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Uchimiya, M.

Publications and source records attributed to Uchimiya, M..

5 recordsLinked to original sources

PFOA induced metabolic and immune perturbations in a SARS-2 infection model

This study evaluates the impact of PFOA exposure on the metabolome and immune response to SARS-2 using a ferret model. Ferrets were separated into control or PFOA-exposed groups (10/mg/kg/day) and challenged with SARS-2. Longitudinal analyses encompassing clinical assessments, serological profiling, histopathology, and untargeted nuclear magnetic resonance (NMR) metabolomics revealed significant metabolic and immunological perturbations. We found prominent effects of PFOA exposure on metabolism, which resulted in altered metabolic responses to SARS-2 infection. PFOA exposure was also associated with impaired immune function, as evidenced by decreased serum IgG levels, increased viral loads, and prolonged peak infectivity. These findings underscore the consequences of PFOA exposure on host metabolism and immunity during infectious diseases.

pharmacology and toxicology↗

Dynamic Reworking of Marine Diatom Endometabolomes

A large annual carbon flux occurs through the oceans labile dissolved organic carbon (DOC) pool, with carbon influx dominated by phytoplankton-derived metabolites and outflux by heterotrophic bacterioplankton uptake. We addressed the dynamics of this flux between marine primary and secondary producers through analysis of the Thalassiosira pseudonana CCMP1335 endometabolome, a proxy for labile DOC release during phytoplankton excretion and mortality. Diatom strains acclimated at one of three different temperatures (14{degrees}C, 20{degrees}C, or 28{degrees}C) were then cultured either axenically or with the bacterium Ruegeria pomeroyi DSS-3, and their endometabolites analyzed by NMR. Osmolytes were by far the most dynamic, exhibiting concentration differences up to 150-fold between conditions; median concentration variation across identified endometabolites was [~]1.5-fold. Differential expression of diatom metabolic pathways suggested changes in synthesis rates as a mechanism for endometabolome remodeling. Consistent with expectations of high turnover, endometabolite mean lifetimes prior to bacterial uptake were <2 h to 12 h. ImportanceThe role of labile DOC in the transfer of marine carbon between phytoplankton and heterotrophic bacteria was first recognized 40 years ago, yet the identity and dynamics of phytoplankton metabolites entering the labile DOC pool are still poorly known. Using metabolome and transcriptome profiling, we found dynamic composition and concentration of diatom endometabolites, depending on growth conditions and arising over time frames as short as a single growth cycle. This strong response to external conditions, both biotic and abiotic, has implications for downstream processing and fate of ocean carbon by heterotrophic bacteria.

ecology↗

PyINETA: Open-source platform for INADEQUATE-JRES integration in NMR metabolomics

Annotating compounds with high confidence is a critical element in metabolomics. 13C-detection NMR experiment INADEQUATE (incredible natural abundance double-quantum transfer experiment) stands out as a powerful tool for structural elucidation, whereas this valuable experiment is not often included in metabolomics studies. This is partly due to the lack of community platform that provides structural information based INADEQUATE. Also, it is often the case that a single study uses various NMR experiments synergistically to improve the quality of information or balance total NMR experiment time, but there is no public platform that can integrate the outputs of INADEQUATE and other NMR experiments either. Here, we introduce PyINETA, Python-based INADEQUATE network analysis. PyINETA is an open-source platform that provides structural information of molecules using INADEQUATE, conducts database search, and integrates information of INADEQUATE and a complementary NMR experiment 13C J-resolved experiment (13C-JRES). Those steps are carried out automatically, and PyINETA keeps track of all the pipeline parameters and outputs, ensuring the transparency of annotation in metabolomics. Our evaluation of PyINETA using a model mouse study showed that our pipeline successfully integrated INADEQUATE and 13C-JRES. The results showed that 13C-labeled amino acids that were fed to mice were transferred to different tissues, and, also, they were transformed to other metabolites. The distribution of those compounds was tissue-specific, showing enrichment of particular metabolites in liver, spleen, pancreas, muscle, or lung. The value of PyINETA was not limited to those known compounds; PyINETA also provided fragment information for unknown compounds. PyINETA is available on NMRbox.

