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Shimono, Y.

Publications and source records attributed to Shimono, Y..

6 recordsLinked to original sources

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↗

Contrasting ecological communities in rice paddy fields under conventional and no-fertilizer farming practices

Global crop production is essential for providing energy and nutrients to humans, but agricultural systems contribute substantially to environmental issues, making it crucial to find sustainable methods for crop production. In this study, we conducted extensive field monitoring of two rice paddy fields in Kyoto Prefecture, Japan, where a rice variety, Hinohikari, was cultivated to investigate how ecological communities influence rice growth and yields under two contrasting farming practices: conventional farming and no-fertilizer farming. We had three objectives: (1) to monitor rice growth and ecological dynamics to create a comprehensive ecological time series using quantitative environmental DNA metabarcoding and complementary monitoring methods, (2) to identify ecological variables that causally affect rice performance using nonlinear time series analysis, and (3) to examine the effects of the two farming practices on ecological variables and rice performance. As expected, the no-fertilizer paddy field showed lower rice growth and yields but still produced 40-50% of the yields of the conventional field. Ecological monitoring revealed contrasting ecological communities between the two fields, particularly among plant species on the paddy ridges and microbial taxa. Twenty-five taxa had statistically clear causal influences on rice performance. While the per-abundance influences of the causal taxa were largely similar in both paddy fields, their abundances were different, contributing to the differences in the overall effects of these taxa on the rice performance. These findings suggest that the abundance of causal taxa, along with nutrient conditions, may have driven differences in rice growth between the two paddy fields.

ecology↗

Gene expression shapes the patterns of parallel evolution of herbicide resistance in the agricultural weed Monochoria vaginalis

The evolution of herbicide resistance in weeds is an example of parallel evolution, through which genes encoding herbicide target proteins are repeatedly represented as evolutionary targets. The number of herbicide target-site genes differs among species, and little is known regarding the effects of duplicate gene copies on the evolution of herbicide resistance. We investigated the evolution of herbicide resistance in Monochoria vaginalis, which carries five copies of sulfonylurea target-site acetolactate synthase (ALS) genes. Suspected resistant populations collected across Japan were investigated for herbicide sensitivity and ALS gene sequences, followed by functional characterisation and ALS gene expression analysis. We identified over 60 resistant populations, all of which carried resistance-conferring amino acid substitutions exclusively in MvALS1 or MvALS3. All MvALS4 alleles carried a loss-of-function mutation. Although the enzymatic properties of ALS encoded by these genes were not markedly different, the expression of MvALS1 and MvALS3 was prominently higher among all ALS genes. The higher expression of MvALS1 and MvALS3 is the driving force of the biased representation of genes during the evolution of herbicide resistance in M. vaginalis. Our findings highlight that gene expression is a key factor in creating evolutionary hotspots.

plant biology↗

Evaluation of seasonal dynamics of fungal DNA assemblages in a flow-regulated stream in a restored forest using eDNA metabarcoding

Investigation of seasonal variation in fungal communities is essential for understanding biodiversity and ecosystem functions. However, the conventional sampling method, with substrate removal and high spatial heterogeneity of community composition, makes surveying the seasonality of fungal communities challenging. Recently, water environmental DNA (eDNA) analysis has been explored for its utility in biodiversity surveys. In this study, we assessed whether the seasonality of fungal communities can be detected by monitoring eDNA in a forest stream. We conducted monthly water sampling in a forest stream over two years and used DNA metabarcoding to identify fungal eDNA. The stream water contained DNA from functionally diverse aquatic and terrestrial fungi, such as plant decomposers, parasites, and mutualists. The variation in the fungal assemblage showed a regular annual periodicity, meaning that the assemblages in a given season were similar, irrespective of the year or sampling. Furthermore, the strength of the annual periodicity varied among functional groups. Our results suggest that forest streams may act as a "trap" for terrestrial fungal DNA derived from different habitats, allowing the analysis of fungal DNA in stream water to provide information about the temporal variation in fungal communities in both the aquatic and the surrounding terrestrial ecosystems.

ecology↗

Drastic shift in flowering phenology, an instant reproductive isolation mechanism, explains the population structure of Imperata cylindrica in Japan

Reproductive isolation plays an important role in population differentiation and speciation, thus enhancing biodiversity in wild plants. Hybridisation sometimes involves rapid reproductive isolation between parents and their hybrids through the novel traits of hybrids derived from a new combination of genomes. Here, we report how a hybrids new phenotype contributes to rapid reproductive isolation between two ecotypes of Imperata cylindrica. The two ecotypes differ in their flowering phenology and habitats. An analysis with genetic markers revealed that hybrid populations consisted of only F1 individuals. Both parental ecotypes flowered in spring, but F1s flowered in fall. This drastic shift in flowering phenology prevented backcrossing parental ecotypes to F1. F1s flowered in fall and dispersed seeds in winter. The germination percentage of seeds set on F1 was extremely low in their habitats, and seedlings did not survive due to the low temperatures in winter, resulting in the absence of a F2 generation. In conclusion, flowering phenology mismatch promotes reproductive isolation between parents and F1, resulting in a hybrid population consisting of only F1s.

evolutionary biology↗

The local state of chromatin compaction at transcription start sites controls transcription levels

A defined amount of transcript is produced from transcription start sites (TSSs) of each gene, suggesting that the binding frequency of RNA polymerase varies among genes. However, what structure in chromatin controls this frequency remains elusive. We established a method to fractionate chromatin according to its degree of three-dimensional compaction. Nucleosomes were evenly detected through all of the fractions, but histone H1 was more highly enriched in the more compact chromatin fractions. Similarly, HP1 and MBD2b were more abundant in more compact chromatin, while the levels of tri-methylated H3 (Lys9) and 5-methyl cytosine subtly increased. Via genome-wide analyses, nearly the entire genome was found to exist in compact chromatin without variations between repeat and non-repeat sequences; however, active TSSs were rarely found in compact chromatin. Based on a correlation between weak compaction and RNA polymerase binding at TSSs, it appears that local states of chromatin compaction determine transcription levels.

molecular biology↗