Biology subjects

Hiraga, K.

Publications and source records attributed to Hiraga, K..

4 recordsLinked to original sources

bioRxiv2026

Multimodal phenotyping reveals plant-food-related dietary information in serum Raman spectra of community-dwelling Japanese adults

Healthy dietary patterns are associated with long-term health, but diet-quality scores do not reveal how habitual dietary information is represented in human biological phenotypes. Here we linked habitual dietary assessment with preceding health records and contemporaneous clinical chemistry, serum metabolomics and serum Raman spectra in community-dwelling Japanese adults. Higher diet quality corresponded to a more favorable preceding health profile, but did not define discrete states across contemporary multivariate phenotypes. Instead, specific dietary information was recoverable across these layers: Raman spectra provided predictive information complementary to clinical and metabolomic measurements for multiple dietary variables. Raman variation corresponding to {beta}-carotene equivalent could be traced to carotenoid-assigned bands and aligned with a broader plant-food-related dietary dimension. These findings show that habitual diet is represented not as a single biological state but through biologically traceable dietary dimensions distributed across complementary phenotypic layers.

bioinformatics↗

bioRxiv2025

Tegmental atrophy in isolated REM sleep behaviour disorder: Ex vivo-informed in vivo imaging

Isolated rapid eye movement (REM) sleep behaviour disorder (iRBD) is an early-stage synucleinopathy characterized by brainstem pathology. In rodents, the pontine tegmentum contains an REM sleep centre, the sublaterodorsal nucleus (SLD), which expresses corticotropin-releasing hormone binding protein (CRHBP). While the involvement of brainstem pathophysiology is thus implicated in iRBD, its solid evidence remains scarce in humans due to the difficulty in identifying small brainstem nuclei with conventional MRI technology alone. Here, we aimed to detect tegmental atrophy in iRBD with voxel-based morphometry (VBM) analysis combined with a novel human brainstem atlas. Structural MRIs from 98 patients with iRBD and 114 controls were analysed to investigate grey matter volume (GMV) using VBM. Our unique approach involved detailed assessments of the VBM results, guided by a high-resolution MRI-based atlas of the human brainstem. This brainstem atlas was founded on ex vivo MRI of 10 postmortem human specimens. We validated it with CRHBP immunostaining, which aided in identifying putative REM sleep-regulating nuclei in humans. We applied this brainstem atlas to identify atrophy in specific brainstem regions in iRBD and correlate their volumes with clinical measures, including autonomic functions. VBM revealed a focal cluster of grey matter atrophy in the dorsal pontine tegmentum of iRBD patients, including the laterodorsal tegmental nucleus, ventral part (LDTgV) and the pedunculopontine tegmental nucleus (PTg). Our atlas-based analysis confirmed the LDTgV as the site of most conspicuous atrophy, revealing a significant volume reduction in iRBD patients compared to controls with a moderate effect size (Cohens d = 0.46, Bonferroni-corrected p = 0.019). Furthermore, greater atrophy in the LDTgV and the PTg was associated with more severe autonomic dysfunction as measured by Scales for Outcomes in Parkinsons Disease-Autonomic dysfunction (SCOPA-AUT) scores (partial r = -0.237, p = 0.019 and partial r = -0.236, p = 0.019, respectively). Histological analysis confirmed that the LDTgV is selectively enriched with CRHBP-positive neurons, a putative marker for REM sleep-on neurons. We provided novel evidence for the involvement of LDTgV, the putative human homolog of the murine SLD, in iRBD. The present findings advance our understanding of the neuroanatomical basis of iRBD and will contribute to the development of early biomarkers for -synucleinopathies.

neuroscience↗

bioRxiv2024

Regional heterogeneities of oligodendrocytes determine biased distribution pattern of Ranvier nodes along single axons in sound localization circuit

Spacing of Ranvier nodes along myelinated axons is a critical determinant of conduction velocity, influencing spike arrival timing and hence neural circuit function. In the chick brainstem auditory circuit, the pattern of nodal spacing varies regionally along single axons, enabling precise binaural integration for sound localization. Using this model, we investigated the potential factors underlying the biased nodal spacing pattern. 3D morphometry revealed that these axons were almost fully myelinated by oligodendrocytes exhibiting distinct morphologies and cell densities across regions after hearing onset. The structure of axons did not affect internodal length. Inhibiting vesicular release from the axons did not affect internodal length or oligodendrocyte morphology, but caused unmyelinated segments on the axons by suppressing oligodendrogenesis near the presynaptic terminals. These results suggest that the regional heterogeneity in the intrinsic properties of oligodendrocytes is a prominent determinant of the biased nodal spacing pattern in the sound localization circuit, while activity-dependent signaling supports the pattern by ensuring adequate oligodendrocyte density. Our findings highlight the importance of oligodendrocyte heterogeneity in fine-tuning neural circuit function.

neuroscience↗

bioRxiv2020

Mutation Maker, An Open Source Oligo Design Software for Mutagenesis and De Novo Gene Synthesis Experiments

Protein engineering is the discipline of developing useful proteins for applications in research, therapeutic and industrial processes by modification of naturally occurring proteins or by invention of de novo proteins. Modern protein engineering relies on the ability to rapidly generate and screen diverse libraries of mutant proteins. However, design of mutant libraries is typically hampered by scale and complexity, necessitating development of advanced automation and optimization tools that can improve efficiency and accuracy. At present, automated library design tools are functionally limited or not freely available. To address these issues, we developed Mutation Maker, an open source mutagenic oligo design software for large-scale protein engineering experiments. Mutation Maker is not only specifically tailored to multi-site random and directed mutagenesis protocols, but also pioneers bespoke mutagenic oligo design for de novo gene synthesis workflows. Enabled by a novel bundle of orchestrated heuristics, optimization, constraint-satisfaction and backtracking algorithms, Mutation Maker offers a versatile toolbox for gene diversification design at industrial scale. Supported by in-silico simulations and compelling experimental validation data, Mutation Maker oligos produce diverse gene libraries at high success rates irrespective of genes or vectors used. Finally, Mutation Maker was created as an extensible platform on the notion that directed evolution techniques will continue to evolve and revolutionize current and future-oriented applications.

bioinformatics↗