Biology subjects

Uchida, T.

Publications and source records attributed to Uchida, T..

4 recordsLinked to original sources

bioRxiv2021

All-trans retinoic acid induces GADD34 gene expression via transcriptional regulation by Six1-TLE3 and post-transcriptional regulation by p38-TTP in skeletal muscle

All-trans retinoic acid (ATRA) increases the sensitivity to unfolded protein response (UPR) in differentiating leukemic blasts. The downstream transcriptional factors of PERK, a major arm of UPR, regulates muscle differentiation. However, the role of growth arrest and DNA damage-inducible protein 34 (GADD34), one of the downstream factors of PERK, and the effects of ATRA on GADD34 expression in muscle remain unclear. In this study, we identified ATRA increased the GADD34 expression independent of the PERK signal in the gastrocnemius muscle of mice. ATRA up-regulated GADD34 expression through the transcriptional activation of it via inhibiting the interaction of homeobox Six1 and transcription co-repressor TLE3 with the MEF3-binding site on the GADD34 gene promoter in myoblasts. ATRA also inhibited the interaction of TTP, which induces mRNA degradation, with AU-rich element on GADD34 mRNA via p38 MAPK, resulting in the instability of GADD34 mRNA. Overexpressed GADD34 in myoblasts changes the type of myosin heavy chain in myotubes. These results suggest ATRA increases GADD34 expression via transcriptional and post-transcriptional regulation in myoblasts, which changes muscle fiber type in myotubes.

biochemistry↗

bioRxiv2021

Validity and sensitivity of an inertial measurement unit-driven biomechanical model of motor variability for gait

Motor variability in gait is frequently linked to fall risk, yet field-based biomechanical joint evaluations are scarce. We evaluated the validity and sensitivity of an inertial measurement unit (IMU)-driven biomechanical model of joint angle variability for gait. Fourteen healthy young adults completed seven-minute trials of treadmill gait at several speeds and arm swing amplitudes. Joint kinematics were estimated by IMU- and optoelectronic-based models using OpenSim. We calculated range of motion (ROM), magnitude of variability (meanSD), local dynamic stability ({lambda}max), persistence of ROM fluctuations (DFA), and regularity (SaEn) of each angle over 200 continuous strides, and evaluated model accuracy (e.g., RMSD: root mean square difference), consistency (ICC2,1: intraclass correlation), biases, limits of agreement, and sensitivity to within-participant gait responses (effects of Speed and Swing). RMSDs of joint angles were 1.7-7.5{degrees} (pooled mean of 4.8{degrees}), excluding ankle inversion. ICCs were mostly good- excellent in the primary plane of motion for ROM and in all planes for meanSD and {lambda}max, but were poor-moderate for DFA and SaEn. Modeled Speed and Swing responses for ROM, meanSD, and {lambda}max were similar. Results suggest that the IMU-driven model is valid and sensitive for field-based assessments of joint angles and several motor variability features.

bioengineering↗

bioRxiv2020

Transcriptome analysis of sevoflurane exposure effects at the different brain regions

BackgroundsSevoflurane is a most frequently used volatile anaesthetics, but its molecular mechanisms of action remain unclear. We hypothesized that specific genes play regulatory roles in whole brain exposed to sevoflurane. Thus, we aimed to evaluate the effects of sevoflurane inhalation and identify potential regulatory genes by RNA-seq analysis. MethodsEight-week old mice were exposed to sevoflurane. RNA from four medial prefrontal cortex, striatum, hypothalamus, and hippocampus were analysed using RNA-seq. Differently expressed genes were extracted. Their gene ontology terms and the transcriptome array data of the cerebral cortex of sleeping mice were analysed using Metascape, and the gene expression patterns were compared. Finally, the activities of transcription factors were evaluated using a weighted parametric gene set analysis (wPGSA). JASPAR was used to confirm the existence of binding motifs in the upstream sequences of the differently expressed genes. ResultsThe gene ontology term enrichment analysis result suggests that sevoflurane inhalation upregulated angiogenesis and downregulated neural differentiation in the whole brain. The comparison with the brains of sleeping mice showed that the gene expression changes were specific to anaesthetized mice. Sevoflurane induced Klf4 upregulation in the whole brain. The transcriptional analysis result suggests that KLF4 is a potential transcriptional regulator of angiogenesis and neural development. ConclusionsKlf4 was upregulated by sevoflurane inhalation in whole brain. KLF4 might promote angiogenesis and cause the appearance of undifferentiated neural cells by transcriptional regulation. The roles of KLF4 might be key to elucidating the mechanisms of sevoflurane induced functional modification in the brain.

genetics↗

bioRxiv2020

Cystal structure of inhibitor-bound human MSPL/TMPRSS13 that can activate high pathogenic avian influenza

Infection of certain influenza viruses is triggered when its hemagglutinin (HA) is cleaved by host cell proteases such as proprotein convertases and type II transmembrane serine proteases (TTSP). HA with a monobasic motif is cleaved by trypsin-like proteases, including TMPRSS2 and HAT, while the multibasic motif found in high pathogenicity avian influenza HA is cleaved by furin, PC5/6, or MSPL. MSPL belongs to the TMPRSS family and preferentially cleaves [R/K]-K-K-R{downarrow} sequences. Here, we solved the crystal structure of the extracellular region of human MSPL in complex with an irreversible substrate-analog inhibitor. The structure revealed three domains clustered around the C-terminal -helix of the SPD. The inhibitor structure and its putative model show that the P1-Arg inserts into the S1 pocket, whereas the P2-Lys and P4-Arg interacts with the Asp/Glu-rich 99-loop that is unique to MSPL. Based on the structure of MSPL, we also constructed a homology model of TMPRSS2, which is essential for the activation of the SARS-CoV-2 spike protein and infection. The model may provide the structural insight for the drug development for COVID-19.

biophysics↗