N-alkyl substituted armeniaspirol analogs show potent antibiotic activity and have low susceptibility to resistance.

The armeniaspirol family of antibiotics have been shown to inhibit the ATP-dependent proteases ClpXP and ClpYQ and to disrupt the electrical membrane potential (ΔΨ) bacterial proton motive force. The synthesis and characterization of first generation armeniaspirol analogs shows the N-alkyl group is amenable to modification. Herein we synthesize eleven second generation N-alkyl analogs and show they display excellent antibiotic potency against multiple MRSA strains and retain the ability to disrupt membrane electrical potential.

Antibacterial Polymers Based on Two Orthogonal Binding Motifs Coalesce with Bacterial Matter.

Addressing the growing concern about antibiotic-resistant bacteria, we have developed a series of polymers exhibiting intrinsic antibacterial activities with a dual-targeting system that induces physical lysis upon copolymer coalescence with bacterial matter. These polymers are equipped with two orthogonal binding motifs that form electrostatic interactions and dynamic covalent complexes on bacterial surfaces and exhibit potent antibacterial activity against Gram-positive and Gram-negative bacteria. The effect of the chemical composition and architecture of copolymers incorporating phenylboronic acid and quaternary ammonium groups on the antimicrobial activities was systematically examined.

Surface Functionalization of Nanocarriers with Anti-EGFR Ligands for Cancer Active Targeting.

Active cancer targeting consists of the selective recognition of overexpressed biomarkers on cancer cell surfaces or within the tumor microenvironment, enabled by ligands conjugated to drug carriers. Nanoparticle (NP)-based systems are highly relevant for such an approach due to their large surface area which is amenable to a variety of chemical modifications. Over the past decades, several studies have debated the efficiency of passive targeting, highlighting active targeting as a more specific and selective approach.

Multi-omic quantitative trait loci link tandem repeat size variation to gene regulation in human brain.

Tandem repeat (TR) size variation is implicated in ~50 neurological disorders, yet its impact on gene regulation in the human brain remains largely unknown. In the present study, we quantified the impact of TR size variation on brain gene regulation across distinct molecular phenotypes, based on 4,412 multi-omics samples from 1,597 donors, including 1,586 newly sequenced ones. We identified ~2.

Conjoined partners: efficacy and side effects of grafting and dsRNA application on the microbial endophyte population of grapevine plants inoculated with two esca-related fungal pathogens.

Grafting has been exploited since 7000 BC to enhance productivity, disease resistance, and adaptability of cultivated plants to stressful conditions especially in woody crops such as grapevine (Vitis spp.). In contrast, the application of sequence specific double-stranded RNAs (dsRNAs) to control fungal pathogens and insect pests has only been recently developed.