Biology subjects

Takao, T.

Publications and source records attributed to Takao, T..

7 recordsLinked to original sources

bioRxiv2026

Structural characterization of a pseudaminic acid-modified lateral flagellar filament from Vibrio alginolyticus

Bacterial flagellar filaments are often modified by glycans, but the structural basis and physiological significance of flagellin glycosylation remain poorly understood in many species. Vibrio alginolyticus produces lateral flagella for surface-associated motility in viscous environments, with LafA forming its filament as flagellin. A maf homolog encoding a putative flagellin glycosylation factor is located immediately downstream of lafA, suggesting that the lateral filament is glycosylated. To investigate this possibility, we purified the lateral flagellar filament from V. alginolyticus and determined the structure at 2.37 [A] resolution by electron cryomicroscopy. Upon model building of LafA in the map, we identified additional densities connected to five serine residues, possibly corresponding to O-linked pseudaminic acid modifications. Mass spectrometric analyses identified these modifications as pseudaminic acid attached to Ser148, Ser173, Ser183, Ser189, and Ser197. Deletion of maf abolished lateral flagella formation and motility, and these defects were restored by complementation with maf. These results demonstrate that the Vibrio lateral flagellar filament is extensively modified by pseudaminic acid and that Maf is required for filament formation. Our findings provide the first structural insight into the glycosylation of Vibrio lateral flagellar filament and establish a framework for understanding the role of flagellin glycosylation in surface-associated motility.

microbiology↗

bioRxiv2026

The Role of Human-Specific lncRNA in Hyaline Cartilage Development

One of the distinctive characteristics of humans is their bipedalism. To achieve upright bipedal walking, the angles of the pelvis and femur have been altered. Although evolutionary hypotheses on the transition to bipedalism exist, the molecular mechanisms remain unclear. This study attempts to elucidate these mechanisms using a system for inducing hyaline cartilage-like tissue from human iPS cells via limb bud like mesenchymal cells. Focus was placed on non-coding RNAs, known for their potential in generating biological diversity. Bulk RNA sequencing was conducted to compare the expression and functions of human-specific long non-coding RNAs between limb bud like mesenchymal cells and induced hyaline cartilage-like tissue. The results indicated that human-specific lncRNAs, significantly upregulated in hyaline cartilage-like tissue, may regulate genes related to the extracellular matrix. These findings suggest the potential to develop regenerative cartilage tissue with enhanced ECM quality through controlling human-specific lncRNAs. Additionally, studying human-specific lncRNAs could elucidate mechanisms of diseases that are less common in other species but more prevalent in humans.

bioinformatics↗

bioRxiv2025

Scaffold-free cryopreservable cartilage grafts obtained from hiPSC-derived chondroprogenitor cells for airway reconstruction with growth adaptability

Pediatric tracheal reconstruction remains a major clinical challenge because of limited graft availability and the need for growth-adaptive materials. Current approaches, such as costal cartilage grafting and use of scaffold-based constructs, often suffer from complications including graft resorption, donor site morbidity, and poor integration. Here, we present scaffold-free cartilage grafts (chondro-plates) derived from expandable limb-bud mesenchymal cells generated from human leukocyte antigen-homozygous human induced pluripotent stem cells. These grafts are cryopreservable and maintain their hyaline cartilage phenotype after a brief pre-culture. In both rat and rabbit tracheal defect models, chondro-plates supported robust cartilage regeneration, epithelial reconstitution, and neovascularization. Importantly, in a pediatric-like growing rat model, chondro-plates preserved luminal patency and structural integrity, outperforming autologous costal cartilage. This study demonstrates a clinically viable, off-the-shelf strategy for tracheal reconstruction using scalable, immunocompatible, and growth-adaptive cartilage grafts.

bioengineering↗

bioRxiv2025

SGCRNA: Spectral Clustering-Guided Co-Expression Network Analysis Without Scale-Free Constraints for Multi-Omic Data

