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Ogasawara, R.

Publications and source records attributed to Ogasawara, R..

3 recordsLinked to original sources

Ribonuclease L Regulates Antiviral Responsiveness through Cleavage of XBP1 mRNA

During viral infection, viral replication perturbs endoplasmic reticulum (ER) homeostasis and triggers the unfolded protein response (UPR). XBP1s, a transcription factor generated by one branch of the UPR, is known to potentiate both innate and adaptive immunity, but its role in antiviral responses remains incompletely understood beyond its ability to augment type I interferon (IFN) mRNA induction. Here, we show that XBP1s positively regulates the RIG-I-like receptors (RLRs), ribonuclease L (RNase L), and protein kinase R (PKR) pathways, indicating that it enhances all three major antiviral response pathways. We further show that RNase L activation rapidly decreases XBP1 mRNA levels in an RNase activity-dependent manner, leading to a prompt reduction in XBP1s expression. Consistent with this, RNase L deletion significantly increased both thapsigargin-mediated XBP1s induction and XBP1s expression following Japan encephalitis virus infection. Poly(I:C)-induced IFNB mRNA expression was significantly enhanced in RNase L-knockout cells. This enhancement was completely abolished by RNase L reconstitution. XBP1 knockdown also significantly attenuated IFNB mRNA expression in RNase L-knockout cells. These findings suggest a negative-feedback loop in which RNase L suppresses XBP1s, thereby fine-tuning antiviral responsiveness during viral infection. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC="FIGDIR/small/713401v1_ufig1.gif" ALT="Figure 1000"> View larger version (19K): org.highwire.dtl.DTLVardef@112d312org.highwire.dtl.DTLVardef@df79a9org.highwire.dtl.DTLVardef@1ac571borg.highwire.dtl.DTLVardef@18ac610_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

Ectoine production by newly isolated halophilic methanotroph Methylotuvimicrobium percolatum using surplus methane from anaerobic digestion

Anaerobic digestion (AD) processes that convert waste such as livestock wastewater into biomethane for energy recovery are expanding globally. However, biogas exceeding storage capacity is typically flared, resulting in the release of carbon dioxide, a greenhouse gas. To address this issue, we focused on halophilic methane-oxidizing bacteria (methanotrophs) capable of converting methane into ectoine, a high-value compatible solute widely used in more than 400 cosmetic active ingredients and valued at approximately US$1,000/kg. Nevertheless, research on halophilic methanotrophs and ectoine biosynthesis remains limited. Here, we report the successful isolation of the Type I methanotroph Methylotuvimicrobium percolatum from activated sludge in a brackish water environment. Complete genome sequencing revealed genes for methane oxidation, osmoadaptation, and notably the ectABCask cluster responsible for ectoine biosynthesis. Activity tests under varying NaCl concentrations confirmed ectoine production, with a maximum yield of 20.1 mg ectoine/g-DCW achieved at 25% methane, 30 {degrees}C, and 3 wt% salinity. Biomass growth remained robust up to 6% salinity but declined sharply at higher NaCl concentrations, indicating that optimal conditions for growth and ectoine synthesis do not entirely coincide. These findings advance the fundamental understanding of halophilic methanotroph physiology and highlight their potential as sustainable platforms for converting surplus methane from AD processes into commercially valuable ectoine.

microbiology↗

Visualizing ATP Dynamics in Live Mice

ABSTRACTAnalysis of the dynamics of adenosine triphosphate (ATP) is vital to quantitatively define the actual roles of ATP in biological activities. Here, we applied a genetically encoded Förster resonance energy transfer biosensor “GO-ATeam” and created a transgenic mouse model that allows systemic ATP levels to be quantitatively, sensitively, noninvasively, and spatiotemporally measured under physiological and pathological conditions. We used this model to readily conduct intravital imaging of ATP dynamics under three different conditions: during exercise, in all organs and cells; during myocardial infarction progression; and in response to the application of cardiotoxic drugs. These findings provide compelling evidence that the GO-ATeam mouse model is a powerful tool to investigate the multifarious functions of cellular ATP in vivo with unprecedented spatiotemporal resolution in real-time. This will inform predictions of molecular and morphological responses to perturbations of ATP levels, as well as the elucidation of physiological mechanisms that control ATP homeostasis.One Sentence Summary Intravital real-time imaging of ATP dynamics in multiple organs using GO-ATeam mice, can be used to quantitatively, sensitively, noninvasively, and spatiotemporally measure systemic ATP levels and provide a platform for preclinical pharmacological studies.Competing Interest StatementM.Yamamoto is involved in a pending patent related to GO-ATeam mice. H.I. holds a patent for ATeam probe. All other authors declare no competing interests.View Full Text

physiology↗