Does the Act on the Safety of Regenerative Medicine in Japan ensure “safety”?: Implications of low adverse event reporting

再生医療法に基づく再生医療で生じる有害事象の報告状況を調査 --報告件数の少なさは何を意味するのか？. 京都大学プレスリリース. 2023-11-20.Does the Act on the Safety of Regenerative Medicine in Japan ensure “Safety”？ : Implications of low adverse event reporting. 京都大学プレスリリース. 2023-11-20.Public document analysis reveals that the adverse events reported for therapeutic administration under the Act on the Safety of Regenerative Medicine (ASRM) in Japan are substantially fewer than those under the Pharmaceuticals and Medical Devices Act. This study highlights the flawed reporting mechanisms and unmet legislative intentions of the ASRM

Frequency and Distribution of Candida Species from Denture Wearers

Species of Candida were isolated from 100 denture wearers, who were examined for grade of denture stomatitis, degree of denture plaque accumulation and other clinical features. Candida albicans was the dominant species isolated from denture surfaces followed by Torulopsis glabrata and Candida tropicalis. Statistical analysis of the results revealed close relationships between the grade of denture stomatitis and the degree of denture plaque accumulation or the fungal concentration on the denture surface, and also between the degree of denture plaque accumulation and fungal concentration on the denture surface. Furthermore, the grade of denture stomatitis correlated with the period of denture wearing but not with the patient's age. The fungal concentration on denture surface also correlated with the patient's age and the period of denture wearing

Le caricaturiste Auguste Bouquet

Auguste Bouquet est peintre, lithographe, graveur et caricaturiste. Il réalise également de nombreuses lithographies de caricatures pour les journaux suivants: La Caricature et Le Charivari. Cependant, il n’y a pas beaucoup de travaux sur Auguste Bouquet, qui inspire pourtant certains auteurs comme Honoré Daumier, J.-J. Grandville et Charles Philipon.L’effacement d’Auguste Bouquet est certainement dû au fait qu’il ne participe pas à l’aventure de la « Poire », engendrée par Charles Philipon. Ce dernier réussit un tour de force qui est de représenter le roi sous la forme d’un fruit, la poire, comme métaphore, afin de ne pas avoir à dessiner son vrai visage. Mais Auguste Bouquet peut-il être considéré véritablement comme une personne importante dans le développement de la caricature en France ?Pour éclaircir la contribution de Bouquet à l’histoire de la caricature et le rôle des journaux illustrés satiriques, nous regardons la courte vie de ce mystérieux caricaturiste, nous analysons ses oeuvres, puis nous considérons le problème de la censure en particulier concernant la situation sociale, à travers la présentation du roi, Louis-Philippe.Auguste Bouquet est avant tout connu en tant que portraitiste de Jean-Gaspard Deburau mais n’est pas particulièrement estimé dans le domaine de la caricature. Mais, en connaissant le contexte politique de l’époque de Bouquet, il est inévitable de souligner la subtilité de la satire dans ses caricatures. De fait, dans le dernier article de La Caricature, Charles Philipon cite son nom en troisième position des caricaturistes de son journal.Après réflexion, il ne fait aucun doute, que Bouquet joue un rôle non négligeable dans la diffusion de la représentation de Louis-Philippe sous forme de poire. La contribution d’Auguste Bouquet a ainsi été sous-estimée

A dominant-negative FGF1 mutant (the R50E mutant) suppresses tumorigenesis and angiogenesis.

