Cortical excitability, a phenomenon in which the cell cortex is dynamically patterned with waves of F-actin assembly, has been described in a variety of animal model systems, including embryos of mamm...

The human pathogen Pseudomonas aeruginosa is particularly notorious for its multiple resistance mechanisms. A new concept for anti-infectives is the “pathoblocker” approach, which targets virulence factors to disarm rather than kill pathogens and thus attenuates the development of resistance. Based on the estrogen receptor modulator raloxifene, which had previously been identified as a potential biosynthesis inhibitor of the virulence factor pyocyanin via in silico screening, analogues have been developed as pathoblockers against P. aeruginosa. These compounds reduce the production of pyocyanin by binding to the phenazine biosynthesis enzyme PhzB. Structure–activity relationships (SAR) were explored using nano differential scanning fluorimetry, isothermal titration calorimetry, and 12 X-ray cocrystal structures. Compared to raloxifene, congener 20c shows a 60-fold lower affinity for the human estrogen receptor with a 15-fold increase in pyocyanin inhibitory activity. The comprehensive structural information gathered in this study paves the way for the development of improved pathoblockers with increased potency and selectivity.

Centrosomes are highly dynamic organelles, and maintaining their stability is crucial for spindle pole integrity and bipolar spindle formation. Centrosomes consist of a pair of centrioles surrounded b...

Abstract. The microtubule motor dynein is critical for the assembly and positioning of mitotic spindles. In C. elegans, these dynein functions have been extensi