Mosquitoes carried larvicide to breeding sites, cutting egg counts by 70 per cent
In a randomized Melbourne field trial, stations that enlisted mosquitoes to carry larvicide and fungus to breeding sites cut egg counts by 70 per cent; the human disease analysis was added later. Other whole-organism studies found that deleting either of two DOC genes left a fungus nearly sterile while deleting both did not, and linked enoxolone's effect in a roughly 3,000-compound zebrafish screen to the receptor HNF4 alpha.
Science··Morning
Mosquitoes ferried treatment to their breeding sites
In a randomized field trial around Melbourne, researchers placed 100 autodissemination stations in each of 6 areas for 8 weeks and left 6 areas untreated as controls. The stations use the larvicide pyriproxyfen and the fungus Beauveria bassiana, relying on Aedes notoscriptus mosquitoes to carry them to breeding sites. Egg counts in intervention areas were on average 70 per cent lower than in control areas. Human Buruli ulcer notifications were also lower in intervention zones, but that analysis was designed after the trial, case numbers were small and the confidence interval did not exclude no effect. The robust primary result is the drop in mosquito eggs.[1]
Deleting both genes restored fertility
The PLOS Biology study followed determinant-of-communication proteins working with the STRIPAK signaling complex in the fungus Sordaria macrospora. Deleting either SmDOC1 or SmDOC2 alone severely impaired fruiting-body formation and left strains nearly sterile. Deleting both genes together restored wild-type development and fertility. Proximity mapping placed both proteins near components of the pheromone-response MAP kinase pathway, while yeast two-hybrid experiments supported direct interactions between SmDOC1 and MEK2 and MAK2. The result strengthens the interpretation that the proteins have balanced, mutually antagonistic roles rather than acting as simple backups for one another.[2]
A licorice-root compound emerged in zebrafish
The eLife team screened roughly 3,000 compounds with LipoGlo, a light-based readout of apolipoprotein B-containing lipoproteins in live zebrafish. Of 49 distinct hits that lowered the particles, 19 passed additional criteria and 7 underwent extensive characterization. The licorice-root component enoxolone significantly lowered lipoproteins only in animals carrying a functional form of the receptor HNF4 alpha; HNF4 alpha inhibitors also reduced levels. The highest concentration affected fish development, and enoxolone has other known effects that can raise blood pressure in people. The study demonstrates how a whole-animal screen can expose a mechanism, rather than recommending a drug.[3]
