Biology subjects

Yokoyama, Y.

Publications and source records attributed to Yokoyama, Y..

8 recordsLinked to original sources

bioRxiv2026

Topical sulforaphane exacerbates disease and promotes the accumulation of inflammatory CD8+ T cells in a dermatitis model

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by skin barrier dysfunction and immune activation. Antioxidants such as sulforaphane (SFN) have shown benefit in mouse models of AD and are being explored as topical therapies. Objectives: We investigated the immune mechanisms through which topical SFN affects skin pathology in the MC903-induced AD-like dermatitis. Materials and Methods: We used flow cytometry to characterize skin immune cell infiltration, activation, and cytokine production. Genetic and pharmacological loss-of-function studies were used to determine the contribution of specific immune cell populations and signaling pathways. Results: Although topical application of SFN by itself caused no skin inflammation, it exacerbated MC903-induced dermatitis. Disease exacerbation was accompanied by robust T cell infiltration to skin, particularly by CD8 + T cells, and was significantly attenuated in TCR{beta}-deficient and {beta}2 m-deficient mice. In addition to a Type 2 inflammatory response, the skin CD8 + T cells exhibited a Type 1 inflammatory program characterized by IFN{gamma} production that was largely absent among CD4 + T cells. Loss of IFN{gamma} signaling attenuated SFN-mediated disease exacerbation. Blocking lymphocyte egress with FTY720 markedly reduced the SFN-induced increase in skin CD8 + T cells, suggesting that the increase was primarily dependent on recruitment from the periphery rather than local expansion. Conclusion: Topical SFN worsens MC903-induced dermatitis through a mechanism involving the peripheral accumulation of IFN{gamma}-producing CD8 + T cells in skin. These findings demonstrate that SFN can exert context-dependent pro-inflammatory effects and underscore the need to evaluate its effects carefully when considering topical medical or cosmetic applications.

immunology↗

bioRxiv2025

Nutrient Acquisition Drives Edwardsiella tarda Pathogenesis in Necrotizing Soft Tissue Infection

Necrotizing soft tissue infections (NSTIs) are rapidly progressive and life-threatening diseases caused by diverse bacterial pathogens. While classical virulence factors such as toxins and secretion systems have been extensively characterized, the role of metabolic fitness in supporting bacterial survival within the nutrient-restricted host environment remains underexplored. Edwardsiella tarda, a human-pathogenic bacterium implicated in NSTIs, represents an emerging model for studying non-canonical pathogenic strategies. Here, we employed transposon-directed insertion site sequencing (TraDIS) to identify genes critical for E. tarda survival in a murine soft tissue infection model. A genome-wide screen revealed 41 genes significantly depleted during the infection, including those involved in iron and zinc acquisition (fetB, zupT), vitamin biosynthesis (pdxK, cobA), and polyamine metabolism (speB). Functional assays using defined minimal media demonstrated that supplementation with vitamin B6 or putrescine enhanced bacterial growth, validating their contribution to fitness under nutrient-limited conditions. Our findings indicate that E. tarda pathogenesis is driven not solely by classical virulence factors but also by its ability to acquire essential nutrients and adapt metabolically to host-imposed nutritional stress. This study provides the first genome-wide fitness map for E. tarda during soft tissue infection and reveals new targets for therapeutic intervention that disrupt nutrient acquisition systems. These results also emphasize the broader relevance of metabolic adaptation as a determinant of virulence in invasive bacterial infections. IMPORTANCENecrotizing soft tissue infections (NSTIs) are severe, rapidly progressing bacterial infections with high morbidity and mortality. Although classical virulence factors such as toxins have been widely studied, much less is known about how pathogens adapt metabolically to survive within the nutrient-restricted environment in host tissues. This study uses Edwardsiella tarda, an emerging NSTI pathogen, as a model to identify genes required for in vivo fitness using transposon insertion sequencing (TraDIS). By revealing the critical roles of nutrient acquisition and metabolic adaptation, rather than toxin production alone, this work challenges conventional paradigms of bacterial virulence. Our findings suggest that targeting bacterial nutrient acquisition pathways may offer a novel therapeutic approach to control invasive infections. Furthermore, this study provides the first genome-wide fitness map of E. tarda during soft tissue infection, offering a valuable resource for future research into polymicrobial wound infections and host-pathogen nutrient competition.

