Biology subjects

Fukui, T.

Publications and source records attributed to Fukui, T..

3 recordsLinked to original sources

bioRxiv2025

A skeletal muscle-sympathetic nerve-intestine network underlies muscle inflammation and atrophy induced by immobilization

Immobility is a common cause of muscle atrophy, but the underlying mechanisms have remained unclear. Here we show that limb immobilization in mice elicits inflammation and atrophy of skeletal muscle that are preventable by neutralizing antibodies to the chemokine CXCL10. Limb immobilization also induced changes to the gut microbiota and intestinal inflammation, and either sterilization of the intestine with antibiotics or administration of 10-hydroxy-cis-12-octadecenoic acid--a linoleic acid-derived gut microbial metabolite--prevented intestinal and muscle inflammation as well as muscle atrophy induced by immobilization, implicating intestinal inflammation in muscle inflammation and atrophy. Limb immobilization activated sympathetic nerves and increased {beta}2-adrenergic receptor gene (Adrb2) expression in the intestine. Single-cell RNA-sequencing analysis revealed that, among cells expressing Adrb2 in the intestine, immobilization increased only the population of macrophages. Pharmacological inhibition or macrophage-specific ablation of Adrb2 prevented immobilization-induced intestinal and muscle inflammation. Our results thus implicate a previously unrecognized muscle-nerve-intestine network in immobilization-induced muscle atrophy.

molecular biology↗

bioRxiv2024

Discovering cancer stem-like cells using Spatial transcriptomic analysis: Nuclear factor I X as a novel therapeutic target for gastric cancer

BackgroundGastric cancer (GC) is characterized by significant intratumoral heterogeneity and stem cells presenting as promising therapeutic targets. Despite advancements in spatial transcriptome analysis, unexplored targets for addressing cancer stemness remain unknown. This study aims to identify Nuclear Factor IX (NFIX) as a critical regulator of cancer stemness in GC and evaluate its clinicopathological significance and function. MethodsSpatial transcriptome analysis was conducted on GC. NFIX expressions correlation with clinicopathological factors and prognosis was assessed through immunostaining in 127 GC cases. Functional analyses in cancer cell lines validated these findings. ResultsSpatial transcriptome analysis stratified GC tissues based on genetic profiles, pinpointing CSC-like cells and further refined the classification to identify and highlight the NFIXs significance, validated by Monocle 3 and CytoTRACE analyses. Knockdown experiments in cancer cell lines demonstrated the involvement of NFIX in cancer cell proliferation and kinase activity. ConclusionsThis study underscores spatial transcriptome analysiss role in refining GC tissue classification and identifying therapeutic targets, highlighting NFIX as pivotal. NFIX expression correlates with poor prognosis and drives GC progression, suggesting its potential as a novel therapeutic target for personalized GC therapies.

pathology↗

bioRxiv2024

Ribonanza: deep learning of RNA structure through dual crowdsourcing

Prediction of RNA structure from sequence remains an unsolved problem, and progress has been slowed by a paucity of experimental data. Here, we present Ribonanza, a dataset of chemical mapping measurements on two million diverse RNA sequences collected through Eterna and other crowdsourced initiatives. Ribonanza measurements enabled solicitation, training, and prospective evaluation of diverse deep neural networks through a Kaggle challenge, followed by distillation into a single, self-contained model called RibonanzaNet. When fine tuned on auxiliary datasets, RibonanzaNet achieves state-of-the-art performance in modeling experimental sequence dropout, RNA hydrolytic degradation, and RNA secondary structure, with implications for modeling RNA tertiary structure.

biophysics↗