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Revale, S.

Publications and source records attributed to Revale, S..

3 recordsLinked to original sources

Propagation of seminal toxins through binary expression gene drives can suppress polyandrous populations

Gene drives can be highly effective in controlling a target population by disrupting a female fertility gene. To spread across a population, these drives require that disrupted alleles be largely recessive so as not to impose too high of a fitness penalty. We argue that this restriction may be relaxed by using a double gene drive design to spread a split binary expression system. One drive carries a dominant lethal/toxic effector alone and the other a transactivator factor, without which the effector will not act. Only after the drives reach sufficiently high frequencies would individuals have the chance to inherit both system components and the effector be expressed. We explore through mathematical modeling the potential of this design to spread dominant lethal/toxic alleles and suppress populations. We show that this system could be implemented to spread engineered seminal proteins designed to kill females, making it highly effective against polyandrous populations.

bioinformatics↗

Ly6Chi monocytes are metabolically reprogrammed in the blood during inflammatory stimulation allowing for macrophage lineage commitment

Acute inflammation is a rapid and dynamic process involving the recruitment and activation of multiple cell types in a co-ordinated and precise manner. Using cell tracking, linage tracing and single cell transcriptomics we investigated the origin and transcriptional reprogramming of monocytes and macrophages in acute inflammation. Monocyte trafficking and adoptive transfer experiments revealed that monocytes undergo rapid phenotypic change as they exit the blood and give rise to monocyte-derived macrophages that persist during the resolution of inflammation. Single cell transcriptomics revealed significant heterogeneity within the surface marker defined CD11b+Ly6G-Ly6Chi monocyte population within the blood and at the site of inflammation. Lineage trajectory analysis revealed that Ly6Chi monocytes in the blood are re-programmed into a defined differentiation pathway following inflammatory stimulus. We show that two major transcriptional reprogramming events occur during the initial 6 h of Ly6Chi monocyte mobilisation, one in the blood priming monocytes for migration and a second at the site of inflammation. Pathway analysis revealed an important role for oxidative phosphorylation (OxPhos) during both these reprogramming events in a subset of M2-like cells. Experimentally we also demonstrate that OxPhos is essential for murine and human monocyte chemotaxis. These new findings opening up the possibility that altering monocyte metabolic capacity towards OxPhos could facilitate enhanced macrophage M2-like polarisation to aid inflammation resolution and tissue repair.

immunology↗

Research gaps and new insights in the intriguing evolution of Drosophila seminal proteins

While the striking effects that seminal fluid proteins (SFPs) exert on females are fairly conserved among Diptera, they exhibit remarkable evolutionary lability. Consequently, most SFPs lack detectable homologs among the repertoire of SFPs of phylogenetically distant species. How such a rapidly changing proteome "manages" to conserve functions across taxa is a fascinating question. However, this and other pivotal aspects of SFPs evolution remain elusive because discoveries on these proteins have been mainly restricted to the model D. melanogaster. Here, we provide an overview of the current knowledge on the inter-specific divergence of Drosophila SFPs and compile the increasing amount of relevant genomic information from multiple species. Capitalizing the accumulated knowledge in D. melanogaster, we present novel sets of high-confidence SFP candidates and transcription factors presumptively involved in regulating the expression of SFPs. We also address open questions by performing comparative genomic analyses that failed to support the existence of conserved SFPs shared by most dipterans and indicated that gene co-option is the most frequent mechanism accounting for the origin of Drosophila SFP-coding genes. We hope our update establishes a starting point to integrate, as more species are assayed for SFPs, further data and thus, to widen the understanding of the intricate evolution of these proteins.

evolutionary biology↗