systems biology↗

Function and Importance of Marine Bacterial Transporters of Plankton Exometabolites

Metabolite exchange within marine microbial communities transfers carbon and other major elements through global cycles and forms the basis of microbial interactions. Yet lack of gene annotations and concern about the quality of existing ones remain major impediments to revealing the metabolite-microbial network. We employed an arrayed mutant library of the marine bacterium Ruegeria pomeroyi DSS-3 to experimentally annotate substrates of organic compound transporter systems, using mutant growth and compound drawdown analyses to link transporters to their substrates. Mutant experiments verified substrates for thirteen R. pomeroyi transporters. Four were previously hypothesized based on gene expression data (taurine, glucose/xylose, isethionate, and cadaverine/putrescine/spermidine); five were previously hypothesized based on homology to experimentally annotated transporters in other bacteria (citrate, glycerol, N-acetylglucosamine, fumarate/malate/succinate, and dimethylsulfoniopropionate); and four had no previous annotations (thymidine, carnitine, cysteate, and 3-hydroxybutyrate transporter). These bring the total number of experimentally-verified organic carbon influx transporters to 17 of 126 in the R. pomeroyi genome. In a longitudinal study of a coastal phytoplankton bloom, expression patterns of the experimentally annotated transporters linked them to different stages of the bloom, and also led to the hypothesis that citrate and 3-hydroxybutyrate were among the most highly available bacterial substrates. Improved functional knowledge of these gatekeepers of organic carbon uptake is facilitating better characterization of the surface ocean metabolite network.

microbiology↗

Diel Investments in Phytoplankton Metabolite Production Influenced by Associated Heterotrophic Bacteria

Organic carbon transfer between photoautotrophic and heterotrophic microbes in the surface ocean mediated through metabolites dissolved in seawater is a central but poorly understood process in the global carbon cycle. In a synthetic microbial community in which diatom extracellular release of organic molecules sustained growth of a co-cultured bacterium, metabolite transfer was assessed over two diel cycles based on per cell quantification of phytoplankton endometabolites and bacterial transcripts. Of 31 phytoplankton endometabolites identified and classified into temporal abundance patterns, eight could be matched to patterns of bacterial transcripts mediating their uptake and catabolism. A model simulating the coupled endometabolite-transcription relationships hypothesized that one category of outcomes required an increase in phytoplankton metabolite synthesis in response to the presence of the bacterium. An experimental test of this hypothesis confirmed higher endometabolome accumulation in the presence of bacteria for all five compounds assigned to this category - leucine, glycerol-3-phosphate, glucose, and the organic sulfur compounds dihydroxypropanesulfonate and dimethylsulfoniopropionate. Partitioning of photosynthate into rapidly-cycling dissolved organic molecules at the expense of phytoplankton biomass production has implications for carbon sequestration in the deep ocean. That heterotrophic bacteria can impact this partitioning suggests a previously unrecognized influence on the oceans carbon reservoirs. Significance StatementMicrobes living in the surface ocean are critical players in the global carbon cycle, carrying out a particularly key role in the flux of carbon between the ocean and atmosphere. The release of metabolites by marine phytoplankton and their uptake by heterotrophic bacteria is one of the major routes of microbial carbon turnover. Yet the identity of these metabolites, their concentration in seawater, and the factors that affect their synthesis and release are poorly known. Here we provide experimental evidence that marine heterotrophic bacteria can affect phytoplankton production and extracellular release of metabolites. This microbial interaction has relevance for the partitioning of photosynthate between dissolved and particulate carbon reservoirs in the ocean, an important factor in oceanic carbon sequestration.

ecology↗