49 research outputs found
Identification and characterization of a novel non-structural protein of bluetongue virus
Bluetongue virus (BTV) is the causative agent of a major disease of livestock (bluetongue). For over two decades, it has been widely accepted that the 10 segments of the dsRNA genome of BTV encode for 7 structural and 3 non-structural proteins. The non-structural proteins (NS1, NS2, NS3/NS3a) play different key roles during the viral replication cycle. In this study we show that BTV expresses a fourth non-structural protein (that we designated NS4) encoded by an open reading frame in segment 9 overlapping the open reading frame encoding VP6. NS4 is 77–79 amino acid residues in length and highly conserved among several BTV serotypes/strains. NS4 was expressed early post-infection and localized in the nucleoli of BTV infected cells. By reverse genetics, we showed that NS4 is dispensable for BTV replication in vitro, both in mammalian and insect cells, and does not affect viral virulence in murine models of bluetongue infection. Interestingly, NS4 conferred a replication advantage to BTV-8, but not to BTV-1, in cells in an interferon (IFN)-induced antiviral state. However, the BTV-1 NS4 conferred a replication advantage both to a BTV-8 reassortant containing the entire segment 9 of BTV-1 and to a BTV-8 mutant with the NS4 identical to the homologous BTV-1 protein. Collectively, this study suggests that NS4 plays an important role in virus-host interaction and is one of the mechanisms played, at least by BTV-8, to counteract the antiviral response of the host. In addition, the distinct nucleolar localization of NS4, being expressed by a virus that replicates exclusively in the cytoplasm, offers new avenues to investigate the multiple roles played by the nucleolus in the biology of the cell
The unfolded protein response in immunity and inflammation.
The unfolded protein response (UPR) is a highly conserved pathway that allows the cell to manage endoplasmic reticulum (ER) stress that is imposed by the secretory demands associated with environmental forces. In this role, the UPR has increasingly been shown to have crucial functions in immunity and inflammation. In this Review, we discuss the importance of the UPR in the development, differentiation, function and survival of immune cells in meeting the needs of an immune response. In addition, we review current insights into how the UPR is involved in complex chronic inflammatory diseases and, through its role in immune regulation, antitumour responses.This work was supported by the Netherlands Organization for Scientific Research Rubicon grant 825.13.012 (J.G.); US National Institutes of Health (NIH) grants DK044319, DK051362, DK053056 and DK088199, and the Harvard Digestive Diseases Center (HDDC) grant DK034854 (R.S.B.); National Institutes of Health grants DK042394, DK088227, DK103183 and CA128814 (R.J.K.); and European Research Council (ERC) Starting Grant 260961, ERC Consolidator Grant 648889, and the Wellcome Trust Investigator award 106260/Z/14/Z (A.K.).This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nri.2016.6
Work–Family Conflict and Job Outcomes Among Prison Officers in Ghana: A Test of Mediation and Moderation Processes
This study examines the mediating effect of job stress and the moderating effect of job autonomy on the relationship between work-to-family conflict (WFC) and job satisfaction and organizational commitment. It uses cross-sectional data from 1062 prison officers sampled from 31 prison establishments in Ghana. The results of structural equation modelling (SEM) analysis showed that WFC was negatively associated with job satisfaction and organizational commitment. Job stress significantly mediated the influence of WFC on job satisfaction and organizational commitment. The negative influence of WFC on job satisfaction and organizational commitment was less for prison officers with higher levels of job autonomy than for those with lower levels of autonomy. These findings suggest the need for correctional organizations to adopt family-friendly measures that facilitate officers’ ability to integrate their work and family responsibilities
Welche Macht darf es denn Sein? Tracing ‘Power’ in German Foreign Policy Discourse
The relationship between ‘Germany’ and ‘power’ remains a sensitive issue. While observers tend to agree that Germany has regained the status of the most powerful country in Europe, there is debate whether that is to be welcomed or whether that is a problem. Underpinning this debate are views, both within Germany and amongst its neighbours, regarding the kind of power Germany has, or should (not) have. Against this backdrop, the article reviews the dominant role conceptions used in the expert discourse on German foreign policy since the Cold War that depict Germany as a particular type of ‘power’. Specifically, we sketch the evolution of three prominent conceptions (constrained power, civilian power, hegemonic power) and the recent emergence of a new one (shaping power). The article discusses how these labels have emerged to give meaning to Germany’s position in international relations, points to their normative and political function, and to the limited ability of such role images to tell us much about how Germany actually exercises power