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The mammalian longevity associated acetylome
Real-space heterogeneous reconstruction, refinement, and disentanglement of CryoEM conformational states with HetSIREN
Abstract Single-particle analysis by Cryo-electron microscopy (CryoEM) provides direct access to the conformations of macromolecules. Traditional methods assume discrete conformations, while newer algorithms estimate conformational landscapes representing the different structural states a biomolecule explores. This work presents HetSIREN, a deep learning-based method that can fully reconstruct or refine a CryoEM volume in real space based on the structural information summarized in a conformational latent space. HetSIREN is defined as an accurate space-based method that allows spatially focused analysis and the introduction of sinusoidal hypernetworks with proven high analytics capacities. Continuing with innovations, HetSIREN can also refine the images’ pose while conditioning the network with additional constraints to yield cleaner high-quality volumes, as well as addressing one of the most confusing issues in heterogeneity analysis, as it is the fact that structural heterogeneity estimations are entangled with pose estimation (and to a lesser extent with CTF estimation) thanks to its decoupling architecture.
Self-adaptive and large-area sprayable thermal management coatings for energy saving
Shape morphing of soft robotics by pneumatic torsion strip braiding
Proton-coupled electron transfer controls peroxide activation initiated by a solid-water interface
Chloroplast precursor protein preClpD overaccumulation triggers multilevel reprogramming of gene expression and a heat shock-like response
Uncovering nitroxoline activity spectrum, mode of action and resistance across Gram-negative bacteria
Abstract Nitroxoline is a bacteriostatic quinoline antibiotic, known to form complexes with metals. Its clinical indications are limited to uncomplicated urinary tract infections, with a susceptibility breakpoint only available for Escherichia coli . Here, we test > 1000 clinical isolates and demonstrate a much broader activity spectrum and species-specific bactericidal activity, including Gram-negative bacteria for which therapeutic options are limited due to multidrug resistance. By combining genetic and proteomic approaches with direct measurement of intracellular metals, we show that nitroxoline acts as a metallophore, inducing copper and zinc intoxication in bacterial cells. The compound displays additional effects on bacterial physiology, including alteration of outer membrane integrity, which underpins nitroxoline’s synergies with large-scaffold antibiotics and resensitization of colistin-resistant Enterobacteriaceae in vitro and in vivo. Furthermore, we identify conserved resistance mechanisms across bacterial species, often leading to nitroxoline efflux.