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Biology subjects

Izawa, T.

Publications and source records attributed to Izawa, T..

4 recordsLinked to original sources

geneSTRUCTURE: A Modern Platform for Visualization of Gene Structures

Even in the era of genomics and pan-genomics, the gene remains the fundamental unit of heredity. Accurate visualization of gene structures provides essential insights into the organization, regulation, and evolution of each gene. Representing elements such as exons, introns, untranslated regions, and functional domains in a clear and interpretable format is particularly important for analyzing complex gene architectures and for communicating results effectively. Despite the availability of several visualization tools, many are limited in their ability to incorporate user-defined annotations or to support interactive and customizable figure generation, which reduces their utility in modern analytical workflows. To address these limitations, we developed geneSTRUCTURE, both command-line-interface and web-based application designed to provide flexible and user-friendly visualization of gene structures based on widely used annotation formats, GFF3 and GTF. In addition to visualizing core gene components, the platform allows users to overlay supplemental annotations, including mutation sites and protein domains, and to adjust layout features in real time. By combining a modern interface with annotation flexibility and high-resolution output, geneSTRUCTURE offers a robust solution for gene-level visualization.

bioinformatics↗

Systemic aldehyde storm induced by allyl alcohol exposure results in extensive hepatic ferroptosis in Aldh2*2 knock-in mice

Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme that detoxifies multiple aldehyde species in the body. The ALDH2*2 allele (E487K) is one of the most common gene polymorphisms in humans, resulting in dysfunction of its enzyme activity. This study investigated in vivo mechanism of acute liver injury caused by exposure to allyl alcohol (AA) using Aldh2*2 knock-in (KI) mice with the same amino acid replacement as human ALDH2*2. A rapid burst of plasma acrolein as an active metabolite of AA, as well as plasma endogenous reactive aldehydes malondialdehyde (MDA) and formaldehyde, was observed at 10 min after exposure to 75 mg/kg of AA in the Aldh2*2 KI homozygous mice, which was not evident in the wild-type mice. Hepatocellular necrosis was more extensive in the Aldh2*2 KI homozygous mice than in the wild-type mice, which was preceded by hepatic glutathione depletion and was coincident with an accumulation of acrolein, MDA, and 4-hydroxy-2-nonenal adducts and iron deposition, suggesting an involvement of ferroptosis in the exacerbation of hepatic necrosis. Recovery from hepatic glutathione depletion was delayed in the homozygous mice compared with the wild-type mice, with a decreasing tendency of hepatic expression of cystine transporter xCT. These results suggest that increased hepatic glutathione consumption, due to decreased aldehyde detoxification capacity, can sensitize the Aldh2*2 KI homozygous mice to hepatic ferroptosis after the rapid "aldehyde storm". Our study revealed a crosstalk between aldehyde metabolism and ferroptosis pathways and potential health impacts of endogenous reactive aldehydes on ALDH2*2 carriers.

pathology↗

Delayed protein translocation protects mitochondria against toxic CAT-tailed proteins

Ribosome-associated quality control (RQC) protects cells against toxic effects of faulty polypeptides produced by stalled ribosomes. However, mitochondria are vulnerable to C-terminal alanyl-and-threonyl (CAT)-tailed proteins that are generated in this process and faulty nuclear-encoded mitochondrial proteins are handled by the recently discovered mitoRQC. Here, we performed a genome-wide screen in yeast to identify additional proteins involved in mitoRQC. We found that Pth2, a peptidyl-tRNA hydrolase in the mitochondrial outer membrane, influences aggregation of CAT-tailed proteins without majorly affecting the CAT-tailing process itself. Peptidyl-tRNA hydrolase activity is essential during this process, yet the activity of Pth2 can be substituted by another peptidyl-tRNA hydrolase, upon proper localization. Our data suggest that Pth2 acts through modulating protein translocation and that mitochondrial proteostasis network is relieved through increased access of CAT-tailed proteins to cytosolic chaperones. Other hits obtained in the screen show that, in general, delayed protein translocation protects mitochondria against toxic CAT-tailed proteins.

cell biology↗

Dynamics of dominance: maneuvers, contests, and assessment in the posture-scalemovements of interacting zebrafish

While two-body fighting behavior occurs throughout the animal kingdom to settle dominance disputes, important questions such as how the dynamics ultimately lead to a winner and loser are unresolved. Here we examine fighting behavior at high-resolution in male zebrafish. We combine multiple cameras, a large volume containing a transparent interior cage to avoid reflection artifacts, with computer vision to track multiple body points across multiple organisms while maintaining individual identity in 3D. In the body point trajectories we find a spectrum of timescales which we use to build informative joint coordinates consisting of relative orientation and distance. We use the distribution of these coordinates to automatically identify fight epochs, and we demonstrate the post-fight emergence of an abrupt asymmetry in relative orientations-a clear and quantitative signal of hierarchy formation. We identify short-time, multi-animal behaviors as clustered transitions between joint configurations, and show that fight epochs are spanned by a subset of these clusters, which we denote as maneuvers. The resulting space of maneuvers is rich but interpretable, including motifs such as "attacks" and "circling". In the longer-time dynamics of maneuver frequencies we find differential and changing strategies, including that the eventual loser attacks more often towards the end of the contest. Our results suggest a reevaluation of relevant assessment models in zebrafish, while our approach is generally applicable to other animal systems.

biophysics↗