Biology subjects

Koto, A.

Publications and source records attributed to Koto, A..

3 recordsLinked to original sources

bioRxiv2026

DiverScan: attention-guided exploratory analysis of animal behaviour across diverse comparative experiments

High-throughput tracking yields rich time-series data of animal behaviour, yet extracting biological insight remains a bottleneck, even for simple control--treatment comparisons. Existing analyses struggle to pinpoint the multiple, nonlinearly intertwined differences hidden in the data and fail to generalise across diverse recording set-ups. Here we present DiverScan, a deep-learning framework for attention-guided exploratory analysis of behavioural time series. DiverScan disentangles condition-dependent behavioural differences by pairing a loss function tailored to data exploration with an attention-branch architecture, and highlights condition-specific behavioural features visually and with explanatory text generated by a large language model. DiverScan is validated on a synthetic benchmark and on datasets from seven laboratories spanning multiple species and both single- and multi-animal behaviour. Beyond recovering known phenotypes, we demonstrate that DiverScan helps researchers generate new hypotheses across these diverse datasets. Available as Jupyter notebooks with a graphical user interface and flexible input formats, DiverScan can integrate into existing behavioural-analysis pipelines.

animal behavior and cognition↗

bioRxiv2022

New SNCA mutation and structures of α-synuclein filaments from juvenile-onset synucleinopathy

A 21-nucleotide duplication in one allele of SNCA was identified in a previously described disease with abundant -synuclein inclusions that we now call juvenile-onset synucleinopathy (JOS). Both wild-type -synuclein and its insertion mutant containing seven additional residues (MAAAEKT) after residue 22 were present in sarkosyl-insoluble material that was extracted from frontal cortex of the individual with JOS and examined by electron cryo-microscopy. The structures of JOS filaments, comprising either a single protofilament, or a pair of protofilaments, revealed a new -synuclein fold that differs from the folds of Lewy body diseases and multiple system atrophy (MSA). The JOS fold consists of a compact core, the sequence of which (residues 36-100 of wild-type -synuclein) is unaffected by the mutation, and two disconnected density islands (A and B) of mixed sequences. There is a non-proteinaceous cofactor bound between the core and island A. The JOS fold resembles the common substructure of MSA type I and type II dimeric filaments, with its core segment approximating the C-terminal body of MSA protofilaments B and its islands mimicking the N-terminal arm of MSA protofilaments A. The partial similarity of JOS and MSA folds extends to the locations of their cofactor-binding sites. Our findings provide insight into a likely mechanism of JOS fibrillation in which mutant -synuclein of 147 amino acids forms a nucleus with the JOS fold, around which wild-type and mutant proteins assemble during elongation.

neuroscience↗

bioRxiv2019

Dynamics of bacterial cell proliferation inhibited by specific proteins for effective horizontal transmission of the integrative and conjugative element ICEclc

The integrative and conjugative element ICEclc, a prevalent mobile element in proteobacteria, is one of the experimental models for horizontal gene transfer. ICEclc is usually retained in a bacterial chromosome, but can be excised and transferred from the donor to other bacterial lineages. The horizontal transmission is accomplished by developing specialized transfer competent (tc) cells in the donor population. The tc cells entirely dedicate to the ICE transmission by sacrificing their proliferation, which results in an increase in the transfer frequency. The cell growth impairment is mediated by two specific genes, parA and shi, on ICEclc, but its mechanistic details and cellular dynamics are still unknown. We here developed fluorescence reporter strains to monitor intracellular behavior of ParA and Shi proteins as well as host cellular proliferation at the single-cell level. Superresolution imaging revealed that ParA colocalized with the host nucleoid while Shi diffused in cytoplasm during the growth impairment. Mutations in the Walker A motif of ParA diminished the inhibitory effect. Combining quantitative time-lapse microscopy and numerical simulations using mathematical models, we found that ParA and Shi initially blocked cell division and then, as time elapsed, inhibited cellular elongation. The parA-shi locus is highly conserved in other ICEs, and the ParA-Shi-mediated growth inhibition was still observed in different proteobacterial species, suggesting that the ICEs have evolved the system to efficiently distribute themselves in the niche. The results of our study provide mechanistic insight into the novel and unique system on ICEs and help to understand such epistatic interaction between ICE genes and host physiology that entails efficient horizontal gene transfer.\n\nAuthor summaryHorizontal gene transfer is a major diving force for bacterial evolution, which is frequently mediated by mobile DNA vectors, such as plasmids and bacteriophages. Integrative and conjugative elements (ICEs) are a relatively new class of mobile vectors, which normally integrate in a host chromosome but under certain conditions can be excised and transferred from the host to a new recipient cell via conjugation. Recent genomic studies estimated that ICEs are more abundant than plasmids among bacteria. Why so prevalent? One of the characteristics of ICEclc, an ICE model in proteobacteria, is that it develops specialized cells which entirely dedicate to the ICE horizontal transmission by repressing their proliferation. Here, we qualitatively and quantitatively describe two proteins, which are expressed from ICEclc when it transfers, and how they actually inhibit the host cell growth. Our results suggest that the system has evolved for the efficient horizontal transmission and is widely conserved in the ICE family.

microbiology↗