Biology subjects

Yasuda, M.

Publications and source records attributed to Yasuda, M..

9 recordsLinked to original sources

bioRxiv2026

The Onset of Breathing at Birth Switches Off Regenerative Capacity

Many mammalian tissues, including the central nervous system (CNS), lose regenerative capacity in adulthood, but when and how this transition is initiated remains unclear. By monitoring mTOR activity, an evolutionarily conserved readout of cellular growth and intrinsic regenerative potential, we found that mTOR signaling declines within minutes after birth in murine CNS neurons and in other organs such as the heart and skeletal muscles. Focusing on retinal ganglion cells (RGCs), we show that this abrupt decline is driven primarily by CO2 exhalation following the onset of breathing after birth. Using real-time in vivo imaging of RGCs during the earliest postnatal period, we further discover that breathing-induced CO2 exhalation rapidly causes intracellular alkalinization, activates an AMPK-family kinase, SNF-related kinase (SNRK), which in turn suppresses mTOR signaling. Importantly, this process remains reversible in adulthood: CO2 inhalation or Snrk deletion restores mTOR activity in RGCs and enables robust regeneration of their axons after injury. Similar CO2 inhalation-induced mTOR reactivation occurs across multiple cell types and organs, suggesting a general mechanism by which breathing-associated CO2/pH signaling shapes the regenerative capacity across life and pointing to a potential CO2-based strategy for promoting tissue regeneration.

neuroscience↗

bioRxiv2026

Reconstruction of FACS-partitioned Adaptive Immune Receptor Repertoires from FACS-partitioned B and T Cell Subsets

Adaptive immune-receptor repertoire sequencing (AIRRseq) is crucial for understanding immune system diversity and its relationship to disease dynamics. Partitioning of total B and T cells into their major subsets with distinct immunological functions - IgM+ vs. class-switched B cells (IgG+ > IgA+) and CD4+ vs. CD8+ T cells, respectively - allows for AIRRseq-based analysis of the unique contributions of each compartment to the overall immune response, a major advantage over traditional bulk sequencing workflows. However, data from these subsets is not directly comparable with the vast majority of publicly available AIRRseq data, which comes from unfractionated B and T cells, an important incompatibility. Here we investigate computational methods for reconstructing complete AIRRseq repertoires from partitioned B and T cell subsets in diverse individuals. Peripheral blood mononuclear cells (PBMCs) were partitioned via positive selection of IgM+ B-cell subsets and CD4+ T cells using immunomagnetic beads; genomic DNA was then extracted and B- and T-cell receptors were sequenced. Four reconstruction methods are introduced and evaluated for concordance with matching unpartitioned repertoires to assess preservation of key repertoire characteristics. Results show that these methods enable accurate estimates of overall immune-repertoire diversity from B- and T-cell subsets in a way that simply pooling the sequence data from sub-repertoires cannot.

immunology↗

bioRxiv2025

HuBIE: The Human Blood Immunome Encyclopedia Of TCRs and BCRs in Bloodstream Infections and Cancer

T and B cells are central to adaptive immunity, where they identify and neutralize foreign antigens and cancer neo-antigens. Large-scale elucidation of T- and B-cell receptors (TCRs and BCRs) through immune-repertoire sequencing promises novel diagnostics, prognostic markers, and therapeutic strategies. However, progress is hampered by small cohort sizes, a lack of real-world patient diversity, and heterogeneous sample processing, impeding cross-study comparability. To overcome these limitations, here we introduce the Human Blood Immunome Encyclopedia (HuBIE), comprising immune-repertoire data from 2,614 samples collected from 1,941 participants. The cohort includes a range of bloodstream infections, several cancer types, and control participants, with many individuals providing longitudinal samples. We employed Roches immune receptor Primer Extension Target Enrichment (immunoPETE) platform to perform simultaneous targeted sequencing of T-cell receptor {beta} chains (TRB), T-cell receptor {delta} chains (TRD), and immunoglobulin heavy chains (IGH), thereby profiling TCRs and BCRs in all participants. We provide a comprehensive description of immune-repertoire diversity in cancer and bloodstream infections and examine variations across demographic variables such as age and race. We find significant differences in TRB and IGH composition across ethnic groups, and show that the fall in repertoire diversity with age follows distinct patterns for TRB, TRD, and IGH and is accompanied by age-related differences in VJ gene usage. Finally we demonstrate that greater immunological diversity is associated with improved survival but only for elderly participants. HuBIE thus constitutes a valuable resource for the immune-repertoire community, enabling large-scale mapping of the human immunome to accelerate development of diagnostics, prognostic biomarkers, and innovative therapeutic strategies.

