Tributyltin Inhibits Neural Induction of Human Induced Pluripotent Stem Cells

Tributyltin (TBT), one of the organotin compounds, is a well-known environmental pollutant. In our recent study, we reported that TBT induces mitochondrial dysfunction, in human-induced pluripotent stem cells (iPSCs) through the degradation of mitofusin1 (Mfn1), which is a mitochondrial fusion factor. However, the effect of TBT toxicity on the developmental process of iPSCs was not clear. The present study examined the effect of TBT on the differentiation of iPSCs into the ectodermal, mesodermal, and endodermal germ layers. We found that exposure to nanomolar concentration of TBT (50 nM) selectively inhibited the induction of iPSCs into the ectoderm, which is the first step in neurogenesis. We further assessed the effect of TBT on neural differentiation and found that it reduced the expression of several neural differentiation marker genes, which were also downregulated by Mfn1 knockdown in iPSCs. Taken together, these results indicate that TBT induces developmental neurotoxicity via Mfn1-mediated mitochondrial dysfunction in iPSCs

Development of a preoperative prediction model for new-onset diabetes mellitus after partial pancreatectomy

ABSTRACT: Pancreatectomy is an invasive surgery that is sometimes associated with complications. New-onset diabetes mellitus sometimes develops after partial pancreatectomy and severely affects the patient's quality of life. This study aimed to develop a preoperative prediction model of new-onset diabetes mellitus after partial pancreatectomy, which will help patients and surgeons to achieve more easily better common decisions on regarding whether to perform partial pancreatectomy. This retrospective cohort study analyzed medical records of patients who underwent partial pancreatectomy (total pancreatectomy excluded) from April 1, 2008, to February 28, 2016, which were available in the database provided by Medical Data Vision Co., Ltd. (Tokyo, Japan). The predictors were preoperative age, body mass index, hemoglobin A1c level, blood glucose level, and indication for partial pancreatectomy. The outcome was the development of new-onset diabetes mellitus at 1 to 12 months after partial pancreatectomy. We used a logistic regression model and calculated the scores of each predictor. To determine test performance, we assessed discrimination ability using the receiver operating characteristic curve and calibration with a calibration plot and the Hosmer-Lemeshow test. We also performed internal validation using the bootstrap method. Of 681 patients, 125 (18.4%) had new-onset diabetes mellitus after partial pancreatectomy. The developed prediction model had a possible range of 0 to 46 points. The median score was 13, and the interquartile range was 9 to 22. The C-statistics of the receiver operating characteristic curve on the score to predict the outcome was .70 (95% confidence interval [CI], .65-.75). Regarding the test performance, the Hosmer-Lemeshow test was not significant (P = .17), and calibration was good. In the bootstrapped cohorts, the C-statistics was .69 (95% CI, .62-.76). We developed a preoperative prediction model for new-onset diabetes mellitus after partial pancreatectomy. This would provide important information for surgeons and patients when deciding whether to perform partial pancreatectomy

Application of a Heat- and Steam-Generating Sheet Increases Peripheral Blood Flow and Induces Parasympathetic Predominance

To promote the practical application of a Japanese traditional medical treatment, such as hot compresses, we developed a plaster-type warming device consisting of a heat- and steam-generating sheet (HSG sheet). First, we tested its effects when applied to the anterior abdominal wall or lumbar region of women complaining of a tendency towards constipation. Application of the sheet to either region produced a feeling of comfort in the abdomen, as assessed by a survey of the subjects. The significant increases in the total hemoglobin observed in these regions suggested an increase in peripheral blood flow, and significant increases in the HF component on ECG and in the amplitude of gastric motility suggested parasympathetic predominance. We concluded that application of the HSG sheet improves the peripheral hemodynamics and autonomic regulation, induces a feeling of comfort in the abdomen, and provides a beneficial environment for the improvement of gastrointestinal movements

