Biology subjects

Asakura, T.

Publications and source records attributed to Asakura, T..

8 recordsLinked to original sources

bioRxiv2026

Region-specific molecular regulatory programs define epithelial identity, progenitor states, and mucus homeostasis in human distal airways

Small distal airways differ from proximal large airways in structure, airflow dynamics, and epithelial composition, and represent a central site of muco-obstructive lung disease pathogenesis. However, due in part to their inaccessibility, the molecular mechanisms that establish regional epithelial identity and govern mucociliary defense in distal airway epithelia remain poorly defined. Here, we integrate transcriptomic, secretomic, and chromatin accessibility analyses of matched primary human large and small airway epithelial cultures to define region-specific regulatory networks. We identify distal airway-specific transcriptional and chromatin programs required for maintaining epithelial identity and mucus homeostasis. Loss of NKX2-1 impairs distal airway secretory cell (DASC) differentiation and shifts mucus properties toward a disease-associated state. Lineage-resolved organoid assays identify an NKX2-1-high distal airway basal cell population with hybrid basal-secretory features as a selective progenitor for DASCs. Collectively, these findings establish a molecular framework for distal airway epithelial biology and define mechanisms regulating region-specific mucociliary host defense.

Cell Biology↗

bioRxiv2025

Airway Epithelial SARS-CoV-2 Infectious and Repair Responses: Relationships to Age, Sex, and Post-COVID Pulmonary Syndromes

The long-term pulmonary sequelae of SARS-CoV-2 respiratory infections reflect infection severity, innate and adaptive immunity, and respiratory epithelial repair. This study investigated the acute and reparative responses as a function of age and sex in primary human bronchial epithelial (HBE) cultures utilizing a 14-day SARS-CoV-2 infection protocol. SARS-CoV-2 infection peaked at 3 days post-infection (dpi) with an [~] 2 log titer suppression at 14 dpi. SARS-CoV-2 infection induced interferon, interferon-induced gene, and cell damage responses. No age- or sex-dependent effects on SARS-CoV-2 infection were detected. Airway epithelia repaired to an abnormal mucus metaplastic/inflammatory state that reflected potentially beneficial and adverse consequences at 14 dpi. Repair processes were infection severity-dependent, not sex-dependent, and were more robust in young donor cultures. Analyses of long-COVID subjects with persistent pulmonary fibrosis or persistent bronchitic airway diseases exhibited expression of HBE 14 dpi failed repair gene signatures, including ISG gene signatures. Human airway epithelial repair post-SARS-CoV-2 is prolonged and incomplete in vitro over 14 days, and persistently abnormal repair may contribute to phenotypes of people with long-COVID pulmonary syndrome.

cell biology↗

bioRxiv2025

Data-Driven Feed Optimization for Sustainable Aquaculture through Integrated Omics Analysis and Two-stage Bayesian optimization

In aquaculture and livestock farming, developing feed that promotes efficient growth while minimizing environmental impact is crucial for sustainability. We developed a data-driven feed optimization system (DFOS) that integrates omics analysis with machine learning-based optimization technologies. First, DFOS employed Bayesian optimization (BO) to identify the optimal proportions of proteins and lipids, which are crucial feed components. Simultaneously, omics analysis was conducted to assess the physiological response of the targets to a given feed and identify key dietary components essential for growth. Next, BO was used to efficiently modify the combination and proportion of the specific additives identified in the first stage. We demonstrated the efficacy of DFOS by applying it to develop a new feed for the high-demand leopard coral grouper (Plectropomus leopardus) in Southeast Asia. This system provides an efficient data-driven framework for feed optimization across aquaculture and livestock, contributing significantly to more sustainable and productive farming practices.

ecology↗

bioRxiv2025

Repetitive stimulation modifies network characteristics of neural organoid circuits

Neural organoids form complex networks but lack external stimuli and hierarchical structures crucial for refining functional microcircuits. In this study, we modeled the hierarchical and modular network organization by connecting multiple organoids and tested if the connection enhances the external stimuli-induced network refinement. We cultured networks of one, two, or three organoids on high-density microelectrode arrays, applied repetitive stimulation at two input locations from the microelectrodes, and monitored emergence of output signals that can decode the stimulus locations with machine learning algorithms. After two weeks of daily stimulation, networks of three organoids showed significantly higher stimulus decoding capability compared to the simpler one- or two-organoid networks. Long-term stimulation induced pronounced changes in the three-organoid networks response patterns, spontaneous activity, and inter- and intra-organoid functional connectivity. These findings underscore the importance of hierarchical network organization, e.g. creating distinct subnetworks with specialized roles, for stimuli-induced formation of circuits with robust input-output functionality.

