Regulation of Scaffold Cell Adhesion Using Artificial Membrane Binding Proteins.

The rapid pace of development in biotechnology has placed great importance on controlling cell-material interactions. In practice, this involves attempting to decouple the contributions from adhesion molecules, cell membrane receptors, and scaffold surface chemistry and morphology, which is extremely challenging. Accordingly, a strategy is presented in which different chemical, biochemical, and morphological properties of 3D biomaterials are systematically varied to produce novel scaffolds with tuneable cell affinities. Specifically, cationized and surfactant-conjugated proteins, recently shown to have non-native membrane affinity, are covalently attached to 3D scaffolds of collagen or carboxymethyl-dextran, yielding surface-functionalized 3D architectures with predictable cell immobilization profiles. The artificial membrane-binding proteins enhance cellular adhesion of human mesenchymal stem cells (hMSCs) via electrostatic and hydrophobic binding mechanisms. Furthermore, functionalizing the 3D scaffolds with cationized or surfactant-conjugated myoglobin prevents a slowdown in proliferation of seeded hMSCs cultured for seven days under hypoxic conditions.

Proxy molecular diagnosis from whole-exome sequencing reveals Papillon-Lefevre syndrome caused by a missense mutation in CTSC.

Papillon-Lefevre syndrome (PLS) is an autosomal recessive disorder characterised by severe early onset periodontitis and palmoplantar hyperkeratosis. A previously reported missense mutation in the CTSC gene (NM_001814.4:c.899G>A:p.(G300D)) was identified in a homozygous state in two siblings diagnosed with PLS in a consanguineous family of Arabic ancestry. The variant was initially identified in a heterozygous state in a PLS unaffected sibling whose whole exome had been sequenced as part of a previous Primary ciliary dyskinesia study. Using this information, a proxy molecular diagnosis was made on the PLS affected siblings after consent was given to study this second disorder found to be segregating within the family. The prevalence of the mutation was then assayed in the local population using a representative sample of 256 unrelated individuals. The variant was absent in all subjects indicating that the variant is rare in Saudi Arabia. This family study illustrates how whole-exome sequencing can generate findings and inferences beyond its primary goal.