Mutants of the white ABCG Transporter in Drosophila melanogaster Have Deficient Olfactory Learning and Cholesterol Homeostasis.

Drosophila's white gene encodes an ATP-binding cassette G-subfamily (ABCG) half-transporter. White is closely related to mammalian ABCG family members that function in cholesterol efflux. Mutants of white have several behavioral phenotypes that are independent of visual defects. This study characterizes a novel defect of white mutants in the acquisition of olfactory memory using the aversive olfactory conditioning paradigm. The w1118 mutants learned slower than wildtype controls, yet with additional training, they reached wildtype levels of performance. The w1118 learning phenotype is also found in the wapricot and wcoral alleles, is dominant, and is rescued by genomic white and mini-white transgenes. Reducing dietary cholesterol strongly impaired olfactory learning for wildtype controls, while w1118 mutants were resistant to this deficit. The w1118 mutants displayed higher levels of cholesterol and cholesterol esters than wildtype under this low-cholesterol diet. Increasing levels of serotonin, dopamine, or both in the white mutants significantly improved w1118 learning. However, serotonin levels were not lower in the heads of the w1118 mutants than in wildtype controls. There were also no significant differences found in synapse numbers within the w1118 brain. We propose that the w1118 learning defect may be due to inefficient biogenic amine signaling brought about by altered cholesterol homeostasis.

Tailoring nitric oxide release with additive manufacturing to create antimicrobial surfaces.

The current use of implantable and indwelling medical is limited due to potential microbial colonization leading to severe ailments. The aim of this work is to develop bioactive polymers that can be customized based on patient needs and help prevent bacterial infection. Potential benefits of additive manufacturing technology are integrated with the antimicrobial properties of nitric oxide (NO) to develop NO-releasing biocompatible polymer interfaces for addressing bacterial infections. Using filament-based additive manufacturing and polycarbonateurethane-silicone (PCU-Sil) a range of films possessing unique porosities (Disk-60, Disk-40, solid, capped) were fabricated. The films were impregnated with S-nitroso-N-acetyl-penicillamine (SNAP) using a solvent-swelling process. The Disk-60 porous films had the greatest amount of SNAP (19.59 wt%) as measured by UV-vis spectroscopy. Scanning electron microscopy and energy-dispersive X-ray spectroscopy confirmed an even distribution of SNAP throughout the polymer. The films exhibited structure-based tunable NO-release at physiological levels ranging from 7-14 days for solid and porous films, as measured by chemiluminescence. The antibacterial efficacy of the films was studied against Staphylococcus aureus using 24 h in vitro bacterial adhesion assay. The results demonstrated a >99% reduction of viable bacteria on the surface of all the NO-releasing films compared to unmodified PCU-Sil controls. The combination of 3D-printing technology with NO-releasing properties represents a promising technique to develop customized medical devices (such as 3D-scaffolds, catheters, etc.) with distinct NO-release levels that can provide antimicrobial properties and enhanced biocompatibility.