immunology↗

bioRxiv2024

Key taxa of the gut microbiome associated with the relationship between environmental sensitivity and inflammation-related biomarkers

BackgroundIndividual differences in environmental sensitivity are linked to stress-related psychiatric symptoms. In previous research, we found that high environmental sensitivity can be a risk factor for increased inflammation and gut permeability, particularly when gut microbiome diversity is low. However, the specific gut bacterial taxa involved in this interaction remain unclear. This study aimed to identify the key gut microbiome taxa associated with this relationship. MethodsEnvironmental sensitivity, gut microbiome composition, gut permeability (lipopolysaccharide-binding protein, LBP) and inflammation (C-reactive protein, CRP) biomarkers were evaluated in 88 participants. ResultsThe interaction between environmental sensitivity and the relative abundance of the family Marinifilaceae (genus Butyricimonas) was a predictor of CRP levels. Similarly, the interaction between environmental sensitivity and relative abundance of the family Barnesiellaceae (genus Coprobacter), the family Akkermansiace (genus Akkermansia), the genus Family XIII AD3011 group, the genus GCA-900066225, or the genus Ruminiclostridium 1 predicted LBP levels. Individuals with high environmental sensitivity exhibited elevated CRP or LBP levels when the relative abundance of these taxa was low. Conversely, highly sensitive individuals had lower CRP or LBP levels when the relative abundance of these taxa was high. ConclusionThis study suggests that specific taxa serve as one of the protective factors against inflammation and gut permeability in individuals with high environmental sensitivity.

microbiology↗

bioRxiv2023

Contrasting Effects of SARS-CoV-2 Vaccination vs. Infection on Antibody and TCR Repertoires

Antibodies and helper T cells play important roles in SARS-CoV-2 infection and vaccination. We sequenced B- and T-cell receptor repertoires (BCR/TCR) from the blood of 251 infectees, vaccinees, and controls to investigate whether features of these repertoires could predict subjects SARS-CoV-2 neutralizing antibody titer (NAbs), as measured by enzyme-linked immunosorbent assay (ELISA). We sequenced recombined immunoglobulin heavy-chain (IGH), TCR{beta} (TRB), and TCR{delta} (TRD) genes in parallel from all subjects, including select B- and T-cell subsets in most cases, with a focus on their hypervariable CDR3 regions, and correlated this AIRRseq data with demographics and clinical findings from subjects electronic health records. We found that age affected NAb levels in vaccinees but not infectees. Intriguingly, we found that vaccination and infection have an effect on non-productively recombined IGHs, suggesting an effect that precedes clonal selection. We found that repertoires binding capacity to known SARS-CoV-2-specific CD4+ TRBs performs as well as the best hand-tuned approximate or "fuzzy" matching at predicting a protective level of NAbs, while also being more robust to repertoire sample size and not requiring hand-tuning. The overall conclusion from this large, unbiased, clinically well annotated dataset is that B- and T-cell adaptive responses to SARS-CoV-2 infection and vaccination are surprising, subtle, and diffuse. We discuss methodological and statistical challenges faced in attempting to define and quantify such strong-but-diffuse repertoire signatures and present tools and strategies for addressing these challenges.

