Ikegawa, Y. | bioRxiv Science

bioRxiv2024

Recording gamma-secretase activity in living mouse brains

{gamma}-Secretase plays a pivotal role in the central nervous system. Our recent development of genetically encoded Forster resonance energy transfer (FRET)-based biosensors has enabled the spatiotemporal recording of {gamma}-secretase activity on a cell-by-cell basis in live neurons in culture. Nevertheless, how {gamma}-secretase activity is regulated in vivo remains unclear. Here we employ the near-infrared (NIR) C99 720-670 biosensor and NIR confocal microscopy to quantitatively record {gamma}-secretase activity in individual neurons in living mouse brains. Intriguingly, we uncovered that {gamma}-secretase activity may influence the activity of {gamma}-secretase in neighboring neurons, suggesting a potential "cell non-autonomous" regulation of {gamma}-secretase in mouse brains. Given that {gamma}-secretase plays critical roles in important biological events and various diseases, our new assay in vivo would become a new platform that enables dissecting the essential roles of {gamma}-secretase in normal health and diseases.

neuroscience↗

bioRxiv2023

PDB NextGen Archive: Centralising Access to Integrated Annotations and Enriched Structural Information by the Worldwide Protein Data Bank

The Protein Data Bank (PDB) archive is the global repository for public-domain 3D biomolecular structural information. The archival nature of the PDB presents certain challenges pertaining to updating or adding associated annotations from trusted external biodata resources. While each Worldwide PDB (wwPDB) partner has made best efforts to provide up-to-date external annotations, accessing and integrating information from disparate wwPDB data centers can be an involved process. To address this issue, the wwPDB has established the PDB Next Generation or NextGen Archive, developed to centralize and streamline access to enriched structural annotations from wwPDB partners and trusted external sources. At present, the archive provides mappings between experimentally determined 3D structures of proteins and UniProt amino acid sequences, together with domain annotations from Pfam, SCOP2, and CATH databases, and intra-molecular connectivity information. Since launch, the PDB NextGen Archive has seen substantial user engagement with over 3.5 million data file downloads, ensuring researchers have access to accurate, up-to-date, and easily accessible structural annotations. Database URLhttp://www.wwpdb.org/ftp/pdb-nextgen-archive-site

bioinformatics↗