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Naka, I.

Publications and source records attributed to Naka, I..

2 recordsLinked to original sources
bioRxiv2025

High-Coverage Jomon Genomes Provide Insights into Population Structure and Genetic Traits of Ancient Japanese Hunter-Gatherers

We analyzed eight high-coverage Jomon genomes spanning 9,000-2,800 years ago across the Japanese archipelago. Population genomic analyses revealed substantial genetic homogeneity across time and space reflecting post-glacial isolation, yet temporal stratification emerged: Initial Jomon (Iyai) individuals formed the earliest branch with weaker affinities to present-day Japanese. Using genomes from Todoroki and Chidorikubo sites, we estimated Jomon ancestry in mainland Japanese at [~]20%, substantially higher than previous estimates ([~]13%). Polygenic score analyses, based on the direct analysis of Jomon genomes, provided the genetic evidence for their phenotypic predispositions, including elevated BMI and metabolic trait scores, reduced immune-related scores, and larger cardiac dimensions, patterns consistent with hunter-gatherer adaptations. These ancestral genetic influences, including elevated risks for obesity and dyslipidemia, persist in present-day Japanese. Our findings demonstrate that Jomon populations maintained genetic continuity despite ecological diversity, while their greater-than-expected contribution to present-day Japanese reshapes population history models and reveals how ancient adaptations continue influencing contemporary disease susceptibility.

genomics↗
bioRxiv2025

Dual inhibition of glutaminolysis and autophagy suppresses proliferation of Rheumatoid arthritis fibroblast-like synoviocytes and mitigates arthritis in SKG mice

Recent evidence highlights the critical role of immune metabolism in the pathogenesis of rheumatoid arthritis (RA). We previously demonstrated that glutaminase 1 (GLS1), a key enzyme in glutamine metabolism, is upregulated in fibroblast-like synoviocytes from RA patients (RA-FLS) and that GLS1 inhibition exerts an antiproliferative effect on RA-FLS. Glutaminolysis has also been shown to suppress autophagy, raising the possibilitiy that inhibiting glutaminolysis may enhance autophagy. Given this interplay, we hypothesized that dual inhibition of glutaminolysis and autophagy could synergistically suppress RA-FLS proliferation. This study aimed to investigate the effects of combining autophagy and glutaminolysis inhibition on RA-FLS and arthritis in SKG mice. We utilized chloroquine (CQ) as an autophagy inhibitor and compound 968 (C968), a GLS1 inhibitor, to suppress glutaminolysis. Treatment with C968 upregulated LC3B and ATG5 expression and increased LC3-II protein levels in RA-FLS, indicative of enhanced autophagy. Furthermore, C968 promoted autophagosome formation in RA-FLS. These findings confirm that glutaminolysis inhibition enhances autophagy in RA-FLS. The combination of C968 and CQ significantly inhibited RA-FLS proliferation and increased apoptotic cell death. Moreover, C968-CQ co-treatment markedly alleviated arthritis severity in SKG mice. Our findings suggest that concurrent suppression of glutaminolysis and autophagy represents a promising therapeutic strategy for RA.

immunology↗