Functional Assessment of Missense Variants in the ABCC6 Gene Implicated in Pseudoxanthoma Elasticum, a Heritable Ectopic Mineralization Disorder.

Pseudoxanthoma elasticum, a heritable multisystem ectopic mineralization disorder, is caused by inactivating mutations in the ABCC6 gene. The encoded protein, ABCC6, a transmembrane transporter, has a specialized efflux function in hepatocytes by contributing to plasma levels of inorganic pyrophosphate, a potent inhibitor of mineralization in soft connective tissues. Reduced plasma inorganic pyrophosphate levels underlie the ectopic mineralization in pseudoxanthoma elasticum. In this study, we characterized the pathogenicity of three human ABCC6 missense variants using an adenovirus-mediated liver-specific ABCC6 transgene expression system in an Abcc6-/- mouse model of pseudoxanthoma elasticum. Variants p.L420V and p.R1064W were found benign because they had abundance and plasma membrane localization in hepatocytes similar to the wild-type human ABCC6 transgene, normalized plasma inorganic pyrophosphate levels, and prevented mineralization in the dermal sheath of vibrissae in muzzle skin, a phenotypic hallmark in the Abcc6-/- mice. In contrast, p.S400F was shown to be pathogenic because it failed to normalize plasma inorganic pyrophosphate levels and had no effect on ectopic mineralization despite its normal expression and proper localization in hepatocytes. These results showed that adenovirus-mediated hepatic ABCC6 expression in Abcc6-/- mice can provide a model system to effectively elucidate the multifaceted functional consequences of human ABCC6 missense variants identified in patients with pseudoxanthoma elasticum.

Assessment of physical, microstructural, thermal, techno-functional and rheological characteristics of apple (Malus domestica) seeds of Northern Himalayas.

In this research, two common apple seed cultivars Viz: 'Golden Delicious' (GD) and 'Red Delicious' (RD) of Northern Himalayan region were characterized for physical, techno-functional, microstructure, thermal, and rheological properties. Seeds showed a significant difference in width, arithmetic, and geometric mean diameters, volume, and surface area. Proximate analysis results revealed that seed flours have high oil content (> 20%) and are potentially rich sources of protein (> 40%). Color analysis of flours indicated their satisfactory whiter color with higher brightness values (L* ˃ 75), resulting from the reduced particle size which allows greater light penetration and relatively lower a* (< 1.5) and b* (< 11) values. Techno-functional attributes including water/oil absorption capacity, emulsifying capacity, and emulsion stability were significantly higher in RD than GD flour. There was also a significant difference in the average particle size of seed flours. Flour micrographs indicated the presence of oval/spherical-shaped starch granules embedded in dense protein matrix while, Differential Scanning calorimeter (DSC) revealed exothermic transition enthalpies for seed flours. Additionally, seed flours depicted high elastic modulus (G'), suggesting their suitability for modifying food texture. It was concluded that apple seeds exhibit significant potential for use in formulating protein-enriched foods while contributing to reducing industrial wastage.