Biology subjects

Benner, S.

Publications and source records attributed to Benner, S..

3 recordsLinked to original sources

bioRxiv2026

DNA Ligases Discriminate Between Natural and Non-Natural Base Pairs

Artificially Expanded Genetic Information Systems (AEGIS) increase the information content of nucleic acids by including new nucleobase pairings that are orthogonal to those of canonical Watson-Crick nucleobases. DNA ligases do not form direct interactions with the nucleobases during catalytic turnover, suggesting that these enzymes should efficiently and faithfully join double-stranded AEGIS substrates. Here we report the systematic investigation into the validity of this hypothesis for structurally-diverse DNA ligases employing substrates built from the eight nucleotide hachimoji genetic alphabet, where orthogonality is achieved by rearranging the hydrogen bonding patterns seen in canonical Watson-Crick pairs. We find that single, or multiple, non-canonical bases are well tolerated at the 5-end of the nick. However, tracts of consecutive non-canonical bases at the 3-end of the break significantly decrease ligation efficiency or abolish it altogether. Possible reasons for this apparent bias against non-canonical nucleobases could include incompatibility in electrostatic interactions between the ligase active site and the non-canonical substrates or altered conformational preferences and/or dynamics in key catalytic intermediates. We also observe single hachimoji mismatches are ligated more frequently than mis paired canonical bases, potentially due to promiscuous pairing of tautomeric forms of the non-canonical bases.

biochemistry↗

bioRxiv2026

eeeHive: a new HF RFID-based automated behavioral monitoring system for group-housed animals with high spatiotemporal resolution

Long-term, automated tracking of group-housed social animals using RFID (radio frequency identification) is a promising approach in ethological neuroscience. However, low-frequency (LF) RFID, while long-established in the field, is constrained by its inherent low data rates, which lead to two critical limitations: (1) compromised spatiotemporal resolution, and (2) the inability to identify multiple tags (animals) simultaneously. To address these limitations, we developed eeeHive, a high-frequency (HF) RFID-based animal tracking system with a fully custom hardware architecture that enables high-speed, multiplexed antenna polling and concurrent multi-tag reading. The polling time per antenna in eeeHive was 5.9 ms, with an additional 8.2 ms read time per tag. We applied the system to track 24 mice for one week, and six common marmosets for seven weeks. The system successfully tracked individuals even within dense clusters, revealing complex behavioral traits characterized by spatial utilization, temporal dynamics, behavioral regularity, and inter-individual relationships. Additional tests with Japanese fire-bellied newts and Nile tilapia juveniles demonstrated comparable tracking performance in aquatic environments. Taken together, eeeHive overcomes the inherent limitations of conventional LF RFID, establishing a powerful HF RFID-based platform for fine-scale behavioral tracking of group-housed animals across terrestrial and aquatic species.

animal behavior and cognition↗

bioRxiv2024

Single MAPT knock-in mouse models of frontotemporal dementia for sharing with the neurodegenerative research community

We recently reported development of human MAPT knock-in mice that carry single or double pathogenic mutations of frontotemporal dementia. However, it takes more than 14 months for the line with the most aggressive phenotypes to exhibit tau pathology without forming high-order tau oligomers, along with concomitant abnormal behavior. We thus generated MAPT knock-in mice carrying triple mutations, among which the MAPTP301S;Int10+3;S320F line exhibited robust pathology starting earlier than 6 months. Tau accumulation took place mainly in the thalamus, hypothalamus, amygdala and entorhinal cortex, but less so in the hippocampus, leading to synaptic loss, atrophy and behavioral abnormalities. Crossbreeding MAPTP301S;Int10+3;S320F with App knock-in mice AppNL-G-F resulted in the manifestation of tau pathology in the hippocampus and cortex. These mutant mice will be valuable tools for understanding the mechanisms of frontotemporal dementia, Alzheimers disease and other tauopathies.

neuroscience↗