A bioinspired peptide scaffold with high antibiotic activity and low in vivo toxicity

Bacterial resistance to almost all available antibiotics is an important public health issue. A major goal in antimicrobial drug discovery is the generation of new chemicals capable of killing pathogens with high selectivity, particularly multi-drug-resistant ones. Here we report the design, preparation and activity of new compounds based on a tunable, chemically accessible and upscalable lipopeptide scaffold amenable to suitable hit-to-lead development. Such compounds could become therapeutic candidates and future antibiotics available on the market. The compounds are cyclic, contain two D-amino acids for in vivo stability and their structures are reminiscent of other cyclic disulfide-containing peptides available on the market. The optimized compounds prove to be highly active against clinically relevant Gram-negative and Gram-positive bacteria. In vitro and in vivo tests show the low toxicity of the compounds. Their antimicrobial activity against resistant and multidrug-resistant bacteria is at the membrane level, although other targets may also be involved depending on the bacterial strain.

Cómo enseñar matemáticas en las primeras edades a partir de contextos de vida cotidiana = How to teach mathematics to young students based on everyday contexts

This paper stresses the importance of developing mathematical thought in young children based on everyday contexts, since these are meaningful learning situations with an interdisciplinary, globalised focus. The first part sets out the framework of reference that lays the theoretical foundations for these kinds of educational practices. The second part gives some teaching orientations for work based on everyday contexts. It concludes with the presentation of the activity 'We’re off to the cinema to learn mathematics!'