Timely identification of emerging antigenic variants is critical to influenza vaccine design. The accuracy of a sequence-based antigenic prediction method relies on the choice of amino acids substitution matrices. In this study, we first compared a comprehensive 95 substitution matrices reflecting various amino acids properties in predicting the antigenicity of influenza viruses by a random forest model. We then proposed a novel algorithm called joint random forest regression (JRFR) to jointly consider top substitution matrices. We applied JRFR to human H3N2 seasonal influenza data from 1968 to 2003. A 10-fold cross-validation shows that JRFR outperforms other popular methods in predicting antigenic variants. In addition, our results suggest that structure features are most relevant to influenza antigenicity. By restricting the analysis to data involving two adjacent antigenic clusters, we inferred a few key amino acids mutation driving the 11 historical antigenic drift events, pointing to experimentally validated mutations. Finally, we constructed an antigenic cartography of all H3N2 viruses with hemagglutinin (the glycoprotein on the surface of the influenza virus responsible for its binding to host cells) sequence available from NCBI flu database, and showed an overall correspondence and local inconsistency between genetic and antigenic evolution of H3N2 influenza viruses.
In order to study duck microsatellites, we constructed a library enriched for (CA)n, (CAG)n, (GCC)n and (TTTC)n. A total of 35 pairs of primers from these microsatellites were developed and used to detect polymorphisms in 31 unrelated Peking ducks. Twenty-eight loci were polymorphic and seven loci were monomorphic. A total of 117 alleles were observed from these polymorphic microsatellite markers, which ranged from 2 to 14 with an average of 4.18 per locus. The frequencies of the 117 alleles ranged from 0.02 to 0.98. The highest heterozygosity (0.97) was observed at the CAUD019 microsatellite locus and the lowest heterozygosity (0.04) at the CAUD008 locus, and 11 loci had heterozygosities greater than 0.50 (46.43%). The polymorphism information content (PIC) of 28 loci ranged from 0.04 to 0.88 with an average of 0.42. All the above markers were used to screen the polymorphism in other bird species. Two markers produced specific monomorphic products with the chicken DNA. Fourteen markers generated specific fragments with the goose DNA: 5 were polymorphic and 9 were monomorphic. But no specific product was detected with the peacock DNA. Based on sequence comparisons of the flanking sequence and repeat, we conclude that 2 chicken loci and 14 goose loci were true homologous loci of the duck loci. The microsatellite markers identified and characterized in the present study will contribute to the genetic map, quantitative traits mapping, and phylogenetic analysis in the duck and goose. duck / microsatellite marker / enriched library / polymorphism / cross-species amplification
The prevalence of anxiety disorders is higher in women than in men. Yet preclinical studies on anxiety are mostly performed in male subjects. This may have limited our understanding of mechanisms contributing to anxiety disorders. Since fear conditioning is considered an important factor in the etiology of anxiety disorders, the present study aimed to investigate the effect of sex and estrous cycle on conditioned fear and the anxiolytic effect of benzodiazepines in rats. We measured the fear-potentiated startle response in male and female rats during different estrous cycle stages and performed a replication study in a separate cohort. In addition, we assessed the response to diazepam (0-3.0 mg/kg IP) and chlordiazepoxide (0-10 mg/kg IP) in male and female rats in proestrous/estrous and diestrous stage. Our results showed that there were no sex differences in the expression of fear-potentiated startle. The estrous cycle also did not affect the fear-potentiated startle response. In addition, male and female rats did not differ in their fear-potentiated startle response following treatment with either diazepam or chlordiazepoxide. In conclusion, the current study shows that male and female rats do not differ in their conditioned fear response and the responsiveness to benzodiazepines. The results further indicate that conditioned fear-related processes are not affected by gonadal hormone fluctuations in this paradigm. These findings may suggest that the higher prevalence of anxiety disorders in women more likely results from differences in responding to previous experiences or differences in other predisposing factors, rather than differences in conditioned fear per se.
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