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Bono, L.

Publications and source records attributed to Bono, L..

2 recordsLinked to original sources

Maintenance of viral diversity through influenza transmission bottlenecks: a within-host branching-process model

Viral populations can experience a dramatic reduction in population size and genetic diversity during transmission between donor and recipient hosts. Transmission bottlenecks can therefore decrease the evolutionary potential of viral populations, slowing adaptation by increasing the strength of genetic drift and decreasing the strength of selection. Recent barcoded influenza experiments in guinea pigs showed that recipient animals receive a diverse viral inoculum but lose most of that diversity within one to two days. The resulting bottleneck therefore arises not at physical transfer but during early viral growth in the recipient. We develop a branching-process framework to quantify how much of this loss follows from stochasticity in early growth alone. Each transmitted lineage is treated as an independent stochastic process governed by measurable viral parameters. We recover these parameters from viral growth rates estimated from observed viral load. A residual filter for each animal then captures any additional loss imposed by the recipient host. Applied to twenty-four recipient animals, the model reveals two distinct groups. For roughly half of the animals, the stochastic extinction during early growth already accounts for the observed loss. For the remaining animals, the additional host filter is severe. Only about one in a hundred free virions pass through. This decomposition offers a quantitative entry point for future work on immune contributions to transmission bottlenecks.

evolutionary biology↗

Analysis of gene network bifurcation during optic cup morphogenesis in zebrafish

SummarySight depends on the tight cooperation between photoreceptors and pigmented cells. Both derive from common progenitors in which a single gene regulatory network (GRN) bifurcates into the neural retina (NR) and retinal-pigmented epithelium (RPE) programs. Although genetic studies have identified upstream nodes controlling these networks, their regulatory logic remains poorly investigated. Here, we characterize transcriptome dynamics (RNA-seq) and chromatin accessibility (ATAC-seq) in segregating NR/RPE populations in zebrafish. Analysis of active cis-regulatory modules and enriched transcription factor (TF) motives suggest extensive network redundancy and context-dependent TF activity. Downstream targets identification highlights an early recruitment of desmosomal genes in the flattening RPE, revealing Tead factors as upstream regulators. Investigation of GRNs dynamics uncovers an unexpected sequence of TF recruitment during RPE specification, which is conserved in humans. This systematic interrogation of the NR/RPE bifurcation should improve both genetic counselling for eye disorders and hiPSCs-to-RPE differentiation protocols for cell-replacement therapies in degenerative diseases.Competing Interest StatementThe authors have declared no competing interest.View Full Text

developmental biology↗