Search

Calcium/calmodulin-dependent serine protein kinase (CASK) is a membrane-associated guanylate kinase (MAGUK) protein that is associated with neurodevelopmental disorders. CASK is thought to have both pre- and postsynaptic functions, but the mechanism and consequences of its functions in the brain have yet to be elucidated, because homozygous CASK-knockout (CASK-KO) mice die before brain maturation. Taking advantage of the X-chromosome inactivation (XCI) mechanism, here we examined the synaptic functions of CASK-KO neurons in acute brain slices of heterozygous CASK-KO female mice. We also analyzed CASK-knockdown (KD) neurons in acute brain slices generated by in utero electroporation. Both CASK-KO and CASK-KD neurons showed a disruption of the excitatory and inhibitory (E/I) balance. We further found that the expression level of the N-methyl-d-aspartate receptor subunit GluN2B was decreased in CASK-KD neurons and that overexpressing GluN2B rescued the disrupted E/I balance in CASK-KD neurons. These results suggest that the down-regulation of GluN2B may be involved in the mechanism of the disruption of synaptic E/I balance in CASK-deficient neurons.

Extensive and thick permeable strata are found beneath many reservoir sites. The leakage problem in these reservoirs can be effectively solved by constructing a full geomembrane liner design. However, applying this particular solution for the reservoir induces novel engineering problems. The air bulging produced beneath the geomembrane results in geomembrane rupture and causes a renewed leakage in reservoirs. The groundwater level may be relatively low during construction because of seasonal variation and dewatering. Geomembranes isolate pore air from the atmosphere, and a significant amount of air is trapped in the pores of the unsaturated soil above the groundwater level. The rise in the groundwater level or the compression of soil decreases pore-air volume and increases pore pressure, thereby causing air bulging to occur and prompting the ultimate destruction of the geomembrane. The presence of air bulging beneath the geomembrane is studied in the design process of the Datun Reservoir in Dezhou City, Shandong Province, China. Investigation results reveal that a rise in the groundwater level significantly influences the air bulging beneath the geomembrane. The French drain is set to prevent air bulging beneath the geomembrane from occurring. The 75-m French drain spacing is not reasonable because the air pressure beneath the geomembrane will result in air bulging. A comparison among French drains with spacings of 25 m and 50 m indicates that the original design comprising French drains spaced 50 m apart is reasonable and economical.