Biology subjects

Hata, H.

Publications and source records attributed to Hata, H..

5 recordsLinked to original sources

bioRxiv2026

Resolution-standardized evaluation of ligand atomic coordinates in crystallographic structures using machine learning

Accurate assessment of ligand coordinate-density consistency across different resolutions remains challenging in macromolecular crystallography. We introduce the atomic Box Correlation Coefficient (aBCC), an atom-level metric for evaluating the consistency between ligand atomic coordinates and electron density in a resolution-standardized framework. To predict aBCC values from electron-density maps, we developed QAEmap, a machine-learning model based on three-dimensional convolutional neural networks (3D-CNNs). The model was trained using Fourier-truncated electron-density maps and corresponding ligand coordinates generated from high-resolution structures in the Protein Data Bank. It was evaluated using both Fourier-truncated electron-density maps and experimentally determined PDB structures. was evaluated using both Fourier-truncated electron-density maps and experimentally determined PDB structures.The prediction accuracy gradually decreased with decreasing resolution, but remained reliable up to [~]3.5 [A]. These results demonstrate that aBCC enables resolution-standardized atom-wise evaluation of coordinate-density consistency across different resolutions and provide a foundation for further development and refinement of machine learning-based coordinate validation. SynopsisWe introduce the atomic box correlation coefficient (aBCC), a machine learning-based metric for the resolution-standardized atom-level evaluation of ligand coordinate-density consistency in crystallographic structures. aBCC provides a common framework for assessing and communicating the local coordinate reliability between structural biologists and researchers in structure-based drug discovery.

molecular biology↗

bioRxiv2024

Homoploid Hybrid Speciation in a Marine Pelagic Fish Megalaspis cordyla (Carangidae)

Homoploid hybrid speciation (HHS) is an enigmatic evolutionary process where new species arise through hybridization of divergent lineages without changes in chromosome number. Although increasingly documented in various taxa and ecosystems, convincing cases of HHS in marine fishes have been lacking. This study presents evidence of HHS in Torpedo scad Megalaspis cordyla based on comprehensive genomic, morphological, and ecological analyses. A Principal Component Analysis using thousands of SNPs identified three sympatric clusters in the western Pacific. Genome-wide differentiation between the clusters and the admixed nature of a cluster between the others were evident from population genomic analyses, species tree estimation, mitochondrial DNA divergence, and tests of introgression. Multiple statistical methods for hybrid detection also supported the admixed ancestry of this cluster. Moreover, model-based demographic inference favored a hybrid speciation scenario over introgression. Examination of occurrence data and ecologically relevant morphological characters suggested ecological differences between the clusters, potentially contributing to reproductive isolation and niche partitioning in sympatry. The clusters are morphologically distinguishable and thus can be taxonomically recognized as separate species. The hybrid cluster is restricted to the coasts of Taiwan and Japan, where all three clusters coexist. The parental clusters are additionally found in lower latitudes such as the coasts of the Philippines, Vietnam, Thailand, and Malaysia, where they display non-overlapping distributions. Given the geographical distributions, estimated times of the species formation, and patterns of historical demographic changes, we propose that the Pleistocene glacial cycles were the primary driver of HHS in this system. Based on this argument, we develop an ecogeographic model of HHS in marine coastal ecosystems, including a novel hypothesis to explain the initial stages of HHS.

evolutionary biology↗

bioRxiv2024

Development of a new genotype-phenotype linked antibody screening system

Antibodies are powerful tools for the therapy and diagnosis of various diseases. In addition to conventional hybridoma-based screening, recombinant antibody-based screening has become a common choice; however, its application is hampered by two factors: 1) screening starts after Ig gene cloning and recombinant antibody production only, and 2) the antibody is composed of paired chains, heavy and light, commonly expressed by two independent expression vectors. Here, we introduce a method for the rapid screening of recombinant monoclonal antibodies by establishing a Golden Gate-based dual-expression vector and in-vivo expression of membrane-bound antibodies. Using this system, we demonstrate the rapid isolation of influenza cross-reactive antibodies with high affinity from immunized mice within 7 days. This system is particularly useful for isolating therapeutic or diagnostic antibodies, e.g., during foreseen pandemics. Impact StatementA Golden Gate-based dual-expression vector enables rapid screening, which facilitates efficient isolation of high-affinity cross-reactive antibodies for therapeutic or diagnostic use and provides a crucial advance for pandemic preparedness.

bioengineering↗

bioRxiv2020

Expert programmers have fine-tuned cortical representations of source code

Expertise enables humans to achieve outstanding performance on domain-specific tasks, and programming is no exception. Many have shown that expert programmers exhibit remarkable differences from novices in behavioral performance, knowledge structure, and selective attention. However, the underlying differences in the brain are still unclear. We here address this issue by associating the cortical representation of source code with individual programming expertise using a data-driven decoding approach. This approach enabled us to identify seven brain regions, widely distributed in the frontal, parietal, and temporal cortices, that have a tight relationship with programming expertise. In these brain regions, functional categories of source code could be decoded from brain activity and the decoding accuracies were significantly correlated with individual behavioral performances on source-code categorization. Our results suggest that programming expertise is built up on fine-tuned cortical representations specialized for the domain of programming.

neuroscience↗

bioRxiv2019

High pressure inhibits signaling protein binding to the flagellar motor and bacterial chemotaxis through enhanced hydration

In the chemotaxis of Escherichia coli, the cells behavioral switch involves binding of the phosphorylated form of the chemotaxis signaling protein CheY (CheYp) to the flagellar motor protein FliM, which induces the motor to rotate clockwise; otherwise, the motor rotates counterclockwise. To investigate high-pressure effects on CheYp-FliM binding at atomic resolution, we conduct molecular dynamics simulations of monomeric CheYp, the N-terminal fragment of the FliM (FliMN) that binds to CheYp, and the complex that forms between those proteins at pressures ranging from 0.1 to 100 MPa. The results show that the active form of monomeric CheYp is maintained even at 100 MPa but high pressure increases the water density in the first hydration shell and can cause conformational change of the C-terminal helix. The dissociation process of the complex is investigated by parallel cascade selection molecular dynamics (PaCS-MD), revealing that high pressure considerably induces water penetration into the complex interface. Pressure dependence of standard binding free energy calculated by the Markov state model indicates that the increase of pressure from 0.1 to 100 MPa weakens the binding by [~] 10 kcal/mol. Using high-pressure microscopy, we observed that high hydrostatic pressure reversibly fixes the motor rotation in the counter-clockwise orientation, which supports the notion that high pressure inhibits the binding of CheYp to FliM. We conclude that high pressure induces water penetration into the complex interface, which interferes with CheYp-FliM binding and prevents motor reversal.

biophysics↗