24 research outputs found

    Conserved Charged Amino Acids within Sendai Virus C Protein Play Multiple Roles in the Evasion of Innate Immune Responses

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    One of the accessory proteins of Sendai virus (SeV), C, translated from an alternate reading frame of P/V mRNA has been shown to function at multiple stages of infection in cell cultures as well as in mice. C protein has been reported to counteract signal transduction by interferon (IFN), inhibit apoptosis induced by the infection, enhance the efficiency of budding of viral particles, and regulate the polarity of viral genome-length RNA synthesis to maximize production of infectious particles. In this study, we have generated a series of SeV recombinants containing substitutions of highly conserved, charged residues within the C protein, and characterized them together with previously-reported C′/C(−), 4C(−), and F170S recombinant viruses in infected cell cultures in terms of viral replication, cytopathogenicity, and antagonizing effects on host innate immunity. Unexpectedly, the amino acid substitutions had no or minimal effect on viral growth and viral RNA synthesis. However, all the substitutions of charged amino acids resulted in the loss of a counteracting effect against the establishment of an IFN-α-mediated anti-viral state. Infection by the virus (Cm2′) containing mutations at K77 and D80 induced significant IFN-β production, severe cytopathic effects, and detectable amounts of viral dsRNA production. In addition to the Cm2′ virus, the virus containing mutations at E114 and E115 did not inhibit the poly(I:C)-triggered translocation of cellular IRF-3 to the nucleus. These results suggest that the C protein play important roles in viral escape from induction of IFN-β and cell death triggered by infection by means of counteracting the pathway leading to activation of IRF-3 as well as of minimizing viral dsRNA production

    Corrigendum to "Late Holocene climate anomaly concurrent with fire activity and ecosystem shifts in the eastern Australian Highlands" [Sci. Total Environ. 802 (2021)149542].

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    The authors regret that the printed version of the above article contained a transcription error in the m/z 1048 peak area column for the branched GDGTs (Table S2). This error affected the GDGT-inferred summer air temperature presented in Figs. 3, 4 and 5, and some of the calibrations presented Fig. S2. The GDGT-inferred temperatures have been recalculated and are presented below. The authors would like to apologise for any inconvenience caused. The corrected GDGT-inferred summer air temperature (Fig. 3) is largely within the uncertainty of the temperature calibration (2.0 °C RMSE, Pearson et al., 2011). While the pattern of the temperature variations over the last 3500 years remains unchanged, the GDGT-inferred summer air temperature is between 0.4 and 3.3 degrees lower than was originally presented. The interpretations of Thomas et al. (2022) are unaffected, with reconstructed changes in temperature at Club Lake still associated with several other palaeoenvironmental proxies. Section 4.1 “Our reconstruction of MSAT varies between about 13 and 16 °C, and appears to display a long-term increase in temperature averaging ~0.1 °C per century (Fig. 3).” should be “Our reconstruction of MSAT varies between about 10 and 15 °C, and appears to display a long-term increase in temperature averaging ~0.13 °C per century (Fig. 3).” Section 4.2 “The reconstructed temperature of 16.2 ± 1 °C (which is higher than the contemporary Thredbo AWS mean summer temperature) must therefore be treated with caution.” should be “The reconstructed temperature of 15.7 ± 1 °C (which is higher than the contemporary Thredbo AWS mean summer temperature) must therefore be treated with caution.” The updated figures and Supplementary information table and figure related to this corrigendum are presented below. [Figure presented] [Figure presented] [Figure presented

    Orthovanadate Stimulates cAMP Phosphodiesterase 3 Activity in Isolated Rat Hepatocytes through Mitogen-Activated Protein Kinase Activation Dependent on cAMP-Dependent Protein Kinase

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