Biology subjects

Ichikawa, S.

Publications and source records attributed to Ichikawa, S..

9 recordsLinked to original sources

bioRxiv2026

Gut bacterial composition and predicted functional profiles associated with depressive symptom burden in Japanese adults recruited independently of depression diagnosis

Reported associations between depressive symptoms and the gut microbiota have been inconsistent, particularly with respect to predicted microbial function. We conducted an exploratory cross-sectional study of 17 adults to examine associations of depressive symptom burden with fecal bacterial composition and predicted functional potential. Depressive symptoms were assessed using the Japanese version of the Center for Epidemiologic Studies Depression Scale (CES-D); 13 participants scored <16 and 4 met the screening cutoff ([≥]16) for elevated depressive symptoms. Bacterial communities were profiled by 16S ribosomal RNA gene sequencing. Weighted UniFrac community structure differed between groups by permutational multivariate analysis of variance. Exploratory taxonomic analysis identified 31 features differentiating the groups. Among features enriched in the higher CES-D group, those assigned to Veillonella, Parabacteroides, and Porphyromonadaceae showed the highest linear discriminant analysis scores, whereas Firmicutes and several Lachnospiraceae- and Ruminococcaceae-related taxa were enriched in the lower CES-D group. PICRUSt2-predicted functional profiles differed between groups across four annotation systems. At the MetaCyc pathway level, the lower CES-D group showed nominally higher predicted purine salvage and several amino acid, phospholipid, and coenzyme A biosynthesis I pathways, whereas the higher CES-D group showed nominally higher predicted de novo pyrimidine deoxyribonucleotide biosynthesis, several TCA-cycle variants, glucose/xylose and N-acetylneuraminate degradation, the glycolysis/Entner-Doudoroff superpathway, and the urea cycle. These findings provide exploratory evidence that depressive symptom burden is associated with gut bacterial composition and predicted functional profiles among Japanese adults recruited independently of depression diagnosis.

microbiology↗

bioRxiv2026

DNA cytosine methylation modulates UV resistance and nucleotide excision repair gene expression in Escherichia coli

Bacterial survival after ultraviolet (UV) exposure is shaped not only by the extent of DNA damage but also by the physiological state-dependent capacity for DNA repair. Here, we examined the mechanisms underlying growth phase-dependent UV resistance in Escherichia coli K-12 exposed to 262 nm UV irradiation. Stationary-phase cells required higher UV fluence for log inactivation than exponential-phase cells, whereas the levels of UV-induced DNA damage, assessed by cyclobutane pyrimidine dimer staining and real-time PCR, did not differ markedly between the two growth phases. Deletion of nucleotide excision repair (NER) genes, including uvrA, uvrB, uvrC, and uvrD, markedly reduced survival after UV irradiation, indicating that NER is essential for the high UV resistance of stationary-phase cells. Quantitative real-time reverse transcription PCR showed stronger UV-induced expression of several DNA repair and UV resistance genes, including uvrA, uvrB, cho, umuC, and umuD, in stationary-phase cells than in exponential-phase cells. Furthermore, deletion of the DNA cytosine methyltransferase gene dcm increased UV resistance and enhanced the expression of uvrB, cho, umuC, umuD, and sulA in stationary-phase cells. These findings suggest that DNA cytosine methylation modulates UV resistance in E. coli, at least in part by influencing NER- and SOS-associated gene expression.

microbiology↗

bioRxiv2026

Gut microbiome composition and predicted functions relate to growth and behavior in a Japanese preschool cohort

Early childhood is a period of rapid brain maturation and gut microbiome assembly, when emerging behavioral difficulties can shape later mental health and learning trajectories. Microbiota-gut-brain communication has been implicated in neurodevelopment through microbial metabolites and immune signaling. However, most pediatric evidence comes from high-risk or clinically referred cohorts, and gut microbiome-related correlates of typical behavioral variation in community-based preschool children remain poorly defined. In a cross-sectional sample of typically developing Japanese preschool children, here we show that behavioral variation within normative ranges is associated with distinct microbiome configurations: internalizing domains cluster with signatures consistent with higher inflammatory potential and elevated nucleotide biosynthesis, whereas somatic complaints and withdrawn behavior associate with reduced respiratory and fermentative activity. Sleep-related difficulties show the broadest predicted functional footprint, including enrichment of pathways related to methyl-donor and heme biosynthesis, while externalizing domains associate with pathways involved in cell-envelope and carbohydrate remodeling. In contrast, age, height, and weight track canonical maturation of gut microbiome composition, indicating that behavioral associations are not simple proxies of growth. Together, these findings extend early-life microbiome research by resolving domain-specific associations in a low-risk Asian community sample and highlighting pathway-level candidates that may interface with neurodevelopment.

