Disease-associated nonsense and frame-shift variants resulting in the truncation of the GluN2A or GluN2B C-terminal domain decrease NMDAR surface expression and reduce potentiating effects of neurosteroids.

N-methyl-D-aspartate receptors (NMDARs) play a critical role in normal brain function, and variants in genes encoding NMDAR subunits have been described in individuals with various neuropsychiatric disorders. We have used whole-cell patch-clamp electrophysiology, fluorescence microscopy and in-silico modeling to explore the functional consequences of disease-associated nonsense and frame-shift variants resulting in the truncation of GluN2A or GluN2B C-terminal domain (CTD). This study characterizes variant NMDARs and shows their reduced surface expression and synaptic localization, altered agonist affinity, increased desensitization, and reduced probability of channel opening.

SCRAMBLER: A Tool for CRISPR Array Reconstruction and Its Application for Analysis of the Structure of Prokaryotic Populations.

CRISPR arrays are prokaryotic genomic loci consisting of repeat sequences alternating with unique spacers acquired from foreign nucleic acids. As one of the fastest-evolving parts of the genome, CRISPR arrays can be used to differentiate closely related prokaryotic lineages and track individual strains in prokaryotic communities. However, the assembly of full-length CRISPR arrays sequences remains a problem.