Tomato root-associated Sphingobium harbors genes for catabolizing toxic steroidal glycoalkaloids

トマト根に定着する細菌からトマトの毒を分解する酵素を発見 --土壌微生物が植物の分泌する有害成分を解毒するメカニズムの理解に貢献--. 京都大学プレスリリース. 2023-10-02.Roots of Bloody Mary. Tomato root-associated Sphingobium harbors genes for neutralizing toxic compound. 京都大学プレスリリース. 2023-10-06.Plant roots exude various organic compounds, including plant specialized metabolites (PSMs), into the rhizosphere. The secreted PSMs enrich specific microbial taxa to shape the rhizosphere microbiome, which is crucial for the healthy growth of the host plants. PSMs often exhibit biological activities; in turn, some microorganisms possess the capability to either resist or detoxify them. Saponins are structurally diverse triterpene-type PSMs that are mainly produced by angiosperms. They are generally considered as plant defense compounds. We have revealed that α-tomatine, a steroid-type saponin secreted from tomato (Solanum lycopersicum) roots, increases the abundance of Sphingobium bacteria. To elucidate the mechanisms underlying the α-tomatine-mediated enrichment of Sphingobium, we isolated Sphingobium spp. from tomato roots and characterized their saponin-catabolizing abilities. We obtained the whole-genome sequence of Sphingobium sp. RC1, which degrades steroid-type saponins but not oleanane-type ones, and performed a gene cluster analysis together with a transcriptome analysis of α-tomatine degradation. The in vitro characterization of candidate genes identified six enzymes that hydrolyzed the different sugar moieties of steroid-type saponins at different positions. In addition, the enzymes involved in the early steps of the degradation of sapogenins (i.e., aglycones of saponins) were identified, suggesting that orthologs of the known bacterial steroid catabolic enzymes can metabolize sapogenins. Furthermore, a comparative genomic analysis revealed that the saponin-degrading enzymes were present exclusively in certain strains of Sphingobium spp., most of which were isolated from tomato roots or α-tomatine-treated soil. Taken together, these results suggest a catabolic pathway for highly bioactive steroid-type saponins in the rhizosphere

Detailed analyses of the crucial functions of Zn transporter proteins in alkaline phosphatase activation

Numerous zinc ectoenzymes are metalated by zinc and activated in the compartments of the early secretory pathway before reaching their destination. Zn transporter (ZNT) proteins located in these compartments are essential for ectoenzyme activation. We have previously reported that ZNT proteins, specifically ZNT5-ZNT6 heterodimers and ZNT7 homodimers, play critical roles in the activation of zinc ectoenzymes, such as alkaline phosphatases (ALPs), by mobilizing cytosolic zinc into these compartments. However, this process remains incompletely understood. Here, using genetically-engineered chicken DT40 cells, we first determined that Zrt/Irt-like protein (ZIP) transporters that are localized to the compartments of the early secretory pathway play only a minor role in the ALP activation process. These transporters included ZIP7, ZIP9, and ZIP13, performing pivotal functions in maintaining cellular homeostasis by effluxing zinc out of the compartments. Next, using purified ALP proteins, we showed that zinc metalation on ALP produced in DT40 cells lacking ZNT5-ZNT6 heterodimers and ZNT7 homodimers is impaired. Finally, by genetically disrupting both ZNT5 and ZNT7 in human HAP1 cells, we directly demonstrated that the tissue-nonspecific ALP-activating functions of both ZNT complexes are conserved in human cells. Furthermore, using mutant HAP1 cells, we uncovered a previously-unrecognized and unique spatial regulation of ZNT5-ZNT6 heterodimer formation, wherein ZNT5 recruits ZNT6 to the Golgi apparatus to form the heterodimeric complex. These findings fill in major gaps in our understanding of the molecular mechanisms underlying zinc ectoenzyme activation in the compartments of the early secretory pathway

