A single point mutation in the LN domain of LAMA2 causes muscular dystrophy and peripheral amyelination.

Mutations in the gene encoding the basal lamina (BL) component laminin alpha2 (LAMA2) cause merosin-deficient congenital muscular dystrophy 1A (MDC1A), a complex disorder that includes hypomyelination and myodegeneration. In dystrophia muscularis (dy) mice bearing Lama2 mutations, myofibers and Schwann cells fail to assemble stable BLs, which are thought to be crucial for myofiber survival and Schwann cell differentiation. Here, we describe defects in a new allele of Lama2 in mice, nmf417, in which a point mutation substitutes Arg for Cys79 at a universally conserved CxxC motif in the laminin N-terminal (LN) domain; this domain mediates laminin-laminin interactions. nmf417 homozygosity caused progressive myodegeneration and severe peripheral amyelination in nerve roots, similar to previous Lama2 mutations, but without the pervasive BL thinning previously associated with the disorder. In direct contrast to the previously characterized dy and dy2J alleles, nmf417 homozygous myofibers frequently had thickened BLs. Severe amyelination in nmf417-mutant nerve roots suggested complete laminin 2 inactivation for Schwann cells, although myelinated fibers had normal BLs. The results reveal crucial roles for the LN domain CxxC motif in both nerve and muscle, but challenge expected relationships between LN-domain function, Ln2 activity and BL stability. The nmf417 mutation provides a defined animal model in which to investigate mechanisms and treatments for moderate forms of MDC1A

Use of NIR light and upconversion phosphors in light-curable polymers

OBJECTIVE: Light-curable polymers are commonly used in restorative surgery, prosthodontics and surgical procedures. Despite the fact of wide application, there are clinical problems due to limitations of blue light penetration: application is restricted to defects exposed to the light source, layered filling of defect is required. METHODS: Combining photo-activation and up conversion allows efficient polymer hardening by deep penetrating near-infrared (NIR) light. The prerequisite 450 nm blue light to polymerize dental resins could be achieved by filler particles, which absorb the incident NIR irradiation and convert it into visible light. RESULTS: The on spot generated blue light results in uniform polymer hardening. Composite samples of 5mm thickness were cured two times faster than pure polymer cured by blue light (30 and 60 s, respectively). Overall degree of monomer conversion resulted in higher values of more than 40%. The enhanced transmission of NIR light was confirmed by optical analysis of dentin and enamel. The NIR transmittance surge in the 800-1200 nm window could improve sealing of complex and deep caries lesions. SIGNIFICANCE: We demonstrate faster curing and an improved degree of polymerization by using upconversion filler particles as multiple light emission centers. This study represents an alternative approach in curing dental resins by NIR source