Inbreeding-Driven Innate Behavioral Changes in Drosophila melanogaster.

Drosophila melanogaster has long been used to demonstrate the effect of inbreeding, particularly in relation to reproductive fitness and stress tolerance. In comparison, less attention has been given to exploring the influence of inbreeding on the innate behavior of D. melanogaster. In this study, multiple replicates of six different types of crosses were set in pair conformation of the laboratory-maintained wild-type D. melanogaster. This resulted in progeny with six different levels of inbreeding coefficients. Larvae and adult flies of varied inbreeding coefficients were subjected to different behavioral assays. In addition to the expected inbreeding depression in the-egg to-adult viability, noticeable aberrations were observed in the crawling and phototaxis behaviors of larvae. Negative geotactic behavior as well as positive phototactic behavior of the flies were also found to be adversely affected with increasing levels of inbreeding. Interestingly, positively phototactic inbred flies demonstrated improved learning compared to outbred flies, potentially the consequence of purging. Flies with higher levels of inbreeding exhibited a delay in the manifestation of aggression and courtship. In summary, our findings demonstrate that inbreeding influences the innate behaviors in D. melanogaster, which in turn may affect the overall biological fitness of the flies.

Design and Immunoinformatic Assessment of Candidate Multivariant mRNA Vaccine Construct against Immune Escape Variants of SARS-CoV-2.

To effectively counter the evolving threat of SARS-CoV-2 variants, modifications and/or redesigning of mRNA vaccine construct are essentially required. Herein, the design and immunoinformatic assessment of a candidate novel mRNA vaccine construct, DOW-21, are discussed. Briefly, immunologically important domains, N-terminal domain (NTD) and receptor binding domain (RBD), of the spike protein of SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs) were assessed for sequence, structure, and epitope variations. Based on the assessment, a novel hypothetical NTD (h-NTD) and RBD (h-RBD) were designed to hold all overlapping immune escape variations. The construct sequence was then developed, where h-NTD and h-RBD were intervened by 10-mer gly-ala repeat and the terminals were flanked by regulatory sequences for better intracellular transportation and expression of the coding regions. The protein encoded by the construct holds structural attributes (RMSD NTD: 0.42 Å; RMSD RBD: 0.15 Å) found in the respective domains of SARS-CoV-2 immune escape variants. In addition, it provides coverage to the immunogenic sites of the respective domains found in SARS-CoV-2 variants. Later, the nucleotide sequence of the construct was optimized for GC ratio (56%) and microRNA binding sites to ensure smooth translation. Post-injection antibody titer was also predicted (~12000 AU) to be robust. In summary, the construct proposed in this study could potentially provide broad spectrum coverage in relation to SARS-CoV-2 immune escape variants.