Biology subjects

Hirasawa, K.

Publications and source records attributed to Hirasawa, K..

6 recordsLinked to original sources

bioRxiv2026

Sensitivity of Human Coronaviruses (HCoVs) to Heme Metabolism: Mechanisms Underlying Antiviral Effects

Heme metabolism regulates the availability of heme, an iron-containing molecule essential for oxygen transport, mitochondrial respiration, electron transfer, and enzymatic reactions. Increasing evidence implicates heme metabolism in regulating viral infection, potentially representing an important innate antiviral mechanism. Components of both heme biosynthesis and degradation pathways exhibit antiviral activity against different viruses; however, their contributions and conservation across human coronaviruses remain incompletely defined. We investigated the impact of modulating heme metabolism on infection by seasonal human coronaviruses HCoV-OC43 and HCoV-229E. Treatment with 5-aminolevulinic acid (5-ALA) produced cell line-dependent antiviral effects, with robust inhibition in H1299 cells and selective HCoV sensitivity in MRC-5 cells. These differences correlated with intracellular accumulation of protoporphyrin IX (PPIX), suggesting that cellular metabolic capacity influences antiviral efficacy. In contrast, components of the heme degradation pathway, including heme oxygenase-1 (HO-1), carbon monoxide, and biliverdin, did not exhibit antiviral effects against HCoV-OC43 or HCoV-229E. PPIX and synthetic porphyrin CoPPIX inhibited early infection through direct viral inactivation. Collectively, these findings indicate that antiviral effects of heme metabolism against seasonal human coronaviruses are primarily driven by direct inactivation by PPIX rather than cellular antiviral responses induced by the heme degradation pathway

microbiology↗

bioRxiv2022

Tackling Mitosis Domain Generalization in Histopathology Images with Color Normalization

In this report, we propose a method for mitosis detection in histopathology images of MIDOG2022 challenge dataset. Our method is based on unsupervised domain adaptation at inputlevel, and a combination of color normalization and object detection. We evaluate our method by using the preliminary test set including 20 cases and obtain 0.716 F1 score.

bioengineering↗

bioRxiv2022

Antiviral roles of interferon regulatory factor (IRF)-1, 3 and 7 against human coronavirus infection

Interferon regulatory factors (IRFs) are key elements of antiviral innate responses that regulate transcription of interferons (IFNs) and IFN-stimulated genes (ISGs). As many human coronaviruses are known to be sensitive to IFN, antiviral roles of IRFs are yet to be fully understood. TypeI or II IFN treatment protected MRC5 cells from infection of human coronavirus 229E, but not human coronavirus OC43. Infection of 229E or OC43 efficiently upregulated ISGs, indicating that antiviral transcription is not suppressed during their infection. Antiviral IRFs, IRF1, IRF3 and IRF7, were activated in cells infected with 229E, OC43 or severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2). RNAi knockdown and overexpression of the IRFs demonstrated that IRF1 and IRF3 have antiviral property against OC43 while only IRF3 and IRF7 are effective to restrict 229E infection. Our study demonstrates that IRF3 plays critical roles against infection of human coronavirus 229E and OC43, which may be an anti-human coronavirus therapeutic target.

microbiology↗

bioRxiv2021

Structure and mechanism of oxalate transporter OxlT in an oxalate-degrading bacterium in the gut microbiota

Oxalobacter formigenes is an oxalate-degrading bacterium in the gut microbiota that absorbs food-derived oxalate to use this as a carbon and energy source and thereby helps reduce the risk of kidney stone formation of the host animals 1-4. The bacterial oxalate transporter OxlT uptakes oxalate from the gut to bacterial cells and excrete formate as a degradation product, with a strict discrimination from other carboxylates that serve as nutrients 5-7. Nevertheless, the underlying mechanism remains unclear. Here, we present crystal structures of oxalate-bound and ligand-free OxlT in two different conformations, occluded and outward-facing states. The oxalate binding site contains two basic residues that form salt bridges with a dicarboxylate substrate while preventing the conformational switch to the occluded state without an acidic substrate, a disallowed state for an antiporter 8, 9. The occluded ligand-binding pocket can accommodate oxalate but not larger dicarboxylates, such as metabolic intermediates. The permeation pathways from the binding pocket are completely blocked by extensive interdomain hydrophobic and ionic interactions. Nevertheless, a molecular dynamics simulation showed that a flip of a single side chain neighbouring the substrate is sufficient to trigger the gate opening. The OxlT structure indicates the underlying metabolic interactions enabling favourable symbiosis at a molecular level.

