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Biology subjects

Kawamoto, Y.

Publications and source records attributed to Kawamoto, Y..

4 recordsLinked to original sources

Genomic and phenotypic consequences of long-term isolation and small population size in Yakushima macaques

The relative roles of genetic drift, inbreeding, and natural selection in island evolution have been fundamental themes in evolutionary biology for nearly a century. However, empirical studies have yet to reach a consensus, and research integrating both genotypes and phenotypes in primates remains limited. The present study aims to estimate the demographic history of an island primate population, the Yakushima macaque (Macaca fuscata yakui), and evaluate the genomic and morphological consequences of its isolation. To this end, we conducted population genetic analyses based on whole-genome sequencing and geometric morphometric analyses of cranial shape. Our results indicate that M. f. yakui has been isolated with an effective population size of several thousand individuals for over 100,000 years. Although we detected signatures of purifying selection, deleterious alleles have not been sufficiently purged. The degree of fluctuating asymmetry in males was slightly, yet significantly, higher in M. f. yakui than in mainland populations, whereas this trend was not observed in females. Marginal evidence of directional selection was found for cranial size, but not for shape. Overall, our findings suggest that due to long-term isolation, genetic drift and inbreeding have exerted a substantial influence on shaping genotypic and phenotypic variation in this island population.

evolutionary biology↗

Co-targeting an AMPK--MAPK axis reprograms CAFs and suppresses PDAC

Pancreatic ductal adenocarcinoma (PDAC) is a fatal cancer characterized by limited therapeutic options and a highly treatment-resistant tumor microenvironment. Beyond tumor-intrinsic genetic alterations, growing evidence indicates that host-microbiome interactions influence cancer progression through microbial metabolites. However, how microbiome-derived metabolites influence oncogenic signaling in PDAC remains unclear. Here, integrated profiling revealed a consistent reduction of the microbial metabolite acetic acid in fecal samples from treatment-naive patients with PDAC and in a genetically defined Drosophila model recapitulating key PDAC driver alterations. Acetic acid activates AMP-activated protein kinase, and pharmacological activation of this pathway together with inhibition of mitogen-activated protein kinase signaling suppressed tumor growth in fly and mouse models. Combined pathway targeting restored AMPK activity and suppressed cancer-associated fibroblast activation. These findings identify a microbiome-associated metabolic vulnerability in PDAC and suggest that coordinated targeting of metabolic and oncogenic signaling may restrain tumor progression and improve therapeutic strategies.

cancer biology↗

The microRNA regulatory landscape of skeletal muscle-derived extracellular vesicles

Skeletal muscle-derived extracellular vesicles (SkM-EVs) have recently been recognized as novel endocrine factors capable of facilitating inter-organ communication between skeletal muscle and distant organs. These vesicles transport various molecular cargoes, including microRNAs (miRNAs), which are essential regulators of post-transcriptional gene expression. In this study, we characterized the miRNA composition of SkM-EVs using small RNA sequencing and elucidated their putative biological roles via comprehensive bioinformatics analyses. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the predicted miRNA targets revealed that SkM-EV miRNAs are involved in several key pathways, including the FoxO signaling pathway, the insulin signaling pathway, and cancer-related pathways. Our findings suggest that SkM-EV miRNAs may simultaneously promote muscle differentiation and exert protective effects against diabetes and cancer development. These findings provide new insights into the systemic regulatory roles of SkM-EVs and highlight their therapeutic potential for muscular, metabolic, and oncological disorders.

physiology↗

Highly Versatile, Non-Invasive Method for Collecting Buccal DNA from Free-Ranging Non-Human Primates

Non-invasive techniques for collection of DNA samples of suitable quality and quantity are important for improving the efficiency of genetic wildlife research. The development of a non-invasive method for collection of DNA samples from wild stump-tailed macaques (Macaca arctoides) is described herein. Sterilized polyester rope was cut into 10 cm pieces, which were then soaked in a 20% sugar solution to bait individuals. Rope swabs were immediately collected and transferred to a lysis buffer solution after subjects had picked up, chewed, and discarded them. DNA was later extracted from the buffer. Quantitative real-time PCR and both allelic dropout and genotype failure rates were used to compare the quantity and quality of the buccal DNA samples to those of intestinal slough cell DNA samples collected from freshly dropped feces. The buccal samples yielded significantly more DNA (27.1 {+/-} 33.8 ng/{micro}L) than did the fecal samples (11.4 {+/-} 15.4 ng/{micro}L) and exhibited lower allelic dropout and genotyping failure rates for the 10 autosomal microsatellites investigated. Buccal cell collection was also simple, inexpensive, reliable, and less time-consuming compared to fecal sampling. Thus, this method should facilitate genome-wide studies of non-human primates and other wildlife species.

genetics↗