Midface and upper airway dysgenesis in FGFR2-related craniosynostosis involves multiple tissue-specific and cell cycle effects.

Midface dysgenesis is a feature of more than 200 genetic conditions in which upper airway anomalies frequently cause respiratory distress, but its etiology is poorly understood. Mouse models of Apert and Crouzon craniosynostosis syndromes exhibit midface dysgenesis similar to the human conditions. They carry activating mutations of , which is expressed in multiple craniofacial tissues during development.

Mutations in the accessory subunit NDUFB10 result in isolated complex I deficiency and illustrate the critical role of intermembrane space import for complex I holoenzyme assembly.

An infant presented with fatal infantile lactic acidosis and cardiomyopathy, and was found to have profoundly decreased activity of respiratory chain complex I in muscle, heart and liver. Exome sequencing revealed compound heterozygous mutations in NDUFB10, which encodes an accessory subunit located within the PD part of complex I. One mutation resulted in a premature stop codon and absent protein, while the second mutation replaced the highly conserved cysteine 107 with a serine residue.

Structure-activity relationship studies of the tricyclic indoline resistance-modifying agent.

Previously we discovered a tricyclic indoline, N-[2-(6-bromo-4-methylidene-2,3,4,4a,9,9a-hexahydro-1H-carbazol-4a-yl)ethyl]-4-chlorobenzene-1-sulfonamide (1, Of1), from bioinspired synthesis of a highly diverse polycyclic indoline alkaloid library, that selectively resensitizes methicillin-resistant Staphylococcus aureus strains to β-lactam antibiotics. Herein, we report a thorough structure-activity relationship investigation of 1, which identified regions of 1 that tolerate modifications without compromising activity and afforded the discovery of a more potent analogue with reduced mammalian toxicity.