biochemistry↗

bioRxiv2020

Development of Microsatellite Markers for a Soricid Water Shrew Chimarrogale platycephalus, and the Success of Individual Identification Using It.

The soricid water shrew, Chimarrogale platycephalus, is a mammal species endemic to the Japanese Islands. They inhabit the islands of Honshu and Kyushu, and are considered to be extinct in Shikoku. Information on this water shrew from Honshu and Kyushu is also scarce, and C. platycephalus is registered on the Japanese Governments red list as an endangered species. Almost all study areas such as regarding their ethology, ecology, also their phylogenetics are lacking. The delay in these foundational studies is due to difficulties related to them being both nocturnal and aquatic. In order to study of C. platycephalus, it is essential to conduct field research in mountain streams at night under such circumstances. In response to such difficult circumstances, we established a genetic analysis method using the feces of C. platycephalus, and as a result the accumulation of data on their phylogenetic evolution and phylogeography has increased which has improved our understanding of this species. Furthermore in this study, development of microsatellite markers was carried out, and a total of 21 loci marker analyses were performed. In addition, in order to confirm the credibility of these 21 microsatellite markers, as being able to validly differentiate individuals, all markers were examined using the fecal and tissues specimens from verified separately reared individuals (12 individuals) with the known history of having been reared in an aquarium. As a result, it was revealed that if analyses of the 12 loci were possible, individual differentiation with 100% accuracy was possible. The development of microsatellite markers in this study, and the establishment of individual identification methods by means of this will be expected to greatly contribute to future ecological and ethological research, population genetics and biogeographical research of the water shrew, C. platycephalus.

evolutionary biology↗

bioRxiv2020

MEK reduces cancer-specific PpIX accumulation through the RSK-ABCB1 and HIF-1α-FECH axes

The efficacy of aminolevulinic acid (5-ALA)-based photodynamic diagnosis (5-ALA-PDD) and photodynamic therapy (5-ALA-PDT) is dependent on the 5-ALA-induced cancer-specific accumulation of protoporphyrin IX (PpIX). We previously reported that inhibition of oncogenic Ras/MEK increases PpIX accumulation in cancer cells by reducing PpIX efflux through ATP-binding cassette sub-family B member 1 (ABCB1) as well as PpIX conversion to heme by ferrochelatase (FECH). Here, we sought to identify the downstream pathways of Ras/MEK involved in the regulation of PpIX accumulation via ABCB1 and FECH. First, we demonstrated that Ras/MEK activation reduced PpIX accumulation in RasV12-transformed NIH3T3 cells and HRAS transgenic mice. Knockdown of p90 ribosomal S6 kinases (RSK) 2, 3, or 4 increased PpIX accumulation in the RasV12-transformed NIH3T3 cells. Further, treatment with an RSK inhibitor reduced ABCB1 expression and increased PpIX accumulation. Moreover, HIF-1 expression was reduced when the RasV12-transformed NIH3T3 cells were treated with a MEK inhibitor, demonstrating that HIF-1 is a downstream element of MEK. HIF-1 inhibition decreased the activity of FECH and increased PpIX accumulation. Finally, we demonstrated the involvement of RSKs and HIF-1 in the regulation of PpIX accumulation in human cancer cell lines (DLD-1, SNB-75, Hs 578T, and MDA MB 231). These results demonstrate that the RSK-ABCB1 and HIF-1-FECH axes are the downstream pathways of Ras/MEK involved in the regulation of PpIX accumulation.

cancer biology↗