microbiology↗

bioRxiv2025

Organo-metal coprecipitation contributes to stable organic carbon fraction in mangrove soil

Prediction of the impact of anthropogenic disturbances and global change on organic carbon (OC) pools in mangrove soils requires a detailed understanding of the mechanisms underlying OC stabilization. Using density fractionation to physically separate OC fractions with varying degrees of mineral association and protection, this study aimed to assess distributions of these fractions and the geochemical factors influencing the most dominant and refractory mineral-associated, high-density fraction (HF) in mangrove soil. We conducted forest-wide soil sampling in the Gaburumata mangrove forest on Ishigaki Island, Japan, along three transects (upstream, midstream, downstream) and at five depths (until 100 cm). The OC in HF (OCHF) was the oldest (median {Delta}14C value of -13.81{per thousand}) and contributed most significantly to total soil OC (43%-63%) and nitrogen (64%-85%). Among the extractable metals analyzed (aluminum [Al], iron [Fe], calcium [Ca], and magnesium [Mg]) with different crystallinity, only organically complexed Al and Fe showed strong positive correlations with OCHF. Together with high OCHF:Fe ratios that surpassed the maximum sorptive capacity of Fe oxides, these results indicate that co-precipitation of OC and Fe was the dominant mode of organo-mineral associations. The low clay content reduced the importance of Ca and Mg on OCHF, as these divalent cations typically facilitate OC stabilization through cation bridging between negatively charged clay surfaces and organic matter. Furthermore, the {Delta}14C-OC relationship suggested efficient incorporation of mangrove-derived modern C into HF, in addition to the pre-existing old C. Thus, mangrove expansion is likely to enhance stable soil OC pools in addition to increasing plant biomass and litter. Overall, this study proposes a biogeochemical mechanism for how stable mangrove OC is newly formed, as well as maintained, with ramifications for global mangrove expansion and plantation efforts.

ecology↗

bioRxiv2023

Origami-based growing tube model for reproducing shell shapes

Mathematical models for shell morphology have been well-studied in theoretical morphology. The growing tube model proposed by Takashi Okamoto was developed to reproduce heteromorph ammonoids and can generate various shells by changing three parameters: curvature, torsion, and enlarging ratio. Previous studies in theoretical morphology have employed computers to visualize mathematical models. However, computers are not accessible to everyone, and merely observing the graphics of the reproduced shells does not deepen understanding of the mathematical model. Therefore, in this study, we considered using origami, which is inexpensive and readily available, to make users understand mathematical models through hands-on folding. First, we simplified the crease pattern of seashells, originally devised by an origami artist Tomoko Fuse, to create a basic crease pattern. We then identified the crease pattern elements corresponding to the three parameters in the growing tube model and the aperture-apex position determiner. Based on them, we reproduced various shell shapes, including a heteromorph-ammonoid-like shape, with origami. Finally, we investigated the constraints between parameters in the origami-growing tube model. The origami-growing tube model is expected to help disseminate mathematical models and promote theoretical biology.

scientific communication and education↗

bioRxiv2023

The microbiota and immune system non-genetically affect offspring phenotypes transgenerationally

Summary paragraphThe host-microbiota relationship has evolved to shape mammalian processes, including immunity, metabolism, and development1-3. Host phenotypes change in direct response to microbial exposures by the individual. Here we show that the microbiota induces phenotypic change not only in the individual but also in their succeeding generations of progeny. We found that germ-free mice exhibit a robust sebum secretion defect and transcriptional changes in various organs, persisting across multiple generations despite microbial colonization and breeding with conventional mice. Host-microbe interactions could be involved in this process, since T cell-deficient mice, which display defective sebum secretion4, also transgenerationally transmit their phenotype to progeny. These phenotypes are inherited by progeny conceived during in vitro fertilization using germ-free sperm and eggs, demonstrating that epigenetic information in the gametes is required for phenotypic transmission. Accordingly, small non-coding RNAs that can regulate embryonic gene expression5 were strikingly and similarly altered in gametes of germ-free and T cell-deficient mice. Thus, we have uncovered a novel mechanism whereby the microbiota and immune system induce phenotypic changes in successive generations of offspring. This epigenetic form of inheritance could be advantageous for host adaptation to environmental perturbation, where phenotypic diversity can be introduced more rapidly than by genetic mutation.