bioengineering↗

bioRxiv2024

Dysregulated Airway Host Defense in Hyper IgE Syndrome due to STAT3 Mutations

RationaleHyper IgE syndrome (STAT3-HIES), also known as Jobs syndrome, is a rare immunodeficiency disease typically caused by dominant-negative STAT3 mutations. STAT3-HIES syndrome is characterized by chronic pulmonary infection and inflammation, suggesting impairment of pulmonary innate host defense. ObjectivesTo identify airway epithelial host defense defects consequent to STAT3 mutations that, in addition to reported mutant STAT3 immunologic abnormalities, produce pulmonary infection. MethodsSTAT3-HIES sputum was evaluated for biochemical/biophysical properties. STAT3-HIES excised lungs were harvested for histology; bronchial brush samples were collected for RNA sequencing and in vitro culture. A STAT3-HIES-specific mutation (R382W), expressed by lentiviruses, and a STAT3 knockout, generated by CRISPR/Cas9, were maintained in normal human bronchial epithelia under basal or inflammatory (IL1{beta}) conditions. Effects of STAT3 deficiency on transcriptomics, and epithelial ion channel, secretory, antimicrobial, and ciliary functions were assessed. Measurements and Main ResultsMucus concentrations and viscoelasticity were increased in STAT3-HIES sputum. STAT3-HIES excised lungs exhibited mucus obstruction and elevated IL1{beta} expression. STAT3 deficiency impaired CFTR-dependent fluid and mucin secretion, inhibited expression of antimicrobial peptides, cytokines, and chemokines, and acidified airway surface liquid at baseline and post-IL1{beta} exposure in vitro. Notably, mutant STAT3 suppressed IL1R1 expression. STAT3 mutations also inhibited ciliogenesis in vivo and impaired mucociliary transport in vitro, a process mediated via HES6 suppression. Administration of a {gamma}-secretase inhibitor increased HES6 expression and improved ciliogenesis in STAT3 R382W mutant cells. ConclusionsSTAT3 dysfunction leads to multi-component defects in airway epithelial innate defense, which, in conjunction with STAT3-HIES immune deficiency, contributes to chronic pulmonary infection.

cell biology↗

bioRxiv2024

Comparative study on the accuracy of speech recognition using a contact microphone attached to the surface of the head and neck

The accuracy of speech recognition through an air-conducted microphone can be less accurate under a highly noisy environment or when the volume of the users voice is relatively low. One solution to this problem is the use of contact microphones. However, neither the microphone locations that provide optimal speech recognition accuracy for each user nor the mechanisms underlying these contact forces have been clarified. In this study, we experimentally investigated the effects of placement, contact force, user gender, and speech recognition platform on the accuracy of speech recognition with contact microphones placed on the surface of the head and neck. The experimental results indicated that the mechanism underlying the influence of each factor on speech recognition accuracy differs for speech acquired at the neck and head locations. In particular, the effect of the users gender was significant for the neck-acquired sound, but not the head-acquired sound. The results also revealed that the microphone contact force did not affect the recognition accuracy or user discomfort for the head-acquired sound. Moreover, the results of speech recognition experiments in a simulated noisy environment showed that bone-conducted sounds acquired on the head and neck surfaces were more robust than air-conducted sounds.

physiology↗

bioRxiv2022

A model of persistent post SARS-CoV-2 induced lung disease for target identification and testing of therapeutic strategies

COVID-19 survivors develop post-acute sequelae of SARS-CoV-2 (PASC), but the mechanistic basis of PASC-associated lung abnormalities suffers from a lack of longitudinal samples. Mouse-adapted SARS-CoV-2 MA10 produces an acute respiratory distress syndrome (ARDS) in mice similar to humans. To investigate PASC pathogenesis, studies of MA10-infected mice were extended from acute disease through clinical recovery. At 15-120 days post-virus clearance, histologic evaluation identified subpleural lesions containing collagen, proliferative fibroblasts, and chronic inflammation with tertiary lymphoid structures. Longitudinal spatial transcriptional profiling identified global reparative and fibrotic pathways dysregulated in diseased regions, similar to human COVID-19. Populations of alveolar intermediate cells, coupled with focal upregulation of pro-fibrotic markers, were identified in persistently diseased regions. Early intervention with antiviral EIDD-2801 reduced chronic disease, and early anti-fibrotic agent (nintedanib) intervention modified early disease severity. This murine model provides opportunities to identify pathways associated with persistent SARS-CoV-2 pulmonary disease and test countermeasures to ameliorate PASC.

microbiology↗

bioRxiv2020

A Novel DNA Chromatography Method to Distinguish M. abscessus Subspecies and Macrolide Susceptibility

RationaleThe clinical impact of infection with Mycobacterium abscessus complex (MABC), a group of emerging non-tuberculosis mycobacteria (NTM), is increasing. Mycobacterium abscessus subsp. abscessus/bolletii frequently shows natural resistance to macrolide antibiotics, whereas Mycobacterium abscessus subsp. massiliense is generally susceptible. Therefore, rapid and accurate discrimination of macrolide-susceptible MABC subgroups is required for effective clinical decisions about macrolide treatments for MABC infection. ObjectivesTo develop a simple and rapid diagnostic that can identify MABC isolates showing macrolide susceptibility. MethodsWhole genome sequencing (WGS) was performed for 148 clinical or environmental MABC isolates from Japan to identify genetic markers that can discriminate three MABC subspecies and the macrolide-susceptible erm(41) T28C sequevar. Using the identified genetic markers, we established PCR based- or DNA chromatography-based assays. Validation testing was performed using MABC isolates from Taiwan. Measurements and Main ResultsWe identified unique sequence regions that could be used to differentiate the three subspecies. Our WGS-based phylogenetic analysis indicated that M. abscessus carrying the macrolide-susceptible erm(41) T28C sequevar were tightly clustered, and identified 11 genes that were significantly associated with the lineage for use as genetic markers. To detect these genetic markers and the erm(41) locus, we developed a DNA chromatography method that identified three subspecies, the erm(41) T28C sequevar and intact erm(41) for MABC in a single assay within one hour. The agreement rate between the DNA chromatography-based and WGS-based identification was 99.7%. ConclusionsWe developed a novel, rapid and simple DNA chromatography method for identification of MABC macrolide susceptibility with high accuracy.

microbiology↗