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Biology subjects

Ohkura, N.

Publications and source records attributed to Ohkura, N..

6 recordsLinked to original sources

Collective AI use is associated with researcher engagement: Real-time evidence from a scientific conference

Recent large-scale bibliometric analyses suggest that individual AI use can increase productivity while reducing downstream engagement and topic diversity. Here we ask whether collective AI deployment is associated with shared engagement. Using an Audience Response Engagement (ARE) system at NGS Expo 2025 (N=110 biomedical researchers), we captured real-time consensus and generated updated visualizations within minutes. Our data reveal a substantial gap between adoption and transparency: 93.6% of researchers use AI at least weekly, yet only 5.5% consistently disclose this usage--a 17-fold disparity. This pattern is consistent with systemic policy uncertainty (39.1% report unclear guidelines). Behavioral clustering identifies a "High-Concern" group (31%) as a candidate for targeted interventions: highest productivity yet lowest disclosure. These findings suggest that collective AI deployment in physical settings is associated with shared engagement.

scientific communication and education↗

Oral antigen exposure under co-stimulation blockade generates Treg cells to establish immune tolerance despite prior sensitization

Antigen-specific oral tolerance is effective in preventing harmful immune responses in antigen-non-sensitized animals but difficult to be induced in those already antigen-primed. Here, we show in mice that feeding of antigen-containing diet generates peripherally derived regulatory T (pTreg) cells that exhibit a tissue-adapted effector phenotype. The antigen feeding also enables the generated pTreg cells to acquire Treg-specific epigenomic changes in Treg signature genes including Foxp3, hence the stability of Treg-specific function. Cessation of antigen feeding, however, results in decline in oral tolerance with diminution of pTreg cells. Transcriptomic analysis has revealed that the induced pTreg cells predominantly express CD101. CD101+ Treg cells with a similar phenotype and epigenetic alterations can also be generated in vitro from antigen-primed naive CD4+ T cells by blockade of CD28-mediated co-stimulation during TGF-{beta}-dependent Treg induction. Furthermore, in vivo CD28 signal blockade by CTLA-4-immunoglobulin fusion protein (CTLA4-Ig) before antigen feeding can establish oral tolerance in the mice precedingly antigen-sensitized by a non-oral route. The blockade facilitates differentiation of antigen-specific conventional T cells into CD101+ pTreg cells. Thus, continuous oral antigen administration combined with CD28 co-stimulation blockade generates CD101+ antigen-specific functionally stable pTreg cells, which can establish long-term systemic antigen-specific immune tolerance even in antigen-pre-sensitized animals.

immunology↗

Spatial transcriptomics elucidates medulla niche supporting germinal center response in myasthenia gravis thymoma

Myasthenia gravis (MG) is known to be epidemiologically associated with abnormalities of the thymus, an organ that maintains central tolerance. However, due to the complexity of the thymus, specific characteristics related to the pathogenesis of MG remain elusive. In our study, we attempted to narrow down the features associated with MG using spatial transcriptome analysis of thymoma and thymic hyperplasia samples. We found that the majority of thymomas were constituted by the cortical region, whereas the medullary region was localized in comparatively restricted areas. Moreover, the medullary region contained polygenic enrichment, MG-specific germinal center structures, and a supporting immune microenvironment. Additionally, neuromuscular medullary thymic epithelial cells (nmTECs), previously identified as MG-specific autoantigen-producing cells, were situated at the cortico-medullary junction. The immune microenvironment in the medulla was characterized by a specific chemokine pattern and specific immune cells, such as CCR7+ migratory dendritic cells (migDCs) and effector regulatory T (Treg) cells. Furthermore, similar germinal center structures and immune microenvironments were observed in the medulla during thymic hyperplasia. This study indicates that the medulla and junction areas are related to the pathology of MG, suggesting that these areas should be the focus of future studies on MG pathogenesis and drug targeting.

immunology↗

Single-cell transcriptome landscape of circulating CD4+ T cell populations in human autoimmune diseases

CD4+ T cells are a key mediator of various autoimmune diseases; however, how they contribute to disease development remains obscure primarily because of their cellular heterogeneity. Here, we evaluated CD4+ T cell subpopulations by decomposition-based transcriptome characterization together with canonical clustering strategies. This approach identified 12 independent transcriptional gene programs governing whole CD4+ T cell heterogeneity, which can explain the ambiguity of canonical clustering. In addition, we performed a meta-analysis using public single-cell data sets of over 1.8M peripheral CD4+ T cells from 953 individuals by projecting cells onto the reference and cataloged cell frequency and qualitative alterations of the populations in 20 diseases. The analyses revealed that the 12 transcriptional programs were useful in characterizing each autoimmune disease and predicting its clinical status. Moreover, genetic variants associated with autoimmune diseases showed disease-specific enrichment within the 12 gene programs. The results collectively provide a landscape of single-cell transcriptomes of CD4+ T cell subpopulations involved in autoimmune disease.

immunology↗

Myasthenia gravis-specific aberrant neuromuscular gene expression by medullary thymic epithelial cells in thymoma

Myasthenia gravis (MG) is a neurological disease caused by autoantibodies against neuromuscular-associated proteins. While MG is frequently developed in thymoma patients, the etiologic factors for MG are not well understood. Here, by constructing a comprehensive atlas of thymoma using bulk and single-cell RNA-seq, we identified ectopic expression of neuromuscular molecules in MG-associated thymoma (MG-thymoma). These molecules were originated from a distinct subpopulation of medullary thymic epithelial cells (mTECs), which we named neuromuscular mTECs (nmTECs). MG-thymoma also exhibited microenvironments dedicated to autoantibody production, including ectopic germinal center formation, T follicular helper cell accumulation, and type 2 conventional dendritic cell migration. Cell-cell interaction analysis also predicted the interaction between nmTECs and T/B cells via CXCL12-CXCR4. The enrichment of nmTECs presenting neuromuscular molecules within MG-thymoma was further confirmed by immunohistochemically and by cellular composition estimation from MG-thymoma transcriptome. Altogether, this study suggests that nmTECs play a significant role in MG pathogenesis via ectopic expression of neuromuscular molecules.

immunology↗

VIRTUS: a pipeline for comprehensive virus analysis from conventional RNA-seq data

The possibility that RNA transcripts from clinical samples contain plenty of virus RNAs has not been pursued actively so far. We here developed a new tool for analyzing virus-transcribed mRNAs, not virus copy numbers, in the data of conventional and single-cell RNA-sequencing of human cells. Our pipeline, named VIRTUS (VIRal Transcript Usage Sensor), was able to detect 763 viruses including herpesviruses, retroviruses, and even SARS-CoV-2 (COVID-19), and quantify their transcripts in the sequence data. This tool thus enabled simultaneously detecting infected cells, the composition of multiple viruses within the cell, and the endogenous host gene expression profile of the cell. This bioinformatics method would be instrumental in addressing the possible effects of covertly infecting viruses on certain diseases and developing new treatments to target such viruses. Availability and implementationVIRTUS is implemented using Common Workflow Language and Docker under a CC-NC license. VIRTUS is freely available at https://github.com/yyoshiaki/VIRTUS. Supplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