microbiology↗

bioRxiv2023

Histone methyltransferase SUV39H1 regulates the Golgi complex via the nuclear envelope-spanning LINC complex

Cell motility is related to the higher-order structure of chromatin. Stimuli that induce cell migration change chromatin organization; such stimuli include elevated histone H3 lysine 9 trimethylation (H3K9me3). We previously showed that depletion of histone H3 lysine 9 methyltransferase, SUV39H1, suppresses directional cell migration. However, the molecular mechanism underlying this association between chromatin and cell migration remains elusive. The Golgi apparatus is a cell organelle essential for cell motility. In this study, we show that loss of H3K9 methyltransferase SUV39H1 but not SETDB1 or SETDB2 causes dispersion of the Golgi apparatus throughout the cytoplasm. The Golgi dispersion triggered by SUV39H1 depletion is independent of transcription, centrosomes, and microtubule organization, but is suppressed by depletion of any of the following three proteins: LINC complex components SUN2, nesprin-2, or microtubule plus-end-directed kinesin-like protein KIF20A. In addition, SUN2 is closely localized to H3K9me3, and SUV39H1 affects the mobility of SUN2 in the nuclear envelope. Further, inhibition of cell motility caused by SUV39H1 depletion is restored by suppression of SUN2, nesprin-2, or KIF20A. In summary, these results show the functional association between chromatin organization and cell motility via the Golgi organization regulated by the LINC complex.

cell biology↗

bioRxiv2022

Paradoxical tumor suppressive role of the musculoaponeurotic fibrosarcoma gene in colorectal cancer

Somatic cell reprogramming using the microRNAs miR200c, miR-302s, and miR-369s leads to increased expression of cyclin-dependent kinase inhibitors in human colorectal cancer (CRC) cells and suppressed tumor growth. Here, we investigated whether these microRNAs inhibit colorectal tumorigenesis in CPC;Apc mice, which are prone to colon and rectal polyps. Repeated administration of microRNAs inhibited polyp formation. Microarray analysis indicated that c-MAF, which reportedly shows oncogene-like behavior in multiple myeloma and T-cell lymphoma, decreased in tumor samples but increased in microRNA-treated normal mucosa. Immunohistochemistry identified downregulation of c-MAF as an early tumorigenesis event in CRC, with low c-MAF expression associated with poor prognosis. Of note, c-MAF expression and p53 protein levels were inversely correlated in CRC samples. c-MAF knockout led to enhanced tumor formation in azoxymethane/dextran sodium sulfate-treated mice, with activation of cancer-promoting genes. c-MAF may play a tumor-suppressive role in CRC development.

molecular biology↗

bioRxiv2019

A novel effect of the antigenic peptides position for presentation upon MHC class I

MHC-I molecules are expressed on the cell surface complexed with oligopeptides, most of which are generated from intracellular proteins by the ubiquitin-proteasome pathways and would be roughly proportional to the relative abundance of proteins and their rate of degradation. Thus MHC-I together with peptides function as immunological self-markers to exhibit the information about the repertoire of proteins expressed in a given cell to the immune system, and this process is called antigen (Ag) direct-presentation. Herein, we report a novel rule for the preference of peptides selected for the direct presentation; the N-terminally located antigenic peptides are more efficiently complexed with MHC-I than the C-terminally located peptides on the same protein. The superiority is largely dependent upon de novo proteins synthesis, degradation by proteasomes, and less dependent upon stabilities of proteins, indicating that this difference derived from rapidly degraded newly synthesized proteins such as defective ribosomal products (DRiPs). The effects of those N-terminal predominance was comparable with the enhanced MHC-I presentation by IFN-{gamma} suggesting that they might play important roles in the adaptive immunity.

immunology↗