Conductive hearing loss does not affect spatial learning and memory in middle-aged guinea pigs.

Hearing loss (HL) in mid-life has been suggested as a risk factor for cognitive decline. It is unclear whether this relationship is due to deprivation of auditory input alone, degenerative processes, or a combination. Animal models are useful to investigate underlying neural mechanisms as human studies can be confounded by various factors.

Lewis Acids and Electron-Withdrawing Ligands Accelerate CO Coordination to Dinuclear Cu Compounds.

A series of dinuclear molecular copper complexes were prepared and used to model the binding and Lewis acid stabilization of CO in heterogeneous copper CO reduction electrocatalysts. Experimental studies (including measurement of rate and equilibrium constants) and electronic structure calculations suggest that the key kinetic barrier for CO binding may be a σ-interaction between Cu and the incoming CO ligand. The rate of CO coordination can be increased upon the addition of Lewis acids or electron-withdrawing substituents on the ligand backbone.

Screening, large-scale production and structure-based classification of cystine-dense peptides.

Peptides folded through interwoven disulfides display extreme biochemical properties and unique medicinal potential. However, their exploitation has been hampered by the limited amounts isolatable from natural sources and the expense of chemical synthesis. We developed reliable biological methods for high-throughput expression, screening and large-scale production of these peptides: 46 were successfully produced in multimilligram quantities, and >600 more were deemed expressible through stringent screening criteria.

Accurate de novo design of hyperstable constrained peptides.

Naturally occurring, pharmacologically active peptides constrained with covalent crosslinks generally have shapes that have evolved to fit precisely into binding pockets on their targets. Such peptides can have excellent pharmaceutical properties, combining the stability and tissue penetration of small-molecule drugs with the specificity of much larger protein therapeutics. The ability to design constrained peptides with precisely specified tertiary structures would enable the design of shape-complementary inhibitors of arbitrary targets.