Ca2+-induced release of IQSEC2/BRAG1 autoinhibition under physiological and pathological conditions.

IQSEC2 (aka BRAG1) is a guanine nucleotide exchange factor (GEF) highly enriched in synapses. As a top neurodevelopmental disorder risk gene, numerous mutations are identified in Iqsec2 in patients with intellectual disabilities accompanied by other developmental, neurological, and psychiatric symptoms, though with poorly understood underlying molecular mechanisms. The atomic structures of IQSECs, together with biochemical analysis, presented in this study reveal an autoinhibition and Ca2+-dependent allosteric activation mechanism for all IQSECs and rationalize how each identified Iqsec2 mutation can alter the structure and function of the enzyme.

SNX17 Mediates Dendritic Spine Maturation via p140Cap.

Sorting nexin17 (SNX17) is a member of the sorting nexin family, which plays a crucial role in endosomal trafficking. Previous research has shown that SNX17 is involved in the recycling or degradation of various proteins associated with neurodevelopmental and neurological diseases in cell models. However, the significance of SNX17 in neurological function in the mouse brain has not been thoroughly investigated.

Sodium-calcium exchanger isoform-3 targeted Withania somnifera (L.) Dunal therapeutic intervention ameliorates cognition in the 5xFAD mouse model of Alzheimer's disease.

The third isoform of the Na-Ca exchanger (NCX3) is crucial for a physiological fine-tuning of the Ca fluxes in excitable tissues. In this view, the NCX3 accounts for the aberrant Ca influx seen during neuronal excitotoxicity, such as in Alzheimer's disease (AD). However, little is known about NCX3 regulation and functional properties.

Preparation and characterization of POSS-containing poly(perfluoropolyether)methacrylate hybrid copolymer and its superhydrophobic coating performance.

To design a mechanically stable and superhydrophobic coating, a polyhedral oligomeric silsesquioxane (POSS)-containing poly(perfluoropolyether)methacrylate (PFPEM) hybrid copolymer (PFPEM-POSS) was synthesized a free-radical solution polymerization with PFPEM, 1,1,2,2-perfluorooctyl acrylate, methyl (meth)acrylate, -butyl acrylate, hydroxypropyl acrylate, methacryloxy propyl trimethoxy silane, and methacrylisobutyl POSS; and azobisisobutyronitrile as an initiator. Hydrophobic coatings were formed on substrates by a facile one-step dip-coating method in a solution mixture of diethylene glycol dimethyl ether with the PFPEM-POSS hybrid copolymer. The chemical structure of the PFPEM-POSS copolymer and the surface morphology and performance of the PFPEM-POSS coatings were investigated.