Fibroblast growth factor-1 (FGF1) and FGF2 play a critical role in angiogenesis, a formation of new blood vessels from existing blood vessels. Integrins are critically involved in FGF signaling through crosstalk. We previously reported that FGF1 directly binds to integrin αvβ3 and induces FGF receptor-1 (FGFR1)-FGF1-integrin αvβ3 ternary complex. We previously generated an integrin binding defective FGF1 mutant (Arg-50 to Glu, R50E). R50E is defective in inducing ternary complex formation, cell proliferation, and cell migration, and suppresses FGF signaling induced by WT FGF1 (a dominant-negative effect) in vitro. These findings suggest that FGFR and αvβ3 crosstalk through direct integrin binding to FGF, and that R50E acts as an antagonist to FGFR. We studied if R50E suppresses tumorigenesis and angiogenesis. Here we describe that R50E suppressed tumor growth in vivo while WT FGF1 enhanced it using cancer cells that stably express WT FGF1 or R50E. Since R50E did not affect proliferation of cancer cells in vitro, we hypothesized that R50E suppressed tumorigenesis indirectly through suppressing angiogenesis. We thus studied the effect of R50E on angiogenesis in several angiogenesis models. We found that excess R50E suppressed FGF1-induced migration and tube formation of endothelial cells, FGF1-induced angiogenesis in matrigel plug assays, and the outgrowth of cells in aorta ring assays. Excess R50E suppressed FGF1-induced angiogenesis in chick embryo chorioallantoic membrane (CAM) assays. Interestingly, excess R50E suppressed FGF2-induced angiogenesis in CAM assays as well, suggesting that R50E may uniquely suppress signaling from other members of the FGF family. Taken together, our results suggest that R50E suppresses angiogenesis induced by FGF1 or FGF2, and thereby indirectly suppresses tumorigenesis, in addition to its possible direct effect on tumor cell proliferation in vivo. We propose that R50E has potential as an anti-cancer and anti-angiogenesis therapeutic agent ("FGF1 decoy")

Endoscopic Laser Treatment for Pediatric Nasal Allergy

We have used the carbon dioxide (CO2) laser and the gallium aluminium arsenide (GaAlAs) diode laser with flexible fiber delivery instruments for vaporization of the inferior nasal turbinate in pediatric patients since 1993. Under endoscopic control, the whole inferior turbinate was vaporized by 5–10 W laser output delivered via an optical fiber. Generally, the nasal mucosa changes into normal mucosa, and symptoms improve. The greatest symptomatic improvement was in nasal obstruction. The results obtained by the two laser devices were similar although they have had different characteristics. Endoscopic laser surgery is effective in the treatment of pediatric nasal allergy

A Novel Fibroblast Growth Factor-1 (FGF1) Mutant that Acts as an FGF Antagonist

Background: Crosstalk between integrins and FGF receptors has been implicated in FGF signaling, but the specifics of the crosstalk are unclear. We recently discovered that 1) FGF1 directly binds to integrin avb3, 2) the integrin-binding site and FGF receptor (FGFR) binding site are distinct, and 3) the integrin-binding-defective FGF1 mutant (R50E) is defective in inducing FGF signaling although R50E still binds to FGFR and heparin and induces transient ERK1/2 activation. Principal Findings: We tested if excess R50E affect DNA synthesis and cell survival induced by WT FGF1 in BaF3 mouse pro-B cells expressing human FGFR1. R50E suppressed DNA synthesis and cell proliferation induced by WT FGF1. We tested if WT FGF1 and R50E generate integrin-FGF1-FGFR ternary complex. WT FGF1 induced ternary complex formation (integrin-FGF-FGFR1) and recruitment of SHP-2 to the complex in NIH 3T3 cells and human umbilical endothelial cells, but R50E was defective in these functions. It has been reported that sustained ERK1/2 activation is integrin-dependent and crucial to cell cycle entry upon FGF stimulation. We thus determined the time-course of ERK1/2 activation induced by WT FGF1 and R50E. We found that WT FGF1 induced sustained activation of ERK1/2, but R50E was defective in this function. Conclusions/Significance: Our results suggest that 1) R50E is a dominant-negative mutant, 2) Ternary complex formation is involved in FGF signaling, 3) The defect of R50E to bind to integrin may be directly related to the antagonistic action o

Cryo-electron microscopic structure of the nucleoprotein-RNA complex of the European filovirus, Lloviu virus