microbiology↗

bioRxiv2026

Two-step polar plastid migration via F-actin and microtubules ensures unequal inheritance during asymmetric division of Arabidopsis zygote

The zygote is the origin of development, and in most angiosperms, it divides asymmetrically to establish the apical-basal axis. In Arabidopsis thaliana, various organelles in the zygote undergo polar migration along actin filaments (F-actin), resulting in unequal inheritance, but the behavior of plastids, essential precursors of chloroplasts, has remained unclear. Here, using quantitative live-cell imaging, we reveal that plastids undergo two-step polar migration: they first move apically together with the nucleus along F-actin, and when nuclear migration slows, they switch to microtubule (MT)-dependent migration to move further apically. This results in unequal plastid inheritance by the apical cell. Although these plastids are amyloplasts containing starch granules, starch is dispensable for migration, unlike the gravity response. Instead, a fertilization-activated MAP kinase pathway is required for polar plastid migration. Our results demonstrate that the zygote possesses a spatiotemporal regulatory mechanism that ensures unequal plastid inheritance at the onset of plant ontogeny.

plant biology↗

bioRxiv2025

Multi-omics Analysis of Human Blood Cells Reveals Unique Features of Age-associated Type2 CD8 Memory T cells

Aging impacts immune function, but the mechanisms driving age-related changes in immune cell subsets remain unclear. To explore age-dependent changes in immune cell populations, we analyzed human peripheral blood mononuclear cells (PBMCs) from a cohort of healthy donors aged 20-82 years using a 36-color spectral flow cytometry panel focused on T cells. We identified a unique population of memory CD8 T cells, which lack CXCR3 and produce a Th2-like cytokine response, accumulate with age. We discovered an age-dependent bias in naive CD8 T cells toward Th2 cytokine production, accompanied by transcriptional and epigenetic changes supporting this phenotype. Moreover, health outcome association analysis linked the accumulation of these unique CXCR3- central memory CD8 T cells to asthma, chronic liver conditions, and type 2 diabetes. Together, our results support the model that an age-dependent drift in epigenetic regulation towards a Th2-like phenotype drives a pathogenic Th2-like immune population.

immunology↗

bioRxiv2025

Induced tolerance to UV stress drives survival heterogeneity in isogenic E. coli cell populations

The emergence of transiently tolerant bacterial subpopulations challenges our understanding of stress tolerance mechanisms. While much is known about antibiotic tolerance, it remains unclear whether similar mechanisms contribute to survival under ultraviolet (UV) stress. Here, we employed a modified Luria-Delbruck fluctuation test to investigate the presence of pre-existing UV-tolerant subpopulations in Escherichia coli. Our results showed no significant evidence of pre-stress UV tolerance. Instead, the data suggest that survival is primarily driven by inducible DNA repair responses activated after UV exposure. Furthermore, sequential low-dose UV exposures yielded higher-than-expected survival, suggesting that transient tolerance can be induced following initial UV exposure, likely through active DNA repair processes. These findings indicate that E. coli survives UV stress via an induced, rather than pre-existing, mechanism of tolerance.

microbiology↗

bioRxiv2023

Brefeldin A and M-COPA block the export of RTKs from the endoplasmic reticulum via simultaneous inactivation of ARF1, ARF4, and ARF5

