Significance: Despite the availability of various anti-seizure medications, nearly 1/3 of epilepsy patients experience drug-resistant seizures. These patients are left with invasive surgical options that do not guarantee seizure remission. The development of novel treatment options depends on elucidating the complex biology of seizures and brain networks.
View Article and Find Full Text PDFDevelopmental and epileptic encephalopathies (DEEs), a class of devastating neurological disorders characterized by recurrent seizures and exacerbated by disruptions to excitatory/inhibitory balance in the brain, are commonly caused by mutations in ion channels. Disruption of, or variants in, were implicated as causal for a set of DEEs, but the underlying mechanisms were clouded because is expressed in both excitatory and inhibitory neurons, undergoes extensive alternative splicing producing multiple isoforms with distinct functions, and the overall roles of FGF13 in neurons are incompletely cataloged. To overcome these challenges, we generated a set of novel cell-type-specific conditional knockout mice.
View Article and Find Full Text PDFThe CoA thioester of 2-(carboxymethyl)cyclohexane-1-carboxylic acid has been identified as a metabolite in anaerobic naphthalene degradation by the sulfate-reducing culture N47. This study identified and characterised two acyl-CoA dehydrogenases (ThnO/ThnT) and an intramolecular CoA-transferase (ThnP) encoded within the substrate-induced thn operon, which contains genes for anaerobic degradation of naphthalene. ThnP is a CoA transferase belonging to the family I (Cat 1 subgroup) that catalyses the intramolecular CoA transfer from the carboxyl group of 2-(carboxymethyl)cyclohexane-1-carboxyl-CoA to its carboxymethyl moiety, forming 2-carboxycyclohexylacetyl-CoA.
View Article and Find Full Text PDFThe mechanical bond is emerging as a novel design element in catalyst development. Here, we report a series of 1,1'-binaphthyl-2,2'-diol (BINOL) based catalysts in which the number of interlocked macrocycles is varied. Unsurprisingly, the macrocycles have a profound steric influence on the catalytic performance of these molecules.
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