Cellular mRNA of higher eukaryotes and many viral RNA are methylated at the N-7 and 2′-O positions of the 5′ guanosine cap by specific nuclear and cytoplasmic methyltransferases (MTases), respectively. Whereas N-7 methylation is essential for RNA translation and stability 1, the function of 2′-O methylation has remained uncertain since its discovery 35 years ago 2-4. Here, we show that a West Nile virus (WNV) mutant (E218A) that lacks 2′-O MTase activity was attenuated in wild type primary cells and mice but was pathogenic in the absence of type I interferon (IFN) signaling. 2′-O methylation of viral RNA did not affect IFN induction in WNV-infected fibroblasts but instead modulated the antiviral effects of IFN-induced proteins with tetratricopeptide repeats (IFIT), which are interferon-stimulated genes (ISG) implicated in regulation of protein translation. Poxvirus and coronavirus mutants that lacked 2′-O MTase activity similarly showed enhanced sensitivity to the antiviral actions of IFN and specifically, IFIT proteins. Our results demonstrate that the 2′-O methylation of the 5′ cap of viral RNA functions to subvert innate host antiviral responses through escape of IFIT-mediated suppression, and suggest an evolutionary explanation for 2′-O methylation of cellular mRNA: to distinguish self from non-self RNA. Differential methylation of cytoplasmic RNA likely serves as a paradigm for pattern recognition and restriction of propagation of foreign viral RNA in host cells.

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Purpose – The purpose of the study is to focus on the enhancement of knowledge management (KM) performance and the relationship between organizational culture and KM process intention of individuals because of the diversity of organizational cultures (which include results-oriented, tightly controlled, job-oriented, closed system and professional-oriented cultures). Knowledge is a primary resource in organizations. If firms are able to effectively manage their knowledge resources, then a wide range of benefits can be reaped such as improved corporate efficiency, effectiveness, innovation and customer service. Design/methodology/approach – The survey methodology, which has the ability to enhance generalization of results (Dooley, 2001), was used to collect the data utilized in the testing of the research hypotheses. Findings – Results- and job-oriented cultures have positive effects on employee intention in the KM process (creation, storage, transfer and application), whereas a tightly controlled culture has negative effects. Research limitations/implications – However, it would have been better to use a longitudinal study to collect useful long-term data to understand how the KM process would be influenced when organizational culture dimensions are changed through/by management. This is the first limitation of this study. According to Mason and Pauleen (2003), KM culture is a powerful predictor of individual knowledge-sharing behavior, which is not included in this study. Thus, this is the second limitation of this paper. Moreover, national culture could be an important issue in the KM process (Jacks et al., 2012), which is the third limitation of this paper for not comprising it. Practical implications – In researchers’ point of view, results- and job-oriented cultures have positive effects, whereas a tightly controlled culture has a negative effect on the KM process intention of the individual. These findings provide evidences that challenge the perspective of Kayworth and Leidner (2003) on this issue. As for practitioners, management has a direction to modify their organizational culture to improve the performance of KM process. Social implications – Both behavioral and value perspectives of the organizational cultural dimensions (results-oriented, tightly control, job-oriented, sociability, solidarity, need for achievement and democracy) should be examined to ascertain their effects firstly on KM culture and then on the KM process intention of the individual. It is hoped that the current study will spawn future investigations that lead to the development of an integrated model which includes organizational culture, KM culture and the KM process intention of the individual. Originality/value – The results-oriented, loosely controlled and job-oriented cultures will improve the effectiveness of the KM process and will also increase employees’ satisfaction and willingness to stay with the organization.

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SummaryThe IFITMs inhibit influenza A virus (IAV) replication in vitro and in vivo. Here, we establish that the antimycotic heptaen, amphotericin B (AmphoB), prevents IFITM3-mediated restriction of IAV, thereby increasing viral replication. Consistent with its neutralization of IFITM3, a clinical preparation of AmphoB, AmBisome, reduces the majority of interferon’s protective effect against IAV in vitro. Mechanistic studies reveal that IFITM1 decreases host-membrane fluidity, suggesting both a possible mechanism for IFITM-mediated restriction and its negation by AmphoB. Notably, we reveal that mice treated with AmBisome succumbed to a normally mild IAV infection, similar to animals deficient in Ifitm3. Therefore, patients receiving antifungal therapy with clinical preparations of AmphoB may be functionally immunocompromised and thus more vulnerable to influenza, as well as other IFITM3-restricted viral infections.

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Substituent effects on the photophysical and electrochemical properties of 1,7-diaryl-substituted perylene diimides (1,7-Ar(2)PDIs) have been carefully explored. Progressive red-shifts of the absorption and emission maxima were observed when the electron-donating ability of these substituents was increased. Linear Hammett correlations of 1/lambda(max) versus sigma(+) were observed in both spectral analyses. The positive slopes of the Hammett plots suggested that the electronic transitions carry certain amounts of photoinduced intramolecular charge-transfer (PICT) character from the aryl substituents to the perylene diimide core which leads to the reduction of the electron density on the substituents. The substituent electronic effects originated mainly from the perturbation of the core PDI HOMO energy level by the substituents. This conclusion was supported by PM3 analyses and confirmed by cyclic voltammetry experiments. More interestingly, the Ph(2)NC(6)H(4)-substituted PDI, 4i, showed an unusual dual-band absorption that spans from 450 to 750 nm. We tentatively assigned these two bands as the charge-transfer band and the PDI core absorption, respectively.