ヨーロッパに分布するエボラウイルス近縁ウイルスの増殖機構を解明 --広範囲の抗フィロウイルス療法の開発に期待--. 京都大学プレスリリース. 2023-04-10.Lloviu virus (LLOV) is a novel filovirus detected in Schreiber’s bats in Europe. The isolation of the infectious LLOV from bats has raised public health concerns. However, the virological and molecular characteristics of LLOV remain largely unknown. The nucleoprotein (NP) of LLOV encapsidates the viral genomic RNA to form a helical NP-RNA complex, which acts as a scaffold for nucleocapsid formation and de novo viral RNA synthesis. In this study, using single-particle cryo-electron microscopy, we determined two structures of the LLOV NP-RNA helical complex, comprising a full-length and a C-terminally truncated NP. The two helical structures were identical, demonstrating that the N-terminal region determines the helical arrangement of the NP. The LLOV NP-RNA protomers displayed a structure similar to that in the Ebola and Marburg virus, but the spatial arrangements in the helix differed. Structure-based mutational analysis identified amino acids involved in the helical assembly and viral RNA synthesis. These structures advance our understanding of the filovirus nucleocapsid formation, and provide a structural basis for the development of anti-filoviral therapeutics

Feeding the outer bran fraction of rice alters hepatic carbohydrate metabolism in rats

Dietary intake of fiber-rich food has been reported to contribute to multiple health benefits. The aim of the current study is to investigate the effects of a diet containing the outer bran fraction of rice (OBFR), which is rich in insoluble fiber, on the intestinal environment and metabolite profiles of rats. Fourteen 8-week-old male Sprague–Dawley rats were divided into a control group and an OBFR group. For a period of 21 days, the control group was fed a control diet, while the OBFR group was fed a diet containing 5% OBFR. Metabolomics analysis revealed drastic changes in the cecal metabolites of the rats fed the OBFR diet. Furthermore, in the plasma and liver tissue, the concentrations of metabolites involved in pyruvate metabolism, the pentose phosphate pathway, gluconeogenesis, or valine, leucine, isoleucine degradation were changed. Concordantly, the OBFR diet increased the expression of genes encoding enzymes involved in these metabolic pathways in the livers of the rats. Collectively, these results suggest that the OBFR diet altered the concentrations of metabolites in the cecal contents, plasma, and liver, and the hepatic gene expressions of rats, and that this may have mainly contributed to carbohydrate metabolism in the liver

Gene Expression and Protein Synthesis in Mitochondria Enhance the Duration of High-Speed Linear Motility in Boar Sperm

Sperm motility patterns are continuously changed after ejaculation to fertilization in the female tract. Hyperactivated motility is induced with high glucose medium in vitro or the oviduct fluids in vivo, whereas sperm maintain linear motility in the seminal plasma or the uterine fluids containing low glucose. Therefore, it is estimated that sperm motility patterns are dependent on the energy sources, and the mitochondrial oxidative phosphorylation is activated to produce ATP in low glucose condition. To elucidate these hypotheses, boar sperm was incubated in different energy conditions with the transcription and translation inhibitors in vitro. Sperm motility parameters, mitochondrial activity, ATP level, gene expression and protein synthesis were analyzed. Sperm progressive motility and straight-line velocity were significantly increased with decreasing glucose level in the incubation medium. Moreover, the mitochondrial protein turnover meaning transcription and translation from mitochondrial genome in sperm is activated during incubation. Incubation of sperm with mitochondrial translation inhibitor (D-chloramphenicol) suppressed mitochondrial protein synthesis, mitochondrial activity and ATP level in sperm and consequently reduced the linear motility speed, but not the motility. Thus, it is revealed that the mitochondrial central dogma is active in sperm, and the high-speed linear motility is induced in low glucose condition via activating the mitochondrial activity for ATP generation.This work was supported in part by Livestock Promotional Funds of Japan Racing Association (JRA) grant no. H30-279 and by Hiroshima Cryopreservation Service Co., grant no. H30-1 (to MS). ZZ was supported by China Scholarship Council during a visit of “Zhendong Zhu” to Hiroshima University (#CSC201706300110).The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphys.2019.00252/full#supplementary-materia