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Effect of Juvenile Social Isolation on Excitability of Prefrontal Pyramidal Cells With Different Subcortical Axonal Projections

2026-02-26T16:30:12Z

タイトル: Effect of Juvenile Social Isolation on Excitability of Prefrontal Pyramidal Cells With Different Subcortical Axonal Projections 著者: Nishihata, Yosuke; Yoshino, Hiroki; Ogawa, Yoichi; Sugimura, Taketoshi; Okamura, Kazuya; Kimoto, Sohei; Yamamuro, Kazuhiko; Makinodan, Manabu; Saito, Yasuhiko; Kishimoto, Toshifumi 抄録: Background: Social experience during development is crucial for the functional maturation of the prefrontal cortex (PFC). Juvenile social isolation (JSI) causes severe PFC dysfunction. JSI reduces intrinsic excitability and excitatory synaptic inputs for a subtype of layer-5 (L5) pyramidal cells showing prominent h-current (PH cells) in the medial PFC. PH cells do not have commissural or associational cortical output; instead, they project into subcortical areas. However, which subcortical area is the projection target of L5 pyramidal cells affected by JSI remains unascertained. Methods: Using retrograde neuronal tracing, we identified L5 pyramidal cells having three different projection targets: the mediodorsal thalamus, striatum, or pontine nuclei. We elucidated differences in functional properties among the three subclasses of L5 pyramidal cells and examined how JSI affects the intrinsic membrane properties and excitatory inputs for each class of L5 pyramidal cells. Results: Pyramidal cells projecting to the pontine nuclei had more excitatory synaptic inputs and more distinguishing intrinsic properties than pyramidal cells projecting to the mediodorsal thalamus and striatum. JSI increased the firing responsiveness of pyramidal cell projecting to mediodorsal thalamus and reduced excitatory synaptic inputs only onto pyramidal cells projecting to the pontine nuclei. Conclusion: JSI affects the development of L5 pyramidal cells based on their projection target. 内容記述: © 2025 Nishihata, Yoshino, Ogawa, Sugimura, Okamura, Kimoto, Yamamuro, Makinodan, Saito and Kishimoto. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Genetic analysis using long-read sequencing to overcome the difficulties in VWF gene

2026-02-26T16:30:11Z

タイトル: Genetic analysis using long-read sequencing to overcome the difficulties in VWF gene 著者: Ye, Sheng; Eura, Yuka; Matsumoto, Masanori; Kokame, Koichi 抄録: Background: Genetic defects in von Willebrand factor (VWF) can lead to von Willebrand disease (VWD). Identifying causative or modifier variants of VWF is crucial for the diagnosis, classification, and clinical management of VWF disorders. However, owing to the length (178 kb) and complexity of VWF and the presence of the pseu dogene VWFP1, Sanger sequencing or short-read next-generation sequencing is often challenging. Objectives: This study aimed to establish a long-read sequencing method using Oxford nanopore technology (ONT) to overcome difficulties associated with VWF gene analysis. Methods: Genetic analyses were established using genomic DNA from a healthy donor and validated using 3 VWF disorder patient samples. Long-range ( 15 kb) polymerase chain reaction was optimized to obtain 21 amplicons covering the entire VWF gene, avoiding unwanted amplification due to repetitive sequences and VWFP1. ONT nanopore sequencing data were analyzed using software programs, including Clair3, Long shot, and Sniffles. The identified candidate variants were verified by several approaches such as Sanger sequencing and haplotyping. Results: The entire VWF gene was successfully read using ONT nanopore sequencing, with > 200 variants called in each patient sample. A rare missense variant,p.(Gln2442His) and a rare 2599 bp deletion were identified in patients 2 and 3,respectively. However, the deletion was confirmed as long-range polymerase chain reaction artifacts, which warrant attention when using this method. Conclusion: This study presents an optimal solution using ONT nanopore sequencing to identify variants in VWF, which may improve the diagnosis of VWF disorders. 内容記述: © 2025 The Author(s). Published by Elsevier Inc. on behalf of International Society on Thrombosis and Haemostasis. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Evaluation of post-tetanic motor evoked potential as an augmentation technique under partial neuromuscular blockade during craniotomy