immunology↗

bioRxiv2023

Interactions between environmental sensitivity and gut microbiota are associated with biomarkers of stress-related psychiatric symptoms

BackgroundHumans vary in their sensitivity to stressful and supportive environments and experiences. Such individual differences in environmental sensitivity are associated with mechanisms of stress-related psychiatric symptoms. In recent years, researchers have focused on bidirectional interactions in the brain-gut-microbiota axis as a neurophysiological pathway contributing to the mechanisms of stress-related psychiatric symptoms, and evidence is rapidly accumulating. MethodsData on environmental sensitivity, gut microbiota, gut permeability (lipopolysaccharide-binding protein; LBP) and inflammation (C-reactive protein; CRP) were collected from 90 adults (50% female; Mage = 42.1; SDage = 10.0). Environmental sensitivity was measured using a self-report questionnaire. Study participants feces were analyzed, and observed operational taxonomic units for richness, Shannons index for evenness, and phylogenetic diversity for biodiversity were evaluated as indicators of gut microbiota. In addition, participants serum was analyzed for CRP and LBP. We investigated whether the interaction between environmental sensitivity and gut microbiota is associated with biomarkers of inflammation and gut permeability. ResultsThe interaction between environmental sensitivity and gut microbiota (excluding the Shannons index) explained the levels of these biomarkers. Individuals with high environmental sensitivity displayed higher levels of CRP and LBP, when the richness and diversity of the gut microbiota was low. However, even highly susceptible individuals had lower levels of CRP and LBP, when the richness and diversity of the gut microbiota was high. ConclusionsOur study indicates that high environmental sensitivity can be a risk factor for inflammation and gut permeability, when the gut microbiota diversity is low, suggesting a brain-gut-microbiota axis interaction.

microbiology↗

bioRxiv2022

PTEN-induced kinase 1 gene single-nucleotide variants as biomarkers in adjuvant chemotherapy for colorectal cancer

BackgroundFluoropyrimidine-based adjuvant chemotherapy is globally recommended for postoperative stage III colon cancer and high-risk stage II patients. However, adjuvant chemotherapy is often associated with severe adverse events and is not highly effective in preventing recurrence. Therefore, a recurrence-prevention biomarker of adjuvant chemotherapy for colorectal cancer is necessary for providing such treatments to appropriate patients. Autophagy (including mitophagy) is activated under chemotherapy-induced stress and contributes to chemotherapy resistance. Expression of autophagy-related genes and their single-nucleotide polymorphisms are reported to be effective predictors of chemotherapy response in some cancers. Our goal was to evaluate the relationship between the single-nucleotide variants of autophagy-related genes and recurrence rates to identify the recurrence-prevention biomarkers of adjuvant chemotherapy in colorectal cancer. MethodsWe analyzed surgical or biopsy specimens from 84 patients who underwent radical surgery followed by fluoropyrimidine-based adjuvant chemotherapy at Saitama Medical University International Medical Center between January and December 2016. Using targeted enrichment sequencing, we identified single-nucleotide variants and insertions/deletions in 50 genes, including autophagy-related genes, and examined their association with colorectal cancer patient relapse rates. ResultsWe detected 560 single-nucleotide variants or insertions/deletions in the target region. The results of Fishers exact test indicated that the recurrence rate of colorectal cancer after adjuvant chemotherapy was significantly lower in patients with the single- nucleotide variants (c.1018G>A [p < 0.005] or c.1562A>C [p < 0.01]) of the mitophagy-related gene PTEN-induced kinase 1. ConclusionsThe two single-nucleotide variants of this mitophagy-related gene may be biomarkers of non-recurrence in colorectal cancer patients who received postoperative adjuvant chemotherapy.

cancer biology↗

bioRxiv2020

Emergence and evolution of antimicrobial resistance genes and mutations in Neisseria gonorrhoeae

