メロンとキュウリのＡＣＣ合成酵素遺伝子の構造的特徴とＧＵＳトランジェントアッセイによるプロモーター活性

In orader to clarify the differences in regulatory mechanism(s) of the expression of 1-aminocyclopropane-1-carboxylate(ACC) synthase(ACS)genes during ripening in climacteric melon fruit and non-climacteric cucumber fruit, two sets of their genomic DNA sequences, including ca. 2kb of the promoter regions were determined, using PCR-based methods. ACS genes from melon (CMe-ACS1,2) were structurally similar to their counterpart from cucumber (CS-ACS1,2) in terms of size and position of exons and introns, restriction map, and sequencd identity of exeons, introns, proximal 5'-flanking promoter regions and splice junction. Southern blot analysis indicated that each ACS gene is present as a single copy. Transient promoter activity was investigated with two constructs of promoter-β-glucuronidase (GUS) fusion, CMe-ACS1:GUS and CS-ACS1:GUS, in mature mesocarp tissue of the two fruits. In melon disks, GUS activities conferred by the promoters of both CS-ACS1 (-2098～+42) and CMe-ACS-1(-2187～+67) were detected, which were decreased by treatment with 1-methylcyclopropene(1-MCP), an ethylene action inhibitor. In cucumber disks, however, only CS-ACS1:GUS was expressed; the activity was decreased with 1-MCP, and it was not affected by propylene. These results suggest that the promoter of CS-ACS1 has a potential to be expressed in the mesocarp tissue of ripening melon fruit, and that the difference in ethylene biosynthesis between melon and cucumber during ripening may be due to the difference in capability of forming trans-acting factor(s), not due to their ACS1 promoter activities.クライマクテリック型果実のメロンとノンクライマクテリック型果実のキュウリの果実追熟に伴う１-アミ ノシクロプロパン-１-カルボン酸（ACC）合成酵素（ACS）遺伝子の発現調節機構の相違を明らかにするた めに，それぞれ２種類のACSのゲムノDNA配列（約２kb）をPCR法を基にして決定した．メロンのACS 遺伝子は，エキソンとイントロンのサイズおよび位置，制限酵素地図，エキソン・イントロン・近位の５’上 流プロモーター領域・スプライシング部位の塩基配列において，それぞれ対応するキュウリのACS遺伝子 とよく似た構造をしていた．サザンブロック解析の結果，各ACS遺伝子はシングルコピーとして存在する と考えられた．CMe-ACS1とCS-ACS1の一過的プロモーター活性をβ-グルクロニダーゼ（GUS）をレポ ーター遺伝子として両果実の成熟果肉を用いて調べた．メロン切片では，CS-ACS1（－2098～＋42）なら びにCMe-ACS1（－2187～＋67）のプロモーター発現によるGUS活性が検出され，エチレン作用阻害剤 の１-メチルシクロプロペン（１-MCP）処理によって減少した．しかし，キュウリ切片においては，CS-ACS1： GUSのみでGUSが発現し，活性は１-MCP処理で減少し，プロピレン処理ではコントロールと同レベル であった．これらの結果より，CS-ACS1のプロモーターがメロン成熟果肉組織で発現する潜在能力をもつ こと，メロンとキュウリの成熟に伴うエチレン生合成の相違はACS1プロモーター活性によるものではなく， 両者のトランス因子合成能の相違によることが示唆された

クモ膜下出血による脳組織の代謝障害について

金沢大学医学部研究課題/領域番号:X00120----987069, 研究期間(年度):1974出典：「クモ膜下出血による脳組織の代謝障害について」研究成果報告書　課題番号：X00120----987069（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-X00120----987069/）を加工して作

脳血管障害(とくに脳出血)時における急性期病態生理学的研究

金沢大学医学部研究課題/領域番号58480300, 研究期間(年度):1983 – 1984出典：研究課題「脳血管障害(とくに脳出血)時における急性期病態生理学的研究」課題番号58480300（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-58480300/）を加工して作

