon coupling strength, chirality, or ferroelectricity properties. In particular, the layered nature of 2D/quasi-2D perovskites allows us to exfoliate them to thin plates to integrate with other materials to form heterostructures, the fundamental structural units for optoelectronic devices, which would greatly extend the functionalities in view of the diversity of 2D/quasi-2D perovskites. In this paper, the recent achievements of 2D/quasi-2D perovskite-based heterostructures are reviewed. First, the structure and physical properties of 2D/quasi-2D perovskites are introduced. We then discuss the construction and characterizations of 2D/quasi-2D perovskite-based heterostructures and highlight the prominent optical properties of the constructed heterostructures. Further, the potential applications of 2D/quasi-2D perovskite-based heterostructures in photovoltaic devices, light emitting devices, photodetectors/phototransistors, and valleytronic devices are demonstrated. Finally, we summarize the current challenges and propose further research directions in the field of 2D/quasi-2D perovskite-based heterostructures