2026-02-26T00:40:11Z

タイトル: Evaluation of post-tetanic motor evoked potential as an augmentation technique under partial neuromuscular blockade during craniotomy 著者: Oi, Ayako; Hayashi, Hironobu; Uemura, Keiko; Miyabayashi, Tomoshige; Takatani, Tsunenori; Matsuda, Ryosuke; Abe, Ryuichi; Nakagawa, Ichiro; Kawaguchi, Masahiko 抄録: Objective: In craniotomies requiring motor evoked potential (MEP) monitoring, avoiding neuromuscular blockade (NMB) is preferable, but its complete avoidance poses risks of unexpected movement. This retrospective study investigates the application of a post-tetanic MEP augmentation technique to enhance baseline recording of transcranial stimulation MEP (Tc-MEP) under partial NMB during craniotomy. Methods: Twenty-six patients were included. The level of partial NMB was maintained at a train-of-four ratio of approximately 40 %. Monophasic constant-current stimulation was applied on the craniotomy side with + 20 % of the threshold intensity. Post-tetanic Tc-MEP, involving tetanic stimulation of the median nerve 1s before transcranial stimulation, was performed on patients who failed to record using conventional baseline recording. Results: The post-tetanic Tc-MEP technique successfully improved the success rate of baseline recording from 61.5 % to 100 %. Application of post-tetanic Tc-MEP significantly increased amplitudes in both the upper (p = 0.04) and lower limbs (p < 0.01) compared to before post-tetanic Tc-MEP. No patients had unexpected movements. Conclusions: This study indicates that post-tetanic Tc-MEP enhanced the success rate of baseline recording during craniotomy under partial NMB. Significance: The combination of partial NMB and post-tetanic Tc-MEP could be a useful regimen for craniotomy with MEP monitoring, addressing both safety concerns and successful baseline recording. 内容記述: © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

5-Aminolevulinic Acid: A Novel Approach to Improving Radioresistance in Prostate Cancer

2026-02-25T16:30:11Z

タイトル: 5-Aminolevulinic Acid: A Novel Approach to Improving Radioresistance in Prostate Cancer 著者: Maesaka, Fumisato; Nakai, Yasushi; Yoshida, Takanori; Tomizawa, Mitsuru; Shimizu, Takuto; Owari, Takuya; Onishi, Kenta; Miyake, Makito; Kuniyasu, Hiroki; Fujimoto, Kiyohide; Tanaka, Nobumichi 抄録: Abstract: Background/Objectives: Prostate cancer (PCa) cells may acquire radioresistance during radiation therapy (RT), resulting in PCa recurrence. This study was aimed at investigating the radiosensitizing effect of 5-aminolevulinic acid (5-ALA) on radioresistant PCa cells. Methods: Radioresistant PCa cells were developed through successive irradiation of two human PCa cell lines (PC-3 and DU 145) and a murine PCa cell line (Myc-CaP). The radiosensitivity of these PCa cells and the radiosensitizing effect of 5-ALA were evaluated using clonogenic assays. Mitochondrial accumulation of protoporphyrin IX (PpIX) and mitochondrial reactive oxygen species (ROS) were evaluated. A syngeneic mouse model with radioresistant PCa was established, and the immunohistochemistry of cell specimens from PCa patients with local recurrence after primary RT was examined. Results: Ra dioresistant PCa cells showed lower radiosensitivity compared to parental PCa cells. In radioresistant PCa cells with 5-ALA administration, compared to the group administered irradiation alone, the survival rate after irradiation was significantly reduced by promoting mitochondria-mediated apoptosis caused by increased PpIX accumulation and mitochondrial ROS generation. Similar results were observed in vivo. However, compared with parental PCa cells, radioresistant PCa cells were less affected by the radiosensitizing effect of 5-ALA, owing to decreased PpIX accumulation and mitochondrial ROS production caused by upregulated expression of the drug transporter ABCG2. ABCG2 expression was upregulated in human PCa specimens with post-RT recurrence. Conclusions: 5-ALA　anced the antitumor effects of RT in radioresistant PCa cells; however, ABCG2 upregu lation decreased PpIX accumulation, resulting in a reduced radiosensitizing effect of 5-ALA on radioresistant PCa cells compared with that on parental PCa cells. ABCG2 could be a potential therapeutic target for overcoming radioresistance. 内容記述: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/ licenses/by/4.0/).