Nurse Education: time to get it right

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Protein-directed ribosomal frameshifting temporally regulates gene expression

Programmed −1 ribosomal frameshifting is a mechanism of gene expression, whereby specific signals within messenger RNAs direct a proportion of translating ribosomes to shift −1 nt and continue translating in the new reading frame. Such frameshifting normally occurs at a set ratio and is utilized in the expression of many viral genes and a number of cellular genes. An open question is whether proteins might function as $\textit{trans}$-acting switches to turn frameshifting on or off in response to cellular conditions. Here we show that frameshifting in a model RNA virus, encephalomyocarditis virus, is $\textit{trans}$-activated by viral protein 2A. As a result, the frameshifting efficiency increases from 0 to 70% (one of the highest known in a mammalian system) over the course of infection, temporally regulating the expression levels of the viral structural and enzymatic proteins.This work was supported by Wellcome Trust grants (088789) and (106207), UK Biotechnology and Biological Research Council (BBSRC) grant (BB/J007072/1) and a European Research Council (ERC) European Union's Horizon 2020 research and innovation programme grant (646891) to A.E.F.; by BBSRC grant (BB/L000334/1) and UK Medical Research Council grant (MR/M011747/1) to I.B.; by a BBSRC PhD studentship to L.K.F.; and by a Wellcome Trust PhD scholarship to J.D.J

Norovirus Regulation of the Innate Immune Response and Apoptosis Occurs via the Product of the Alternative Open Reading Frame 4

Small RNA viruses have evolved many mechanisms to increase the capacity of their short genomes. Here we describe the identification and characterization of a novel open reading frame (ORF4) encoded by the murine norovirus (MNV) subgenomic RNA, in an alternative reading frame overlapping the VP1 coding region. ORF4 is translated during virus infection and the resultant protein localizes predominantly to the mitochondria. Using reverse genetics we demonstrated that expression of ORF4 is not required for virus replication in tissue culture but its loss results in a fitness cost since viruses lacking the ability to express ORF4 restore expression upon repeated passage in tissue culture. Functional analysis indicated that the protein produced from ORF4 antagonizes the innate immune response to infection by delaying the upregulation of a number of cellular genes activated by the innate pathway, including IFN-Beta. Apoptosis in the RAW264.7 macrophage cell line was also increased during virus infection in the absence of ORF4 expression. In vivo analysis of the WT and mutant virus lacking the ability to express ORF4 demonstrated an important role for ORF4 expression in infection and virulence. STAT1-/- mice infected with a virus lacking the ability to express ORF4 showed a delay in the onset of clinical signs when compared to mice infected with WT virus. Quantitative PCR and histopathological analysis of samples from these infected mice demonstrated that infection with a virus not expressing ORF4 results in a delayed infection in this system. In light of these findings we propose the name virulence factor 1, VF1 for this protein. The identification of VF1 represents the first characterization of an alternative open reading frame protein for the calicivirus family. The immune regulatory function of the MNV VF1 protein provide important perspectives for future research into norovirus biology and pathogenesis

Nursing students perceptions of learning in the clinical setting of the Dedicated Education Unit

Aim.  This paper reports a study to explore nursing students' experience of learning in the clinical setting of a Dedicated Education Unit using a communities of practice framework. Background.  The Bachelor of Nursing curriculum at the University of Canberra is clinically focused, recognizing the importance of learning to be a nurse in and from practice. A communities of practice framework underpins the philosophy of the Dedicated Education Unit model of clinical practicum. Method.  In this exploratory qualitative study, a convenience sample of 25 second and third year nursing students participated in focus group discussions, conducted in 2004, to share their views of learning in the Dedicated Education Unit, a newly established model of clinical education. Findings.  Three major themes were identified: acceptance, learning and reciprocity, and accountability. Acceptance of students by clinicians assisted students to engage in nursing work. Students acknowledged the importance of peer learning in sharing experiences, reinforcing knowledge and enhancing confidence. Students accepted responsibility for their work and they valued this responsibility, but some questioned whether participation in all aspects of work constituted a learning opportunity. Conclusion.  Engagement and participation in the clinical workplace are valuable for nursing students. Strategies to support learning in the workplace can be shared with students and clinicians. Further research to test the theoretical premises of the communities of practice framework in clinical nursing education is required.Griffith Health FacultyNo Full Tex