Role of the B Allele of Influenza A Virus Segment 8 in Setting Mammalian Host Range and Pathogenicity.

UNLABELLED: Two alleles of segment 8 (NS) circulate in nonchiropteran influenza A viruses. The A allele is found in avian and mammalian viruses, but the B allele is viewed as being almost exclusively found in avian viruses. This might reflect the fact that one or both of its encoded proteins (NS1 and NEP) are maladapted for replication in mammalian hosts. To test this, a number of clade A and B avian virus-derived NS segments were introduced into human H1N1 and H3N2 viruses. In no case was the peak virus titer substantially reduced following infection of various mammalian cell types. Exemplar reassortant viruses also replicated to similar titers in mice, although mice infected with viruses with the avian virus-derived segment 8s had reduced weight loss compared to that achieved in mice infected with the A/Puerto Rico/8/1934 (H1N1) parent. In vitro, the viruses coped similarly with type I interferons. Temporal proteomics analysis of cellular responses to infection showed that the avian virus-derived NS segments provoked lower levels of expression of interferon-stimulated genes in cells than wild type-derived NS segments. Thus, neither the A nor the B allele of avian virus-derived NS segments necessarily attenuates virus replication in a mammalian host, although the alleles can attenuate disease. Phylogenetic analyses identified 32 independent incursions of an avian virus-derived A allele into mammals, whereas 6 introductions of a B allele were identified. However, A-allele isolates from birds outnumbered B-allele isolates, and the relative rates of Aves-to-Mammalia transmission were not significantly different. We conclude that while the introduction of an avian virus segment 8 into mammals is a relatively rare event, the dogma of the B allele being especially restricted is misleading, with implications in the assessment of the pandemic potential of avian influenza viruses. IMPORTANCE: Influenza A virus (IAV) can adapt to poultry and mammalian species, inflicting a great socioeconomic burden on farming and health care sectors. Host adaptation likely involves multiple viral factors. Here, we investigated the role of IAV segment 8. Segment 8 has evolved into two distinct clades: the A and B alleles. The B-allele genes have previously been suggested to be restricted to avian virus species. We introduced a selection of avian virus A- and B-allele segment 8s into human H1N1 and H3N2 virus backgrounds and found that these reassortant viruses were fully competent in mammalian host systems. We also analyzed the currently available public data on the segment 8 gene distribution and found surprisingly little evidence for specific avian host restriction of the B-clade segment. We conclude that B-allele segment 8 genes are, in fact, capable of supporting infection in mammals and that they should be considered during the assessment of the pandemic risk of zoonotic influenza A viruses.Wellcome Trust (Grant ID: 108070/Z/15/Z), Medical Research Council (Grant ID: MR/K000276/1), Biotechnology and Biological Sciences Research Council (Grant IDs: BB/J004324/1, BB/J01446X/1), Division of Intramural Research National Institute of Allergy and Infectious Diseases, University Of Edinburgh (Chancellor’s Fellowship)This is the final version of the article. It first appeared from the American Society for Microbiology via http://dx.doi.org/10.1128/JVI.01205-1

Call Cultures in Orang-Utans?

BACKGROUND: Several studies suggested great ape cultures, arguing that human cumulative culture presumably evolved from such a foundation. These focused on conspicuous behaviours, and showed rich geographic variation, which could not be attributed to known ecological or genetic differences. Although geographic variation within call types (accents) has previously been reported for orang-utans and other primate species, we examine geographic variation in the presence/absence of discrete call types (dialects). Because orang-utans have been shown to have geographic variation that is not completely explicable by genetic or ecological factors we hypothesized that this will be similar in the call domain and predict that discrete call type variation between populations will be found. METHODOLOGY/PRINCIPAL FINDINGS: We examined long-term behavioural data from five orang-utan populations and collected fecal samples for genetic analyses. We show that there is geographic variation in the presence of discrete types of calls. In exactly the same behavioural context (nest building and infant retrieval), individuals in different wild populations customarily emit either qualitatively different calls or calls in some but not in others. By comparing patterns in call-type and genetic similarity, we suggest that the observed variation is not likely to be explained by genetic or ecological differences. CONCLUSION/SIGNIFICANCE: These results are consistent with the potential presence of 'call cultures' and suggest that wild orang-utans possess the ability to invent arbitrary calls, which spread through social learning. These findings differ substantially from those that have been reported for primates before. First, the results reported here are on dialect and not on accent. Second, this study presents cases of production learning whereas most primate studies on vocal learning were cases of contextual learning. We conclude with speculating on how these findings might assist in bridging the gap between vocal communication in non-human primates and human speech

Treatment perceptions in patients with asthma: Synthesis of factors influencing adherence

BACKGROUND: Non-adherence to asthma treatment is a contributing factor for poorly controlled asthma. AIM: The aim of this systematic review is to explore patients' perceptions of their inhaled asthma treatment, and how these relate to adherence, using both qualitative and quantitative data. METHODS: Pre-determined search terms and inclusion criteria were used to search electronic databases (The Cochrane Library, MEDLINE, EMBASE and PsycINFO). Two researchers screened titles and abstracts using the Rayyan web app and data were extracted in relation to psychological components (beliefs about, and attitudes towards, medicines) and adherence. RESULTS: Of 1638 papers, 36 met the inclusion criteria. Key themes were: Perceived need for treatment - all 12 studies using the BMQ to measure patients' perceived need for treatment found that patients' beliefs about their necessity for treatment were associated with adherence-; Concerns about treatment - immediate and long-term side effects (58%), worries about safety (19%), and potential addiction to asthma medication (31%)-; and Perceived social stigma - 22% of studies reported that embarrassment contributed to poor adherence. CONCLUSIONS: Acknowledging and addressing patient treatment beliefs and perceptual barriers to adherence is integral to designing adherence interventions for asthma patients. Further research is needed to better our understanding of the relationship between treatment perceptions and adherence

The Cambridge History of Welsh Literature

This is the first comprehensive, single-volume history of the literature of Wales. The volume contains chapters covering the whole range of Welsh literature, from post-Roman Britain to post-devolution Wales, with many of the later chapters providing holistic accounts of literature in Welsh and literature in English within a single genre or a single period of literary production