The effect of 5' and 3' non-translated regions on the expression of a transgene from a Newcastle disease virus vector.

Newcastle disease virus (NDV) is an avian virus and a promising vector for the development of vaccines for veterinary and human use. The optimal vaccine vector performance requires a stable high-level expression of a transgene. The foreign genes are usually incorporated in the genome of NDV as individual transcription units, whose transcription and subsequent translation of the mRNA are regulated by the 5' and 3' untranslated regions (UTRs) flanking the open reading frame of the transgene. Here, we investigated if the UTRs derived from the cognate NDV genes would increase the expression of a model protective antigene from an NDV vector. Our results show that in chicken DF1 cells, none of the UTRs tested significantly outperformed generic short sequences flanking the transgene, while in human HeLa cells, UTRs derived from the M gene of NDV statistically significantly increased the expression of the transgene. The UTRs derived from the HN gene significantly downregulated the transgene expression in both cell cultures. Further experiments demonstrated that NDV UTRs differently affect the mRNA abundance and translation efficacy. While both M and HN UTRs decreased the level of the transgene mRNA in infected cells compared to the mRNA flanked by generic UTRs, M, and particularly, HN UTRs strongly increased the mRNA translation efficacy. The major determinants of translation enhancement are localized in the 5'UTR of HN. Thus, our data reveal a direct role of NDV UTRs in translational regulation, and inform future optimization of NDV vectors for vaccine and therapeutic use.

Do autistic adults spontaneously reason about belief? A detailed exploration of alternative explanations.

Southgate et al.'s (Southgate 2007 Psychol. Sci. 18, 587-92 (doi:10.1111/j.1467-9280.2007.01944.x)) anticipatory-looking paradigm has presented exciting yet inconclusive evidence surrounding spontaneous mentalizing in autism. The present study aimed to develop this paradigm to address alternative explanations for the lack of predictive eye movements on false-belief tasks by autistic adults. This was achieved through implementing a multi-trial design with matched true-belief conditions, and both high and low inhibitory demand false-belief conditions. We also sought to inspect if any group differences were related to group-specific patterns of attention on key events. Autistic adults were compared with non-autistic adults on this adapted implicit mentalizing task and an established explicit task. The two groups performed equally well in the explicit task; however, autistic adults did not show anticipatory-looking behaviour in the false-belief trials of the implicit task. Critically, both groups showed the same attentional distribution in the implicit task prior to action prediction, indicating that autistic adults process information from social cues in the same way as non-autistic adults, but this information is not then used to update mental representations. Our findings further document that many autistic people struggle to spontaneously mentalize others' beliefs, and this non-verbal paradigm holds promise for use with a wide range of ages and abilities.