Normal receptor tyrosine kinases (RTKs) need to reach the plasma membrane (PM) for ligand-induced activation, whereas its cancer-causing mutants can be activated before reaching the PM in organelles, such as the Golgi/trans-Golgi network (TGN). Inhibitors of protein export from the endoplasmic reticulum (ER), such as brefeldin A (BFA) and 2-methylcoprophilinamide (M-COPA), can suppress the activation of mutant RTKs in cancer cells, suggesting that RTK mutants cannot initiate signaling in the ER. BFA and M-COPA block the function of ADP-ribosylation factors (ARFs) that play a crucial role in ER-Golgi protein trafficking. However, which ARFs among AFR family proteins are inhibited by BFA or M-COPA, that is, which ARFs are involved in RTKs transport from the ER, remain unclear. In this study, we showed that M-COPA blocked the export of not only KIT but also PDGFRA/EGFR/MET RTKs from the ER. ER-retained RTKs could not fully transduce anti-apoptotic signals, thereby leading to cancer cell apoptosis. Moreover, single knockdown of ARF1, ARF3, ARF4, ARF5, or ARF6 could not block ER export of RTKs, indicating that BFA/M-COPA treatment cannot be mimicked by knockdown of only one ARF member. Interestingly, simultaneous transfection of ARF1, ARF4, and ARF5 siRNAs mirrored the effect of BFA/M-COPA treatment. Consistent with these results, in vitro pulldown assays showed that BFA/M-COPA blocked the function of ARF1, ARF4, and ARF5. Taken together, these results suggest that BFA/M-COPA targets at least ARF1, ARF4, and ARF5; in other words, RTKs require the simultaneous activation of ARF1, ARF4, and ARF5 for their ER export.

cell biology↗

bioRxiv2023

Determining the structure of protein-bound ceramides, essential lipids for skin barrier function

Protein-bound ceramides, specialized ceramides covalently bound to corneocyte surface proteins, are essential for skin permeability barrier function. However, their exact structure and target amino acid residues are unknown. Here, we found that epoxy-enone (EE) ceramides, precursors of protein-bound ceramides, as well as their synthetic analog, formed stable conjugates only with Cys among nucleophilic amino acids. NMR spectroscopy revealed that the {beta}-carbon of the enone was attached by the thiol group of Cys via a Michael addition reaction. We confirmed the presence of Cys-bound EE ceramides in mouse epidermis by mass spectrometry analysis of protease-digested epidermis samples. EE-ceramides were reversibly released from protein-bound ceramides via sulfoxide elimination. We found that protein-bound ceramides with reversible release properties accounted for approximately 60% of total protein-bound ceramides, indicating that Cys-bound EE ceramides are the predominant protein-bound ceramides. Our findings provide clues to the molecular mechanism of skin barrier formation by protein-bound ceramides. HighlightsO_LIEpoxy-enone (EE) ceramides form stable conjugates with Cys. C_LIO_LICys binds to the {beta}-carbon of the enone via a Michael addition reaction. C_LIO_LICys-bound EE ceramides exist in the mouse epidermis. C_LIO_LICys-bound EE ceramides are the predominant protein-bound ceramides. C_LI In BriefProtein-bound ceramides are specialized ceramides essential for skin permeability barrier function. In the present study, we determined the exact structure of protein-bound ceramides as Cys-bound epoxy-enone ceramides where the {beta}-carbon of the epoxy-enone ceramides is attached by Cys residues of corneocyte surface proteins via a Michael addition reaction.

cell biology↗

bioRxiv2023

The Cyclimids: Degron-inspired cereblon binders for targeted protein degradation

Cereblon (CRBN) is an E3 ligase substrate adapter widely exploited for targeted protein degradation (TPD) strategies. However, achieving efficient and selective target degradation is a preeminent challenge with ligands that engage CRBN. Here, we report that the cyclimids, ligands derived from the C-terminal cyclic imide degrons of CRBN, exhibit distinct modes of interaction with CRBN and offer a facile approach for developing potent and selective bifunctional degraders. Quantitative TR-FRET-based characterization of 60 cyclimid degraders in binary and ternary complexes across different substrates revealed that ternary complex binding affinities correlated strongly with cellular degradation efficiency. Our studies establish the unique properties of the cyclimids as versatile warheads in TPD and a systematic biochemical approach for quantifying ternary complex formation to predict their cellular degradation activity, which together will accelerate the development of degraders that engage CRBN.

biochemistry↗