Ribavirin Contributes to Hepatitis C Virus Suppression by Augmenting pDC Activation and Type 1 IFN Production

Ribavirin is used as a component of combination therapies for the treatment of chronic hepatitis C virus (HCV) infection together with pegylated interferon and/or direct-acting antiviral drugs. Its mechanism of action, however, is not clear. Direct antiviral activity and immunomodulatory functions have been implicated. Plasmacytoid dendritic cells (pDCs) are the principal source of type 1 interferon during viral infection. The interaction of pDCs with HCV-infected hepatocytes is the subject of intense recent investigation, but the effect of ribavirin on pDC activation has not been evaluated. In this study we showed that ribavirin augments toll-like receptors 7 and 9-mediated IFNα/β expression from pDCs and up-regulated numerous interferon-stimulated genes. Using the H77S.3 HCV infection and replication system, we showed that ribavirin enhanced the ability of activated pDCs to inhibit HCV replication, correlated with elevated induction of IFNα. Our findings provide novel evidence that ribavirin contributes to HCV inhibition by augmenting pDCs-derived type 1 IFN production.     

Dynamic Model and Motion Characteristics of an Underwater Glider with Manta-inspired Wings

An underwater glider with bionic wings controlled by two operating modes is proposed to perform a variety of marine explo-ration tasks.The system composition of...     

Effects of two species of inorganic arsenic on the nutrient physiology of rice seedlings

This paper reports on a hydroponics experiment that was conducted to investigate the effect of inorganic arsenics on the seedlings of the rice cultivar Shanyou63. The seedlings were subjected to two treatments, i.e., As(III) and As(V). The results showed that the morphological traits of the seedlings were significantly altered after the arsenic treatments. Analysis of nitrogen, phosphorus, potassium, and arsenic contents of the roots and leaves of the seedlings indicated that the absorption of phosphorus and potassium was mainly affected by As(III), while that of nitrogen was mainly affected by As(V). The expression of 12 genes involved in the absorption and utilization of nitrogen, phosphorus, and potassium were all observed to be down-regulated after the arsenic treatments. As(V) significantly affected the absorption and utilization of nitrogen, while As(III) significantly affected those of phosphorus and potassium. The result obtained by real-time FQ-PCR regarding the difference in the gene expressions agreed with that of our hydroponics experiment.     

Development of an α-amylase reporter system for efficient screening of clones with highly expressed heterologous protein in Hansenula polymorpha

To check feasibility and effectiveness of the α-amylase reporter system, two vectors were designed and tested using hepatitis B virus surface antigen (HBsAg) and Homo sapiens granulocyte-macrophage colony stimulating factor 2 (hGM-CSF2) as a model. By integrating the vector containing two independent cassettes into the same genome locus, high-producing clones of HBsAg (or hGM-CSF2) were screened using the α-amylase as a reporter. Results show there was a positive correlation (Correlation coefficient, R ² > 0.95) between the yield of recombinant proteins and the α-amylase activity of corresponding transformants, which was independent of the gene dosage.     

Effects of partially replacing barley or corn with raw and micronised CDC SO-I oats on productive performance of lactating dairy cows

Recently, a new genotype of oat (cv. CDC SO-I, containing low-hull lignin and high-fat groat), has been developed. The objective of this study was to determine the effects of partially replacing barley and corn with the new oat and its micronisation on lactating performance of dairy cows. In a double 4 x 4 Latin square design, eight lactating dairy cows (732 +/- 46 kg body weight [BW]; parity 4 +/- 2) received total mixed rations with a forage-to-concentrate ratio of 50:50 (DM basis). The four treatments were: T1, barley only (control); T2, raw oat, replacing 42% barley of T1; T3, micronised oat, replacing 42% barley of T1; and T4, raw oat and corn blend, replacing 100% barley of T1. The results showed that dairy cows fed the new oats (T2, T3) produced more fat (p < 0.05) and more fat corrected milk (p < 0.10) than cows fed barley only (T1). The performance of cows fed the new oat and corn blend (T4) was not significantly different from other treatments. The micronisation significantly reduced protein degradability (74 vs. 63%,p < 0.05), but increased starch degradability (87 vs. 93%,p < 0.05) of the new oat. However, the overall results suggested that micronisation did not show a significant impact on milk production. The newly developed CDC SO-I oat can replace 42% barley (in T1) as a concentrate supplement in dairy total mixed rations with an increased yield of milk fat and fat corrected milk.     

Insights into the molecular basis of tick-borne encephalitis from multiplatform metabolomics

BackgroundTick-borne encephalitis virus (TBEV) is the most prevalent arbovirus, with a tentative estimate of 10,000 to 10,500 infections occurring in Europe and Asia every year. Endemic in Northeast China, tick-borne encephalitis (TBE) is emerging as a major threat to public health, local economies and tourism. The complicated array of host physiological changes has hampered elucidation of the molecular mechanisms underlying the pathogenesis of this disease.Methodology/Principle findingsSystem-level characterization of the serum metabolome and lipidome of adult TBEV patients and a healthy control group was performed using liquid chromatography tandem mass spectrometry. By tracking metabolic and lipid changes during disease progression, crucial physiological changes that coincided with disease stages could be identified. Twenty-eight metabolites were significantly altered in the sera of TBE patients in our metabolomic analysis, and 14 lipids were significantly altered in our lipidomics study. Among these metabolites, alpha-linolenic acid, azelaic acid, D-glutamine, glucose-1-phosphate, L-glutamic acid, and mannose-6-phosphate were altered compared to the control group, and PC(38:7), PC(28:3;1), TAG(52:6), etc. were altered based on lipidomics. Major perturbed metabolic pathways included amino acid metabolism, lipid and oxidative stress metabolism (lipoprotein biosynthesis, arachidonic acid biosynthesis, leukotriene biosynthesis and sphingolipid metabolism), phospholipid metabolism and triglyceride metabolism. These metabolites were significantly perturbed during disease progression, implying their latent utility as prognostic markers.Conclusions/SignificanceTBEV infection causes distinct temporal changes in the serum metabolome and lipidome, and many metabolites are potentially involved in the acute inflammatory response and immune regulation. Our global analysis revealed anti- and pro-inflammatory processes in the host and changes to the entire metabolic profile. Relationships between metabolites and pathologies were established. This study provides important insight into the pathology of TBE, including its pathology, and lays the foundation for further research into putative markers of TBE disease.     

Lysobacter enzymogenes antagonizes soilborne bacteria using the type IV secretion system

Soil microbiome comprises numerous microbial species that continuously interact with each other. Among the modes of diverse interactions, cell–cell killing may play a key role in shaping the microbiome composition. Bacteria deploy various secretion systems to fend off other microorganisms and Type IV Secretion System (T4SS) in pathogenic bacteria was shown to function as a contact-dependent, inter-bacterial killing system only recently. The present study investigated the role played by T4SS in the killing behaviour of the soilborne biocontrol bacterium Lysobacter enzymogenes OH11. Results showed that L. enzymogenes OH11 genome encompasses genes encoding all the components of T4SS and effectors potentially involved in inter-bacterial killing system. Generation of knock-out mutants revealed that L. enzymogenes OH11 uses T4SS as the main contact-dependent weapon against other soilborne bacteria. The T4SS-mediated killing behaviour of L. enzymogenes OH11 decreased the antibacterial and antifungal activity of two Pseudomonas spp. but at the same time, protected carrot from infection by Pectobacterium carotovorum. Overall, this study showed for the first time the involvement of T4SS in the killing behaviour of L. enzymogenes and its impact on the multiple interactions occurring in the soil microbiome.