Antimicrobial resistance in Neisseria gonorrhoeae is a global health concern. Strains from two internationally circulating sequence types, ST-7363 and ST-1901, have acquired resistance to treatment with third-generation cephalosporins mainly due to the emergence of mosaic penA alleles. These two STs were first detected in Japan; however, when and how the mosaic penA alleles emerged and spread to other countries remains unknown. Here, we addressed the evolution of penA alleles by obtaining complete genomes from three Japanese ST-1901 clinical isolates harboring mosaic penA allele 34 (penA-34) dating from 2005 and generating a phylogenetic representation of 1,075 strains sampled from 37 countries. We also sequenced the genomes of 103 Japanese ST-7363 N. gonorrhoeae isolates from 1996-2005 and reconstructed a phylogeny including 88 previously sequenced genomes. Based on an estimate of the time of emergence of ST-1901 harboring mosaic penA-34 and ST-7363 harboring mosaic penA-10, and >300 additional genome sequences of Japanese strains representing multiple STs isolated in 1996-2015, we suggest that penA-34 in ST-1901 was generated from penA-10 via recombination with another Neisseria species, followed by a second recombination event with a gonococcal strain harboring wildtype penA-1. Following the acquisition of penA-10 in ST-7363, a dominant sub-lineage rapidly acquired fluoroquinolone resistance mutations at GyrA 95 and ParC 87-88, possibly due to independent mutations rather than horizontal gene transfer. Literature data suggest the emergence of these resistance determinants may reflect selection from the standard treatment regimens in Japan at that time. Our findings highlight how recombination and antibiotic use across and within Neisseria species intersect in driving the emergence and spread of drug-resistant gonorrhea. Author summaryAntimicrobial resistance is recognized as one of the greatest threats to human health, and Neisseria gonorrhoeae resistance is classified as one of the most urgent. The two major internationally spreading lineages resistant. to first line drugs likely originated in Japan, but when and how their genetic resistance determinants emerged remain unknown. In this study, we conducted an evolutionary analysis using clinical N. gonorrhoeae isolates from 37 countries, including a historical collection of Japanese isolates, to investigate the emergence of resistance in each of the two major lineages. We showed that the penA allele responsible for resistance to cephalosporins, the first-line treatment for gonorrhea, was possibly generated by two recombination events, one from another Neisseria species and one from another N. gonorrhoeae lineage. We also showed that mutations responsible for resistance to a previously widely used antibiotic treatment occurred twice independently in one of the two major lineages. The emergence of the genetic resistance determinants potentially reflects selection from the standard treatment regimen at that time. Our findings highlight how recombination (horizontal gene transfer) and antibiotic use across and within a bacterial species intersect in driving the emergence and spread of antimicrobial resistance genes and mutations.

microbiology↗

bioRxiv2020

Iodine staining as a useful probe for distinguishing amyloid fibril polymorphs

ABSTRACTIt is recently suggested that amyloid polymorphism, i.e., structural diversity of amyloid fibrils, has a deep relationship with pathology. However, its prompt recognition is almost halted due to insufficiency of analytical methods for detecting polymorphism of amyloid fibrils sensitively and quickly. Here, we propose that iodine staining, a historically known reaction that was firstly found by Virchow, can be used as a method for distinguishing amyloid polymorphs. When insulin fibrils were prepared and iodine-stained, they exhibited different colors depending on polymorphs. Each of the colors was inherited to daughter fibrils by seeding reactions. The colors were fundamentally represented as a sum of three absorption bands in visible region between 400-750 nm, and the bands showed different titration curves against iodine, suggesting that there are three specific iodine binding sites. The analysis of resonance Raman spectra and polarization microscope suggested that several polyiodide ions composed of I3− and/or I5− were formed on the grooves or the edges of β-sheets. It was concluded that the polyiodide species and conformations formed are sensitive to surface structure of amyloid fibrils, and the resultant differences in color will be useful for detecting polymorphism in a wide range of diagnostic samples.Competing Interest StatementThe authors have declared no competing interest.View Full Text

biochemistry↗