Tara up-regulates E-cadherin transcription by binding to the Trio RhoGEF and inhibiting Rac signaling

In the absence of Tara, Trio binds to E-cadherin and increases activation of the E-cadherin transcriptional repressor Tbx3

Endoscopic Treatment of Sinonasal Glomangiopericytoma: A Case Report in Light of the Literature

A 71-year-old Japanese male patient presented with a rare case of Glomangiopericytoma (GPC) of the left nasal with obstruction. Complete resection with endoscopic surgery was performed. Immunohistochemical staining for smooth muscle actin, β catenin, cyclin D1, vimentin, and factor 13 were helpful in establishing a definitive diagnosis. Extranasal treatment has been traditionally performed for successful management. However, recent advances in endoscopic treatment have enabled complete endoscopic resection of GPC, minimizing morbidity and facilitating subsequent surveillance for recurrence. Endoscopic management should be considered in suitable cases

『現代日本語書き言葉均衡コーパス』の文境界修正

国立国語研究所 コーパス開発センター 非常勤研究員マンパワーグループ株式会社国立国語研究所 理論・構造研究系 非常勤研究員国立国語研究所 コーパス開発センター 非常勤研究員国立国語研究所 言語資源研究系国立国語研究所 コーパス開発センター 技術補佐員(元)国立国語研究所 コーパス開発センター プロジェクト研究員文部科学省国立国語研究所 言語資源研究系国立国語研究所 言語資源研究系国立国語研究所 言語資源研究系国立国語研究所 言語資源研究系国立国語研究所 言語資源研究系Adjunct Researcher, Center for Corpus Development, NINJALManpower Group Co., LtdAdjunct Researcher, Department of Linguistic Theory and Structure, NINJALAdjunct Researcher, Center for Corpus Development, NINJALDepartment of Corpus Studies, NINJAL(former) Technical Staff, Center for Corpus Development, NINJALPostdoctoral Research Fellow, Center for Corpus Development, NINJALMinistry of Education, Culture, Sports, Science, and TechnologyDepartment of Corpus Studies, NINJALDepartment of Corpus Studies, NINJALDepartment of Corpus Studies, NINJALDepartment of Corpus Studies, NINJALDepartment of Corpus Studies, NINJAL『現代日本語書き言葉均衡コーパス』第1.0版(Maekawa et al. 2014)(以下BCCWJ)には「文境界」の情報がアノテーションされているが,その認定基準の妥当性について従来から様々な指摘がある(小西ほか2014,長谷川2014,田野村2014)。この問題に対処するために,国立国語研究所コーパス開発センターでは2013年から2014年にかけて,BCCWJの修正を行った。本稿ではその修正作業について報告する。第1.0版におけるBCCWJ 文境界情報の問題は,コーパス構築の過程において文境界を含む文書構造タグの整備と形態素列レベルの情報の整備とを並行して行ったために,文字情報を用いる文境界処理にとどまったことに由来する。今回,形態論情報に基づいた文境界基準を策定し,問題の解消を試みた。文境界修正の指針を示すとともに,文境界修正に用いた作業環境と,修正件数について報告する。In December 2011, the National Institute for Japanese Language and Linguistics (NINJAL) released a 100-million-word balanced corpus - the Balanced Corpus of Contemporary Written Japanese (BCCWJ) DVD Version 1.0 - which was compiled from 2006 through 2011. Some users have pointed out some issues concerning sentence delimitation in the BCCWJ. To address these issues, we - NINJAL - performed a complete survey and correction, beginning in 2013 and ending in 2014. This article reports the revision work on sentence delimitation in the BCCWJ. The problems with the BCCWJ DVD Version 1.0 derive from the string-based definition. We could not obtain any morpheme information for the sentence delimitation task because of the task parallelism between sentence delimitation annotation and morpheme annotation. The method used this time was morpheme based. We present the morpheme-based annotation guidelines, annotation environment, and basic statistics of the corpus correction