Weighted Gene Co-expression Network Analysis (WGCNA) is among the most widely employed methods in bioinformatics. WGCNA enables the identification of gene clusters (modules) exhibiting correlated expression patterns, the association of these modules with traits, and the exploration of candidate biomarker genes by focusing on hub genes within the modules. WGCNA has been successfully applied in diverse biological contexts. However, conventional algorithms manifest three principal limitations: the assumption of scale-free topology, the requirement for parameter tuning, and the neglect of regression line slopes. These limitations are addressed by SGCRNA. SGCRNA provides Julia functions for the analysis of co-expression networks derived from various types of biological data, such as gene expression data. The Julia packages and their source code are freely available at https://github.com/C37H41N2O6/SGCRNA.

bioinformatics↗

bioRxiv2025

Modeling the human limb skeletal development using human pluripotent stem cell-derived skeletal assembloid

Despite recent advances in pluripotent stem cell-based approaches to induce skeletal cells, recapitulating human limb skeletal development in terms of structure and longitudinally oriented growth remains an unresolved challenge. Here, we report a method to differentiate human pluripotent stem cells into region-specific skeletal organoids harboring GDF5+PRG4+ interzone/articular chondrocyte progenitors (IZ/ACPs) and SP7+ growth plate chondrocytes (GPCs) via PRRX1+ limb-bud mesenchymal cells. Comparative analysis demonstrated marked similarities of IZ/ACP and GPC organoids to the human embryonic limb, and graft fate and regenerative capacity in vivo were further characterized. We also mimicked the limb skeletal developmental process in a spatially structured manner by vertically positioning two IZ/ACP organoids at both ends of a GPC organoid to generate a human skeletal assembloid. Notably, this human skeletal assembloid recapitulated endochondral ossification with longitudinal skeletal growth upon transplantation. In summary, our study provides a novel research platform for human limb skeletal development and disease.

bioengineering↗

bioRxiv2024

Biological age prediction using a novel DNN model based on steroid metabolic pathways

Aging involves the progressive accumulation of cellular damage, leading to systemic decline and age-related diseases. Despite advances in medicine, accurately predicting Biological Age (BA) remains challenging due to the complexity of aging processes and the limitations of current models. This study introduces a novel method for predicting BA using a Deep Neural Network (DNN) based on steroid metabolic pathways. We analyzed 22 steroids from 148 serum samples of individuals aged 20 to 73, using 98 samples for model training and 50 for validation. Our model reflects the often-overlooked fact that aging heterogeneity expands over time and uncovers sex-specific variations in steroid interactions. This study identified key markers, including cortisol (COL), which underscore the role of stress-related and sex-specific steroids in aging. The resulting model establishes a biologically meaningful and robust framework for predicting BA across diverse datasets, supporting more targeted strategies in aging research and disease management.

bioinformatics↗

bioRxiv2022

Cleavage of the Jaw1 C-terminal region enhances its augmentative effect on the Ca2+ release via inositol 1,4,5-trisphosphate receptors

Jaw1, a tail-anchored protein with 39 carboxyl (C)-terminal amino acids, is oriented to the lumen of the endoplasmic reticulum and outer nuclear membrane. We previously reported that Jaw1, as a member of the KASH protein family, plays a role in maintaining nuclear shape via its C-terminal region. Furthermore, we recently reported that Jaw1 functions as an augmentative effector of Ca2+ release from the endoplasmic reticulum by interacting with the inositol 1,4,5-trisphosphate receptors (IP3Rs). Intriguingly, the C-terminal region is partially cleaved, meaning that Jaw1 exists in the cell in at least two forms: uncleaved and cleaved. However, the mechanism of the cleavage event and its physiological significance remain to be determined. In this study, we demonstrate that the C-terminal region of Jaw1 is cleaved after its insertion by the signal peptidase complex (SPC). Particularly, our results indicate that the SPC with the catalytic subunit SEC11A, but not SEC11C, specifically cleaves Jaw1. Furthermore, using a mutant with a deficit in the cleavage event, we demonstrate that the cleavage event enhances the augmentative effect of Jaw1 on the Ca2+ release ability of IP3Rs. Summary statementThe C-terminal region of Jaw1, a tail-anchored protein, is cleaved by signal peptidase complex and this cleavage event enhances the augmentative effect of Jaw1 on the Ca2+ release activity of inositol 1,4,5-trisphosphate receptors

cell biology↗