排尿機能の中枢機序

金沢大学医学部研究課題/領域番号:X44120-----70026, 研究期間(年度):1969出典：研究課題「排尿機能の中枢機序」課題番号 X44120-----70026（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-X44120-----70026/）を加工して作

Cognitive dysfunction and amyloid β accumulation are ameliorated by the ingestion of green soybean extract in aged mice

AbstractThe effects of soybean extracts were investigated in senescence-accelerated (SAMP10) mice, a mouse model of brain senescence with cognitive dysfunction. Mature soybeans are usually yellow. However, the green soybean retains green color after being ripened. Cognitive functions were significantly better-preserved in aged mice fed green soybean than age-matched control mice with or without yellow soybean feeding. Molecular mechanisms of the beneficial effect of green soybean on brain functions were examined through transcriptome analysis of SAMP10 hippocampus. The high expression of Ptgds was significantly associated with green soybean diet, which encodes lipocalin-type prostaglandin D2 synthase, a putative endogenous amyloid β(Αβ)-chaperone. In consonance, Aplp1 expression was significantly reduced, a member of amyloid precursor proteins. Furthermore, the amount of Aβ 40 and 42 was reduced in the insoluble fraction of cerebral cortex. These results suggest that the intake of green soybean ameliorates cognitive dysfunction of aged mice through the reduction of Aβ accumulation

Efficacy of prophylactic clip closure in reducing the risk of delayed bleeding after colorectal endoscopic submucosal dissection in patients on anticoagulant therapy: Multicenter prospective study

Ogiyama H., Kato M., Yamaguchi S., et al. Efficacy of prophylactic clip closure in reducing the risk of delayed bleeding after colorectal endoscopic submucosal dissection in patients on anticoagulant therapy: Multicenter prospective study. Digestive Endoscopy , (2024); https://doi.org/10.1111/den.14761.Objectives: The high rate of delayed bleeding after colorectal endoscopic submucosal dissection (ESD) in patients undergoing anticoagulant therapy remains a problem. Whether prophylactic clip closure reduces the rate of delayed bleeding in these patients is unclear. This study aimed to evaluate the efficacy of prophylactic clip closure in patients receiving anticoagulants. Methods: This multicenter prospective interventional trial was conducted at nine referral centers in Japan. Patients regularly taking anticoagulants, including warfarin potassium or direct oral anticoagulants, and undergoing ESD for colorectal neoplasms were enrolled. The discontinuation of anticoagulants was minimized according to recent guidelines. After the ESD, post-ESD ulcers were prophylactically closed using endoclips. The primary end-point was the incidence of delayed bleeding. The sample size was 45 lesions, and prophylactic clip closure was considered effective when the upper limit of the 90% confidence interval (CI) for delayed bleeding did not exceed 20%. Results: Forty-five lesions were used, and three were excluded. Complete closure was achieved in 41/42 lesions (97.6%). The overall delayed bleeding rate was low, at 4.9% (2/41; 90% [CI] 0.8–14.5), which was significantly lower than that at the prespecified threshold of 20% (P = 0.007). The median closure procedure time was 17 min, and the median number of clips was nine. No massive delayed bleeding requiring transfusion, interventional radiology, or surgery was observed, and no thromboembolic events were observed. Conclusion: Prophylactic clip closure may reduce the risk of delayed bleeding following colorectal ESD in patients receiving anticoagulants. Trial registration: UMIN Clinical Trial Registry (UMIN000036734)

Mutations in the hepatitis B virus preS2 region and abrogated receptor activity for polymerized human albumin.

The preS2 region of the hepatitis B virus (HBV) has been reported to have human polymerized albumin receptor (PAR) activity, which correlates with viral replication. Here, we studied the genomic sequence of the preS region from rare patients lacking PAR activity, despite active viral replication. PAR and DNA polymerase activity was identified in 178 HBe antigen-positive HBV carriers, and a significant correlation between 2 markers was shown, except in 2 hepatitis patients lacking PAR activity. Nucleotide sequences of the preS region of HBV from both patients were examined by direct sequencing of PCR products. In one patient, a 45-base deletion was found to overlap half of the putative polymerized human albumin binding site in the preS2 region. In the other patient, a point mutation at the first nucleotide of the start codon of the preS2 region of HBV was found. There was no such genomic change in the 3 control HBV sequences. These results indicate that the preS2 region is necessary for binding of polymerized human albumin, and this is the first report of naturally existing mutant virus with no or low PAR activity.</p

