Epileptiform activity in brain organoids derived from patient with Glucose Transporter 1 Deficiency Syndrome.

Introduction: Glucose Transporter 1-Deficiency Syndrome (GLUT1-DS) is a rare genetic disorder caused by mutations in the gene encoding for GLUT1 and characterized by impaired glucose uptake in the brain. This leads to brain hypometabolism and the development of symptoms that include epilepsy, motor dysfunctions and cognitive impairment. The development of patient-specific models is a valuable tool for understanding the pathophysiology of rare genetic disorders and testing new therapeutic interventions.

Involvement of the contralateral hippocampus in ictal-like but not interictal epileptic activities in the kainate mouse model of temporal lobe epilepsy.

Objective: Animal and human studies have shown that the seizure-generating region is vastly dependent on distant neuronal hubs that can decrease duration and propagation of ongoing seizures. However, we still lack a comprehensive understanding of the impact of distant brain areas on specific interictal and ictal epileptic activities (e.g.

A Clickable Bioorthogonal Sydnone-Aglycone for the Facile Preparation of a Core 1 -Glycan-Array.

Protein--glycosylation has been shown to be essential for many biological processes. However, determining the exact relationship between -glycan structures and their biological activity remains challenging. Here we report that, unlike azides, sydnones can be incorporated as an aglycon into core 1 -glycans early-on in their synthesis since it is compatible with carbohydrate chemistry and enzymatic glycosylations, allowing us to generate a small library of sydnone-containing core 1 -glycans by chemoenzymatic synthesis.

Fast and Efficient Postsynthetic DNA Labeling in Cells by Means of Strain-Promoted Sydnone-Alkyne Cycloadditions.

Sydnones are highly stable mesoionic 1,3-dipoles that react with cyclooctynes through strain-promoted sydnone-alkyne cycloaddition (SPSAC). Although sydnones have been shown to be valuable bioorthogonal chemical reporters for the labeling of proteins and complex glycans, nucleic acids have not yet been tagged by SPSAC. Evaluation of SPSAC kinetics with model substrates showed fast reactions with cyclooctyne probes (up to k=0.

Impacting Bacterial Sialidase Activity by Incorporating Bioorthogonal Chemical Reporters onto Mammalian Cell-Surface Sialosides.

Bioorthogonal chemical reporters, in synergy with click chemistry, have emerged as a key technology for tagging complex glycans in living cells. This strategy relies on the fact that bioorthogonal chemical reporters are highly reactive species while being biologically noninvasive. Here, we report that chemical reporters and especially sydnones may have, on the contrary, enormous impact on biomolecule processing enzymes.