Biology subjects

Tsujimoto, Y.

Publications and source records attributed to Tsujimoto, Y..

3 recordsLinked to original sources

bioRxiv2025

Molecular signature of COVID-19 prior to its exacerbation by multi-omics survey

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic due to its high transmissibility and ability to evade innate immune responses. Comprehensive characterization of the disease is essential for elucidating its pathophysiology and clinical progression. In this study, we performed multi-omics analyses of plasma samples collected from SARS-CoV-2-positive patients prior to clinical deterioration of coronavirus disease 2019 (COVID-19). These samples revealed the potential of previously reported clinical parameters, including CRP and neutrophil level, to predict COVID-19 exacerbation in the early stage. Our analysis identified a novel panel of molecules that precede the clinical manifestations associated with COVID-19 progression. These candidate biomarkers exhibited strong correlations with previously reported clinical and immunological parameters. Notably, several inflammation-related markers showed inverse associations with specific interferon subtypes, including IFN-6 and IFN-8, potentially reflecting mechanisms of SARS-CoV-2-mediated immune evasion. Our findings contribute to the understanding of virus-induced acute exacerbation and offer a valuable foundation for future pandemic research.

microbiology↗

bioRxiv2025

Molecular bases for USP48 cis-activity regulation and hyperactivation by Cushing's disease-associated mutations

Ubiquitin-specific protease 48 (USP48) is a deubiquitinating enzyme involved in various pathophysiological processes, including DNA repair, tumorigenesis, and inflammation. Somatic mutations in USP48 (M415I/V) are associated with pituitary tumors in Cushings disease. These variants lead to increased USP48 enzyme activity and adrenocorticotropic hormone (ACTH) hypersecretion, a key feature of Cushings disease, indicating a direct link to the condition. Using biochemical experiments and in silico structural analyses, we identified Y414 in the catalytic USP domain as a critical residue for USP48 activity. In the wild-type USP domain, the Y414 side chain was oriented to closed, which led to catalytic triad misalignment and weak ubiquitin recognition. We also found that the C-terminal region (CTR) of USP48 is a cis-activating region. It interacts with the USP domain and ubiquitin tail, thereby facilitating the alignment of the catalytic triad and enhancing ubiquitin recognition ability. Additionally, genomic analyses of pituitary tumors in Japanese patients with Cushings disease (n=46) confirmed that USP48 M415I/V variants occurred at a frequency of 10%, which is consistent with previous reports. Our structural model suggests that M415I/V sterically interferes with and fixes the closed Y414 side chain to open, resulting in catalytic triad alignment and increased ubiquitin recognition ability. Furthermore, USP48 with M415I/V showed enhanced CTR-mediated activity, indicating that the open Y414 side chain and CTR can cause hyperactivation. This study provides a molecular basis for the novel cis-activation regulation of USP48 and its hyperactivation by Cushings disease-associated variants. Significance StatementThe regulatory mechanisms of DUB activity are not yet fully understood. This study identifies the CTR of USP48 as an activity-promoting region, a mechanism also present in USP7 and potentially other closely related DUBs such as USP40 and USP47. Despite the disease association of some DUBs, developing drugs to inhibit specific DUB members or variants remains challenging. The substitutions of USP48 M415 embedded in the USP domain to Ile/Val are associated with Cushings disease, which lacks adequate targeted therapeutics. This study reveals that these variants alter the orientation of Y414, leading to hyperactivation. These findings provide a molecular basis for developing USP48M415I/V-specific inhibitors for Cushings disease therapy.

molecular biology↗

bioRxiv2020

Canopy micrometeorology monitoring in diverse climates innovatively improves the evaluation heat-induced sterility of rice under climate change

This study is the first and unique of open-field studies to assess the determination process of heat-induced spikelet sterility (HISS) of rice by using the same variety and the same monitoring system, MINCER (Micrometeorological Instrument for Near Canopy Environment of Rice), covering the major-rice growing regions from Sub-Saharan Africa, South, Southeast, and East Asia, and USA. Applying the observation data from the monitoring network, MINCERnet, to the canopy heat balance model, IM2PACT, it was quantitatively corroborated in open-field conditions worldwide that the canopy and panicle transpiration and their evaporative cooling effect played a great role on the micrometeorological gap between the ambient air temperature and the panicle temperature, and that the sterility rate due to HISS in open-fields can be evaluated accurately in diverse climates by the mean panicle temperature at flowering hours in the flowering period. The heat balance structure suggested that the risk of HISS should be higher in high humidity climates rather than in dry climates also in the future, which lead to the importance of the humidity accuracy as well as of the air temperature in climate scenarios and their spatial downscaling for future prediction of rice heat stress and production. Applying the heat-tolerant variety was suggested to be able to keep the sterility due to HISS low in all climates. It is needed of the approach using the panicle temperature as indicator of HISS by intervening sub-model and/or monitoring of micrometeorology inside the canopy to reduce uncertainties in future rice yield prediction under various adaptation measures.

plant biology↗