The interferon-induced 2'-5'-oligoadenylate synthetases (OAS) are important for the antiviral activity of interferons. The human and murine OAS gene families each contain four genes: OAS1, OAS2, OAS3 and OASL, all having one or more conserved OAS units composed of five translated exons. The OASL gene has both an OAS unit and a C-terminus of two ubiquitin-like repeats. In this study, we demonstrate that murine Oasl1 protein is inactive while murine Oasl2 is active as an OAS. Further more, murine Oasl2 requires double-stranded RNA as co-factor. The affinity of murine Oasl2 for the double-stranded RNA activator is higher than that of human OAS1 (p42 isoform). We propose a model for the evolutionary origin of the murine Oasl1 and Oasl2 genes. The identification of a human orthologue (hOASL2) to the murine Oasl2 gene establishes that the OASL gene was duplicated prior to the radiation of the rodent and primate groups. We suggest that murine Oasl2, which has both enzymatic activity and a ubiquitin-like domain, is a functional intermediate between the active OAS species and the inactive human OASL1/murine Oasl1 proteins. In addition, we propose that murine Oasl1 appears to have gained a hitherto uncharacterized function independent of 2'-5'-linked oligoadenylate synthesis.

The diagnosis and treatment of head and neck cancer (HNC) can have substantial impact on swallowing function, nutritional balance, physical function and quality of life (QoL). Early initiated swallowing exercises are hypothesized to improve swallowing function in HNC patients. The aim was to investigate the effects of swallowing exercises and progressive resistance training (PRT) during radiotherapy on swallowing function, physical function and QoL in patients with pharynx-, larynx-, oral cavity cancer or unknown primary compared to usual care. In a multi-centre RCT participants were assigned to (a) twice-weekly PRT and daily swallowing exercises throughout treatment or (b) usual care. Outcomes were measured at end of treatment and 2, 6 and 12 months after. Primary outcome was penetration aspiration score (PAS). Data were analysed on an “intention-to-treat” basis by GEE logistic regression model, linear mixed effects model and cox regression. Of 371 invited HNC patients, 240 (65%) enrolled. Five participants were excluded. At 12 months follow-up, 59 (25%) participants were lost. Analyses showed significant effect on mouth opening, QoL, depression and anxiety at 12 months when comparing intervention to non-active controls. The trial found no effect on swallowing safety in HNC undergoing radiotherapy, but several positive effects were found on secondary outcomes when comparing to non-active controls. The intervention period may have been too short, and the real difference between groups is too small. Nevertheless, the need to identify long-lasting intervention to slow down or avoid functional deteriorations is ever more crucial as the surviving HNC population is growing.

The 2'-5'-oligoadenylate synthetases (OASs) are members of a family of interferon-induced proteins playing an important role in the antiviral effect of interferons as well as being involved in apoptosis and control of cellular growth. Based on sequence data from the murine BAC clone (RP23-39M18), and a number of EST and IMAGE clones and the Celera Mouse database, we identified twelve Oas genes in the mouse genome, all localized to the chromosome 5F region. In contrast to the single OAS1 gene found in humans, we identified eight closely linked Oas1 genes in the murine genome, together with the genes of Oas2 and Oas3. Compared to the single OASL gene found in humans, two genes of OAS-like proteins, Oasl1 and Oasl2, were identified. All the putative genes seem to be transcribed. The exon/intron structures of the murine Oas genes were found to be identical to those of the human genes.

IntroductionDysphagia is highly prevalent in patients with acquired brain injury (ABI) and is associated with high morbidity and mortality. However, dysphagia management varies greatly between units and internationally, and there is currently no consensus, standard intervention or treatment. A review mapping the existing literature on dysphagia treatment is needed. In this paper, the protocol for a scoping review to identify and map dysphagia treatment following ABI is outlined.ObjectiveThe objective of the scoping review is to systematically map the existing research literature to answer the research question: Which non-surgical, non-pharmacological interventions are used in the treatment of dysphagia in patients with moderate and severe acquired brain injury in the acute and subacute phase? Methods and analysisThe methodological framework for the study is based on methodology by Arksey and O’Malley and methodological advancement by Levac et al. We will search electronic databases in June 2019: MEDLINE (Ovid); Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library); EMBASE (Ovid); CINAHL (EBSCO); PsycINFO; Science Citation Index Expanded on Web of Science; OTseeker; Speechbite and PEDro. The search terms will be limited to patients with moderate to severe ABI and dysphagia. Four review authors will independently conduct an initial screening of title and abstract and subsequent full-text review of included studies. Data will be extracted and summarised in diagrammatic or tabular form (numerical summary), and a descriptive format (narrative summary). The strategy for data synthesis entails qualitative methods to categorise the interventions based on the treatment modality and subgroup diagnosis.Ethics and disseminationScoping the existing literature will provide a foundation for further evaluating and developing our dysphagia treatment and inform future studies assessing the effectiveness of treatments. The review is part of an ongoing expansive research into dysphagia. The results will be disseminated through a peer-reviewed publication and conference presentations.