A machine learning model for predicting the lymph node metastasis of early gastric cancer not meeting the endoscopic curability criteria

The version of record of this article, first published in Gastric Cancer, is available online at Publisher’s website: https://doi.org/10.1007/s10120-024-01511-8.Background: We developed a machine learning (ML) model to predict the risk of lymph node metastasis (LNM) in patients with early gastric cancer (EGC) who did not meet the existing Japanese endoscopic curability criteria and compared its performance with that of the most common clinical risk scoring system, the eCura system. Methods: We used data from 4,042 consecutive patients with EGC from 21 institutions who underwent endoscopic submucosal dissection (ESD) and/or surgery between 2010 and 2021. All resected EGCs were histologically confirmed not to satisfy the current Japanese endoscopic curability criteria. Of all patients, 3,506 constituted the training cohort to develop the neural network-based ML model, and 536 constituted the validation cohort. The performance of our ML model, as measured by the area under the receiver operating characteristic curve (AUC), was compared with that of the eCura system in the validation cohort. Results: LNM rates were 14% (503/3,506) and 7% (39/536) in the training and validation cohorts, respectively. The ML model identified patients with LNM with an AUC of 0.83 (95% confidence interval, 0.76–0.89) in the validation cohort, while the eCura system identified patients with LNM with an AUC of 0.77 (95% confidence interval, 0.70–0.85) (P = 0.006, DeLong’s test). Conclusions: Our ML model performed better than the eCura system for predicting LNM risk in patients with EGC who did not meet the existing Japanese endoscopic curability criteria. Mini-abstract: We developed a neural network-based machine learning model that predicts the risk of lymph node metastasis in patients with early gastric cancer who did not meet the endoscopic curability criteria

Vagus-macrophage-hepatocyte link promotes post-injury liver regeneration and whole-body survival through hepatic FoxM1 activation

The mechanisms underlying the regenerative capacity of the liver are not fully understood. Here, the authors show that the acute regenerative response to liver injury in mice is regulated by the communication involving the vagus nerve, macrophages, and hepatocytes, leading to hepatic FoxM1 activation and promotion of overall survival

A novel artificial intelligence-based endoscopic ultrasonography diagnostic system for diagnosing the invasion depth of early gastric cancer

The version of record of this article, first published in Journal of Gastroenterology, is available online at Publisher’s website: https://doi.org/10.1007/s00535-024-02102-1.Background: We developed an artificial intelligence (AI)-based endoscopic ultrasonography (EUS) system for diagnosing the invasion depth of early gastric cancer (EGC), and we evaluated the performance of this system. Methods: A total of 8280 EUS images from 559 EGC cases were collected from 11 institutions. Within this dataset, 3451 images (285 cases) from one institution were used as a development dataset. The AI model consisted of segmentation and classification steps, followed by the CycleGAN method to bridge differences in EUS images captured by different equipment. AI model performance was evaluated using an internal validation dataset collected from the same institution as the development dataset (1726 images, 135 cases). External validation was conducted using images collected from the other 10 institutions (3103 images, 139 cases). Results: The area under the curve (AUC) of the AI model in the internal validation dataset was 0.870 (95% CI: 0.796–0.944). Regarding diagnostic performance, the accuracy/sensitivity/specificity values of the AI model, experts (n = 6), and nonexperts (n = 8) were 82.2/63.4/90.4%, 81.9/66.3/88.7%, and 68.3/60.9/71.5%, respectively. The AUC of the AI model in the external validation dataset was 0.815 (95% CI: 0.743–0.886). The accuracy/sensitivity/specificity values of the AI model (74.1/73.1/75.0%) and the real-time diagnoses of experts (75.5/79.1/72.2%) in the external validation dataset were comparable. Conclusions: Our AI model demonstrated a diagnostic performance equivalent to that of experts